TRANSITION-STATE STRUCTURAL VARIATION AND MECHANISTIC CHANGE

An important link between theoretical and experimental views of organic reactivity is provided by More O'Ferrall-Jencks diagrams, which are commonly used in empirical discussions of reaction mechanisms and of changes in transition-state structure. We have performed semiempirical AM1 molecular-orbital calculations for S(N)2 displacements on alpha-substituted alkyl substrates and for general acid-catalysed hydride reduction of a carbonyl group which demonstrate transition-state structural variations in accord with the predictions of these diagrams. We provide an example of a possible danger associated with the use of these diagrams in considerations of mechanistic change. We have examined the changeover in mechanism from S(N)2 to S(N)1 occurring in the degenerate reaction H2O + CHR'R''OH2+ --> +H2OCHR'R'' + OH2 as the alpha-substituents R' and R'' are altered. The methyl (R' = R'' = H) and ethyl (R' = H, R'' = Me) substrates react by the S(N)2 mechanism, whereas the isopropyl (R' = R'' = Me), methoxymethyl (R' = H, R'' = OMe) and methoxyethyl (R' = Me, R'' = OMe) substrates follow the S(N)1 mechanism. The mechanisms merge according to the classical model of Doering and Zeiss, with the Sl intermediate appearing with essentially the same structure and energy as the disappearing S(N)2 transition state.