氮杂环化合物的绿色合成研究

氮杂环化合物大多数都是具有生理活性的物质，例如喹喔啉化合物与苯二氮卓类化合物，因此研究氮杂环化合物骨架的构建方法具有一定意义。绿色化学的迅速发展迫切要求化学家发展清洁、经济和环境较友好条件下的有机合成方法。其中，水相反应与绿色固体酸催化剂的使用都是实现绿色有机合成的重要途径，它们非常具有潜力，近些年受到了广泛关注。本论文的主要工作是围绕水相及固体酸催化条件下两类具有生物活性的含氮杂环小分子的合成方法而开展的，具体包括以下内容： 1. 研究和探索出了两类绿色固体酸催化剂蒙脱土（Mont. K-10）和杂多酸(H4SiW12O40), 在水相条件下成功合成出喹喔啉化合物的有效方法。两个催化体系都以无毒无公害的水作反应溶剂，实验条件温和，操作安全简便，反应速度快，底物普适性强，产率高，且产物易分离收集。两类固体酸催化剂，对设备腐蚀性小，可回收循环使用，对环境无公害; 蒙脱土催化大部分底物能得到当量产率的产物，硅钨酸催化催化剂负载量小。 2. 实现了无溶剂条件下，以杂多酸（H3PW12O40）作催化剂，高效合成1,5-苯二氮卓衍生物的合成方法。该催化体系具有以下一些优势：实验条件温和，反应速度较快，底物普适性良好，产物易分离收集，反应过程中没有加入其它有机溶剂，绿色环保。 ‘Green Chemistry’ is currently a major issue of modern chemistry. It is widely acknowledged that there is a growing need for more environmentally acceptable processes in the chemical industry. New green catalysts and green reaction media are the important and efficient strategies in green chemistry. New green catalysts include solid acid catalysts, solid base catalysts, metal catalysts not only possess higher activity and selectivity, but also are easily separated from reaction system. Green reaction media include water, supercritical fluids and ionic liquids can not only substitute traditional toxic and harmed organic solvents, but also improve reaction activity and selectivity. Meanwhile water is a promising green reaction medium for use in modern chemistry because it has a number of advantages such as the cheapest solvent available on earth, being non-hazardous and non-toxic to the environment. Solid acids had also attracted much attention for realizing green chemistry due to their unique acidity, high activity and efficiency as organic catalysts. Nitrogen-containing heterocyclic compounds of different ring sizes such as quinoxaline and benzodiazepine are the important pharmacologically active compounds. Due to the wide biological significance of these compounds, the synthesis of these types of compounds have received a great deal of attention. Despite the large availability of methods to construct nitrogen-containing heterocyclic compounds, there is still a strong need to further explore green methods to efficiently and safely synthesize these compounds. Thus, we aim at developing efficient and green methodology for the synthesis of quinoxaline and benzodiazepine carried out under water condition with solid acid catalysts. The contents of this dissertation are listed as the following: 1. We have developed two catalytic systems for the synthesis quinoxaline via the condensation of an aryl 1,2-diamine with a 1,2-diketone compound in the presence of Mont. K-10 or H4SiW12O40 as a catalyst in water solvent. Both of these two methods can be applied to wide range of substrates, tolerating aryl 1,2-diamine/1,2-diketone with the electron donating/drawing substituent. Operational simplicity, the ambient conditions, use of an economically convenient catalyst, use of water as a desirable solvent, high yields and short reaction times are the key features of these two protocols. 2. We developed a convenient and efficient protocol for the synthesis of a variety of 1,5-benzodiazepines in high yields via condensation of aryl o-phenylenediamine derivatives with a variety of ketones using H3PW12O40 as a green recyclable and heterogeneous catalyst under solvent-free condition. The simple experiment procedure combined with ease of recovery and reuse of this catalyst make this procedure quite simple, more convenient and environmentally benign.

重离子放射增敏药物的研制及辐照对喹喔啉的作用

马蔺子是鸢尾科植物马蔺的干燥成熟的种子。本科植物的种子中富含对醌类化合物，据报道马蔺子甲素具有对γ射线的辐射增敏作用。本文研究了马蔺子甲素的分鉴定，基衍生物的制备以及对荷 S180 小鼠的重离子增敏作用。在研究马蔺子甲素 Q 以及衍生物 Q1-Q8 对荷 S180 小鼠的辐射增敏作用时，分别在有氧和乏氧条件下进行，小鼠被随机分成 6 组，对照组，γ射线照射组，碳离子照射组，背地里纯用药组，γ射线合并用药组，碳离子合并且药级。乏氧条件是通过夹住小鼠的茶瘤肢造成局部缺氧 20 分钟。马蔺子甲素及衍生物用叶温 -80 及生理一盐水稀释，在辐照前用药。γ射线的照射剂量为18Gy,而碳离子选用剂量为 6Gy， 肿瘤体积每隔 2 天测定一次，我们通过计算肿瘤的抑瘤率（IR），增敏比（SER），氧搁置比（OER）发现，在乏氧情况下 Q、Q7、Q8 全并碳离子的增敏比大于有氧情况下，同时氧搁置比降低，而抑瘤率和体外细胞毒率（HCR）的选择性增加。这一结论表明，某些对醌类化合物有选择性的增加乏氧细胞的敏感性。肿瘤中的乏氧细胞一直被认为是放疗不能完全奏效的主要原因，生物还原性药物在肿瘤的治疗中能杀死实体瘤中对射线不敏感的细胞。SR-4233 是一苯并三嗪二氧化物，它已被证明具有放射增敏作用，并且有选择性的细胞毒作用。通过 Beirut 瓜合成了两个（M1，M2） 喹喔啉类化合物，对荷 S180 小鼠的增敏作用实验分为 6 组，在乏氧情况下，单纯碳离子照射的抑瘤率 58.8%，而合并 M2 为 66.36%，合并 M1 为 70.1%。通过紫外光激发 M1 分子的 ESR 谱发现，此类化合物在光激发下发生 O-N=C-C=N-O 体系的的电子转移引起的双键转移，形成氮氧双自由基。推测碳离子可能产生更多的稳定自由基作用于 S180 瘤组织。同时研究了用重离子对乙酰甲喹、喹酰氨醇及 BF0 的结构改性，其可能性及机理通过对其结构与生物活性的分析得到，因为辐照生成的产物复杂且量非常小，分析结构工作困难，然而发现经辐照后搞菌作用明显提高。从这个实验我们和道重离子与药物分子的作用不仅有能量的沉积而且有质量的沉积，这不同于X，γ射线。由于这种原因重离子引起药物结构改变较X，γ射线更重要，重离子作用机制有自己的特点，有待于深入认识，因此加强重离子药物分子改性的基础研究有重要意义。

Synthesis, photoluminescence, and theoretical studies of novel Cu(I) complex

A novel diimine Cu(I)complex [Cu(ABPQ)(DPEphos)]BF4 [ABPQ and DPEphos are acenaphtho[1,2-b]bipyrido[2,3-h:3,2-f]quinoxaline and bis(2-(diphenylphosphanyl)phenyl) ether, respectively] is synthesized, and its photophysical properties are experimentally and theoretically characterized. The emission bands centered at ca. 400/470 and 550 nm of [Cu(ABPQ)(DPEphos)]BF4 are attributed to the ligand-centered pi -> pi* transition and the metal-to-ligand charge transfer d pi(Cu) -> pi*(N-N) transition, respectively. The luminescence quantum yield of [Cu(ABPQ)(DPEphos)]BF4 in CHCl3 is found to be about five times higher than that of [Cu(Phen)(DPEphos)]BF4.

Synthesis and Application of Thiadiazoloquinoxaline-Containing Chromophores as Dopants for Efficient Near-Infrared Organic Light-Emitting Diodes

series of a donor-acceptor-donor type of near-infrared (NIR) fluorescent chromophores based on [1,2,5]thiadiazolo[3,4-g]quinoxaline (TQ) as an electron acceptor and triphenylamine as an electron donor are synthesized and characterized. By introducing pendent phenyl groups or changing the pi-conjugation length in the TQ core, we tuned tile energy levels of these chromophores, resulting in the NIR emission in a range from 784 to 868 nm. High thermal stability and glass transition temperatures allow these chromophores to be used as dopant emitters, which can be processed by vapor deposition for the fabrication of organic light-emitting diodes (OLEDs) having the multilayered structure of ITO/MoO3/NPB/Alq(3):dopant emitter/BCP/Alq(3)/LiF/Al. The electroluminescence spectra of the devices based on these new chromophores cover a range from 748 to 870 nm. With 2 wt % of dopant 1, the LED device shows an exclusive NIR emission at 752 nm with the external quantum efficiency (EQE) as high as 1.12% over a wide range of current density (e.g., around 200 mA cm(-2)).