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.