本文關鍵詞： 碳氫活化 分子碘 喹啉氮氧化物 磺�；� 雜環(huán)砜類化合物　出處：《鄭州大學》2017年碩士論文　論文類型：學位論文

【摘要】：喹啉是典型的芳香雜環(huán)化合物,是一類構成生命的重要基礎化合物,在農業(yè)、藥物化學等領域扮演著重要的角色。然而喹啉類化合物很容易在人體內被氧化形成2-羥基衍生物,從而大大降低甚至失去了它的藥物活性及生物活性,因此人們常常在喹啉的2位進行修飾,從而阻止這樣一個氧化過程的發(fā)生,同時,砜類化合物作為一類非常重要的有機合成中間體,在藥物、有機合成、工業(yè)等領域展現了其廣泛的物理、化學及生物活性,而以往合成2-砜基喹啉的方法十分有限,因此,開發(fā)一種快速高效、綠色合成2-砜基喹啉的方法具有重要意義。近年來,由于通過C-H鍵的直接官能團化的合成策略具有步驟簡單、原子經濟等突出優(yōu)點,吸引了越來越多科學家的關注與參與,過渡金屬催化作用下發(fā)展起來的C-H鍵活化的新合成方法層出不窮。然而需要指出的是,目前C-H鍵的活化主要是通過金屬的參與來實現的,而這些金屬當中有些是貴金屬,甚至是毒性金屬。因而發(fā)展無金屬條件下C-H鍵的活化,應該成為當前化學合成領域追求的研究方向。目前僅有的合成2-砜基喹啉的方法包括:(1)通過銅催化的定向C-H鍵活化,由喹啉氮氧化物合成2-砜基喹啉氮氧化物,而后可通過進一步的脫氧反應得到2-砜基喹啉,但此方法缺點是需要金屬催化,并且需要兩步反應得到目標產物;(2)在H-亞磷酸酯輔助活化下室溫條件下由喹啉氮氧化物合成2-砜基喹啉,但反應需要同樣當量的H-亞磷酸酯活化劑(3)在NaI/TBHP或I2/H2O2作用下,由喹啉氮氧化物合成2-砜基喹啉,但反應需多當量的碘活化劑。特別需要指出的是,碘單質或含碘的化合物作為一種廉價易得、簡單高效的催化劑,近年來開始代替金屬,催化有機反應。本論文報道一種在微量碘單質參與的無金屬條件下,以喹啉氮氧化物和廉價易得的亞磺酸鈉鹽為反應底物,室溫下一鍋煮快速高效的合成2-砜基喹啉類化合物的新方法。與以往報道的方法相對比,該方法的最顯著優(yōu)勢有:無金屬、條件溫和、操作簡單、快速高效、廣泛的底物適用性等,同時,在機理研究方面,本論文通過大量輔助性實驗,對機理進行了深入探討,并詳細闡明了相關實驗機理。本論文主要的研究內容:1.調研文獻,總結歸納以往碘試劑參與的催化合成反應,以及2-砜基喹啉類衍生物的定向合成及應用。2.建立了以磺酰氯做砜源,在四丁基碘化銨(TBAI)的輔助作用下,合成2-砜基喹啉的新方法。利用此方法共合成了6個目標產物,且均已經過1H NMR、13C NMR、HRMS的數據鑒定。3.研究機理后認為,TBAI之所以能促進喹啉氮氧的磺�；磻�,主要是因為TBAI與磺酰氯能同步的生成碘單質與亞磺酸鹽。故又建立了以喹啉氮氧化物與亞磺酸鈉鹽為反應底物,在碘單質的輔助下,高效合成2-砜基喹啉的新方法。以喹啉氮氧和苯亞磺酸鈉為起始反應物,分別從碘試劑種類及用量、苯亞磺酸鈉的用量、溶劑的種類、溫度等多個方面進行實驗條件的篩選及優(yōu)化。在最佳反應條件下,通過該方法高效合成了24個目標產物,且均已經過1H NMR、13C NMR、HRMS的數據鑒定。此方法廣泛適用于芳香、脂肪亞磺酸鈉鹽及帶有不同取代基的喹啉氮氧化物和異喹啉氮氧化物作反應底物。4.通過自由基阻斷劑、氮氣保護等實驗手段,對實驗機理進行深入的研究,并詳細闡述了相關實驗機理,機理如下:
[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:

【學位授予單位】：鄭州大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：O626

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