The syntheses of 4-nitro thiol benzoate esters of ethyl
2-mercaptoacetate, thioglycolic acid,
2-(dimethylamino)ethanethiol, and
2-(N,N,N-trimethylammono)ethanethiol
iodide (10
−
13) have
been carried out and their rates of hydrolysis at 50 °C studied as a
function of pH. Thiol esters 10
and 13 have linear pH−log k
obs
profiles indicative of an exclusive specific base attack of
OH-. Thiol
esters 11 and 12 exhibit a plateau in their
pH/log k
obs profiles due to the participation of
pendant
carboxylate and dimethylamino groups, respectively, most probably as
intramolecular general bases.
At higher pH, specific base catalysis 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 for the pendant dimethylamino
group. The hydrolysis of
12 in the presence of Ellman's reagent produces the
Ellman's anion at a rate that is identical to
that for disappearance of the thioester, consistent with a general base
process where the thiolate
anion product of hydrolysis is produced in the rate-limiting
step.