Intramoleclar Nucleophilic Catalysis during Alkaline Hydrolysis of Nonenolizable β-Keto-Esters

Article abstract of DOI:10.1021/ja00279a048

Kinetic and 18O-labeling studies demonstrate that in the hydrolysis of nonenolizable acetoacetate esters, the carbonyl hydrate acts as a nucleophilic catalyst.A cyclic four-membered lactone is formed and later opens.Structure/reactivity studies showed the rate-determining step to be a function of the pKa of the leaving group and the substituent bound to C3 of the acetoacetate residue.Rate accelerations of 4 to E4 were observed for hydrolyses of the corresponding p-nitrophenyl esters, depending on the substituent at C3.