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.
Fife
Thomas H
TH
Department of Biochemistry, University of Southern California, Los Angeles, California 90089-9560, USA. tfife@hsc.usc.edu
Singh
Randhir
R
Bembi
Ramesh
R
D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods; D004952:Esters / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D015394:Molecular Structure; D013696:Temperature; D014867:Water / Q000737:chemistry; D062367:ortho-Aminobenzoates / Q000737:chemistry*
D004952:Esters; D062367:ortho-Aminobenzoates; D014867:Water; C031385:anthranilic acid