Kinetics and Mechanism of the Hydrolysis of Anilide Acetals

Article abstract of DOI:10.1021/ja00413a024

A kinetic study of the hydrolysis of anilide acetals ArC(OMe)2NMeAr' is reported.At high pH (>10) a pH independent C-O cleavage reaction is observed producing methanol and benzimidatonium ion; the latter is further hydrolyzed to amide and ester products.Substituent and solvent effects support a simple ionizaiton mechanism with a transition state near the ion.At pH <10, the anilide acetals hydrolyze to benzoate ester, aniline, and methanol in a reaction involving initial nitrogen protonation and C-N cleavage to a dialkoxy carbocation and aniline.At pH 7-10 this reaction shows specific H⁺ catalysis attributable to pre-equilibrium protonation followed by rate-determining cleavage.Estimation of the pK_a of the protonated anilide acetal (-1) provides an estimate of its rate of C-N cleavage (ca.10⁸ s^-1) which is near the diffusion limit.At pH <7 there is a change in the rate-determining step in product formation in this C-N cleavage reaction, and what is observed kinetically is the decomposition of the hemiorthoester ArC(OMe)2OH, the product of hydration of the dialkoxy carbocation.The principal piece of evidence for the changeover is the observation that the rate constants in acid solution are independent of the aniline moiety of the anilide acetal.