高等学校化学学报 ›› 2018, Vol. 39 ›› Issue (4): 688-694.doi: 10.7503/cjcu20170594

• 有机化学 • 上一篇    下一篇

吡唑并[2,3-c]吡喃酮衍生物的一锅法熔融合成

崔思乾1, 卢俊瑞1(), 谢志强2(), 卢博为3, 刘金彪1, 刘梅2, 马瑶1, 胡新龙1, 李贾东1   

  1. 1. 天津理工大学化学化工学院, 天津 300384
    2. 天津瑞岭化工有限公司, 天津 300384
    3. 天津大学化工学院, 天津 300072
  • 收稿日期:2017-08-31 出版日期:2018-04-10 发布日期:2018-03-22
  • 作者简介:联系人简介: 卢俊瑞, 男, 博士, 教授, 博士生导师, 主要从事新型精细化学品合成方面的研究. E-mail:lujunrui@tjut.edu.cn;谢志强, 男, 工程师, 主要从事新型精细化学品合成方面的研究. E-mail:785202876@qq.com
  • 基金资助:
    国家自然科学基金(批准号: 21476174, 21176194)资助

One-pot Fasion Synthesis of Pyrano[2,3-c]pyrazol-6-one Derivatives

CUI Siqian1, LU Junrui1,*(), XIE Zhiqiang2,*(), LU Bowei3, LIU Jinbiao1, LIU Mei2, MA Yao1, HU Xinlong1, LI Jiadong1   

  1. 1. College of Chemistry and Chemical Engineering, Tianjin University of Technology, Tianjin 300384, China
    2. Tianjin Ruiling Chemical Co., Ltd., Tianjin 300384, China
    3. School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China
  • Received:2017-08-31 Online:2018-04-10 Published:2018-03-22
  • Contact: LU Junrui,XIE Zhiqiang E-mail:lujunrui@tjut.edu.cn;785202876@qq.com
  • Supported by:
    † Supported by the National Natural Science Foundation of China(Nos.2117619, 21476174)

摘要:

在无溶剂条件下, 以双分子的β-酮酸酯和取代肼为原料进行升温熔融反应, 经一锅法合成了15种不同取代的吡唑并[2,3-c]吡喃酮类化合物(4a~4o). 化合物4a~4o的结构经红外光谱(IR)、 核磁共振波谱(NMR)和高分辨质谱(HRMS)确证. 该方法克服了传统合成方法中溶剂对环境造成的污染及分步合成的不便, 收率可达40%~85%. 该方法具有无溶剂参与、 条件温和、 收率高及操作简便等优点, 符合绿色化学和节约型经济理念. 研究了反应速度、 产率与取代基的关系; 利用超高液相色谱-高分辨质谱联用(UPLC-HRMS)仪检测跟踪反应, 发现并确定了新的中间体C, 据此提出了一种新的反应机理. 此外, 中间体C含有四元环结构, 并以稳定的形式存在, 此类中间体的发现为制备四取代的环丁烷类化合物提供了新思路.

关键词: 无溶剂法, 熔融法, 一锅法, 吡唑并[2,3-c]吡喃酮, 反应机理

Abstract:

Pyrano[2,3-c]pyrazol-6-ones are widely used in the field of medicine and pesticide as a kind of skeletal molecules with high research value and important biological activity. In this work, 15 different substituted pyrano[2,3-c]pyrazol-6-ones(4a-4o) were synthesized rapidly and efficiently under solvent-free conditions by one-pot reaction with two molecules β-keto ester and substituted hydrazine as the starting materials. The yields ranged from 40% to 85%. The products were confirmed by infrared spectroscopy(IR), nuclear magnetic resonance spectroscopy(NMR) and high resolution mass spectrometry data(HRMS). Compared with the traditional synthetic methods, this work overcomes the environmental pollution caused by the use of solvent and the inconvenience of stepwise reaction and has the advantages of solvent-free, mild condition, high yield and easy operation, which also conforms to the green chemistry and economical economy. In addition, the relationship between the reaction rate and yield with the substituent was discussed. The melting reaction process was tracked by ultra-high performance liquid chromatography/high resolution mass spectrometry(UPLC-HRMS) and a new intermediates C was found and identified. Accordingly, a new reaction mechanism for this kind of reaction was proposed, which gave a new understanding of this kind of reaction. In addition, the intermediate C contains a quaternary ring structure but exists in a stable form, which provides a new method for the synthesis of four substituted cyclic butane compounds and ideas for constructing the unstable carbocyclic ring.

Key words: Solvent-free method, Melting method, One-pot reaction, Pyrano[2,3-c]pyrazol-6-one derivative, Reaction mechanism

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