【作者】 刘冰；

【导师】 梁福顺；

【作者基本信息】 东北师范大学 ， 有机化学， 2015， 硕士

【摘要】 多组分反应是由简单的起始原料构建复杂的分子,其具有成键高效、原子经济性、产物结构复杂等特点。近年来,作为强有力的合成工具在合成化学、组合化学以及天然产物合成等领域具有广泛应用。异喹啉酮类衍生物,是生物碱的基本结构单元。同时还具有多种生物活性,如舒张血管、强心剂、降血压、抗糖尿病和抗癌等。异吲哚酮衍生物,作为母核结构广泛存在于天然产物中,也具有一定的生物活性及药理活性。由于这两类化合物潜在的应用前景,因此找到一种简单高效的合成方法显得尤为重要。本文着重讨论了无过渡金属催化的五元和六元芳杂环化合物的形成过程。反应从2-乙酰基-2-酰胺基环氧乙烷底物出发,以二氯甲烷作溶剂,在室温条件下与芳醛和丙二腈发生三组分反应。研究发现,通过改变碱的种类和延长反应时间就可得到两种完全不同的产物,即为异喹啉酮和异吲哚酮衍生物,而这则完全取决于环氧乙烷衍生物的顺反结构。根据实验事实,对两种杂环化合物的合成提出了可能反应机理:异喹啉酮的合成经历了串联Knoevenagel缩合,分子间迈克尔加成,分子内碳环合(形成六元碳环),经由氰基负离子消除的芳构化和分子内氮环合(形成六元氮杂环)等过程;异吲哚酮衍生物的合成除了经过上述的过程之外,还可能经过水解、脱羧和再环合过程。此多组分反应,构建了1个六元碳环、1个五元/六元氮环,高效的生成了4支C-C键和1支C-N键。所合成的一系列衍生物的结构已经过核磁共振氢谱、碳谱、高分辨质谱以及X-ray单晶衍射表征。该反应的提出为杂环化合物的合成提供了一种新方法。更多还原

【Abstract】 Multicomponent reactions(MCRs) serve as a powerful tool in recent years for assembly of complex structures from simple starting materials. These highly effect reactions are widely used in both combinatorial synthesis and are particularly useful for the construction of diverse nature products due to the advantages of greater bonding-efficiency, atom economy and structural complexity.Isoquinolinones constitute an important class of alkaloids, which displays important biological activities including vasorelaxation, cardiotonic effects, reduse blood press, antiglycuresis and anticancer effects. The isoindolinones contain the scaffold in many compounds of the natural products and exhibit an array of promising biological and pharmacological properties. It is the most important to find a methodology which constitutes the most simple and direct high-yield approach to a variety target molecules because of the potential application prospect.This paper lay emphasis on the syntheses of five and six-numbered heteroaromatic compounds without metal catalysis. The synthesis accomplished via the three component reaction of 2-acetyl-oxirane-2-carboxamides, arylaldehydes and malononitrile at room temperature using DCM as the solvent. We found that two entirely different product can be got from cis- and trans- substrates by changing the type of the base and extend the time, isoquinolinones and isoindolinones. Based on all the experiment results, we proposed the plausible mechanism: for the formation of isoquinolinones, The process involves tandem Knoevenagel condensation,intermolecular Michael addition, intramolecular carbo-cyclization(to form the six-membered carbon ring), aromatization via elimination of the cyanide anion and intramolecular azacyclization(to form the six-membered nitrogen ring); for the synthesis of isoindolinones, except undergos the same progress, it may also contain hydrolysis, decarbonation and recyclation. One six-numbered carbon ring and one five-numbered/six-numbered nitrogen ring were formed in this multicomponent reaction, in addition, this reaction highly effect construct 4 C-C bond and 1 C-N bond.All of the new conpounds were characterized by 1HNMR spectra, 13 CNMR spectra,High resolution mass spectra(HMRS) and the X-ray single-crystal diffraction. This is the new synthesis method of heterocyclic compounds.更多还原