Acid‐catalysed hydrolysis of methoxy‐substituted trityl trifluoroethyl ethers: a kinetic and computational investigation of leaving group effects

Abstract

AbstractTrityl trifluoroethyl (TFE) ether and its 4‐methoxy, 4,4′‐dimethoxy‐, and 4,4′,4″‐trimethoxy‐substituted analogues have been prepared; the dimethoxy and trimethoxy compounds undergo ready acid‐catalysed hydrolysis at constant ionic strength = 1 mol dm−3 at 25°C. The monomethoxy compound is less reactive and the parent trityl analogue showed minimal reactivity. Using presently reported and literature kinetics results with pKa values of protonated substrates, first‐order rate constants covering 12 orders of magnitude have been determined for heterolysis/dissociation of 11 protonated dimethoxytrityl derivatives DMTrYH+ where YH = H2O, CF3CH2OH, ArNH2 and RNH2. There is a good correlation between logarithms of these rate constants and the pKa values of the conjugate acids (Y) of the nucleofuges YH. Enthalpies and corresponding free energies at 25°C for the dissociation of the specifically solvated ions CH3 (YH = MeOH and CF3CH2OH, n = 1; H2O, n = 2; and NH3, n = 3) have been calculated at the B3LYP/6‐31+G* level. Corresponding gas phase calculations have also been carried out for Ph3C (YH = H2O, n = 2; MeOH, n = 1; CF3CH2OH, n = 1 and NH3, n = 3) and, in addition, structures for these solvated ions with (YH = H2O, MeOH and NH3) have been calculated. The specifically solvated ion Ph3CO(H)CH2CF3(H2O)+ does not correspond to a stable bonded species in the gas phase, which suggests that acid‐catalysed fragmentation of methoxy‐substituted analogues of Ph3COCH2CF3 in aqueous solution are concerted with proton transfer in which case the hydrolytic cleavage will be general acid catalysed. Copyright © 2008 John Wiley & Sons, Ltd.