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 phthalimide with secondary amines

Abstract

The reaction rates of the cleavage of phthalimide (PTH) were studied at 30°C in buffer solutions of trimethylamine, triethylamine, triethanolamine, carbonate, piperidine, dimethylamine, morpholine, piperazine and N‐methylpiperazine at different pH values. The reactivity of carbonate, triethylamine and triethanolamine toward PTH could not be detected under the experimental conditions applied. However, triethylamine 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 Brønsted 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 Brønsted 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.

Kinetic evidence for the occurrence of general acid-base catalysis in N-methylhydroxylaminolysis of N-ethoxycarbonylphthalimide (NCPH)

“…In the aminolysis of maleimide, primary amines [3] did not show GA -GB catalysis while secondary [4] and tertiary [5] amines showed GA -GB and GA catalysis, respectively. Such a selective reactivity of primary, secondary, and tertiary amines could not be detected in the aminolysis of phthalimide [6], NCPH [7], and N-hydroxyphthalimide [8]. General base catalysis has been observed in the reactions of hydroxylamine with NCPH [7], N-hydroxyphthalimide [9], and in the reaction of N-methylhydroxylamine with N-hydroxyphthalimide [10].…”

Effect of CH3CN-H2O and CH3CN solvents on rate of reaction of phthalimide with piperidine

“…14,20 Although the present data obtained in mixed aqueous-acetonitrile solvents are not sufficient to discuss any detailed mechanism, it appears that there is no change in mechanism with change in the composition of CH 3 CN-H 2 O solvent. The mechanism for the reaction of Pip with PTH in mixed CH 3 CN-H 2 O solvents may be as shown in Scheme 1, where T AE is a highly reactive transient intermediate.…”

Kinetics and mechanism of alkaline hydrolysis of 4‐nitrophthalimide in the absence and presence of cationic micelles

“…The values of k obs remained unchanged with the change in the total concentration of carbonate buffer from 0.1 to 0.7 M at pH These results show that the pH-10.2 Ϯ 0.1. independent rate of hydrolysis of NPTH is insensitive to general base catalysis. The rate of alkaline hydrolysis of phthalimide [15] and N-hydroxyphthalimide [13] were found to be insensitive and sensitive, respectively, to general base catalysis.…”