N1-取代吡唑类中间体合成的一种新方法
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摘要
[目的]寻找一种广谱高效的合成N1-取代吡唑类中间体的新方法。[方法]以溴化镍、4,5-双二苯基膦-9,9-二甲基氧杂蒽和2,4,6-三甲基苯基溴化镁合成一种在空气中稳定的催化剂,通过该催化剂催化~1H-吡唑与卤代芳杂环化合物生成N1-取代的吡唑类化合物。[结果]通过优化确定了最佳反应条件,一步反应,收率为30.2%～95.7%,化合物结构及催化剂结构均经过~1H NMR确认。[结论]该催化剂可有效催化~1H-吡唑与卤代芳杂环的合成,尤其对反应活性较低的氯取代芳环具有高效的催化作用,反应条件温和。催化剂所用原料廉价易得,制备简单且在空气环境下稳定。
[Aims] The aim is to find a new way which is broad spectrum and efficient to synthesize N1-substituted pyrazole derivatives. [Methods] A catalyst which is stable in the air was synthesized by nickel bromide, 4,5-double two phenylphosphine-9,9-two methyl oxanthracene and 2,4,6-three methyl phenyl bromide, this catalyst can catalyze the formation of pyrazole derivatives of N1-substituted by ~1H-pyrazole and halogenated heterocyclic compound. [Results] The optimized process was determined by optimization of reaction conditions. The yield was 30.2-95.7%, and the product and catalyst were confirmed by ~1H NMR. [Conclusions] The catalyst can effectively catalyze the synthesis of 1H-pyrazole and halogenated heterocyclic ring, especially for the chlorinated aromatic compound which has a low reactive activity, and the reaction conditions are mild. The raw materials used in the catalyst are cheap and easy to obtain, simple to prepare and stable in the air environment.
[Aims] The aim is to find a new way which is broad spectrum and efficient to synthesize N1-substituted pyrazole derivatives. [Methods] A catalyst which is stable in the air was synthesized by nickel bromide, 4,5-double two phenylphosphine-9,9-two methyl oxanthracene and 2,4,6-three methyl phenyl bromide, this catalyst can catalyze the formation of pyrazole derivatives of N1-substituted by ~1H-pyrazole and halogenated heterocyclic compound. [Results] The optimized process was determined by optimization of reaction conditions. The yield was 30.2-95.7%, and the product and catalyst were confirmed by ~1H NMR. [Conclusions] The catalyst can effectively catalyze the synthesis of 1H-pyrazole and halogenated heterocyclic ring, especially for the chlorinated aromatic compound which has a low reactive activity, and the reaction conditions are mild. The raw materials used in the catalyst are cheap and easy to obtain, simple to prepare and stable in the air environment.
引文
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[6]ADRIAN H,KELLIE W,SO Y C L,et al.Regioselective Synthesis,NMR,and Crystallographic Analysis of N1-Substituted Pyrazoles[J].The Journal of Organic Chemistry,2017,82(17):8864-8872.
[2]刘长令.世界农药信息手册[M].北京:化学工业出版社,2000:40.
[3]聂英坤,张凤山,孙凤琴,等.类风湿性关节炎的治疗现状与进展[J].临床荟萃,2004(2):119-120.
[4]SELWOOD D L,BRUMMELL D G,BUDWORTH J,et al.Synthesis and Biological Evaluation of Novel Pyrazoles and Indazoles as Activators of the Nitric Oxide Receptor,Soluble Guanylate Cyclase[J].J Med Chem,2001,44(1):78-93.
[5]赵雪英,陈志兵.吡唑类化合物合成方法的研究进展[J].宿州学院学报,2008(3):97-100,57.
[6]ADRIAN H,KELLIE W,SO Y C L,et al.Regioselective Synthesis,NMR,and Crystallographic Analysis of N1-Substituted Pyrazoles[J].The Journal of Organic Chemistry,2017,82(17):8864-8872.
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