Reaction of Thiols with Phenylgyoxal To Give Thiolesters of Mandelic Acid. 2. Intramolecular Genaral-Base Catalysis and Change in Rate-Determinimg Step

Article abstract of DOI:10.1021/ja00373a041

Reactions of phenylglyoxal (1) with N-(2-mercaptoethyl)morpholine (2a) and -piperidine (2b) to give the thiolesters (4) of mandelic acid have been kinetically investigated at 30 deg C.The reaction proceeds through the initial formation of a hemithioacetal (3) (rapid equilibration with the equilibrium constant K_h = 400-1500 M^-1) and its rearrangement via the intramolecular general-base-catalyzed proton transfers to form 4.The pH-rate profile and primary kinetic isotope effects showed that the deprotonation to form an enediol intermediate (5) is rate determining in the reaction with 2a.In the case of 2b, a change in the rate-determining step was observed.At pH < 8 the deprotonation is rate determining, but at higher pH(D) the isotope exchange between the α hydrogen of 3 and the solvent deuterium (in D2O) was found by both NMR and kinetic analysis; the reprotonation of 5 to form 4 becomes rate determining.Any significant metal ion catalysis was not detected with Zn²⁺, Mg²⁺, and Ca²⁺ in aqueous solutions even at low ionic strength.