两步一锅法合成1,2,3-三氮唑的方法学研究

发布时间：2018-06-28 12:57

  本文选题：芳基碘化物 + CuAAC反应　； 参考：《河南师范大学》2017年硕士论文

【摘要】：自2001年由诺贝尔化学奖获得者Sharpless首次提出点击化学(click chemistry)的概念以来,以叠氮化合物与末端炔的环加成(CuAAC)反应成为“点击化学”中的经典。点击化学可广泛应用于医药、农药、电极表面修饰、染料、生化试剂、高分子及功能聚合材料等各个领域。由于端基炔的局限性及其昂贵性,探求一种更有效、区域选择性更好的有机催化的叠氮化物-醛[3+2]环加成反应也成为继CuAAC反应之后的又一热点。本论文的主要工作简要介绍如下:本文第一部分对芳基叠氮化合物的研究进展、两组分合成1,2,3-三氮唑和多组分合成1,2,3-三氮唑的合成方法进展及三氮唑化合物在医药、农药及工业生产等各个领域的应用进展方面进行了综述。本文第二部分研究了CuI/DBU(1,8-二氮杂二环[5.4.0]十一碳-7-烯)和Cu(OAc)2·H2O/DBU(1,8-二氮杂二环[5.4.0]十一碳-7-烯)两个催化体系分别作用于芳基碘与叠氮化钠的亲核取代反应,建立了一种合成芳基叠氮化合物的新方法。通过对反应条件的优化,主要包括催化剂的筛选、碱的筛选、溶剂的选择、催化体系用量的比例控制以及温度的考察,得到最优的反应条件:CuI(20 mol%),DBU(30 mol%),1.2当量叠氮化钠,DMSO,95℃;或者Cu(OAc)2·H2O(10 mol%),DBU(15 mol%),1.2当量叠氮化钠,DMSO,95℃。该方法具有反应时间短、普适性好、收率高等优点,并探索可能的催化机理。本文第三部分建立了芳基碘、叠氮化钠和端基炔的三组分两步一锅法合成1,2,3-三氮唑的研究方法。通过对反应条件的优化,得到最佳的反应条件:第一步,1.0 mmol芳基碘,1.2 mmol叠氮化钠,3.0 mL DMSO,10 mol%的Cu(OAc)2·H2O和20 mol%的DBU,95℃;第二步,室温,0.5 mmol端基炔。该方法将原位生成的芳基叠氮化合物不经分离直接引入到端基炔上,避免了从反应混合物中分离所产生的危险性叠氮化合物。该方法操作简便、普适性好。本文第四部分建立了芳基碘、叠氮化钠和醛的三组分两步一锅法合成1,2,3-三氮唑的研究方法。通过对反应条件的优化,得到最佳的反应条件:第一步,1.0 mmol芳基碘,1.2 mmol叠氮化钠,3.0 mL DMSO,10 mol%的Cu(OAc)2·H2O和20 mol%的DBU,95℃;第二步,室温,0.5 mmol醛。该方法将原位生成的芳基叠氮化合物不经分离直接引入到醛上,避免了从反应混合物中分离所产生的危险性叠氮化合物。该方法操作简便,对底物适用范围广。
[Abstract]:Since Sharpless, Nobel laureate in chemistry, first introduced the concept of click-chemistry (click chemistry) in 2001, the cycloaddition of azide compounds with terminal acetylene has become a classic in click-chemistry. Click chemistry can be widely used in medicine, pesticide, electrode surface modification, dyes, biochemical reagents, polymer and functional polymeric materials and other fields. Because of the limitation of terminal acetylene and its high cost, the search for a more effective and better regioselectivity of azide aldehyde [32] cycloaddition reaction has become another hot spot after CuAAC reaction. The main work of this thesis is as follows: in the first part of this paper, the progress of the research on aryl azide compounds, the synthesis methods of 1ttriazole and multicomponent synthesis, and the application of triazoles in medicine, The progress in application of pesticide and industrial production is reviewed. In the second part of this paper, we studied the nucleophilic substitution of aryl iodine with sodium azide by Cui / DBU (1) -diaza-dicyclo [5.4.0] undecyl -7-ene and Cu (OAC) _ 2H _ 2O / DBU (1) -diaza-dicyclo [5.4.0] undecyl -7-ene, respectively. A new method for the synthesis of aryl azide compounds was established. Through the optimization of reaction conditions, including the screening of catalyst, the selection of alkali, the selection of solvent, the proportion control of catalyst system and the investigation of temperature, the optimum reaction conditions were obtained as follows: 1: CuI (20 mol%) DBU (30 mol%) 1. 2 equivalent sodium azide at 95 鈩，

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