The metal-ion-promoted water- and hydroxide-ion-catalysed hydrolysis of amides

Abstract

Rate constants have been determined for the hydrolysis of 8-trifluoroacetamidoquinoline-2-carboxylic acid and N-(6-carboxypicolinyl)-2,4-dinitroaniline in water at 70 °C. The hydrolysis reactions of these amides in the absence of metal ions are OH^– catalysed at pH values >7. Divalent metal ions (Co²⁺, Ni²⁺, and Zn²⁺) have a significant catalytic effect on the rates of hydrolysis. Binding of the metal ions to the amides is strong, and saturation occurs at low metal ion concentrations ( <0.01 mol dm^–3) At saturating concentrations of the metal ions k_obs is pH independent at pH < 7. Thus, the metal-ion-catalysed reactions are water reactions or a kinetic equivalent. Metal-ion-promoted OH^– catalysed reactions are not observed. In contrast, the Ni²⁺ catalysed hydrolysis of the β-lactam, N-(8-quinolyl)azetidin-2-one proceeds through a metal-ion-promoted OH^– reaction. A 0.01 mol dm^–3 concentration of Ni²⁺(non-saturating) provides a rate enhancement of 10⁵ over that observed in the absence of metal ion. The type of metal ion catalysis observed in amide hydrolysis, i.e., pH independent or OH^– dependent must be determined by the nature of the rate-determining step and the ease of C–N bond breaking. A metal-ion-promoted OH^– catalysed reaction will occur at pH values near neutrality when C–N bond breaking is facile and nucleophilic attack is rate determining, whereas when C–N bond breaking is difficult and therefore part of the rate-determining step, the reaction will be pH independent because of the requirement for protonation of the nitrogen leaving group.