6-溴(氯)-2-氯甲基-3-喹啉甲酸乙酯的合成方法研究

Study on the synthesis of ethyl 6-bromo or 6-chloro-2-chloromethyl quinoline-3-carboxylate

以邻硝基苯甲醛为起始原料,经还原和氨基保护合成2-乙酰胺基苯甲醛(1)。应用环境友好的聚乙二醇-400为溶剂,以N-卤代丁二酰亚胺为卤代试剂对化合物2-乙酰胺基苯甲醛(1)进行卤代,制备了5-溴(氯)-2-乙酰胺基苯甲醛(2a,2b)。在三甲基氯硅烷(TMSCl)催化作用下,5-溴(氯)-2-乙酰胺基苯甲醛(2a,2b)与4-氯乙酰乙酸乙酯发生Friedlnder缩合反应,合成目标产物6-溴(氯)-2-氯甲基-3-喹啉甲酸乙酯(3a,3b)。其中2a,2b,3a,3b的结构经IR、1H NMR、13C NMR、MS得以确定。

In the present investigation,N-（ 2-formylphenyl） acetamide（ 1） was first prepared in a good yield of 78. 0% via the reduction reaction of o-nitrobenzaldehyde followed by acetylation of the arising 2-amino group. The resulting N-（ 2-formylphenyl） acetamide（ 1） was then underwent the halogenation reaction with N-halosuccinimide using eco-friendly PEG-400 as solvent at room temperature to afford N-（ 4-halo-substituted-2-formylphenyl） acetamides（ 2a, 2b） in 91. 5% and 88. 6% yields,respectively. Subsequently,compounds N-（ 4-halo-2-formylphenyl） acetamides（ 2a,2b） were subjected to the Friedlnder condensation reaction with 4-chloroacetoacetate with the chlorotrimethylsilane（ TMSCl） as catalyst to achieve the synthesis of the desired title compounds,namely ethyl 6-halo-2-chloromethyl quinoline-3-carboxylates（ 3a,3b）. Compounds 2a,2b,3a,3b were confirmed by IR,1HNMR,13 CNMR and MS.