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

Trityl 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 degrees C. The monomethoxy compound is less reactive and the parent trityl analogue showed minimal reactivity. Using presently reported and literature kinetics results with pK(a) 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 (YH2+) of the nucleofuges YH. Enthalpies and corresponding free energies at 25 degrees C for the dissociation of the specifically solvated ions CH3 - YH(H2O)(+)(n) (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) (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 Ph3C - O(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 Ph3C - OCH2CF3 in aqueous solution are concerted with proton transfer in which case the hydrolytic cleavage will be general acid catalysed. Copyright (c) 2008 John Wiley & Sons, Ltd.