Protolytic Catalysis of Anilide Methanolysis. Spectator Catalysis of Leaving-Group Departure

Article abstract of DOI:10.1021/jo00178a015

Substituted phenols serve as general-acid catalysts of leaving-group departure from the adduct of methoxide ion with m-NO2C6H4N(CH3)COCF3 in methanol at 25 deg C.Sufficiently high concentrations of general acid convert methoxide addition to the rate-limiting step, allowing determination of rate constants for methoxide addition to substrate carbonyl (k_a = 300 M^-1 s^-1), for overall solvent-assisted leaving-group departure (k_e = k_ak_e^'/k_-a = 5.9 M^-1 s^-1) and for overall general-acid-catalyzed leaving-group departure (k_BH = k_ak_BH^'/k_-a = 2400 +/- 1200 M^-2 s^-1 for five substituted phenols with pKa's from 12.7 to 14.6).Thus the Broensted α ca. 0.It is suggested that the general acid is a spectator at spontaneous expulsion of the leaving group, producing catalysis by fast subsequent trapping of CH3NAr-.The Jencks clock shows the tetrahedral intermediate to have a minimum characteristic lifetime of 1-10 ns.