Intramolecular General Base Catalyzed Ester Hydrolysis. The Hydrolysis of 2-Aminobenzoate Esters

Rate constants have been obtained for the hydrolysis of the trifluoroethyl, phenyl, and p-nitrophenyl esters of 2-aminobenzoic acid at 50 degrees C in H(2)O. The pseudo-first-order rate constants, k(obsd), are pH independent from pH 8 to pH 4 (the pK(a) of the amine group conjugate acid). The 2-aminobenzoate esters hydrolyze with similar rate constants in the pH-independent reactions, and these water reactions are approximately 2-fold slower in D(2)O than in H(2)O. The most likely mechanism involves intramolecular general base catalysis by the neighboring amine group. The rate enhancements in the pH-independent reaction in comparison with the pH-independent hydrolysis of the corresponding para substituted esters or the benzoate esters are 50-100-fold. In comparison with the hydroxide ion catalyzed reaction, the enhancement in k(obsd) at pH 4 with the phenyl ester is 10(5)-fold. Intramolecular general base catalyzed reactions are assessed in respect to their relative advantages and disadvantages in enzyme catalysis. A general base catalyzed reaction can be more rapid at low pH than a nucleophilic reaction that has a marked dependence on pH and the leaving group.