Amine Catalysis of the Hydrolysis of Trifluoroacetanilide

Article abstract of DOI:10.1021/jo01301a026

Only hydrolysis products could be isolated from the reaction of trifluoroacetanilide I with aqueous n-butylamine buffer at pH 10.5.Kinetic studies of the decomposition of trifluoroacetanilide I in aqueous morpholine, n-butylamine, piperidine and trimethylamine buffers were also conducted.The most reasonable scheme for the reaction mechanism, compatible with all data, is presented in Scheme I and involves the general-base-catalyzed decomposition of the intermediate III which can be formed by hydroxide ion or water addition to I.Utilizing the constants of Table I, eq 6 is capable of predicting observed rate constants with an error of l ess than 9 percent (see Tables II an III).Some variation in values for these constants for trimethylamine buffers is observed and attributed to possible activity changes for the solutions.Deuterium isotope rate effects were determined for these constants in morpholine buffers.A value of k₁^H2O_/k2D2O of 0.39 was obtained and may indicate the presence of a third pathway for the generation of III (eq 9), involving the hydration of the anion II.A value of k₄^H2O_/k4D2O of 1.65 and a Broensted β value of 0.23 for k₄ are interpreted to indicate general-base catalysis by the amine buffer.The low values for these quantities are indicative of a transition state involving an early proton transfer.General-base catalysis of proton transfer for the k₄ step is also indicated by the fact that trimethylamine appears to behave mechanistically, similar to the other amines used.The value of 8.8 obtained for k₃^H2O_/k3D2O clearly shows proton transfer to be occuring in this step as well.The results of this study thus support those suggested previously in that the hydrolysis of I undergoes a change in rate-determining step in mild alkaline aqueous solutions.This occurs because of the combination of the poor leaving ability of the anilinium ion and acyl activation present in the substrate trifluoroacetanilide.