Theoretical studies on the acid hydrolysis of acetamide

Abstract

The mechanism of the A2 hydrolysis of acetamide has been investigated theoretically using MNDO Method. Fully optimized geometries of all species at the stationary points corresponding to energy minima and energy maxima along the reaction coordinate are determined for the two reaction paths: the rate-determining nucleophilic attack of water on the carbonyl carbon (i) of the O-protonated tautomer and (ii) of the N-protonated form. Results show that the latter provides a lower energy path by 7.5 Kcal Mol compared to the former.Tetrahedral species' found were not at the energy minima but at or near the saddle points. Optimizied structures and formal charges on heavy atoms showed that the bond interchange with the concurrent proton interchange takes place at the rate-determining step. The negative charge on N atom was found to increase in the rate-determining step relative to that of the ground state, the O-protonated acetamide, and hence substitution of electron withdrowing group on N is predicted to depress the activation energy in agreement with the experimental results.