以肟酯为原料合成N-杂环化合物反应的研究
发布时间：2018-12-12 11:12
【摘要】：含氮杂环化合物广泛存在于农药、医学以及材料科学等研究领域中。例如,吡唑并吲哚酮类化合物是一类具有生物活性的分子骨架,多取代吡啶衍生物尤其是三氟甲基取代的吡啶化合物在医药领域中的用途也十分广泛。鉴于N-杂环化合物具有重大的实际应用价值,其合成方法学研究一直都是有机合成化学领域研究的热点。合成氮杂环化合物的研究方法已有大量文献报道,从廉价易得的原料出发,高效、高选择性构建含氮杂环化合物一直是有机合成化学研究者追求的目标。本论文研究旨在以肟酯为原料、过渡金属或非金属试剂为催化剂,发展吡唑并吲哚酮衍生物、2,4-二芳基吡啶衍生物以及三氟甲基取代吡啶衍生物等N-杂环化合物的合成方法学,具体研究内容如下:1、以2-取代吲哚和肟酯为原料,以铜盐为催化剂,在氧气氛围中,通过分子间成环实现吲哚N1/C2/C3同时官能团化反应,制备吡唑并吲哚酮衍生物。该方法使用的催化剂氯化铜,是一种廉价易得的过渡金属试剂。相比以往合成氮杂环化合物的研究方法,该方法具有成本低、反应条件温和、产率高、底物适应性广、官能团兼容性好、副产物对环境无污染、目标产物易于分离提纯等优点。此方法的原料肟酯既作为“氮”源,又作为内部氧化剂引发吲哚的有氧氧化成环反应,为合成吡唑并吲哚酮衍生物提供了一条新的途径。2、以肟酯和烯醛为原料,在单质碘和三乙胺的共同促进下,高效、高化学选择性制备2,4-二芳基吡啶衍生物。该方法使用的添加剂单质碘和三乙胺廉价易得,而且该反应条件简单,易操作。通过初步的机理研究实验表明,该反应可能是经过一种自由基途径进行的。3、以肟酯和三氟甲基试剂为原料,在碘化铵促进下,加入连二亚硫酸钠为还原剂,合成具有重要医用价值的三氟甲基取代的吡啶衍生物。进一步研究发现,使用肟酯、醛类和三氟甲基试剂为原料,在碘化铵促进下,以三乙胺为添加剂,可以通过一锅法合成2,3,4,6-四取代三氟甲基吡啶衍生物。该方法无需使用过渡金属催化剂、条件简单、产率高,为合成三氟甲基取代吡啶衍生物提供了一种新途径。
[Abstract]:Nitrogen heterocyclic compounds are widely used in pesticide, medicine and material science. For example, pyrazole indole ketones are a kind of molecular skeleton with biological activity. Polysubstituted pyridine derivatives, especially trifluoromethyl substituted pyridine compounds, are also widely used in the field of medicine. Since N-heterocyclic compounds have great practical application value, their synthetic methodology has always been a hot spot in the field of organic synthesis chemistry. The research methods for the synthesis of nitrogen-heterocyclic compounds have been reported in a large number of literatures. Starting from cheap and easily available raw materials, the construction of nitrogen-containing heterocyclic compounds with high efficiency and high selectivity has always been the goal pursued by the researchers of organic synthesis chemistry. The aim of this paper is to develop pyrazole indole derivatives using oxime ester as raw material and transition metal or nonmetallic reagent as catalyst. The synthesis methods of N-heterocyclic compounds, such as 2-diarylpyridine derivatives and trifluoromethyl substituted pyridine derivatives, were studied as follows: 1. Using 2-substituted indole and oxime ester as raw materials, copper salt as catalyst, In oxygen atmosphere, pyrazolyl indole derivatives were synthesized by simultaneous functional reaction of indole N1/C2/C3 through intermolecular ring formation. The catalyst used in this method is copper chloride, which is a cheap and easily available transition metal reagent. Compared with the previous research methods for the synthesis of nitrogen heterocyclic compounds, this method has the advantages of low cost, mild reaction conditions, high yield, wide substrate adaptability, good functional compatibility, no pollution of byproducts to the environment and easy separation and purification of the target products. The oxime ester of this method is used as a "nitrogen" source as well as an internal oxidant to initiate the aerobic oxidation of indole, which provides a new way for the synthesis of pyrazolindoleone derivatives. 2Oxime ester and aldehydes are used as raw materials. Under the promotion of simple iodine and triethylamine, 2o 4-diaryl pyridine derivatives were synthesized with high efficiency and high chemical selectivity. The simple iodine and triethylamine additives used in this method are cheap and easy to obtain, and the reaction conditions are simple and easy to operate. The experimental results show that the reaction may be carried out by a free radical pathway. With oxime ester and trifluoromethyl reagent as raw materials, sodium dithioate was added as reductant with the help of ammonium iodide. Synthesis of trifluoromethyl substituted pyridine derivatives with important medical value. It was further found that the derivatives of 2o 3N 4N 6 Tetra substituted trifluoromethyl pyridine could be synthesized by one pot method using oxime ester, aldehyde and trifluoromethyl reagents as raw materials, with the promotion of ammonium iodide and triethylamine as additives. The method has the advantages of simple conditions and high yield, which provides a new way for the synthesis of trifluoromethyl substituted pyridine derivatives.
【学位授予单位】：湘潭大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O626
[Abstract]:Nitrogen heterocyclic compounds are widely used in pesticide, medicine and material science. For example, pyrazole indole ketones are a kind of molecular skeleton with biological activity. Polysubstituted pyridine derivatives, especially trifluoromethyl substituted pyridine compounds, are also widely used in the field of medicine. Since N-heterocyclic compounds have great practical application value, their synthetic methodology has always been a hot spot in the field of organic synthesis chemistry. The research methods for the synthesis of nitrogen-heterocyclic compounds have been reported in a large number of literatures. Starting from cheap and easily available raw materials, the construction of nitrogen-containing heterocyclic compounds with high efficiency and high selectivity has always been the goal pursued by the researchers of organic synthesis chemistry. The aim of this paper is to develop pyrazole indole derivatives using oxime ester as raw material and transition metal or nonmetallic reagent as catalyst. The synthesis methods of N-heterocyclic compounds, such as 2-diarylpyridine derivatives and trifluoromethyl substituted pyridine derivatives, were studied as follows: 1. Using 2-substituted indole and oxime ester as raw materials, copper salt as catalyst, In oxygen atmosphere, pyrazolyl indole derivatives were synthesized by simultaneous functional reaction of indole N1/C2/C3 through intermolecular ring formation. The catalyst used in this method is copper chloride, which is a cheap and easily available transition metal reagent. Compared with the previous research methods for the synthesis of nitrogen heterocyclic compounds, this method has the advantages of low cost, mild reaction conditions, high yield, wide substrate adaptability, good functional compatibility, no pollution of byproducts to the environment and easy separation and purification of the target products. The oxime ester of this method is used as a "nitrogen" source as well as an internal oxidant to initiate the aerobic oxidation of indole, which provides a new way for the synthesis of pyrazolindoleone derivatives. 2Oxime ester and aldehydes are used as raw materials. Under the promotion of simple iodine and triethylamine, 2o 4-diaryl pyridine derivatives were synthesized with high efficiency and high chemical selectivity. The simple iodine and triethylamine additives used in this method are cheap and easy to obtain, and the reaction conditions are simple and easy to operate. The experimental results show that the reaction may be carried out by a free radical pathway. With oxime ester and trifluoromethyl reagent as raw materials, sodium dithioate was added as reductant with the help of ammonium iodide. Synthesis of trifluoromethyl substituted pyridine derivatives with important medical value. It was further found that the derivatives of 2o 3N 4N 6 Tetra substituted trifluoromethyl pyridine could be synthesized by one pot method using oxime ester, aldehyde and trifluoromethyl reagents as raw materials, with the promotion of ammonium iodide and triethylamine as additives. The method has the advantages of simple conditions and high yield, which provides a new way for the synthesis of trifluoromethyl substituted pyridine derivatives.
【学位授予单位】：湘潭大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O626
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