Calculations of kinetic isotope effects in the Hofmann eliminations of substituted (2-phenylethyl)trimethylammonium ions

Abstract

Theoretical calculations of kinetic isotope effects (KIE) for the Hofmann elimination of the (2-phenylethyl)trimethylammonium ion (I,Z = H) have been carried out for an extensive series of transition-state models encompassing the Elcb-like region of the E2 mechanistic spectrum. The reaction coordinate employed corresponded to the irreversible fragmentation of the base-H'-C/sub ..beta../-C/sub ..cap alpha../-N system, with proton transfer being the dominant contributor. Structural parameters (bond distances and angles) were related to the independent bond orders n/sub ..cap alpha..-N/ and n/sub ..beta..-H'/ by empirical and semiempirical relationships. The most probable transition-state structure for the reaction was determined by interpolation of the experimental values for the ..beta..-D/sub 2/ and /sup 15/N KIE into plots of the trends of the calculated KIE. The nonsolvated models obtained in this manner gave only poor agreement between calculated and experimental secondary deuterium (..cap alpha..-D/sub 2/) and leaving group deuterium (N(CD/sub 3/)/sub x/(CH/sub 3/)/sub 3-x/, x = 1 to 3) KIE; explicit consideration of differential solvation of the reactant and transition state afforded the most chemically reasonable resolution of these discrepancies. Using solvated models, transition-state structures were also determined for the Hofmann elimination of parasubstituted derivatives of I (Z = OCH/sub 3/, Cl, CF/sub 3/). These transition statesmore » are related by a shift parallel to the central E2 diagogonal of an O'Ferrall-Jencks reaction diagram, as predicted by Thorton, indicating that, in the absence of other factors (differing solvent or base, etc.), the extent to which negative charge is accumulated at C..beta.. in the transition state is solely a factor of the leaving group. Both independent bond orders (n/sub ..cap alpha..-N/ and n/sub ..beta..-H'/) exhibit a linear dependence on the sigma value of the substituent, allowing for the first time prediction of transition states.« less