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

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.