Дисертації з теми "Nitroarene"

Project I 2-Deoxystreptamine (2-DOS), the most conserved central scaffold of aminoglycosides, is known to specifically recognize the 5'-GU-'3 sequence step through highly conserved hydrogen bonds and electrostatic interactions within and without the context of aminoglycosides (Figure 1a). We proposed that a novel monomeric unnatural amino acid building block using 2-DOS as a template would allow us to develop RNA binding molecules with higher affinity and selectivity than those currently available. Conjugating two or more of the monomeric building blocks by an amide bond would introduce extra hydrogen bonding donors and acceptors that are absent in natural aminoglycosides and increase specificity of binding to a target RNA through a network of hydrogen bonds. In addition, the amide conjugation between the monomeric building blocks places two GU-base recognizing amines at 5 Å… distance, which is equal to the distance of neighboring base stacks in dsRNAs We hypothesized that targeting dsRNAs containing multiple consecutive 5'-GU-'3 sequence steps would become possible by connecting two or more of the monomeric building blocks by amide bonds. According to the proposed hypothesis, we designed three dimeric 2-DOS compounds connected by an amide bond. These three targets include the dimeric 2-DOS substrate connected by an amide bond, the dimeric 2-DOS containing the sugar moiety from Neamine, and a dimeric 2-DOS connected by a urea linker. These compounds were then tested for sequence specific binding against 8 different RNA strands, and for antibacterial activity against E. coli, actinobacter baumannii and klebsiella. Project II A dual optimization approach was used for to enhance the catalytic activity and chemoselectivity for nitro reduction. In this approach the composition of the nanoparticles and electronics effects of the polymer were studied towards nitro reduction. Bimetallic Ruthenium-Cobalt nanoparticles showed exceptional catalytic activity and chemoselectivity compared to monometallic Ruthenium nanoparticles. The electronic effects of the polymer also had a significant effect on the catalytic activity of the bimetallic nanoparticles. The electron-deficient poly(4-trifluoromethylstyrene) supported bimetallic nanoparticles undergo nitro reduction in 20 minutes at room temperature, whereas electron-rich poly(4-methylstyrene) and poly(4-methoxystyrene) supported bimetallic nanoparticles to longer reaction times to go to completion. Electronics of the polymers also effects the change in mechanism of nitroreduction. Polystyrene bimetallic Ruthenium-Cobalt nanoparticles showed excellent yields and chemoselectivity towards nitro functional group in the presence of easily reducible functional groups like alkenes, alkynes, allyl ethers, propargyl ethers. Monometallic ruthenium nanoparticles also showed excellent reactivity and chemoselectivity towards azide reduction in the presence of easily reducible functional groups. Interestingly monometallic ruthenium nanoparticles showed regioselective reduction of primary azides in the presence of secondary and benzylic azides, also aromatic azides can be selectively reduced in the presence of secondary azides. These polystyrene supported nanoparticles are heterogeneous and are easily separated from the reaction mixture and reused multiple times without significant of catalytic activity.

Le SmI₂ en tant que réactif de transfert monoélectronique a été largement utilisé en chimie organique depuis les premiers travaux de Kagan. Cependant, la quantité stœchiométrique ou en excès de SmI₂ et d'additifs toxique tels que HMPA sont utilisés normalement pour améliorer la réactivité. De plus, à cause de sa sensibilité à l'oxygène, le stockage de la solution de SmI₂ dans le THF est difficile. Récemment, nous avons développé une nouvelle méthode électrocatalytique basée sur la régénération électrochimique de Sm²⁺. Par rapport à la réactivité du SmI₂ classique, notre approche utilise une quantité catalytique de Sm. Premièrement, pour la réduction de nitroarènes, la réaction a sélectivement fourni les composés aromatiques azoïques et les anilines en fonction du solvant choisi. Notamment, c'est la première fois que la réaction Sm²⁺ se produit dans le méthanol dans le cas des anilines. Deuxièmement, dans le cas de la réduction des sulfoxydes par SmI₂, en général, l'HMPA était nécessaire comme additif. Dans notre procédé électrocatalytique, les sulfoxydes ont été transformés en sulfures avec une chimiosélectivité élevée et des excellents rendements toujours à température ambiante sans besoin ni de HMPA ni d’atmosphère protectrice. Enfin, les dérivés d'isoindolinone sont des séries de produits importants en chimie organique, la réduction des phtalimides est l'approche la plus pratique pour les obtenir. Avec les alcools, l'alcoxylation réductrice de phtalimides a eu lieu pour la première fois avec le Sm²⁺ électrocatalytique dans nos conditions. Et si on ajoute d'autres sources de protons, ce procédé a fourni les ω-hydroxylactames et isoindolinones correspondants avec des rendements élevés
The SmI₂ as a single electron transfer reagent has been widely used in organic chemistry since the pioneering works by Kagan. However, the stoichiometric or excess amount of SmI₂ and harmful additives such as HMPA are used normally to enhance the reactivity, moreover, due to the oxygen sensitive, the storage of SmI₂ solution is difficult.Recently, we have developed a new electrocatalytic method based on the electrochemical regeneration of Sm²⁺. Compared to the classic SmI₂ reaction, our process occurred with a catalytic amount of Sm. In the reduction of nitroarenes, it selectively afforded the azo aromatic compounds and anilines depending on different solvents system. Notably, it’s the first time that the Sm²⁺ reaction occurred in the methanol. Normally, the HMPA was the additive in the reduction of sulfoxides by SmI₂. Under our electrocatalytic process, the sulfoxides were converted into sulfides in high chemoselectivity and yield at room temperature without HMPA and protecting atmosphere.The isoindolinone derivatives are series of important products in organic chemistry, the reduction of phthalimides is the most convenient approach to provide them. With alcohols, the unprecedented Sm²⁺ electrocatalyzed reductive alkoxylation of phthalimides was established. Moreover, adding other proton sources, this process afforded the corresponding ω-hydroxylactams and isoindolinones

Palladium Catalyzed Reactions: Reductive Cyclization of Nitroarenes, and Oxidative Carbonylation of Aniline Abstract: The thesis is divided into two main chapters: reductive cyclization of nitroarenes, and oxidative carbonylation of aniline. The first chapter involves developing a catalytic system for carbazoles synthesis through reductive cyclization of 2-nitrobiphenyls employing phenyl formate as an in-situ source of CO. Thus, the synthetic chemist can avoid handling pressurized CO lines and perform the reaction in a pressure tube, a cheap and readily available tool for any laboratory. Moreover, the developed protocol can tolerate both air and moisture and can be performed using undried and undistilled commercial DMF. Several carbazoles bearing a wide range of substituents were synthesized in good to excellent yields including some with valuable pharmaceutical or thermo/electrical applications. The reaction could be performed on the grams scale affording carbazole in a very good yield (85%) without the need for chromatographic purification, making our synthetic strategy even more attractive and economically advantageous. The second chapter deals with the palladium/iodide couple which is the most investigated catalytic system for the oxidative carbonylation of amines to give ureas or carbamates. In reinvestigating it, we found that the most prominent role of iodide is to etch the stainless steel of the autoclave employed in most of previous works, releasing in solution small amounts of iron salts. The latter are much better promoters than iodide itself. Iron and iodide have a complex interplay and, depending on relative ratios, can even deactivate each other. The presence of a halide is beneficial, but chloride is better than iodide in this respect. The ideal Fe/Pd ratio is around 10, but even an equimolar amount of iron with respect to palladium (0.02 mol% with respect to aniline, corresponding to 12 ppm Fe with respect to the whole solution) is sufficient to boost the activity of the catalytic system. Such small amount may also come from Fe(CO)5 impurities present in the CO gas when stored in steel tanks. The role of the solvent has also been investigated. It was found that the reason for the better selectivity in some cases is at least in part due to a hydrolysis of the solvent itself, which removes the coproduced water.

La nadph-cytochrome p-450 reductase (ncpr) catalyse, dans les microsomes hepatiques, la reduction monoelectronique du nilutamide en un radical anion nitro. L'oxydation de ce radical par l'oxygene genere un cycle d'oxydoreduction formant des especes reactives de l'oxygene. Celles-ci entrainent un stress oxydatif responsable de la toxicite du nilutamide sur les hepatocytes isoles. Le nilutamide inhibe d'autre part le transfert des electrons au niveau du complexe un de la chaine respiratoire mitochondriale. Cet effet provoque une diminution de la formation d'atp responsable de la toxicite accrue du nilutamide sur les hepatocytes isoles incubes sans glucose. La ncpr ne catalyse pas la reduction monoelectronique du flutamide en un radical anion nitro. En revanche, les cytochromes p-450 appartenant aux familles 1a et 3a catalysent l'activation metabolique du flutamide en metabolite(s) reactif(s) qui consomment le glutathion et se fixent sur les proteines hepatiques. Le flutamide inhibe d'autre part le transfert des electrons au niveau des complexes un et deux de la chaine respiratoire mitochondriale. La formation de metabolites reactifs et l'inhibition de la respiration mitochondriale sont responsables de la toxicite du flutamide sur les hepatocytes isoles. La production d'intermediaires reactifs et la toxicite mitochondriale pourraient contribuer a expliquer la toxicite hepatique de ces deux nitroarenes utilises en clinique humaine dans le traitement des cancers metastases de la prostate

Les composés hétérocycliques aminés représentent une des plus importantes classes de structures d’intérêt pour la recherche pharmaceutique. Plus de 90% des composés dans ce domaine de recherche comportent au moins une de ces structures privilégiées. Parmi les méthodes les plus connues permettant l’accès aux composés aminés, la chimie des dérivés nitrés joue un rôle particulièrement important. Nous avons donc développé une réaction multicomposante activée par les hautes pressions au cours de laquelle un dérivé nitroaromatique réagit tout d’abord en tant qu’hétérodiène avec un diénophile enrichi électroniquement, dans une cycloaddition [4+2] à demande électronique inverse, pour générer un nitronate intermédiaire, qui lui-même réagit en tant que dipole dans une cycloaddition [3+2] subséquente menant au composé nitrosoacétalique. Ces composés sont d’intéressants motifs synthétiques, permettant un accès rapide aux composés hétérocycliques azotés après la rupture des liaisons N-O. Nous avons montré que la réaction pouvait être appliquée à un large panel de substrats nitroaromatiques. La cycloaddition [4+2]/[3+2] domino a ainsi été appliquée à plusieurs types de nitroaromatiques, tel que les indoles, thiophènes, benzofurannes, furannes, imidazoles, naphtalènes, et même au benzène. Les composés hétérocycliques aminés que nous pouvons générer par cette méthodologie comportent tous un carbone tétrasubsitué adjacent à l’atome d’azote. De tels motifs structuraux, sont difficiles d’accès par d’autres méthodes de synthèse. Notre méthode comporte l’avantage d’impliquer des réactifs de départ simples d’accès et de mener, en deux ou trois étapes seulement, aux composés désaromatisés polycycliques
Aminated heterocycles represent one of the most important structural classes of interest for the pharmaceutical research. More than 90% of the compounds in the field bear at least one of these “privileged-structures”. Among the oldest methods to get access to aminated molecules, those relying on the chemistry of nitro derivatives play a particularly important role. We thus have developed a multicomponent methodology in which, under hyperbaric activation, a nitroarene derivative first reacts as an inverse electron demand heterodiene with an electroenriched dienophile, to generate an intermediate nitronate that undergoes a subsequent [3+2] cycloaddition, leading to a nitrosoketal derivative. Such compounds are useful synthetic scaffolds, giving an easy access to nitrogenated motifs, after cleavage of the N-O bonds, for instance. We have shown that this domino [4+2]/[3+2] cycloaddition process can be applied to a wide panel of nitroaromatic substrates including indoles, thiophenes, benzofurans, furans, imidazoles, naphtalenes, and even benzene, for instance. The aminated compounds generated by this methodology all bear a tetrasubstituted center adjacent to the nitrogen atom. Such structural motifs are of difficult access by other synthetic methods. Our method thus bears the advantage of involving simple starting materials to lead, in two or three synthetic steps only, to dearomatized aminated polycycles

On the basis the multifacet reactivity of the azaheterocycles, this thesis work is focused on the study of heterocyclic systems such as 1-(2-quinolyl)-2-propen-1-ol , phenyl(2-quinolyl)methanol, (2-quinolyl)(4-tolyl)methanol, and 3-methyl-4-nitro-5-(trichloromethyl)isoxazole in different domains.

碩士
中原大學
化學研究所
102
In this thesis, primary aromatic amines were synthesized from the corresponding nitroarenes via photoreaction. The reaction was found to be more efficient when irradiated with a broad band of 306 nm UV light; and the acidity of aluminium oxide was found to be important. When reactions are completed, products could be isolated by acid-base extraction, or by column chromatography. We also tried to synthesize primary aromatic amines from the corresponding nitroarenes without sensitizer in 2-propanol by photoreaction. The photoinduced reduction of primary nitroarenes using a continuous flow system to shorten reaction time and increase efficiency of the reaction were also investigated. Without the usage of transition metal and by recycling the solvent, this photochemical reduction of nitroarene fits the concept of green chemistry.

碩士
中國醫藥學院
環境醫學研究所
87
HPLC/ECD/Flu was adopted in this study, accompanying with the use of separate column of TOSOH ODS-80TM ψ4.6 mm x150 mm and analytical column of Kaseisorb LC ODS ψ4.6 mm x 250 mm. The mobile phase was ACN：monochloroacetic=7：3（v/v），pH=4.7. The variations from ten times of continous analysis on peak areas and peak heights were all less than 6%. The calibration regression reached high above 0.999 and good reduction efficiency could be obtained by taking the advantage of Benzene:Ethanol(3:1, v/v) under sampling extraction. The detection limits of these four kinds of nitro polycyclic aromatic hydrocarbons are specified below：1,8-Dinitropyrene is 1.71 pg；1,6-Dinitropyrene，1.61 pg；1,3-Dinitropyrene，1.03 pg；1-Nitropyren is 2.20 pg. As to the application of the original samples, the median and geometry average concentration could be obtained：1,8-DNP is 97.50、61.84 pg/m3；1,6-DNP is 35.52、38.14 pg/m3；1,3-DNP is 59.72、 64.72 pg/m3；1-NP is 229.00、222.28 pg/m3.

碩士
國立臺北科技大學
分子科學與工程系有機高分子碩士班
107
Aromatic amines are vital precursors in the synthesis of dyes, pigments, agrochemicals, polymers, herbicides, and pharmaceuticals. Much attention has been paid to the synthesis methods because of their wide applications. Traditionally, aromatic nitro group reductions are carried out by catalytic hydrogenations in the presence of metal catalysts, such as Palladium on carbon, Platinum oxide or Raney Nickel. However, due to the flammability of hydrogen which may cause hazardous explosion, many groups tried to seek safer and economical catalytic systems for reduction of nitro group in the past decade. For example, porous nanostructured catalyst can be prepared by adding metal catalyst and supporting material in sequential thermal pyrolysis procedure in high temperature and Oxygen-free atmosphere to reduce the used amount of catalyst and shorten the reaction time. On the other hand, conducting analogous reaction in water and reusing the catalyst is rarely mentioned in published literature. Thus, we developed a FeCl3·6H2O/cationic 2,2’-bipyridyl aqueous catalytic system using hydrazine monohydrate as reducing agent for reduction of nitroarenes and successfully synthesized various amine derivatives with high selectivity and good functional group tolerance. Furthermore, the catalytic aqueous solution could be reused for several times with high yields. To achieve the goal of green chemistry, we established a low-cost catalytic system with both safety and environmental characteristics.