论文总字数：20695字

摘 要

芳香硫醚是一类具有多样生理活性及独特物理化学性质的含硫化合物，在医药、农业、染料工业和材料等领域都有着广泛的应用价值，是当今研究的焦点和热点之一。为了获得芳基硫醚类化合物，科学家们发展了一系列构建硫醚的方法，包括酸碱催化，铁（III）卟啉催化二硫化物与烯烃反应，钯催化有机卤化物与硫醇偶联等。这些方法，尤其是利用金属催化剂的合成技术已经成熟，部分方法收率甚至超过95%。然而这些方法存在反应条件苛刻、操作繁杂、成本较高且环境污染大的不足。因此研究者们急需开发反应条件温和、环境友好且高效的合成方法。

α-重氮酯易于制备，在光照、加热等条件下脱去氮气形成高反应活性的卡宾中间体，通过卡宾介导的各类反应可以高效构筑多种化学键，其中S-H插入反应可以构筑C-S键，在有机合成和药物合成领域得到广泛应用。路易斯酸和Brønsted酸可活化重氮化合物，研究有机分子作为金属催化剂的替代物，对于提高催化剂的适用性和可操作性具有重要意义。此外，介孔二氧化硅具有优异的物理性能，硅的高亲氧性有助于形成六元环结构，从而提高质子在质子酸中的亲电性，显著提高质子酸的催化能力。

本课题以α-重氮酯和苯硫醇类化合物为原料，使用负载在介孔二氧化硅上的三氟甲基磺酸为催化剂，在室温下无溶剂反应，从而合成一系列芳基硫醚类化合物。该方法反应时间短，产率高，且催化剂可重复使用，符合绿色化学的要求。

关键词：芳基硫醚 α-重氮酯 质子酸 绿色化学

Green synthesis of aryl sulfide skeleton

Abstract

Aromatic sulfides are a class of sulfur-containing compounds with diverse physiological activities and unique physical and chemical properties. They are widely used in medicine, agriculture, dye industry and materials, and are one of the focuses and hotspots of research today. In order to obtain aryl sulfide compounds, scientists have developed a series of methods for constructing sulfides, including use of acid and base catalysts. Other approaches involve the use of iron(III) porphyrin catalysts in the addition of disulfides to olefins, while alternative routes to thioethers include palladium-catalyzed coupling of organic halides with thiols and so on. These methods, especially the synthesis technology using metal catalysts, are well-developed, and the yield of some methods even exceeds 95%. However, these methods have the disadvantages of harsh reaction conditions, complicated operation, high cost and great environmental pollution. Therefore, researchers urgently need to develop efficient and environmentally friendly synthetic methods with mild reaction conditions.

The α-diazoesters are easy to prepare and can be dediazonized to highly reactive carbene intermediates under thermolytic or photolytic conditions. Chemical bonds can be efficiently constructed by carbene mediated reactions, including the insertion reaction of carbene into S-H bonds which is an effective method for constructing C-S bonds. Thus the α-diazoesters have received extensive application in organic synthesis and pharmaceutical synthesis. Lewis acids and Brønsted acids can activate diazo compounds, and developing organic molecules as a substitute for metal catalysts is of great significance for improving the suitability and operability of the catalysts. In addition, mesoporous silica has excellent physical properties, and the high oxygen affinity of Si helps to the formation of six-membered cyclic structure that increases the electrophilicity of proton in protic acid, significantly improving the protonic acid Catalytic capacity.

This project used α-diazoesters and benzenethiol compounds as starting materials, using trifluoromethanesulfonic acid supported on mesoporous silica as catalyst at room temperature without a solvent to synthesize a series of aryl sulfur ether compounds. The method has short reaction time, high yield, and the catalyst can be used repeatedly, which achieves the requirements of green chemistry.

Key Words: aryl sulfide; α-diazoesters; Brønsted acid; Green Chemistry

目 录

摘要 I

Abstract II

第一章 文献综述 1

1.1 S-H插入反应构筑硫醚的研究背景 1

1.2 质子酸催化构建C-X键的研究背景 6

1.3 介孔二氧化硅负载质子酸为催化剂的研究背景 7

1.4 结语 8

第二章 实验内容 9

2.1 实验思路 9

2.2 实验材料 9

2.2.1 实验仪器 9

2.2.2 实验试剂 10

2.3 实验方法 10

2.3.1 TFMSA@SBA-15催化剂的制备 10

2.3.2 α-重氮酯的制备 11

2.3.3 α-重氮酯参与的S-H插入反应构筑C-S键 12

2.4 实验结果与讨论 15

2.4.1 TFMSA@SBA-15的催化活性研究的结果： 15

2.4.2 TFMSA@SBA-15的可重复使用性研究的结果： 15

2.4.3 底物普适性研究的结果： 17

第三章 结论与展望 22

参考文献 23

致谢 27

第一章 文献综述

1.1 S-H插入反应构筑硫醚的研究背景

C-S键广泛存在于具有重要生物活性的各种天然和合成分子中^[1-2]。其中芳香杂环硫醚是一类具有多样生理活性及独特物理化学性质的含硫化合物，在医药、农业、染料工业和材料等领域都有着广泛的应用价值，是当今研究的焦点和热点之一^[3]。其作为一种重要的结构单元广泛存在于天然产物、药物有机功能材料中，例如：芳基硫代吲哚(Arylthioindole)是一种新型微管蛋白的抑制剂；头孢唑林(Cefazolin)对葡萄球菌、肺炎球菌、大肠杆菌等具有较强的作用；奥美拉唑硫醚(Ufiprzole)是用来合成治疗胃食管反流性疾病药物的重要中间体。同时，通过氧化作用合成具有手性的亚砜类化合物芳硫醚被发现具有很好的药物活性^[4]和工业用途^[5]。例如：含有氮杂环的手性亚砜化合物一般具有药物活性和生物活性^[3b]。OPC-29030是很好的血小板粘附剂；ZD3638是一种抗精神病药物（图1-1）^[6]。

请支付后下载全文，论文总字数：20695字