过渡金属催化的含氮杂环化合物的合成与修饰

发布时间：2018-04-11 07:28

本文选题：过渡金属催化 + 偶联反应　；参考：《沈阳师范大学》2017年硕士论文

【摘要】：近年来,作为有力的合成手段,过渡金属催化的偶联反应和碳氢键活化反应发展迅速,含氮和含硫杂环化合物因其特殊的结构及生物活性,对其的研究也日渐丰富。因此,利用过渡金属催化的偶联反应和碳氢键活化反应来实现含氮杂环化合物的合成与修饰受到越来越多的关注。本文在此基础上对吡唑并噻嗪类衍生物、异喹啉类衍生物、含氮稠杂环化合物的合成以及吲哚啉类衍生物的修饰做了较为细致的研究,成果如下:开发了一种高效的铜催化的三组分的“一锅两步法”合成吡唑并噻嗪衍生物的新方法。该反应使用廉价易得的1-(2-卤代苯基)-3-烷基丙-2-炔-1-酮衍生物,盐酸肼和β-二硫代甲酯为底物原料,在温和的条件下,使用碘化亚铜作为催化剂,碳酸铯为碱,乙腈作溶剂,三组分下分为两步一锅就可以成功合成相对应的吡唑并噻嗪衍生物。所得到的目标产物含有羰基或卤素等具有功能性的官能团,为进一步的修饰提供了便利和可能。报道了一种高效实用的铱催化的合成异喹啉衍生物的新方法,该方法在铱催化剂的催化作用下,同时实现碳氢键活化反应和环化反应的串联。反应采用易得的苯甲酰亚胺衍生物和α-重氮羰基化合物作为原料,[Cp*IrCl2]2作催化剂,六氟锑酸银为添加剂,甲醇作溶剂,在温和的条件下,即可高收率制得异喹啉衍生物。该反应对于不同的官能团都显示出优异的容忍性,且分离简单,给异喹啉衍生物的合成提供了一条新的路线。开发了一种高效实用的铑催化吲哚啉C-7位胺化的新方法。该反应采用苯并异VA唑衍生物为胺化试剂,以吲哚啉衍生物为反应底物,[Cp*RhCl2]2为催化剂,六氟锑酸银为添加剂,四氢呋喃为溶剂,在温和的条件下,实现吲哚啉C-7位的胺化,得到相应的目标产物具有氨基、羰基、醛基、卤素或硝基等具有功能性的官能团,可以进行更深入的修饰或在药物合成领域发挥作用。开发了一种简单实用的方法,该方法以芳基唑和α-二氮羰基化合物作为底物,[Cp*RhCl2]2为催化剂,六氟锑酸银为添加剂,四氢呋喃为溶剂,在温和的条件下,通过Rh(III)催化的连续C-H键活化和环化,合成有价值的含氮稠杂环化合物。在该方案中,使用的芳基唑包括吡唑,苯并咪唑和1,2,4-三唑,并且大多数吡唑在温和条件下都可以顺利而有效地进行反应。这为用于候选药物筛选的多种潜在生物活性含氮稠杂环化合物的构建提供了新的可替代方法。
[Abstract]:In recent years, as a powerful method of synthesis, transition metal-catalyzed coupling reactions and hydrocarbon bond activation reactions have developed rapidly. Because of their special structure and biological activity, the studies of nitrogen-containing and sulfur-containing heterocyclic compounds have become increasingly abundant.Therefore, more and more attention has been paid to the synthesis and modification of nitrogen-containing heterocyclic compounds by transition metal-catalyzed coupling reaction and hydrocarbon bond activation reaction.In this paper, the synthesis of pyrazolyl thiazide derivatives, isoquinoline derivatives, nitrogen-containing heterocyclic compounds and the modification of indoline derivatives were studied in detail.The results are as follows: a new method for the synthesis of pyrazolium thiazide derivatives by a "one pot two step method" with three components catalyzed by copper has been developed.In this reaction, a cheap and easily obtained 1-hali-2-halophenyl-3-alkylpropyl-2-acetyne-1-one derivative was used, hydrazine hydrochloride and 尾 -dithiomethyl ester as substrate materials, copper iodide as catalyst, cesium carbonate as base and acetonitrile as solvent, under mild conditions.The corresponding pyrazolium thiazide derivatives can be successfully synthesized from the three components in two steps and one pot.The target product contains functional functional groups such as carbonyl or halogen, which provides convenience and possibility for further modification.A new method for the synthesis of isoquinoline derivatives catalyzed by iridium is reported in this paper. The method can realize the series reaction of hydrocarbon bond activation and cyclization under the catalysis of iridium catalyst.Isoquinoline derivatives were synthesized by using easily obtained benzoimide derivatives and 伪 -diazo carbonyl compounds as raw materials, [Cp*IrCl2] 2 as catalyst, silver hexafluoroantimonate as additive and methanol as solvent under mild conditions.The reaction showed excellent tolerance for different functional groups and simple separation, which provided a new route for the synthesis of isoquinoline derivatives.A high efficient and practical rhodium-catalyzed amination of indoline C-7 was developed.In this reaction, the amination of indoline C-7 was realized under mild conditions by using benzo-iso-VA derivatives as amination reagent, indoline derivatives as reaction substrate, [Cp*RhCl2] 2 as catalyst, silver hexafluoroantimonate as additive, tetrahydrofuran as solvent, and mild conditions.The corresponding target products have functional functional groups such as amino, carbonyl, aldehyde, halogen or nitro, which can be modified more deeply or play an important role in the field of drug synthesis.A simple and practical method was developed, using aryl azole and 伪 -diazo carbonyl compounds as substrates, [Cp*RhCl2] 2 as catalyst, silver hexafluoroantimonate as additive, tetrahydrofuran as solvent, under mild conditions.The valuable nitrogen-containing dense heterocyclic compounds were synthesized by continuous C-H bond activation and cyclization catalyzed by RhCII.In this scheme, aryl azoles are used, including pyrazole, benzimidazole and 1-triazole, and most pyrazoles can react smoothly and effectively under mild conditions.This provides a new alternative method for the construction of a variety of potential bioactive heterocyclic compounds containing nitrogen for drug candidate screening.
【学位授予单位】：沈阳师范大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O626

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