钯催化的若干反应及其在药物中间体合成中的应用

发布时间：2018-09-05 14:14

【摘要】：金属催化偶联反应因其应用的广泛性,备受化学家们的关注,己经在化学、生物、药物修饰和材料构建等领域得到了广泛的应用。传统的均相金属催化反应中,催化剂难以回收、金属残留量高、价格昂贵。我们课题组开发了一种非均相聚苯胺负载钯催化剂。该催化剂中的氮元素对金属有一定的配位能力,从而可以较好的抓住金属,降低金属泄漏,减少产品中的金属残留。作为非均相催化剂,聚苯胺负载钯可方便地回收并多次循环利用。该催化剂已成功运用于Heck反应。另一方面,近年来,碳-氢键活化取得了飞速的发展。这一技术应用于药物合成,可减少废弃物的产生,缩短合成路线,降低合成成本,有重要的工业应用价值。因此,我们对此做了一定的探索性研究。我们用相应的烯烃作前体,来进行温和的钯催化的烯烃氢官能团化反应,该方法避免使用导向基团,并且钯-氢物种对烯烃的反应为顺式插入,从而实现碳-碳键和碳-杂键的构建,具有一定的可行性和实用性。本文主要研究了若干钯催化反应在药物中间体合成中的应用,研究内容如下:1、研究了大量制备、长期储存的聚苯胺负载钯催化剂的稳定性,及其在Suzuki反应与Sonogashira反应中的催化活性,并合成大量相关衍生物,通过核磁、气相质谱、红外等数据确定产物结构,最高产率可达到99%和96%。实验表明,该催化剂可以长期储存而不失活,且被成功应用于拉帕替尼和炔孕酮药物中间体的修饰中。2、研究了钯催化烯烃氢芳基化的方法,通过对各项反应条件的调控,并由气相色谱仪确定产物结构和产率。该反应更倾向于通过L*PdH对烯烃的插入反应,最后由芳基卤化物与中间体反应,从而构建碳-碳键。
[Abstract]:Metal catalytic coupling reactions have been widely used in chemistry, biology, drug modification and material construction because of their wide application. In the traditional homogeneous metal catalytic reaction, the catalyst is difficult to recover, the metal residue is high and the price is high. A heterogeneous Polyaniline supported palladium catalyst was developed. The nitrogen element in the catalyst has a certain coordination ability to the metal, so it can better grasp the metal, reduce the metal leakage, and reduce the metal residue in the product. As heterogeneous catalysts, Polyaniline supported palladium can be easily recovered and reused for many times. The catalyst has been successfully used in Heck reaction. On the other hand, carbon-hydrogen bond activation has made rapid progress in recent years. The application of this technology to the synthesis of drugs can reduce the production of waste, shorten the synthetic route and reduce the cost of synthesis, which has important industrial application value. Therefore, we have done some exploratory research on this. We used the corresponding olefins as precursors for a mild palladium catalyzed hydrofunctionalization of olefins, avoiding the use of guided groups, and the palladium hydrogen species reacted with cis-insertion of olefins. It is feasible and practical to construct carbon-carbon bond and carbon-heterogeneity bond. In this paper, the applications of some palladium catalyzed reactions in the synthesis of pharmaceutical intermediates were studied. The research contents are as follows: 1. The stability of a large number of prepared, long stored Polyaniline supported palladium catalysts was studied. And its catalytic activity in Suzuki reaction and Sonogashira reaction, and the synthesis of a large number of related derivatives. The structure of the product was determined by NMR, GC-MS, IR and so on. The highest yield can reach 99% and 96% respectively. The results show that the catalyst can be stored for a long time without loss of activity, and has been successfully used in the modification of drug intermediates Rapatini and propargesterone. The method of palladium catalyzed hydroarylation of olefin was studied. The structure and yield of the product were determined by gas chromatograph. The reaction is more inclined to the insertion reaction of olefins by L*PdH, and finally to the reaction of aryl halides with intermediates to form carbon-carbon bonds.
【学位授予单位】：扬州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O621.251;TQ460.1

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