JOCR Journal of Organic Chemistry Research 2330-5231 Scientific Research Publishing 10.12677/JOCR.2020.82002 JOCR-36520 JOCR20200200000_34546349.pdf 化学与材料 固载化FeCl 3催化合成螺环苯并吡喃[2,3-b]吲哚类衍生物 Synthesis of Spirooxindole-Chromeno[2,3-b]Indole Derivatives Promoted by Immobilized Solid Lewis Acid Catalyst FeCl 3 雪松 2 1 顺明 2 1 上海庚彩新材料科技有限公司,鞍山七彩化学股份有限公司上海研发中心,上海 null 15 07 2020 08 02 15 23 © Copyright 2014 by authors and Scientific Research Publishing Inc. 2014 This work is licensed under the Creative Commons Attribution International License (CC BY). http://creativecommons.org/licenses/by/4.0/

高分子固载Lewis酸催化剂相比传统Lewis酸催化剂,在基本保留其原有催化活性、反应条件更温和等特点的同时,还具有对设备低腐蚀性、易于实现连续化、环境友好等显著优点,因而在医药化工领域具有十分广阔的产业化应用前景。本文利用一种固载FeCl 3催化剂,即将FeCl 3与聚苯乙烯反应制成负载型氯化铁催化剂(PS-FeCl 3),催化靛红、苯酚以及2-卤代吲哚化合物的多组分串联环化反应“一锅法”高效合成螺环苯并吡喃[2,3-b]吲哚类衍生物。 Polymer-supported Lewis acid catalysts is dominion over traditional ones in a number of aspects for instance; it retains its original catalytic activity, mild reaction conditions are required, which integrate remarkable advantages in catalyst regeneration, low corrosiveness of equipment, easy achievement of continuous production, environment-friendly aspects, etc. since there are great prospects of wide range of applications in the pharmaceutical and fine chemical industry. In this work, an immobilized solid Lewis acid catalyst (PS-FeCl 3) was prepared, which catalyzed the multi-component reaction casecade of isatin, phenol and 2-haloindole in one-pot manner to provide diverse spirooxindole-chromeno[2,3-b]indole derivatives with high efficiency.

路易斯酸,固载催化剂,三氯化铁,螺环苯并吡喃[2 3-b]吲哚,多组分串联反应, Lewis Acid Immobilized Solid Catalyst PS-FeCl3 Spirooxindole-Chromeno[2 3-b]Indole Multi-Component Reaction
固载化FeCl<sub>3</sub>催化合成螺环苯并吡喃[2,3-b]吲哚类衍生物<sup> </sup>

刘雪松,于顺明*

上海庚彩新材料科技有限公司,鞍山七彩化学股份有限公司上海研发中心,上海

收稿日期:2020年6月28日;录用日期:2020年7月8日;发布日期:2020年7月15日

摘 要

高分子固载Lewis酸催化剂相比传统Lewis酸催化剂,在基本保留其原有催化活性、反应条件更温和等特点的同时,还具有对设备低腐蚀性、易于实现连续化、环境友好等显著优点,因而在医药化工领域具有十分广阔的产业化应用前景。本文利用一种固载FeCl3催化剂,即将FeCl3与聚苯乙烯反应制成负载型氯化铁催化剂(PS-FeCl3),催化靛红、苯酚以及2-卤代吲哚化合物的多组分串联环化反应“一锅法”高效合成螺环苯并吡喃[2,3-b]吲哚类衍生物。

关键词 :路易斯酸,固载催化剂,三氯化铁,螺环苯并吡喃[2,3-b]吲哚,多组分串联反应

Copyright © 2020 by author(s) and beplay安卓登录

This work is licensed under the Creative Commons Attribution International License (CC BY 4.0).

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1. 引言

螺环吲哚酮骨架是天然产物及药物活性分子中的一类十分重要的结构单元 [ 1 ] [ 2 ] [ 3 ]。螺环吲哚酮类化合物被发现具有十分广谱的生物活性,如抗癌、抗菌、降糖、降血压、抗HIV、抗结核、抗疟疾等 [ 4 ] [ 5 ]。同时,螺环吲哚酮类衍生物一般含有多个手性中心,拥有复杂的立体化学结构。因此,发展高效的合成方法来构建这类骨架化合物成为近些年有机合成化学和药物化学研究的热点领域 [ 6 ]。

其中,苯并吡喃[2,3-b]吲哚是一类同时具有吲哚和苯并吡喃骨架的杂环化合物 [ 7 ]。许多含有苯并吡喃[2,3-b]吲哚结构的化合物被发现具有良好的生物活性,如抗疟疾 [ 8 ]、抗癌 [ 9 ] 和抗增殖 [ 10 ] 活性等。但是到目前为止,关于该类化合物合成方法的报道还是非常少,而且基本都是通过多步反应实现的 [ 11 ]。因而,发展更加高效的合成方法来获得具有全新的苯并吡喃[2,3-b]吲哚类化合物具有重要意义。FeCl3是廉价易得、环境友好的重要Lewis酸,能溶于多种有机溶剂,广泛用做有机合成的催化剂。FeCl3经过活性炭、SiO2、高分子材料和离子交换树脂等材料负载后可以作为Lewis酸催化剂促进多种有机反应。固载FeCl3具有稳定性高、易于回收重复使用等优点,因而受到广泛关注。最近,我们也报道了FeCl3促进的2-卤代吲哚与3-羟基-3-(2-羟基苯基)-2-吲哚酮经多步反应,最后环化反应生成复杂的苯并吡喃[2,3-b]吲哚结构的方法 [ 12 ]。

本文通过反应条件筛选优化,发现了路易斯酸FeCl3可催化靛红、苯酚及2-卤代吲哚类化合物的多组分串联环化反应。文中参考文献方法制备了聚苯乙烯负载型FeCl3催化剂(PS-FeCl3)。在PS-FeCl3的促进下,我们以靛红、苯酚以及2-卤吲哚类化合物为起始物料,通过多组分“一锅法”反应,高效合成了一系列螺环苯并吡喃[2,3-b]吲哚类衍生物。该反应具有条件温和,操作简便,催化剂性能稳定,底物适用性广泛等特点。

2. 结果与讨论 2.1. 反应条件筛选与优化

首先,我们以N-甲基靛红1a (1.0 equiv)、4-甲基苯酚2a (1.0 equiv)以及N-乙酰基-2-氯吲哚3a (1.2 equiv)为起始原料,筛选各种酸(包括路易斯酸、质子酸及固载路易斯酸等)为催化剂进行反应的条件筛选及优化(表1)。筛选了一系列Lewis酸,如FeCl3、FeBr3、Fe(OTf)3、Sc(OTf)3、Cu(OTf)2、Zn(OTf)2、In(OTf)3、BF3·OEt2以及质子酸CF3SO3H和CF3CO2H等,发现大部分酸都能在室温下促进该反应发生,但反应进展均比较缓慢,转化率也较低。而且,随着延长反应时间或升高反应温度,2-氯吲哚3a均有部分分解,导致反应产率降低。FeCl3催化该三组分反应的效率最好,转化速度较快,但同样3a分解的进程也会加快。最后,当使用固载FeCl3(PS-FeCl3,3.0 eq.)时,虽然反应速度较为缓慢(24 h),但反应较为温和,3a的分解明显减少,最终可以较高产率(80%)获得环化产物4a (表1)。

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