發(fā)布時(shí)間：2018-02-27 17:27

  本文關(guān)鍵詞： N-磺酰基脒衍生物 叔胺 仲胺 磺酰氯 疊氮化鈉 一鍋法　出處：《鄭州大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：N-磺�；�(RSO_2N=CHNR_2)及其衍生物在有機(jī)化學(xué)、藥物化學(xué)及農(nóng)藥等領(lǐng)域具有極其重要的地位,經(jīng)常作為中間體被用于合成具有生物活性的天然產(chǎn)物、雜環(huán)化合物和藥物,還可作為催化劑以及金屬配體來催化有機(jī)反應(yīng)。近年來對(duì)其合成方法的研究被逐漸地報(bào)道出來,這些方法主要包括:(1)在堿存在的條件下,由磺酰氯與脒鹽酸鹽通過Hinsberg反應(yīng)合成N-磺�；�,(2)在銅(I)催化下通過磺酰疊氮、炔與仲胺的三組分反應(yīng)合成N-磺�；�,(3)在DEAD或FeCl_3催化下,由磺酰疊氮與叔胺直接反應(yīng)合成N-磺�；�,(4)在Na I/TBHP或NBS的催化下由磺酰胺與甲酰胺的反應(yīng)合成N-磺�；�。但上述方法存在磺酰疊氮原料昂貴不易得,副產(chǎn)物較多,底物適用范圍較窄,催化劑用量較大,并且條件不易控制等缺點(diǎn)。因而尋求簡單、便捷、條件較溫和的合成N-磺�；叩姆椒ㄒ恢笔腔瘜W(xué)與醫(yī)藥工作者的研究熱點(diǎn),也是極具挑戰(zhàn)的領(lǐng)域之一。本論文提出了在溴化銅的催化作用下,使用廉價(jià)易得的磺酰氯、疊氮化鈉與叔胺或仲胺反應(yīng),通過一鍋法快速高效合成N-磺�；呋衔锏男路椒�。與已報(bào)道的方法相比,該方法具有原料與催化劑廉價(jià)易得、易于保存,一鍋法反應(yīng)、操作簡單方便,底物適用范圍廣等顯著優(yōu)點(diǎn)。并且利用自由基阻斷,氮?dú)獗Ｗo(hù)等實(shí)驗(yàn)手段對(duì)實(shí)驗(yàn)機(jī)理進(jìn)行了深入的研究與探討。本論文主要從以下幾個(gè)方面進(jìn)行闡述:1.本論文第一章對(duì)N-磺�；呒捌溲苌锏男再|(zhì)、合成方法及實(shí)際應(yīng)用等進(jìn)行了系統(tǒng)的總結(jié)與歸納。2.第二章以對(duì)甲苯磺酰氯、疊氮化鈉與三乙胺為基本反應(yīng)原料,對(duì)反應(yīng)物的用量、催化劑的種類及其用量、溶劑的種類、反應(yīng)時(shí)間、反應(yīng)溫度等方面進(jìn)行了系統(tǒng)的優(yōu)化篩選,得到了最佳反應(yīng)條件:0.5 mmol的磺酰氯、0.6 mmol的疊氮化鈉、0.5 mmol的叔胺,加入5 mol%的溴化銅,置于5毫升的1,2-二氯乙烷溶劑之中,70°C攪拌反應(yīng)3個(gè)小時(shí),產(chǎn)率為78%;以對(duì)甲苯磺酰氯、疊氮化鈉與二乙胺為基本反應(yīng)原料,經(jīng)過篩選得到了最佳反應(yīng)條件:0.5 mmol的磺酰氯、1.0 mmol的疊氮化鈉、1.25 mmol的二級(jí)胺與5 mol%的溴化銅分別在5.0m L1,2-二氯乙烷中70°C條件下分別攪拌1小時(shí),將二級(jí)胺與溴化銅的反應(yīng)液緩慢滴加到磺酰氯與疊氮化鈉的反應(yīng)液中,滴加完以后繼續(xù)反應(yīng)2小時(shí)。3.在最佳反應(yīng)條件下對(duì)模板反應(yīng)的適用性進(jìn)行了考察,以各種苯磺酰氯、疊氮化鈉與和多種三級(jí)胺為底物,高效合成了25個(gè)目標(biāo)產(chǎn)物。利用自由基阻斷,氮?dú)獗Ｗo(hù)等實(shí)驗(yàn)手段對(duì)實(shí)驗(yàn)機(jī)理進(jìn)行了深入的研究與探討,并提出了相關(guān)的實(shí)驗(yàn)機(jī)理,反應(yīng)機(jī)理如下:4.在最佳反應(yīng)條件下對(duì)模板反應(yīng)與二級(jí)胺反應(yīng)的適用性進(jìn)行了考察,以個(gè)種苯磺酰氯和多種二級(jí)胺為底物,高效合成了12個(gè)目標(biāo)產(chǎn)物,證明了該反應(yīng)有一定的適用性。并提出了該反應(yīng)的反應(yīng)機(jī)理。反應(yīng)機(jī)理如下:
[Abstract]:N- sulfonylamidine (RSO2NX) and its derivatives play an extremely important role in the fields of organic chemistry, pharmaceutical chemistry and pesticides, and are often used as intermediates in the synthesis of natural products, heterocyclic compounds and drugs with biological activity. They can also be used as catalysts and metal ligands to catalyze organic reactions. In recent years, studies on their synthesis methods have been gradually reported. These methods mainly include: 1) in the presence of alkali, N- sulfonylamidine 2 was synthesized from sulfonyl chloride and amidine hydrochloride by Hinsberg reaction. N-sulfonyl amidine was synthesized by three component reaction of acetylene with secondary amine under the catalysis of copper (I). N- sulfonyl amidine was synthesized by the reaction of acetylene with secondary amine. N- sulfonyl amidine was synthesized under the catalysis of DEAD or FeCl_3. N- sulfonyl amidine was synthesized by direct reaction of sulfonyl azide with tertiary amine. N- sulfonyl amidine was synthesized by the reaction of sulfonamide with formamide under the catalysis of Na / TBHP or NBS. The application range of substrates is narrow, the amount of catalyst is large, and the conditions are not easy to control. Therefore, it has been a hot research topic for chemical and pharmaceutical workers to seek a simple, convenient and mild method for the synthesis of N-sulfonamidine. In this paper, the reaction of sodium azide with tertiary amines or secondary amines by using cheap and easily available sulfonyl chloride under the catalysis of copper bromide is proposed. A new method for the rapid and efficient synthesis of N-sulfonamidine by one-pot method is described. Compared with the reported method, the method has the advantages of cheap and easy to obtain raw materials and catalysts, easy to preserve, one-pot reaction, and simple and convenient operation. The substrate has a wide range of advantages and uses free radicals to block it. The mechanism of the experiment was studied by nitrogen protection and other experimental methods. In this paper, the following aspects are discussed: 1. In the first chapter, the properties of N-sulfonamidine and its derivatives are discussed. The synthesis method and practical application were systematically summarized and concluded. 2. In chapter 2, the basic reaction materials were p-toluenesulfonyl chloride, sodium azide and triethylamine, the amount of reactants, the kinds and amounts of catalysts, the kinds of solvents, and so on. The optimum reaction conditions were obtained, such as reaction time and reaction temperature. The optimum reaction conditions were as follows: 1: 0.5 mmol sulfonyl chloride 0.6 mmol sodium azide 0.5 mmol tertiary amine, 5 mol% copper bromide was added, 5 mol% copper bromide was added, and 5 mol% copper bromide was added. The reaction was agitated at 70 擄C for 3 hours in a 5 ml 1g / 2- dichloroethane solvent in a yield of 78. The raw materials for the reaction were p-toluenesulfonyl chloride, sodium azide and diethylamine. The optimum reaction conditions were obtained by screening the optimum reaction conditions: sodium azide 1. 25 mmol secondary amine and 5 mol% copper bromide 1. 0 mmol sulfonyl chloride 1. 0 mmol and 5 mol% copper bromide respectively stirring for 1 hour in 70 擄C of 5. 0 mL / L 1 / 2-dichloroethane, respectively. The reaction solution of secondary amine and copper bromide was added slowly to the reaction solution of sulfonyl chloride and sodium azide, and then the reaction continued for 2 hours. 3. The applicability of template reaction was investigated under the optimum reaction conditions, and various benzenesulfonyl chloride were used. A total of 25 target products were efficiently synthesized from sodium azide and various tertiary amines. The experimental mechanism was studied by means of free radical blocking and nitrogen protection, and the related experimental mechanism was proposed. The reaction mechanism is as follows: 4. Under the optimum reaction conditions, the applicability of the template reaction and the second-order amine reaction was investigated. Twelve target products were synthesized efficiently using benzene sulfonyl chloride and several secondary amines as the substrates. It is proved that the reaction has some applicability, and the reaction mechanism is put forward. The reaction mechanism is as follows:
【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：O623.8

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