Solvent Molecules Play a Role in an SNAr Reaction

Abstract

Reaction between 4-nitrobenzonitrile and sodium methoxide (MeONa) exhibits unexpectedly low conversion and puzzling kinetics behavior, which is in sharp contrast to the prediction that reaction would be rapid and thorough made by density functional theory (DFT) calculations under implicit solvation. Free energy surfaces (FES) obtained by explicit solvation model including 62 solvent molecules differ greatly from those with implicit solvation. The real nucleophile is not methoxide anion but methanol-methoxide complex, and it is the entropy effect due to solvent molecules that modifies the FES. It is the first work revealing the significant modification of FES by explicit solvation for small molecule reactions.