Origin of Enhanced Reactivity of a Microsolvated Nucleophile in Ion Pair SN2 Reactions: The Cases of Sodium p-Nitrophenoxide with Halomethanes in Acetone

In a kinetic experiment on the S(N)2 reaction of sodium p-nitrophenoxide with iodomethane in acetone-water mixed solvent, Humeres et al (J. Org. Chem. 2001, 66, 1163) found that the reaction depends strongly on the medium; and the fastest rate constant was observed in pure acetone. The present work tries to explore why acetone can enhance the reactivity of the title reactions. Accordingly we make a mechanistic study on the reactions of sodium p-nitrophenoxide with halomethanes (CH3X, X = Cl, Br, I) in acetone by using a supramolecular/continuum model at the PCM-MP2/6-311+G(d,p)//B3LYP/6-311-04+G(d,p) level, in which the ion pair nucleophile is microsolvated by one to three acetone molecules. We compared the reactivity of the microsolvated ion pair nucleophiles with solvent-free ion pair and anionic ones Our results clearly reveal that the microsolvated ion pair nucleophile is favorable for the S(N)2 reactions; meanwhile, the origin of the enhanced reactivity induced by microsolvation of the nucleophile is discussed in terms of the geometries of transition state (TS) structures and activation Strain model, suggesting that lower deformation energies and stronger interaction energies between the deformed reactants in the TS lead to the lower overall reaction barriers for the S(N)2 reaction of microsolvated sodium p-nitrophenoxide toward halomethanes in acetone.