PIDA作用下构建二氮杂卓母核结构的方法学研究

发布时间：2018-12-09 18:37

【摘要】：时至今日，杂环结构合成尽管已经经历了多年的发展，但对于杂环结构合成的新方法的寻找仍然是药物化学领域的一个关注热点。二苯并[b,e][1,4]二氮杂卓结构是具有重要作用的一种杂环化合物，它广泛存在于很多具有生理活性的药物之中。高价碘试剂经过多年的研究，因其在形成例如碳碳键、碳氧键和碳氮键的过程中独特的氧化能力，在提高不同种类杂环化合物的产量时仍然在被应用。而且，众所周知，高价碘试剂在与N-甲氧胺化合物反应时可以产生稳定的氮正离子中间体，再经历分子内的芳香亲电环合过程可以得到不同种类的含氮杂环化合物。本文中的研究主要包含以下几个方面： 1.通过相关文献的调研与启发以及本课题组先前的有关研究工作，我们设计了一种由通过高价碘试剂氧化介导形成碳氮键来完成含有二苯并[b,e][1,4]二氮杂卓结构的杂环构建的方法。 2.甲氧基取代的氮化合物因为甲氧基的供电子效应，在氧化环合反应过程中可以形成一个稳定的氮正离子中间体。因此，我们尝试着将这种理论应用于实践来完成这个分子内的芳香亲电环合反应，以得到不同的含氮杂环化合物。 3.根据电子效应和空间效应的影响，我们设计了16个在底物体系中两个芳环都含有不同取代基的样例，以验证取代基团对反应产率的影响。 4.甲氧基可以在还原性条件下脱掉从而完成更广的应用。去甲氧基的结构可以简便的合成更多的二苯并[b,e][1,4]二氮杂卓衍生物。该论文方法的明显特征是其适用底物范围的广泛性、温和的反应条件以及氧化偶合这一关键步骤中无重金属参与的特点。而且最终产物上的甲氧基可以脱去以制备更多酰胺结构上的衍生物。
[Abstract]:Up to now, heterocyclic synthesis has been developed for many years, but the search for new methods of heterocyclic structure synthesis is still a hot topic in the field of drug chemistry. The structure of dibenzo [BNE] [1 (4)] azodiazepines is an important heterocyclic compound, which is widely found in many physiologically active drugs. High valence iodine reagents have been studied for many years because of their unique oxidation ability in the formation of carbon-carbon bonds, carbon-oxygen bonds and carbon-nitrogen bonds, so they are still used to increase the yield of different heterocyclic compounds. Furthermore, it is well known that high valence iodine reagents can produce stable nitrogen cationic intermediates when they react with N-methoxylamine compounds, and then undergo intramolecular aromatic electrophilic cyclization to obtain different kinds of nitrogen-containing heterocyclic compounds. The research in this paper mainly includes the following aspects: 1. Through the research and inspiration of relevant literature and previous research work of our group, we have designed a carbon-nitrogen bond mediated by oxidation of high valence iodine reagent to complete the synthesis of dibenzo [b]. E] method for constructing heterocyclic structures of diazepines. 2. Due to the electron donor effect of methoxy, a stable intermediate of nitrogen ions can be formed during the oxidative cyclization of methoxy substituted nitrogen compounds. Therefore, we try to apply this theory to practice to complete the aromatic-electrophilic cyclization of this molecule to obtain different nitrogen-containing heterocyclic compounds. 3. According to the influence of electron effect and space effect, we designed 16 samples with two aromatic rings containing different substituents in the substrate system to verify the effect of substituents on the yield of the reaction. 4. Methoxy groups can be removed under reductive conditions for wider application. The structure of demethoxy can be used to synthesize more dibenzo [BX] [1 + 4] diazazepines. The obvious characteristics of this method are its wide range of suitable substrates, mild reaction conditions and the absence of heavy metals in the key step of oxidative coupling. And the end product of methoxy can be removed to prepare more derivatives of amide structure.
【学位授予单位】：天津大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R914

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