Modeling protic to dipolar aprotic solvent rate acceleration and leaving group effects in S(N)2 reactions: A theoretical study of the reaction of acetate ion with ethyl halides in aqueous and dimethyl sulfoxide solutions

The S(N)2 reactions between acetate ions and ethyl chloride, ethyl bromide, and ethyl iodide in aqueous and dimethyl sulfoxide (DMSO) solutions were theoretically investigated at an ab initio second-order M?ller-Plesset perturbation level of theory for geometry optimizations and at a fourth-order M?ller-Plesset perturbation level for energy calculations. The solvent effect was included by the polarizable continuum model using the Pliego and Riveros parametrization for DMSO and the Luque et al. scale factor for the water solution. The calculated DeltaG() values of 24.9, 20.0, and 18.5 kcal mol(-1) in a DMSO solution for ethyl chloride, ethyl bromide, and ethyl iodide are in good agreement with the estimated experimental values of 22.3, 20.0, and 16.6 kcal mol(-1), respectively. In an aqueous solution, the theoretical Delta G++ barriers of 26.9, 23.1, and 22.1 kcal mol(-1) are also in good agreement with the estimated experimental values of 26.1, 25.2, and 24.7 kcal mol(-1), respectively. The present ab initio calculations are reliable to predict the absolute and relative reactivities of ethyl halides in a DMSO solution, but in the aqueous phase, the results are less accurate. The protic to dipolar aprotic solvent rate acceleration is theoretically predicted, although this effect is underestimated. We suggest that further improvement of the present results could be obtained by including liquid-phase optimization in both solvents and treating specific solvation by water molecules for the reaction in the aqueous phase.