利多卡因合成工艺的优化研究

Study on optimization of lidocaine synthetic process

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.