可见光诱导酚类化合物的官能团化研究

发布时间：2019-04-04 08:50

【摘要】：催化领域中的一个关键目标是研发新型的活化惰性小分子的方法,通过新的成键模式来提高反应过程中资源与能源的利用率以及目标产物的合成效率。在过去的十几年里,有机合成领域里自由基化学的复兴也复活了研究者们对光化学的研究兴趣。光催化反应过程中能够产生特殊的开壳反应活性中间体,而这在其他催化剂的作用下很难甚至无法获得。另外,光具有储量大、绿色环保和可再生等本质属性,这使得光催化方法符合现代有机化学所倡导的安全环保、绿色高效的时代要求。酚类化合物及其衍生物是一类非常重要的医药中间体和化工原料。溴代酚是一种常见的有机合成中间体,在材料、医药及农药等方面具有重要作用。由酚类物质直接合成的苯并呋喃骨架化合物具有潜在的生物活性,能表现出抗炎、抗氧化和抗癌等多种生理功能。以邻氨基酚或醇为原料构建的苯并VA嗪(唑)酮类化合物在生物、医药与农药等领域具有重要意义,例如抗艾滋药物依法韦仑就含有该特征结构。本文以酚类化合物为中心反应底物,通过可见光诱导的途径研究了它在常温常压条件下的各种官能团化反应,如溴代、[3+2]环加成、酯化/酰胺化和直接胺化等。采用四溴化碳作为氧化淬灭剂及溴源,以Ru(bpy)_3Cl_2为光催化剂,在可见光诱导条件下实现酚类化合物的溴代反应。溴代酚产物被认为是由溴负离子原位氧化生成的溴单质与酚进行亲电加成而来。而且烯烃在相同条件下也能生成相应的双键被溴加成的产物,这进一步证明了反应过程中溴单质的生成。该方法采用固态的四溴化碳作为溴源,避免了常规合成方法中所使用的高毒性液溴,研究出一种更绿色环保、节能高效的溴代方法。使用过硫酸钠为氧化剂,在可见光诱导或者加热条件下实现了酚类与烯烃类之间的[3+2]环加成反应,以较好的产率得到了一系列二氢苯并呋喃类化合物,并一步合成了天然产物Corsifunan A。S_2O_8~(2-)在光照或加热条件下被分解为强氧化性的SO_4~(·-),它能将底物酚氧化成酚氧自由基从而与烯烃进行[3+2]环加成反应。对比传统合成方法中所采用的强酸、重金属等苛刻条件,该方法提供了一种更温和环保、经济节能的途径。在可见光催化条件下,以Ru(bpy)_3Cl_2为光催化剂,实现了邻氨基酚或醇与四溴化碳、空气或溶剂中的水份的三组分反应,合成了一系列五元环或六元环的苯并VA嗪(唑)酮类化合物。四溴化碳参与氧化淬灭后生成的三溴化碳自由基直接参与了反应产物中羰基碳原子的构成。并且,采用连续流动工艺实现了扩大量反应以及对光催化剂的回收与利用。该合成方法的特点在于产物中的羰基来源于两个不同的组分,即碳来源于四溴化碳而氧来源于水,避免了在常规合成方法中所使用的如光气等剧毒原料以及废料的产生。以过硫酸钾为氧化剂,在可见光照射条件下实现了酚类化合物与杂环类二苯胺化合物的直接交叉脱氢胺化来合成环状三苯胺的反应。该合成方法无需任何催化剂,反应条件简单温和,反应产率很高,而且产物的化学选择性单一。最重要的是,该方法避免了底物的提前活化,直接以两分子底物脱氢偶联的方式生成了新的碳氮键。在前期工作基础上,进一步对非环状三苯胺类进行了合成工艺研究。在有机光催化剂2,4,6-三苯基吡喃盐的作用下,实现了简单温和条件下的酚类化合物与非环状二苯胺类化合物的直接交叉脱氢胺化反应,合成了一系列非环状的三苯胺单体。通过荧光淬灭实验以及EPR测试等,推断该反应涉及了双自由基交叉偶联的反应机理。而且,通过计算该反应的量子产率基本确定了反应中存在自由基增链过程。该方法创新性地拓宽了底物适用范围,避免了常规胺化偶联方法中所需的高温、金属催化以及反应底物提前活化的条件。两种类型的胺化反应都是通过氧化生成的酚氧自由基与氮自由基进行自由基交叉偶联而来。
[Abstract]:One of the key objectives in the field of catalysis is the development of a new method of activating inert small molecules, which improves the utilization ratio of resources and energy and the synthesis efficiency of the target product in the reaction process by a new bonding mode. In the past decade, the revival of free-radical chemistry in the field of organic synthesis has also raised the researchers' interest in photochemistry. A special open-shell reactive intermediate can be produced during the photocatalytic reaction, which is difficult or even impossible to obtain under the influence of other catalysts. In addition, that light has the essential attribute of large reserves, green environment protection and renewable energy, which make the photocatalytic method accord with the requirements of the era of safety, environmental protection and green and high efficiency advocated by the modern organic chemistry. The phenolic compounds and their derivatives are a kind of very important medical intermediate and chemical raw material. Bromophenol is a common organic synthesis intermediate and plays an important role in the fields of material, medicine and pesticide. The benzo-phenylene skeleton compound which is directly synthesized by the phenolic substance has the potential biological activity, and can show various physiological functions such as anti-inflammation, anti-oxidation and anti-cancer. The benzo-VA-(1) ketone compound, which is constructed with o-aminophenol or alcohol as a raw material, has important significance in the fields of biology, medicine and pesticide, for example, the anti-AIDS drug according to the law contains the characteristic structure. In this paper, phenolic compounds are used as a central reaction substrate, and various functional groups of the phenolic compounds under normal pressure and normal pressure are studied through visible light induction, such as bromination,[3 + 2] ring addition, esterification/ deamination and direct amination. The bromination of phenolic compounds was carried out under visible light-induced conditions by using tetrabromized carbon as an oxidation-quenching agent and a bromine source, and using Ru (bpy) _ 3Cl _ 2 as a photocatalyst. The bromophenol product is considered to be the bromine simple substance generated by the in-situ oxidation of the bromide anion and the phenol are electrophilic addition. And the olefin can also generate the corresponding double bond by the bromine addition product under the same condition, which further proves the generation of the bromine simple substance in the reaction process. The method adopts the solid-state tetrabromocarbon as a bromine source, avoids the high-toxicity liquid bromine used in the conventional synthesis method, and studies a more green and environment-friendly, energy-saving and high-efficiency bromination method. using sodium persulfate as the oxidizing agent, the[3 + 2] cycloaddition reaction between the phenol and the olefin class is realized under the condition of visible light induction or heating, and a series of dihydro-benzene and the sulfur-containing compounds are obtained at a good yield, The natural product, Corsifanan A. S _ 2O _ 8 ~ (2-), was decomposed into a strong oxidizing SO2-4 ~ (路-) under the condition of light or heating, and the substrate phenol can be oxidized into phenol-oxygen free radicals to carry out the[3 + 2] cycloaddition reaction with the olefin. Compared with the severe conditions of strong acid and heavy metal used in the traditional synthesis method, the method provides a more gentle environment-friendly and economic energy-saving way. Under the condition of visible light catalysis, a series of five-membered ring or six-membered ring of benzene is synthesized by using Ru (bpy) _ 3Cl _ 2 as a photocatalyst, and a series of five-membered ring or six-membered ring-containing benzo-VA-(1) ketone compound is synthesized. And the tribromocarbon free radicals generated after the tetrabrominating carbon is involved in the oxidation quenching are directly involved in the formation of the carbon atoms in the reaction product. And the continuous flow process is adopted to realize the expansion reaction and the recovery and utilization of the photocatalyst. The synthesis method is characterized in that the carbon source in the product is derived from two different components, namely, the carbon is derived from the carbon tetrabromide and the oxygen is derived from water, and the production of highly toxic raw materials such as phosgene and the like, such as phosgene, and the like, which is used in the conventional synthesis method, is avoided. By using potassium persulfate as the oxidizing agent, the direct cross-dehydrogenation amination of the phenolic compound and the heterocyclic diphenylamine compound is realized under the condition of visible light irradiation to synthesize the reaction of the cyclic triphenylamine. The synthesis method does not need any catalyst, the reaction conditions are simple and mild, the reaction yield is high, and the chemical selectivity of the product is single. Most importantly, the method avoids the advance activation of the substrate, and generates a new carbon-nitrogen bond in a manner that the two-molecule substrate is dehydrogenated and coupled directly. The synthesis process of non-cyclic triphenylamine is further studied on the basis of the preliminary work. The direct cross-dehydrogenation amination of the phenolic compound and the non-cyclic dianiline compound under simple and mild conditions is realized under the action of the organic photocatalyst 2,4,6-triphenylamine salt, and a series of non-cyclic triphenylamine monomers are synthesized. The reaction mechanism of the double-radical cross-coupling was deduced by the fluorescence quenching experiment and the EPR test. Furthermore, by calculating the quantum yield of the reaction, there is a basic determination of the free radical chain-increasing process in the reaction. The method innovatively widens the application range of the substrate and avoids the conditions of high temperature, metal catalysis and advance activation of the reaction substrate required in the conventional amination coupling method. Both types of amination reactions are based on the free-radical cross-coupling of the free radical of the phenol and the free radicals generated by the oxidation.
【学位授予单位】：哈尔滨工业大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：O621.251

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