Computational study of the alkaline hydrolysis of acetanilide

RHF/6-31 + G(d), B3LYP/6-31 + + G(d,p), and QCISD/6-31 + + G(d,p) quantum mechanical computations were carried out in studying the mechanism of alkaline hydrolysis of acetanilide. The computations showed that in both gas phase and water solution the rate determining stage of the reaction is the nucleophilic addition of the hydroxide ion and formation of a tetrahedral intermediate (TD). The first stage is followed by low energy conformational transformation yielding a structure that is favourable for the next process. The decomposition of the tetrahedral intermediate is shown to be a concerted process involving cleavage of the C-N bond and spontaneous proton transfer. No evidence is found for the formation of a dianion intermediate along the reaction pathway. The theoretical computations reveal that the energy profile of the reaction is quite different in gas phase and in solution. All stationary points in water have higher energy than the reactants. The reaction is exothermic in both gas phase and solution. (C) 2004 Elsevier B.V. All rights reserved.