Mechanism of the Aminolysis of Alkyl Benzimidates

Article abstract of DOI:10.1021/ja00388a048

The aminolysis of a series of ring- and alkyl-substituted benzimidates proceeds through a mechanism involving the formation and decomposition of a tetrahedral intermediate as evidenced by a change in rate-determining step with changing pH.On the alkaline side of the pH-rate profile, formation of the tetrahedral intermediate from the free amine and protonated benzimidate is rate determining.Structure reactivity correlations for this step show a late (intermediate-like) transition state with β_nuc = 0.61, β₀ = -0.47 (for O-substituted benzimidates), and ρ = 1.49.There is no evidence for a kinetically significant proton-transfer step.The addition of water to alkyl benzimidates follows β₀ = -0.56.On the acidic side of the pH-rate profile for aminolysis, the breakdown of the intermediate with expulsion of alcohol is the rate-determining step, as evidenced by the observation of an exchange reaction of methoxyamine for ammonia.The neutral tetrahedral intermediate (T₀) partitions between acid-catalyzed expulsion of alcohol, ammonia, and methoxyamine with partition ratios of approximately 1/1/300, respectively.The expulsion of alcohol also occurs by a spontaneous (water catalyzed) reaction characterized by β₀ = -1.30 and ρ = -0.01, suggesting a late (product-like) transition state for this reaction.The expulsion of alcohol through a general-acid-catalyzed reaction is characterized by relatively low Broensted α values of 0.40-0.49.The decrease in α with decreasing pK of the leaving alcohol can be described by an interaction coefficient p_xy' = 1/c₅ = δα/δpK_1g = 0.05.This reaction can be described on a structure-reactivity diagram by a diagonal reaction coordinate that represents concerted proton transfer and C-O bond cleavage in the transition state.The effect of structure on the direction of acid-catalyzed expulsion of alcohols and amines from addition compounds is reviewed briefly.