2-硝基-1 H-咪唑甲酸乙酯衍生物的合成  

Synthesis of Ethyl 2-Nitro-1 H-imidazolecar Boxylate Derivatives

作　　者：王顺 马鸿钊 陈夏彬 石靖 杨科 李正义[1] WANG Shun;MA Hongzhao;CHEN Xiabin;SHI Jing;YANG Ke;LI Zhengyi(Jiangsu Key Laboratory of Advanced Catalytic Materials and Technology,School of Petrochemical Engineering,Changzhou University,Changzhou 213164,China;Jiangsu Huajing Molecular Imaging and Pharmaceutical Research Institute Co.,Ltd.,Changshu 215500,China)

机构地区：[1]常州大学石油化工学院江苏省绿色催化材料与技术重点实验室,江苏常州213164 [2]江苏华景分子影像与药物研究院有限公司,江苏常熟215500

出　　处：《合成化学》2023年第12期956-961,共6页Chinese Journal of Synthetic Chemistry

基　　金：江苏省先进催化与绿色制造协同创新中心资助项目。

摘　　要：2-硝基咪唑是一种重要的医药中间体,可用于合成多种抗癌药物,通过对其结构进行修饰,有望开发新型活性药物分子。以2-氨基嘧啶和3-溴丙酮酸乙酯为起始原料,经过缩合环化、肼解、氧化和取代合成了一系列1-烷基-2-硝基-1 H-咪唑-5-甲酸乙酯(7a~7d)及其同分异构体1-烷基-2-硝基-1 H-咪唑-4-甲酸乙酯(8a~8d),该方法克服了传统合成路线中氮原子上取代基仅为甲基的局限性。研究不同取代基对2种异构体比例的影响,结果表明:随着取代基团的给电子能力增强,更加有利于化合物7的生成。所有合成化合物的结构都经过1 H NMR,13 C NMR和MS(ESI)确证或表征。2-Nitroimidazole is an important pharmaceutical intermediate,which can be used to synthesize a variety of anticancer drugs.By modifying its structure,it is expected to develop new active drug molecules.In this paper,using 2-aminopyrimidine and ethyl 3-bromopyruvate as starting materials,a series of ethyl 1-alkyl-2-nitro-1 H-imidazole-5-carboxylates(7a~7d)and their isomers ethyl 1-alkyl-2-nitro-1 H-imidazole-4-carboxylates(8a~8d)were synthesized by the process of condensation cyclization,hydrazinolysis,oxidation,and substitution.This method overcame the limitation that the substituent on the nitrogen atom was only a methyl group in the traditional synthetic route.The effect of different substituents on the ratio of the two isomers was investigated,and the results showed that the formation of compounds 7 were more favorable as the electron-donating ability of the substituents increased.The structures of all synthesized compounds were confirmed or characterized by 1 H NMR,13 C NMR and MS(ESI)analyses.

关 键 词：2-硝基-1 H-咪唑甲酸乙酯 合成 同分异构体 电子效应 位阻效应 构效关系 医药中间体 

分 类 号：O621.3[理学—有机化学]