A new method for synthesis of fluorine compounds using an unusual Grignard reaction of halothane with ketones

Abstract

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 Grignart 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 °C, and on warming to 0 °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 ( 3b) and acetophenone ( 3c) reacted similarly to give corresponding products. ▪