Intramolecular catalysis in the hydrolysis of glycosides and acetals

Abstract

The hydrolyses of 2-carboxyphenyl β-D-glucoside, 2-carboxyphenyl α-D-glucoside, 2-methoxymethoxybenzoic acid, and 8-methoxymethoxy-1-naphthoic acid follow kinetic laws of the form Rate =kobs[total substrate]=k1[un-ionised form]+k2[un-ionised form]×aH+. At pH 4–5 the hydrolyses of all of these compounds are substantially faster than those of analogous compounds lacking a carboxy-group. The possibility that the carboxy-group is providing intramolecular nucleophilic catalysis in the hydrolysis of 2-methoxymethoxybenzoic acid was excluded by showing that methoxymethyl salicylate and benzo-1,3-dioxan-4-one are not intermediates. A mechanism involving intramolecular general-acid catalysis is preferred and this is shown to be consistent with the solvent isotope effect, k1(H2O)/k1(D2O)= 1·43, and the rate-enhancing effect of a nitro-substituent at position 4. Similar isotope and substituent effects are observed in the hydrolysis of 2-carboxyphenyl β-D-glucoside which is therefore considered to react via a similar mechanism.