Studies on Models for Tetrahydrofolic Acid. V.A Kinetically Significant Transport Process in General Base Catalyzed Aminolysis of a Formamidine

The methoxyaminolysis of the unsymmetrically substituted formamidine I exhibits general base catalysis by amines, phosphate, and carboxylates. The catalytic constants are best correlated in the Bronsted relationship by two straight lines of d β ≃ 1 and β ≃ 0 for pK_BH⁺ < 1.5 and pK_BH⁺ > 1.5, respectively, suggesting the existence of a short-lived covalent intermediate and kinetically significant transport processes. The data support a mechanism in which two sequential proton transfers occur, perhaps within a single encounter complex, the rate-limiting steps being (1) diffusion-controlled encounter of the intermediate and general base species for strong bases, and (2) either diffusion separation of or a “reorganization” within the encounter complex for weaker bases. General considerations for the aminolysis of amidines and certain enzymic reactions.