Equilibrium and stereoscopic isotope effects

The thesis describes experiments on isotope effects on steric and other interactions that may be used to test, for example, the validity of empirical potential functions for non-bonded interactions involving hydrogen. The earlier serendipitous observation of shifts in π → π* UV absorption bands on deuteriation is exploited as a possible probe for examination of the electronic and geometric changes accompanying deuteriation.
The effect of deuterium substitution on the free energy differences of conformational equilibria with hydrogen in two possible environments is studied for a series of 2-substituted-1,3-dioxanes and 3-phenyl-3,5,5-trimethylcyclohexanone. The time-averaged NMR chemical shifts of suitable protons in the deuteriated and undeuteriated molecules are used to indicate the positions of the equilibria in several solvents, and model compounds are used to provide shift values from which free energy differences for the equilibrating systems may be calculated with the same systematic errors in both the undeuteriated and deuteriated systems. Possible sources of error are discussed, and the largest is shown to be the standard deviation of measurement of the time-averaged NMR chemical shift differences, leading to errors of 1 to 2 cal/mole in isotope effects from -2 to +16 cal/mole on strain energies ~ 4 kcal/mole. The measured effects were not always of a sign compatible with a reduction of "size" on changing from an undeuteriated to a deuteriated group.
Preliminary investigations of systems for which isotope effects on intermolecular proton exchange may be measured, are reported, and isotope effects on the free energy differences between the two hydroxyl groups of partially deuteriated 3,5-di-t-buryl-2,6-dihydroxyacetophenone and of partially deuteriated 3,5-di-t-butyl-2,6-dihydroxybenzaldehyde O-methyloxime of 50 and 20 cal/mole respectively, protium being favoured in the intramolecularly hydrogen bonded group, are measured by the NMR chemical shifts of hydroxyl proton signals. These chemical shift values are used in conjunction with the hydroxyl proton chemical shifts of suitable models to determine the quoted isotopic changes in free energy differences.
Isotopic changes in the intensities of UV absorption bands are measured for cis- and trans-3,5-di-t-butylcyclohexane-1,3-diones and interpreted in terms of changes in the free energy difference between keto-enol and diketo tautomers. No such change was detected on deuteriation of acetylacetone, contrary to the results reported by Allred and Thompson.
Isotopic shifts in the frequency position of the centroids of UV bands are measured by "difference" spectrometry, a technique whose applicability and accuracy is illustrated by the reproducibility and insensitivity to calibration errors of shifts in the centroids of the IR carbonyl stretching bands between a series of cyclohexanone derivatives measured in the same way. The UV band shifts are interpreted as isotopic changes of differences in the potential energy between the ground state and geometrically different excited states for the enol forms of the above diketones and a series of 4-aminopyridine derivatives.
All the observed effects are interpreted in terms of the reduction of zero-point vibrational energy accompanying substitution of deuterium for hydrogen. However the effect of the smaller "size" of deuteriated groups on steric strain energies appears to be accompanied by isotope effects on other contributions, for example those caused by bond polarities, to non-bonded interactions which may enhance or diminish the "size" effect.