- Metal-free selective synthesis of 2-substituted benzimidazoles catalyzed by Br?nsted acidic ionic liquid: Convenient access to one-pot synthesis of N-alkylated 1,2-disubstituted benzimidazoles
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A novel efficient method for the selective synthesis of 2-substituted benzimidazoles is described through condensation reaction of o-phenylenediamines with a wide rang of aliphatic, aromatic and heteroaromatic aldehyde substrates using Br?nsted acidic ionic liquid as a reusable catalyst under metal-free conditions at ambient temperature. Notably, Dodecylimidazolium hydrogen sulfate ([DodecIm][HSO4]) is the most efficient catalyst for good to excellent yields of the corresponding products (up to 98%). Subsequently, this protocol was successfully applied for the preparation of N-alkylated 1,2-disubstituted benzimidazoles in high to excellent yields via sequential one-pot reaction. In addition, catalysts are recycled at least four times without significant loss in activity.
- Senapak, Warapong,Saeeng, Rungnapha,Jaratjaroonphong, Jaray,Promarak, Vinich,Sirion, Uthaiwan
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p. 3543 - 3552
(2019/05/29)
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- Studies on the synthesis, characterization, cytotoxic activities and plasmid DNA binding of platinum(II) complexes having 2-subsituted benzimidazole ligands
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The aim of this study was to synthesize and evaluate the cytotoxic activities and plasmid DNA interaction of some new platinum(II) complexes, which may have potent cytotoxic activity and low side effects, with benzimidazole derivatives containing some amino acid residues as substituents in their 2 position. Seven 2-subtituted benzimidazole derivatives (1–7) (2-(H, methyl isopropyl, isobutyl, sec-butyl 1H-imidazol-4-ylmethyl or 4-hydroxybenzyl)benzimidazole, respectively), seven platinum(II) complexes with two chlorido leaving groups (1a–7a) and six platinum(II) complexes with an oxalato leaving group (2b–7b) bearing the benzimidazole carrier ligand were synthesized. The chemical structures of the compounds were characterized by their elemental analysis, IR, 1H NMR, and HRMS spectra. The compounds were evaluated for their cytotoxic activities against human HeLa cervical cancer cell lines. The interaction of all the ligands and their complexes with plasmid DNA and their restriction endonuclease reactions with BamHI and HindIII enzymes were investigated by agarose gel electrophoresis. Compounds 1a, 3a, 3b, 6, 7a and 7b, having 2-(H, isopropyl, 1H-imidazol-4-ylmethyl or 4-hydroxybenzyl)benzimidazole carrier ligands, have moderate in vitro cytotoxic activity, close to that of carboplatin.
- Gozelle, Mahmut,Sülo?lu, Aysun K?l??,Selmano?lu, Güldeniz,Ramazano?lu, Nagehan,A??k, Leyla,Gümü?, Fatma
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p. 298 - 308
(2019/02/06)
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- An efficient NaHSO3-promoted protocol for chemoselective synthesis of 2-substituted benzimidazoles in water
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An efficient protocol for chemoselective synthesis of 2-substituted benzimidazoles from a variety of aliphatic/aromatic/ heteroaryl aldehydes and o-phenylenediamine derivatives promoted by NaHSO3 in water had been developed. The amount of NaHSO3 had a great effect on the reaction selectivity of 2-substituted benzimidazole and 1,2-disubstituted benzimidazole when the reaction was carried out in water. When the amount of the NaHSO3 was more than 11 equivalents, the 2-substituted benzimidazole could be highly selectively formed as the sole product. NaHSO3 was firstly reacted with aldehyde to form the aldehyde sodium bisulfite, which reacted with o-phenylenediamine to form the 2-substituted benzimidazole and inhibited the formation of 1,2-disubstituted benzimidazole. This protocol solved the poor selectivity problem appearing in traditional method when cyclocondensation between o-phenylenediamine and aldehydes. The method also had advantage of simple work up by filtrating the single 2-substituted benzimidazole precipitates from reaction mixture at the end of the reaction without further purification. In addition, the method was applicable to both electron-rich and electron-poor starting materials, which was successfully used for synthesizing nine novel 2-substituted benzimidazole derivatives containing a 1,2,3-triazole moiety. They were characterized by NMR, IR and HRMS spectrum. Moreover, this method had been applied to a large scale synthesis of 2-substituted benzimidazole derivatives.
- Jiang, Yu-Qin,Jia, Shu-Hong,Li, Xi-Yong,Sun, Ya-Min,Li, Wei,Zhang, Wei-Wei,Xu, Gui-Qing
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p. 1265 - 1276
(2019/01/28)
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- Direct Synthesis of Benzimidazoles by Dehydrogenative Coupling of Aromatic Diamines and Alcohols Catalyzed by Cobalt
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Herein, we present the base-metal-catalyzed dehydrogenative coupling of primary alcohols and aromatic diamines to selectively form functionalized 2-substituted benzimidazoles, liberating water and hydrogen gas as the sole byproducts. The reaction is catalyzed by pincer complexes of Earth-abundant cobalt under base-free conditions.
- Daw, Prosenjit,Ben-David, Yehoshoa,Milstein, David
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p. 7456 - 7460
(2017/11/10)
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- Decarboxylative Coupling of α-Keto Acids with ortho-Phenylenediamines Promoted by an Electrochemical Method in Aqueous Media
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An electrochemical method for the decarboxylative coupling of α-keto acids with ortho-phenylenediamines was developed. The reaction proceeded smoothly in aqueous solution under air and metal catalyst-free conditions to afford 2-substituted benzimidazoles in good yields. Benzothiazoles could also be synthesized by this protocol. (Figure presented.) .
- Wang, Hai-Bin,Huang, Jing-Mei
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supporting information
p. 1975 - 1981
(2016/07/06)
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- Efficient and versatile catalysis of N-alkylation of heterocyclic amines with alcohols and one-pot synthesis of 2-aryl substituted benzazoles with newly designed ruthenium(ii) complexes of PNS thiosemicarbazones
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Ruthenium(ii) carbonyl complexes with phosphine-functionalized PNS type thiosemicarbazone ligands [RuCl(CO)(EPh3)(L)] (1-6) (E = P or As, L = 2-(2-(diphenylphosphino)benzylidene) thiosemicarbazone (PNS-H), 2-(2-(diphenylphosphino)benzylidene)-N-methylthiosemicarbazone (PNS-Me), 2-(2-(diphenylphosphino)benzylidene)-N-phenylthiosemicarbazone (PNS-Ph)) have been synthesized and characterized by elemental analysis and spectroscopy (IR, UV-Vis, 1H, 13C, 31P-NMR) as well as ESI mass spectrometry. The molecular structures of complexes 1, 2 and 6 were identified by means of single-crystal X-ray diffraction analysis. The analysis revealed that all the complexes possess a distorted octahedral geometry with the ligand coordinating in a uni-negative tridentate PNS fashion. All the ruthenium complexes (1-6) were tested as catalyst for N-alkylation of heteroaromatic amines with alcohols. Notably, complex 2 was found to be a very efficient and versatile catalyst towards N-alkylation of a wide range of heterocyclic amines with alcohols. Complex 2 can also catalyze the direct amination of 2-nitropyridine with benzyl alcohol to the corresponding secondary amine. Furthermore, a preliminary examination of performance for N,N-dialkylation of diamine showed promising results, giving good conversion and high selectivity. In addition, N-alkylation of ortho-substituted anilines (-NH2, -OH and -SH) led to the one-pot synthesis of 2-aryl substituted benzimidazoles, benzoxazoles and benzothiazoles, also revealing the catalytic activity of complex 2. This journal is the Partner Organisations 2014.
- Ramachandran, Rangasamy,Prakash, Govindan,Selvamurugan, Sellappan,Viswanathamurthi, Periasamy,Malecki, Jan Grzegorz,Ramkumar, Venkatachalam
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supporting information
p. 7889 - 7902
(2014/05/20)
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- Iron phthalocyanine as an efficient and versatile catalyst for N-alkylation of heterocyclic amines with alcohols: One-pot synthesis of 2-substituted benzimidazoles, benzothiazoles and benzoxazoles
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An efficient and versatile iron phthalocyanine catalyzed method has been developed for N-alkylation of various amines with alcohols. Readily available alcohols were used as alkylating agents for direct N-alkylation of aminobenzothiazoles, aminopyridines and aminopyrimidines. N-Alkylation of ortho-substituted anilines (-NH2, -SH and -OH) led to the synthesis of 2-substituted benzimidazoles, benzothiazoles and benzoxazoles in one pot.
- Bala, Manju,Verma, Praveen Kumar,Sharma, Upendra,Kumar, Neeraj,Singh, Bikram
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supporting information
p. 1687 - 1693
(2013/09/24)
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- Combined Pd/C and montmorillonite catalysis for one-pot synthesis of benzimidazoles
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A series of nineteen benzimidazoles were prepared from ortho-nitroanilines by one-pot transfer hydrogenation, condensation, and dehydrogenation enabled by the concurrent use of two heterogeneous catalysts: montmorillonite-K10 and Pd/C. This strategy was further employed to accomplish a five-step, three-component synthesis of an antifungal benzimidazoquinazoline by using a simple one-pot procedure.
- Weires, Nicholas A.,Boster, Jared,Magolan, Jakob
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supporting information
p. 6508 - 6512
(2013/01/15)
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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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- Efficient synthesis of functionalized benzimidazoles and perimidines: Ytterbium chloride catalyzed C-C bond cleavage
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An efficient method is developed for the synthesis of functionalized benzimidazoles and perimidines by the condensation of aryl diamines with β-carbonyl compounds catalyzed by ytterbium chloride. The reactions give good yields under mild conditions. A mechanism involving a lanthanide activated C-C bond cleavage is proposed. An efficient method is developed for the synthesis of functionalized benzimidazoles and perimidines by the condensation of aryl diamines with β-carbonyl compounds catalyzed by ytterbium chloride. The reactions give good yields under mild conditions. A mechanism involving a lanthanide activated C-C bond cleavage is proposed. Copyright
- Cai, Lijian,Ji, Xiaofeng,Yao, Zhigang,Xu, Fan,Shen, Qi
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experimental part
p. 1880 - 1886
(2012/06/18)
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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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- Towards organo-click reactions: Development of pharmaceutical ingredients by using direct organocatalytic bio-mimetic reductions
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Economic and environmentally friendly bio-mimetic one-pot three and four-component Knoevenagel-hydrogenation (K-H), five-component Knoevenagel-hydrogenation-alkylation (K-H-A) and six-component Knoevenagel-hydrogenation-alkylation-Huisgen cycloaddition (K-H-A-HC) reactions of aldehydes, CH-acids, o-phenylenediamine, alkyl halides and azides using proline, proline-metal carbonate and proline-metal carbonate-Cu I-catalysis, respectively have been developed. Many of K-H and K-H-A compounds have direct application in pharmaceutical chemistry. The Royal Society of Chemistry.
- Ramachary, Dhevalapally B.,Reddy, G. Babul
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p. 4463 - 4468
(2008/09/19)
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