氮杂环卡宾钯配合物催化合成含联苯类及异黄酮类化合物中药活性成分的研究

N-heterocyclic carbene palladium complexes: applications for the synthesis of active ingredients of traditional chinese medicine including biphenyl derivatives and isoflavones

目的通过氮杂环卡宾钯催化的Suzuki-Miyaura偶联反应,合成一系列联苯类化合物及异黄酮类化合物。方法将设计合成的氮杂环卡宾钯配合物作为催化剂,以芳基硼酸、卤代芳烃为底物,分别考察催化剂用量、反应溶剂和碱等影响因素,确定最优反应条件,在最优条件下催化合成含联苯类及异黄酮类化合物中药活性成分,分离纯化得到目标产物。结果设计合成了1个氮杂环卡宾钯配合物,将它作为催化剂,筛选出了催化Suzuki-Miyaura偶联反应的最优条件:以氮杂环卡宾钯配合物(0.001 mmo L)作催化剂,无水乙醇为溶剂,K_3PO_4(1.5 mmo L)为碱,反应温度为80℃,反应时间为4 h,在空气中直接反应。在最优条件下,催化合成了7个联苯类化合物及7个异黄酮类化合物,结构均通过MS、1H NMR和13C NMR进行了表征。结论本文设计合成的氮杂环卡宾钯配合物催化活性高,合成条件温和,后处理操作简单。本研究对含联苯类和异黄酮类化合物中药活性成分的全合成、半合成或者结构修饰具有一定的参考价值。

Objective To synthesize biphenyl derivatives and isoflavones by Suzuki-Miyaura cross-coupling reactions catalyzed by N-heterocyclic carbene palladium complexes. Methods A N-heterocyclic carbene palladium complexes was synthesized and developed as an efficient catalyst for the coupling reaction of aryl boronic acids and aryl halides. The optimal reaction conditions were determined via the change of catalyst loading, solvent and alkali. Under the optimal conditions, biphenyl derivatives and isoflavones were obtained. Results A N-heterocyclic carbene palladium complexes was synthesized. The optimal conditions were as follows： 0.001 mol N-heterocyclic carbene palladium complexes as catalyst,Et OH as solvent,1.5mmo L K3PO4 as alkali,reaction for 4 h in the air at 80 ℃. Seven biphenyl derivatives and seven isoflavones were obtained and characterized by MS,1H NMR and13 C NMR. Conclusion A N-heterocyclic carbene palladium complexes has been synthesized and successfully developed as an efficient catalyst for the SuzukiMiyaura cross-coupling reactions. The research could provide reference for synthetic, semi-synthetic or structure modification of active ingredients traditional Chinese medicine.