摘要
研究了重要的农药中间体1-甲基-3-三氟甲基-4-吡唑甲酸的合成工艺。以氰基乙酸钠为原料,经缩合,酰化,成环以及水解制得。各步比较适宜的工艺条件为:缩合反应:在40～45℃下反应5 h,氰基乙酸钠与N-甲氧亚甲基-N,N-二甲胺甲磺酸盐的摩尔比为1:2.5,选用毒性较低的乙醇代替二氯甲烷为溶剂,收率由文献值67%提高到93.7%;酰化反应:以三乙胺为缚酸剂,选用三氟乙酰氯代替剧毒气体光气作为酰化剂,配料摩尔比为1:1.5:2(N,N-二甲基氨基丙烯腈:三氟乙酰氯:三乙胺),收率78.6%;环化反应:以甲醇和水的混合溶剂为反应体系,收率74.3%。该工艺收率高、原料廉价易得、反应温和以及操作简便,因此具有较好的工业价值。中间体和产品的结构经1H-NMR确定。
An improved synthesis technology of 1-methyl-3-trifluoromethyl-4-pyrazole carboxylic acid which is an important intermediate of pesticides was studied. The title compound was synthesized by sodium cyanoacetate via condensation, acylation, cyclization and hydrolysis. The suitable reaction conditions were found as follows. The condensation reaction was carried out at 40-45℃ for 5 h, and in which the ethanol was used as solvent, the molar ratio of sodium cyanoacetate to N-（methoxymethylene）-N,N-dimethylaminium methanesulfonate is 1：2.5, and under above conditions the yield was improved from 67% （reported in the literatures） to 93.7%. During acylation, TEA was used as acid-capturer, trifluoroacetyl chloride was used to replace phosgene as acylating reagent and the yield of 78.6% was obtained when the molar ratio of 3-（dimethylamino）acrylonitrile, trifluoroacetyl chloride and TEA is 1：1.5：2. The cyclization reaction was carried out in a mixed solvent of methanol and water, and the product yield of 74.3% was obtained. The structures of the intermediates and product were confirmed by ^1H-NMR. The proposed process has quite good industrial value because of its high yields, cheap and easily available raw materials, moderate reaction conditions and convenient operations.
出处
《高校化学工程学报》
EI
CAS
CSCD
北大核心
2012年第3期470-474,共5页
Journal of Chemical Engineering of Chinese Universities
基金
国家自然科学基金(21176213)
浙江省重点科技创新团队-绿色制药工艺科技创新团队(2010R50043)
