- Design, synthesis and biological evaluation of novel quinoline-based carboxylic hydrazides as anti-tubercular agents
-
In this study, seventeen novel quinoline-based carboxylic hydrazides were designed as potential anti-tubercular agents using molecular hybridization approach and evaluated in-silico for drug-likeness behavior. The compounds were synthesized, purified, and characterized using spectral techniques (like FTIR, 1H NMR, and Mass). The in-vitro anti-tubercular activity (against Mycobacterium tuberculosisH37Ra) and cytotoxicity against human lung fibroblast cells were studied. Among the tested hydrazides, four compounds (6h, 6j, 6l, and 6m) exhibited significant anti-tubercular activity with MIC values below 20?μg/mL. The two most potent compounds of the series, 6j and 6m exhibited MIC values 7.70 and 7.13?μg/mL, respectively, against M.?tuberculosis with selectivity index >26. Structure–activity relationship studies were performed for the tested compounds in order to explore the effect of substitution pattern on the anti-tubercular activity of the synthesized compounds.
- Chander, Subhash,Ashok, Penta,Cappoen, Davie,Cos, Paul,Murugesan, Sankaranarayanan
-
-
Read Online
- Toward the synthesis of 6-hydroxyquinoline starting from glycerol via improved microwave-assisted modified Skraup reaction
-
An efficient and modified Skraup reaction and Bamberger rearrangement in neat water were developed using nitrobenzene and an inexpensive, abundant and environmentally-friendly glycerol under microwave irradiation conditions was furnish regioselectively to the 6-hydroxyquinoline. The target compound was obtained in 77% yield via efficient domino reaction with a "one pot eleven steps".
- Saggadi, Hanen,Luart, Denis,Thiebault, Nicolas,Polaert, Isabelle,Estel, Lionel,Len, Christophe
-
-
Read Online
- Application of Electron-Rich Covalent Organic Frameworks COF-JLU25 for Photocatalytic Aerobic Oxidative Hydroxylation of Arylboronic Acids to Phenols
-
Visible-light-driven organic reactions are environmentally friendly green chemical transformations among which photosynthetic oxidative hydroxylation of arylboronic acids to phenols has attracted increasing research interest during the very recent years. Given the efficiency and reusability of heterogeneous catalysts, COF-JLU25, an electron-rich COF-based photocatalyst constructed by integrating electron-donating blocks 1,3,6,8-tetrakis(4-aminophenyl)pyrene (PyTA) and 4-[4-(4-formylmethyl)-2,5-dimethoxyphenyl] benzaldehyde (TpDA), was selected as a photocatalyst for the oxidative hydroxylation of arylboronic acids. In our studies, COF-JLU25 demonstrated excellent photocatalytic activity with high efficiency, robust reusability, and low catalyst loading, showcasing an application potential of previously underexplored COF-based photocatalyst composed solely of electron-rich units.
- Xiao, Guangjun,Li, Wenqian,Chen, Tao,Hu, Wei-Bo,Yang, Hui,Liu, Yahu A.,Wen, Ke
-
supporting information
p. 3986 - 3991
(2021/03/29)
-
- Monomeric vanadium oxide: A very efficient species for promoting aerobic oxidative dehydrogenation of N-heterocycles
-
Monomeric active species are very interesting in heterogeneous catalysis. In this work, we proposed a method to prepare VOx-NbOy@C catalysts, which involve the one-pot hydrothermal synthesis of inorganic/organic hybrid materials containing V/Nb followed by thermal treatment under a reducing atmosphere. The prepared catalysts were characterized using different techniques, such as high-angle annular dark-field scanning transmission electron microscopy and X-ray absorption fine structure spectroscopy. It was shown that monomeric VOx species were dispersed homogeneously in the catalysts. The VOx-NbOy@C catalysts displayed high performance in the aerobic oxidative dehydrogenation of N-heterocycles to aromatic heterocycles. It was demonstrated that the selectivity of reaction over the catalyst with a very small amount of V (0.07 wt%) was much higher than that over the NbOy@C, and the catalyst also exhibited excellent stability in the reaction. The detailed study indicated that monomeric VO2 species were the most effective for promoting the reaction. This journal is
- Xie, Zhenbing,Chen, Bingfeng,Zheng, Lirong,Peng, Fangfang,Liu, Huizhen,Han, Buxing
-
p. 431 - 437
(2021/01/11)
-
- Biocatalytic Cross-Coupling of Aryl Halides with a Genetically Engineered Photosensitizer Artificial Dehalogenase
-
Devising artificial photoenzymes for abiological bond-forming reactions is of high synthetic value but also a tremendous challenge. Disclosed herein is the first photobiocatalytic cross-coupling of aryl halides enabled by a designer artificial dehalogenase, which features a genetically encoded benzophenone chromophore and site-specifically modified synthetic NiII(bpy) cofactor with tunable proximity to streamline the dual catalysis. Transient absorption studies suggest the likelihood of energy transfer activation in the elementary organometallic event. This design strategy is viable to significantly expand the catalytic repertoire of artificial photoenzymes for useful organic transformations.
- Fu, Yu,Huang, Jian,Wu, Yuzhou,Liu, Xiaohong,Zhong, Fangrui,Wang, Jiangyun
-
supporting information
p. 617 - 622
(2021/02/03)
-
- Radical-anion coupling through reagent design: hydroxylation of aryl halides
-
The design and development of an oxime-based hydroxylation reagent, which can chemoselectively convert aryl halides (X = F, Cl, Br, I) into phenols under operationally simple, transition-metal-free conditions is described. Key to the success of this approach was the identification of a reducing oxime anion which can interact and couple with open-shell aryl radicals. Experimental and computational studies support the proposed radical-nucleophilic substitution chain mechanism.
- Chechik, Victor,Greener, Andrew J.,James, Michael J.,Oca?a, Ivan,Owens-Ward, Will,Smith, George,Ubysz, Patrycja,Whitwood, Adrian C.
-
p. 14641 - 14646
(2021/11/17)
-
- Superacid-promoted synthesis of quinoline derivatives
-
A series of vinylogous imines have been prepared from anilines and cinnamaldehydes. These substrates react in superacidic media to provide quinolines and related compounds. A mechanism for the conversion is proposed which involves the cyclization of dicationic superelectrophilic intermediates. Aromatization of the quinoline ring is thought to occur by superacid-promoted elimination of benzene.
- Klumpp, Douglas A.,Stentzel, Michael R.,Vuong, Hein
-
supporting information
(2020/01/24)
-
- Palladium-Catalyzed Hydroxylation of Aryl Halides with Boric Acid
-
Boric acid, B(OH)3, is proved to be an efficient hydroxide reagent in converting (hetero)aryl halides to the corresponding phenols with a Pd catalyst under mild conditions. Various phenol products were obtained in good to excellent yields. This transformation tolerates a broad range of functional groups and molecules, including base-sensitive substituents and complicated pharmaceutical (hetero)aryl halide molecules.
- Song, Zhi-Qiang,Wang, Dong-Hui
-
supporting information
p. 8470 - 8474
(2020/11/18)
-
- Visible-light-promoted aerobic oxidative hydroxylation of arylboronic acids in water by hydrophilic organic semiconductor
-
A green and sustainable catalytic system was developed based on perylenediimide (PDI) organic semiconductor for the aerobic oxidative hydroxylation of arylboronic acids in aqueous solution with visible light. By using PDI-SN, a hydrophilic organic semiconductor, which can activate oxygen to produce superoxide radicals in aqueous solution, this reaction proceeds under ambient conditions: water as the solvent and air as the oxidant, giving various phenols as products with high yields. In contrast to methods using organic solvents, this novel process has the potential of green industrial application.
- Yu, Kunyi,Zhang, Hanjie,Sheng, Yuqiang,Zhu, Yongfa
-
supporting information
(2020/06/23)
-
- Reversible aerobic oxidative dehydrogenation/hydrogenation of N-heterocycles over AlN supported redox cobalt catalysts
-
N-heterocycles with quinoline and tetrahydroquinoline structures are highly important in pharmaceutical and chemical industries, and their highly efficient mutual transformations are vital but still challenging. In the present work, AlN supported redox cobalt catalysts (Co3O4/AlN and Co/AlN) were prepared, which could achieve the reversible aerobic oxidative dehydrogenation/hydrogenation of N-heterocycles with good performances. The catalytic performances were stem from the strong interaction between Co species with AlN support, which were confirmed by the characterizations of Raman, XPS, UV–vis DRS, and H2-TPR etc. Both of the catalysts showed good stabilities and reusabilities for the titled reactions. Besides, the gram-scale experiments achieved with good yields to corresponding products, revealing the present protocol possesses great potential applications in industry. The strategy of using redox Co-based catalyst not only provides a potential catalyst for the reversible hydrogenation/oxidative dehydrogenation reactions but also replenishes methods for constructing of other redox catalyst, especially with AlN as a carrier.
- He, Zhen-Hong,Sun, Yong-Chang,Wang, Kuan,Wang, Zhong-Yu,Guo, Pan-Pan,Jiang, Chong-Shan,Yao, Man-Qing,Li, Zhu-Hui,Liu, Zhao-Tie
-
-
- Cu(I)/sucrose-catalyzed hydroxylation of arenes in water: The dual role of sucrose
-
A protocol for the hydroxylation of aryl halides catalyzed by copper(I) and sucrose in neat water has been developed. The dual role of sucrose, the reaction pathway, and the high selectivity for hydroxylation were investigated using a combination of experimental and theoretical techniques. This journal is
- Murata, Shigeo,Takagi, Mio,Takita, Ryo,Watanabe, Ayako,Watanabe, Kohei
-
supporting information
p. 7827 - 7831
(2020/11/02)
-
- Multi-Functional Oxidase Activity of CYP102A1 (P450BM3) in the Oxidation of Quinolines and Tetrahydroquinolines
-
Tetrahydroquinoline, quinoline, and dihydroquinolinone are common core motifs in drug molecules. Screening of a 48-variant library of the cytochrome P450 enzyme CYP102A1 (P450BM3), followed by targeted mutagenesis based on mutation-selectivity correlations from initial hits, has enabled the hydroxylation of substituted tetrahydroquinolines, quinolines, and 3,4-dihydro-2-quinolinones at most positions around the two rings in good to high yields at synthetically relevant scales (1.5 g L?1 day?1). Other oxidase activities, such as C?C bond desaturation, aromatization, and C?C bond formation, were also observed. The enzyme variants, with mutations at the key active site residues S72, A82, F87, I263, E267, A328, and A330, provide direct and sustainable routes to oxy-functionalized derivatives of these building block molecules for synthesis and drug discovery.
- Li, Yushu,Wong, Luet L.
-
p. 9551 - 9555
(2019/08/06)
-
- Photoinduced Hydroxylation of Organic Halides under Mild Conditions
-
Presented in this paper is photoinduced hydroxylation of organic halides, providing a mild access to a range of functionalized phenols and aliphatic alcohols. These reactions generally proceed under mild reaction conditions with no need for a photocatalyst or a strong base and show a wide substrate scope as well as excellent functional group tolerance. This work highlights the unique role of NaI that allows a challenging transformation to proceed under mild reaction conditions.
- Cai, Yue-Ming,Xu, Yu-Ting,Zhang, Xin,Gao, Wen-Xia,Huang, Xiao-Bo,Zhou, Yun-Bing,Liu, Miao-Chang,Wu, Hua-Yue
-
supporting information
p. 8479 - 8484
(2019/10/16)
-
- Identification of an Oxalamide Ligand for Copper-Catalyzed C?O Couplings from a Pharmaceutical Compound Library
-
A typical pharmaceutical compound library is stocked with molecular diversity and could provide a platform for the discovery of new ligand structures. Herein, we describe the use of this approach in combination with high throughput screening to identify N,N’-bis(thiophene-2-ylmethyl)oxalamide as a ligand that is generally effective for copper-catalyzed C?O cross-couplings to prepare both biarylethers as well as phenols under mild conditions.
- Chan, Vincent S.,Krabbe, Scott W.,Li, Changfeng,Sun, Lijie,Liu, Yue,Nett, Alex J.
-
-
- Quinospirooxazine-based photochromic compound and preparation method thereof
-
The present invention contains a spirooxazine-based photochromic compound containing a quinoline ring, and a preparation method thereof, and relates to an organic photochromic material, wherein the compound has the following chemical structural general formula defined in the specification, R1 is CH3, and R2 is a group defined in the specification or -N(C2H5)2. The preparation method comprises: (1)synthesis of 6-hydroxyquinoline; (2) synthesis of 5-nitroso-6 hydroxyquinoline; (3) synthesis of 5-nitroso-6-hydroxyquinoline metal complex; and (4) synthesis of quinospirooxazine-based photochromiccompound. According to the present invention, the preparation method is simple, the preparation cost is low, and the compound has advantages of good fatigue resistance, good color tone, wide application range and high yield compared with the existing spirooxazine-based photochromic compound.
- -
-
Paragraph 0029; 0031-0032; 0057; 0059-0060; 0077-0080
(2019/05/16)
-
- Reversible Dehydrogenation and Hydrogenation of N-Heterocycles Catalyzed by Bimetallic Nanoparticles Encapsulated in MIL-100(Fe)
-
Pd?Ni bimetallic nanoparticles (BMNPs) encapsulated in MIL-100(Fe) (Pd-Ni@MIL-100(Fe) was fabricated and employed as an efficient catalyst for the reversible dehydrogenation/hydrogenation of N-Heterocycles derivatives in water under mild conditions. Excellent catalytic performance for both reactions endows Pd-Ni@MIL-100(Fe) great potential value in organic chemistry. Alloying Pd with Ni can enhance the catalytic performance due to the bimetallic synergy. Both Lewis acidity and ordered mesoporous structure of MIL-100(Fe) are beneficial to the performance of the catalyst owing to its stabilization of BMNPs, reduction of the electron density of Pd atoms and enhancement of substrates adsorption capacity.
- Zhang, Jia-Wei,Li, Dan-Dan,Lu, Guo-Ping,Deng, Tao,Cai, Chun
-
p. 4980 - 4986
(2018/10/15)
-
- Synthesis of Complex Phenols Enabled by a Rationally Designed Hydroxide Surrogate
-
The conversion of aryl halides to phenols under mild reaction conditions is a longstanding and formidable challenge in organic chemistry. Herein, we report the rational design of a broadly applicable Pd-catalyzed method to prepare phenols with benzaldehyde oxime as a hydroxide surrogate. These reactions occur under mildly basic conditions and enable the late-stage hydroxylation of several functionally-dense drug-like aryl halides.
- Fier, Patrick S.,Maloney, Kevin M.
-
supporting information
p. 4478 - 4482
(2017/04/13)
-
- Dehydrogenation of Nitrogen Heterocycles Using Graphene Oxide as a Versatile Metal-Free Catalyst under Air
-
Graphene oxide (GO) has been developed as an inexpensive, environmental friendly, metal-free carbocatalyst for the dehydrogenation of nitrogen heterocycles. Valuable compounds, such as quinoline, 3,4-dihydroisoquinoline, quinazoline, and indole derivatives, have been successfully used as substrates. The investigation of various oxygen-containing molecules with different conjugated systems indicated that both the oxygen-containing groups and large π-conjugated system in GO sheets are essential for this reaction. (Figure presented.).
- Zhang, Jingyu,Chen, Shiya,Chen, Fangfang,Xu, Wensheng,Deng, Guo-Jun,Gong, Hang
-
supporting information
p. 2358 - 2363
(2017/07/22)
-
- Palladium Nanoparticles Stabilized by Metal–Carbon Covalent Bonds as an Expeditious Catalyst for the Oxidative Dehydrogenation of Nitrogen Heterocycles
-
The first method for the dehydrogenation of nitrogen heterocycles catalyzed by a palladium nanocatalyst was developed. Carbon–metal covalent-bond-stabilized nanoparticles were found to be efficient for the dehydrogenation process in the presence of tert-butyl hydroperoxide. A variety of N-heterocycles were transformed into functionalized quinolines in medium to excellent yields in water as the solvent under mild conditions by a simple operation.
- Sun, Xiao-Tao,Zhu, Jie,Xia, Yun-Tao,Wu, Lei
-
p. 2463 - 2466
(2017/07/12)
-
- Reagent Design and Ligand Evolution for the Development of a Mild Copper-Catalyzed Hydroxylation Reaction
-
Parallel synthesis and mass-directed purification of a modular ligand library, high-throughput experimentation, and rational ligand evolution have led to a novel copper catalyst for the synthesis of phenols with a traceless hydroxide surrogate. The mild reaction conditions reported here enable the late-stage synthesis of numerous complex, druglike phenols.
- Fier, Patrick S.,Maloney, Kevin M.
-
supporting information
p. 3033 - 3036
(2017/06/07)
-
- Copper-Catalyzed Hydroxylation of (Hetero)aryl Halides under Mild Conditions
-
The combination of Cu(acac)2 and N,N′-bis(4-hydroxyl-2,6-dimethylphenyl)oxalamide (BHMPO) provides a powerful catalytic system for hydroxylation of (hetero)aryl halides. A wide range of (hetero)aryl chlorides bearing either electron-donating or -withdrawing groups proceeded well at 130 °C, delivering the corresponding phenols and hydroxylated heteroarenes in good to excellent yields. When more reactive (hetero)aryl bromides and iodides were employed, the hydroxylation reactions completed at relatively low temperatures (80 and 60 °C, respectively) at low catalytic loadings (0.5 mol % Cu).
- Xia, Shanghua,Gan, Lu,Wang, Kailiang,Li, Zheng,Ma, Dawei
-
supporting information
p. 13493 - 13496
(2016/10/31)
-
- Quinoline synthesis by improved Skraup-Doebner-Von Miller reactions utilizing acrolein diethyl acetal
-
A robust synthetic method has been developed as an improvement to the venerable Skraup-Doebner-Von Miller reaction providing access to various quinoline products. The straightforward procedure utilizes acrolein diethyl acetal as a three-carbon annulation partner with aniline substrates in a monophasic, organic solvent-free reaction medium. Differentially substituted aniline precursors were found to be compatible with the reaction conditions and the corresponding quinoline products are isolated in moderate to good yields.
- Ramann, Ginelle A.,Cowen, Bryan J.
-
supporting information
p. 6436 - 6439
(2015/11/16)
-
- Quinoline and phenanthroline preparation starting from glycerol via improved microwave-assisted modified Skraup reaction
-
An efficient "green" modified Skraup reaction in neat water was developed using inexpensive, abundant and environmentally-friendly glycerol under microwave irradiation conditions. Starting from aniline derivatives, various quinolines were obtained in 10-66% yields. The use of nitroaniline led to the corresponding phenanthrolines in 15-52% yields, respectively. This journal is the Partner Organisations 2014.
- Saggadi, Hanen,Luart, Denis,Thiebault, Nicolas,Polaert, Isabelle,Estel, Lionel,Len
-
p. 21456 - 21464
(2014/06/10)
-
- Unusually Broad Substrate Profile of Self-Sufficient Cytochrome P450 Monooxygenase CYP116B4 from Labrenzia aggregata
-
A new member of the CYP116B subfamily - P450LaMO - was discovered in Labrenzia aggregata by genomic data mining. It was successfully overexpressed in Escherichia coli, purified, and subsequently characterized spectroscopically, and its catalytic properties were assessed. Substrate profiling of the P450LaMO revealed that it was a versatile catalyst, exhibiting hydroxylation and epoxidation activities as well as O-dealkylation and asymmetric sulfoxidation activities. Diverse compounds, including alkylbenzenes, aromatic bicyclic molecules, and terpenoids, were shown to be hydroxylated by P450LaMO. Such diverse catalytic activities are uncommon for the bacterial P450s, and the P450LaMO -mediated stereoselective hydroxylation of inactivated C - H bonds - ubiquitous and relatively unreactive in organic molecules - is particularly unusual. The self-sufficient nature of P450LaMO, coupled with its broad substrate range, highlights it as an ideal template for directed evolution towards various applications.
- Yin, Yue-Cai,Yu, Hui-Lei,Luan, Zheng-Jiao,Li, Ren-Jie,Ouyang, Peng-Fei,Liu, Jing,Xu, Jian-He
-
p. 2443 - 2449
(2015/03/03)
-
- Unusually Broad Substrate Profile of Self-Sufficient Cytochrome P450 Monooxygenase CYP116B4 from Labrenzia aggregata
-
A new member of the CYP116B subfamily - P450LaMO - was discovered in Labrenzia aggregata by genomic data mining. It was successfully overexpressed in Escherichia coli, purified, and subsequently characterized spectroscopically, and its catalytic properties were assessed. Substrate profiling of the P450LaMO revealed that it was a versatile catalyst, exhibiting hydroxylation and epoxidation activities as well as O-dealkylation and asymmetric sulfoxidation activities. Diverse compounds, including alkylbenzenes, aromatic bicyclic molecules, and terpenoids, were shown to be hydroxylated by P450LaMO. Such diverse catalytic activities are uncommon for the bacterial P450s, and the P450LaMO -mediated stereoselective hydroxylation of inactivated C-H bonds - ubiquitous and relatively unreactive in organic molecules - is particularly unusual. The self-sufficient nature of P450LaMO, coupled with its broad substrate range, highlights it as an ideal template for directed evolution towards various applications.
- Yin, Yue-Cai,Yu, Hui-Lei,Luan, Zheng-Jiao,Li, Ren-Jie,Ouyang, Peng-Fei,Liu, Jing,Xu, Jian-He
-
p. 2443 - 2449
(2015/08/24)
-
- The ketene-surrogate coupling: Catalytic conversion of aryl iodides into aryl ketenes through ynol ethers
-
tert-Butoxyacetylene is shown to undergo Sonogashira coupling with aryl iodides to yield aryl-substituted tert-butyl ynol ethers. These intermediates participate in a [1,5]-hydride shift, which results in the extrusion of isobutylene and the generation of aryl ketenes. The ketenes are trapped in situ with multiple nucleophiles or undergo electrocyclic ring closure to yield hydroxynaphthalenes and quinolines.
- Zhang, Wenhan,Ready, Joseph M.
-
supporting information
p. 8980 - 8984
(2014/11/07)
-
- Copper MOF: Scope and limitation in catalytic hydroxylation and nitration of aryl halides
-
The potential catalytic application of MOFs like [Cu3(btc) 2] (btc=1,3,5-benzenetricarboxylate), [Cu(bdc)] (bdc=1,4- benzenedicarboxylate), [Cu(pymo)2] (pymo=2-hydroxypyrimidinalote) and [Cu(im)2] (im=imidazolate) was explored in the hydroxylation and nitration of aryl halides. Cu3(btc)2 was found to be superior for both the reactions furnishing good to excellent yields of the respective products. The studies demonstrated that MOFs are not recyclable, attributable to their instability in the highly polar and basic conditions demanded for these reactions. Complete transformation of MOFs to copper oxide nanoparticles occurred in hydroxylation, whereas significant alteration in frameworks was observed for the recovered catalyst in nitration.
- Priyadarshini,Amal Joseph,Kantam, M. Lakshmi,Sreedhar
-
p. 6409 - 6414
(2013/07/26)
-
- Efficient microwave-assisted Pd-catalyzed hydroxylation of aryl chlorides in the presence of carbonate
-
An efficient microwave-assisted, palladium-catalyzed hydroxylation of aryl chlorides in the presence of a weak base carbonate was developed, which rapidly converts aryl and heteroaryl chlorides to phenols, and can be used when the aryl chloride is functionalized with a ketone, aldehyde, ester, nitrile, or amide.
- Yu, Chao-Wu,Chen, Grace S.,Huang, Chen-Wei,Chern, Ji-Wang
-
supporting information; experimental part
p. 3688 - 3691
(2012/08/28)
-
- Demethylation of aromatic methyl ethers using ionic liquids under microwave irradiation
-
An efficient demethylation reaction for aromatic methyl ethers has been developed. Deprotection reactions give high yields with butylpyridinium bromide under microwave irradiation. Basic and acidic functional groups are tolerated if the reaction is performed under acidic conditions.
- Passiniemi, Mikko,Myllymaeki, Mikko J.,Vuokko, Juha,Koskinen, Ari M.P.
-
scheme or table
p. 48 - 52
(2012/04/10)
-
- Novel carbamates as orally active acetylcholinesterase inhibitors found to improve scopolamine-induced cognition impairment: Pharmacophore-based virtual screening, synthesis, and pharmacology
-
A systematic virtual screening (VS) experiment, consisting of the development of 3D-pharmacophore, screening of virtual library, synthesis, and pharmacology, is reported. The predictive pharmacophore model (correlation = 0.955) with one H-bond donor and three hydrophobic features was developed using HypoGen on a training set of 24 carbamates as AChE inhibitors. The model was validated on a test set of 40 carbamates (correlation = 0.844). The pharmacophore-based VS of virtual library led to the identification of novel carbamates as potent AChE inhibitors. The synthesis and pharmacological evaluation of nine carbamates against three diverse assay systems, namely (i) in vitro Ellman method, (ii) in vivo passive avoidance test, and (iii) aldicarb-sensitivity assay, led to the discovery of orally active novel AChE inhibitors which improved scopolamine-induce cognition impairment in Swiss male mice. Finally, two novel lead compounds 85 and 86 are selected as candidate molecules for further optimization.
- Chaudhaery, Shailendra S.,Roy, Kuldeep K.,Shakya, Neeraj,Saxena, Gunjan,Sammi, Shreesh Raj,Nazir, Aamir,Nath, Chandishwar,Saxena, Anil K.
-
supporting information; experimental part
p. 6490 - 6505
(2010/11/18)
-
- Reduction of nitroarenes followed by propanol group transfer from tris(3-hydroxypropyl)- amine and cyclization leading to quinolines under heterogeneous Pd-C catalysis
-
Nitroarenes having electron-donating or -withdrawing substituents are reduced to anilines and cyclized with tris(3- hydroxypropyl)amine in the presence of a catalytic amount of Pd-C along with tin(II) chloride and isopropanol in dioxane-H2O medium to give the corresponding quinolines in good to excellent yields. Copyright
- Cho, Chan Sik,Kim, Tae Gyun,Yoon, Nam Sik
-
experimental part
p. 291 - 293
(2010/08/04)
-
- BICYCLIC TRIAZOLES AS PROTEIN KINASE MODULATORS
-
The present disclosure provides bicyclic triazole protein kinase modulators and methods of using these compounds to treat diseases mediated by kinase activity.
- -
-
Page/Page column 87
(2008/12/05)
-
- Facile cleavage of ethers in ionic liquid
-
Various alkyl ethers were efficiently cleaved by treating them with pyridinium halides in ionic liquid, and the desired products were obtained in excellent yields.
- Cheng, Lili,Aw, Carlin,Ong, Siew Siang,Lu, Yixin
-
supporting information; experimental part
p. 2008 - 2010
(2009/08/14)
-
- The selective reaction of aryl halides with KOH: Synthesis of phenols, aromatic ethers, and benzofurans
-
The direct and selective synthesis of phenols from aryl/heteroaryl halides and KOH has been achieved through the use of highly active monophosphine-based catalysts derived from Pd2dba3 and ligands L1 or L2 and the biphasic solvent system 1,4-dioxane/H2O. We have also demonstrated a one-pot method of phenol formation/alkylation for the preparation of alkyl aryl ethers from aryl halides. In many instances, this protocol overcomes limitations in existing Pd-catalyzed coupling reactions of aliphatic alcohols with aryl halides. Finally, we demonstrate that substituted benzofurans can be prepared efficiently via a Pd-catalyzed phenol formation/cyclization protocol starting from 2-chloroaryl alkynes. Copyright
- Anderson, Kevin W.,Ikawa, Takashi,Tundel, Rachel E.,Buchwald, Stephen L.
-
p. 10694 - 10695
(2007/10/03)
-
- Cleavage of aromatic methyl ethers by chloroaluminate ionic liquid reagents
-
We have discovered serendipitously that chloroaluminate ionic liquids can cleave aromatic methyl ethers under surprisingly mild conditions. Three ionic liquids, viz. [TMAH]-[Al2Cl7], [BMIM][Al2Cl7], and [EMIM][Al2Cl6I], and aluminum chloride were compared in the selective demethylation of 4,5-dimethoxyindanone at the 4-methoxy-function. The ionic liquids exhibited a remarkably high selectivity (96:4) in comparison with aluminum chloride (70:30). In addition, the reaction time was drastically shortened when the ionic liquids were used. Interestingly, the three ionic liquids displayed the same reactivity in the demethylation of 4,5-dimethoxyindanone. Considering the lower cost and the bulk availability of the precursors of [TMAH][Al2Cl7], we conclude that this is the most attractive ionic liquid from an industrial point of view. To make the large-scale application of [TMAH][Al2Cl7] feasible, we have developed a safe upscalable method for its preparation. Furthermore, the scope of ether cleavage by the ionic liquid reagent [TMAH][Al2Cl7] was investigated and it was found that aromatic methyl-, al- lyl-, and benzyl-ether cleavage is applicable to a variety of heterocyclic compounds. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.
- Kemperman, Gerardus J.,Roeters, Theodorus A.,Hilberink, Peter W.
-
p. 1681 - 1686
(2007/10/03)
-
- PROCESS FOR CONVERTING HYDROXY HETEROAROMATICS TO ARYLAMINES
-
A process of converting a hydroxy heteroaromatic compound to an arylamine, comprising the steps of : 1) treating a salt of a hydroxy heteroaromatic compound with an alkylating agent; and 2) treating the reaction mixture with a Smiles solvent system and raising the temperature of the reaction mixture; and a compound made according to the above process.
- -
-
-
- Indium metal as a reducing agent in organic synthesis
-
The low first ionisation potential (5.8 eV) of indium coupled with its stability towards air and water, suggest that this metallic element should be a useful reducing agent for organic substrates. The use of indium metal for the reduction of C=N bonds in imines, the heterocyclic ring in benzo-fused nitrogen heterocycles, of oximes, nitro compounds and conjugated alkenes and the removal of 4-nitrobenzyl protecting groups is described. Thus the heterocyclic ring in quinolines, isoquinolines and quinoxalines is selectively reduced using indium metal in aqueous ethanolic ammonium chloride. Treatment of a range of aromatic nitro compounds under similar conditions results in selective reduction of the nitro groups; ester, nitrile, amide and halide substituents are unaffected. Likewise indium in aqueous ethanolic ammonium chloride is an effective method for the deprotection of 4-nitrobenzyl ethers and esters. Indium is also an effective reducing agent under non-aqueous conditions and α-oximino carbonyl compounds can be selectively reduced to the corresponding N-protected amine with indium powder, acetic acid in THF in the presence of acetic anhydride or di-tert-butyl dicarbonate. Conjugated alkenes are also reduced by indium in THF-acetic acid.
- Pitts,Harrison,Moody
-
p. 955 - 977
(2007/10/03)
-
- Process for converting hydroxy heteroaromatics to arylamines
-
A process of converting a hydroxy heteroaromatic compound to an arylamine, comprising the steps of: (1) treating a salt of a hydroxy heteroaromatic compound with an alkylating agent; and (2) treating the reaction mixture with a Smiles solvent system and raising the temperature of the reaction mixture; and A compound made according to the above process.
- -
-
-
- Indium as a reducing agent: Deprotection of 4-nitrobenzyl ethers and esters
-
Indium in aqueous ethanolic ammonium chloride is an effective method for the deprotection of 4-nitrobenzyl ethers and esters.
- Moody, Christopher J.,Pitts, Michael R.
-
p. 1575 - 1576
(2007/10/03)
-
- Quinolinoxy phenylsulphonamides
-
New phenylsulphonamide of the formula in which STR1 R1 represents a pyridyl, quinolyl or isoquinolyl radical which is unsubstituted or substituted by halogen, alkyl, cycloalkyl, alkoxy, cyano, nitro, halogenoalkyl, halogenoalkoxy, alkoxycarbonyl or alkylsulphonyl, R2 represents hydrogen, cyano, nitro, halogen, alkyl, alkoxy, halogenoalkyl, halogenoalkoxy or alkoxycarbonyl, R3 represents an aryl radical which is unsubstituted or monosubstituted, disubstituted or trisubstituted by halogen, halogenoalkyl, halogenoalkoxy, alkyl, alkoxy, alkylthio, alkylsulphonyl, cyano, nitro or alkoxycarbonyl, the substituents being identical or different, or represents pentafluorophenyl or represents a straight-chain, branched or cyclic alkyl which is unsubstituted or substituted by halogen, aryl, aryloxy, cyano, alkoxycarbonyl, alkoxy, alkylthio or trifluoromethyl, and X represents an --O--, --A--B-- or --B--A-- group where A denotes --O--, STR2 and B denotes --CH2 -- or STR3 where R1 does not represent a pyridyl radical when x represents an --O-- group, and salts thereof are prepared by reacting appropriate amines with sulphonyl halides. The substituted phenylsulphonamides can be employed as active compounds for inhibiting enzymatic reactions and for inhibiting thrombocyte aggregations.
- -
-
-
- Method of inhibiting leukotriene biosynthesis by oral administration of p-aminophenols or derivatives thereof
-
A method is provided for inhibiting leukotriene biosynthesis and thus treating asthma, psoriasis or inflammation by oral administration of p-aminophenols having the structure STR1 wherein m is 0 to 5; X is CH or N; R1 and R2 may be the same or different and are H, lower alkyl, aryl, hydroxy, hydroxyalkyleneoxy, alkylthio, alkoxy, alkanoyloxy, aryloxy, halo, carboxy, alkoxycarbonyl or amido; R3 is H, lower alkyl, alkanoyl or aroyl; and R4 is H, lower alkyl, benzoyl or alkanoyl, and including acid-addition salts thereof, with the proviso that when R4 is benzoyl, R2 is other than H.
- -
-
-
- AMINODEMETHOXYLATION IN QUINOLINES AND NAPHTHALENES
-
Substitution of the methoxy group in inactivated aromatic and heterocyclic substrates by alkylamines takes place by bimolecular nucleophilic substitution at a saturated carbon atom with the formation of phenolic intermediates and subsequent substitution of the hydroxyl group by the alkylamino group.In the temperature range between 150 and 200 deg C in the presence of ammonium chloride the substitution of the hydroxy group in 1- and 2-hydroxynaphthalenes and 6-, 7-, and 8-hydroxyquinolines, and of the methoxy group in 1- and 2-methoxynaphthalenes and 6-, 7-, and 8-methoxyquinolines takes place almost quantitatively.
- Terenin, V. I.,Gerasimenko, V. A.,Nikishova, N. G.,Kurts, A. L.,Afanas'eva, T. A.,Bundel', Yu. G.
-
p. 1890 - 1896
(2007/10/02)
-
- Quinoline compounds and compositions thereof
-
p-Aminophenols are provided having the structure STR1 wherein m is 0 to 5; X is CH or N; R1 and R2 may be the same or different and are H, lower alkyl, aryl, hydroxy, hydroxyalkyleneoxy, alkylthio, alkoxy, alkanoyloxy, aryloxy, halo, carboxy, alkoxycarbonyl or amido; R3 is H, lower alkyl, alkanoyl or aroyl; and R4 is H, lower alkyl or alkanoyl, and including acid-addition salts thereof, with the proviso that when X is CH, m is 0 and R1 is H, and when R4 is H, R2 is other than alkoxy, H or hydroxy, and when R4 is benzoyl, R2 is other than H. These compounds together with the compounds defined in the above proviso are useful as inhibitors of leukotriene production and as such are useful as antiallergy, anti-inflammatory and anti-psoriatic agents.
- -
-
-
- Solvolysis of the Quinoline 5,6- and 7,8-Oxides: Effect of the Ring Nitrogen
-
pH-rate profiles for the hydrolysis of quinoline arene oxides were measured in 1:9 dioxane-water at 25 deg C (0.1 M NaClO4) and compared with the parent carbocylic compound naphthalene 1,2-oxide.Unlike naphthalene 1,2-oxide whose hydrolysis rate shows a first-order dependence on hydronium ion concentration (kH) below pH 5, rates for the quinoline 5,6- and 7,8-oxides show a kH reaction (0.14 and 1.54 M-1 s-1 for quinoline 5,6- and 7,8-oxides, respectively), but plateau below pH 2-3. pH-independent rate constants in the low-pH plateau are 2.7E-5 and 1.7E-3 s-1for the 5,6- and 7,8-oxides, respectively.On the basis of studies of the N-methyl cation of the 5,6-oxide (kobsd -1 at pH 1.8), it is concluded that the low-pH plateau is due to lack of reactivity for the N-protonated quinoline oxides.Also unlike naphthalene oxide, the quinoline oxides show a reaction with hydroxide ion (kOH rate) that results in the formation of trans dihydrodiols.In acid, quinoline 5,6-oxide, but not quinoline 7,8-oxide, gives a significant yield (20percent) of the trans dihydrodiol product and provides the first example of a benzo-ring arene oxide that forms dihydrodiol product under acidic conditions.Other products of the acid-catalyzed reaction of the 5,6-oxide are 5- (73percent) and 6- (7percent) hydroxyquinolines.The 7,8-oxide upon solvolysis in acid gave exclusively 8-hydroxyquinoline.The 100-1000 fold decrease in reactivity of the quinoline oxides, relative to naphthalene oxide in the pH range of 1-10, can be accounted for in terms of the presence of their ring nitrogens and the differences in the pKa values of these nitrogens.
- Bushman, Daniel R.,Sayer, Jane M.,Boyd, Derek R.,Jerina, Donald M.
-
p. 2688 - 2691
(2007/10/02)
-
- ARENE OXIDES AND trans-DIHYDRODIOLS OF QUINOLINE
-
Arene oxides and trans-dihydrodiols at the 5,6- and 7,8-positions of quinoline have been synthesized.High stability of both arene oxides allowed identification of the 5,6-oxide as a liver microsomal metabolite of quinoline.Both arene oxides are converted to trans-dihydrodiols by microsomal epoxide hydrolase.
- Agarwal, S. K.,Boyd, D. R.,Porter, H. P.,Jennings, W. B.,Grossman, S. J.,Jerina, D. M.
-
p. 4253 - 4256
(2007/10/02)
-
- TOTAL REACTIVITY OF PYRIDINE AND QUINOLINE VIA THE REACTIONS OF ARYLBENZOATES WITH HYDROXIDE ION. APPARENT SUBSTITUENT CONSTANS FOR SOME N-HETEROAROMATIC GROUPS
-
A new set of apparent ? values was evaluated for the aza substitution of all positions in pyridyl and quinolyl groups on the basis of the alkaline hydrolysis of aryl benzoates.The enhanced reactivities of 4-pyridyloxy- and 4-quinolyloxy- groups were first estimated quantitatively.
- Sawada, Masami,Ichihara, Masaharu,Ando, Takashi,Yukawa, Yasuhide,Tsuno, Yuho
-
p. 4733 - 4736
(2007/10/02)
-
- Selectivity in the Hydrogenation of 6- and 8-Substituted-quinolines
-
Quinoline (1) and the 6- or 8-substituted-quinolines (2)-(14) (R = Me, Pri, But, Ph, OMe, OH, CF3, or F) were hydrogenated catalytically on platinum under either weakly basic (solvent MeOH) or strongly acidic (solvent CF3CO2H) conditions.In methanol the only product was the corresponding 1,2,3,4-tetrahydro-compound.In trifluoroacetic acid, compounds hydrogenated in the benzene ring were isolated as major products; both electron-withdrawing and electron-donating substituents at C-6 or C-8 cause (sometimes drastic) reduction in yield.The products were characterized by their 1H and 13C n.m.r. spectra.
- Hoenel, Michael,Vierhapper, Friedrich W.
-
p. 1933 - 1939
(2007/10/02)
-