INTRAMOLECULAR CATALYSIS OF THIOL ESTER HYDROLYSIS BY A TERTIARY AMINE AND A CARBOXYLATE

The syntheses of 4-nitro thiol benzoate esters of ethyl 2-mercaptoacet ate, thioglycolic acid, 2-(dimethylamino)ethanethiol, and 2(N,N,N,-tri methylammono)ethanethiol iodide (10-13) have been carried out and thei r rates of hydrolysis at 50 degrees C studied as a function of pH. Thi ol esters 10 and 13 have linear pH-log k(obs) profiles indicative of a n exclusive specific base attack of OH-. Thiol esters 11 and 12 exhibi t a plateau in their pH/log k(obs) profiles due to the participation o f pendant carboxylate and dimethylamino groups, respectively, most pro bably as intramolecular general bases. At higher pH, specific base cat alysis becomes predominant for both 11 and 12. In the plateau region, the hydrolysis of 12 is subject to a solvent deuterium kinetic isotope effect of 2.2, consistent with the operation of a general base role f or the pendant dimethylamino group. The hydrolysis of 12 in the presen ce of Ellman's reagent produces the Ellman's anion at a rate that is i dentical to that for disappearance of the thioester, consistent with a general base process where the thiolate anion product of hydrolysis i s produced in the rate-limiting step.