- Nitration of quinoline 1-oxide: Mechanism of regioselectivity
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The acidity dependence of orientation in the nitration of quinoline 1- oxide was investigated by using the trifluoromethanesulfonic acid (TFSA)- trifluoroacetic acid (TFA) system and the antimony pentafluoride (SbF5)- TFSA system. These systems provide a wider range of acidity than that of aqueous sulfuric acid. Comparison of the behavior of quinoline 1-oxide and 1- methoxyquinolinium triflate in acidic and neutral media demonstrated that O- protonated quinoline 1-oxide is nitrated at the 5- and 8-positions, and the free (unprotonated) molecule is nitrated at the 4-position. This result is consistent with theoretical expectation. It was also discovered that nitration at the 5-position increasingly predominates over that at the 8- position as the acidity is increased.
- Yokoyama, Akihiro,Ohwada, Tomohiko,Saito, Shinichi,Shudo, Koichi
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- Hypervalent Iodine(III)-Mediated Regioselective Cyanation of Quinoline N-Oxides with Trimethylsilyl Cyanide
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A regioselective cyanation of quinoline N-oxides with trimethylsilyl cyanide was developed by using (Diacetoxyiodo) benzene (PIDA) as mediated hypervalent iodine(III) reagent under metal-free and base-free reaction conditions to obtain 2-cyanoquinolines. The efficient PIDA reagent could play the role of an activator of the substrates and an accelerator of N?O bond cleavage. The reaction system featured a wide range of substrate suitability and high yields. The procedure was enlarged gram-scale to synthesize the tuberculosis (TB) inhibitor. Finally, according to some experimental results, a plausible mechanism for the cyanation reaction is proposed. (Figure presented.).
- Xu, Feng,Li, Yuqin,Huang, Xin,Fang, Xinjie,Li, Zhuofei,Jiang, Hongshuo,Qiao, Jingyi,Chu, Wenyi,Sun, Zhizhong
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supporting information
p. 520 - 525
(2018/12/13)
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- Regioselective Cyanation of Six-Membered N-Heteroaromatic Compounds Under Metal-, Activator-, Base- and Solvent-Free Conditions
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A regioselective cyanation of heteroaromatic N-oxides with trimethylsilyl cyanide has been developed to obtain 2-substituted N-heteroaromatic nitrile without the requirement of any external activator-, metal-, base-, and solvent. The present protocol is a straightforward, one-pot heteroaromatic C?H cyanation process, and proceeds smoothly in conventional heating but also under microwave irradiation with shorter reaction times. This approach now allows access to a broad class of quinoline N-oxides and other heteroarene N-oxides with high to good yields and can also be scaled up to obtain gram quantities. Further application of this process was observed and utilized in late-stage cyanation of the anti-malarial drug quinine as well as transformation of the 2-cyanoazines to a series of biologically important molecules. Based on the experimental observations, a plausible mechanism has also been proposed highlighting the dual role of trimethylsilyl cyanide as a nitrile source and as an activating agent. (Figure presented.).
- Sarmah, Bikash Kumar,Konwar, Monuranjan,Bhattacharyya, Dipanjan,Adhikari, Priyanka,Das, Animesh
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supporting information
p. 5616 - 5625
(2019/11/22)
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- Conformational and structural analysis of bis(4-chloroquinoline-N-oxide)hydrogen tribromide
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The X-ray diffraction and conformational study of bis(4-chloroquinoline-N-oxide)hydrogen tribromide is performed. Two conformations corresponding to the minima on the energy curve are found by DFT using the ABINIT software. The model of one of the conformers generally matches with the structure determined experimentally for this compound using X-ray diffraction. In both instances, the structure with the dihedral angle (quinoline - N-O-H) close to 90° is most favorable, which is explained in terms of resonance theory and steric factors. It is concluded that oxygen atoms in the complex are in the sp3 hybridization state and the sp2 hybrid state of the oxygen atom is not possible here due to steric factors.
- Romanov,Nizhnik, Ya. P.,Fofanov
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p. 365 - 369
(2015/06/08)
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- Copper-catalyzed direct amination of quinoline N-oxides via C-H bond activation under mild conditions
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A highly efficient and concise one-pot strategy for the direct amination of quinoline N-oxides via copper-catalyzed dehydrogenative C-N coupling has been developed. The desired products were obtained in good to excellent yields for 22 examples starting from the parent aliphatic amines. This methodology provides a practical pathway to 2-aminoquinolines and features a simple system, high efficiency, environmental friendliness, low reaction temperature, and ligand, additives, base, and external oxidant free conditions.
- Zhu, Chongwei,Yi, Meiling,Wei, Donghui,Chen, Xuan,Wu, Yangjie,Cui, Xiuling
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supporting information
p. 1840 - 1843
(2014/05/06)
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- A3 ADENOSINE RECEPTOR ALLOSTERIC MODULATORS
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The present invention provides 2,4-disubstituted quinoline derivatives being an A3 adenosine receptor modulator (A3RM), for use in the treatment of a condition which is treatable by adenosine, an A3 adenosine receptor (A3AR) agonist or an A3 adenosine receptor antagonist. In one embodiment, the 2,4-disubstituted quinoline derivatives are for use in the treatment of a condition treatable by an adenosine or an A3AR agonist, treatment being achieved by enhancing activity of a protein (by binding of said 2,4 disubstituted quinoline derivative to the A3AR). Some conditions treatable by the 2,4 disubstituted quinoline derivative when used for enhancing activity include, malignancy, an immuno-compromised affliction, high intraocular pressure or a condition associated with high intraocular pressure. The invention also provides method for treatment of a subject having a condition treatable by adenosine, an A3AR agonist or an A3AR antagonist making use of the defined 2,4-disubstituted quinoline derivative (s), and pharmaceutical composition and comprising said derivative and a kit comprising the derivative and instructions for use thereof. One specific 2,4-disubstituted quinoline derivative comprises N-{2-[(3,4-dichlorophenyl)amino]quinolin-4-yl}cyclohexanecarboxamide In one embodiment, the 2,4-disubstituted quinoline derivatives in accordance with the invention are formulated in a form suitable for oral administration.
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Page/Page column 28; 1/2
(2010/04/03)
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- A series of 2,4-disubstituted quinolines as a new class of allosteric enhancers of the adenosine A3 receptor
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The adenosine receptor subfamily consists of the adenosine A1, A2A, A2B, and A3 receptors, which are localized in a variety of tissues throughout the human body. It is, therefore, a challenge to develop receptor specific ligands with improved tissue selectivity. Allosteric modulators could have these therapeutic advantages over orthosteric ligands. In the present study, a series of 2,4-disubstituted quinolines were synthesized on the basis of the structure of LUF6000 (34). Compound 27 (LUF6096) was able to allosterically enhance agonist binding to a similar extent as 34. In addition, this new compound showed low, if any, orthosteric affinity for any of the adenosine receptors. In a functional assay, compound 27 showed improved activity in comparison to 34, as it increased both the intrinsic efficacy and the potency of the reference agonist Cl-IB-MECA at the human adenosine A 3 receptor.
- Heitman, Laura H.,G?bly?s, Anikó,Zweemer, Annelien M.,Bakker, Renée,Mulder-Krieger, Thea,Van Veldhoven, Jacobus P. D.,De Vries, Henk,Brussee, Johannes,Ijzerman, Adriaan P.
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supporting information; experimental part
p. 926 - 931
(2010/01/07)
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- An unusual de-nitro reduction of 2-substituted-4-nitroquinolines
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The treatment of a variety of 2-substituted-4-nitroquinolines with Sn in the presence of concentrated hydrochloric acid in ethanol at 70 °C for 2-4 h afforded unusual de-nitro products 2-substituted-quinolines in good yields.
- Zhou, Yu,Li, Jian,Liu, Hong,Zhao, Linxiang,Jiang, Hualiang
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p. 8511 - 8514
(2007/10/03)
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- Spectroscopic Study of Hydrophobic Interaction of Heterocyclic Amine N-Oxides with Cyclodextrins
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Electronic spectra of aromatic amine N-oxides show a marked blue shift with the change of solvent polarity from aprotic solvents to protic ones.This is very useful to examine the hydrophobic interaction between the amine N-oxides and cyclodextrins (CyD) in water.Among the various systems studied a typical example is the system of 4-nitroquinoline N-oxide (4NQO) and 2,6-di-O-methyl-β-cyclodextrin in water.A clear red shift of the ultraviolet (UV) spectrum of 4NQO was observed upon inclusion complex formation, indicating directly that the CyD cage environment is much more hydrophobic than in water.Thermodynamic and spectroscopic constants pertinent to those inclusion complex formations were evaluated and the results are discussed in relation to the complex formation mechanisms.
- Uno, Bunji,Kaida, Naoki,Kawakita, Toshio,Kano, Kenji,Kubota, Tanekazu
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p. 3753 - 3759
(2007/10/02)
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- KINETICS OF N-OXIDATION OF COMPOUNDS OF THE QUINOLINE SERIES AND ISOMERIC BENZOQUINOLINES BY PERBENZOIC ACID IN CHLOROFORM AND AQUEOUS DIOXANE
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The kinetics of the N-oxidation with perbenzoic acid of 15 derivatives of quinoline and benzoquinoline in chloroform and 19 compounds in 50percent aqueous dioxane at 20, 25, 30, and 35 deg C were subjected to a comparative study.The rate constants, parameters of Arrhenius equation, and the activation energies for the N-oxidation of the indicated monoazines were determined.A scale of the reactivities of derivatives of the quinoline series and benzoquinolines was calculated within the framework of general perturbation theory.
- Lokhov, R. E.
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