Theoretical study on oxygen exchange accompanying alkaline hydrolysis of esters and amides. The role of water for the exchange reaction

The hydrolysis of esters and amides accompanies a fast reaction, which resu lts in exchange of carbonyl O-18 to O-16 coming from solvent water. The pre sent study considered two paths as the oxygen exchange mechanism. One, Path 1 called the direct path, is the mechanism that a proton of the OH fragmen t directly moves from the OH to the O-18 fragment in the tetrahedral interm ediate. The other, Path 2 called the water-assisted mechanism, is that one water molecule assists transferring a proton to make an (OH)-O-18 fragment. The MP2/6-31 + G* level of theory estimated rather high Delta E(gas)double dagger(TD) for the direct path of methylacetate and N-methylacetamide (21. 8 and 19.7 kcal mol(-1), respectively). The Delta E(gas)double dagger(H2O), the activation barrier for the water-assisted mechanism, is very low both for the ester (3.8 kcal mol(-1)) and for the amide (2.8 kcal mol(-1)). The Delta G double dagger(H2O) and Delta G double dagger(OH), calculated activa tion free energies including solvent effect, are small in comparison with t hose observed for the breakdown of TD intermediates to exchange or hydrolys is products. The present MO calculation suggests that one solvent water act s as one of the reactants and facilitates both proton transfer from the OH fragment and proton acceptance from the water to form the new (OH)-O-18 fra gment. It is likely that the oxygen exchange reaction accompanying hydrolys is of esters and amides proceeds via the water-assisted mechanism. (C) 1999 Elsevier Science B.V. All rights reserved.