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.

Formation of Polycyclic Aromatic Hydrocarbons and Nitrogen Containing Polycyclic Aromatic Compounds in Titan's Atmosphere, the Interstellar Medium and Combustion

Several different mechanisms leading to the formation of (substituted) naphthalene and azanaphthalenes were examined using theoretical quantum chemical calculations. As a result, a series of novel synthetic routes to Polycyclic Aromatic Hydrocarbons (PAHs) and Nitrogen Containing Polycyclic Aromatic Compounds (N-PACs) have been proposed. On Earth, these aromatic compounds originate from incomplete combustion and are released into our environment, where they are known to be major pollutants, often with carcinogenic properties. In the atmosphere of a Saturn's moon Titan, these PAH and N-PACs are believed to play a critical role in organic haze formation, as well as acting as chemical precursors to biologically relevant molecules. The theoretical calculations were performed by employing the ab initio G3(MP2,CC)/B3LYP/6-311G** method to effectively probe the Potential Energy Surfaces (PES) relevant to the PAH and N-PAC formation. Following the construction of the PES, Rice-Ramsperger-Kassel-Markus (RRKM) theory was used to evaluate all unimolecular rate constants as a function of collision energy under single-collision conditions. Branching ratios were then evaluated by solving phenomenological rate expressions for the various product concentrations. The most viable pathways to PAH and N-PAC formation were found to be those where the initial attack by the ethynyl (C2H) or cyano (CN) radical toward a unsaturated hydrocarbon molecule led to the formation of an intermediate which could not effectively lose a hydrogen atom. It is not until ring cyclization has occurred, that hydrogen elimination leads to a closed shell product. By quenching the possibility of the initial hydrogen atom elimination, one of the most competitive processes preventing the PAH or N-PAC formation was avoided, and the PAH or N-PAC formation was allowed to proceed. It is concluded that these considerations should be taken into account when attempting to explore any other potential routes towards aromatic compounds in cold environments, such as on Titan or in the interstellar medium.

Design, Synthesis and Characterization of N-Containing Organic Compounds

The needed of new intermediates/products for screening in the fields of drug discovery and material science is the driving force behind the development of new methodologies and technologies. Organic scaffolds are privileged targets for this scouting. Among them a priority place must be attributed to those including nitrogen functionalities in their scaffolds. It comes out that new methodologies, allowing the introduction of the nitrogen atom for the synthesis of an established target or for the curiosity driven researches, will always be welcome. The target of this PhD Thesis’ work is framed within this goal. Accordingly, Chapter 1 reports the preparation of new N-Heteroarylmethyl 3-carboxy-5-hydroxy piperidine scaffold, as potential and selective α-glucosidase inhibitors. The proposed reversible uncompetitive mechanism of inhibition makes them attractive as interesting candidate for drug development. Chapter 2 is more environmentally method-driven research. Eco-friendly studies on the synthesis of enantiomerically pure 1,4-dihydropyridines using “solid” ammonia (magnesium nitride) is reported via classical Hantzch method. Chapter 3 and Chapter 4 may be targeted as the core of the Thesis’s research work. Chapter 3 reports the studies addressed to the synthesis of N-containing heterocycles by using N-trialkylsilylimine/hetero-Diels–Alder (HAD) approach. New eco-friendly methodology as MAOS (Microwave Assisted Organic Synthesis) has been used as witness of our interest to a sustainable chemistry. Theoretical calculations were adopted to fully clarify the reaction mechanism. Chapter 4 is dedicated to picture the most recent studies performed on the application of N-Metallo-ketene imines (metallo= Si, Sn, Al), relatively new intermediates which are becoming very popular, in the preparation of highly functionalized N-containing derivatives, accordingly to the Thesis’ target. Derivatives obtained are designed in such a way that they could be of interest in the field of drug and new material chemistry.

Occurrence, gas/particle partitioning and carcinogenic risk of polycyclic aromatic hydrocarbons and their oxygen and nitrogen containing derivatives in Xi'an, central China

29 parent- and alkyl-polycyclic aromatic hydrocarbons (PAHs), 15 oxygenated-PAHs (OPAHs), 11 nitrated-PAHs (NPAHs) and 4 azaarenes (AZAs) in both the gaseous and particulate phases, as well as the particulate-bound carbon fractions (organic carbon, elemental carbon, char, and soot) in ambient air sampled in March and September 2012 from an urban site in Xi'an, central China were extracted and analyzed. The average concentrations (gaseous+particulate) of 29PAHs, 15OPAHs, 11NPAHs and 4AZAs were 1267.0±307.5, 113.8±46.1, 11.8±4.8 and 26.5±11.8ngm(-3) in March and 784.7±165.1, 67.2±9.8, 9.0±1.5 and 21.6±5.1ngm(-3) in September, respectively. Concentrations of 29PAHs, 15OPAHs and 11NPAHs in particulates were significantly correlated with those of the carbon fractions (OC, EC, char and soot). Both absorption into organic matter in particles and adsorption onto the surface of particles were important for PAHs and OPAHs in both sampling periods, with more absorption occurring in September, while absorption was always the most important process for NPAHs. The total carcinogenic risk of PAHs plus the NPAHs was higher in March. Gaseous compounds, which were not considered in most previous studies, contributed 29 to 44% of the total health risk in March and September, respectively.

Vibrational assignments of five-membered heterocyclic compounds. Normal vibrations of oxazolidine-2-one and -2-thione

Infrared spectra of oxazolidine-2-one (Oxo), -2-thione (Oxt) and their N-deuteriated derivatives have been measured over the range 4000-20 cm−1. The fundamental frequencies of these molecules have been assigned on the basis of normal coordinate calculations carried out using a Urey-Bradley potential function supplemented with valence type constants for the out-of-plane modes of the planar skeleton. The results of the vibrational analyses are discussed and correlated with the assignments available for the other related five membered heterocyclic molecules.

Nitrogen-containing carbon nanotubes

Carbon nanotubes containing small amounts of nitrogen are produced by the pyrolysis of aza-aromatics such as pyridine, methylpyrimidine and triazine over cobalt nanoparticles in an Ar atmosphere; good yields of such nanotubes are obtained by carrying out the pyrolysis of a mixture of pyridine and Fe(CO)(5) in flowing Ar + H-2.

Transmetalation reactions with nitrogen-containing

The transmetalation reaction of the aryllithium compound [Li(NCN)](2) (NCN is the monoanionic