关键词: 盐酸氟桂利嗪, 哌嗪, 双(4-氟苯基)溴甲烷, 肉桂醇

Abstract: Flunarizine dihydrochloride was synthesized with fluorobenzene and cinnamyl alcohol as starting material; bis(4-fluorophenyl)methane bromide was formed through Friedel-Craft reaction,hydrolysis,reduction and bromination of fluorobenzene; trans-1-cinnamylpiperazine was prepared from cinnamyl alcohol and thionyl chloride,then reacted further with bis(4-fluorophenyl) methane bromide to form flunarizine dihydrochloride through chlorination and substitution reaction. Repetitive experiments were conducted to verify experiment stability. The optimal technological condition for the synthesis of flunarizine hydrochloride was found as n(fluorobenzene):n(AlCl₃):n(PEG-400)=1:1.1:0.04,stirred at 45℃ for 2h,n(bis(4-fluorophenyl)-methanone):n(sodium borohydride)=1:0.6 with ethyl alcohol as solvent,stirred at 50℃ for 2h,NBS and AIBN as the reactants,n(4,4'-difluorobenzhydrol):n(NBS):n(AIBN)=1:1:0.03,stirred at 80℃ for 3h,n(cinnamyl chloride):n(1,4-diazacyclohexane)=1:3.5,stirred at 50℃ for 1.5h,under which rough cinnamyl piperazine was purified by washing,extraction and saltification,and this single step yield was up to 56.2%,the total yield of flunarizine dihydrochloride was up to 30.0% with the purity over 99%,higher than 18.5% of original. The structure of product was characterized by IR and MS.

Key words: flunarizine dihydrochloride, 1,4-diazacyclohexane, bis(4-fluorophenyl)methane bromide, cinnamyl alcohol