CHEMICAL INDUSTRY AND ENGINEERING PROGRESS 2013年第32卷第10期 ·2486·化 工 进 展
1-苯基吲哚的合成
冯筱晴1.2，唐 龙1，王瑞瑞1，王羚竹1，宋国强1
（1常州大学制药与生命科学学院，江苏 常州 213164；2常州市药品制造与质量控制工程重点实验室，
江苏 常州 213164）
摘 要：以二苯胺和乙二酰氯为起始原料经偶联、酰化、还原反应得到1-苯基吲哚，并探索了其影响因素。结果表明合成中间体N ,N -二苯基-2-氯-2-氧代乙酰胺的较佳条件为：n (二苯胺)：n (乙二酰氯)=1∶3，反应温度20～25 ℃，反应2.5 h ，收率98.02%，HPLC 纯度97.68%；产品1-苯基靛红的较优合成工艺条件为： n (N ,N -二苯 基-2-氯-2-氧代乙酰胺) ：n (无水AlCl 3)=1∶3，反应温度10 ℃，反应时间2 h ，收率86.76%，HPLC 纯度98.45%；目标产物1-苯基吲哚的最佳工艺条件为：n (1-苯基靛红)：n (硼氢化钠)=1∶3，n (1-苯基靛红)：n (氯化锌)=1∶0.05，反应温度110 ℃，反应时间12 h ，收率72.41%，HPLC 纯度98.14%。产品及中间体结构经1H NMR 、MS 和显微熔点仪分析表征确认。
关键词：二苯胺；N ,N -二苯基-2-氯-2-氧代乙酰胺；1-苯基靛红；1-苯基吲哚；合成
中图分类号：TQ 246.7 文献标志码：A 文章编号：1000–6613（2013）10–2486–05
DOI ：10.3969/j.issn.1000-6613.2013.10.037
Synthesis of 1-phenylindole
FENG Xiaoqing 1，
2，TANG Long 1，WANG Ruirui 1，WANG Lingzhu 1，SONG Guoqiang 1 （1School of Pharmaceutical Engineering ＆Life Science ，Changzhou University ，Changzhou 213164，Jiangsu ，China ；2Changzhou’s Key Laboratory of Pharmaceutical Manufacture and Quality Control Engineering ，Changzhou 213164，
Jiangsu ，China ）
Abstract ：In this paper ，n-phenylaniline and oxalyl chloride were used to prepare 1-phenylindole. The experimental conditions ，such as material ratio ，reaction time ，the amount of catalyst and so on were investigated. The optimal conditions of the coupling reaction were found as ：n (n -phenyl -aniline)∶n (oxalyl chloride) =1∶3，reaction temperature 20—25 ℃，reaction time 2.5 h ，under which the yield of 1-(diphenylamino)-2-chloro-ethanedione was up to 98.02% based on n -phenyl -aniline and the purity was 97.68% as determined by HPLC. The best reaction conditions for preparing 1-phenyl isatin were found as ：n (1-(diphenylamino)-2-chloro-ethanedione)∶n (Anhydrous AlCl3)=1∶3，reaction temperature 10 ℃，reaction time 2 h ，under which the yield of 1-phenylisatin was 86.76% based on 1-(diphenylamino)- 2-chloro-ethanedione and the purity was 98.45% as determined by HPLC. The reduction reaction conditions were optimized as ：n (1-phenylisatin)∶n (sodium borohydride) = 1∶3，n (1-phenylisatin)∶n (zinc chloride) = 1∶0.05，reaction temperature 110 ℃，reaction time 12 h ，under which the yield of 1-phenylisatin was 72.41% based on 1-phenylisatin and the purity was 98.14% as determined by HPLC. The structures of the product were identified by 1H NMR ，MS and Micro melting point instrument.
第一作者：冯筱晴（1974—），女，博士，讲师，主要从事医药中间体的合成。联系人：宋国强，高级工程师，主要从事医药中间体的研究与开发。E-mail drugs@https://www.doczj.com/doc/6517539388.html, 。 收稿日期：2013-03-07；修改稿日期：2013-04-09。 基金项目：江苏省产学研前瞻性联合研究项目（BY-2013024-20）、江
苏省研究生科研创新计划（CXZZ12_0730）及江苏省高等学校大学生创新创业训练计划（201310292005Z ）项目。