Heavy-atom isotope effects on the alkaline hydrolysis of methyl formate: the role of hydroxide ion in ester hydrolysis

Abstract

Carbonyl carbon, carbonyl oxygen, and nucleophile oxygen isotope effects were measured for the alkaline hydrolysis of methyl formate in water at 25 o C. The carbonyl carbon isotope effect is k 12 /k 13 =1.0338, the isotope effect for the carbonyl oxygen is k 16 /k 18 =0.999, and that for the oxygen nucleophile is k 16 /k 18 =1.023. These isotope effects are consistent with a stepwise mechanism in which the formation of the tetrahedral intermediate is largely rate-determining. The isotope effect on the oxygen nucleophile suggests that the attacking nucleophile in aqueous alkali is water with general base assistance from hydroxide