溴化铜催化一锅法合成N-磺酰基脒化合物

发布时间：2018-02-27 17:27

本文关键词： N-磺酰基脒衍生物叔胺仲胺磺酰氯叠氮化钠一锅法　出处：《郑州大学》2017年硕士论文　论文类型：学位论文

【摘要】：N-磺酰基脒(RSO_2N=CHNR_2)及其衍生物在有机化学、药物化学及农药等领域具有极其重要的地位,经常作为中间体被用于合成具有生物活性的天然产物、杂环化合物和药物,还可作为催化剂以及金属配体来催化有机反应。近年来对其合成方法的研究被逐渐地报道出来,这些方法主要包括:(1)在碱存在的条件下,由磺酰氯与脒盐酸盐通过Hinsberg反应合成N-磺酰基脒,(2)在铜(I)催化下通过磺酰叠氮、炔与仲胺的三组分反应合成N-磺酰基脒,(3)在DEAD或FeCl_3催化下,由磺酰叠氮与叔胺直接反应合成N-磺酰基脒,(4)在Na I/TBHP或NBS的催化下由磺酰胺与甲酰胺的反应合成N-磺酰基脒。但上述方法存在磺酰叠氮原料昂贵不易得,副产物较多,底物适用范围较窄,催化剂用量较大,并且条件不易控制等缺点。因而寻求简单、便捷、条件较温和的合成N-磺酰基脒的方法一直是化学与医药工作者的研究热点,也是极具挑战的领域之一。本论文提出了在溴化铜的催化作用下,使用廉价易得的磺酰氯、叠氮化钠与叔胺或仲胺反应,通过一锅法快速高效合成N-磺酰基脒化合物的新方法。与已报道的方法相比,该方法具有原料与催化剂廉价易得、易于保存,一锅法反应、操作简单方便,底物适用范围广等显著优点。并且利用自由基阻断,氮气保护等实验手段对实验机理进行了深入的研究与探讨。本论文主要从以下几个方面进行阐述:1.本论文第一章对N-磺酰基脒及其衍生物的性质、合成方法及实际应用等进行了系统的总结与归纳。2.第二章以对甲苯磺酰氯、叠氮化钠与三乙胺为基本反应原料,对反应物的用量、催化剂的种类及其用量、溶剂的种类、反应时间、反应温度等方面进行了系统的优化筛选,得到了最佳反应条件:0.5 mmol的磺酰氯、0.6 mmol的叠氮化钠、0.5 mmol的叔胺,加入5 mol%的溴化铜,置于5毫升的1,2-二氯乙烷溶剂之中,70°C搅拌反应3个小时,产率为78%;以对甲苯磺酰氯、叠氮化钠与二乙胺为基本反应原料,经过筛选得到了最佳反应条件:0.5 mmol的磺酰氯、1.0 mmol的叠氮化钠、1.25 mmol的二级胺与5 mol%的溴化铜分别在5.0m L1,2-二氯乙烷中70°C条件下分别搅拌1小时,将二级胺与溴化铜的反应液缓慢滴加到磺酰氯与叠氮化钠的反应液中,滴加完以后继续反应2小时。3.在最佳反应条件下对模板反应的适用性进行了考察,以各种苯磺酰氯、叠氮化钠与和多种三级胺为底物,高效合成了25个目标产物。利用自由基阻断,氮气保护等实验手段对实验机理进行了深入的研究与探讨,并提出了相关的实验机理,反应机理如下:4.在最佳反应条件下对模板反应与二级胺反应的适用性进行了考察,以个种苯磺酰氯和多种二级胺为底物,高效合成了12个目标产物,证明了该反应有一定的适用性。并提出了该反应的反应机理。反应机理如下:
[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 掳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 掳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:
【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】：O623.8

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