Husigen-Click环加成反应论文：Husigen-Click环加成反应 1，2，3-三氮唑 香豆素 双膦酸 超声波

Husigen-Click环加成反应论文：Husigen-Click环加成反应 1，2，3-三氮唑 香豆素 双膦酸 超声波 Husigen-Click环加成反应论文:Husigen-Click环加成反应 1，2，3-三氮唑 香豆素 双膦酸 超声波 【中文摘要】唑类是临床上应用最广泛的抗菌药物。1,2,3-三氮 唑由于其不容易被生物降解和容易形成氢键增加了其与生物大分子 的结合能力,被作为一个极具吸引力的连接单元广泛应用。结构中含 有1,2,3-三氮唑的化合物具有广泛的生理活性,如抗HIV、抗菌、治 疗神经性精神错乱、选择性β3肾上腺素受体激动剂等。近年 来,1,2,3-三氮唑作为一种重要的药效团,已经被用于多肽、DNA、RNA 和糖类等化合物结构修饰中,并表现出良好的效果。由Sharpless和 Melda课组发现的亚铜催化有机叠氮和炔的1,3-偶极环加成反应, 又称为Huisen-click反应,是引入1,2,3-三氮唑的有效方法。然而 目前的催化体系中大部分需要加入 【英文摘要】Azoles are the largest class of antifungal agents in clinical use.1,2,3-Triazole moieties are attractive connecting units, as they are stable to metabolic degradation and capable of hydrogen bonding, which can be favorable in binding of biomolecular targets and solubility. Compounds containing a 1,2,3-triazole moiety show various biological activities such as anti-HIV, anti-microbial, anti-allergic, and selectiveβ3 adrenergic receptor agonist. Recently,1,2,3-triazole moiety, as an important pharmacophore, was widely introduced in to peptides, DNA, RNA and carbohydrates and so on. And the modifications showed good results. With respect to introducing 1,2,3-triazole groups in to organic molecules, copper(?)-catalyzed 1,3-dipolar Huisgen cycloaddition reaction of azides and terminal alkynes (CuAAC), which is also called Huisgen-click reaction, discovered by the groups of Sharpless and Meldal, is a useful approach. The most common catalyst systems for CuAAC involved generating the needed Cu(?) catalyst in situ by using a Cu(?) salt in the presence of a reducing agent. Copper(?) salts were used in the presence of the additional bases or ligands on most occasions. In addition, the most employed solvents for CuAAC are water/organic co-solvent mixtures.Green or sustainable chemistry has now attained the status of a major scientific discipline and the studies in this area have led to the development of cleaner and relatively benign chemical processes with many new technologies being developed each year. Green chemistry encourages the design of processes that minimize the use of hazardous substance and seeks to reduced and prevent pollution at its source. Ultrasonic-assisted organic synthesis is a powerful technique that is being used more and more to accelerate organic reaction rate. In the work describe in this report, by introducing ultrasound irradiation into “on water” CuCl-catalyzed 1,3-dipolar Huisgen cycloaddition, the reaction efficiencies were notably promoted towards a wide variety of applicable azides and alkynes at room temperature, and a series of coumarin derivatives and bisphosphonate derivatives linked with 1,2,3-triazole moiety were synthesized using the optimized conditions.Recently development catalyst systems for Huisgen-click reaction were first reviewed in chapter 1. Then in chapter 2, the reaction between propargyl phenyl ether and 7-(3-azidopropoxy)coumarin was selected as a model reaction for optimizing the reaction conditions by investigating the influence of ultrasound on the effeciency of cycloaddition with different Cu(?) salts. The results show that (1) the efficiency of the model reaction was profoundly promoted by ultrasound irradiation in terms of the cycloadditon rate and the target yield under the designed conditions; (2) CuCl showed the best catalytic efficiency among tested Cu(?) salts, such as CuBr, Cul, CuCN and Cu2O; (3) The optimized reaction condition, including using CuCl as the catalyst and pure water as the reaction solvent at room temperature under ultrasound irradiation condsition, was then successfully applied to a wide variety of applicable azides and alkynes. It is especially worth mentioning that a relatively high synthetic efficiency was also shown when mixed phase synthesis was involved under ultrasound irradiation condition. Nineteen 1,4-disubstituted triazole derivatives, including three novel compounds were synthesized under the optimized conditions. Their structures were confirmed by IR, ESI MS and NMR. In chapter 3 and 4, the mothod established was applied to the synthsis of coumarin derivatives containing 1,2,3-triazole moiety. Twenty coumarin derivatives linked with 1,2,3-triazoles are new compounds and their structures were confirmed by IR, ESI MS and NMR. In chapter 5, three bisphosphonate derivatives linked with 1,2,3-triazoles in its side chain were synthesized. The important 1,2,3-triazole-containing esters, used to synthesis the final 1,2,3-triazole-containing bisphosphonates were also synthesized by the Huisgen-click reaction using CuCl as the catalyst, H2O as the solvent under the help of ultrasound at room temperature. 【关键词】Husigen-Click环加成反应 1，2，3-三氮唑 香豆素 双膦酸 超声波 【英文关键词】Husigen-Click cycloaddition 1,2,3-triazole bisphosphonates coumarin ultrasound interaction 【目录】绿色高效超声辅助Huisgen-Click反应及其在香豆素和双膦酸新型衍生物合成中的应用 摘要 4-5 Abstract 5-6 目录 7-10 第一章 绪论 10-22 1.1 Huisgen-click反应简介及催化体系研究进展 10-19 1.1.1 “Huisgen-click”的简介 10-11 1.1.2 Huisgen-Click反应铜催化剂的分类 11-18 1.1.2.1 金属铜作催化剂 11 1.1.2.2 二价铜盐+还原剂体系作催化剂 11-13 1.1.2.3 亚铜盐作催化剂 13-17 1.1.2.4 二价铜作催化剂 17-18 1.1.3 Huisgen-Click反应的催化机理 18-19 1.2 水做溶剂的Huisgen-Click反应综述 19-20 1.3 三唑类分子的药理活性 20 1.4 论文的思路和研究内容 20-22 第二章 绿色高效超声辅助Huisgen-click反应研究 22-41 2.1 引言 22 2.2 实验部分 22-39 2.2.1 仪器与试剂 22-23 2.2.2 模型反应底物的合成 23-24 2.2.2.1 苯基炔丙基醚的合成 23 2.2.2.2 7-(3-叠氮基丙氧基)香豆素的合成 23-24 2.2.3 催化体系筛选 24-30 2.2.3.1 溶剂及超声筛选 24-26 2.2.3.2 催化剂筛选 26-27 2.2.3.3 超声功率对模型反应影响 27 2.2.3.4 催化剂用量的考察 27-28 2.2.3.5 超声波加速机理探讨 28-30 2.2.4 方法适用性研究 30-39 2.2.4.1 炔类衍生物合成 30-31 2.2.4.2 炔类衍生物表征 31-32 2.2.4.3 叠氮 乙酸乙酯、苄基叠氮及叠氮苯的合成 32-33 2.2.4.4 三氮唑衍 生物合成 33-35 2.2.4.5 三氮唑衍生物表征 35-39 2.3 本章小结 39-41 第三章 Huisgen-click在7-羟基香豆素衍生 物合成中的应用 41-52 3.1 引言 41 3.2 含有1,2,3-三 氮唑7-羟基香豆素衍生物的合成 41-43 3.3 含三氮唑结构的 香豆素衍生物的表征 43-49 3.4 结果与讨论 49-51 3.4.1 新型香豆素三唑类衍生物的波谱学特征 49 3.4.1.1 香豆素三唑类衍生物的IR图谱特征 49 3.4.1.2 香豆素三唑类衍生物的NMR图谱特征 49 3.4.2 目标化合物1,4取代构型的确定 49-51 3.5 本章小结 51-52 第四章 Huisgen-click在4-羟基香豆素衍生 物合成中的应用 52-61 4.1 引言 52 4.2 含有1,2,3-三 氮唑4-羟基衍生物的合成 52-54 4.3 含三氮唑结构的4羟基 香豆素衍生物的表征 54-58 4.4 结果与讨论 58-60 4.4.1 香豆素三氮唑衍生物波谱解析 58-60 4.5 本章小结 60-61 第五章 Huisgen-click在双膦酸衍生物合成 中的应用 61-72 5.1 引言 61-63 5.2 含有1,2,3-三氮 唑双膦酸衍生物的合成 63-67 5.2.1 双膦酸5-1-6的合成 63-64 5.2.2 双膦酸5-2-6的合成 64-66 5.2.3 双膦 酸5-3-6的合成 66-67 5.3 结果与讨论 67-71 5.3.1 合成讨论 67 5.3.2 双膦酸化合物波谱学 67-71 5.4 小结 71-72 第六章 结论 72-73 参考文献 73-81 部分化合物附图 81-90 在校期间发表论文 90-91 致谢 91 】1.3.9.9.3.8.8.4.8 1.3.8.1.1.3.7.2.1 【索购找 同时提供论文写作一对一辅导和论文发表服务。 【说明】本文仅为中国学术文献总库合作提供，无涉版权。作者如有异议请与总库或学校联系。