3-甲基-4-吡唑甲酸和3,5-二甲基-4-吡唑甲酸的合成  

Synthesis of 3-Methyl-1H-pyrazole-4-carboxylic Acid and 3,5-Dimethyl-1H-pyrazole-4-carboxylic Acid

作　　者：陈娟[1] 席海涛[1] 张秀芹[1] 孟启[1] 姜艳[1] 孙小强[1] 

机构地区：[1]江苏工业学院江苏省精细石油化工重点实验室,江苏常州213164

出　　处：《精细化工》2007年第2期199-201,208,共4页Fine Chemicals

基　　金：国家自然科学基金资助项目(20272019)

摘　　要：吡唑甲酸衍生物是制备新型杀虫剂的中间体。为了简化工艺条件，降低生产成本，以乙酰乙酸乙酯与原甲酸三乙酯为原料，乙酸酐为溶剂，加热回流4h，合成了乙氧亚甲基乙酰乙酸乙酯（Ⅰ），收率为75％；然后在0—5℃冰浴中缓慢滴加w（NH：NH：·H2O）=80％的水合肼，室温反应0．5h，与Ⅰ环合生成3．甲基-4-吡唑甲酸乙酯，收率77％，熔点46—47℃；最后经埘（NaOH）=10％的水溶液水解，制得目标产物3-甲基-4-吡唑甲酸，收率88％，熔点237—238℃。用类似的方法以乙酰乙酸乙酯和乙酰氯为原料，经缩合、环合和水解3步反应合成了3，5-二甲基4-吡唑甲酸，3步反应的收率分别为52％、75％、85％。中间产物及目标产物的结构经熔点、IR、MS、1HNMR和13CNMR表征得以证实。在实验室小试的基础上，放大50倍进行了中试，目标产物的收率与小试结果一致。适合工业化生产。Pyrazole formate derivatives are intermediates for preparing new insecticides. In order to simplify technological conditions and reduce production costs, ethyl 2-（ ethoxymethylene）-3- oxobutanoate（ Ⅰ ） was synthesized from ethyl aeetoaeetate and ethyl orthoformate in 75 % yield. The reaction was performed by refluxing in acetic anhydride for 4 h. Then w （ NHENH2·H2O ） = 80% hydrazine hydrate was dropped slowly to Ⅰ at 0 - 5 ℃ on ice - water bath to produce ethyl 3-methyl- 1H-pyrazole- 4-earboxylate（ Ⅱ ） by eyelization at r. t. for 0. 5 h in 75% yield, m. p. 46 - 47℃. Finally,3-methyl-lH-pyrazole-4-earboxylie acid was obtained by hydrolysis of Ⅱ in w（NaOH） = 10% aqueous sodium hydroxide in 88 % yiled, m. p. 237 - 238 ℃. 3 ＇, 5-Dimethyl-1H-pyrazole-4-earboxylie acid was synthesized from ethyl aeetoaeetate and aeetyl chloride with the similar method by condensation,eyelization and hydrolysis, respectively in 52% , 75% and 85% yield. Structures of the intermediates and the products were confirmed by m. p. , IR, MS, 1HNMR and 13CNMR. Enlargement experiments were carried out on a 50-fold scale and the yields of the target products were identical with those in small tests. The process was suitable for industrial production.

关 键 词：3-甲基-4-吡唑甲酸 3 5-二甲基-4-吡唑甲酸 乙酰乙酸乙酯 

分 类 号：TQ031.2[化学工程]