Steric and solvation effects in ionic S(N)2 reactions.


Journal Article

This paper explores the contribution of solvation to the overall steric effects of S(N)2 reactions observed in solution. The reactions of chloride ion with a series of alkyl chloronitriles, RCH(CN)Cl (R = methyl, ethyl, isopropyl, tert-butyl) were investigated both experimentally and theoretically. These reactions serve as a model system for the parent reactions, Cl(-) + RCH(2)Cl, which are too slow to measure. Each additional substitution at the beta-carbon lowers the reactivity, clearly demonstrating a steric hindrance effect. The magnitude of the steric effect, however, is not significantly different in the gas phase and in solution. We conclude that the solvation energies of the corresponding S(N)2 transition states must be similar regardless of size of the substituent. This lack of size dependence in the current system is in sharp contrast with many other ionic systems such as ionization of simple alkyl alcohols, where solvation depends strongly on size. We propose that the weak size dependence results from the compensation between a direct shielding effect of the substituent and an indirect ionic solvation effect, which arises from the geometric perturbations introduced by the substitution. The conclusion is further supported by calculations using polarizable continuum models and QM/MM simulations.

Full Text

Duke Authors

Cited Authors

  • Chen, X; Regan, CK; Craig, SL; Krenske, EH; Houk, KN; Jorgensen, WL; Brauman, JI

Published Date

  • November 2009

Published In

Volume / Issue

  • 131 / 44

Start / End Page

  • 16162 - 16170

PubMed ID

  • 19842649

Pubmed Central ID

  • 19842649

Electronic International Standard Serial Number (EISSN)

  • 1520-5126

International Standard Serial Number (ISSN)

  • 0002-7863

Digital Object Identifier (DOI)

  • 10.1021/ja9053459


  • eng