摘 要

联烯的主要结构由两个碳碳双键并联而成，其相邻的两套Π轨道相互垂直的特殊结构决定了其不同于其他化合物的特殊性质。研究表明，联烯能够有效的参与到亲电亲核加成以及串联环化等反应中；联烯酮作为重要的联烯类化合物之一，具有吸电子的取代基，因此具有更强的反应活性，被广泛用于有机小分子化合物的合成等多种有机化学合成反应中。

吲哚酮类化合物及其衍生物广泛存在于天然化合物中，是一类重要的含氮杂环化合物，具有较强的生物活性，常作为有机合成的中间体及配体被广泛应用到有机合成、农药合成及功能材料等的合成中。含有吲哚酮结构的化合物通常具有消炎、杀菌、抗病毒、抗高血压和抗肿瘤等生物活性，因此其也被广泛应用于药物合成领域。故此，发展有效地构建含有吲哚酮骨架结构化合物的合成方法被广泛关注。

本文以廉价易得的N-芳基丙烯酰胺为原料，分别以碳酸铯和碳酸钾为碱，考察零价钯催化下N-芳基丙烯酰胺与 β-氯代烯酮通过 Heck反应-碳氢键活化-插入反应的连续过程制备生物活性物质螺-1，3-二氢吲哚-2-酮类化合物。同时通过控制实验条件考察串联反应过程，筛选最佳配体、碱的类型及用量、最佳溶剂及反应温度，最终得到串联反应的最佳条件。实验结果表明，丙烯酰胺和氯代烯酮反应中，当反应温度维持在100℃，加入5 mol% Pd₂(dba)₃作催化剂，20 mol% PPh₃作配体，3.5电化学的当量的K₂CO₃作碱，CH₃CN作溶剂时，生成捕集产物的产率最大；当反应温度维持在100℃，5 mol% Pd₂(dba)₃作催化剂，20 mol% PPh₃作配体，3.5电化学当量的Cs₂CO₃作碱，PhMe/CH₃CN（1：1）作溶剂时，生成插入产物的产率最大。

关键词：碘代丙烯酰胺；氯代烯酮；吲哚酮；串联反应；插入；

Abstract

The main structure of allene consists of two carbon-carbon double bonds connected in parallel. The adjacent two sets of Π orbitals are perpendicular to each other, which determines their special properties different from other compounds. Studies have shown that allenes can effectively participate in electrophilic nucleophilic addition and tandem cyclization reactions; as one of the important allene compounds, allenone has an electron-withdrawing substituent and therefore has a stronger reaction The activity is widely used in the synthesis of small organic compounds and other organic chemical synthesis reactions.

Indolone compounds and their derivatives are widely present in natural compounds. They are an important class of nitrogen-containing heterocyclic compounds with strong biological activity. They are often used as intermediates and ligands in organic synthesis and are widely used in organic synthesis , In the synthesis of pesticides and functional materials. Compounds containing indolone structures usually have anti-inflammatory, bactericidal, anti-viral, anti-hypertensive, and anti-tumor biological activities, so they are also widely used in the field of drug synthesis. Therefore, the development of synthetic methods for effectively constructing compounds containing indolinone skeleton structure has been widely concerned.

In this paper, the cheap and easily available N-aryl acrylamide is used as a raw material, and cesium carbonate and potassium carbonate are used as bases, respectively. The continuous process of bond activation-insertion reaction prepares the biologically active substance spiro-1,3-dihydroindol-2-one. At the same time, through the control of experimental conditions to investigate the tandem reaction process, the best ligand, the type and amount of base, the best solvent and the reaction temperature were screened, and finally the best conditions for the tandem reaction were obtained. The experimental results show that in the reaction of acrylamide and chlorenone, when the reaction temperature is maintained at 100℃, 5 mol% Pd₂ (dba) ₃ is added as a catalyst, 20 mol% PPh₃ is used as a ligand, and 3.5 electrochemical equivalents of K₂CO₃ are used as When the base is CH₃CN as the solvent, the yield of the trapped product is the largest; when the reaction temperature is maintained at 100 ℃, 5 mol% Pd₂ (dba)₃ is used as the catalyst, 20 mol% PPh₃ is used as the ligand, and 3.5 electrochemical equivalent of Cs₂CO₃ is used When base, PhMe / CH₃CN (1: 1) is used as the solvent, the yield of intercalated product is the largest.

Key Words：Iodine acrylamide；Chlorinated ketene；Indole ketene；Cascade reaction;insertion.

目录

武汉理工大学毕业设计（论文） 1

摘 要 3

目录 5

第1章 绪论 6

1.1 含氮杂环化合物简介 6

1.2 吲哚酮 8

1.2.1 吲哚简介 8

1.2.2 吲哚酮简介 9

1.2.3 1，3-二氢吲哚-2酮类化合物的合成方法 10

1.3 联烯酮简介 10

1.4 本论文的讨论内容 11

第2章 实验部分 12

2.1 主要仪器与反应试剂 12

2.2 试剂精制方法 14

2.2.1 石油醚的精制 14

2.3实验步骤与方法 14

2.3.1碘代丙烯酰胺1a-1e的合成 14

2.3.2 (E)-β-氯代-β-正戊基烯酮的制备： 18

2.3.3 碘代丙烯酰胺与(E)-β-氯代-β-正戊基烯酮成环反应的最佳条件探索 18

2.3.4 碘代丙烯酰胺与β-氯代烯酮反应的底物扩展研究 20

第 3 章 结论与展望 21

3.1 原料及产物的核磁共振图谱 21

3.1.1 碘代丙烯酰胺1a-1e核磁数据 21

3.1.2 β-氯代-β-正戊基烯酮核磁数据 22

3.2 碘代丙烯酰胺1a-e与氯代烯酮反应2a的最佳条件探索结果 23

3.3 碘代丙烯酰胺与氯代烯酮反应的底物扩展结果 25

3.4产物4a-e的核磁共振图谱 26

3.5 总结 34

参考文献 35

致 谢 38

第1章 绪论

1.1 含氮杂环化合物简介

含氮杂环化合物是指具有环状结构的化合物中成环原子除碳原子外还含有氮原子的化合物，其结构多样，数量庞大。含氮杂环化合物可大致分为单杂环和稠杂环，其中单杂环可分为五元和六元杂环，稠杂环根据是否含有苯环分为苯稠杂环和杂稠杂环。常见的五元杂环有吡咯、噻唑、咪唑、吡唑等类别；常见的六元杂环有吡啶和嘧啶等种类；稠杂环中则例如喹啉属于苯稠杂环，嘌呤属于杂稠杂环（fig.1.1）。

Fig.1.1 Examples of nitrogen-containing heterocycles

含氮杂环化合物广泛的存在于自然界和生物活性物质中，往往是生物体的组成成分和代谢产物的基本结构单元，例如Guanine（鸟嘌呤）和Cytosine（胞嘧啶）是核苷酸的组成成分；Riboflavin（维生素 B2）可以起到促进发育和细胞再生的作用(fig.1.2)。

Fig.1.2 Examples of bioactive N-heterocyclic compounds