The Timing of the Proton-Transfer Process in Carbonyl Additions and Related Reactions. General-Acid-Catalyzed Hydrolysis of Imines and N-Acylimines of Benzophenone

Article abstract of DOI:10.1021/ja00530a046

Observed general-acid-catalyzed hydrolysis of benzophenone imines, Ph2C=NR, or the kinetically equivalent general-base-catalyzed hydrolysis of the conjugate acids Ph2C=N⁺HR, corresponds mechanistically to general-base-catalyzed amine expulsion from the conjugate acid (T⁺) of the tetrhedral intermediate from water addition to Ph2C=NR.Broensted β values for this catalysis by carboxylate and cacodylate ions are 0.96 (for R = H), 0.93 (for R = C2H4CN), and 0.76 (for R = CH2CN).These results, combined with calculations that suggest that amine expulsion from the zwitterionic intermediate, T^+/-, from ammonia is slower than diffusion processes involving T^+/- and catalyst, are consistent with a mechanism in which a simple proton transfer process is not rate determining.Because of the stability of T^+/- it is likely that catalysis in this system is "enforced" by the lifetime of this intermediate.We suggest that catalysis of these reactions is observed because hydrogen bonding of T^+/- to the conjugate acid of the catalyst provides an energetic advantage by stabilizing both T^+/- and the transition state for amine expulsion from this species.Hydrolysis of N-acyl benzophenone imines, Ph2C=NC(O)CH2X (X = H, OCH3, or Cl), involves a rapid, favorable equilibrium for addition of water across the C=N bond, followed by amide expulsion from the carbinolamide.The latter process, analogous to amine expulsion from carbinolamines, is subject to weak general acid catalysis with Broensted α values of 0.5-0.6.This catalysis probably corresponds mechanistically either to (1) bifunctional or "one-encounter" catalysis in which one or both of the proton-transfer processes is "concerted" with C-N cleavage, or (2) general base catalysis of the expulsion of the O-protonated amide from Ph2C(OH)N⁺HC(OH)CH2X.For uncatalyzed carbinolamide cleavage a cyclic transition state with intramolecular proton transfer to the acyl oxygen is suggested to explain the observed insensitivity to substituents, X, of amide expulsion from the neutral carbinolamides, Ph2C(OH)NHC(O)CH2X.