Divalent metal ion catalysis of acetal hydrolysis; effects of oxycarbocation stability and leaving group basicity

Abstract

Large catalytic effects by low concentrations of Ni2+, Co2+, and Zn2+ were observed in the hydrolysis of 2-(8-quinolyloxy)tetrahydropyran, 6-(8-quinolyloxy)tetrahydropyran-2-carboxylic acid, and ethyl 6-(8-quinolyloxy)tetrahydropyran-2-carboxylate in H2O at 50 °C (µ 0.1M), even though metal ion binding to the acetals is weak. Plots of kobsvs. metal ion concentration are linear even at metal ion concentrations as high as 0.01M. At constant metal ion concentration the reactions are pH-independent at pH >5. The minimum rate enhancement with these compounds at 0.01M-Ni2+ is more than 104 at pH 7.0; Co2+ and Zn2+ are three-fold less effective than Ni2+. The rate constants for oxonium ion catalysis and metal ion catalysis are affected alike by changes in basicity and oxycarbocation stability in 8-quinolyl acetals; these features vary over a wide range (from substituted benzaldehyde methyl 8-quinolyl acetals to 8-quinolyl β-D-glucopyranoside). With each acetal the second-order rate constants for oxonium ion and metal ion catalysis are similar, which indicates that the large rate enhancements observed in the metal-ion-catalysed reactions are due to relative concentration effects of the metal ions in comparison with oxonium ion. Metal ion catalysis was not observed in the hydrolysis of acetals of 2-hydroxymethylpyridine nor in the hydrolysis of m-methoxybenzaldehyde 6-carboxy-2-pyridylmethyl methyl acetal. As in the case of general-acid-catalysed reactions, metal ion catalysis in acetal hydrolysis is highly dependent on leaving group ability; it does not occur when the leaving group is an aliphatic alcohol even in cases where the intermediate oxycarbocation is quite stable (a methoxybenzyl ion) and metal ion binding to the acetal is strong. There are striking mechanistic similarities between intramolecular metal ion catalysis and general acid catalysis in acetal hydrolysis because both reactions involve stabilization of the leaving group in the transition state of the pH-independent C–O bond-breaking reaction.