Abstract
1,2-trans-Glycosides hydrolyze through a
range of mechanisms under conditions of different pH, 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 (k(H3O+)/k(D3O+)
= 0.63) 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 exhibited general catalysis with a single proton in
flight with 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,
which is 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,
and to a minor degree, nucleophilic aromatic substitution. Under mildly basic
conditions, a bimolecular dissociative mechanism is implicated through an
inverse solvent isotope effect of k(HO–)/k(DO–)
= 0.5 and a strongly negative entropy of activation (deltaS‡ = –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.
Supplementary materials
Title
SI 280121
Description
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