非过渡金属催化的有氧氧化体系的构建及应用

发布时间：2018-11-26 20:00

【摘要】：氧化反应是有机合成中最基本的转化之一,而选择性氧化反应则是最重要而且富有挑战性的研究课题。许多传统的氧化方法在安全性和环境友好性等方面存在一定的缺点。氧气因为其来源丰富、价格便宜、清洁等优点越来越受到人们的重视。从经济性和环保角度考虑,在氧化反应中使用氧气作为氧化剂无疑是最好的选择。发展合适的催化剂和催化体系用于选择性有氧氧化反应依旧是科学家们研究的热点。近年来,以稳定的氮氧自由基(TEMPO、AZADOs、ABNO)和DDQ等为代表的催化剂越来越多地应用于选择性催化氧化反应中。在文献及本课题组前期研究工作的基础上,我们成功构建了几种非过渡金属催化的有氧氧化体系,并将其应用于氧化反应中。构建了ABNO/TBN/KPF_6/O_2催化氧化体系,该反应体系以ABNO为催化剂,TBN和KPF6为助催化剂,氧气为终端氧化剂,水为绿色反应溶剂。以环己醇为模型底物考察了不同的盐类助催化剂、氮氧自由基催化剂、ABNO的用量、氧气压力、反应温度、TBN和KPF_6用量等因素对反应的影响。在优化的反应条件下,反应1.5 h,产物环己酮的气相内标收率可达到96%。此外,在底物拓展中发现,活泼仲醇与不活泼仲醇均能在此催化体系下高效反应生成目标产物,一系列酮类化合物能够在此水相反应中方便地得到。构建了ABNO/KOH/O_2催化氧化体系,将其应用于合成2-取代-4H-3,1-苯并VA嗪和2-取代喹唑啉类化合物中。该体系以ABNO为催化剂,KOH为重要的助催化剂,氧气为终端氧化剂。以邻氨基苄醇和苯甲醛的反应为模型反应,考察了KOH、氧气、氮氧自由基催化剂、碱、溶剂等因素对反应的影响。在优化的反应条件下,制备了一系列2-取代-4H-3,1-苯并VA嗪和2-取代喹唑啉类化合物,产物收率达72-97%。在机理探究中,着重考察了KOH的作用,结果表明,KOH促进了ABNOH到ABNO之间的循环。探索了一种新型氮杂金刚烷-氮氧自由基的合成路线。该反应路线以1,3-金刚烷二醇作为起始原料,通过开环、羟醛反应、羟基保护、成肟、还原、关环、脱碘、脱保护、氧化等反应步骤,最终合成了4-(2-羟基苯基)甲基-1-甲基-2-氮杂金刚烷氮氧自由基。构建了DDQ/TBN/AcOH/O_2催化氧化体系,将其成功应用于二芳基甲烷sp~3C-H键有氧氧化反应中。在最优的反应条件下,二芳基甲烷化合物能以较高收率直接转变成二芳基酮化合物。在机理探究部分,考察了AcOH在反应中的作用,利用同位素标记的方法确定了H_2O在反应中的作用。研究发现,二芳基甲烷首先与AcOH在DDQ的催化下发生CDC反应生成中间产物,然后H_2O作为亲核试剂参与了中间产物到产物的转化。
[Abstract]:Oxidation is one of the most basic transformations in organic synthesis, and selective oxidation is the most important and challenging research topic. Many traditional oxidation methods have some shortcomings in safety and environmental friendliness. Oxygen is getting more and more attention because of its rich source, low price, clean and so on. From the point of view of economy and environmental protection, oxygen as oxidant is undoubtedly the best choice in oxidation reaction. The development of appropriate catalysts and catalytic systems for selective aerobic oxidation is still a hot topic for scientists. In recent years, catalysts such as stable nitrogen-oxygen free radicals (TEMPO,AZADOs,ABNO) and DDQ have been increasingly used in selective catalytic oxidation reactions. On the basis of literature and previous research work of our group, we have successfully constructed several non-transition metal-catalyzed aerobic oxidation systems and applied them to oxidation reactions. The catalytic oxidation system of ABNO/TBN/KPF_6/O_2 was constructed. The reaction system consisted of ABNO as catalyst, TBN and KPF6 as cocatalyst, oxygen as terminal oxidant and water as green reaction solvent. Using cyclohexanol as the model substrate, the effects of different salt cocatalyst, nitroxyl radical catalyst, amount of ABNO, oxygen pressure, reaction temperature, TBN and KPF_6 dosage on the reaction were investigated. Under the optimized reaction conditions, the gas phase internal standard yield of cyclohexanone can reach 96% for 1.5 h. In addition, it is found that active secondary alcohols and inactive secondary alcohols can efficiently react to the target products in this catalytic system, and a series of ketones can be easily obtained in this aqueous phase reaction. The catalytic oxidation system of ABNO/KOH/O_2 was constructed and applied to the synthesis of 2-substituted -4H-3H-3-benzo-VA and 2-substituted quinazoline compounds. In this system, ABNO is used as catalyst, KOH as important cocatalyst and oxygen as terminal oxidant. Taking the reaction of o-aminobenzyl alcohol and benzaldehyde as the model reaction, the effects of KOH, oxygen, nitroxyl radical catalyst, alkali and solvent on the reaction were investigated. A series of 2-substituted -4H-3H-1-benzo VA and 2-substituted quinazoline compounds were prepared under the optimized reaction conditions. The yield of the products was 72-97. In the study of mechanism, the role of KOH is emphatically investigated. The results show that KOH promotes the cycle between ABNOH and ABNO. A new synthetic route of azadamantane-nitroxyl radical was explored. The reaction route starts with 1: 3-adamantanediol. The reaction steps are ring opening, hydroxaldehyde reaction, hydroxyl protection, oxime formation, reduction, ring closing, deiodization, deprotection, oxidation and so on. Finally, 4-(2-hydroxyphenyl) methyl-1-methyl-2-azamantane nitroxyl radical was synthesized. The DDQ/TBN/AcOH/O_2 catalytic oxidation system was constructed and successfully applied to the aerobic oxidation of diaryl methane sp~3C-H bond. Under the optimum reaction conditions, the diarylmethane compounds can be directly converted into diaryl ketones in high yield. In the part of mechanism exploration, the role of AcOH in the reaction was investigated, and the role of H _ 2O in the reaction was determined by means of isotope labeling. It is found that diarylmethane first reacts with AcOH in the presence of DDQ to produce intermediate products, and then H _ S _ 2O acts as nucleophilic reagent to participate in the conversion of intermediate products to products.
【学位授予单位】：浙江工业大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：O643.36

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