摘要
以环丙基甲基酮为起始原料,五氯化磷为氯化试剂,采用先氯化后消除的工艺合成了依非韦伦关键中间体环丙基乙炔。针对二氯代物中间体(1,1-二氯乙基)环丙烷和一氯代物中间体(1-氯乙烯基)环丙烷消除反应活性的不同,分别在三乙胺和氢氧化钾存在下进行分步消除反应,对消除反应的实验条件进行了优化。得到优化的合成条件为:在3%吡啶(以环丙基甲基酮质量为基准,下同)、10~15℃下进行氯化反应;以三乙胺为碱,回流状态下进行一步消除反应;在KOH/DMSO体系中于110℃进行二步消除反应。在该条件下,以环丙基甲基酮计,环丙基乙炔单程收率可达49%。同时建立了三乙胺的回收套用工艺,进一步降低了成本,具有良好的工业化前景。
Cyclopropyl acetylene,as a key intermediate of efavirenz,was synthesized by chlorination followed by elimination using cyclopropyl methyl ketone as starting material and phosphorus pentachloride as chlorination reagent.For the different elimination reactivity of dichlorinated intermediate,(1,1-dichloroethyl)cyclopropane,and monchlorinated intermediate,(1-chlorovinyl)cyclopropane,the stepwise elimination reactions were carried out in the presence of triethylamine and potassium hydroxide,respectively.The experimental conditions of elimination reaction were optimized.The results showed that the chlorination reaction was conducted in 3%pyridine(based on the mass of cyclopropyl methyl ketone,the same below),at 10~15℃.Taking triethylamine as base,one step elimination reaction was carried out under reflux.Two-steps elimination reaction was performed at 110℃in the KOH/DMSO system.Under these conditions,a one-way yield as high as 49%of cyclopropyl acetylene was obtained based on cyclopropyl methyl ketone.At the same time,the recycling process for triethylamine was established,which further reduced the cost and had a good prospects for industrialization.
作者
张洁
陈亚红
田丰收
王瑞勇
ZHANG Jie;CHEN Ya-hong;TIAN Feng-shou;WANG Rui-yong(College of Chemistry and Molecular Engineering,Zhengzhou University,Zhengzhou450000,Henan,China;Collegeof Chemistry and Chemical Engineering,ZhoukouNormal University,Zhoukou466001,Henan,China)
出处
《精细化工》
EI
CAS
CSCD
北大核心
2019年第10期2147-2150,共4页
Fine Chemicals
基金
河南省科技厅科技攻关项目(1721102310626)
关键词
依非韦伦
环丙基甲基酮
环丙基乙炔
精细化工中间体
efavirenz
cyclopropyl methyl ketone
cyclopropyl acetylene
fine chemical intermediates
