摘 要

近几十年来，科研工作者们对含氟药物的研究兴趣日益增长。三氟甲硒基作为一种特殊的含氟官能团，在合成预防和治疗癌症的生物活性分子方面具有潜在的应用价值。利用亲核或亲电取代的方式实现直接的三氟甲硒基化反应已取得一些进展。其中，亲电取代的三氟甲硒基化反应仅有以CF₃SeCl和F₃CSeSeCF₃作为-SeCF₃源的相关报道。因此，发展亲电取代的三氟甲硒基化反应的新方法具有一定研究价值。

本文进行了[Me₄N][SeCF₃]对富电子芳烃的亲电三氟甲硒基化反应的研究，工作内容主要包括三方面内容：

第一部分：根据文献描述的方法，制备[Me₄N][SeCF₃]。

第二部分：以吲哚为模板底物，利用高效液相色谱技术，筛选出[Me₄N][SeCF₃]对富电子芳烃的直接三氟甲硒基化反应的最佳反应条件。

第三部分：考察[Me₄N][SeCF₃]对富电子芳烃的直接三氟甲硒基化反应的适用性，拓展底物适应范围。

研究结果表明：[Me₄N][SeCF₃]不仅可以发生亲核的三氟甲硒基化反应，也可在一定条件下发生亲电的三氟甲硒基化反应。在本文中，我们发现[Me₄N][SeCF₃]被氧化后可进一步与一些富电子芳烃发生亲电取代反应，这就可以为含三氟甲硒基功能分子的合成提供一种新途径，同时也可以进一步拓展[Me₄N][SeCF₃]的应用范围。

关键词：三氟甲硒基化；富电子芳烃；氧化；

Abstract

In recent decades, researchers have increased their interest in fluorine-containing drugs. As a special fluorine-containing function group, trifluoromethylselenol group has potential research value in the synthesis of bioactive molecules which is helpful to prevent and treat cancer. The nucleophilic and electrophilic direct trifluoromethylselenoation has made some progresses. In the electrophilic reactions, only trifluoromethylselenolation using CF₃SeCl and F₃CSeSeCF₃ as the source of SeCF₃ were reported. Therefore, it is significant to the development of a new method for electrophilic trifluoromethylselenolation.

In this thesis, the trifluoromethylselenolation of the electron-rich aromatics by [Me₄N][SeCF₃] was achieved. The work includes three parts:

Part I: [Me₄N][SeCF₃] was synthesized according to the literature.

Part Ⅱ: By using indole as the template substrate, the optimal reaction conditions for the direct trifluoroselenylation of the electron-rich aromatics by [Me₄N][SeCF₃] were studied .

Part Ⅲ: The applicability of [Me₄N][SeCF₃] for the direct trifluoromethylselenolation of electron-rich arenes was explored and the substrate scope of the reaction was investigated.

The results showed that [Me₄N][SeCF₃] could undergo both nucleophilic trifluoromethyl selenolation and electrophilic trifluoromethylselenolation under different reaction conditions. In this work, we found that [Me₄N][SeCF₃] successfully trifluoromethylselenolated some electron-rich arenes in the presence of oxidants. This provides a new approach for the synthesis of trifluoromethylselenol-containing functional molecules which could further expand the application of [Me₄N][SeCF₃].

Key words: trifluoromethylselenolation; electron-rich arenes; oxidant

目录

摘要 I

Abstract II

第1章 绪论 1

1.1 有机氟化学的发展概述 1

1.2 含氟药物概述 1

1.3 三氟甲硒基化反应的研究进展 3

1.4 研究目的和内容 7

第2章 [Me₄N][SeCF₃]对富电子芳烃的直接三氟甲硒基化反应研究 8

2.1 [Me₄N][SeCF₃]的制备 8

2.1.1 实验依据 8

2.2 [Me₄N][SeCF₃]对富电子芳烃的直接三氟甲硒基化反应条件筛选 8

2.2.1 催化剂的筛选 9

2.2.2 反应温度、时间条件的筛选 10

2.2.3 氧化剂的筛选 11

2.2.4 溶剂的筛选 12

2.2.5 空气，水的存在对反应结果的影响 13

2.2.6 [Me₄N][SeCF₃]的用量 14

2.3 [Me₄N][SeCF₃]对富电子芳烃的直接三氟甲硒基化反应 15

第3章 实验部分 17

3.1 主要实验试剂与仪器 17

3.2 [Me₄N][SeCF₃]的合成步骤 19

3.3 富电子芳烃的三氟甲硒基化 20

3.4 本章小结 22

第4章 总结 23

参考文献 24

附录 26