GENERAL-BASE-CATALYZED INTRA-MOLECULAR AMINOLYSIS OF THIOL ESTERS - CYCLIZATION OF S-NORMAL-PROPYL ORTHO-(2-IMIDAZOLYL)THIOLBENZOATE - RELATIONSHIP OF THE UNCATALYZED AND BASE-CATALYZED NUCLEOPHILIC REACTIONS

Rate constants have been obtained at 30 °C in H2O for hydrolysis of S-n-propyl o-(2-imidazolyl)thiolbenzoate. The reaction involves rapid formation and subsequent breakdown of an acylimidazole intermediate. A plot of log k0 for cyclization vs. pH is linear with a slope of 1.0 at all pH values. The contributions to k0 of the uncatalyzed neutral species and apparent hydroxide ion catalyzed reactions are equal at the pKa of the nucleophile. The kinetic data indicate that cyclization to a tetrahedral intermediate is an equilibrium step, breakdown of the tetrahedral intermediate being rate determining. The value of kOH for cyclization of the thiol ester is 5 × 106 greater than for hydrolysis of n-propyl thiolbenzoate. In comparison with bimolecular attack of imidazole on n-propyl thiolbenzoate the effective molarity of the neighboring imidazolyl neutral species is 1.6 × 103 M while that of the imidazolyl anion is 7 × 102 M. General base catalysis is observed in the intramolecular nucleophilic reaction. The value of the Brønsted coefficient ×β is 1.0, indicating that the rate-determining step is a proton transfer in the thermodynamically unfavorable direction. This step may be proton abstraction by the base from a neutral tetrahedral intermediate. This relationship appears to be general for intramolecular aminolysis reactions in the 2-substituted benzoate system. © 1979, American Chemical Society. All rights reserved.