摘 要

Celecoxib（塞来昔布）也被称为Celebrex，在历史上，被人们记为用作解热和抗炎的畅销药物。近年来，人们对塞来昔布的应用越来越广泛，已经不再是简单的在解热镇痛方面的应用，越来越多的人将塞来昔布应用在其他方面疾病的治疗上，并且取得了卓越的成就，因此，对塞来昔布的进一步研究将具有非常重要的理论意义与实用价值。

在杂环化学中，有机螺环类化合物的开发已经逐渐成为了一个热点方向。有别于常见有机化合物，有机螺环化合物结构的优势性使其不仅仅毒副作用小，而且对环境的影响也是非常小甚至没有。其中，因为含有杂原子的螺环类化合物具有独有的作用机理以及低抗药性，这使其在化学领域中引起了广泛的关注。

碳-氢键、碳-碳键和碳-杂原子等非活性化学键是形成众多有机化合物的结构基础。C-H键活化被公认为一种绿色合成方式，C-H键活化不仅可以缩短合成路线，并且还可以提升原子的经济价值。

关环反应是一种合成多环状化合物的常见方法，拥有非常大的应用价值。环状结构特别是杂环结构（如内酯、内酰胺、四氢呋喃等杂环）以核心单元广泛出现在药物、生理活性物质及天然产物中，这使得环状结构特别是杂环结构的简洁高效构建一直是有机合成化学家的重点研究领域。这也为设计醛类化合物惰性C-H键活化引发的关环反应，实现简洁多样性导向合成提供了目标复杂分子库。

我们研究碱催化的2(5H)-呋喃酮与苯甲醛反应，从而达到简洁合成含有环状核心单元结构的药物、生理活性物质的目标。本文主要研究了碱催化的2(5H)-呋喃酮与苯甲醛的反应，以塞来昔布为原料，并将之氧化为苯甲醛类的化合物，而后再和2(5H)-呋喃酮发生关环反应，最后对其结构与性质进行表征，得到具有螺环结构的塞来昔布衍生物，从而实现对塞来昔布的进一步研究与应用。

关键词: 塞来昔布；C-H键活化；螺环化合物；合成

Abstract

Celecoxib, also known as Celebrex，has been described as the best-selling drug and has historically been used as a drug with antipyretic and anti-inflammatory effects. In recent years, the application of celecoxib has become more and more widely used. It is no longer a simple application of application of celecoxib antipyretic and analgesic drugs. More and more people apply celecoxib to treat other diseases. , and has made remarkable achievements, so further research on celecoxib will have very important significance.

Research on organic spiro compounds has gradually become one of the hot areas in heterocyclic chemistry. Different from common organic compounds, the structural advantages of organic spiro compounds make them not only less toxic and side effects, but also have minimal impact on the environment. Among them, spiro compounds containing heteroatoms have attracted widespread attention in the chemical field because of their unique mechanism of action and low drug resistance.

A large number of organic compounds are based on non-active chemical bonds such as carbon-hydrogen bonds, carbon-carbon bonds, and carbon-heteroatoms. C-H bond activation is a well-established method for green synthesis. C-H bond activation can shorten the synthetic route and improve atomic economy.

The ring-closing reaction is an important means for synthesizing multicyclic compounds. It has important theoretical significance and extensive applications. The cyclic structures, especially heterocyclic rings (such as lactones, lactams, tetrahydrofurans and other heterocycles) are widely available in core units. In medicines, physiologically active substances and natural products, this has made the concise and efficient construction of cyclic structures, especially heterocyclic structures, a key area of research for organic synthesis chemists. This also provides a target complex molecular library for the design of a simple C-H bond-activated ring reaction for aldehyde compounds and for simple and versatile orientation synthesis.

We studied the base-catalyzed reaction of 2(5H)-furanone with benzaldehyde to achieve the goal of succinctly synthesizing drugs and physiologically active substances containing a ring core unit structure. In this paper, we mainly studied the reaction of base-catalyzed 2(5H)-furanone with benzaldehyde, using celecoxib as raw material, and further oxidized it to benzaldehyde compound, and then further related to 2(5H)-furanone. The ring reaction, and finally its structure and properties were characterized to obtain spirocycline drugs with celecoxib as the parent, so as to achieve further research and application of celecoxib.

Keywords: Celecoxib； C-H bond activation；spiro compound；synthesis

目录

第1章 绪论 1

1.1 引言 1

1.2 塞来昔布的应用 2

1.3 塞来昔布衍生物的应用 4

1.4 螺环化合物的应用 6

1.5 研究目的 10

1.6常见合成方法 11

1.7本实验设计合成路线 13

1.8实验的技术方案及产物的表征 14

第2章 实验部分 15

2.1 仪器与试剂 15

2.2实验步骤 16

2.2.1 塞来昔布的氧化 16

2.2.2 化合物a与N-乙基马来酰亚胺反应 17

2.2.3 化合物b与2(5H)-呋喃酮反应 18

2.3产物的结构表征 20

第3章 实验结果与讨论： 22

3.1溶剂筛选结果与讨论 22

3.2温度筛选结果与讨论 22

第4章 结论 23

参考文献 24

附 录 26