【作者】 王永强；

【导师】 王震；

【作者基本信息】 兰州大学 ， 药学（专业学位）， 2020， 硕士

【摘要】 氧化反应在生产生活中扮演着非常重要的角色,氧气参与的反应是其中非常重要的一部分。氧气作为氧化剂具有绿色环保,原子经济性高,廉价易得,产物无污染等特点,因此被广泛的应用于有机合成中。目前氧气参与的氧化反应大致可以分为以下几类:氧化偶联反应,过渡金属催化的氧化反应,光催化反应和碳碳键断裂等反应。近年来,氧气参与的反应已经取得了显著的进展,但是对氧气参与反应的开发始终是研究的热点。因此,借助绿色环保的氧气作为氧化剂,我分别完成了以下工作:1)氧气参与的C=O和C=C键的构建——靛红和异靛的合成反应:文献报道的由吲哚或吲哚酮氧化来合成靛红的方法通常需要使用I₂或者PIDA等氧化剂,造成额外副产物的产生;合成异靛的方法往往需要在酸性条件下长时间回流,且产率不高。为了避免以上现象,我们开发了廉价易得的碘化钠作为添加剂,氧气作为氧化剂的靛红和异靛的合成反应。该反应在四氢呋喃（THF）溶液中得到一系列靛红衍生物,而在二甲基亚砜（DMSO）溶液中,高选择性的得到一系列靛红二聚物——异靛。此外,该反应为我们实验室前期提出的“氧化传递”策略的实验验证提供了有力的支持。相信该反应可以为有机化学、药物化学、材料化学和染料行业中应用广泛的靛红和异靛的合成提供简洁高效的方法。2)氧气参与的C-S/Se/Te键的构建——芳基二硫醚脱硫生成芳基硫醚的反应:合成芳基硫醚的方法主要有过渡金属催化的偶联反应,C-H官能团化反应和亲核取代反应,但是这些方法大多数存在反应条件苛刻,导向基难以脱除,底物范围窄等不足。因此,我们利用碘化亚铜作催化剂,菲啰啉作配体,碳酸钾作碱,在氧气条件下实现了芳基二硫醚脱除二氧化硫生成芳基硫醚的反应;该反应具有宽广的底物范围和良好的官能团兼容性,对敏感的烯烃、醛、酮、酯基、酰胺、氰基等官能团都能兼容。借助该反应,我们成功地实现了82个相关化合物的合成,包括抗抑郁药物沃替西汀和具有环张力的碗状有机功能材料分子,为进一步生物活性评价、药物开发和有机功能材料的应用奠定了基础。更多还原

【Abstract】 Oxidization reactions play an important role in production and life,and the oxidization reaction with oxygen is a significant part.Oxygen,as a green oxidant,is widely used in organic chemistry,on account of its high atomic economy,low cost,pollution-free and other characteristics.At present,the oxidization reactions with oxygen are classified as oxidative coupling,transition-metal catalyzed oxidization,light-catalyzed reactions and carbon-carbon bond breaking reactions.The oxidation reaction with oxygen has been remarkably developed,but to exploit new methods for oxidization with oxygen is still a research hotspot.Therefore,with the help of the green oxidant oxygen,I have completed the following projects respectively.1)Construction of C=O and C=C bonds with oxygen------synthesis of isatins and isoindigos:Extra oxidant usch as I₂ or PIDA are usually used in the methods for synthesis of isatin by oxidization of indole or indolone,which results in the formation of additional by-products.Refluxing in acid conditions for a long time and low yields is often needed in the protocols for synthesis of isoindigos.To avoid the above deficiencies,we exploied a reaction for syntheses of isatins and isoindigoes,using NaI as the additive,O₂ as the oxidant.A series of isatins were obtained in THF.However,isoindigos,the diploymer of isatins,were gained with good selection when THF was replaced by DMSO.Furthermore,this protocol provide a powerful support for experimental verification of“oxidation relay strategy”proposed by our group earlier.We believe that this method may provide a concise and efficient protocol for synthesis of isatins and isoindigos,which could be widely used in organic chemistry,medicinal chemistry,materials chemistry and dye industry.2)Construction of C-S/Se/Te bonds with oxygen------desulfuration of aryl disulfides to generate the aryl sulfides:The approaches for synthesis of aryl thioether mainly include coupling reaction catalyzed by transition-metal,C-H bond functionalization and nucleophilic substitution.But many of these methods have several deficiencies,such as:harsh conditions,difficulty escaped directing group and narrow substrate scope.Therefore,exploiting CuI as the catalyst,phenanthroline as the ligand,and K₂CO₃ as the base,the desulfuration of aryl disulfides to generate the aryl sulfides under oxygen atmosphere was achieved.This approach has broad substrates scope and excellent functional group tolerance.It is even compatible with several sensitive groups such as alkene,ketone,ester,amide,cyanide,alkene,nitro and methylsulfonyl.With the help of this reaction,we have synthesized 82 correlative products including challenging bowl-shaped organic materials with great ring tension.The powerful strategy holds promise for the discovery of biological sulfur-lead compounds,sulfur-containing medicine and functional organic materials synthesis.更多还原