中间体6-氯-5-甲氧基吲哚合成工艺研究

Study on the Synthesis of 6-Chloro-5-methoxy-1H-indole

以3-氯-4-甲氧基苯胺和水合氯醛、盐酸羟胺为原料,通过Sandmeyer异亚硝基乙酰替苯胺合成法制备得6-氯-5-甲氧基靛红,再由硼氢化钠/三氟化硼乙醚体系还原制备得目标化合物,总收率达49.52%（以3-氯-4-甲氧基苯胺计）。实验考察了酰胺化反应温度和反应时间、成环反应温度、还原体系种类及还原剂用量对反应收率的影响,较佳的酰胺化反应温度和反应时间为90℃回流反应10 min,较优的成环反应温度为80～85℃,选用更加安全的硼氢化钠/三氟化硼乙醚体系作为还原剂,较优的还原剂用量比为n（硼氢化钠）∶n（三氟化硼乙醚）∶n（6-氯-5-甲氧基靛红）=4.0∶2.5∶1.0。所有产物结构均通过1HNMR、13CNMR和元素分析等进行了表征。

6-Chloro-5-methoxy-1 H-isatin was prepared with Sandmeyer Isonitrosoacetanilide Isatin Synthesis method by using 3-chloro-4-methoxyaniline,chloral hydrate and hydroxylamine hydrochloride as raw materials,then was reduced to 6-chloro-5-methoxy-1 H-indole through NaBH4/BF3-Et2O reduction system with the total yield of 49. 52%（calculated by 3-chloro-4-methoxyaniline）.The effects of amination reaction temperature and time,annulation temperature,reductant species and reductant dosage on the yields were investigated.The modified acetylation reaction temperature and time,annulation reaction temperature,better reductant were 90 ℃（reflux） for 10 min,80 ～ 85 ℃ and sodium borohydride/boron trifluoride etherate,respectively.The best molar ratio of sodium borohydride,boron trifluoride etherate,and 6-chloro-5-methoxy-1 H-isation was 4. 0 ∶ 2. 5 ∶ 1. 0. The structure of all products was characterized by 1HNMR,13CNMR,elemental analysis and so on.