2-氯烟酸的合成方法
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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 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 of2-chloronicotinic acid was 63.4% with the purity of 99.6%. The optimal reaction conditions for the synthesis of2-chloronicotinic acid were obtained,and the synthetic conditions were mild and suitable for industrial production.
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 of2-chloronicotinic acid was 63.4% with the purity of 99.6%. The optimal reaction conditions for the synthesis of2-chloronicotinic acid were obtained,and the synthetic conditions were mild and suitable for industrial production.
引文
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[2]王斐英,彭林,邓聪迩,等.2-氯烟酸绿色合成工艺[J].合成化学,2016,24(7):620-623.
[3]JIN L Q,LI Y F,LIU Z Q,et al.Characterization of a newly isolated strain Rhodococcus erythropolis ZJB-09149transforming 2-chloro-3-cyanopyridine to 2-chloronicotinic acid[J].New Biotechnol,2011,28(6):610-615.
[4]SAID A.Process for the production of pure white2-chloronicotinic acid.US,4144238[P].1979-03-13.
[5]ADEL S,WALLIS B.Process for pure white 2-chloronicotinic acid.DE,2713316[P].1977-10-27.
[6]FUMIYA H.Preparation of 2-chloro-3-cyanopyridine and2-chloronicotinic acid.JP,56169672[P].1981-12-26.
[7]ZHANG T Y,SCRIVEN E F V.Processes for producing2-halonicotonic acid derivatives and precursors thereto.US,5493028[P].1994-01-11.
[8]刘军安,魏晓磊.2-氯烟酸的合成[J].化学与生物工程,2010,27(4):36-37.
[9]SCHRODER L.Preparation of 2-chloropyridine 3-carboxylic acid esters.US,4987232[P].1991-01-22.
[10]陆孙彬,季红楼,高小山.一种2-氯烟酸的合成方法.CN,102993092[P].2013-03-27.
[11]聂文娜.2-氯烟酸合成工艺研究[J].河北化工,2006,29(10):14-15.