Chichibabin-type偶联反应在构建联氮杂芳烃中的应用

本项目以“BTC/catalyst/solvent”组合为氯化试剂，首次成功地对多种羟基氮杂芳烃进行了系统性无磷氯化研究，为我国严格限磷的环保措施提供一种有益的帮助。在对该反应的拓展试验中，着重探索Chichibabin-type反应及其应用试验。BTC/catalyst和易挥发溶剂进行无磷氯化后的反应液，在脱除溶剂之后的残余物含有羰基氮杂芳烃鎓盐等亲电活性物，本项目创造性地利用此活性物作为Chichibabin-type反应的底物，与格氏试剂发生加成反应，所得的加成物再经常规的氧化芳构化反应之后，转化成为与常规钯催化偶联产物有差异的偶联产物。 预计本项目可以为构建联氮杂芳烃类化合物提供一种可避免诸如钯等重金属污染的有效合成方法，这在制药工业上显得尤其有意义。

This project used a combination of chlorination reagents, BTC / catalyst / solvent for the first time to successfully carry out a systemic phosphorus-free chlorination of a variety of hydroxy-azaarenes, providing a useful help for China's strict phosphorus-limiting environmental protection. In the expansion test of this reaction, the application test of Chichibabin-type reaction is emphasized. The reaction solution of phosphorus-free chlorination by BTC / catalyst in a volatile solvent, contains electrophilic active substances such as carbonyl azaarene onium. This project creatively uses this active substance as the substrate of Chichibabin-type reaction to carry out an addition reaction with Grignard reagents, and the resulting adduct can be converted into a coupling product after being oxidatively aromatized, which is different from the conventional palladium-catalyzed coupling product. It is expected that this project can provide an effective synthetic method to avoid the pollution of heavy metals such as palladium for the construction of bi-aza-arenes, which might be especially meaningful in the pharmaceutical industry.