Thorpe-Ingold acceleration of oxirane formation is mostly a solvent effect.
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-methylation. Thus, the gem-dimethyl acceleration of oxirane formation for 1-3 is found to be predominantly a solvent effect.
Department of Chemistry, Yale University, 225 Prospect Street, New Haven, Connecticut 06520-8107, USA.
Jakub
J
Kostal
William L
WL
Jorgensen
D002728:Chlorohydrins / Q000737:chemistry; D003500:Cyclization; D005027:Ethylene Oxide / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008958:Models, Molecular; D008968:Molecular Conformation; D009010:Monte Carlo Method; D011789:Quantum Theory; D012997:Solvents / Q000737:chemistry*; D013816:Thermodynamics
D002728:Chlorohydrins; D012997:Solvents; D005027:Ethylene Oxide