Organic Chemistry

Unimolecular, bimolecular and intramolecular hydrolysis mechanisms of 4-nitrophenyl β-D-glucopyranoside

Spencer Williams University of Melbourne


1,2-trans-Glycosides hydrolyze through different mechanisms at different pH values, but systematic studies are lacking. Here we report the pH-rate constant profile for the hydrolysis of 4-nitrophenyl β-D-glucoside. An inverse kinetic isotope effect of k(H3O+)/k(D3O)+ = 0.65 in the acidic region indicates that the mechanism requires the formation of the conjugate acid of the substrate for the reaction to proceed, with heterolytic cleavage of the glycosidic C-O bond. Reactions in the pH-independent region exhibit general catalysis with a single proton in flight, a normal solvent isotope effect of kH/kD = 1.5, and when extrapolated to zero buffer concentration show a small solvent isotope effect k(H2O)/k(D2O) = 1.1, consistent with water attack through a dissociative mechanism. In the basic region, solvolysis in 18O-labelled water and H2O/MeOH mixtures allowed detection of bimolecular hydrolysis and neighboring group participation, with a minor contribution of nucleophilic aromatic substitution. Under mildly basic conditions, a bimolecular concerted mechanism is implicated through an inverse solvent isotope effect of k(HO)/k(DO) = 0.5 and a strongly negative entropy of activation (DS = –13.6 cal mol–1 K–1). Finally, at high pH, an inverse solvent isotope effect of k(HO)/k(DO) = 0.6 indicates that the formation of 1,2-anhydrosugar is the rate determining step.


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Supplementary material

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SI 100621