One-electron reduction of halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) by free radicals. Radiation chemical model system for reductive metabolism

Abstract

The reaction mechanism of one-electron and radical-induced degradation of the general anaesthetic halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) has been investigated for γ-irradiated, oxygen-free aqueous solutions containing various alcohols or formate. Modern ion chromatography and conventional g.c.–m.s. methods were used as analytical tools for identification of end products. This includes quantitative determination of Cl– ions in the presence of Br– ions. Reduction of halothane by hydrated electrons, various alcohol radicals, and ĊO2– proceeds via Br– elimination and CF3ĊHCl radical formation as initial step. t-Butyl alcohol radicals ĊH2C(CH3)2OH abstract bromine atoms to yield BrCH2C(CH3)2OH which suffers base-catalysed Br– elimination. Chain reactions leading to high Br– yields are observed in solutions containing propan-2-ol, ethanol, methanol, and formate. Based on 2k= 109 mol–1 dm3 s–1 for the dimerization of 2 CF3ĊHCl radicals the following rate constants have been measured: k(CF3ĊHCl + propan-2-ol)= 670 mol–1 dm3 s–1, k(CF3ĊHCl + ethanol)= 130 mol–1 dm3 s–1, k(CF3ĊHCl + methanol)= 27 mol–1 dm3 s–1 and k(CF3ĊHCl + formate)= 2 900 mol–1 dm3 s–1 Dimerization of CF3ĊHCl leads to CF3CHClCHClCF3 which suffers base-catalysed HCl elimination to yield the two stereoisomers of CF3CHCClCF3. The halothane results are compared with corresponding findings in CCl4-containing systems.