Degradation Kinetics of Carumonam in Aqueous Solution

Abstract

The degradation and kinetics of carumonam (1) in aqueous solution were investigated by highperformance liquid chromatography (HPLC) at 35°C and an ionic strength of 0.5 over the pH range of 0 to 10. All the main degradation products observed by HPLC were isolated and identified. It was concluded that these products were formed by a combination of five reactions, a β-lactam ring-opening reaction, reversible C₃-epimerization, reversible syn-anti isomerization, desulfonation, and a decarbamoylation reaction. The overall rate of degradation was of pseudo-first-order type and was influenced by solvolytic, hydrogen ion, and hydroxide ion catalysis. Simultaneous reversible C₃-epimerization and β-lactam ring-opening reaction, which occur in neutral and alkaline solutions, proved to be catalyzed by hydroxide ion. The pH-rate profile for 1 exhibited a unique W-shape due to syn-anti isomerization in a specific pH region. The maximum stability of 1 was observed in the pH range of 4.9 to 5.8. The theoretical pH-rate profile agreed well with the experimental data, and primary salt effect was also considered theoretically. The activation energies determined at μ=0.5 were 22.3, 15.6 and 17.5 kcal/mol at pH 4.40, 7.01 and 8.88, respectively.