前体药物烟酸丁香酚酯的合成优化及其终点控制  

Improvement on Synthesis of Nicotinic Acid Prodrug Nicotinic Acid EugenolEster and the Control Method of Endpoint

作　　者：厉智明 邵玲莉[2] 王以昊 罗宇航 刘佳慧 Li Zhiming;Shao Lingli;Wang Yihao;Luo Yuhang;Liu Jiahui(Zhejiang Shengtai Safety Technology Co.,Ltd.,Hangzhou 310000,China;Pharmaceutical College,Jinhua Polytechnic,Jinhua 321007,China)

机构地区：[1]浙江圣泰安全技术有限公司,浙江杭州310000 [2]金华职业技术学院制药学院,浙江金华321007

出　　处：《山东化工》2022年第9期9-11,共3页Shandong Chemical Industry

基　　金：2021年浙江省大学生科技创新活动计划暨新苗计划项目(2021R474015)。

摘　　要：对前体药物烟酸丁香酚酯的合成工艺进行了优化,在三乙胺和DAMP共同催化作用下,烟酰氯与丁香酚酰化反应合成了目标产物,采用薄层色谱法进行终点控制。通过L_(9)(3^(4))正交试验优化了合成工艺条件,经红外光谱和核磁证实,结果表明优化工艺条件为:反应物的物质的量比n(酰氯)∶n(丁香酚)=1.2∶1,反应温度为40℃、反应时间4.0 h,催化剂采用三乙胺+DMAP,该条件下烟酸丁香酚酯的产率达到93.09%。薄层色谱法条件为固定相采用硅胶GF254为固定相,展开剂为V(石油醚)∶V(乙醚)=4∶1。该合成方法简化了步骤,收率高,终点控制方法操作简单。The improved synthetic process for the preparation of nicotinic acid eugenol ester was present,the target product was synthesized by acylation of nicotinyl chloride with eugenol catalyzed by triethylamine and DMAP,the endpoint was controlled by TLC.The synthesis conditions were optimized by L_(9)(3^(4))orthogonal test and was confirmed by IR and 1H NMR.The result showed that the optimum conditions were obtained as follow:mass ratio of substances of nicotinyl chloride to eugenol of 1.2∶1,reaction temperature of 40℃,reaction time of 4.0 h,and the catalyst of triethylamine+DMAP,under which the yield could reach 93.09%.The conditions of TLC were as below:the stationary phase of GF 254,the developing agent of petroleum ether and ether(4∶1).The operation process takes the advantages of simplified procedures,high yield,and easy operation of endpoint control method.

关 键 词：烟酸丁香酚酯 合成 终点控制 优化 薄层色谱 

分 类 号：TQ463[化学工程—制药化工]