- Ring expansion vs. cleavage of the exocyclic double bond of 2- cycloalkylidenedihydrobenzothiazoles and -benzimidazoles by methanesulfonyl azide
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Deprotonation of the 2-cycloalkylbenzothiazolium perchlorates 1f-h with sodium hydride in the presence of methanesulfonyl azide (3) affords the spirocyclic dihydro-1,4-benzothiazines 9f-h together with small amounts of the 2-iminobenzothiazole 5. The 2-cycloalkylidenedihydrobenzimidazoles 11e-h are generated by deprotonation with potassium hydride from the corresponding 2-cycloalkylbenzimidazolium salts 10e-h, and trapped with 3 to yield the zwitterions 12e-h. Whereas 12h is thermally unstable, 12e-g are isolated and thermolysed at 20-80 °C. The cyclopropyl zwitterion 12e decomposes in an ill-defined way, only at temperatures above 80 °C. In contrast, 12f,g, and, in particular, 12h, decompose more readily to furnish the products of ring expansion (13f-h) and those of a [3 + 2] cycloreversion (6 and 14) of intermediate spirocyclic triazolines. Products that might be indicative of the intervention of hypothetical zwitterions of type 8 cannot be detected.
- Quast, Helmut,Ivanova, Svetlana
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- Cobalt-Catalyzed Sustainable Synthesis of Benzimidazoles by Redox-Economical Coupling of o-Nitroanilines and Alcohols
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This study reveals cobalt-catalyzed sustainable synthesis of benzimidazoles by redox-economical coupling of o-nitroanilines and alcohols. The major advantage of this report is the use of a commercially available cheap cobalt catalyst to produce a wide variety of 2-substituted benzimidazoles by hydrogen autotransfer without using any additional external redox reagent and costly ligand system. A thorough mechanistic insight of the reaction is proposed by performing a series of control experiments.
- Das, Sanju,Mallick, Samrat,De Sarkar, Suman
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p. 12111 - 12119
(2019/10/02)
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- Phosphorous acid functionalized polyacrylonitrile fibers with a polarity tunable surface micro-environment for one-pot C-C and C-N bond formation reactions
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The preparation and application of fiber catalysts have attracted much attention. However, research on the effect of the micro-environment of fiber catalysts on the catalytic activities though of special importance is limited. In this work, a novel strategy for the synthesis of phosphoric acid-functionalized polyacrylonitrile fibers with a polarity tunable surface micro-environment by hydrophobic groups for one-pot C-C and C-N bond formation reactions is reported. The special hydrophobic surface micro-environment of the fiber catalysts is proven to promote the catalytic activities impressively in cyclocondensation of β-ketoesters with 2-aminobenzamides, the Knoevenagel condensation as well as the multi-component Biginelli reactions in green solvents. Both the surface synergy of the catalytic sites and hydrophobic auxiliary groups (benzyl or n-butyl) in the surface of fiber catalysts and interface acceleration in reaction medium play an important role in the highly efficient promotion of catalytic activity. Thereby a surface synergistic mechanism is proposed to explain the micro-environment effect. In addition, the fiber catalysts could be simply separated from the reaction system using tweezers and directly used in the next cycle without further treatment. Importantly, even after 10 reaction cycles in water or ethanol, there is no significant loss in their catalytic activity. The results indicate that the phosphoric acid functionalized fibers show green and sustainable potential for industrial production.
- Xu, Gang,Wang, Lu,Li, Mengmeng,Tao, Minli,Zhang, Wenqin
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supporting information
p. 5818 - 5830
(2017/12/26)
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- Catalytic Oxidative Coupling of Primary Amines under Air: A Flexible Route to Benzimidazole Derivatives
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Benzimidazoles are of fundamental importance in chemistry and biology, and the development of efficient, environmentally benign methods for their preparation remains a key challenge for organic chemists. In a biomimetic approach inspired by copper amine oxidases, we disclose herein the scope and factors influencing the success of the cooperative action of CuBr2 as electron-transfer mediator and a topaquinone-like substrate-selective catalyst in the oxidative cyclocondensation of primary amines with o-aminoanilines. This one-pot atom-economic multistep process, which works under green conditions with ambient air as the terminal oxidant, low loadings of catalyst, and equimolar amounts of commercially available amine substrates, is particularly suitable for the preparation of 1,2-disubstituted benzimidazoles. Furthermore, it allows the functionalization of nonactivated primary aliphatic amines, which are known to be challenging substrates for non-enzymatic catalytic aerobic systems.
- Nguyen, Khac Minh Huy,Largeron, Martine
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p. 1025 - 1032
(2016/03/01)
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- Catalyst free approach to benzimidazoles using air as the oxidant at room temperature
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A green and practical method to construct benzimidazoles, which are ubiquitous structural units in a number of biologically active compounds, has been developed. The catalyst and additive free conditions, using air as oxidant and the mild conditions make
- Zhang, Chun,Zhang, Liangren,Jiao, Ning
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supporting information
p. 3273 - 3276
(2013/01/16)
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- Synthesis of benzimidazoles by PIDA-promoted direct C(sp2)-H imidation of N-arylamidines
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A metal-free synthesis of diversified benzimidazoles from N-arylamidines through a phenyliodine(III) diacetate (PIDA) promoted intramolecular direct C(sp2)-H imidation has been developed. The reaction proceeds smoothly at 0 °C or ambient temperature to provide the desired products in good to excellent yields. The synthesis of 2-alkyl- or 2-alkyl-fused benzimidazoles, which are generally inaccessible by similar Pd- or Cu-catalyzed approaches, can also be achieved. Copyright
- Huang, Jinbo,He, Yimiao,Wang, Yong,Zhu, Qiang
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p. 13964 - 13967
(2013/01/15)
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- Discovery of dual inducible/neuronal nitric oxide synthase (iNOS/nNOS) inhibitor development candidate 4-((2-cyclobutyl-1 H-imidazo[4,5- b ]pyrazin-1-yl)methyl)-7,8-difluoroquinolin-2(1 H)-one (KD7332) Part 2: Identification of a novel, potent, and selective series of benzimidazole- quinolinone iNOS/nNOS dimerization inhibitors that are orally active in pain models
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Three isoforms of nitric oxide synthase (NOS), dimeric enzymes that catalyze the formation of nitric oxide (NO) from arginine, have been identified. Inappropriate or excessive NO produced by iNOS and/or nNOS is associated with inflammatory and neuropathic pain. Previously, we described the identification of a series of amide-quinolinone iNOS dimerization inhibitors that although potent, suffered from high clearance and limited exposure in vivo. By conformationally restricting the amide of this progenitor series, we describe the identification of a novel series of benzimidazole-quinolinone dual iNOS/nNOS inhibitors with low clearance and sustained exposure in vivo. Compounds were triaged utilizing an LPS challenge assay coupled with mouse and rhesus pharmacokinetics and led to the identification of 4,7-imidazopyrazine 42 as the lead compound. 42 (KD7332) (J. Med. Chem. 2009, 52, 3047 -3062) was confirmed as an iNOS dimerization inhibitor and was efficacious in the mouse formalin model of nociception and Chung model of neuropathic pain, without showing tolerance after repeat dosing. Further 42 did not affect motor coordination up to doses of 1000 mg/kg, demonstrating a wide therapeutic margin.
- Payne, Joseph E.,Bonnefous, Céline,Symons, Kent T.,Nguyen, Phan M.,Sablad, Marciano,Rozenkrants, Natasha,Zhang, Yan,Wang, Li,Yazdani, Nahid,Shiau, Andrew K.,Noble, Stewart A.,Rix, Peter,Rao, Tadimeti S.,Hassig, Christian A.,Smith, Nicholas D.
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supporting information; experimental part
p. 7739 - 7755
(2011/02/22)
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- Copper-catalyzed synthesis of benzimidazoles via cascade reactions of o-haloacetanilide derivatives with amidine hydrochlorides
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(Chemical Equation Presented) We have developed an efficient method for the synthesis of benzimidazoles via cascade reactions of o-haloacetoanilide derivatives with amidine hydrochlorides. The protocol uses 10 mol % CuBr as the catalyst, CS2CO
- Yang, Daoshan,Fu, Hua,Hu, Liming,Jiang, Yuyang,Zhao, Yufen
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p. 7841 - 7844
(2008/12/22)
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- Spiro-cyclic beta-amino acid derivatives as inhibitors of matrix metalloproteases and TNF-alpha converting enzyme (TACE)
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The present application describes novel spiro-cyclic β-amino acid derivatives of formula I: or pharmaceutically acceptable salt forms thereof, wherein ring B is a 3-13 membered carbocycle or heterocycle, ring C forms a 3-11 membered spiro-carbocycle or spiro-heterocycleon ring B, and the other variables are defined in the present specification, which are useful as as matrix metalloproteinases (MMP), TNF-α converting enzyme (TACE), and/or aggrecanase inhibitors.
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- Cyclic hydroxamic acids as inhibitors of matrix metalloproteinases and/or TNF-alpha converting enzyme (TACE)
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The present application describes novel cyclic hydroxamic acids of formula I: or pharmaceutically acceptable salt forms thereof, wherein ring B is a 5-7 membered cyclic system containing from 0-2 heteroatoms selected from O, N, NR1, and S(O)p, and 0-1 carbonyl groups and the other variables are defined in the present specification, which are useful as inhibitors of matrix metalloproteinases (MMP), TNF-α converting enzyme (TACE), aggrecanase or a combination thereof, pharmaceutical compositions containing the same, and methods of using the same.
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