IOCAS-IR
五元芳杂环新型合成方法研究
李晓伟
Subtype硕士
Thesis Advisor史大永
2020-05-22
Degree Grantor中国科学院大学
Place of Conferral中国科学院海洋研究所
Degree Name理学硕士学位
Keyword杂环化合物 好氧氧化 多组分反应 一锅反应
Abstract

芳杂环化合物广泛存在于天然产物中,并多应用于医药、农业、材料及日化等众多领域,是一类具有重要应用价值的有机化合物。因此,芳杂环的构建是有机合成中的重要研究领域,引起了研究人员们的极大兴趣。其中,苯并噻唑、吡咯、呋喃和噻吩衍生物是最为常见且重要的芳杂环化合物。到目前为止,文献中关于构建这类杂环化合物的方法虽然有很多,但是仍存在一些问题,比如反应条件剧烈、污染严重、操作繁琐等。因此,在本论文中我们主要围绕这四种杂环化合物的合成来展开研究,希望开发出高效、低污染且具有通用性的合成方法来解决这一问题。

首先以文献综述的形式分别介绍了苯并噻唑、吡咯、呋喃和噻吩类化合物的重要作用及各自合成方法的研究现状。在此基础上,我们提出了三组分构建苯并噻唑类化合物和一锅两步法合成常见五元杂环的想法,具体取得的成果如下:

1. 我们实现了乙酸促进的三组分氧氧化反应,利用该策略我们选择性的合成了一系列复杂的2-硫烷基苯并噻唑类化合物我们以容易获得的2-氨基苯硫酚、α,β-不饱和醛和各种芳基硫酚化合物为底物,氧气作为绿色氧化剂,乙酸为促进剂,实现了苯并噻唑杂环的构建。该方法条件温和,操作简单,无过渡金属参与,底物适用范围广,官能团兼容性好,可进一步应用合成各种复杂的天然产物及生物医药活性分子同时,该反应具有完全的区域选择性,为合成复杂分子提供了强有力的方法。

2. 我们通过把廉价过渡金属Cu催化的芳基丙酮类化合物的羰基α-Csp3-H的氧化偶联生成1,4-二酮化合物的反应和经典的Paal-Knorr反应联系起来,进行了一锅两步法合成吡咯、呋喃和噻吩五元杂环化合物的研究。我们经一系列的条件筛选,最后确定廉价的特戊酸铜为催化剂,2,2’-联吡啶为配体,二叔丁基过氧化物为氧化剂,环己烷中实现芳基丙酮C(sp3)-C(sp3)偶联合成了1,4-二酮化合物,并初步进行了底物的拓展,收率良好进一步在添加剂作用下原位进行Paal-Knorr反应,从而完成向五元芳杂环化合物的转化

Other Abstract

Aromatic heterocyclic compounds, frequently found in natural products, is a class of organic compounds with important application value, which are widely used in many fields such as medicine, agriculture, materials, and daily chemicals, etc. Therefore, the construction of aromatic heterocycles is an important research area in organic synthesis, which has attracted great interest from researchers. Among them, benzothiazole, pyrrole, furan and thiophene derivatives are the most common and important aromatic heterocyclic compounds. So far, although there are many methods for constructing such heterocyclic compounds in the literature, some problems are still existed, such as harsh reaction conditions, serious pollution, and tedious work-up procedures. Therefore, in this paper, we mainly focus on the synthesis of these four heterocyclic compounds,  developing an efficient, low pollution, and universal synthesis method to solve this problem.

At the beginning of the paper, the important roles of benzothiazoles, pyrroles, furans, and thiophenes and development status of their synthetic methods were summarized firstly through literature review. On this basis, we proposed the idea of generating benzothiazole compounds via a three-component reaction, and synthesizing common five-membered heterocyclic rings in a “one-pot and two-step method”. The specific achievements of this paper are as follows:

1. We have achieved a three-component aerobic oxidation reaction promoted by acetic acid. Using this strategy, we have synthesized a series of complex 2-thioarylbenzothiazoles with high selectivity. In this reaction, easily available 2-aminothiophenols, α,β-unsaturated aldehydes, and various aryl thiophenols were used as substrates for the construction of benzothiazole heterocycles with oxygen as a green oxidant and acetic acid as a promoter. Mild conditions, simple operation, no transition-metal involvement, wide range of substrates, and good functional group compatibility make this method very practical for the synthesis of various complex natural products and biomedical active molecules. At the same time, the reaction has a complete regioselectivity, providing a powerful method for the synthesis of complex molecules.

2. By linking the reaction of the oxidative coupling of the carbonyl α-Csp3-H of aryl acetones catalyzed by the inexpensive transition-metal Cu to 1,4-diketone compounds and the classic Paal-Knorr reaction, we studied the synthesis of pyrroles, furans and thiophenes by "one-pot and two-step method". After a series of conditions screening, the C(sp3)-C (sp3) coupling of aryl acetones was developed in cyclohexane to synthesize 1,4-diketone compounds using inexpensive copper pivalate as a catalyst, 2,2'-bipyridine as a ligand, and di-tert-butyl peroxide as an oxidant. We initially expanded the substrate of this reaction with good yields. Further, the Paal-Knorr reaction will be performed in situ under the addition of additives for the synthesis of five-membered aromatic heterocyclic compounds.

MOST Discipline Catalogue理学
Language中文
Document Type学位论文
Identifierhttp://ir.qdio.ac.cn/handle/337002/164691
Collection中国科学院海洋研究所
实验海洋生物学重点实验室
Recommended Citation
GB/T 7714
李晓伟. 五元芳杂环新型合成方法研究[D]. 中国科学院海洋研究所. 中国科学院大学,2020.
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201728006812012-李晓伟—(3675KB)学位论文 暂不开放CC BY-NC-SA
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