7-卤代吲哚的合成工艺研究  

STUDY ON THE SYNTHESIS OF 7-HALOINDOLE

作　　者：刘长春[1] 程进[1] 蒋若愚[1] 刘承先[1] 李雪莲[1] 薛叙明[1] Liu Changchun;Cheng Jin;Jiang Ruoyu;Liu Chengxian;Li Xuelian;Xue Xuming(College of Chemistry and Materials Engineering, Changzhou Institute of Engineering and Technology, Changzhou, 213164, Jiangsu, China)

机构地区：[1]常州工程职业技术学院化学与材料工程学院,江苏常州213164

出　　处：《精细石油化工》2018年第3期39-45,共7页Speciality Petrochemicals

基　　金：江苏高校品牌专业建设工程资助项目(PPZY2015B178);江苏省高校优秀中青年教师和校长境外研修计划资助

摘　　要：以邻卤代苯胺和水合氯醛、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7-卤代靛红,再经硼氢化钠/三氟化硼乙醚体系还原制备得7-卤代吲哚。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,所有产物结构均通过~1H NMR、^(13) C NMR和元素分析等进行了表征。结果表明,制备7-氟吲哚、7-溴吲哚、7-氯吲哚时,较佳的酰胺化反应温度和反应时间分别为回流10min、80℃4h和80℃3h,较佳的成环反应温度分别为80℃、85℃和80℃,较优的还原体系为硼氢化钠/三氟化硼乙醚体系,较优的还原剂用量为n(硼氢化钠)∶n(三氟化硼乙醚)∶n(7-卤代靛红)=3.0∶2.25∶1。该工艺具有成本低、反应条件温和、收率较高,操作简便等优点,适合批量制备7-卤代吲哚。7-Halogenated isatins were prepared with Sandmeyer isonitrosoacetanilide isatin synthesis method by using o-halogenated aniline,the chloral hydrate and the hydroxylamine hydrochloride as raw materials,then were reduced to 7-halogenoindoles through NaBH4/BF4-Et2 O reduction system.The effects of acetylation reaction temperatures and times,annulation reaction temperatures,different reductants on the yield of products were investigated.All products＇ structures were characterized by ^1 H NMR,^13C NMR and elemental analysis.The result shows that the optimized processes for 7-fluoroindole,7-chloroindole and 7-bromoindole were：acetylation reaction temperatures and times were reflux for 10 min,80℃for 4 hand 80℃for 3 h;annulation reaction temperatures were 80℃,85℃ and 80 ℃;better reductant is sodium borohydride/boron trifluoride etherate;the molar ration of sodium borohydride,boron trifluoride etherate and 7-halogenated isatins was 3.0∶2.25∶1,respectively.Compared with the reported synthesis of 7-halogenoindoles,this improved synthesis process is readily accessible,safer with mild reaction conditions,low cost,high yield and good prospects for industrial applications.

关 键 词：7-卤代吲哚 7-氟吲哚 7-氯吲哚 7-溴吲哚 Sandmeyer异亚硝基乙酰替苯胺合成法 硼氢化钠/三氟化硼乙醚 

分 类 号：TQ460.3[化学工程—制药化工]