title: Hydrolysis mechanisms for indomethacin and acemethacin in perchloric acid.
abstract: The acid-catalyzed hydrolysis reactions of the antiinflammatory drugs indomethacin and acemethacin were investigated at 25.0 degrees C in a number of strongly concentrated perchloric acid media. The reaction rates were evaluated by UV measurements, and the intermediate species were detected by UV-vis, 1H NMR, 13C NMR, and mass spectroscopy measurements. A switchover from an A-2 to an A-1 mechanism as a function of the medium acidity is reported for the acid-catalyzed hydrolyses of the amide group of both indomethacin and acemethacin. In the A-2 hydrolysis, two water molecules are involved in the rate-determining step. An analysis of the kinetic data collected for acemethacin by the different techniques used reveals a complex mechanism, indomethacin being a metabolite intermediate species in the hydrolysis of acemethacin. The rate constants for the hydrolysis of the acemethacin ester group were considerably larger compared to those of the amide group.
authors: Universidad de Burgos, Departamento de Química, 09001 Burgos, Spain.
authors: B
authors: B
authors: García
authors: F J
authors: FJ
authors: Hoyuelos
authors: S
authors: S
authors: Ibeas
authors: J M
authors: JM
authors: Leal