Ellis

Abstract

The reactions of hydrazine with ethyl acetate, methoxyethyl acetate, and probably 2-chloroethyl acetate exhibit a change in rate-determining step with decreasing pH similar to that with methyl formate; no such change is observed with trifluoroethyl or phenyl acetates. Structure-reactivity correlations suggest identical transition state structures and rate-determining steps for the general base-catalyzed reactions of alkyl and phenyl esters, but for the uncatalyzed reactions there is a leveling of the rate with changing leaving group for the alkyl esters that requires a different mechanism from that of the phenyl esters. This change in mechanism and a requirement for proton transfer in the reactions of primary and secondary amines are also evident in the slow reactions of tertiary amines with alkyl esters. Bifunctional cyclic mechanisms are excluded by the effectiveness of tertiary amines as general base catalysts for hydrazinolysis. A mechanism of aminolysis is proposed that is consistent with these and other data. With most esters, the attack of amine to form the labile intermediate T is rapid and reversible, and the rate-determining step at high pH is the trapping of this intermediate by proton removal with a general base, a proton switch through water (alkyl esters), or the direct breakdown of T to products (phenyl esters). For very fast reactions, there is a change to rate-determining formation of T accompanied by a sharp decrease in sensitivity to substituent effects. The application of these considerations to the mechanism of chymotrypsin catalysis is de- scribed.