THE METAL-ION-PROMOTED WATER-ION-CATALYZED AND HYDROXIDE-ION-CATALYZED HYDROLYSIS OF AMIDES

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 kobs 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 Ni 2+ (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.