【作者】 荣良策；

【导师】 魏贤勇；

【作者基本信息】 中国矿业大学 ， 化学工艺， 2013， 博士

【摘要】 多组分反应是将多个底物放在一个反应器中，不经过中间体的分离，一步构建产物的操作方法。由于其具有操作简单、反应连续、原子经济性等优点而满足有机合成、药物合成的需要而受到广泛关注。本论文采用多组分反应的合成方法，设计合成一些可能具有药物活性的含氮、含氧和含硫杂环化合物。论文首先综述了近年来国内外多组分反应在合成杂环化合物方面的应用，简要介绍本论文的研究内容、研究目的和意义，以及本论文多组分操作的方法。本论文主要研究了二苯乙酮、芳醛和脲(或者碳酸胍)三组分无溶剂反应，一步构建了具有较大空间位阻嘧啶化合物。同时使用芳醛、2-吡啶乙酮和碳酸胍（或者氰基胍）合成部分含氮的多齿配体化合物；第四部分研究以2,4-噻唑烷-二酮、芳醛、丙二腈和正丁胺(或者环丙胺、3-吡啶甲胺)为反应底物，不需要使用任何催化剂，四组分反应有效、方便的一步构建5-氨基噻吩衍生物，这是一条不同于传统的Gewald反应合成噻吩的新方法。反应中发现2,4-噻唑烷-二酮发生了开环反应参与了噻吩结构的形成。实验结果表明反应对不同结构的胺具有良好的适应性；此外，研究了2-噻吩甲酰三氟丙酮、芳醛、达米酮和醋酸铵四组分反应方便的合成一系列新的喹啉衍生物(含有1,4-二氢吡啶核)。同时研究了2-噻吩甲酰三氟丙酮、芳醛和脲合成含有噻吩基的嘧啶衍生物，这是对Biginelli反应新的发展，本操作方法选择性好，底物适应范围广，较易构建化合物库；在第六部分研究了无溶剂条件下芳醛、四氢萘酮和环己酮的三组分反应有效的合成含氧杂环化合物呫吨醇，在简单操作下合成结构复杂的化合物说明了多组分反应的有效性，这些化合物都是首次报道的。同时意外发现芳醛和芳酮五组分反应合成环己醇衍生物的途径，这是合成环己醇反应新的发展，对合成的机理给以详细解析；最后，以活性化合物丙二腈参与的多组分反应合成吡啶化合物，也获得仔细研究，反应中意外获得了四氢化萘化合物，同时研究了异喹啉化合物的有效合成，本文为这几类化合物的合成研究提供了新的合成路线。研究表明，多组分反应是合成含氮、含氧和含硫杂环化合物的有效的方法。特别对于一些结构复杂的杂环化合物合成尤其如此。研究中发现无溶剂反应对多组分反应合成杂环化合物是一个有力的途径。每个系列都合成大量化合物，可以非常容易的构建小分子杂环化合物库。论文共合成139个化合物，绝大多数为首次合成的结构。所有产物都通过红外、核磁和高分辨质谱等分析手段对化合物的结构进行了详细的表征。部分化合物的晶体结构分析进一步确证的化合物结构。论文对每个系列化合物的的合成提出了可能的反应机理。所有研究的反应都具有反应操作简便、条件温和、反应时间短、产率高、以及原子经济等诸多优点。更多还原

【Abstract】 Multicomponent reaction (MCR) is the one-pot method for the synthesis of compoundsby taking many substrates into a reactor without separating intermediate products. Becauseof its simple operation, continuous reaction, atom economy, and meeting the need oforganic and pharmaceutical synthesis, this method has brought the much attention of people.In this dissertation, we designed and prepared some containing nitrogen, oxygen and sulfurheterocyclic compounds using multicomponent reactions. At first, the recent review ofsynthesis heterocyclic compounds using multicomponent reaction at home and abroad wasintroduced. The contents, purpose, significance and the operation of multicomponentreaction experiments about this dissertation were also involved in this part.The larger steric hindrance pyrimidines have been synthetized by one-potmulticomponent reaction of1,2-diphenylethanone, aromatic aldehydes and urea (orguanidine carbonate) under solvent-free conditions. At the same time, somenitrogen-containing polydentate ligands have been prepared from the raction of aromaticaldehydes,1-(pyridin-2-yl)ethanone and guanidine carbonate (or cyanoguanidine). In partfour, an efficient and convenient method for the preparation of5-amino-dihydrothiophenederivatives by four-component reaction of thiazolidine-2,4-dione, aromatic aldehyde,malononitrile and n-butylamine (or cyclopropanamine, pyridin-3-ylmethanamine) withoutusing any other catalysts was reported. It was found that the thiazolidine-2,4-dione byopening its ring to take part in constructing thiophene derivatives. This is a new process forsynthesis of thiophene derivatives with good adaptability about the different structures ofthe amines, and is different from classical the Gewald reaction. Furthermore, a series of newtype kuinoline derivatives (containing1,4-dihydropyridines core) were synthetized byfour-component reaction of4,4,4-trifluoro-1-(thiophen-2-yl)butane-1,3-dione, aromaticaldehyde,5,5-dimethylcyclohexane-1,3-dione (dimedonecas) and ammonium acetatewithout using any catalysts under room temperature. Simultaneously, containing-thienylpyrimidine derivatives were synthetized from4,4,4-trifluoro-1-(thiophen-2-yl)butane-1,3-dione, aromatic aldehyde and urea, and this is the new development of Biginellireaction. The advantages of these processes are good selectivity, broad substrate scope, easyconstruction of compounds libraries. In part six, the containing oxygen heterocycliccompounds, xanthydrol derivatives were efficiently prepared by the three-componentreaction of aromatic aldehyde,3,4-dihydronaphthalen-1(2H)-one, and cyclohexanone undersolvent-free conditions. It shows the effectiveness of multicomponent reaction for the synthesis of these complex structures with a very simple operation. The products ofxanthydrol were the first reported. We find an unexpected way to synthesize cyclohexanolderivatives from five-component reaction, and this is the new development for synthesis ofthese compounds. At last, the pyridine compounds have been synthetized viamulticomponent reaction by malononitrile taking part in the reaction, and the unexpectedtetrahydronaphthalene derivatives have been obtained in our research. At the same time, wereported the efficient method for synthesis of isoquinoline derivatives. There are all newprocesses for synthesis of these compounds.The results of the experiment show that multicomponent reaction is an efficient methodfor constructing of nitrogen-containing, oxygen-containin and sulfur-containingheterocyclic compounds. Especially, it may be the best method for constructing somecomplex heterocyclic compounds. Becaue of synthetizing many compounds for each series,there would very easy to constructing small molecule heterocyclic compounds libraries. Inthis dissertation,139compounds have been synthesized and most of them were reported forthe first time. All the structures of the products were confirmed on the basis of IR,1H NMRspectra, and highresolution mass spectrometry (HRMS), and some compounds wereadditionally confirmed by X-ray diffraction analysis. The possible reaction mechanismswere proposed in the text. The advantages of these reported reactions are simple operation,mild reaction conditions, short reaction time, high yields, and atomic economy.更多还原