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。
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 HC1 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 reaction conditions for the synthesis of 2-chloronicotinic acid were obtained, and the synthetic conditions were mild and suitable for industrial production.
作者
吕培
姚强
张超
LYU Pei;YAO Qiang;ZHANG Chao(Key Laboratory of Agi-Food Safety of Anhui Province,School of Resources and Environment,Anhui Agricultural University,Hefei 23003)
出处
《安徽农业大学学报》
CAS
CSCD
2018年第5期955-957,共3页
Journal of Anhui Agricultural University
基金
安徽省自然科学基金项目(1808085QC71)
国家自然科学基金青年基金项目(31701817)共同资助
关键词
2-氯烟酸
关环反应
合成工艺
2-chloronicotinic acid
cyclization reaction
synthesis process
