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

Article abstract of DOI:10.1021/ja00067a008

Carbonyl carbon, carbonyl oxygen, and nucleophile oxygen isotope effects were measured for the alkaline hydrolysis of methyl formate in water at 25 °C. The carbonyl carbon isotope effect is k¹²/k¹³ = 1.0338, the isotope effect for the carbonyl oxygen is k¹⁶/k¹⁸ = 0.999, and that for the oxygen nucleophile is k¹⁶/k¹⁸ = 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.