Hydrolysis of N-Acetyl-p-benzoquinone Imines: pH Dependence of the Partitioning of a Tetrahedral Intermediate

Article abstract of DOI:10.1021/ja00194a046

The hydrolysis reactions of N-acetyl-p-benzoquinone imine, 1a, and its 3,5- and 2,6-dimethyl analogues, 1b and 1c, in the pH range 0.3-10.5 are described.At pH < 6.0 the carbinolamide intermediates 2a-c can be detected by 1H NMR, UV, and HPLC methods.The pH-dependent partitioning of 2a and 2c can be monitored since the reversion of these intermediates to the protonated N-acylimines 5a and 5c leads to products of the conjugate attack of Cl(-), the 3-chloroacetaminophen derivatives 4a and 4c.A mechanism for the hydrolysis of 1a-c (Scheme I) is proposed which accurately predicts the time dependence of the formation of 2 and the final hydrolysis products, the p-benzoquinones 3, and 4.The alternative O-protonation mechanism (Scheme II) is tentatively rejected on the basis of substituent effect data.The relationship of the hydrolysis reactions of 1a-c to those of ordinary imines is discussed.