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

Abstract The hydrolysis of esters and amides accompanies a fast reaction, which results in exchange of carbonyl 18O to 16O coming from solvent water. The present 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 fragment directly moves from the OH to the 18O fragment in the tetrahedral intermediate. The other, Path 2 called the water-assisted mechanism, is that one water molecule assists transferring a proton to make an 18OH fragment. The MP2/6-31+G* level of theory estimated rather high ΔEgas‡(TD) for the direct path of methylacetate and N-methylacetamide (21.8 and 19.7 kcal mol−1, respectively). The ΔEgas‡(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 ΔG‡(H2O) and ΔG‡(OH), calculated activation free energies including solvent effect, are small in comparison with those observed for the breakdown of TD intermediates to exchange or hydrolysis products. The present MO calculation suggests that one solvent water acts as one of the reactants and facilitates both proton transfer from the OH fragment and proton acceptance from the water to form the new 18OH fragment. It is likely that the oxygen exchange reaction accompanying hydrolysis of esters and amides proceeds via the water-assisted mechanism.

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