Hydrolysis of 2-(p-Nitrophenoxy)tetrahydropyran: solvent and α-Deuterium secondary kinetic isotope effects, and relationships with the solvolysis of simple secondary alkyl arenesulfonates and the enzyme-catalysed hydrolysis of glycosides

The effect of solvent composition in aqueous ethanol, trifluoroethanol and hexafluoropropan-2-ol on the rate constant and activation parameters for the uncatalysed hydrolysis of 2-(p-nitrophenoxy)tetrahydropyran (1) was investigated, and the m(YOTs) value is 0.60. This appreciable but less than maximal value is in accordance with an SN1 mechanism with rate-limiting ionization. The -deuterium secondary kinetic isotope effect (-kie) for the uncatalysed hydrolysis of 1 is 1.17 in water (46°C), 1.15 in aqueous trifluoroethanol (50% mole fraction, 70.6°C) and 1.13 in aqueous ethanol (50% mole fraction, 70.6°C). These values correspond to about 1.19 at 25°C, which is characteristic of rate-limiting ionization in an SN1 reaction and appreciably higher than values for enzyme-catalysed glycolysis. The -kie is smaller under aqueous acidic conditions (1.07, 0.1 mol dm-3 hydrochloric acid, 20.2°C) when 1 hydrolyses with acid catalysis. The previously reported -kie for the hydrolysis of 1 in buffered aqueous dioxan (1.063, 25°C) is now seen to correspond to acid-catalysed hydrolysis. These new results for 1 indicate that transition structures in enzyme-catalysed glycolyses with -kie values of less than about 1.15 at 25°C involve a lower degree of carbenium ion character than has hitherto been assumed. Copyright © 2004 John Wiley & Sons, Ltd.