Kinetics and mechanism of aminolysis of phthalimide and N-substituted phthalimides. Evidence for the occurrence of intramolecular general acid-base catalysis in the reactions of ionized phthalimides with primary amines

Abstract

The kinetics and mechanism of the reactions of propane-1,3-diamine (PDA) and 1,4-diazabicyclo-[2.2.2]octane(DABCO) with phthalimide (PTH), N-hydroxyphthalimide (NHPH), and N-bromopropyl-phthalimide (NBPPH) and 2-methoxyethylamine with NHPH and NBPPH are described. Both ionized and non-ionized PTH are reactive toward PDA while only ionized NHPH showed reactivity toward PDA and 2-methoxyethylamine under the experimental conditions imposed. The presence and absence of or weak nucleophilic reactivity of DABCO toward neutral and ionized imides, respectively, are noted for PTH and NHPH. Significant nucleophilic reactivity of primary amines and the absence or considerably low nucleophilic reactivity of DABCO toward ionized PTH and NHPH are attributed to the occurrence of intramolecular general acid–base (GA–GB) catalysis due to the presence of a mobile proton at the nucleophilic site of the nucleophile. This intramolecular GA–GB catalysis seems to decrease with increased steric requirements of the leaving group. Diffusion-controlled trapping stepwise and preassociation stepwise mechanisms are suggested in the amino-lysis of non-ionized phthalimides and ionized phthalimides, respectively. Intermolecular GA and GB catalysis has been detected in the reactions of PDA and 2-methoxyethylamine with ionized NHPH and 2-methoxylethylamine with NHPH and ionized NHPH, respectively. Specific-base catalysis could be detected in the reactions of 2-methoxyethylamine with ionized NHPH. The reactions of monoprotonated PDA with ionized NHPH reveal few of favourable electrostatic effects.