Theoretical study on the reaction mechanism for the hydrolysis of esters and amides under acidic conditions

The mechanisms underlying the hydrolysis of methyl acetate and acetamide under acidic conditions were investigated using the MP2/6-311+G(d,p)//MP2/6-31+G(d,p) level of theory. It was necessary to include two water molecules as reactants to obtain a tetrahedral (TD) intermediate for the A(AC)2 mechanism that Ingold classified for the hydrolysis of methyl acetate. This mechanism includes two TS structures, one for the formation of the TD intermediate and the other for its decomposition. Since the activation energies were calculated to be 15.7 and 18.3 kcal mol(-1), the second step determines the rate of hydrolysis. The calculated value was close to that observed at similar to 16 kcal mol(-1). It was confirmed that the A(AC)2 mechanism had a barrier lower by 9.9 kcal mol(-1) than the A(AL)2 mechanism. The A(AC)2 mechanism is also applicable to the acid-catalyzed hydrolysis of acetamide. It is not the TD intermediate with which the NH3+ moiety forms, but one further step is required to produce the final products, acetic acid and ammonium ion. (c) 2006 Elsevier Ltd. All rights reserved.