Nucleophilic aminoalcohol-catalyzed degradation of indomethacin in aqueous solution

The catalytic effect of ethanolamine and related aminoalcohols on the rate of degradation of indomethacin in alkaline solutions has been shown to be due to a nucleophilic reaction mechanism involving formation of an intermediate ester consisting of p-chlorobenzoic acid and aminoalcohol through the reaction of aminoalcohol hydroxyl group with carbonyl carbon of indomethacin amide group. This ester subsequently undergoes a rapid intramolecular aminolysis to yield a stable p-chlorobenzamide derivative and/or is hydrolyzed to p-chlorobenzoic acid, depending on the chemical structure of aminoalcohols. No catalytic effect was observed with the amines not containing a hydroxyl group.