利多卡因合成工艺的优化研究  

Study on optimization of lidocaine synthetic process

作　　者：刘畅畅 张鑫鑫[1] 雷璞杰 吴海霞[1] LIU Chang-chang;ZHANG Xin-xin;LEI Pu-jie;WU Hai-xia(School of Chemical and Pharmaceutical Engineering,Hebei University of Science and Technology,Shijiazhuang 050091,China)

机构地区：[1]河北科技大学化学与制药工程学院,河北石家庄050091

出　　处：《现代化工》2023年第9期176-178,184,共4页Modern Chemical Industry

摘　　要：利多卡因由2,6-二甲基苯胺先经氯乙酰氯酰化、再经二乙胺胺化两步工艺路线制得。在不加入催化剂的情况下,第2步胺化反应的自然反应时间在8 h以上,耗时太长。通过改变第2步的反应溶剂、底物之间的摩尔比、催化剂和温度等优化反应工艺。结果表明,反应溶剂为乙腈、底物n(N-氯乙酰-2,6-二甲基苯胺)∶n(二乙胺)=1∶2、催化剂为无水碳酸钾1.0 eq+碘化钾0.1 eq、温度为55~70℃时,反应时间缩短了4 h,产品利多卡因摩尔收率达到85.17%,产品纯度达到99.777%。Lidocaine is prepared from 2,6-dimethylaniline by chloroacetyl chlorination at first and then diethylamine amination.Without catalyst,the natural reaction time of amination in the second step spends more than 8 hours.The reaction process is optimized by changing the reaction solvent,the molar ratio between substrates,catalyst and temperature in the second step.The results show that the reaction time is shortened by 4 hours,the molar yield of lidocaine reaches 85.17%and the product purity reaches 99.777%when acetonitrile is served as the reaction solvent,n(N-chloroacetyl-2,6-dimethylaniline):n(diethylamine)=1:2,the temperature is 55-70℃,and anhydrous potassium carbonate 1.0 eq+potassium iodide 0.1 eq is used as the catalyst.

关 键 词：利多卡因 N-氯乙酰-2 6-二甲基苯胺 乙腈 碳酸钾 碘化钾 

分 类 号：R914.4[医药卫生—药物化学]