Talk:Mod:ms7109 module1

Q1: Your energy values are all spot on although it was not necessary to give data to so many decimal places: these are not precisely measured quantities and there is also some degree of error due to random fluctuation from one calculation to the next or one laptop to the next. The analysis of strain contributions is good. Thermodynamic vs kinetic control is correctly described for these examples; as you say for the hydrogenated compounds – you know which product would be formed under thermodynamic control, but for kinetically controlled reactions information about the transition states must be obtained. It is good that you have included some references here, but it should be noted that while Baldwin provided an explanation for endo control, the original “determination” that the endo isomer is preferred was made empirically at the turn of the century by Diels and Alder.

Q2. The approach you have taken makes sense (looking at the part of the structure for which various stable conformations are known). Most of your structures and energy values are good. Your calculation for the up-chair isomer does not have the correct structure – the geometry of the double bond is incorrect. It is important to always check the structure after minimisation to ensure it still has the correct configuration (this can easily be compromised when the structure is tweaked to find different starting points). It would have been good to hear about how else you minimised the structure – were there alternative conformations for the central medium ring? Even if this was not the case, it is worth stating that. The strain in hydrogenation is well described. This type of alkene is specifically termed “hyperstable”. There are some problems in the energy balance you have calculated; in order to balance the hydrogenation equation and get a heat of reaction you need to include the other reactant (hydrogen). Also it is not strictly possible to compare energies of non-isomeric compounds (using molecular mechanics) because the more the structure changes, the greater the difference in the scale being used to measure the energy.

Q3. Good effort getting all those vibrations in! The way you have presented the data here is also great - concise and easily referenced to the relevant structures. Your calculations are all fine, but you should include the energy values you got for these structures also (it’s one of the ways in which the calculation can be assessed on marking – and this will probably also be true for later parts of the course). The orbitals look good and the most nucleophilic double bond is correctly predicted. Discussion of the pi-sigma* interaction and its effect on the IR stretches is good.

Q4. Having all of those jmols in the table is making the page a bit buggy – maybe better to use the option of having a link or button for them. Methyl is definitely the most sensible choice for the R group to save computing time (especially for this brief study). Your energy values are pretty close to expected for the PM6 calculations (MM2 a little off – but it’s difficult to comment on why this might be the case without any image or link). I would say that the major reason for the difference in Ca/Cb and Da/Db is not the anomeric effect but the instability of a trans-fused 5-6 ring system over the more common cis-fused – a range of strains are the cause of this difference. You should have found that using MOPAC A=C and B=D; the structures can’t be distinguished because the true structure is something of a hybrid. MM2 won’t give this result because the method can’t determine that there should be new bonds because its bonds are set by the user. The ratio from your Boltzmann actually suggest that there will be 10^16 more of the unfavoured isomer present; the difference in energy is always a positive quantity and the true form of the equation should be the exponent of a negative number; the actual ratio seems massively biased, but I suppose the difference in energy is pretty big in this case.

MP. Your introduction is good – having a concise summary of the key parts of the paper you’re looking at is a good idea. This first question you look at (epimerisation of menthone) is interesting, but I’m not sure exactly what you’re getting at by the end. If a species undergoes epimerisation in this manner, the result is to obtain the thermodynamic product. If you simply left menthone in the presence of the base, over time you would expect to obtain an equilibrium mixture of the + and – isomers through the common enolate form. What is confusing is that you say complete epimerisation occurs but you have the trans isomer to start with (surely complete epimerisation would mean formation of the cis isomer); the 97:3 ratio seems to be about right given the difference in energies you calculated for the two forms. I think I understand what you are looking at next but there are some issues with terminology: these enolate forms are not transition states, they are intermediates. That said, it is reasonable to calculate the energies of these intermediates to see which is more likely to form and explain why the product distribution may not match the starting distribution. What is odd is that you say the cis enolate is lower in energy that should give the cis relationship in the formylated product, but the product you give in the scheme is actually derived from the trans enolate. Did you mean to say that your calculations here do not match the experimental observations (this needs to be made clearer). Incidentally the energy values obtained may be a little off because there is no counter cation included and also it requires quite sophisticated techniques to accurately model ionic species (usually with solvent modelling included). Your NMR and IR results are fine but it would have been better to look at how close the NMR data for the two isomers is and then analyse whether you can differentiate between the two using computational chemistry – i.e. is it possible to say that you definitely have one isomer because the experimental data matches its computed data much better. Also when talking about the comparison of your results to the literature values it would have been worth commenting on how the authors of the paper worked out which isomer they got (2D NMR probably).