Kinetic evidence for the occurrence of a stepwise mechanism in the aminolysis of maleimide. General acid and base catalysis by secondary amines

Abstract

The reaction rates for nucleophilic cleavage of maleimide have been studied for buffered solutions of eight secondary amines. The reactions of secondary amines with ionized and non-ionized malemide are subject to general acid and general base catalysis, respectively. Non-liner plots of the apparent second-order rate constants at a given pH against total buffer concentrations reveal that the rate-determining step chages as the buffer concentration is increased; this provides evidence for the existence of an intermediate on the reaction path. The rate constants for specific acid-catalysed cleavage of an oxy monoanionic tetrahedral addition intermediate (T^–) display a Brønsted plot of slope (β_nuc) 0.37. The rate constants for general base-catalysed cleavage of non-ionized maleimide (SH) reveal a Brønsted plot of slope (β_nuc1) 0.79. The significantly high value of β_nuc1 is attributed to a normal stepwise mechanism (i.e. diffusion-contraolled trapping mechanism) in which a zwitterionic tetrahedral addition intermediate (T^±) is converted into T^– by general base catalysis. The rate constants for general acid-catalysed

clevage of ionized malemide (S) fit a Brønsted plot of slope (β′_nuc) 0.47. The low value of β′_nuc1 compared with that of β_nuc1 is explained by assuming a preassociation stepwise mechanism in which the highest energy barrier on the reaction co-ordinate involved in the formation of T^– is for nucleophilic attack within the encounter complex. An uncatalysed term in the rate law for the cleavage of maleimide could not be detected under the experimental conditions.