电催化肼、丙二酮和2-溴丙二酸二乙酯三组分合成4-溴吡唑

Electrocatalytic Three-Component Synthesis of 4-Bromopyrazoles from Acetylacetone,Hydrazine and Diethyl Bromomalonate

吡唑是一类重要的五元氮杂环化合物,存在于多种天然产物和药物分子中.4-溴吡唑是一种高价值的吡唑衍生物,不仅具有多种生物活性和药理活性,还被广泛用作有机合成中间体,因此发展新型高效的4-溴吡唑化合物合成方法具有重要的研究意义.本研究发展了一种电化学促进芳香肼、1,2-丙二酮和2-溴丙二酸二乙酯三组分串联环化-溴化反应合成4-溴吡唑化合物的方法,并揭示了其反应机理.反应历程为芳香肼与丙二酮发生环化反应得到吡唑杂环化合物,其发生溴化反应得到4-溴吡唑.2-溴丙二酸二乙酯具有较高的氧化态,防止电解过程中过氧化效应,避免了过量溴化剂的使用.我们还将该方法用于其他溴化杂环化合物的合成.

Pyrazoles are the most important five-membered N-heterocycles as they are present in many natural products and synthetic drugs.Among various pyrazole derivatives,4-bromopyrazoles have attracted great attention because they not only display significant biological activities and physicochemical properties but also serve as valuable synthons in organic chemistry.In this manuscript,an efficient and eco-friendly method for the synthesis of various 4-bromopyrazoles through threecomponent reaction of hydrazine,acetylacetone and 2-bromomalonate was reported and the proposal reaction mechanism was revealed.According to the mechanism,hydrazine reacts with acetylacetone to afford pyrazole firstly,which then converts to 4-bromopyrazole through bromination.This method could also be well applicable for the bromination of other heterocyclic compounds.Given the high oxidation state of diethyl 2-bromomalonate,the peroxidation can be avoided through the electrolysis process,thus the excess amount of brominating agent was not be required.