标题: 于有氧环境利用铜催化进行一锅化环化-酮基化反应合成咪唑并[1,2-a]苯并咪唑及1H-吡咯-1-基-1H-苯并[d]咪唑-5-羧酸乙酯
Copper-Catalysed Aerobic Oxidative Carbocyclization- Ketonization, One-Pot Synthesis of Imidazo[1,2-a]benzimidazole and 1H-pyrrol-1-yl-1H-benzo[d]imidazole-5-carboxylate
作者: 叶尊扬
孙仲铭
Ye, Tzuen-Yang
Sun, Chung-Ming
应用化学系硕博士班
关键字: 有氧环境;一锅化;环化;酮基化;Aerobic Oxidative;One-Pot;Carbocyclization;Ketonization
公开日期: 2016
摘要: 本论文共分做三部份,第一部分是利用铜催化于有氧的环境下一锅化进行环化和酮基化反应合成benzoimidazo[1,2-a]imidazolones,第二部分是单一铜催化于有氧的环境下进行环化和酮基化反应合成1H-pyrrol-1-yl-1H-benzo[d]imidazole-5-carboxylates,第三部分是合成Rosoxacin。
第一部分:以两种铜金属催化末端炔加成到来自于2-aminobenzimidazole与芳香醛形成的亚胺上,并在氧气系统下伴随着分子内环化合成benzoimidazo[1,2-a]imidazolones,此产物上新形成的羰基是来自于氧气,而本实验室成功研究出一种高效合成benzoimidazo[1,2-a]imidazolones的方法,此方法是藉由2-aminobenzimidazole、芳香醛和末端炔在一锅化有氧气条件下得到了新颖的氧化5-exo-dig环化-酮基化联继,此部分的结果已发表在Chem. Comm. 2016, 52, 6621-6624。
第二部分:在第一部分研究中得到了吡咯环的副产物,并进一步研究此副产物如何形成,并使其成为主要产物,以单一铜金属催化末端炔加成到亚胺上形成炔丙胺,于有氧气条件下炔丙胺再一次与末端炔反应形成中间体44,最后伴随着分子内环化,合成1H-pyrrol-1-yl-1H-benzo[d]imidazole-5-carboxylates,而此产物上新形成的羰基是来自于氧气,此研究结果在合成1H-pyrrol-1-yl-1H-benzo[d]imidazole-5-carboxylates提供了新颖的合成方法。
第三部分:在电脑辅助模拟计算下,旧药Rosoxacin在IRAK4 (interleukin-1 receptor-associated kinase 4)有良好的生物活性,而IRAK4是一种蛋白激酶,所以我们就以3-pyridin-4-ylaniline和乙氧基丙二酸酯(ethoxymethylenemalonate ester)在聚磷酸下合环,再以硷水解得到产物Rosoxacin。
This thesis is divided into three parts, the first part is copper-catalysed aerobic oxidative carbocyclization- ketonization, one-pot synthesis of imidazo[1,2-a]benzimidazole, the second part is a single copper-catalysed aerobic oxidative carbocyclization- ketonization, one-pot synthesis of 1H-pyrrol-1-yl-1H-benzo [d] imidazole-5-carboxylates, the third part is a synthetic Rosoxacin.
Part 1: Two copper metal-catalyzed alkyne-terminal addition to the imine derived from 2-aminobenzimidazole with an aromatic aldehyde formed in an oxygen system and accompanied by intramolecular cyclization synthesis benzoimidazo [1,2-a] imidazolones, on this product carbonyl newly formed from oxygen, our laboratory successfully developed a highly efficient synthesis benzoimidazo [1,2-a] imidazolones method, this method is by 2-aminobenzimidazole, aromatic aldehyde and terminal acetylene in one-pot of there oxygen conditions of the novel oxidation 5-exo-dig cyclization - ketonization, the results of this section have been published in Chem Comm 2016, 52, 6621-6624.
Part 2: Obtained in the first part of the study of the side-products of the pyrrole ring, and further study of how the formation of this side-product, and make it the main product formed propargylamine single copper metal-catalyzed alkyne-terminal addition to the imine to oxygen conditions under propargylamine again with a terminal alkyne to form intermediate 44, along with the final intramolecular cyclization, synthesizing 1H-pyrrol-1-yl-1H-benzo [d] imidazole-5-carboxylates, and the newly formed on this product carbonyl from oxygen, this results in the synthesis of 1H-pyrrol-1-yl-1H-benzo [d] imidazole-5-carboxylates provides novel synthetic methods.
Part 3: In the computer-aided simulation, old drugs Rosoxacin in IRAK4 (interleukin-1 receptor-associated kinase 4) has a good biological activity, IRAK4 is a protein kinase, so we have to 3-pyridin-4-ylaniline and ethoxy malonate (ethoxymethylenemalonate ester) in polyphosphate rings, then alkaline hydrolysis to give the product Rosoxacin.
URI: http://etd.lib.nctu.edu.tw/cdrfb3/record/nctu/#GT070352535
http://hdl.handle.net/11536/138950
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