可见光诱导的3-芳酰吲哚化合物的合成研究

发布时间：2018-06-02 22:31

本文选题：可见光 + 脱羧　；参考：《哈尔滨工业大学》2017年硕士论文

【摘要】：3-芳酰吲哚是许多天然产物、药用分子以及生物活性化合物中的常见结构骨架,也是合成许多吲哚衍生物的通用前体。有机合成化学家对于3-芳酰基吲哚化合物的合成研究由来已久。传统的合成方法有以下缺点:需要计量的Lewis酸做催化剂以及严格无水的反应条件;需要用到对环境有污染的POCl3,且受限于以酰胺羰基源;所用试剂官能团容忍性不好等问题。因此在原子经济性和氧化还原经济性以及可持续化学原则的指引下,开发新型高效,条件温和的3-芳酰吲哚化合物合成方法成为有机合成化学家不懈的追求。近年来可见光作为一种环境友好、可持续的能源用于化学转化反应的研究引起了人们的广泛关注。本文利用可见光诱导催化这一策略,实现了3-芳酰基吲哚化合物的高效绿色合成。在可见光诱导下由α-氨基酸芳炔脱羧,氧化偶联合成3-芳酰吲哚化合物的合成反应,合成了一系列3-芳酰吲哚化合物,为此类吲哚衍生物的的合成开辟了新的路径。与传统合成方法相比,反应操作简单,条件温和,区域选择性好,而且反应底物普适性好等。多种芳环、N烷基及亚甲基取代情况的反应底物,在优化的反应条件下,均以中等到良好的收率获得了相应的目标产物。本文提出了可能的反应机理。通过同位素标记实验、循环伏安法氧化电势测定、自由基捕获实验等方法对提出的反应机理进行了验证研究。机理研究表明,在可见光诱导条件下,反应通过单电子转移(SET)过程,分子内的氧化-脱羧偶联实现3-芳酰吲哚化合物的合成。本文合成了16种不同取代情况的3-芳酰吲哚化合物,并对所有的化合物进行了气质联用(GC-MS)、核磁共振谱(NMR)、高分辨质谱(HRMS)、红外光谱(IR)、熔点的表征测试。
[Abstract]:3-aryl indole is a common structural skeleton in many natural products, medicinal molecules and bioactive compounds. It is also a common precursor for the synthesis of many indole derivatives. Organic synthetic chemists have long studied the synthesis of 3-aryl indole compounds. The traditional synthesis methods have the following disadvantages: Lewis acid is used as catalyst and strict anhydrous reaction conditions are needed; POCl _ 3 which is polluted to the environment is used and limited to amide-carbonyl source; the functional group tolerance of the reagent used is poor, and so on. Therefore, under the guidance of atomic economy, redox economy and the principle of sustainable chemistry, it has become an unremitting pursuit for organic synthesis chemists to develop new synthesis methods of 3-aryl indole compounds with high efficiency and mild conditions. In recent years, the study of visible light as an environmentally friendly and sustainable energy for chemical conversion has attracted wide attention. In this paper, the green synthesis of 3-aryl indoles was realized by visible light induced catalysis. A series of 3-aryl indole compounds were synthesized by oxidative coupling of 伪 -amino acid aryl acetylene decarboxylation under visible light, and a series of 3-aryl indoles were synthesized, which opened up a new path for the synthesis of such indole derivatives. Compared with the traditional synthesis method, the reaction process is simple, the reaction conditions are mild, the region selectivity is good, and the substrate is universal, and so on. Under the optimized reaction conditions, the corresponding target products were obtained in medium to good yield for a variety of reaction substrates with N alkyl and methylene substituents. In this paper, the possible reaction mechanism is proposed. The reaction mechanism was verified by isotope labeling experiment, cyclic voltammetry oxidation potential measurement and free radical capture experiment. The mechanism study shows that under the condition of visible light, the synthesis of 3-aryl indoles can be realized by intramolecular oxidation and decarboxylation through single electron transfer (set) process. Sixteen kinds of 3-aryl indoles with different substitutions were synthesized and characterized by GC-MS, NMR, HRMS, IR and melting point.
【学位授予单位】：哈尔滨工业大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O626.13

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