【作者】 王辉；

【导师】 崔秀灵；

【作者基本信息】 郑州大学 ， 有机化学， 2014， 硕士

【摘要】 本论文主要研究了无过渡金属参与杂芳氮氧化合物的二聚化和磷酯化反应，主要研究结果如下：1.喹啉氮氧及其衍生物在无过渡金属条件下的二聚化反应联杂芳氮氧类化合物广泛地应用于有机功能材料、医药中间体及合成化学等领域。目前主要利用两种途径来合成这类化合物：1）多步低温锂化方法；2）金属催化芳卤与有机杂芳金属试剂的偶联反应，前者需要在无水无氧-78oC的苛刻条件下反应，后者需要添加金属催化剂或者氧化剂。因此，寻求一个更有效、方便、环境友好和原子经济的方法是值得期待的。我们开发了在无过渡金属参与的条件下，以tBuOLi为碱、甲苯为溶剂，对杂芳氮氧化合物的二聚化进行了研究。分别通过考察碱、溶剂及温度等因素对反应的影响，得到优化的反应条件，高选择性的实现了杂芳氮氧的二聚化反应，并且以高达93%的收率合成了一系列2,2’-联杂芳单氮氧化合物(Scheme1)。该方法具有条件温和、操作简便和一步完成反应等优点。通过控制实验及文献考察，推测该反应可能经历了一个加成-消去的过程(Scheme2)。2.喹啉氮氧及其衍生物在无金属条件下的磷酯化反应由于芳基及杂芳磷酯化合物在医药中间体、配体化学及材料科学中具有广泛的应用，因此合成这些化合物有着重要的意义。典型的合成方法是通过金属催化偶联反应或化学计量的氧化剂激发膦自由基来完成的，但是存在反应条件苛刻和金属残留等问题。我们研究了在不需要金属催化剂、添加剂和外加氧化剂的条件下，直接合成一系列2-磷酸酯类取代的杂芳氮氧化合物的方法(Scheme3)。该反应具有条件温和、体系简单、环境友好和高区域选择性等优点。通过对照实验验证了该反应可能经历了一个自由基过程(Scheme4)。相比文献报道的锰盐和银盐作为化学计量的氧化剂氧化磷酯成自由基的方法，N-O基团作为内置氧化剂更具有发展潜力，为合成一些杂芳磷酯化合物提供了一个简便的方法。更多还原

【Abstract】 In this thesis, direct dimerization and phosphonation of heteroaromatic N-oxidesunder metal-free conditions are studied. The main results obtained are shown asbelows:1. Dimerization of heteroaromatic N-Oxides under metal-free conditionsBiheteroarematic N-oxides are an important class of compounds, which are usedas chelating ligands in the field of organic synthesis. Conventional methods to buildsuch structure typically involve multistep cryogenic reactions, ortransition-metal-catalyzed Het-X/Het-M coupling reactions. There are problems withthese procedures, such as the harsh reaction conditions, and usage of noble metals,which have limited the applications in laboratory and industry. Herein, we havedeveloped an efficient approach to synthesize biheteroarematic N-oxides compoundsunder metal-free conditions (Scheme1). The optimum reaction conditions aredetermined as follows: in toluene at120oC for3hours by usingtBuOLi (1.5equiv)as the base. This new methodology has been demonstrated to be suitable for thehomocoupling of a broad range of substrates, which affords a broad range of2,2’-biheteroaromatic mono N-oxides in up to93%yields. The result of controlledexperimental results indicated that the dimerization was achieved via a nucleophilicaddition-elimination process (Scheme2). 2. Direct phosphonation of heteroaromatic compounds under metal-and externaloxidant-free conditionsAryl and heteroaryl phosphonates have wide application in many fields, such asmaterial sciences, pharmaceuticals, agricultural chemicals and organic synthesis asligand. They can be achieved through two major mechanisms, including directmetalation and radical process. However, some challenges exist with these proceduresdue to the strong coordinating character of phosphorus reagents with metal center andpotential contamination of the products from the high loading of metal, andrequirement of stoichiometric oxidants. Recently, the contribution of Hartwig, Yu,Glorious, You, Fagnou and our group have disclosed that N-O group could be servedas both directing group, and internal oxidant for the metal-catalyzed dehydrogenativecoupling reaction under external oxidant free conditions.To verify our hypothesis, the condensation of quinoline N-oxide1a withdimethyl H-phosphonate2a was initially chosen as a model reaction to screen thevarious reaction parameters. Finally, the optimal reaction conditions for the directregioselective phosphonation of quinoline N-oxide were identified to be toluene asthe solvent at100oC for20hours (Scheme3). Under the standard reaction conditions,a wide variety of heteroaryl phosphonates were afforded in up to92%yields inchemo-and regioselective manners under external oxidant and metal free conditions. This procedure features with practicality, high efficiency, environmental friendlinessand atomic economy. We deduced that quinoline N-oxides might serve as an internaloxidant for radical initiator to form C-P bond via radical mechanism (Scheme4).更多还原