Thorpe-Ingold acceleration of oxirane formation is mostly a solvent effect.

ABSTRACT: The Thorpe-Ingold hypothesis for the gem-dimethyl effect in the cyclization reactions of 2-chloroethoxide derivatives has been investigated computationally in the gas phase and in aqueous solution. Ab initio MP2/6-311+G(d,p) and CBS-Q calculations reveal little intrinsic difference in reactivity with increasing alpha-methylation for the series of reactants 1-3. However, inclusion of continuum hydration or of explicit hydration through mixed quantum and statistical mechanics (MC/FEP) simulations does reproduce the substantial, experimentally observed rate increases with increasing alpha-methylation. Analysis of the MC/FEP results provides clear evidence that the rate increases stem primarily from increased steric hindrance to hydration of the nucleophilic oxygen atom with increasing alpha-m

SUBMITTER: Kostal J 

PROVIDER: S-EPMC2892976 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature