Dichloromethane → Butoconazole

Participants

Reaction Steps

Next we studied alternative solvents to replace the thionyl chloride in solvent function in the reaction step converting (1-[4-(4-chlorophenyl)-2-hydroxy-n-butyl]-imidazole) (IV) into (1-[4-(4-chlorophenyl)-2-chloro-n-butyl]-imidazole) (V). In the inert solvents which could be taken into account such as dichloromethane, toluene, chlorobenzene and dimethylformamide, the chlorinating reaction yielded a sticky reaction mixture which couldn't be processed. We have surprisingly found, however that when (1-[4-(4-chlorophenyl)-2-hydroxy-n-butyl]-imidazole) (IV) is dissolved in 1,2-dichloroethane and reacted with approximately equimolar amount of thionyl chloride reagent in the presence of catalytic amount of dimethylformamide at 30-35° C. temperature, a crystal suspension is obtained which is easy-to-stir during the whole reaction time, resulting in that chlorination proceeds completely giving 1-[4-(4-chlorophenyl)-2-chloro-n-butyl]-imidazole (V) in quantitative yield. Being the compound sufficiently pure, it is not isolated, but separated by extraction and reacted directly with 2,6-dichlorothiophenol in methyl isobutyl ketone to give 1-[4-(4-chlorophenyl)-2-(2,6-dichlorophenylthio)-n-butyl]-imidazole (VI) (butoconazole).

Provenance & Evidence