碘辅助下2-砜基喹啉类化合物的合成研究

发布时间：2018-01-19 02:28

本文关键词： 碳氢活化分子碘喹啉氮氧化物磺酰化杂环砜类化合物　出处：《郑州大学》2017年硕士论文　论文类型：学位论文

【摘要】：喹啉是典型的芳香杂环化合物,是一类构成生命的重要基础化合物,在农业、药物化学等领域扮演着重要的角色。然而喹啉类化合物很容易在人体内被氧化形成2-羟基衍生物,从而大大降低甚至失去了它的药物活性及生物活性,因此人们常常在喹啉的2位进行修饰,从而阻止这样一个氧化过程的发生,同时,砜类化合物作为一类非常重要的有机合成中间体,在药物、有机合成、工业等领域展现了其广泛的物理、化学及生物活性,而以往合成2-砜基喹啉的方法十分有限,因此,开发一种快速高效、绿色合成2-砜基喹啉的方法具有重要意义。近年来,由于通过C-H键的直接官能团化的合成策略具有步骤简单、原子经济等突出优点,吸引了越来越多科学家的关注与参与,过渡金属催化作用下发展起来的C-H键活化的新合成方法层出不穷。然而需要指出的是,目前C-H键的活化主要是通过金属的参与来实现的,而这些金属当中有些是贵金属,甚至是毒性金属。因而发展无金属条件下C-H键的活化,应该成为当前化学合成领域追求的研究方向。目前仅有的合成2-砜基喹啉的方法包括:(1)通过铜催化的定向C-H键活化,由喹啉氮氧化物合成2-砜基喹啉氮氧化物,而后可通过进一步的脱氧反应得到2-砜基喹啉,但此方法缺点是需要金属催化,并且需要两步反应得到目标产物;(2)在H-亚磷酸酯辅助活化下室温条件下由喹啉氮氧化物合成2-砜基喹啉,但反应需要同样当量的H-亚磷酸酯活化剂(3)在NaI/TBHP或I2/H2O2作用下,由喹啉氮氧化物合成2-砜基喹啉,但反应需多当量的碘活化剂。特别需要指出的是,碘单质或含碘的化合物作为一种廉价易得、简单高效的催化剂,近年来开始代替金属,催化有机反应。本论文报道一种在微量碘单质参与的无金属条件下,以喹啉氮氧化物和廉价易得的亚磺酸钠盐为反应底物,室温下一锅煮快速高效的合成2-砜基喹啉类化合物的新方法。与以往报道的方法相对比,该方法的最显著优势有:无金属、条件温和、操作简单、快速高效、广泛的底物适用性等,同时,在机理研究方面,本论文通过大量辅助性实验,对机理进行了深入探讨,并详细阐明了相关实验机理。本论文主要的研究内容:1.调研文献,总结归纳以往碘试剂参与的催化合成反应,以及2-砜基喹啉类衍生物的定向合成及应用。2.建立了以磺酰氯做砜源,在四丁基碘化铵(TBAI)的辅助作用下,合成2-砜基喹啉的新方法。利用此方法共合成了6个目标产物,且均已经过1H NMR、13C NMR、HRMS的数据鉴定。3.研究机理后认为,TBAI之所以能促进喹啉氮氧的磺酰化反应,主要是因为TBAI与磺酰氯能同步的生成碘单质与亚磺酸盐。故又建立了以喹啉氮氧化物与亚磺酸钠盐为反应底物,在碘单质的辅助下,高效合成2-砜基喹啉的新方法。以喹啉氮氧和苯亚磺酸钠为起始反应物,分别从碘试剂种类及用量、苯亚磺酸钠的用量、溶剂的种类、温度等多个方面进行实验条件的筛选及优化。在最佳反应条件下,通过该方法高效合成了24个目标产物,且均已经过1H NMR、13C NMR、HRMS的数据鉴定。此方法广泛适用于芳香、脂肪亚磺酸钠盐及带有不同取代基的喹啉氮氧化物和异喹啉氮氧化物作反应底物。4.通过自由基阻断剂、氮气保护等实验手段,对实验机理进行深入的研究,并详细阐述了相关实验机理,机理如下:
[Abstract]:Quinoline is typical aromatic heterocyclic compound, is an important basis for a class of compounds, the formation of life in the field of agriculture, pharmaceutical chemistry plays an important role. However, quinoline compounds are easily oxidized to form 2- hydroxy derivatives in the human body, thereby greatly reduced or even lost drug activity and biological activity of it, so people often in 2 quinoline modified, thus preventing such an oxidation process, at the same time, sulfone compounds as intermediates in organic synthesis, very important in medicine, organic synthesis, industrial and other fields to show its wide range of physical, chemical and biological activity, and the previous methods of synthesis of 2- quinoline sulfone is very limited, therefore, the development of a fast and efficient method has important significance for the green synthesis of 2- sulfone quinoline. In recent years, due to the synthetic strategy of direct functional groups via C-H bonds of a step Simple, atom economy and other advantages, has attracted more and more attention and participation of scientists, a new synthesis method of C-H bond emerge in an endless stream developed under the catalysis of transition metal activation. However, it is necessary to point out that the activation of C-H bond is mainly through metal participation to achieve, and some of these metals are precious metals, even toxic metals. Therefore the development of metal under the condition of activation of C-H bond, should become the pursuit of the field of chemical synthesis in the direction of current research. Including the method of synthesis of 2- sulfone quinoline only at present: (1) directed by copper catalyzed C-H bond activation by Quinoline nitrogen oxide synthesis of 2- sulfone quinoline nitrogen then the oxides, 2- can be obtained by deoxidation reaction of quinoline sulfone further, but this method is need to metal catalysis, and two step reaction to obtain the target product; (2) activation in H- phosphite auxiliary Under room temperature conditions by Quinoline nitrogen oxide synthesis of 2- sulfone quinoline, but the reaction requires H- phosphite the same amount of activating agent (3) in NaI/TBHP or I2/H2O2, the synthesis of quinoline N-oxide 2- sulfone quinoline, but the reaction to the equivalent iodine activator. In particular, iodine compounds or iodine as a cheap, simple and efficient catalysts in recent years, began to replace metal, catalysis of organic reactions. This paper reports a metal trace iodine in unconditional participation, with quinoline N-oxide and inexpensive sub sulfonic acid sodium salt as substrate, a new synthesis method of 2- quinoline sulfone compounds at room temperature in one pot quickly. Compared with the method reported in the past, the most significant advantages of this method are: metal free, mild conditions, simple operation, fast and efficient, wide applicability of the substrate, at the same time, in the machine Science research, this paper through a large number of auxiliary experiments on the mechanism are discussed, and expounds the related experimental mechanism. The main research contents in this paper: 1. research literature, summarized the catalytic reaction of iodine reagents in the past, as well as 2- sulfone quinoline derivatives oriented synthesis and application of.2. is established in order to do sulfone sulfonyl chloride source in four Butyl Ammonium Iodide (TBAI) of the auxiliary function, a new synthesis method of 2- sulfone quinoline. Using this method, we synthesized 6 target compounds, and have been through 1H NMR, 13C NMR, HRMS.3. data authentication mechanism research that TBAI is able to promote the sulfonylation of quinoline N-oxides, mainly because the generation of iodine TBAI and sulfonyl chloride and sub synchronous sulfonate. So it is also established with quinoline N-oxide and sulfinic acid sodium salt as the substrate in the auxiliary iodine under the efficient synthesis of 2- sulfone A new method based on quinoline quinoline. The nitrogen oxygen and sodium benzoate as the starting reactant, respectively from the type and amount of iodine reagent, sodium benzene sulphinate dosage, solvent types, screening and optimization aspects of temperature experiment conditions. Under the optimum reaction conditions, through the method of efficient synthesis the 24 target product, and have been through 1H NMR, 13C NMR, data analysis of HRMS. This method is widely used in aromatic sulfinic acid sodium salt and fat with different substituents of quinoline and isoquinoline nitrogen oxides nitrogen oxide as reaction substrate by free radical.4. blocking agent, nitrogen protection, experimental methods, in-depth study on the experimental mechanism, and elaborated the related experimental mechanism, the mechanism is as follows:

【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O626

【相似文献】