Synthesis of N-Acyloxysuccinimides with Short Chain Fatty Acid Residues and the Reactions with Aliphatic Primary Amines in Aqueous Solution

Abstract

The reactions of N-hydroxysuccinimide (1) with fatty acids (2) in the presence of N, N'-dicyclohexylcarbodiimide (DCC) in dioxane gave N-acyloxysuccinimides (3) (CN=211) which were purified by fractional crystallization and silica gel column chromatography. The structures of (3) were determined by GLC-MS.
The reaction of (3) (CN=28) with an aliphatic primary amine in aqueous solution was studied kinetically. N-Acylation of the amine was competitive with decomposition of (3) and its rate is expressed as follows : V=-(k_{1, d}+k₂[Amine])[(3)], where k_{1, d} is the first order rate constant and k₂ is the second order rate. The rate decreased with increasing the length of carbon chain of acid residue (CN) in (3). The slope of log k₂ vs. pH plot was 1.0, indicating nucleophilic attack of the free amino group on the carbonyl carbon in (3). The rate ratio, k₂/k_{1, d}, was maximum at about pH 9. The ratio, 10^-3 k₂/k_{1, d}, was larger than unity for the reaction of (3) with primary amines containing straight chains. The above observations suggest a possibility of (3) be an N-acyl reagent of amino compounds in aqueous solution.