催化的交叉脱氢偶联和双环化反应在构建氮硫杂环中的应用

发布时间：2018-08-10 17:18

【摘要】：本论文由六部分组成。第一部分简要介绍了C-S键的构建,交叉脱氢偶联反应以及双环化反应。其中,C-S键的构建包含以下四个方面内容,分别为金属催化的分子内/分子间C-S键的构建以及无金属催化的分子内/分子间C-S键的构建。交叉脱氢偶联反应主要描述了在无金属条件下,通过交叉脱氢偶联反应构建C-C、C-N、C-O、C-S及C-P键的最新研究进展。双环化反应则是分别对分子内、两组分以及多组分双环化反应在构建碳环,氮杂环,氧杂环,氮氧杂环,氮硫杂环等中的应用进行了较为详细地阐述。基于上述文献的调研,提出了本论文所涉及氮硫杂环合成的选题依据、意义、创新点和研究方法。第二部分介绍了一类新的无金属条件下的交叉脱氢偶联反应,并用其构建了分子内C-S键。利用靛红与α-硫氰基苯乙酮衍生的三乙胺硫醇盐为原料,以I_2为催化剂,在1,4-二氧六环溶剂中反应,高效地合成了苯并[b]噻吩衍生物,实现了无金属条件下C(sp2)-S键的构建。三乙胺硫醇盐芳基上的取代基兼容性广泛,但给电子的取代基相对于吸电子的取代基更能促进该反应的进行。控制实验证实该反应涉及I_2/O_2介导的自由基历程。第三部分描述了一类新的I_2/DMSO介导的交叉脱氢偶联反应用于分子间C-S键的构建。继续选用上述自制的三乙胺硫醇盐为原料,在I_2/DMSO介导下,将其与吲哚衍生物进行分子间反应,高区域选择性地合成了 3-硫醚吲哚衍生物,收率优秀,同时实现了分子间C-S键的交叉脱氢偶联。用富电子的吡咯衍生物取代吲哚拓展上述反应时也可顺利进行,以良好的产率转化为相应的芳硫醚化的吡咯衍生物。吡咯环上的取代基可调控芳硫醚化发生的位置。控制实验证实该反应涉及亲电取代过程而非自由基历程。第四部分发展了一类新的I_2/O_2介导的交叉脱氢偶联反应用于构建分子间N-S键。利用三乙胺硫醇盐和芳基肼为起始原料,在I_2/O_2介导下,高效地合成了官能化的1,2,3-噻二唑衍生物。三乙胺硫醇盐和芳基肼上的取代基均不影响反应的进行。其中,芳基肼上电中性的取代基产率略高于给电子以及吸电子的取代基。控制实验证实该反应涉及I_2/O_2介导的自由基历程。在此基础上,提出了合理的反应机理,其涉及腙的原位形成、S-I键的形成与均裂以及自由基偶联等历程。第五部分介绍了一类新的三乙胺硫醇盐参与的双环化反应。继续利用三乙胺硫醇盐为反应底物,将其与脂肪肼进行反应,意外地经历了串联双环化过程,而非上一章节描述的自由基历程,高化学选择性和区域选择性地得到了一系列吡唑并[3,4-c]喹啉衍生物。基于文献调研以及我们的实验结果,提出了合理的反应机理,其涉及分子间质子交换,互变异构,选择性亲核加成等历程。值得一提的是,没有氢键受体部分的脂肪肼并不适用于该双环化反应。第六部分为实验部分。所有产物都经过了红外光谱、核磁共振氢谱、碳谱、高分辨率质谱的表征,部分化合物的结构得到了单晶X-衍射的确证,同时提供了部分代表性化合物的谱图。
[Abstract]:This paper consists of six parts. The first part briefly introduces the construction of C-S bond, cross-dehydrogenation coupling reaction and bicyclic reaction. The construction of C-S bond includes the following four aspects: the construction of metal-catalyzed intramolecular/intermolecular C-S bond and the construction of non-metal-catalyzed intramolecular/intermolecular C-S bond. Coupling reactions mainly describe the latest progress in the construction of C-C, C-N, C-O, C-S and C-P bonds by cross-dehydrogenation coupling reactions in the absence of metals. Bicyclization reactions compare the applications of intramolecular, two-component and multi-component bicyclic reactions in the construction of carbon, nitrogen, oxygen, nitrogen and sulfur heterocycles, etc. Based on the investigation of the above-mentioned literatures, the basis, significance, innovation and research methods for the synthesis of azo-thiocyanate heterocycles are proposed. In the second part, a new type of cross-dehydrogenation coupling reaction without metal is introduced and used to construct intramolecular C-S bonds. Benzothiophene derivatives were synthesized efficiently from triethylamine mercaptan in 1,4-dioxane solvent using I_2 as catalyst. The C(sp2)-S bond was constructed without metal. The substituents on the aryl groups of triethylamine mercaptan have wide compatibility, but the substituents of electron donors can promote the formation of the C(sp2)-S bond. The reaction was carried out. The controlled experiments confirmed that the reaction involved I_2/O_2-mediated free radical mechanism. In the third part, a new class of I_2/DMSO-mediated cross-dehydrogenation coupling reactions were described for the construction of intermolecular C-S bonds. 3-thioether indole derivatives were synthesized with excellent yield and cross-dehydrogenation coupling of C-S bonds between molecules. The above reaction can also be carried out smoothly by substituting indoles with electron-rich pyrrole derivatives. The corresponding pyrrole derivatives were converted to aryl thioetherylated pyrrole derivatives in good yields. In the fourth part, a new class of I_2/O_2-mediated cross-dehydrogenation coupling reactions were developed to construct intermolecular N-S bonds. Triethylamine mercaptan and aryl hydrazine were used as starting materials and I_2/O_2-mediated cross-dehydrogenation coupling reactions were highly effective. The functionalized 1,2,3-thiadiazole derivatives were synthesized. The substituents on triethylamine mercaptan and arylhydrazine did not affect the reaction. The yield of the electroneutral substituents on arylhydrazine was slightly higher than that of the electron donors and electron donors. Reasonable reaction mechanism is discussed, which involves hydrazone formation in situ, S-I bond formation and homo-cleavage, and free radical coupling. In the fifth part, a new class of triethylamine mercaptan salt is introduced. Triethylamine mercaptan salt is used as reaction substrate to react with aliphatic hydrazine, which has undergone series bicyclization accidentally. A series of pyrazolium [3,4-c] quinoline derivatives have been synthesized with high chemoselectivity and regioselectivity, rather than the free radical mechanism described in the previous chapter. Based on the literature review and our experimental results, a reasonable reaction mechanism has been proposed, which involves intermolecular electron exchange, tautomerism, and selective nucleophilic addition. The sixth part is the experimental part. All the products have been characterized by IR, 1H NMR, C NMR and HRMS. The structure of some of the compounds has been confirmed by single crystal X-ray diffraction, and some of the representative compounds have been provided. Spectrum.
【学位授予单位】：南京大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：O626

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