Abstract
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.
Supplementary materials
Title
SI 09032021
Description
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