烯胺酮与溴代酰胺通过[3+2]环加成构建吡咯烷类化合物  

Construction of Pyrrolidine Compounds by [3+2] Cycloaddition of Enaminones and Bromoamides

作　　者：王青青 袁成 孙绍发 汪钢强 WANG Qingqing;YUAN Cheng;SUN Shaofa;WANG Gangqiang(School of Pharmacy,Hubei University of Science and Technology,Xianning 437100,China;School of Nuclear Technology and Chemistry&Biology,Hubei University of Science and Technology,Xianning 437100,China)

机构地区：[1]湖北科技学院药学院,湖北咸宁437100 [2]湖北科技学院核技术与化学生物学院,湖北咸宁437100

出　　处：《化学与生物工程》2024年第5期44-50,共7页Chemistry & Bioengineering

基　　金：国家自然科学基金面上项目培育计划项目(82173713);国家级大学生创新创业训练计划项目(202110927009)。

摘　　要：吡咯烷是一类具有独特结构的五元含氮杂环化合物,在医药领域应用极其广泛。探究了烯胺酮(1)与溴代酰胺(2)通过[3+2]环加成反应合成多取代吡咯烷类化合物(3a~3p)的方法,通过^(1)HNMR、^(13)CNMR等对其结构进行了表征,并对合成条件进行了优化。结果表明,以1-(苄氧基)-4-苯甲酰基-5-(二甲基氨基)-3,3-二甲基吡咯烷-2-酮(3a)的合成为模型反应,确定最佳合成条件如下:碱为Cs_(2)CO_(3)、碱用量为2.5 eq.、溶剂为CHCl_(3)、0℃冰水浴缓慢转为室温反应,在此条件下,目标化合物3a收率为83%。该合成方法具有原料廉价易得、反应条件温和、操作简单、无需金属催化、对环境影响小等特点。Pyrrolidine is a kind of five-membered nitrogenous heterocyclic compounds with unique structures,which is widely used in medicine field.We investigated the synthesis of polysubstituted pyrrolidine compounds(3a-3p)by[3+2]cycloaddition reaction between enaminones(1)and bromoamides(2),characterized their structures by^(1)HNMR and^(13)CNMR,and optimized the synthesis conditions.The results show that,by using the synthesis of 1-(benzyloxy)-4-benzoyl-5-(dimethylamino)-3,3-dimethylpyrrolidine-2-one(3a)as a model reaction,the optimal synthesis conditions can be determined as follows:Cs_(2)CO_(3)is adopted as the base,the amount of base is 2.5 eq.,the solvent is CHCl_(3),and ice water bath at 0℃slowly converting to room temperature reaction is adopted.Under above conditions,the yield of the target compound 3a is 83%.The synthesis method has the characteristics of cheap raw materials,mild reaction conditions,simple operation,metal-free catalysis,and little environmental impact.

关 键 词：含氮杂环化合物 烯胺酮 溴代酰胺 吡咯烷类化合物 [3+2]环加成 

分 类 号：TQ463.53[化学工程—制药化工]