基于环状酰亚胺还原反应绿色合成环状二级胺化合物  

Green Synthesis of Cyclic Secondary Amine Compounds Based on CyclicImide Reduction Reaction

作　　者：赵能选 陈剑力 朱杰[3] 朱红薇[3] 钱广 ZHAO Nengxuan;CHEN Jianli;ZHU Jie;ZHU Hongwei;QIAN Guang(Zhejiang Avilive Chemical Co.,Ltd.,Jinhua 322118,China;School of Advaced Materials Engineering,Jiaxing Nanhu University,Jiaxing 314001,China;College of Biological,Chemical Science and Engineering,Jiaxing University,Jiaxing 314001,China)

机构地区：[1]浙江埃森化学有限公司,浙江金华322118 [2]嘉兴南湖学院新材料工程学院,浙江嘉兴314001 [3]嘉兴学院生物与化学工程学院,浙江嘉兴314001

出　　处：《合成化学》2023年第9期714-719,共6页Chinese Journal of Synthetic Chemistry

基　　金：国家自然科学基金资助项目(21773094)。

摘　　要：环状二级胺作为重要组成部分广泛存在于具备生物活性的分子中。常见的合成方法主要是采用LiAlH4或者BF3和NaBH4的反应体系将环状酰胺类化合物还原,而危险性和环保隐患制约了其在生产中的应用。以环状酰亚胺为原料,通过BCl3和NaBH4的还原体系实现了环状二级胺的高效及绿色合成。以化合物1a作为模板底物,通过反应条件的筛选得到的最佳工艺条件为:1.0 eq.1a、1.5 eq.BCl3以及4.5 eq.NaBH4在60℃下反应24 h,溶剂为四氢呋喃。经优化后合成了一系列环状二级胺化合物,其结构经1 H NMR,13C NMR和HR-MS(ESI)确证。结果表明:该方法成本低廉,产率较高,可达78%~96%,底物适用范围广,可应用于环上有推电子基或者吸电子基的二级胺的合成。Cyclic secondary amines,as important components,are widely present in biologically active molecules.The common synthesis methods are mainly the reduction of cyclic amide compounds by lithium aluminium hydride or the reaction system of boron fluoride and sodium borohydride,while a series of hazards restrict their application in production.In this paper,cyclic imide was used as raw material to achieve efficient and green preparation of cyclic secondary amine with the reduction system of boron trichloride and sodium borohydride.With compound 1a as template substrate and screening through reaction conditions,the optimal process conditions are as follows:1 eq.1a,1.5 eq.boron trichloride and 4.5 eq.sodium borohydride react at 60℃for 24 h,tetrahydrofuran as solvent.A series of cyclic secondary amines were synthesized through this protocol,and their structures were characterized by 1H NMR,13C NMR,and HR-MS(ESI).The results show that this method is low-cost,high yield up to 78%~96%,a wide application range of substrate,and it can be applied to the synthesis of secondary amines with electron withdrawing or pushing groups on the ring.

关 键 词：还原 绿色工艺 环状二级胺 环状酰亚胺 三氯化硼 硼氢化钠 

分 类 号：O621.3[理学—有机化学]