3-硝基-4-羟基-6-溴喹啉的合成

SYNTHESIS OF 3-NITRO-4-HYDROXY-6-BROMOQUINOLINE

报道了以邻氨基苯甲酸为起始原料,首先经乙酰化、溴化、酰胺水解"一锅法"反应合成2-氨基-5-溴苯甲酸,又经缩合及环合反应合成3-硝基-4-羟基-6-溴喹啉,最后用三光气作为氯化试剂合成3-硝基-4-氯-6-溴喹啉的工艺。优化了2-氨基-5-溴苯甲酸的溴化工艺条件,探讨了缩合反应和环合反应的机理,并对缩合反应、环合反应和氯化反应的工艺条件进行了优化。较佳工艺条件为:1)n(2-乙酰氨基苯甲酸)∶n(Br2)=1∶1.1;2)n(2-氨基-5-溴苯甲酸)∶n(硝基甲烷)∶n(氢氧化钾)=1∶3∶2.1,反应温度20℃,反应时间4.0 h;3)n(5-溴-2-((2-硝基亚乙基)氨基)苯甲酸)∶n(醋酸钾)=1∶1.1,反应温度110℃;4)n(三光气)∶n(3-硝基-4-羟基-6-溴喹啉)=0.35∶1。优化后,6步反应的总收率45.69%,产品纯度98.6%。

2-Amino-5-bromobenzoic acid was synthesized from o-aminobenzoic acid via acetylation, bromination and amide hydrolysis in one-pot. Then, 3-nitro-4-hydroxy-6-bromoquinoline was synthesized via condensation and cyclization. Finally, 3-nitro-4-chloro-6-bromoquinoline was synthesized using triphosgene as chlorination reagent. The bromination conditions of 2-amino-5-bromobenzoic acid were optimized. The mechanism of condensation reaction and cyclization reaction was discussed. The process conditions of condensation reaction, cyclization reaction and chlorination reaction were optimized. The optimum conditions are as follows: 1) Bromination, reacted for 4.0 h at 20 ℃, n(2-acetylaminobenzoic acid)∶n(Br2)=1∶1.1;2) condensation, n(2-amino-5-bromobenzoic acid)∶n(CH3NO2)∶n(KOH)= 1∶3∶2.1;3) cyclization, reacted at 110 ℃,n(5-bromo-2-((2-nitroethylene) amino) benzoic acid)∶n(CH3COOK)=1∶1.1;4) chlorination, n(BTC)∶n(3-nitro-4-chloro-6-bromoquinoline)=0.35∶1. After optimization, the total yield of the six-step reaction was 45.69% with the purity of 98.6%.