Entropy of activation for reactions in the condensed phase: A theoretical study of the S(N)2 alkylation of amines

A theoretical model for the evaluation of the entropy of activation for organic reactions in the condensed phase is proposed. The required partition functions for solutes are computed taking into account the hindered translation and rotation in the solvent cavity. The activation parameters for the alkylation of 3-bromopyridine by iodomethane in acetonitrile were obtained by regression of experimentally determined rate constants to the Eyring equation with different reference volumes. While the gas-phase reference volume affords an entropy of activation of -40.7 cal mol(-1)K(-1), the corresponding calculated quantity at the N1PWlK/CRENBL(.)6-311(+)G(d) level of theory is -34.9 cal mol(-1) K-1. The condensed-phase reference volume gives Delta S-not equal = -24.1 calmol(-1)K(-1), in better agreement with the computed value of -22.6 calmol(-1) K-1.