ChemWiki - User contributions [en]

Rep:Mod:Skilganon2

2013-02-08T15:41:06Z

Ec1210: /* Reference */

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing). Overall sugar A is more likely to be selected during a reaction because of neighbouring group participation.

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23267]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23267]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

[[image:TaxolNMRpic.png|thumb|The NMR for Taxol|left|500px]]

In this calculation, a change was made in the "solvent" module, that is it is replaced with benzene as a solvent due to literature. The Comparison in C 13 NMR is pretty good, as seen above. The main cause of the big difference in number 4 of the analysis is due to spin orbit coupling.

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate. The molecule on the left is called (Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide and the molecule on the right is (E)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide.

(Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide is produced by first using solution of (Z)-2′,4′,6′-trimethoxystyryl-4-methoxy-3-nitrobenzyl sulfide (11, 0.5 g, 1.3 mmol) in 40 mL of glacial acetic acid was cooled to 5 °C on an ice bath. Hydrogenperoxide 30% w/v (0.20 mL, 2.0 mmol) was added and the
mixture was stirred at 5 °C for 6 h. After completion of thereaction, 10% sodium hydrogen carbonate solution (25 mL)was added slowly and stirred for 10 min and extracted with ethyl acetate. The organic layer was washed with water (2 × 25 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by column chromatography (hexane/ethyl acetate) to obtain the title compound.

The compound is further reduced using any reduction method to add a double bond O to the S atom.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation: [[http://hdl.handle.net/10042/23172]] the J coupling was calculated as well! [[http://hdl.handle.net/10042/23237]]

[[image:C13NMRtable.png|thumb|The C13 NMR for the E Isomer|left|500px]]

[[image:hydrogenNMRtable.png|thumb|The H NMR for the E Isomer|center|500px]]

Overall, a relatively good fit was obtained for the C13 NMR, aside from a few gaps and differences. Bearing in mind that in the literature model, the compound may as well be contaminated, so certain shifts are likely to be missing, or extra shifts may be seen in this case. However in general, the ppm of literature and calculated values are within 5 ppm.

The H NMR however pose a larger problem as there are a lot more missing numbers from the literature value. However the values that fit the literature are good.

The NMR for the Z isomer was calculated: [[http://hdl.handle.net/10042/23225]] and the J coupling [[http://hdl.handle.net/10042/23236]], overall the fit is good.

[[image:C13NMR.png|thumb|The C13 NMR for the Z Isomer|left|500px]] [[image:HNMRisomerz.png|thumb|The H NMR for the Z Isomer|500px|center]]

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]] Isomer E has a Sum of electronic and thermal Energies= -1566.424099 HFT, 982931.122kJ/mol whereas Isomer Z has a Sum of electronic and thermal Energies= -1566.433798 HFT, -982937.21kJ/mol, there is only a very slight difference between the two energies.

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==
===Optical Rotation===
The Z optical Rotation was calculated [[http://hdl.handle.net/10042/23234]]Optical Rotation Beta= -4.2889 au, [Alpha] ( 5890.0 A) = -439.64 deg and the E optical Rotation [[http://hdl.handle.net/10042/23220]] Optical Rotation Beta= 4.5416 au, [Alpha] ( 5890.0 A) = 465.54 deg. Opposite, therefore it is valid as there shows a pair of isomers present.

===Circular Dichroism===
[[image:Circulardichro.png|750px|center|thumb|The UV and CD of the E Isomer]]

[[http://hdl.handle.net/10042/23221]] Unfortunately, there are no references I could find to compare this to.

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.
2.Hydrothiolation of benzyl mercaptan to arylacetylene:application to the synthesis of (E) and (Z)-isomers of ON 01910·Na (Rigosertib®), a phase III clinical stage anti-cancer agent†,Venkat R. Pallela,‡a Muralidhar R. Mallireddigari,‡a Stephen C. Cosenza,b Balaiah Akula, a D. R. C. Venkata Subbaiah, b E. Premkumar Reddy b and M. V. Ramana Reddy* b

Rep:Mod:Skilganon2

2013-02-08T15:39:19Z

Ec1210: /* Optical Rotation */

Rep:Mod:Skilganon2

2013-02-08T15:35:05Z

Ec1210: /* Optical Rotation */

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing). Overall sugar A is more likely to be selected during a reaction because of neighbouring group participation.

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23267]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23267]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

[[image:TaxolNMRpic.png|thumb|The NMR for Taxol|left|500px]]

In this calculation, a change was made in the "solvent" module, that is it is replaced with benzene as a solvent due to literature. The Comparison in C 13 NMR is pretty good, as seen above. The main cause of the big difference in number 4 of the analysis is due to spin orbit coupling.

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate. The molecule on the left is called (Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide and the molecule on the right is (E)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide.

(Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide is produced by first using solution of (Z)-2′,4′,6′-trimethoxystyryl-4-methoxy-3-nitrobenzyl sulfide (11, 0.5 g, 1.3 mmol) in 40 mL of glacial acetic acid was cooled to 5 °C on an ice bath. Hydrogenperoxide 30% w/v (0.20 mL, 2.0 mmol) was added and the
mixture was stirred at 5 °C for 6 h. After completion of thereaction, 10% sodium hydrogen carbonate solution (25 mL)was added slowly and stirred for 10 min and extracted with ethyl acetate. The organic layer was washed with water (2 × 25 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by column chromatography (hexane/ethyl acetate) to obtain the title compound.

The compound is further reduced using any reduction method to add a double bond O to the S atom.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation: [[http://hdl.handle.net/10042/23172]] the J coupling was calculated as well! [[http://hdl.handle.net/10042/23237]]

[[image:C13NMRtable.png|thumb|The C13 NMR for the E Isomer|left|500px]]

[[image:hydrogenNMRtable.png|thumb|The H NMR for the E Isomer|center|500px]]

Overall, a relatively good fit was obtained for the C13 NMR, aside from a few gaps and differences. Bearing in mind that in the literature model, the compound may as well be contaminated, so certain shifts are likely to be missing, or extra shifts may be seen in this case. However in general, the ppm of literature and calculated values are within 5 ppm.

The H NMR however pose a larger problem as there are a lot more missing numbers from the literature value. However the values that fit the literature are good.

The NMR for the Z isomer was calculated: [[http://hdl.handle.net/10042/23225]] and the J coupling [[http://hdl.handle.net/10042/23236]], overall the fit is good.

[[image:C13NMR.png|thumb|The C13 NMR for the Z Isomer|left|500px]] [[image:HNMRisomerz.png|thumb|The H NMR for the Z Isomer|500px|center]]

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]] Isomer E has a Sum of electronic and thermal Energies= -1566.424099 HFT, 982931.122kJ/mol whereas Isomer Z has a Sum of electronic and thermal Energies= -1566.433798 HFT, -982937.21kJ/mol, there is only a very slight difference between the two energies.

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==
===Optical Rotation===
The Z optical Rotation was calculated [[http://hdl.handle.net/10042/23234]]Optical Rotation Beta= -4.2889 au.
and the E optical Rotation [[http://hdl.handle.net/10042/23220]] Optical Rotation Beta= 4.5416 au.

===Circular Dichroism===
[[image:Circulardichro.png|750px|center|thumb|The UV and CD of the E Isomer]]

[[http://hdl.handle.net/10042/23221]] Unfortunately, there are no references I could find to compare this to.

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

Rep:Mod:Skilganon2

2013-02-08T15:30:59Z

Ec1210: /* Optical Rotation and Circular Dichroism */

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing). Overall sugar A is more likely to be selected during a reaction because of neighbouring group participation.

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23267]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23267]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

[[image:TaxolNMRpic.png|thumb|The NMR for Taxol|left|500px]]

In this calculation, a change was made in the "solvent" module, that is it is replaced with benzene as a solvent due to literature. The Comparison in C 13 NMR is pretty good, as seen above. The main cause of the big difference in number 4 of the analysis is due to spin orbit coupling.

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate. The molecule on the left is called (Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide and the molecule on the right is (E)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide.

(Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide is produced by first using solution of (Z)-2′,4′,6′-trimethoxystyryl-4-methoxy-3-nitrobenzyl sulfide (11, 0.5 g, 1.3 mmol) in 40 mL of glacial acetic acid was cooled to 5 °C on an ice bath. Hydrogenperoxide 30% w/v (0.20 mL, 2.0 mmol) was added and the
mixture was stirred at 5 °C for 6 h. After completion of thereaction, 10% sodium hydrogen carbonate solution (25 mL)was added slowly and stirred for 10 min and extracted with ethyl acetate. The organic layer was washed with water (2 × 25 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by column chromatography (hexane/ethyl acetate) to obtain the title compound.

The compound is further reduced using any reduction method to add a double bond O to the S atom.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation: [[http://hdl.handle.net/10042/23172]] the J coupling was calculated as well! [[http://hdl.handle.net/10042/23237]]

[[image:C13NMRtable.png|thumb|The C13 NMR for the E Isomer|left|500px]]

[[image:hydrogenNMRtable.png|thumb|The H NMR for the E Isomer|center|500px]]

Overall, a relatively good fit was obtained for the C13 NMR, aside from a few gaps and differences. Bearing in mind that in the literature model, the compound may as well be contaminated, so certain shifts are likely to be missing, or extra shifts may be seen in this case. However in general, the ppm of literature and calculated values are within 5 ppm.

The H NMR however pose a larger problem as there are a lot more missing numbers from the literature value. However the values that fit the literature are good.

The NMR for the Z isomer was calculated: [[http://hdl.handle.net/10042/23225]] and the J coupling [[http://hdl.handle.net/10042/23236]], overall the fit is good.

[[image:C13NMR.png|thumb|The C13 NMR for the Z Isomer|left|500px]] [[image:HNMRisomerz.png|thumb|The H NMR for the Z Isomer|500px|center]]

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]] Isomer E has a Sum of electronic and thermal Energies= -1566.424099 HFT, 982931.122kJ/mol whereas Isomer Z has a Sum of electronic and thermal Energies= -1566.433798 HFT, -982937.21kJ/mol, there is only a very slight difference between the two energies.

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==
===Optical Rotation===
The Z optical Rotation was calculated [[http://hdl.handle.net/10042/23234]] and the E optical Rotation [[http://hdl.handle.net/10042/23220]]

===Circular Dichroism===
[[image:Circulardichro.png|750px|center|thumb|The UV and CD of the E Isomer]]

[[http://hdl.handle.net/10042/23221]] Unfortunately, there are no references I could find to compare this to.

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

Rep:Mod:Skilganon2

2013-02-08T15:24:20Z

Ec1210: /* Circular Dichroism */

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing). Overall sugar A is more likely to be selected during a reaction because of neighbouring group participation.

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23267]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23267]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

[[image:TaxolNMRpic.png|thumb|The NMR for Taxol|left|500px]]

In this calculation, a change was made in the "solvent" module, that is it is replaced with benzene as a solvent due to literature. The Comparison in C 13 NMR is pretty good, as seen above. The main cause of the big difference in number 4 of the analysis is due to spin orbit coupling.

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate. The molecule on the left is called (Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide and the molecule on the right is (E)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide.

(Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide is produced by first using solution of (Z)-2′,4′,6′-trimethoxystyryl-4-methoxy-3-nitrobenzyl sulfide (11, 0.5 g, 1.3 mmol) in 40 mL of glacial acetic acid was cooled to 5 °C on an ice bath. Hydrogenperoxide 30% w/v (0.20 mL, 2.0 mmol) was added and the
mixture was stirred at 5 °C for 6 h. After completion of thereaction, 10% sodium hydrogen carbonate solution (25 mL)was added slowly and stirred for 10 min and extracted with ethyl acetate. The organic layer was washed with water (2 × 25 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by column chromatography (hexane/ethyl acetate) to obtain the title compound.

The compound is further reduced using any reduction method to add a double bond O to the S atom.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation: [[http://hdl.handle.net/10042/23172]] the J coupling was calculated as well! [[http://hdl.handle.net/10042/23237]]

[[image:C13NMRtable.png|thumb|The C13 NMR for the E Isomer|left|500px]]

[[image:hydrogenNMRtable.png|thumb|The H NMR for the E Isomer|center|500px]]

Overall, a relatively good fit was obtained for the C13 NMR, aside from a few gaps and differences. Bearing in mind that in the literature model, the compound may as well be contaminated, so certain shifts are likely to be missing, or extra shifts may be seen in this case. However in general, the ppm of literature and calculated values are within 5 ppm.

The H NMR however pose a larger problem as there are a lot more missing numbers from the literature value. However the values that fit the literature are good.

The NMR for the Z isomer was calculated: [[http://hdl.handle.net/10042/23225]] and the J coupling [[http://hdl.handle.net/10042/23236]], overall the fit is good.

[[image:C13NMR.png|thumb|The C13 NMR for the Z Isomer|left|500px]] [[image:HNMRisomerz.png|thumb|The H NMR for the Z Isomer|500px|center]]

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]] Isomer E has a Sum of electronic and thermal Energies= -1566.424099 HFT, 982931.122kJ/mol whereas Isomer Z has a Sum of electronic and thermal Energies= -1566.433798 HFT, -982937.21kJ/mol, there is only a very slight difference between the two energies.

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==

===Circular Dichroism===
[[image:Circulardichro.png|750px|center|thumb|The UV and CD of the E Isomer]]

[[http://hdl.handle.net/10042/23221]] Unfortunately, there are no references I could find to compare this to.

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

Rep:Mod:Skilganon2

2013-02-08T15:09:31Z

Ec1210: /* Circular Dichroism */

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing). Overall sugar A is more likely to be selected during a reaction because of neighbouring group participation.

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23267]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23267]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

[[image:TaxolNMRpic.png|thumb|The NMR for Taxol|left|500px]]

In this calculation, a change was made in the "solvent" module, that is it is replaced with benzene as a solvent due to literature. The Comparison in C 13 NMR is pretty good, as seen above. The main cause of the big difference in number 4 of the analysis is due to spin orbit coupling.

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate. The molecule on the left is called (Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide and the molecule on the right is (E)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide.

(Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide is produced by first using solution of (Z)-2′,4′,6′-trimethoxystyryl-4-methoxy-3-nitrobenzyl sulfide (11, 0.5 g, 1.3 mmol) in 40 mL of glacial acetic acid was cooled to 5 °C on an ice bath. Hydrogenperoxide 30% w/v (0.20 mL, 2.0 mmol) was added and the
mixture was stirred at 5 °C for 6 h. After completion of thereaction, 10% sodium hydrogen carbonate solution (25 mL)was added slowly and stirred for 10 min and extracted with ethyl acetate. The organic layer was washed with water (2 × 25 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by column chromatography (hexane/ethyl acetate) to obtain the title compound.

The compound is further reduced using any reduction method to add a double bond O to the S atom.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation: [[http://hdl.handle.net/10042/23172]] the J coupling was calculated as well! [[http://hdl.handle.net/10042/23237]]

[[image:C13NMRtable.png|thumb|The C13 NMR for the E Isomer|left|500px]]

[[image:hydrogenNMRtable.png|thumb|The H NMR for the E Isomer|center|500px]]

Overall, a relatively good fit was obtained for the C13 NMR, aside from a few gaps and differences. Bearing in mind that in the literature model, the compound may as well be contaminated, so certain shifts are likely to be missing, or extra shifts may be seen in this case. However in general, the ppm of literature and calculated values are within 5 ppm.

The H NMR however pose a larger problem as there are a lot more missing numbers from the literature value. However the values that fit the literature are good.

The NMR for the Z isomer was calculated: [[http://hdl.handle.net/10042/23225]] and the J coupling [[http://hdl.handle.net/10042/23236]], overall the fit is good.

[[image:C13NMR.png|thumb|The C13 NMR for the Z Isomer|left|500px]] [[image:HNMRisomerz.png|thumb|The H NMR for the Z Isomer|500px|center]]

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]] Isomer E has a Sum of electronic and thermal Energies= -1566.424099 HFT, 982931.122kJ/mol whereas Isomer Z has a Sum of electronic and thermal Energies= -1566.433798 HFT, -982937.21kJ/mol, there is only a very slight difference between the two energies.

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==

===Circular Dichroism===
[[image:Circulardichro.png|750px|center|thumb|The UV and CD of the E Isomer]]

[[http://hdl.handle.net/10042/23221]]

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

Rep:Mod:Skilganon2

2013-02-08T15:08:22Z

Ec1210: /* Circular Dichroism */

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing). Overall sugar A is more likely to be selected during a reaction because of neighbouring group participation.

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23267]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23267]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

[[image:TaxolNMRpic.png|thumb|The NMR for Taxol|left|500px]]

In this calculation, a change was made in the "solvent" module, that is it is replaced with benzene as a solvent due to literature. The Comparison in C 13 NMR is pretty good, as seen above. The main cause of the big difference in number 4 of the analysis is due to spin orbit coupling.

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate. The molecule on the left is called (Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide and the molecule on the right is (E)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide.

(Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide is produced by first using solution of (Z)-2′,4′,6′-trimethoxystyryl-4-methoxy-3-nitrobenzyl sulfide (11, 0.5 g, 1.3 mmol) in 40 mL of glacial acetic acid was cooled to 5 °C on an ice bath. Hydrogenperoxide 30% w/v (0.20 mL, 2.0 mmol) was added and the
mixture was stirred at 5 °C for 6 h. After completion of thereaction, 10% sodium hydrogen carbonate solution (25 mL)was added slowly and stirred for 10 min and extracted with ethyl acetate. The organic layer was washed with water (2 × 25 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by column chromatography (hexane/ethyl acetate) to obtain the title compound.

The compound is further reduced using any reduction method to add a double bond O to the S atom.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation: [[http://hdl.handle.net/10042/23172]] the J coupling was calculated as well! [[http://hdl.handle.net/10042/23237]]

[[image:C13NMRtable.png|thumb|The C13 NMR for the E Isomer|left|500px]]

[[image:hydrogenNMRtable.png|thumb|The H NMR for the E Isomer|center|500px]]

Overall, a relatively good fit was obtained for the C13 NMR, aside from a few gaps and differences. Bearing in mind that in the literature model, the compound may as well be contaminated, so certain shifts are likely to be missing, or extra shifts may be seen in this case. However in general, the ppm of literature and calculated values are within 5 ppm.

The H NMR however pose a larger problem as there are a lot more missing numbers from the literature value. However the values that fit the literature are good.

The NMR for the Z isomer was calculated: [[http://hdl.handle.net/10042/23225]] and the J coupling [[http://hdl.handle.net/10042/23236]], overall the fit is good.

[[image:C13NMR.png|thumb|The C13 NMR for the Z Isomer|left|500px]] [[image:HNMRisomerz.png|thumb|The H NMR for the Z Isomer|500px|center]]

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]] Isomer E has a Sum of electronic and thermal Energies= -1566.424099 HFT, 982931.122kJ/mol whereas Isomer Z has a Sum of electronic and thermal Energies= -1566.433798 HFT, -982937.21kJ/mol, there is only a very slight difference between the two energies.

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==

===Circular Dichroism===
[[image:Circulardichro.png|750px|center|thumb|The UV and CD of the E Isomer]]

[[http://hdl.handle.net/10042/23234]]

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

Rep:Mod:Skilganon2

2013-02-08T15:03:39Z

Ec1210: /* Circular Dichroism */

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing). Overall sugar A is more likely to be selected during a reaction because of neighbouring group participation.

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23267]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23267]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

[[image:TaxolNMRpic.png|thumb|The NMR for Taxol|left|500px]]

In this calculation, a change was made in the "solvent" module, that is it is replaced with benzene as a solvent due to literature. The Comparison in C 13 NMR is pretty good, as seen above. The main cause of the big difference in number 4 of the analysis is due to spin orbit coupling.

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate. The molecule on the left is called (Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide and the molecule on the right is (E)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide.

(Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide is produced by first using solution of (Z)-2′,4′,6′-trimethoxystyryl-4-methoxy-3-nitrobenzyl sulfide (11, 0.5 g, 1.3 mmol) in 40 mL of glacial acetic acid was cooled to 5 °C on an ice bath. Hydrogenperoxide 30% w/v (0.20 mL, 2.0 mmol) was added and the
mixture was stirred at 5 °C for 6 h. After completion of thereaction, 10% sodium hydrogen carbonate solution (25 mL)was added slowly and stirred for 10 min and extracted with ethyl acetate. The organic layer was washed with water (2 × 25 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by column chromatography (hexane/ethyl acetate) to obtain the title compound.

The compound is further reduced using any reduction method to add a double bond O to the S atom.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation: [[http://hdl.handle.net/10042/23172]] the J coupling was calculated as well! [[http://hdl.handle.net/10042/23237]]

[[image:C13NMRtable.png|thumb|The C13 NMR for the E Isomer|left|500px]]

[[image:hydrogenNMRtable.png|thumb|The H NMR for the E Isomer|center|500px]]

Overall, a relatively good fit was obtained for the C13 NMR, aside from a few gaps and differences. Bearing in mind that in the literature model, the compound may as well be contaminated, so certain shifts are likely to be missing, or extra shifts may be seen in this case. However in general, the ppm of literature and calculated values are within 5 ppm.

The H NMR however pose a larger problem as there are a lot more missing numbers from the literature value. However the values that fit the literature are good.

The NMR for the Z isomer was calculated: [[http://hdl.handle.net/10042/23225]] and the J coupling [[http://hdl.handle.net/10042/23236]], overall the fit is good.

[[image:C13NMR.png|thumb|The C13 NMR for the Z Isomer|left|500px]] [[image:HNMRisomerz.png|thumb|The H NMR for the Z Isomer|500px|center]]

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]] Isomer E has a Sum of electronic and thermal Energies= -1566.424099 HFT, 982931.122kJ/mol whereas Isomer Z has a Sum of electronic and thermal Energies= -1566.433798 HFT, -982937.21kJ/mol, there is only a very slight difference between the two energies.

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==

===Circular Dichroism===
[[image:Circulardichro.png|750px|center|thumb|The UV and CD of the E Isomer]]

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

File:Circulardichro.png

2013-02-08T15:03:10Z

Ec1210:

Rep:Mod:Skilganon2

2013-02-08T15:00:37Z

Ec1210: /* Optical Rotation and Circular Dichroism */

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing). Overall sugar A is more likely to be selected during a reaction because of neighbouring group participation.

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23267]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23267]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

[[image:TaxolNMRpic.png|thumb|The NMR for Taxol|left|500px]]

In this calculation, a change was made in the "solvent" module, that is it is replaced with benzene as a solvent due to literature. The Comparison in C 13 NMR is pretty good, as seen above. The main cause of the big difference in number 4 of the analysis is due to spin orbit coupling.

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate. The molecule on the left is called (Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide and the molecule on the right is (E)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide.

(Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide is produced by first using solution of (Z)-2′,4′,6′-trimethoxystyryl-4-methoxy-3-nitrobenzyl sulfide (11, 0.5 g, 1.3 mmol) in 40 mL of glacial acetic acid was cooled to 5 °C on an ice bath. Hydrogenperoxide 30% w/v (0.20 mL, 2.0 mmol) was added and the
mixture was stirred at 5 °C for 6 h. After completion of thereaction, 10% sodium hydrogen carbonate solution (25 mL)was added slowly and stirred for 10 min and extracted with ethyl acetate. The organic layer was washed with water (2 × 25 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by column chromatography (hexane/ethyl acetate) to obtain the title compound.

The compound is further reduced using any reduction method to add a double bond O to the S atom.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation: [[http://hdl.handle.net/10042/23172]] the J coupling was calculated as well! [[http://hdl.handle.net/10042/23237]]

[[image:C13NMRtable.png|thumb|The C13 NMR for the E Isomer|left|500px]]

[[image:hydrogenNMRtable.png|thumb|The H NMR for the E Isomer|center|500px]]

Overall, a relatively good fit was obtained for the C13 NMR, aside from a few gaps and differences. Bearing in mind that in the literature model, the compound may as well be contaminated, so certain shifts are likely to be missing, or extra shifts may be seen in this case. However in general, the ppm of literature and calculated values are within 5 ppm.

The H NMR however pose a larger problem as there are a lot more missing numbers from the literature value. However the values that fit the literature are good.

The NMR for the Z isomer was calculated: [[http://hdl.handle.net/10042/23225]] and the J coupling [[http://hdl.handle.net/10042/23236]], overall the fit is good.

[[image:C13NMR.png|thumb|The C13 NMR for the Z Isomer|left|500px]] [[image:HNMRisomerz.png|thumb|The H NMR for the Z Isomer|500px|center]]

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]] Isomer E has a Sum of electronic and thermal Energies= -1566.424099 HFT, 982931.122kJ/mol whereas Isomer Z has a Sum of electronic and thermal Energies= -1566.433798 HFT, -982937.21kJ/mol, there is only a very slight difference between the two energies.

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==

===Circular Dichroism===
[[image:Circulardichro.png|600px|center|thumb|The UV and CD of the E Isomer]]

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

Rep:Mod:Skilganon2

2013-02-08T14:44:29Z

Ec1210: /* Spectroscopy of an Intermediate related to the Synthesis of Taxol */

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing). Overall sugar A is more likely to be selected during a reaction because of neighbouring group participation.

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23267]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23267]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

[[image:TaxolNMRpic.png|thumb|The NMR for Taxol|left|500px]]

In this calculation, a change was made in the "solvent" module, that is it is replaced with benzene as a solvent due to literature. The Comparison in C 13 NMR is pretty good, as seen above. The main cause of the big difference in number 4 of the analysis is due to spin orbit coupling.

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate. The molecule on the left is called (Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide and the molecule on the right is (E)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide.

(Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide is produced by first using solution of (Z)-2′,4′,6′-trimethoxystyryl-4-methoxy-3-nitrobenzyl sulfide (11, 0.5 g, 1.3 mmol) in 40 mL of glacial acetic acid was cooled to 5 °C on an ice bath. Hydrogenperoxide 30% w/v (0.20 mL, 2.0 mmol) was added and the
mixture was stirred at 5 °C for 6 h. After completion of thereaction, 10% sodium hydrogen carbonate solution (25 mL)was added slowly and stirred for 10 min and extracted with ethyl acetate. The organic layer was washed with water (2 × 25 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by column chromatography (hexane/ethyl acetate) to obtain the title compound.

The compound is further reduced using any reduction method to add a double bond O to the S atom.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation: [[http://hdl.handle.net/10042/23172]] the J coupling was calculated as well! [[http://hdl.handle.net/10042/23237]]

[[image:C13NMRtable.png|thumb|The C13 NMR for the E Isomer|left|500px]]

[[image:hydrogenNMRtable.png|thumb|The H NMR for the E Isomer|center|500px]]

Overall, a relatively good fit was obtained for the C13 NMR, aside from a few gaps and differences. Bearing in mind that in the literature model, the compound may as well be contaminated, so certain shifts are likely to be missing, or extra shifts may be seen in this case. However in general, the ppm of literature and calculated values are within 5 ppm.

The H NMR however pose a larger problem as there are a lot more missing numbers from the literature value. However the values that fit the literature are good.

The NMR for the Z isomer was calculated: [[http://hdl.handle.net/10042/23225]] and the J coupling [[http://hdl.handle.net/10042/23236]], overall the fit is good.

[[image:C13NMR.png|thumb|The C13 NMR for the Z Isomer|left|500px]] [[image:HNMRisomerz.png|thumb|The H NMR for the Z Isomer|500px|center]]

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]] Isomer E has a Sum of electronic and thermal Energies= -1566.424099 HFT, 982931.122kJ/mol whereas Isomer Z has a Sum of electronic and thermal Energies= -1566.433798 HFT, -982937.21kJ/mol, there is only a very slight difference between the two energies.

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

Rep:Mod:Skilganon2

2013-02-08T14:41:35Z

Ec1210: /* Spectroscopy of an Intermediate related to the Synthesis of Taxol */

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing). Overall sugar A is more likely to be selected during a reaction because of neighbouring group participation.

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23267]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23267]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

[[image:TaxolNMRpic.png|thumb|The NMR for Taxol|left|500px]]

In this calculation, a change was made in the "solvent" module, that is it is replaced with benzene as a solvent due to literature. The Comparison in C 13 NMR is pretty good, as seen above.

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate. The molecule on the left is called (Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide and the molecule on the right is (E)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide.

(Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide is produced by first using solution of (Z)-2′,4′,6′-trimethoxystyryl-4-methoxy-3-nitrobenzyl sulfide (11, 0.5 g, 1.3 mmol) in 40 mL of glacial acetic acid was cooled to 5 °C on an ice bath. Hydrogenperoxide 30% w/v (0.20 mL, 2.0 mmol) was added and the
mixture was stirred at 5 °C for 6 h. After completion of thereaction, 10% sodium hydrogen carbonate solution (25 mL)was added slowly and stirred for 10 min and extracted with ethyl acetate. The organic layer was washed with water (2 × 25 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by column chromatography (hexane/ethyl acetate) to obtain the title compound.

The compound is further reduced using any reduction method to add a double bond O to the S atom.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation: [[http://hdl.handle.net/10042/23172]] the J coupling was calculated as well! [[http://hdl.handle.net/10042/23237]]

[[image:C13NMRtable.png|thumb|The C13 NMR for the E Isomer|left|500px]]

[[image:hydrogenNMRtable.png|thumb|The H NMR for the E Isomer|center|500px]]

Overall, a relatively good fit was obtained for the C13 NMR, aside from a few gaps and differences. Bearing in mind that in the literature model, the compound may as well be contaminated, so certain shifts are likely to be missing, or extra shifts may be seen in this case. However in general, the ppm of literature and calculated values are within 5 ppm.

The H NMR however pose a larger problem as there are a lot more missing numbers from the literature value. However the values that fit the literature are good.

The NMR for the Z isomer was calculated: [[http://hdl.handle.net/10042/23225]] and the J coupling [[http://hdl.handle.net/10042/23236]], overall the fit is good.

[[image:C13NMR.png|thumb|The C13 NMR for the Z Isomer|left|500px]] [[image:HNMRisomerz.png|thumb|The H NMR for the Z Isomer|500px|center]]

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]] Isomer E has a Sum of electronic and thermal Energies= -1566.424099 HFT, 982931.122kJ/mol whereas Isomer Z has a Sum of electronic and thermal Energies= -1566.433798 HFT, -982937.21kJ/mol, there is only a very slight difference between the two energies.

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

Rep:Mod:Skilganon2

2013-02-08T14:34:08Z

Ec1210: /* Vibrational Analysis and Comparison */

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing). Overall sugar A is more likely to be selected during a reaction because of neighbouring group participation.

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23267]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23267]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

[[image:TaxolNMRpic.png|thumb|The NMR for Taxol|left|500px]]

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate. The molecule on the left is called (Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide and the molecule on the right is (E)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide.

(Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide is produced by first using solution of (Z)-2′,4′,6′-trimethoxystyryl-4-methoxy-3-nitrobenzyl sulfide (11, 0.5 g, 1.3 mmol) in 40 mL of glacial acetic acid was cooled to 5 °C on an ice bath. Hydrogenperoxide 30% w/v (0.20 mL, 2.0 mmol) was added and the
mixture was stirred at 5 °C for 6 h. After completion of thereaction, 10% sodium hydrogen carbonate solution (25 mL)was added slowly and stirred for 10 min and extracted with ethyl acetate. The organic layer was washed with water (2 × 25 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by column chromatography (hexane/ethyl acetate) to obtain the title compound.

The compound is further reduced using any reduction method to add a double bond O to the S atom.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation: [[http://hdl.handle.net/10042/23172]] the J coupling was calculated as well! [[http://hdl.handle.net/10042/23237]]

[[image:C13NMRtable.png|thumb|The C13 NMR for the E Isomer|left|500px]]

[[image:hydrogenNMRtable.png|thumb|The H NMR for the E Isomer|center|500px]]

Overall, a relatively good fit was obtained for the C13 NMR, aside from a few gaps and differences. Bearing in mind that in the literature model, the compound may as well be contaminated, so certain shifts are likely to be missing, or extra shifts may be seen in this case. However in general, the ppm of literature and calculated values are within 5 ppm.

The H NMR however pose a larger problem as there are a lot more missing numbers from the literature value. However the values that fit the literature are good.

The NMR for the Z isomer was calculated: [[http://hdl.handle.net/10042/23225]] and the J coupling [[http://hdl.handle.net/10042/23236]], overall the fit is good.

[[image:C13NMR.png|thumb|The C13 NMR for the Z Isomer|left|500px]] [[image:HNMRisomerz.png|thumb|The H NMR for the Z Isomer|500px|center]]

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]] Isomer E has a Sum of electronic and thermal Energies= -1566.424099 HFT, 982931.122kJ/mol whereas Isomer Z has a Sum of electronic and thermal Energies= -1566.433798 HFT, -982937.21kJ/mol, there is only a very slight difference between the two energies.

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

Rep:Mod:Skilganon2

2013-02-08T14:33:11Z

Ec1210: /* Vibrational Analysis and Comparison */

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing). Overall sugar A is more likely to be selected during a reaction because of neighbouring group participation.

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23267]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23267]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

[[image:TaxolNMRpic.png|thumb|The NMR for Taxol|left|500px]]

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate. The molecule on the left is called (Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide and the molecule on the right is (E)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide.

(Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide is produced by first using solution of (Z)-2′,4′,6′-trimethoxystyryl-4-methoxy-3-nitrobenzyl sulfide (11, 0.5 g, 1.3 mmol) in 40 mL of glacial acetic acid was cooled to 5 °C on an ice bath. Hydrogenperoxide 30% w/v (0.20 mL, 2.0 mmol) was added and the
mixture was stirred at 5 °C for 6 h. After completion of thereaction, 10% sodium hydrogen carbonate solution (25 mL)was added slowly and stirred for 10 min and extracted with ethyl acetate. The organic layer was washed with water (2 × 25 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by column chromatography (hexane/ethyl acetate) to obtain the title compound.

The compound is further reduced using any reduction method to add a double bond O to the S atom.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation: [[http://hdl.handle.net/10042/23172]] the J coupling was calculated as well! [[http://hdl.handle.net/10042/23237]]

[[image:C13NMRtable.png|thumb|The C13 NMR for the E Isomer|left|500px]]

[[image:hydrogenNMRtable.png|thumb|The H NMR for the E Isomer|center|500px]]

Overall, a relatively good fit was obtained for the C13 NMR, aside from a few gaps and differences. Bearing in mind that in the literature model, the compound may as well be contaminated, so certain shifts are likely to be missing, or extra shifts may be seen in this case. However in general, the ppm of literature and calculated values are within 5 ppm.

The H NMR however pose a larger problem as there are a lot more missing numbers from the literature value. However the values that fit the literature are good.

The NMR for the Z isomer was calculated: [[http://hdl.handle.net/10042/23225]] and the J coupling [[http://hdl.handle.net/10042/23236]], overall the fit is good.

[[image:C13NMR.png|thumb|The C13 NMR for the Z Isomer|left|500px]] [[image:HNMRisomerz.png|thumb|The H NMR for the Z Isomer|500px|center]]

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]] Isomer E has a Sum of electronic and thermal Energies= -1566.424099 HFT, 982931.122kJ/mol whereas Isomer Z has a Sum of electronic and thermal Energies= -1566.433798 HFT, -982937.21kJ/mol

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

Rep:Mod:Skilganon2

2013-02-08T14:24:02Z

Ec1210: /* Vibrational Analysis and Comparison */

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing). Overall sugar A is more likely to be selected during a reaction because of neighbouring group participation.

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23267]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23267]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

[[image:TaxolNMRpic.png|thumb|The NMR for Taxol|left|500px]]

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate. The molecule on the left is called (Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide and the molecule on the right is (E)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide.

(Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide is produced by first using solution of (Z)-2′,4′,6′-trimethoxystyryl-4-methoxy-3-nitrobenzyl sulfide (11, 0.5 g, 1.3 mmol) in 40 mL of glacial acetic acid was cooled to 5 °C on an ice bath. Hydrogenperoxide 30% w/v (0.20 mL, 2.0 mmol) was added and the
mixture was stirred at 5 °C for 6 h. After completion of thereaction, 10% sodium hydrogen carbonate solution (25 mL)was added slowly and stirred for 10 min and extracted with ethyl acetate. The organic layer was washed with water (2 × 25 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by column chromatography (hexane/ethyl acetate) to obtain the title compound.

The compound is further reduced using any reduction method to add a double bond O to the S atom.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation: [[http://hdl.handle.net/10042/23172]] the J coupling was calculated as well! [[http://hdl.handle.net/10042/23237]]

[[image:C13NMRtable.png|thumb|The C13 NMR for the E Isomer|left|500px]]

[[image:hydrogenNMRtable.png|thumb|The H NMR for the E Isomer|center|500px]]

Overall, a relatively good fit was obtained for the C13 NMR, aside from a few gaps and differences. Bearing in mind that in the literature model, the compound may as well be contaminated, so certain shifts are likely to be missing, or extra shifts may be seen in this case. However in general, the ppm of literature and calculated values are within 5 ppm.

The H NMR however pose a larger problem as there are a lot more missing numbers from the literature value. However the values that fit the literature are good.

The NMR for the Z isomer was calculated: [[http://hdl.handle.net/10042/23225]] and the J coupling [[http://hdl.handle.net/10042/23236]], overall the fit is good.

[[image:C13NMR.png|thumb|The C13 NMR for the Z Isomer|left|500px]] [[image:HNMRisomerz.png|thumb|The H NMR for the Z Isomer|500px|center]]

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]] Isomer E has a Sum of electronic and thermal Energies= -1566.424099 HFT, whereas Isomer Z has a Sum of electronic and thermal Energies= -1566.433798 HFT.

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

Rep:Mod:Skilganon2

2013-02-08T13:52:20Z

Ec1210: /* Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule */

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing). Overall sugar A is more likely to be selected during a reaction because of neighbouring group participation.

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23267]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23267]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

[[image:TaxolNMRpic.png|thumb|The NMR for Taxol|left|500px]]

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate. The molecule on the left is called (Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide and the molecule on the right is (E)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide.

(Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide is produced by first using solution of (Z)-2′,4′,6′-trimethoxystyryl-4-methoxy-3-nitrobenzyl sulfide (11, 0.5 g, 1.3 mmol) in 40 mL of glacial acetic acid was cooled to 5 °C on an ice bath. Hydrogenperoxide 30% w/v (0.20 mL, 2.0 mmol) was added and the
mixture was stirred at 5 °C for 6 h. After completion of thereaction, 10% sodium hydrogen carbonate solution (25 mL)was added slowly and stirred for 10 min and extracted with ethyl acetate. The organic layer was washed with water (2 × 25 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by column chromatography (hexane/ethyl acetate) to obtain the title compound.

The compound is further reduced using any reduction method to add a double bond O to the S atom.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation: [[http://hdl.handle.net/10042/23172]] the J coupling was calculated as well! [[http://hdl.handle.net/10042/23237]]

[[image:C13NMRtable.png|thumb|The C13 NMR for the E Isomer|left|500px]]

[[image:hydrogenNMRtable.png|thumb|The H NMR for the E Isomer|center|500px]]

Overall, a relatively good fit was obtained for the C13 NMR, aside from a few gaps and differences. Bearing in mind that in the literature model, the compound may as well be contaminated, so certain shifts are likely to be missing, or extra shifts may be seen in this case. However in general, the ppm of literature and calculated values are within 5 ppm.

The H NMR however pose a larger problem as there are a lot more missing numbers from the literature value. However the values that fit the literature are good.

The NMR for the Z isomer was calculated: [[http://hdl.handle.net/10042/23225]] and the J coupling [[http://hdl.handle.net/10042/23236]], overall the fit is good.

[[image:C13NMR.png|thumb|The C13 NMR for the Z Isomer|left|500px]] [[image:HNMRisomerz.png|thumb|The H NMR for the Z Isomer|500px|center]]

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]]

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

Rep:Mod:Skilganon2

2013-02-08T13:47:33Z

Ec1210: /* NMR Analysis and Comparison */

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing). Overall sugar A is more likely to be selected during a reaction because of neighbouring group participation.

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23267]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23267]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

[[image:TaxolNMRpic.png|thumb|The NMR for Taxol|left|500px]]

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate. The molecule on the left is called (Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide and the molecule on the right is (E)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide.

(Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide is produced by first using solution of (Z)-2′,4′,6′-trimethoxystyryl-4-methoxy-3-nitrobenzyl sulfide (11, 0.5 g, 1.3 mmol) in 40 mL of glacial acetic acid was cooled to 5 °C on an ice bath. Hydrogenperoxide 30% w/v (0.20 mL, 2.0 mmol) was added and the
mixture was stirred at 5 °C for 6 h. After completion of thereaction, 10% sodium hydrogen carbonate solution (25 mL)was added slowly and stirred for 10 min and extracted with ethyl acetate. The organic layer was washed with water (2 × 25 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by column chromatography (hexane/ethyl acetate) to obtain the title compound.

The compound is further reduced using any reduction method to add a double bond O to the S atom.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation: [[http://hdl.handle.net/10042/23172]] the J coupling was calculated as well! [[http://hdl.handle.net/10042/23237]]

[[image:C13NMRtable.png|thumb|The C13 NMR for the E Isomer|left|500px]]

[[image:hydrogenNMRtable.png|thumb|The H NMR for the E Isomer|center|500px]]

Overall, a relatively good fit was obtained for the C13 NMR, aside from a few gaps and differences. Bearing in mind that in the literature model, the compound may as well be contaminated, so certain shifts are likely to be missing, or extra shifts may be seen in this case. However in general, the ppm of literature and calculated values are within 5 ppm.

The H NMR however pose a larger problem as there are a lot more missing numbers from the literature value. However the values that fit the literature are good.

The NMR for the Z isomer was calculated: [[http://hdl.handle.net/10042/23225]] and the J coupling [[http://hdl.handle.net/10042/23236]], overall the fit is good.

[[image:C13NMR.png|thumb|The C13 NMR for the Z Isomer|left|500px]] [[image:HNMRisomerz.png|thumb|The H NMR for the Z Isomer|500px|center]]

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]]

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

Rep:Mod:Skilganon2

2013-02-08T13:46:17Z

Ec1210: /* Spectroscopy of an Intermediate related to the Synthesis of Taxol */

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing). Overall sugar A is more likely to be selected during a reaction because of neighbouring group participation.

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23267]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23267]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

[[image:TaxolNMRpic.png|thumb|The NMR for Taxol|left|500px]]

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate. The molecule on the left is called (Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide and the molecule on the right is (E)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide.

(Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide is produced by first using solution of (Z)-2′,4′,6′-trimethoxystyryl-4-methoxy-3-nitrobenzyl sulfide (11, 0.5 g, 1.3 mmol) in 40 mL of glacial acetic acid was cooled to 5 °C on an ice bath. Hydrogenperoxide 30% w/v (0.20 mL, 2.0 mmol) was added and the
mixture was stirred at 5 °C for 6 h. After completion of thereaction, 10% sodium hydrogen carbonate solution (25 mL)was added slowly and stirred for 10 min and extracted with ethyl acetate. The organic layer was washed with water (2 × 25 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by column chromatography (hexane/ethyl acetate) to obtain the title compound.

The compound is further reduced using any reduction method to add a double bond O to the S atom.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation: [[http://hdl.handle.net/10042/23172]] the J coupling was calculated as well! [[http://hdl.handle.net/10042/23237]]

[[image:C13NMRtable.png|thumb|The C13 NMR for the E Isomer|left|500px]]

[[image:hydrogenNMRtable.png|thumb|The H NMR for the E Isomer|center|500px]]

Overall, a relatively good fit was obtained for the C13 NMR, aside from a few gaps and differences. Bearing in mind that in the literature model, the compound may as well be contaminated, so certain shifts are likely to be missing, or extra shifts may be seen in this case. However in general, the ppm of literature and calculated values are within 5 ppm.

The H NMR however pose a larger problem as there are a lot more missing numbers from the literature value. However the values that fit the literature are good.

The NMR for the Z isomer was calculated: [[http://hdl.handle.net/10042/23225]] and the J coupling [[http://hdl.handle.net/10042/23236]]

[[image:C13NMR.png|thumb|The C13 NMR for the Z Isomer|left|500px]] [[image:HNMRisomerz.png|thumb|The H NMR for the Z Isomer|500px|center]]

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]]

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

Rep:Mod:Skilganon2

2013-02-08T13:44:59Z

Ec1210: /* Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule */

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing). Overall sugar A is more likely to be selected during a reaction because of neighbouring group participation.

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23116]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23117]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

[[image:TaxolNMRpic.png|thumb|The NMR for Taxol|left|500px]]

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate. The molecule on the left is called (Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide and the molecule on the right is (E)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide.

(Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide is produced by first using solution of (Z)-2′,4′,6′-trimethoxystyryl-4-methoxy-3-nitrobenzyl sulfide (11, 0.5 g, 1.3 mmol) in 40 mL of glacial acetic acid was cooled to 5 °C on an ice bath. Hydrogenperoxide 30% w/v (0.20 mL, 2.0 mmol) was added and the
mixture was stirred at 5 °C for 6 h. After completion of thereaction, 10% sodium hydrogen carbonate solution (25 mL)was added slowly and stirred for 10 min and extracted with ethyl acetate. The organic layer was washed with water (2 × 25 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by column chromatography (hexane/ethyl acetate) to obtain the title compound.

The compound is further reduced using any reduction method to add a double bond O to the S atom.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation: [[http://hdl.handle.net/10042/23172]] the J coupling was calculated as well! [[http://hdl.handle.net/10042/23237]]

[[image:C13NMRtable.png|thumb|The C13 NMR for the E Isomer|left|500px]]

[[image:hydrogenNMRtable.png|thumb|The H NMR for the E Isomer|center|500px]]

Overall, a relatively good fit was obtained for the C13 NMR, aside from a few gaps and differences. Bearing in mind that in the literature model, the compound may as well be contaminated, so certain shifts are likely to be missing, or extra shifts may be seen in this case. However in general, the ppm of literature and calculated values are within 5 ppm.

The H NMR however pose a larger problem as there are a lot more missing numbers from the literature value. However the values that fit the literature are good.

The NMR for the Z isomer was calculated: [[http://hdl.handle.net/10042/23225]] and the J coupling [[http://hdl.handle.net/10042/23236]]

[[image:C13NMR.png|thumb|The C13 NMR for the Z Isomer|left|500px]] [[image:HNMRisomerz.png|thumb|The H NMR for the Z Isomer|500px|center]]

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]]

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

File:TaxolNMRpic.png

2013-02-08T13:41:41Z

Ec1210:

Rep:Mod:Skilganon2

2013-02-08T13:40:47Z

Ec1210:

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing). Overall sugar A is more likely to be selected during a reaction because of neighbouring group participation.

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23116]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23117]]

[[image:TaxolNMRpic.png|thumb|The C13 NMR for the E Isomer|left|500px]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate. The molecule on the left is called (Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide and the molecule on the right is (E)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide.

(Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide is produced by first using solution of (Z)-2′,4′,6′-trimethoxystyryl-4-methoxy-3-nitrobenzyl sulfide (11, 0.5 g, 1.3 mmol) in 40 mL of glacial acetic acid was cooled to 5 °C on an ice bath. Hydrogenperoxide 30% w/v (0.20 mL, 2.0 mmol) was added and the
mixture was stirred at 5 °C for 6 h. After completion of thereaction, 10% sodium hydrogen carbonate solution (25 mL)was added slowly and stirred for 10 min and extracted with ethyl acetate. The organic layer was washed with water (2 × 25 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by column chromatography (hexane/ethyl acetate) to obtain the title compound.

The compound is further reduced using any reduction method to add a double bond O to the S atom.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation: [[http://hdl.handle.net/10042/23172]] the J coupling was calculated as well! [[http://hdl.handle.net/10042/23237]]

[[image:C13NMRtable.png|thumb|The C13 NMR for the E Isomer|left|500px]]

[[image:hydrogenNMRtable.png|thumb|The H NMR for the E Isomer|center|500px]]

Overall, a relatively good fit was obtained for the C13 NMR, aside from a few gaps and differences. Bearing in mind that in the literature model, the compound may as well be contaminated, so certain shifts are likely to be missing, or extra shifts may be seen in this case. However in general, the ppm of literature and calculated values are within 5 ppm.

The H NMR however pose a larger problem as there are a lot more missing numbers from the literature value. However the values that fit the literature are good.

The NMR for the Z isomer was calculated: [[http://hdl.handle.net/10042/23225]] and the J coupling [[http://hdl.handle.net/10042/23236]]

[[image:C13NMR.png|thumb|The C13 NMR for the Z Isomer|left|500px]] [[image:HNMRisomerz.png|thumb|The H NMR for the Z Isomer|500px|center]]

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]]

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

Rep:Mod:Skilganon2

2013-02-08T13:03:31Z

Ec1210: /* Comparison */

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing). Overall sugar A is more likely to be selected during a reaction because of neighbouring group participation.

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23116]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23117]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate. The molecule on the left is called (Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide and the molecule on the right is (E)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide.

(Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide is produced by first using solution of (Z)-2′,4′,6′-trimethoxystyryl-4-methoxy-3-nitrobenzyl sulfide (11, 0.5 g, 1.3 mmol) in 40 mL of glacial acetic acid was cooled to 5 °C on an ice bath. Hydrogenperoxide 30% w/v (0.20 mL, 2.0 mmol) was added and the
mixture was stirred at 5 °C for 6 h. After completion of thereaction, 10% sodium hydrogen carbonate solution (25 mL)was added slowly and stirred for 10 min and extracted with ethyl acetate. The organic layer was washed with water (2 × 25 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by column chromatography (hexane/ethyl acetate) to obtain the title compound.

The compound is further reduced using any reduction method to add a double bond O to the S atom.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation: [[http://hdl.handle.net/10042/23172]] the J coupling was calculated as well! [[http://hdl.handle.net/10042/23237]]

[[image:C13NMRtable.png|thumb|The C13 NMR for the E Isomer|left|500px]]

[[image:hydrogenNMRtable.png|thumb|The H NMR for the E Isomer|center|500px]]

Overall, a relatively good fit was obtained for the C13 NMR, aside from a few gaps and differences. Bearing in mind that in the literature model, the compound may as well be contaminated, so certain shifts are likely to be missing, or extra shifts may be seen in this case. However in general, the ppm of literature and calculated values are within 5 ppm.

The H NMR however pose a larger problem as there are a lot more missing numbers from the literature value. However the values that fit the literature are good.

The NMR for the Z isomer was calculated: [[http://hdl.handle.net/10042/23225]] and the J coupling [[http://hdl.handle.net/10042/23236]]

[[image:C13NMR.png|thumb|The C13 NMR for the Z Isomer|left|500px]] [[image:HNMRisomerz.png|thumb|The H NMR for the Z Isomer|500px|center]]

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]]

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

Rep:Mod:Skilganon2

2013-02-08T12:49:53Z

Ec1210:

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing).

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23116]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23117]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate. The molecule on the left is called (Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide and the molecule on the right is (E)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide.

(Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide is produced by first using solution of (Z)-2′,4′,6′-trimethoxystyryl-4-methoxy-3-nitrobenzyl sulfide (11, 0.5 g, 1.3 mmol) in 40 mL of glacial acetic acid was cooled to 5 °C on an ice bath. Hydrogenperoxide 30% w/v (0.20 mL, 2.0 mmol) was added and the
mixture was stirred at 5 °C for 6 h. After completion of thereaction, 10% sodium hydrogen carbonate solution (25 mL)was added slowly and stirred for 10 min and extracted with ethyl acetate. The organic layer was washed with water (2 × 25 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by column chromatography (hexane/ethyl acetate) to obtain the title compound.

The compound is further reduced using any reduction method to add a double bond O to the S atom.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation: [[http://hdl.handle.net/10042/23172]] the J coupling was calculated as well! [[http://hdl.handle.net/10042/23237]]

[[image:C13NMRtable.png|thumb|The C13 NMR for the E Isomer|left|500px]]

[[image:hydrogenNMRtable.png|thumb|The H NMR for the E Isomer|center|500px]]

Overall, a relatively good fit was obtained for the C13 NMR, aside from a few gaps and differences. Bearing in mind that in the literature model, the compound may as well be contaminated, so certain shifts are likely to be missing, or extra shifts may be seen in this case. However in general, the ppm of literature and calculated values are within 5 ppm.

The H NMR however pose a larger problem as there are a lot more missing numbers from the literature value. However the values that fit the literature are good.

The NMR for the Z isomer was calculated: [[http://hdl.handle.net/10042/23225]] and the J coupling [[http://hdl.handle.net/10042/23236]]

[[image:C13NMR.png|thumb|The C13 NMR for the Z Isomer|left|500px]] [[image:HNMRisomerz.png|thumb|The H NMR for the Z Isomer|500px|center]]

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]]

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

Rep:Mod:Skilganon2

2013-02-08T12:44:17Z

Ec1210: /* Vibrational Analysis and Comparison */

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing).

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23116]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23117]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate. The molecule on the left is called (Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide and the molecule on the right is (E)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide.

(Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide is produced by first using solution of (Z)-2′,4′,6′-trimethoxystyryl-4-methoxy-3-nitrobenzyl sulfide (11, 0.5 g, 1.3 mmol) in 40 mL of glacial acetic acid was cooled to 5 °C on an ice bath. Hydrogenperoxide 30% w/v (0.20 mL, 2.0 mmol) was added and the
mixture was stirred at 5 °C for 6 h. After completion of thereaction, 10% sodium hydrogen carbonate solution (25 mL)was added slowly and stirred for 10 min and extracted with ethyl acetate. The organic layer was washed with water (2 × 25 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by column chromatography (hexane/ethyl acetate) to obtain the title compound.

The compound is further reduced using any reduction method to add a double bond O to the S atom.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation: [[http://hdl.handle.net/10042/23172]] the J coupling was calculated as well! [[http://hdl.handle.net/10042/23237]]

[[image:C13NMRtable.png|thumb|The C13 NMR for the E Isomer|left|500px]]

[[image:hydrogenNMRtable.png|thumb|The H NMR for the E Isomer|center|500px]]

Overall, a relatively good fit was obtained for the C13 NMR, aside from a few gaps and differences. Bearing in mind that in the literature model, the compound may as well be contaminated, so certain shifts are likely to be missing, or extra shifts may be seen in this case. However in general, the ppm of literature and calculated values are within 5 ppm.

The H NMR however pose a larger problem as there are a lot more missing numbers from the literature value. However the values that fit the literature are good.

The NMR for the Z isomer was calculated: [[http://hdl.handle.net/10042/23225]] and the J coupling [[http://hdl.handle.net/10042/23236]]

[[image:C13NMR.png|thumb|The C13 NMR for the Z Isomer|left|500px]] [[image:HNMRisomerz.png|thumb|The H NMR for the Z Isomer|500px]]

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]]

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

Rep:Mod:Skilganon2

2013-02-08T12:43:46Z

Ec1210: /* NMR Analysis and Comparison */

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing).

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23116]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23117]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate. The molecule on the left is called (Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide and the molecule on the right is (E)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide.

(Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide is produced by first using solution of (Z)-2′,4′,6′-trimethoxystyryl-4-methoxy-3-nitrobenzyl sulfide (11, 0.5 g, 1.3 mmol) in 40 mL of glacial acetic acid was cooled to 5 °C on an ice bath. Hydrogenperoxide 30% w/v (0.20 mL, 2.0 mmol) was added and the
mixture was stirred at 5 °C for 6 h. After completion of thereaction, 10% sodium hydrogen carbonate solution (25 mL)was added slowly and stirred for 10 min and extracted with ethyl acetate. The organic layer was washed with water (2 × 25 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by column chromatography (hexane/ethyl acetate) to obtain the title compound.

The compound is further reduced using any reduction method to add a double bond O to the S atom.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation: [[http://hdl.handle.net/10042/23172]] the J coupling was calculated as well! [[http://hdl.handle.net/10042/23237]]

[[image:C13NMRtable.png|thumb|The C13 NMR for the E Isomer|left|500px]]

[[image:hydrogenNMRtable.png|thumb|The H NMR for the E Isomer|center|500px]]

Overall, a relatively good fit was obtained for the C13 NMR, aside from a few gaps and differences. Bearing in mind that in the literature model, the compound may as well be contaminated, so certain shifts are likely to be missing, or extra shifts may be seen in this case. However in general, the ppm of literature and calculated values are within 5 ppm.

The H NMR however pose a larger problem as there are a lot more missing numbers from the literature value. However the values that fit the literature are good.

The NMR for the Z isomer was calculated: [[http://hdl.handle.net/10042/23225]] and the J coupling [[http://hdl.handle.net/10042/23236]]

[[image:C13NMR.png|thumb|The C13 NMR for the Z Isomer|left|500px]] [[image:HNMRisomerz.png|thumb|The H NMR for the Z Isomer|500px]]

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]]

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

Rep:Mod:Skilganon2

2013-02-08T12:42:41Z

Ec1210: /* Molecule of choice for study */

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing).

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23116]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23117]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate. The molecule on the left is called (Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide and the molecule on the right is (E)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide.

(Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide is produced by first using solution of (Z)-2′,4′,6′-trimethoxystyryl-4-methoxy-3-nitrobenzyl sulfide (11, 0.5 g, 1.3 mmol) in 40 mL of glacial acetic acid was cooled to 5 °C on an ice bath. Hydrogenperoxide 30% w/v (0.20 mL, 2.0 mmol) was added and the
mixture was stirred at 5 °C for 6 h. After completion of thereaction, 10% sodium hydrogen carbonate solution (25 mL)was added slowly and stirred for 10 min and extracted with ethyl acetate. The organic layer was washed with water (2 × 25 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by column chromatography (hexane/ethyl acetate) to obtain the title compound.

The compound is further reduced using any reduction method to add a double bond O to the S atom.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation: [[http://hdl.handle.net/10042/23172]] the J coupling was calculated as well! [[http://hdl.handle.net/10042/23237]]

[[image:C13NMRtable.png|thumb|The C13 NMR for the E Isomer|left|500px]]

[[image:hydrogenNMRtable.png|thumb|The H NMR for the E Isomer|center|500px]]

Overall, a relatively good fit was obtained for the C13 NMR, aside from a few gaps and differences. Bearing in mind that in the literature model, the compound may as well be contaminated, so certain shifts are likely to be missing, or extra shifts may be seen in this case. However in general, the ppm of literature and calculated values are within 5 ppm.

The H NMR however pose a larger problem as there are a lot more missing numbers from the literature value. However the values that fit the literature are good.

The NMR for the Z isomer was calculated: [[http://hdl.handle.net/10042/23225]] and the J coupling [[http://hdl.handle.net/10042/23236]]

[[image:C13NMR.png|thumb|The C13 NMR for the Z Isomer|left|500px]] [[image:HNMRisomerz.png|thumb|The H NMR for the Z Isomer|right|500px]]

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]]

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

Rep:Mod:Skilganon2

2013-02-08T12:42:17Z

Ec1210: /* Molecule of choice for study */

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing).

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23116]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23117]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate. The molecule on the left is called (Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide and the molecule on the right is (E)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide.

(Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide is produced by first using solution of (Z)-2′,4′,6′-trimethoxystyryl-4-methoxy-3-nitrobenzyl sulfide (11, 0.5 g, 1.3 mmol) in 40 mL of glacial acetic acid was cooled to 5 °C on an ice bath. Hydrogenperoxide 30% w/v (0.20 mL, 2.0 mmol) was added and the
mixture was stirred at 5 °C for 6 h. After completion of thereaction, 10% sodium hydrogen carbonate solution (25 mL)was added slowly and stirred for 10 min and extracted with ethyl acetate. The organic layer was washed with water (2 × 25 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by column chromatography (hexane/ethyl acetate) to obtain the title compound.

The compound is further reduced using any reduction method to add a double bond O to the S atom.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation: [[http://hdl.handle.net/10042/23172]] the J coupling was calculated as well! [[http://hdl.handle.net/10042/23237]]

[[image:C13NMRtable.png|thumb|The C13 NMR for the E Isomer|left|500px]]

[[image:hydrogenNMRtable.png|thumb|The H NMR for the E Isomer|center|500px]]

Overall, a relatively good fit was obtained for the C13 NMR, aside from a few gaps and differences. Bearing in mind that in the literature model, the compound may as well be contaminated, so certain shifts are likely to be missing, or extra shifts may be seen in this case. However in general, the ppm of literature and calculated values are within 5 ppm.

The H NMR however pose a larger problem as there are a lot more missing numbers from the literature value. However the values that fit the literature are good.

The NMR for the Z isomer was calculated: [[http://hdl.handle.net/10042/23225]] and the J coupling [[http://hdl.handle.net/10042/23236]]

[[image:C13NMR.png|thumb|The C13 NMR for the Z Isomer|left|500px]] [[image:HNMRisomerz.png|thumb|The H NMR for the Z Isomer|right|500px]]

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]]

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

Rep:Mod:Skilganon2

2013-02-08T12:39:03Z

Ec1210: /* Molecule of choice for study */

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing).

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23116]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23117]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate. The molecule on the left is called (Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide and the molecule on the right is (E)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide.

(Z)-2′,4′,6′-Trimethoxystyryl-4-methoxy-3-aminobenzyl sulfoxide is produced by first using solution of (Z)-2′,4′,6′-trimethoxystyryl-4-methoxy-3-nitrobenzyl sulfide (11, 0.5 g, 1.3 mmol) in 40 mL of glacial acetic acid was cooled to 5 °C on an ice bath. Hydrogenperoxide 30% w/v (0.20 mL, 2.0 mmol) was added and the
mixture was stirred at 5 °C for 6 h. After completion of thereaction, 10% sodium hydrogen carbonate solution (25 mL)was added slowly and stirred for 10 min and extracted with ethyl acetate. The organic layer was washed with water (2 × 25 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by column chromatography (hexane/ethyl acetate) to obtain the title compound.

The compound is further reduced using any reduction method to add a double bond O to the S atom.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation: [[http://hdl.handle.net/10042/23172]] the J coupling was calculated as well! [[http://hdl.handle.net/10042/23237]]

[[image:C13NMRtable.png|thumb|The C13 NMR for the E Isomer|left|500px]]

[[image:hydrogenNMRtable.png|thumb|The H NMR for the E Isomer|center|500px]]

Overall, a relatively good fit was obtained for the C13 NMR, aside from a few gaps and differences. Bearing in mind that in the literature model, the compound may as well be contaminated, so certain shifts are likely to be missing, or extra shifts may be seen in this case. However in general, the ppm of literature and calculated values are within 5 ppm.

The H NMR however pose a larger problem as there are a lot more missing numbers from the literature value. However the values that fit the literature are good.

The NMR for the Z isomer was calculated: [[http://hdl.handle.net/10042/23225]] and the J coupling [[http://hdl.handle.net/10042/23236]]

[[image:C13NMR.png|thumb|The C13 NMR for the Z Isomer|left|500px]] [[image:HNMRisomerz.png|thumb|The H NMR for the Z Isomer|right|500px]]

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]]

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

File:HNMRisomerz.png

2013-02-08T12:22:27Z

Ec1210:

Rep:Mod:Skilganon2

2013-02-08T12:21:31Z

Ec1210: /* NMR Analysis and Comparison */

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing).

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23116]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23117]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation: [[http://hdl.handle.net/10042/23172]] the J coupling was calculated as well! [[http://hdl.handle.net/10042/23237]]

[[image:C13NMRtable.png|thumb|The C13 NMR for the E Isomer|left|500px]]

[[image:hydrogenNMRtable.png|thumb|The H NMR for the E Isomer|center|500px]]

Overall, a relatively good fit was obtained for the C13 NMR, aside from a few gaps and differences. Bearing in mind that in the literature model, the compound may as well be contaminated, so certain shifts are likely to be missing, or extra shifts may be seen in this case. However in general, the ppm of literature and calculated values are within 5 ppm.

The H NMR however pose a larger problem as there are a lot more missing numbers from the literature value. However the values that fit the literature are good.

The NMR for the Z isomer was calculated: [[http://hdl.handle.net/10042/23225]] and the J coupling [[http://hdl.handle.net/10042/23236]]

[[image:C13NMR.png|thumb|The C13 NMR for the Z Isomer|left|500px]] [[image:HNMRisomerz.png|thumb|The H NMR for the Z Isomer|right|500px]]

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]]

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

File:HNMRisomerZ.txt

2013-02-08T12:19:38Z

Ec1210:

Rep:Mod:Skilganon2

2013-02-08T12:18:58Z

Ec1210: /* NMR Analysis and Comparison */

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing).

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23116]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23117]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation: [[http://hdl.handle.net/10042/23172]] the J coupling was calculated as well! [[http://hdl.handle.net/10042/23237]]

[[image:C13NMRtable.png|thumb|The C13 NMR for the E Isomer|left|500px]]

[[image:hydrogenNMRtable.png|thumb|The H NMR for the E Isomer|center|500px]]

Overall, a relatively good fit was obtained for the C13 NMR, aside from a few gaps and differences. Bearing in mind that in the literature model, the compound may as well be contaminated, so certain shifts are likely to be missing, or extra shifts may be seen in this case. However in general, the ppm of literature and calculated values are within 5 ppm.

The H NMR however pose a larger problem as there are a lot more missing numbers from the literature value. However the values that fit the literature are good.

The NMR for the Z isomer was calculated: [[http://hdl.handle.net/10042/23225]] and the J coupling [[http://hdl.handle.net/10042/23236]]

[[image:C13NMR.png|thumb|The C13 NMR for the Z Isomer|left|500px]] [[image:HNMRisomerZ.png|thumb|The H NMR for the Z Isomer|right|500px]]

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]]

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

File:C13NMR.png

2013-02-08T12:02:48Z

Ec1210:

Rep:Mod:Skilganon2

2013-02-08T12:01:13Z

Ec1210: /* NMR Analysis and Comparison */

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing).

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23116]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23117]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation: [[http://hdl.handle.net/10042/23172]] the J coupling was calculated as well! [[http://hdl.handle.net/10042/23237]]

[[image:C13NMRtable.png|thumb|The C13 NMR for the E Isomer|left|500px]]

[[image:hydrogenNMRtable.png|thumb|The H NMR for the E Isomer|center|500px]]

Overall, a relatively good fit was obtained for the C13 NMR, aside from a few gaps and differences. Bearing in mind that in the literature model, the compound may as well be contaminated, so certain shifts are likely to be missing, or extra shifts may be seen in this case. However in general, the ppm of literature and calculated values are within 5 ppm.

The H NMR however pose a larger problem as there are a lot more missing numbers from the literature value. However the values that fit the literature are good.

The NMR for the Z isomer was calculated: [[http://hdl.handle.net/10042/23225]] and the J coupling [[http://hdl.handle.net/10042/23236]]

[[image:C13NMR.png|thumb|The C13 NMR for the Z Isomer|left|500px]]

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]]

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

Rep:Mod:Skilganon2

2013-02-08T11:45:27Z

Ec1210: /* NMR Analysis and Comparison */

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing).

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23116]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23117]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation: [[http://hdl.handle.net/10042/23172]] the J coupling was calculated as well! [[http://hdl.handle.net/10042/23237]]

[[image:C13NMRtable.png|thumb|The C13 NMR for the E Isomer|left|500px]]

[[image:hydrogenNMRtable.png|thumb|The H NMR for the E Isomer|center|500px]]

Overall, a relatively good fit was obtained for the C13 NMR, aside from a few gaps and differences. Bearing in mind that in the literature model, the compound may as well be contaminated, so certain shifts are likely to be missing, or extra shifts may be seen in this case. However in general, the ppm of literature and calculated values are within 5 ppm.

The H NMR however pose a larger problem as there are a lot more missing numbers from the literature value. However the values that fit the literature are good.

The NMR for the Z isomer was calculated: [[http://hdl.handle.net/10042/23225]] and the J coupling [[http://hdl.handle.net/10042/23236]]

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]]

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

Rep:Mod:Skilganon2

2013-02-08T11:41:47Z

Ec1210: /* NMR Analysis and Comparison */

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing).

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23116]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23117]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation: [[http://hdl.handle.net/10042/23172]] the J coupling was calculated as well! [[http://hdl.handle.net/10042/23237]]

[[image:C13NMRtable.png|thumb|The C13 NMR for the E Isomer|left|500px]]

[[image:hydrogenNMRtable.png|thumb|The H NMR for the E Isomer|center|500px]]

Overall, a relatively good fit was obtained for the C13 NMR, aside from a few gaps and differences. Bearing in mind that in the literature model, the compound may as well be contaminated, so certain shifts are likely to be missing, or extra shifts may be seen in this case. However in general, the ppm of literature and calculated values are within 5 ppm.

The H NMR however pose a larger problem as there are a lot more missing numbers from the literature value. However the values that fit the literature are good.

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]]

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

Rep:Mod:Skilganon2

2013-02-08T11:35:23Z

Ec1210: /* NMR Analysis and Comparison */

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing).

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23116]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23117]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation: [[http://hdl.handle.net/10042/23172]] the J coupling was calculated as well! [[http://hdl.handle.net/10042/23237]]

[[image:C13NMRtable.png|thumb|The C13 NMR for the E Isomer|left|500px]]

[[image:hydrogenNMRtable.png|thumb|The H NMR for the E Isomer|center|500px]]

Overall, a relatively good fit was obtained for the C13 NMR, aside from a few gaps and differences. Bearing in mind that in the literature model, the compound may as well be contaminated, so certain shifts are likely to be missing, or extra shifts may be seen in this case.

The H NMR however pose a larger problem as there are a lot more missing numbers from the literature value. However the values that fit the literature are good.

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]]

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

Rep:Mod:Skilganon2

2013-02-08T11:33:08Z

Ec1210: /* NMR Analysis and Comparison */

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing).

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23116]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23117]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation: [[http://hdl.handle.net/10042/23172]]

[[image:C13NMRtable.png|thumb|The C13 NMR for the E Isomer|left|500px]]

[[image:hydrogenNMRtable.png|thumb|The H NMR for the E Isomer|center|500px]]

Overall, a relatively good fit was obtained for the C13 NMR, aside from a few gaps and differences. Bearing in mind that in the literature model, the compound may as well be contaminated, so certain shifts are likely to be missing, or extra shifts may be seen in this case.

The H NMR however pose a larger problem as there are a lot more missing numbers from the literature value. However the values that fit the literature are good.

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]]

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

Rep:Mod:Skilganon2

2013-02-08T11:28:15Z

Ec1210: /* NMR Analysis and Comparison */

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing).

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23116]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23117]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation: [[ http://hdl.handle.net/10042/23172]]

[[image:C13NMRtable.png|thumb|The C13 NMR for the E Isomer|left|500px]]

[[image:hydrogenNMRtable.png|thumb|The H NMR for the E Isomer|center|500px]]

Overall, a relatively good fit was obtained for the C13 NMR, aside from a few gaps and differences. Bearing in mind that in the literature model, the compound may as well be contaminated, so certain shifts are likely to be missing, or extra shifts may be seen in this case.

The H NMR however pose a larger problem as there are a lot more missing numbers from the literature value. However the values that fit the literature are good.

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]]

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

Rep:Mod:Skilganon2

2013-02-08T11:26:58Z

Ec1210: /* NMR Analysis and Comparison */

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing).

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23116]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23117]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation

[[image:C13NMRtable.png|thumb|The C13 NMR for the E Isomer|left|500px]]

[[image:hydrogenNMRtable.png|thumb|The H NMR for the E Isomer|center|500px]]

Overall, a relatively good fit was obtained for the C13 NMR, aside from a few gaps and differences. Bearing in mind that in the literature model, the compound may as well be contaminated, so certain shifts are likely to be missing, or extra shifts may be seen in this case.

The H NMR however pose a larger problem as there are a lot more missing numbers from the literature value. However the values that fit the literature are good.

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]]

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

Rep:Mod:Skilganon2

2013-02-08T11:26:08Z

Ec1210: /* NMR Analysis and Comparison */

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing).

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23116]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23117]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation

[[image:C13NMRtable.png|thumb|The C13 NMR for the E Isomer|left|500px]]

[[image:hydrogenNMRtable.png|thumb|The H NMR for the E Isomer|left|500px]]

Overall, a relatively good fit was obtained for the C13 NMR, aside from a few gaps and differences. Bearing in mind that in the literature model, the compound may as well be contaminated, so certain shifts are likely to be missing, or extra shifts may be seen in this case.

The H NMR however pose a larger problem as there are a lot more missing numbers from the literature value. However the values that fit the literature are good.

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]]

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

File:C13NMRtable.png

2013-02-08T11:18:25Z

Ec1210:

Rep:Mod:Skilganon2

2013-02-08T11:16:27Z

Ec1210: /* NMR Analysis and Comparison */

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing).

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23116]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23117]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation

[[image:C13NMRtable.png|thumb|The C13 NMR for the E Isomer|left]]

[[image:hydrogenNMRtable.png|thumb|The H NMR for the E Isomer|left]]

Overall, a relatively good fit was obtained, aside from a few gaps and differences. Bearing in mind that in the literature model, the compound may as well be contaminated, so certain shifts are likely to be missing, or extra shift may be seen in this case.

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]]

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

File:HydrogenNMRtable.png

2013-02-08T11:04:19Z

Ec1210:

Rep:Mod:Skilganon2

2013-02-08T11:00:27Z

Ec1210: /* NMR Analysis and Comparison */

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing).

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23116]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23117]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation

{| class="wikitable"
|-
! Calculated Shift(ppm) !! Literature Shift !! Anomaly
|-
| 157.8 || 162.2 ||
|-
| 155.59 || 160.5 ||
|-
| 153.64 || 147.3 ||
|-
| 140.70 || 136.3 ||
|-
| 132.64 || 130.2 ||
|-
| 129.74 || 127.9 ||
|-
| 125.94 || 123.3 ||
|-
| 123.47 || 123 ||
|-
| 114.76 || 116.7 || 120.4
|-
| 110.95 || 110.4 ||
|-
| 105.97 || 105.3 ||
|-
| 103.61 || none ||
|-
| 89.2 || 90.4 ||
|-
| 83.96 || 61.4 ||
|-
| 55.72 || 55.7 ||
|-
| 53.95 || 55.5 ||
|-
| 53.51 || 55.4 ||
|-
| 53.12 || none ||
|-
| 52.70 || none ||
|}

[[image:hydrogenNMRtable.png||450px||thumb||The H NMR for the E Isomer|left]]

Overall, a relatively good fit was obtained, aside from a few gaps and differences. Bearing in mind that in the literature model, the compound may as well be contaminated, so certain shifts are likely to be missing, or extra shift may be seen in this case.

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]]

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

Rep:Mod:Skilganon2

2013-02-08T10:48:33Z

Ec1210: /* NMR Analysis and Comparison */

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing).

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23116]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23117]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation

{| class="wikitable"
|-
! Calculated Shift(ppm) !! Literature Shift !! Anomaly
|-
| 157.8 || 162.2 ||
|-
| 155.59 || 160.5 ||
|-
| 153.64 || 147.3 ||
|-
| 140.70 || 136.3 ||
|-
| 132.64 || 130.2 ||
|-
| 129.74 || 127.9 ||
|-
| 125.94 || 123.3 ||
|-
| 123.47 || 123 ||
|-
| 114.76 || 116.7 || 120.4
|-
| 110.95 || 110.4 ||
|-
| 105.97 || 105.3 ||
|-
| 103.61 || none ||
|-
| 89.2 || 90.4 ||
|-
| 83.96 || 61.4 ||
|-
| 55.72 || 55.7 ||
|-
| 53.95 || 55.5 ||
|-
| 53.51 || 55.4 ||
|-
| 53.12 || none ||
|-
| 52.70 || none ||
|}

Overall, a relatively good fit was obtained, aside from a few gaps and differences. Bearing in mind that in the literature model, the compound may as well be contaminated, so certain shifts are likely to be missing, or extra shift may be seen in this case.

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]]

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

Rep:Mod:Skilganon2

2013-02-08T10:45:51Z

Ec1210:

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing).

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23116]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23117]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation

{| class="wikitable"
|-
! Calculated Shift(ppm) !! Literature Shift !! Anomaly
|-
| 157.8 || 162.2 ||
|-
| 155.59 || 160.5 ||
|-
| 153.64 || 147.3 ||
|-
| 140.70 || 136.3 ||
|-
| 132.64 || 130.2 ||
|-
| 129.74 || 127.9 ||
|-
| 125.94 || 123.3 ||
|-
| 123.47 || 123 ||
|-
| 114.76 || 116.7 || 120.4
|-
| 110.95 || 110.4 ||
|-
| 105.97 || 105.3 ||
|-
| 103.61 || none ||
|-
| 89.2 || 90.4 ||
|-
| 83.96 || 61.4 ||
|-
| 55.72 || 55.7 ||
|-
| 53.95 || 55.5 ||
|-
| 53.51 || 55.4 ||
|-
| 53.12 || none ||
|-
| 52.70 || none ||
|}

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]]

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

Rep:Mod:Skilganon2

2013-02-08T10:23:27Z

Ec1210: /* NMR Analysis and Comparison */

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing).

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23116]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23117]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer. For the Isomer with E conformation

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]]

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

Rep:Mod:Skilganon2

2013-02-08T10:05:51Z

Ec1210: /* NMR Analysis and Comparison */

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing).

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23116]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23117]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====
The NMR was generated from the optimised geometry of the isomer.

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]]

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.

Rep:Mod:Skilganon2

2013-02-08T09:41:52Z

Ec1210: /* Spectroscopy of an Intermediate related to the Synthesis of Taxol */

==The Hydrogenation of Cyclopentadiene Dimer==
===Endo versus Exo Cyclopentadiene===
The Calculated <jmolFile text="Endo conformation of Cyclopentadiene(conformation 2)">Cyclopenta2.mol</jmolFile>:

Stretch: 1.2507
Bend: 20.8483
Stretch-Bend: -0.8357
Torsion: 9.5109
Non-1,4 VDW: -1.5449
1,4 VDW: 4.3206
Dipole/Dipole: 0.4477
Total Energy: 33.9975 kcal/mol

and the calculated <jmolFile text="Exo conformation of Cyclopentadiene(conformation 1)">Cyclopenta1.mol</jmolFile>:

Stretch: 1.2856
Bend: 20.5792
Stretch-Bend: -0.8380
Torsion: 7.6571
Non-1,4 VDW: -1.4171
1,4 VDW: 4.2322
Dipole/Dipole: 0.3776
Total Energy: 31.8766 kcal/mol

The largest contribution towards the difference in energy is the torsion angle. The exo product is more stable by virtue of torsional strain(lower degree of steric congestion), while the endo product is favoured by orbital overlap in the transition state. As a general rule, kinetic control takes place in the endo conformation, while the exo isomer(more thermodinamically stable) forms at a higher temperature.

However, the selectivity at room temperature is dictated by Baldwin's Rule, and in this case a favoured transition state geometry for effective orbital overlap is more desirable, and the endo isomer is the main product. At higher temperature, the thermodinamically more stable product is formed.

It should also be noted that Bredt's rule plays a role in determining the shape of the molecules. Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough.

===Selectivity of the Hydrogenation of the Endo Dimer===
The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 4(conformation 4)">Cyclopenta4.mol</jmolFile>:
Stretch: 1.0969
Bend: 14.5214
Stretch-Bend: -0.5493
Torsion: 12.4985
Non-1,4 VDW: -1.0679
1,4 VDW: 4.5119
Dipole/Dipole: 0.1406
Total Energy: 31.1520 kcal/mol

The Calculated <jmolFile text="Hydrogenation for Dihydro Derivative 3(conformation 3)">Cyclopenta3.mol</jmolFile>:
Stretch: 1.2756
Bend: 19.8651
Stretch-Bend: -0.8339
Torsion: 10.8082
Non-1,4 VDW: -1.2242
1,4 VDW: 5.6322
Dipole/Dipole: 0.1621
Total Energy: 35.6851 kcal/mol

From the calculation above it appears that the conformation 4 endo dimer is the more stable substituted dimer between the two. There is a large difference in energy between the two different substituted compounds. The bending energy contributes the largest to the difference(approximately 5.3kcal/mol), while the torsional is the next largest contribution to the difference. This could be explained by the shapes of both the conformer - by observing conformation 3 (pentadiene substituted compound) we can see an upwards twist in the furthest carbon atom. This suggests that the substituted conformer is highly strained and relieves its pressure by bending upwards, which explains its high torsional strain.

At room temperature, conformation 3 is more likely to exist, whereas at higher temperatures, the more stable conformer 4 takes place due to equilibrium.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
Both the taxols seen below are different only in the position of the carbonyl group. The conformation seen below has its carbonyl group positioned directly anti syn to the neighbouring hydrogen, the calculated energy is seen directly below:

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>taxing1011.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.6340
Bend: 13.9694
Stretch-Bend: 0.3504
Torsion: 20.9828
Non-1,4 VDW: -1.5695
1,4 VDW: 13.9405
Dipole/Dipole: -1.5838
Total Energy: 48.7238 kcal/mol

And the MMFF94 Minimisation shows a slightly higher value:
Final Energy: 66.6127 kcal/mol

The conformation below has its carbonyl group in a gauche position to the Hydrogens. It would appear that the calculation suggests that this conformation is slightly less stable than the above conformation. The torsional strain in the above conformation is lower than the torsional strain of the below conformation, which is expected. The difference that contributes to the slight instability in the above conformation is the Bending Energy. A few calculations were run as seen below as we noticed that by constantly tweaking the conformation ever so slightly, one could obtain an arguably more stable conformation.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>taxing9.5.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 3.1541
Bend: 19.0350
Stretch-Bend: 0.4464
Torsion: 23.4580
Non-1,4 VDW: 0.0933
1,4 VDW: 15.5402
Dipole/Dipole: -1.8340
Total Energy: 59.8929 kcal/mol

Stretch: 3.2568
Bend: 19.2504
Stretch-Bend: 0.3323
Torsion: 20.6342
Non-1,4 VDW: 0.7632
1,4 VDW: 15.3755
Dipole/Dipole: -1.8297
Total Energy: 57.7828 kcal/mol

MM2FF94: Final Energy: 81.2911 kcal/mol

Another conformation was tested to check the validity of the stability of the conformations. It appeared that <jmolFile text="this conformation">taxing9.mol</jmolFile> yielded an unnaturally high instability contributed by the non-1,4 VDW forces. its Van Der Waals forces were increased rather significantly as well, along with the Bend energy:

Stretch: 6.6322
Bend: 85.5655
Stretch-Bend: -0.2209
Torsion: 20.7717
Non-1,4 VDW: 1.4946
1,4 VDW: 31.4737
Dipole/Dipole: -2.7389
Total Energy: 142.9778 kcal/mol

This conformation is almost similar to the most stable conformation above, which goes on to show that the conformers must be at an exact position for it to be stable. The difference in MM2FF94 is due to the different methods used in the calculations. However, that is of little concern as the energies are still comparable relative to one another.

A highly unusual feature about this system is that it violates the brett's rule, which states that bridges are unlikely to form adjacent to alkenes. However both isomers are relatively stable compounds... this could be explained by presence of hyperstable alkenes. Olefinic strain contributes to the stability of the overall alkene system, the strain is caused by the change in structure between the alkene group i.e twisting, decreasing the HOMO-LUMO gap significantly and thus increasing reactivity. Hyperalkenes serve as an opposite of the olefinic strain, in which the MO is so stable that reactivity does not occur. This is because of the shape of the aromatic, in which it is stretched tightly, therefore the carbon double bond alkene cannot undergo twisting - the isomer is therefore unreactive.

==Modelling Using Semi-empirical Molecular Orbital Theory==
The endo stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. Therefore, the Semi-empirical MO theory could illustrate the electronic aspects of reactivity, showing how the molecular orbitals should be taken into account for a holistic method of calculation, and how electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene to a diene===
The first molecule was minimised using <jmolFile text="molecular mechanics">DieneMM.mol</jmolFile> while the second was minimised using <jmolFile text="MOPAC">DieneMopac.mol</jmolFile>. <jmolFile text="Overlay of both method of calculation">DieneMopacOverCorr.mol</jmolFile>.

<pre>
1 C(9)-C(34) 0.1194
1 Cl(12)-Cl(37) 0.1074
1 C(1)-C(26) 0.0963
1 H(25)-H(50) 0.1180
1 C(5)-C(30) 0.0904
1 C(4)-C(29) 0.0411
</pre>

From the detailed calculation above we can see that there is an anchor point carbon 4 and carbon 29 in which both atoms overlay each other well. The largest difference in overlay is seen in carbon 9-carbon 34 and the hydrogen atom 25 and 50. The large difference in the zone shows that the MO effect is more pronounced in these regions and the Molecular Mechanics method of calculation is no longer accurate enough to give us an overall representation.

===Molecular Orbital Analysis of the Diene===
The Molecular Orbital of the Diene was generated using MOPAC method of calculation. The HOMO-1, LUMO, LUMO+1, and LUMO of the MO are seen as below.

{| class="wikitable"
|-
! !! !!
|-
| [[image:DieneHOMO-1aa.png|thumb|HOMO-1|375px|left]] || [[image:DieneHOMOaa.png|thumb|HOMO|375px|center]] || [[image:DieneLUMOaa.png|thumb|LUMO|375px|right]]
|-
| [[image:DieneLUMO+1aa.png|thumb|LUMO+1|375px|left]] || [[image:DieneLUMO+2aa.png|thumb|LUMO+2|375px|center]] ||
|}

The HOMO-1 reflects the molecular symmetry well - overall we can see a relatively strong overall bonding between the MO's as compared to the HOMO, which makes sense as it is more stable overall than the HOMO. For the LUMO level, we start seeing an increase in antibonding MO particularly around the marked(yellow) hydrogen carbon group and its adjacent group, the MO symmetry still retains its shape, therefore the analysis is valid. There is a marked distinction between the LUMO and the LUMO+1 level of the diene - in the LUMO+1 there is a distinct increase in the antibonding orbitals seen opposite the (yellow) hydrogen bond. The orbital symmetry however is retained and is similar to the ones above. Finally, the LUMO+2 has extremely strong antibonding MO's, the red MO's around the aromatic ring is sandwiched between the 2 orbitals, creating a very strong antibonding energy and thus the energy is more unstable. Again, the symmetry is retained in the structure.

===Molecular Electrostatic Potential===
[[image:DieneElectrostaticPot.png|400px|thumb|The Electrostatic Potential Surface of Diene|center]]

The Molecular electrostatic potential is seen as above, the potential was adjusted to show a clear contour between two electrostatic potential. The red surface represents the delocalised electron density. The chlorine atom, which is highly electronegative, is seen surrounded by a blue surface. As there is a distinct difference in the molecular electrostatic potential, the chlorine atom will constantly attract the electron density surrounding the aromatic to form an even contour.

From the diagram we can deduce that the molecular attack will occur from the endo position(opposite to the coloured hydrogen).

===Molecular Vibration===
The <jmolFile text="Molecular Vibration ">Dienelog.log</jmolFile> [[http://hdl.handle.net/10042/23116]] was calculated via SCAN, and 69 different modes of vibrations were obtained, for convenience sake, we will just use frequencies with the highest intensities.

{| class="wikitable"
|-
! Vibration !! Intensity !! Frequency !! Description
|-
| [[image:Diene689.48.53.3587.gif]] || 689.48 || 53.3587 ||Significant Observation: There is no significant vibration observed for this vibration other than the vibration of hydrogen atoms. The high intensity observed is due to the fact that the hydrogen atoms vibrate vigorously.
|-
| [[image:diene770.86.25.1303.gif]] || 770.86 || 25.1303 ||Significant Observation: The carbon atom connected the chlorine atom vibrate vigorously from left to right, in a 'pump' motion, all the hydrogens vibrate back and fourth.
|-
| [[image:diene3033.65.62.7726.gif]] || 3033.65 || 62.7726 ||Significant Observation: In this mode of vibration, there are 4 hydrogen atoms in each aromatic(2 pairs opposite to each other) undergoing stretching, all the other hydrogen atoms remain constant. The stretching of the hydrogen atoms is what causes the intensity to be very high(stretching is much stronger than vibration)
|-
| [[image:diene3178.73.35.1994.gif]] || 3178.73 || 35.1994 ||Significant Observation: Only 2 hydrogen atoms in the aromatic ring with C=C bond undergo stretching. This causes a large intensity peak in the spectrum.
|-
| [[image:770.86.25.1303Diene.gif]] || 770.86 || 25.1303 || Significant Observation: The chlorine atom vibrates back and fourth vigorously.
|-
| [[image:1737.04.4.1981diene.gif]] || 1737.04 || 4.1981 || Significant Observation: The alkene carbons stretches vigorously.
|-
| [[image:1757.34.3.9363diene.gif]] || 1757.34 || 3.9363 || Significant Observation: The alkene carbons stretches vigorously.
|}

[[image:dienevibrationalspectrum.png|1000px|thumb|The Vibrational Spectrum of Diene|center]]
The above shows the overall spectrum of the diene vibration. As explained above, the peaks are relatively clean except for a few modes vibration with exceptionally high reading.

The 1737.04 vibration is what causes endo reaction to take place, whereas the 1757.34 vibration is what causes the exo reaction to take place.

===Monosaccharide chemistry and the mechanism of gylcosidation===
[[image:Overallmonosaccscheme.png|400px|center|thumb|The General Scheme for Monosaccharide Chemistry and the Mechanism]] Gylcosidation reaction is highly specific. The stereochemistry of the C-OAc bond controls the stereochemical outcome of the C-Nu bond by nucleophilic attack. Therefore the objective of this analysis is to use MM2 and MOPAC to obtain a good calculation of the most stable stereoisomer.
====Conformation A====
=====MM2 Calculation=====

{| class="wikitable"
|-
! colspan="2" | Red Bond Stereoisomer Down
! colspan="2" | Red Bond Stereoisomer Up
|-
! Conformation 1
! Conformation 2
! Conformation 3
! Conformation 4
|-
| <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>MM1monosacc.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2c.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm3corrected.mol</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmm4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
| Stretch: 2.8056
Bend: 8.4179
Stretch-Bend: 0.9401
Torsion: 4.1742
Non-1,4 VDW: 2.3914
1,4 VDW: 19.4867
Charge/Dipole: -32.5978
Dipole/Dipole: 8.4465
Total Energy: 14.0647 kcal/mol
|| <pre> Stretch: 2.1932
Bend: 10.2062
Stretch-Bend: 0.8743
Torsion: 2.8637
Non-1,4 VDW: -1.7549
1,4 VDW: 19.3463
Charge/Dipole:-16.4796
Dipole/Dipole:5.6581
Total Energy:22.9073 kcal/mol </pre> || <pre>Stretch: 2.5429
Bend: 12.5313
Stretch-Bend: 1.0197
Torsion: 3.1358
Non-1,4 VDW: 0.3824
1,4 VDW: 19.2395
Charge/Dipole: -23.6631
Dipole/Dipole: 7.2601
Total Energy:22.4486 kcal/mol </pre> || <pre> Stretch: 2.2094
Bend: 10.5693
Stretch-Bend: 0.8279
Torsion: 2.0335
Non-1,4 VDW: -1.9149
1,4 VDW: 19.4674
Charge/Dipole: -17.5154
Dipole/Dipole: 5.0147
Total Energy:20.6920 kcal/mol </pre>
|-
|}

The conformer with the lowest energy is the more stable conformer and therefore most likely to occur - for red bond stereoisomer pointing downwards, conformation 1 is slightly more stable than conformation 2, and is therefore more likely to form. For red bond stereoisomer pointing upwards, conformation 4 is slightly more stable than conformation 3 and is therefore more likely to form.

=====Mopac Calculation=====
{| class="wikitable"
|-
!colspan="2"| Red Bond Stereoisomer Down
!colspan="2"| Red Bond Stereoisomer Up
|-
! Conformation 1 !! Conformation 2 !! Conformation 3 !! Conformation 4
|-
|<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>mopac1.mol</uploadedFileContents>
</jmolApplet></jmol> ||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac2cc.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac3corrected.mol</uploadedFileContents>
</jmolApplet></jmol>||<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;</script>
<uploadedFileContents>Monosaccmopac4.mol</uploadedFileContents>
</jmolApplet></jmol>
|-
|RMS Gradient = 0.09817 (< 0.10000) Heat of Formation = -69.56744 Kcal/Mol ||RMS Gradient = 0.08243 (< 0.10000) Heat of Formation = -57.96477 Kcal/Mol ||RMS Gradient = 0.08484 (< 0.10000) Heat of Formation = -77.33383 Kcal/Mol ||RMS Gradient = 0.09983 (< 0.10000) Heat of Formation = -63.92546 Kcal/Mol
|-
|Overlay of structure: Overall there is a greatest difference in the carbonyl oxygen overlap when comparing both structures. <jmolFile text="Structure">Monosacc1overlay.mol</jmolFile> || Overlay of structure: Overall there is a good overlap between both structures <jmolFile text="Structure">overlay2monosacc.mol</jmolFile> || Overlay of structure || Overlay of structure
|-
|}

For the red bond with stereoisomer Down, conformation 2 is the more stable conformation however, instead of the above conformation 1. This shows the importance of including the MO's into consideration when calculating the overall stability. For Red bond stereoisomer facing up conformation 4 is the more stable conformation.

=====Comparison=====
By using the overlay operation of comparison, we noticed that both method of calculation for conformation 1 portrays a larger difference than the overlay calculation for conformation 2. The carbonyl oxygen overlap the most when comparing both structures for conformation 1. Energy is more stable in conformation 1 MM2 method of calculation, whereas MOPAC method of calculation reveals that conformation 2 is the more stable form isomer. The overlap reveals that the MM2 and MOPAC differs a lot more for conformation 1, therefore showing that conformation is not as stable as conformation 2 when the molecular orbitals are taken into account.

The bond length for both methods of calculations are the same. What differentiates the two overlaps are the bond angles, which could be seen from the mol file generated (a table is not generated because ultimately it will be confusing).

===Conformation B===
====Conformation 1 MM2 Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMMcorrected.mol</uploadedFileContents>
</jmolApplet></jmol>

Stretch: 2.0146
Bend: 13.5355
Stretch-Bend: 0.7007
Torsion: 7.4524
Non-1,4 VDW: -2.4576
1,4 VDW: 17.7419
Charge/Dipole: -10.4939
Dipole/Dipole: -1.0290
Total Energy: 27.4646 kcal/mol

Conformation B only takes this shape as the aromatics are too tightly stable for it to be able to undergo further twisting.

====Conformation 1 Mopac Calculation====
<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>Monosacc1BMopac.mol</uploadedFileContents>
</jmolApplet></jmol>

RMS Gradient = 0.09729 (< 0.10000) Heat of Formation = -77.34347 Kcal/Mol

Like the above, all the calculations of different methods of steroisomers reveal them to minimize to a same point, therefore only one conformation is valid.

==Module 1 Mini Project: Simulation of Spectroscopic Data for a literature molecule==
===Spectroscopy of an Intermediate related to the Synthesis of Taxol===
First Formatted Checkpoint File. [[http://hdl.handle.net/10042/23116]]
Second Calculated Taxol Derivative. [[http://hdl.handle.net/10042/23117]]

Stretch: 4.9603
Bend: 18.6904
Stretch-Bend: 0.7241
Torsion: 24.2746
Non-1,4 VDW: 0.1010
1,4 VDW: 17.6239
Dipole/Dipole: -2.1570
Total Energy: 64.2173 kcal/mol

===NMR Prediction and Analysis===

===Molecule of choice for study===
[[image:experimentalz.png|350px|thumb|The Z conformation for the molecule|left]]
[[image:stereoisomer2.png|350px|thumb|The E conformation for the molecule|right]]
The sketch on left and right shows both the E and Z conformation for the molecule. This is a minimized sketch via ChemBio3D and is therefore relatively accurate.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer2Z.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer Z.

<jmol><jmolApplet><title>Taxol:The most stable conformation(10)</title><color>black</color>
<size>250</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 7;right;</script>
<uploadedFileContents>isomer1E.mol</uploadedFileContents>
</jmolApplet></jmol>
The actual minimized isomer E.

====NMR Analysis and Comparison====

====Vibrational Analysis and Comparison====
[[image:IRspectrumisomer1.png|550px|left|thumb|The IR Spectrum for the E isomer]][[image:IRspectrumisomer2.png|550px|left|thumb|The IR spectrum for the Z isomer]]

From the IR spectrum itself it looks as though isomer Z has the same spectrum as isomer E, however its insenties are a lot lower than that of isomer E. This means that the vibration for isomer Z is less intense than the vibration for isomer E. Below is a table which compares particular peaks of interest between the two molecules. D-space link Isomer E [[http://hdl.handle.net/10042/23180]], Isomer Z [[http://hdl.handle.net/10042/23230]]

{| class="wikitable"
|-
! Vibration E !! Intensity E !! Frequency E (cm<sup>-1</sup>) !! Comparison !! Vibration Z !! Intensity Z !! Frequency Z (cm<sup>-1</sup>)
|-
| [[image:623.73.133.3712isomerE.gif]] || 623.73 || 133.371 || Both the vibrations were selected with the vibrations being as close as possible for an accurate comparison, for both vibrations, the main feature of vibration is the hydrogen atoms situated on the Nitrogen atoms. The Z isomer has a stronger vibration than the E isomer. || [[image:613.78.250.0229isomerZ.gif]] || 613.78 || 250.0229
|-
| [[image:1171.19.219.8983.isomerE2.gif]] || 1171.19 || 219.8983|| In both of these modes of vibration, the main vibrational contributions that arises from these are the O-CH3 groups. The intensity of Isomer E is much larger than the intensity of vibration Z however. || [[image:1163.47.137.7472isomerZ.gif]] || 1163.47 || 137.7472
|-
| [[image:1261.94.252.2410.isomerE.gif]] || 1261.91 || 252.2410 || In this system, the main mode of vibration comes from the adjacent trans or cis alkene adjacent to the S atom. We could thus conclude that the cis mode of vibration is slightly stronger than the trans mode of vibration. || [[image:1232.12.193.3521.isomerZ.gif]] || 1232.12 || 193.3521
|-
| [[image:1656.17.321.8040.isomerE.gif]] || 1656.17 || 321.8040 || In this mode of vibration, the main contribution of vibration comes from the extremely bulky group adjacent to the alkene group(see picture). The carbon atoms undergo intense stretching. However, the stretching frequencies are 8% too high than the average stretch vibration, this has to be taken into account. ||[[image:1654.15.494.7818.isomerZ.gif]] || 1654.15 || 494.7818 ||
|}

Overall, no negative vibrations were obtained, therefore the calculated vibrations were not in their transition states.

==Optical Rotation and Circular Dichroism==

==Reference==
1.Strain energies of some bridgehead olefins as calculated with the MM2 force field Philip M. Warner, Stephen Peacock, Volume 3, Issue 3, pages 417-420.