KINETICS AND MECHANISM OF THE CLEAVAGE OF PHTHALIMIDE IN BUFFERS OF TERTIARY AND SECONDARY-AMINES - EVIDENCE OF INTRAMOLECULAR GENERAL ACID-BASE CATALYSIS IN THE REACTIONS OF PHTHALMIDE WITH SECONDARY-AMINES

The reaction rates of the cleavage of phthalimide (PTH) were studied at 30-degrees-C in buffer solutions of trimethylamine, triethylamine, triethanolamine, carbonate, piperidine, dimethylamine, morpholine, piperazine and N-methyl-piperazine at different pH values. The reactivity of carbonate, triethylamine and triethanolamine toward PTH could not be detected under the experimental conditions applied. However, trimethylamine revealed nucleophilic reactivity toward non-ionized PTH (SH). The steric requirements of triethylamine and triethanolamine are ascribed to the absence of nucleophilic reactivities of these amines toward SH. Secondary amines show nucleophilic reactivity toward both SH and ionized PTH (S-). The absence of nucleophilic reactivity of trimethylamine and the presence of nucleophilic reactivity of secondary amines toward S- are attributed to the occurrence of intramolecular general acid-base catalysis due to the presence of a mobile proton at the nucleophilic site of the nucleophile. Intermolecular general base catalysis was observed in the reactions of SH with all secondary amines except piperidine and such catalysis could be detected in the reactions of S- with morpholine, piperazine and N-methylpiperazine. Nucleophilic second-order rate constants for the reactions of secondary amines with SH (k1) and S- (k2) reveal the Bronsted plots of slopes of ca 0.8 and 0.3, respectively. Similarly, the general base-catalysed third-order rate constants (k4) for the reactions of secondary amines with SH yield a Bronsted plot of slope 1.2. These observations suggest the occurrence of diffusion-controlled trapping stepwise and pre-association stepwise mechanisms in the aminolysis of non-ionized and ionized phthalimide, respectively.