A Method for Synthesis of Fluorine Compounds Using Abnormal Grignard Reaction of Halothane

Article abstract of DOI:10.1021/jo00040a036

The reaction of 2-bromo-2-chloro-1,1,1-trifluoroethane (1) with 2-octanone (3a) in the presence of magnesium did not give 2-chloro-1,1,1-trifluoro-3-methyl-3-nonanol (4a) but 2-bromo-2-chloro-1,1,1-trifluoro-3-methyl-3-nonanol (5a) and 2-chloro-1,1-difluoro-3-methyl-1-nonen-3-ol (6a).This suggested that the primary Grignard reagent, 1-chloro-2,2,2-trifluoroethylmagnesium bromide (2), reacted with excess 1 rather than with the ketone 3a to give 1-bromo-1-chloro-2,2,2-trifluoroethylmagnesium bromide (8), which added to the ketone to give 5a.Detection of 1,1,1-trifluoro-2-chloroethane supported this mechanism.Compound 5a was formed preferentially at -53 deg C, and as the reaction mixture was warmed to 0 deg C, the amount of 5a decreased, while that of 6a increased.Therefore, compound 6a must be formed by reduction of 5a with excess magnesium.Treatment of 6a with hydrogen fluoride gave 2-chloro-1,1,1-trifluoro-3-methyl-2-nonene (9a).Cyclohexanone and acetophenone reacted similarly to give corresponding products.