Intramolecular Electrostatic and General Acid Catalysis in the Hydrolysis of O,S-Thioacetals

Article abstract of DOI:10.1021/ja00521a046

The pH-independent release of thiophenolate ion from phthalaldehydic acid O-methyl S-phenyl thioacetal in H2O at 50 deg C and at pH values where the carboxyl group is ionized is 22 times faster than the corresponding reaction in hydrolysis of the terephthalaldehydic acid derivative.This rate difference arises becouse of electrostatic stabilization of the developing carbanium ion by the neighboring carboxylate ion.In the view of the large amount of C-S bond breaking in the transition state the rate enhancement due to electrostatic effects must be near maximal in water for reactions in which a methoxybenzyl carbonium ion is produced.The plot of log k_obsd vs. pH for release of thiosalicylic acid from phthalaldehydic acid O-methyl S-(o-carboxyphenyl) thioacetal at 50 deg C in 50percent dioxane-H2O shows hydronium ion catalysis at low pH, and from pH 3 to 7 the profile is bell shaped.The value of the rate constant k₂ for hydronium ion catalyzed reaction of the dianionic species is 6*10⁶ greater than the second-order rate constant k_H for hydronium ion catalyzed hydrolysis of the dimethyl ester and is 360-fold greater than the corresponding rate constant of terephthalaldehydic acid O-methyl S-(o-carboxyphenyl) thioacetal.The hydronium ion catalyzed neutral species reaction of phthaladehydic acid O-methyl S-(o-carboxyphenyl) thioacetal is retarded in 50percent dioxane-H2O as compared with H2O, but k₂ is accelerated 50-fold.Both carboxyl groups are participating in hydrolysis of the monoanionic species, i.e., intramolecular general acid catalysis is occurring in conjunction with electrostatic stabilization effects.It is likely that intramolecular general acid catalysis also occurs in hydrolysis of benzaldehyde O-methyl S-(o-carboxyphenyl) thioacetal and terephthalaldehydic acid O-methyl S-(o-carboxyphenyl) thioacetal, but rate enhancements are small in comparison with corresponding O,O-acetals.The significant electrostatic stabilization effects in the general-acid-catalyzed reaction of phthalaldehydic acid O-methyl S-(o-carboxyphenyl) thioacetal in contrast with the absence of such effects in the intramolecular general-acid-catalyzed reaction of phthalaldehydic acid O-methyl O-salicyl acetal shows that much more bond breaking is required in the transition state in reaction of the thioacetal.The factors influencing concerted bifunctional catalysis are discussed.