Conformation measurement rotamers

If two different three-dimensional arrangements in space of the atoms in a molecule are interconvertible merely by free rotation about bonds, they are called conformationsIf they are not interconvertible, they are called configurations Configurations represent isomers that can be separated, as previously discussed in this chapter. Conformations represent conformers, which are rapidly interconvertible and are thus nonseparable. The terms conformational isomer and rotamer are sometimes used instead of conformer . A number of methods have been used to determine conformations. These include X-ray and electron diffraction, IR, Raman, UV, NMR, and microwave spectra, photoelectron spectroscopy, supersonic molecular jet spectroscopy, and optical rotatory dispersion (ORD) and CD measurements. Some of these methods are useful only for solids. It must be kept in mind that the conformation of a molecule in the solid state is not necessarily the same as in solution. Conformations can be calculated by a method called molecular mechanics (p. 178). 

Asymmetrically substituted thioamides 24e-h exist in equilibrium between rotamers 24-1 and 24-11. The NMR spectrum of AT-benzyl-iV-methylmeth-acrylthioamide 24e showed the distribution of 24e-I 24e-II was 55 45 (Scheme 13 and Table 8) [47]. The free energy of activation of the rotational barrier was measured by the temperature-dependent NMR spectra in DMSO at various temperatures. The free energy of activation of the rotation of the (C=S)-N bond could be estimated as 22.7 kcal mokh Furthermore, Table 8 shows the ratio of I II, and all three thioamides 24f-h favor the conformation I with the situation that a benzyl group was placed closely to the thiocarbonyl group on... 

Tam et al. [141] attempted to determine how reliable and accurate CC and DFT/ TDDFT calculations are for this conformationally flexible molecule. In addition, they explored the sensitivity of the chiroptical response to two different factors. One was the accuracy of the mole fractions, and another was how different were the ORs of individual rotamers calculated at different levels of theory. It was found that with DFT, at the B3LYP/aug-cc-pVDZ level, the optical rotations were overestimated while CC yielded better agreement with experiment [141, 142], The predicted gas phase optical rotation, averaged by CC or DFT mole fractions, were not in good agreement with either gas or solution phase experimental measurements. The DFT calculated optical rotations differed between 15 and 65% from experiment. 

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