General acid-catalyzed addition of methanol to (E)-N- benzylideneanilines

The reaction of equilibrium addition of methanol (a-amino ether formation) to benzylideneanilines (C6H5CH=NC6H4Y, with Y = H (1a), 3-Cl (1b), 3-NO, (1c), 4-CN (1d), and 4-NO2(1e)) in methanol is shown to be general acid-catalyzed in carboxylic acid buffers. The mechanism involves fast iminium ion formation followed by base-assisted addition of methanol. The alpha Bronsted exponents are in the 0.67-0.88 range, and a increases with the electron-withdrawing ability of Y. The same mechanism is valid for MeOH2+-catalysis, meaning that two solvent molecules are involved in the addition process, one of them playing the role of base. The equilibrium constant, K, is increased by electron-withdrawing substituents, log K depending linearly on the sigma(-) substituent parameters. The substituent effects on the forward and reverse catalytic rate constants are analyzed by means of the log k = rho(n)sigma(n) + rho(r)(sigma(-) - sigma(n)) + constant (Young-Jencks) equation. For carboxylic acid catalysis, the rho(n) and rho(r) parameters are in keeping with ca. half C-O bond forming or breaking at the transition state. The catalytic rate constants and alpha exponent for elimination of ClCH2CH2OH in methanol from the C6H5CH(OCH2CH2Cl)NH(4-CNC6H4) chloroethyl adduct are compared with those for the elimination of methanol from C6H5CH(OCH3)NH(4-CNC6H4). The chloromethyl group makes the reaction slower and alpha lower. This indicates that proton transfer is a little ahead of C-O bond cleavage at the transition state. Y substituent effects, alpha values, and the effects of the CH2Cl group are interpreted on the basis of a More O'Ferrall - Jencks diagram.