Huisgen-click反应方法研究及其在马来酰亚胺改造中的应用

发布时间：2018-03-26 03:53

本文选题：Huisgen-click反应　切入点：1　出处：《河南师范大学》2014年硕士论文

【摘要】：铜催化的叠氮和炔烃的环加成反应（Huisgen-click反应）是非常重要的有机合成反应之一。自从Sharpless和Meldal各自独立地发现亚铜盐可以催化叠氮和端基炔反应区域选择性地生成1,4-二取代-1,2,3-三氮唑后，Huisgen-click反应在医药、农药、染料、防腐剂、生化试剂、高分子以及功能材料等领域得到了广泛的应用。因此研究Huisgen-click反应的催化体系及其应用是非常有意义的。本论文主要完成了以下三方面的工作：我们发现Cu(OAc)2·H2O/NH2NH2·H2O催化体系能够高效地催化Huisgen-click反应。这个体系不仅可以避免添加载体、稳定剂等，而且反应中不产生任何有害物质。在研究反应机理时，发现原位产生的催化剂是球状的纳米氧化亚铜空心颗粒，尺寸为400-500nm。由于其具有纳米尺寸效应，催化活性更高。同时，伴随着氧化亚铜产生的HOAc有着非常重要的作用。HOAc的作用主要体现在三个方面：HOAc可以打破氧化亚铜的晶格结构，形成醋酸亚铜，而醋酸亚铜可以高效地催化Huisgen-click反应；AcO-作为一个二配体可以与Cu(I)配位形成络合物，从而稳定炔铜中间体，这样有利于炔铜中间体的形成；HOAc可以提供酸性质子，对炔铜中间体与叠氮的关环化以及C-Cu键的质子化起着重要的作用。我们还研究了Cu(II)催化的Huisgen-click反应，并且选择了两个代表性的模板反应系统地研究了CuSO4·5H2O对Huisgen-click反应的加速作用和诱导作用，从而发现了一个热促进的硫酸铜作为催化剂的催化体系。该催化体系具有催化剂用量低、反应速度快、不需要添加其他配体等优点。该催化体系不仅适用于叠氮与炔烃的环加成反应，而且适用于由卤代烷烃、叠氮化钠和炔烃三组分合成1,4-二取代-1,2,3-三氮唑的反应。该催化体系不仅适用于液液均相体系，，也适用于液固非均相体系，甚至适用于固固非均相体系。我们又利用第三章优化出来的催化体系将1,2,3-三氮唑引入到马来酰亚胺化合物中，得到了一系列的马来酰亚胺-三氮唑化合物。用IR、NMR、MS和HRMS等手段进行了结构确证和表征。此外，又进行了体外抗Hela细胞、抗细菌和抗真菌活性测试和筛选，发现部分化合物具有较好的生物活性。这些测试为后续工作奠定了基础。
[Abstract]:The copper catalyzed azide and alkyne cycloaddition reaction (Huisgen-click reaction) is one of the organic synthesis is very important. Since Sharpless and Meldal independently found that Cuprous Salt can generate 1,4- two instead of -1,2,3- three triazole catalyzed azide and alkyne reaction region selectively after Huisgen-click reaction in medicine and pesticide. Dye, preservatives, biochemical reagent, field of polymer and functional materials have been widely used. So the research on the catalytic system of Huisgen-click reaction and its application is very meaningful. This thesis mainly completed the following three aspects of the work:
We found that Cu (OAc) 2 - H2O/NH2NH2 - H2O catalyst system can effectively catalyze the Huisgen-click reaction. This system can not only avoid adding carrier, stabilizer, and does not produce any harmful substances in the reaction. In the study of reaction mechanism, it is found that the catalyst is generated in situ nano cuprous oxide hollow spherical particles, because of its size is 400-500nm. with nanometer size effect, higher catalytic activity. At the same time, along with the HOAc cuprous oxide has the role of.HOAc very important role is mainly reflected in three aspects: the lattice structure of HOAc can break the formation of cuprous oxide, copper acetate, and copper acetate can efficiently catalyze the Huisgen-click reaction; AcO- as a the two ligand and Cu (I) coordination complexes, thereby stabilizing acetylenic copper intermediates, this is conducive to the formation of alkyne intermediate of copper; HOAc can provide the acid properties The intermediates of copper alkynes play an important role in the cyclization of azide and the protonation of C-Cu bonds.
We also studied the Cu (II) catalyzed Huisgen-click reaction, and selected two representative template reaction system in the CuSO4, accelerating effect of 5H2O on the Huisgen-click reaction and the induction, thus found a copper sulfate as promoting catalyst. The catalytic system has low catalyst loading. The reaction speed, do not need to add other ligands. Advantages of this catalytic system is not only suitable for the azide alkyne cycloaddition reaction, and applied by halogenated alkane, sodium azide and alkyne three component synthesis of 1,4- two instead of -1,2,3- three triazole reaction. The catalytic system is not only applicable to all liquid system, is also suitable for liquid solid heterogeneous system, even for solid and solid heterogeneous system.
We use the third chapter out of the optimization of catalytic system 1,2,3- three triazole into maleimide compounds, a series of maleimide - three triazole compounds. IR, NMR, MS and HRMS were used for the identification and characterization. In addition, for in vitro Hela cells. Antibacterial and antifungal activity test and screening, found that some compounds have good biological activity. These tests laid the foundation for the follow-up work.

【学位授予单位】：河南师范大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R914

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