化工进展Issue(4)：1104-1108,5.DOI:10.16085/j.issn.1000-6613.2015.04.035
盐酸氟桂利嗪的合成工艺改进
Improved synthesis of flunarizine dihydrochloride
陈连锋 1张丁 2王风云 1夏明珠 1雷武 1朱其军1
作者信息
- 1. 南京理工大学工业化学研究所，江苏南京 210094
- 2. 盐城格瑞茵化工有限公司，江苏盐城 224400
- 折叠
摘要
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 asn(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.关键词
盐酸氟桂利嗪/哌嗪/双(4-氟苯基)溴甲烷/肉桂醇Key words
flunarizine dihydrochloride/1,4-diazacyclohexane/bis(4-fluorophenyl)methane bromide/cinnamyl alcohol分类
化学化工引用本文复制引用
陈连锋,张丁,王风云,夏明珠,雷武,朱其军..盐酸氟桂利嗪的合成工艺改进[J].化工进展,2015,(4):1104-1108,5.
