Aspirin, aminolysis

Intramolecular general base catalysed reactions (Section II, Tables E-G) present less difficulty. A classification similar to that of Table I is used, but since the electrophilic centre of interest is always a proton substantial differences between different general bases are not expected. This section (unlike Section I, which contains exclusively unimolecular reactions) contains mostly bimolecular reactions (e.g. the hydrolysis of aspirin [4]). Where these are hydrolysis reactions, calculation of the EM still involves comparison of a first order with a second order rate constant, because the order with respect to solvent is not measurable. The intermolecular processes involved are in fact termolecular reactions (e.g. [5]), and in those cases where solvent is not involved directly in the reaction, as in the general base catalysed aminolysis of esters, the calculation of the EM requires the comparison of second and third order rate constants. 

Nitrophenyl esters (3) are activated esters, especially susceptible to nucleophilic groups such as amines. It would be of interest to see if the NH2 groups of polyethylenimines are also effective in the aminolysis of less-activated esters. As a step in this direction we have examined24 the kinetics of deacylation of acetylsalicylate (aspirin, I) and of succinyl-disalicylate (diaspirin, II)... 

With these substrates we have made more extensive rate studies and determined more specifically defined kinetic parameters. If each amine-containing binding domain D on the modified polymer binds aspirin A reversibly in a step preceding aminolysis, the kinetic steps may be represented by... 

From previous determinations of the moles of nitrophenyl acylates cleaved by polyethylenimines we presumed that only the primary amine groups of the polymer were functional in aminolysis and hence we assumed that only these would be effective in the deacylation of acetylsalicylate. To test this assumption we have examined the kinetics of aminolysis of aspirin by isopropylated polyethylenimine. 

Deacylation rates of acetylsalicylate by isopropylated polymer at pH 7.3 were markedly slower than with unmodified polymer (Table III). With 2.4xlO-2 total residue molar concentration of isopropylated and unmodified poly(ethylenimine), respectively, k2, the pseudo-first-order rate for the former was 1.45 x 10-3 min-1, for the latter 1.2 x 10-1 min-1. Clearly, primary amines are the major sites for aminolysis of aspirin. 

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