异硫氰酸酯参与的含氮杂环化合物合成反应研究

发布时间：2018-06-23 10:15

本文选题：异硫氰酸酯 + 二芳基氧磷　；参考：《青岛科技大学》2017年硕士论文

【摘要】：菲啶类和异喹啉类衍生物是两类常见的含氮杂环化合物。含有菲啶骨架的天然生物碱具有特殊的生物活性,例如白屈菜赤碱具有抗菌消炎的生物活性,氧化石蒜碱具有抗癌活性等。此外,菲啶类化合物具有一定的光电特性。异喹啉及其衍生物也广泛存在于天然产物和药物中,具有代表性的有小檗碱类生物碱、细胞毒素生物碱奎诺卡星等。这些生物碱和药物具有抗菌、镇痛、降压等多种类型的生物活性。鉴于这两类化合物在医药等领域的应用价值,如何绿色高效地合成这两类含氮杂环化合物一直是有机化学研究的热点。异硫氰酸酯是一类重要的有机合成中间体,由于其制备简单、稳定性好等优点而被广泛使用。异硫氰酸酯类化合物不仅本身具有生物活性,而且利用其合成的含氮、含硫杂环化合物在生物医药、农药领域有着巨大的应用潜力。二取代氧磷类化合物作为一种特殊的含磷试剂而被用来合成含有磷酰基的各类化合物。二取代氧磷类化合物产生的磷自由基或磷负离子可通过串联环化反应实现杂环化合物的合成。二芳基碘摀盐常被用作一种高效的芳基化试剂,该试剂在金属催化下产生的芳基正离子可以与具有亲核性底物发生串联环化反应构筑杂环骨架化合物。在我们已有对官能团化异硫氰酸酯参与的串联环化反应的研究基础上,我们首先以2-联芳基异硫氰酸酯和二取代氧磷为原料,四水合醋酸锰为路易斯酸催化剂,通过一步构筑C-P/C-C高效地合成了28种取代的6-磷酰基菲啶类衍生物,并研究了取代基对反应的影响。通过机理控制实验证明了非自由基反应的历程,并提出了可能的反应机理。之后我们利用β-芳基异硫氰酸酯或烯基异硫氰酸酯与二芳基碘摀盐的串联环化反应合成了16种取代的1-芳硫基异喹啉类衍生物,并在无金属催化下β-芳基异硫氰酸酯和三氟甲磺酸甲酯反应合成了9种1-甲硫基-3,4-二氢异喹啉类化合物。我们对反应机理做了详细研究,并提出了可能的反应机理。
[Abstract]:Phenanthroline and isoquinoline derivatives are two common nitrogen heterocyclic compounds. The natural alkaloids containing phenanthroline skeleton have special biological activities, such as the antibacterial and anti-inflammatory activity of Chlorophylline, and the anticancer activity of oxylycorine. In addition, phenanthroline compounds have certain photoelectric properties. Isoquinoline and its derivatives are also widely found in natural products and drugs such as berberine alkaloids cytotoxin alkaloids quinoca and so on. These alkaloids and drugs have antibacterial, analgesic, hypotensive and other types of biological activities. In view of the application value of these two kinds of compounds in medicine and other fields, how to synthesize these two kinds of nitrogen-containing heterocyclic compounds efficiently and green has been a hot spot in organic chemistry. Isothiocyanate is an important intermediate in organic synthesis, which is widely used because of its simple preparation and good stability. Isothiocyanates not only have biological activity, but also have great application potential in biomedicine and pesticide field using nitrogen-containing heterocyclic compounds. Disubstituted phosphorus compounds are used as a special phosphorus-containing reagent to synthesize various compounds containing phosphoryl groups. The synthesis of heterocyclic compounds can be achieved by series cyclization of phosphorus free radicals or phosphorus anions produced by disubstituted phosphorus compounds. Diaryl iodide is often used as an efficient arylation reagent. The aryl positive ions produced by the reagent under metal catalysis can react in series with the nucleophilic substrate to form heterocyclic skeleton compounds. On the basis of our studies on the series cyclization of functional isothiocyanates, we first used 2-biarylisothiocyanate and disubstituted phosphorus as raw materials and manganese acetate tetrahydrate as Lewis acid catalyst. Twenty-eight substituted 6-phosphorylphenanthroline derivatives were synthesized by one-step construction of C-P / C-C, and the effects of substituents on the reaction were studied. The process of nonradical reaction was proved by mechanism control experiment, and the possible reaction mechanism was put forward. After that, 16 substituted 1-arylthioisoquinoline derivatives were synthesized by the series cyclization of 尾 -aryl isothiocyanate or allyl isothiocyanate with diaryl iodide. Nine 1-methylthio-4-dihydroisoquinoline compounds were synthesized by the reaction of 尾 -aryl isothiocyanate and methyl trifluoromethyl sulfonate without metal catalysis. We studied the reaction mechanism in detail and put forward the possible reaction mechanism.
【学位授予单位】：青岛科技大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O626

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