2-烷氧基（芳氧基）喹啉及其衍生物的合成研究

发布时间：2018-03-08 11:31

本文选题：喹啉N-氧化物化合物　切入点：烷氧基化　出处：《郑州大学》2016年硕士论文　论文类型：学位论文

【摘要】：由于高的原子经济性,近些年通过碳氢活化发展的新的合成方法层出不穷。碳-杂键的构建更是在有机合成领域占据重要地位,因而通过碳氢活化来构建碳-杂原子的方法被广泛报道,但值得强调的是,目前所报道的碳氢活化的方法通常情况下是在金属,甚至是贵金属或有毒金属的催化作用下进行的,而更加绿色的非金属参与的通过C-H活化来构建碳-杂键的方法还鲜有报道,非金属参与的喹啉C-O键的构建报道更少。喹啉作为一类非常重要的药效基团,广泛存在于天然产物和很多市售药物之中,但喹啉类药物2位在体内极易被氧化而使其失去药效,因而对喹啉2-位取代衍生物的合成改造具有重要意义。另外,α-烷氧基喹啉及其衍生物是有机合成重要的中间体结构,在农业和药物化学领域等展现出其广泛的物理、化学及生物活性,因而,探索无金属条件下通过碳氢活化的方法绿色快速合成α-烷氧基喹啉衍生物的新型合成方法具有重要现实意义。目前报道的合成α-烷氧基喹啉和α-芳氧基喹啉的方法主要有:(1)醇或者酚对α-卤代物亲核取代反应而得到;(2)磺酰氯等活化基团下,喹啉N-氧化合物和醇钠或者酚钠进行亲核加成而得到;(3)通过邻芳炔异氰化物关环脱氢得到。这些已报道方法的显著缺点包括:反应起始物难以制备、反应时间长、需金属催化、反应条件苛刻等等。本论文发展了一种在无金属参与下,以喹啉N-氧化物和醇(酚)为反应底物,由普通H-亚磷酸酯参与碳氢活化的快速高效合成2-烷氧基喹啉衍生物的新方法。与以往报道的方法相比,该方法的显著优势包括:快速高效、条件温和、无金属、原子经济性好、底物适用性广泛等。在机理研究方面,通过核磁磷谱跟踪方法对实验机理进行了深入的探讨,详细阐明了相关实验机理。本论文主要研究内容如下:1、对喹啉类化合物的研究进展和应用情况进行了概括总结。2、以正丙醇和喹啉N-氧化物作为模板反应,H-亚磷酸酯种类及其用量、反应物的用量、碱的种类及其用量、溶剂、四氯化碳用量、反应时间、反应温度等几个方面进行实验条件的优化,得到了最佳反应条件:0.4mmol喹啉N-氧化物,2mmol的正丙醇,0.8mmol的H-亚磷酸二异丙酯,2equiv的二异丙基乙胺,0.5m L四氯化碳,置于3m L的乙腈溶剂之中,常温搅拌反应5个小时。3、在最优反应条件下,考察模板反应的反应底物适用性。此方法广泛适用于醇、酚及带不同取代基的喹啉N-氧化物和异喹啉N-氧化物,共合成了目标产物26个,结构均经过1H NMR、13C NMR、HR MS等数据确认。4、结合31P NMR跟踪实验对实验机理进行了阐述
[Abstract]:Because of the high atomic economy, new synthesis methods developed by hydrocarbon activation are emerging in recent years, and the construction of carbon-heterogeneity bonds plays an important role in the field of organic synthesis. Therefore, the method of constructing carbon-hetero atoms through hydrocarbon activation has been widely reported, but it is worth emphasizing that the methods of hydrocarbon activation currently reported are usually carried out under the catalysis of metals, even precious metals or toxic metals. However, there are few reports of greener nonmetallic participation in C-H activation to construct carbon-heterogeneity bonds, and less on nonmetallic quinoline C-O bonds. Quinoline is a very important group of active groups. It is widely found in natural products and many marketable drugs. However, quinoline drugs are easily oxidized in vivo, causing them to lose their efficacy. In addition, 伪 -alkoxy quinoline and its derivatives are important intermediates in organic synthesis. Chemical and biological activity, therefore, It is of great practical significance to explore a new method for the rapid synthesis of 伪 -alkoxy quinoline derivatives by hydrocarbon activation under metal-free conditions. The formulas for the synthesis of 伪 -alkoxy quinoline and 伪 -aryl quinoline reported at present are of great practical significance. The method mainly consists of 1: 1) alcohol or phenol for nucleophilic substitution of 伪 -halogenates to obtain 2) sulfonyl chloride and other active groups. Quinoline N-oxide compounds are synthesized by nucleophilic addition with sodium alcohol or sodium phenolic acid) obtained by ring closing dehydrogenation of o-arylene isocyanides. These reported disadvantages include the difficulty of preparing reaction initiators, the long reaction time, and the need for metal catalysis. In this paper, we developed a kind of reaction substrate with quinoline N-oxide and alcohol (phenol). A new method for the rapid and efficient synthesis of 2-alkoxy quinoline derivatives by hydrocarbon activation with ordinary H- phosphite. The advantages of this method are as follows: rapid and efficient, mild conditions, no metal, and no metal. The atomic economy is good and the substrate is widely used. In the aspect of mechanism research, the experimental mechanism is deeply discussed by means of nuclear magnetic phosphorus spectrum tracking method. The main research contents of this thesis are as follows: 1. The research progress and application of quinoline compounds are summarized. 2. N-propanol and quinoline N-oxide are used as template reaction of H- phosphorous acid. Types and amounts of esters, The amount of reactants, kinds and amounts of alkali, solvent, carbon tetrachloride, reaction time, reaction temperature and so on were optimized. The optimum reaction conditions were obtained by using 0.5 mL carbon tetrachloride of 0. 8 mmol n-propanol, 0. 8 mmol diisopropyl phosphite and 2 equiv diisopropyl ethylamine, and placed in 3 m L acetonitrile solvent. Under the optimum reaction conditions, the suitability of substrate for template reaction was investigated. This method is widely used in alcohol, phenol, quinoline N-oxide with different substituents and isoquinoline N-oxide. A total of 26 target products were synthesized, the structures of which were confirmed by 1H NMR-13C NMRHR MS et al. 4. The mechanism of the experiment was described in combination with the 31P NMR tracking experiment.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：O626

【相似文献】