Metabolism of 1,1,1,2,2-pentafluorohexane and 1,1-difluorocyclohexane by rat liver microsomes in vitro

Metabolism of 1,1,1,2,2-pentafluorohexane with liver microsomes from phenobarbital-treated rats gave only one metabolite, namely, the 5-hydroxy derivative. Under similar conditions 1,1-difluorocyclohexane was metabolized to give mainly the 3- and 4-hydroxy derivatives in the ratio 1: approximately 5.5. The structures of these metabolites were established by chemical ionization (CI) and/or electron impact (EI) mass spectrometry and confirmed by synthesis in the case of 1,1-difluorocyclohexan-4-ol. Oxidation of 1,1-difluorocyclohexane with lead tetrakis(trifluoroacetate) also gave, inter alia, the 3- and 4-hydroxy derivatives. In saturated hydrocarbons complete replacement of hydrogen by fluorine at one particular carbon will not only block microsomal hydroxylation thereat but will also inhibit hydroxylation at neighbouring hydrogen-bearing carbons, (alpha almost completely, beta markedly, gamma slightly).