3-甲基-4-吡唑甲酸和3,5-二甲基-4-吡唑甲酸的合成

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4 h,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(NH2NH2.H2O)=80%的水合肼,室温反应0.5 h,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w(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。

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

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 acetoacetate and ethyl orthoformate in 75 % yield.The reaction was performed by refluxing in acetic anhydride for 4 h.Then w(NH_2NH_2·H_2O)=80% hydrazine hydrate was dropped slowly to Ⅰ at 0～5 ℃ on ice-water bath to produce ethyl 3-methyl-1H-pyrazole-4-carboxylate(Ⅱ) by cyclization at r.t.for 0.5 h in 75% yield,m.p.46～47 ℃.Finally,3-methyl-1H-pyrazole-4-carboxylic 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-carboxylic acid was synthesized from ethyl acetoacetate and acetyl chloride with the similar method by condensation,cyclization 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 ~(13)CNMR.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.