本文選題：Huisgen-click反應(yīng)　切入點(diǎn)：1　出處：《河南師范大學(xué)》2014年碩士論文

【摘要】：銅催化的疊氮和炔烴的環(huán)加成反應(yīng)（Huisgen-click反應(yīng)）是非常重要的有機(jī)合成反應(yīng)之一。自從Sharpless和Meldal各自獨(dú)立地發(fā)現(xiàn)亞銅鹽可以催化疊氮和端基炔反應(yīng)區(qū)域選擇性地生成1,4-二取代-1,2,3-三氮唑后，Huisgen-click反應(yīng)在醫(yī)藥、農(nóng)藥、染料、防腐劑、生化試劑、高分子以及功能材料等領(lǐng)域得到了廣泛的應(yīng)用。因此研究Huisgen-click反應(yīng)的催化體系及其應(yīng)用是非常有意義的。本論文主要完成了以下三方面的工作： 我們發(fā)現(xiàn)Cu(OAc)2·H2O/NH2NH2·H2O催化體系能夠高效地催化Huisgen-click反應(yīng)。這個(gè)體系不僅可以避免添加載體、穩(wěn)定劑等，而且反應(yīng)中不產(chǎn)生任何有害物質(zhì)。在研究反應(yīng)機(jī)理時(shí)，發(fā)現(xiàn)原位產(chǎn)生的催化劑是球狀的納米氧化亞銅空心顆粒，尺寸為400-500nm。由于其具有納米尺寸效應(yīng)，催化活性更高。同時(shí)，伴隨著氧化亞銅產(chǎn)生的HOAc有著非常重要的作用。HOAc的作用主要體現(xiàn)在三個(gè)方面：HOAc可以打破氧化亞銅的晶格結(jié)構(gòu)，形成醋酸亞銅，而醋酸亞銅可以高效地催化Huisgen-click反應(yīng)；AcO-作為一個(gè)二配體可以與Cu(I)配位形成絡(luò)合物，從而穩(wěn)定炔銅中間體，這樣有利于炔銅中間體的形成；HOAc可以提供酸性質(zhì)子，對炔銅中間體與疊氮的關(guān)環(huán)化以及C-Cu鍵的質(zhì)子化起著重要的作用。 我們還研究了Cu(II)催化的Huisgen-click反應(yīng)，并且選擇了兩個(gè)代表性的模板反應(yīng)系統(tǒng)地研究了CuSO4·5H2O對Huisgen-click反應(yīng)的加速作用和誘導(dǎo)作用，從而發(fā)現(xiàn)了一個(gè)熱促進(jìn)的硫酸銅作為催化劑的催化體系。該催化體系具有催化劑用量低、反應(yīng)速度快、不需要添加其他配體等優(yōu)點(diǎn)。該催化體系不僅適用于疊氮與炔烴的環(huán)加成反應(yīng)，而且適用于由鹵代烷烴、疊氮化鈉和炔烴三組分合成1,4-二取代-1,2,3-三氮唑的反應(yīng)。該催化體系不僅適用于液液均相體系，，也適用于液固非均相體系，甚至適用于固固非均相體系。 我們又利用第三章優(yōu)化出來的催化體系將1,2,3-三氮唑引入到馬來酰亞胺化合物中，得到了一系列的馬來酰亞胺-三氮唑化合物。用IR、NMR、MS和HRMS等手段進(jìn)行了結(jié)構(gòu)確證和表征。此外，又進(jìn)行了體外抗Hela細(xì)胞、抗細(xì)菌和抗真菌活性測試和篩選，發(fā)現(xiàn)部分化合物具有較好的生物活性。這些測試為后續(xù)工作奠定了基礎(chǔ)。
[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.

【學(xué)位授予單位】：河南師范大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R914

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 ;An Approach to New Water-soluble Oligo(ethylene glycol) Camptothecin Analogues by 1,3-Dipolar Cycloaddition[J];Chinese Chemical Letters;2006年07期

本文編號：1666223