氯烟酸的合成方法-安徽农业大学学报.PDF

安徽农业大学学报, 2018, 45(5): 955-957 Journal of Anhui Agricultural University [DOI] 10.13610/ki.1672-352x002 网络出版时间：2018/10/24 13:35:00 [URL] /kcms/detail/34.1162.S1611.004.html 2-氯烟酸的合成方法 吕 培，姚 强，张 超 (安徽农业大学资源与环境学院，安徽省农产品安全重点实验室，合肥 230036) 摘 要：2-氯烟酸是一种重要的农药和医药中间体，从易得廉价原料在可控反应条件下高收率制备2-氯烟酸是 市场迫切需要，报道了一条利用关环反应合成2-氯烟酸的新工艺。以固体光气与N ，N-二甲基甲酰胺为起始原料， 反应生成Vilsmeier 盐与乙烯基正丁醚生成中间体2 ，中间体2 与二甲胺反应生成铵基化合物3 ，进一步与氰基乙酸 乙酯反应可得到2-氰基-5-二甲胺基-2,4-二烯-戊酸乙酯4 ，4 在氯化氢乙醇溶液中关环得到 2-氯烟酸乙酯，水解得 到产物2-氯烟酸。对中间体3 、4 和5 的反应条件进行了优化，合成总收率63.4%，产品纯度达99.6% 。确定了该 工艺反应的最佳反应条件，合成条件温和，适合工业化生产。 关键词：2-氯烟酸；关环反应；合成工艺 中图分类号：S482.4 文献标识码：A 文章编号：1672352X (2018)05095503 Synthesis of 2-chloronicotinic acid LYU Pei, YAO Qiang, ZHANG Chao (Key Laboratory of Agri-Food Safety of Anhui Province, School of Resources and Environment, Anhui Agricultural University, Hefei 230036) Abstract: 2-Chloronicotinic is an important agrochemical and medical intermediates. A process for preparation of 2-chloronicotinic acid in high yield from cheap starting materials and under easily controllable reaction condition is needed. A new synthesis process route was reported from cyclization reaction. The intermediate 2 was obtained using the vinyl butyl ether reacted with Vilsmeier salt, and then reacted with dimethyl amine to provide aminium 3. The intermediate 4 was formed by condensation of 3 with ethyl cyanoacetate, then annulated in HCl ethanol solution to afford the ethyl 2-chloronicotinate. The title product 2-chloronicotinic acid was obtained through hydrolysis of ethyl 2-chloronicotinate. The reaction conditions of intermediate 3, 4 and 5 were optimized, and the total yield of 2-chloronicotinic acid was 63.4% with the purity of 99.6%. The optimal re