吡唑并[2,3-c]吡喃酮衍生物的一锅法熔融合成

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

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.

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（ 4 a—4 o） 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（ UPLCHRMS） 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.