4926-55-0Relevant articles and documents
Robust Photocatalytic Method Using Ethylene-Bridged Flavinium Salts for the Aerobic Oxidation of Unactivated Benzylic Substrates
Pokluda, Adam,Anwar, Zubair,Boguschová, Veronika,Anusiewicz, Iwona,Skurski, Piotr,Sikorski, Marek,Cibulka, Radek
supporting information, p. 4371 - 4379 (2021/04/02)
7,8-Dimethoxy-3-methyl-1,10-ethylenealloxazinium chloride (1a) was found to be a superior photooxidation catalyst among substituted ethylene-bridged flavinium salts (R=7,8-diMeO, 7,8-OCH2O-, 7,8-diMe, H, 7,8-diCl, 7-CF3 and 8-CF3). Selection was carried out based on structure vs catalytic activity and properties relationship investigations. Flavinium salt 1a proved to be robust enough for practical applications in benzylic oxidations/oxygenations, which was demonstrated using a series of substrates with high oxidation potential, i. e., 1-phenylethanol, ethylbenzene, diphenylmethane and diphenylmethanol derivatives substituted with electron-withdrawing groups (Cl or CF3). The unique capabilities of 1a can be attributed to its high photostability and participation via a relatively long-lived singlet excited state, which was confirmed using spectroscopic studies, electrochemical measurements and TD-DFT calculations. This allows the maximum use of the oxidation power of 1a, which is given by its singlet excited state reduction potential of +2.4 V. 7,8-Dichloro-3-methyl-1,10-ethylenealloxazinium chloride (1 h) can be used as an alternative photocatalyst for even more difficult substrates. (Figure presented.).
Discovery and development of 2-aminobenzimidazoles as potent antimalarials
Avery, Vicky M.,Challis, Matthew P.,Creek, Darren J.,De Paoli, Amanda,Devine, Shane M.,Kigotho, Jomo K.,MacRaild, Christopher A.,Norton, Raymond S.,Scammells, Peter J.,Siddiqui, Ghizal
, (2021/06/03)
The emergence of Plasmodium falciparum resistance to frontline antimalarials, including artemisinin combination therapies, highlights the need for new molecules that act via novel mechanisms of action. Herein, we report the design, synthesis and antimalarial activity of a series of 2-aminobenzimidazoles, featuring a phenol moiety that is crucial to the pharmacophore. Two potent molecules exhibited IC50 values against P. falciparum 3D7 strain of 42 ± 4 (3c) and 43 ± 2 nM (3g), and high potency against strains resistant to chloroquine (Dd2), artemisinin (Cam3.IIC580Y) and PfATP4 inhibitors (SJ557733), while demonstrating no cytotoxicity against human cells (HEK293, IC50 > 50 μM). The most potent molecule, possessing a 4,5-dimethyl substituted phenol (3r) displayed an IC50 value of 6.4 ± 0.5 nM against P. falciparum 3D7, representing a 12-fold increase in activity from the parent molecule. The 2-aminobenzimidazoles containing a N1-substituted phenol represent a new class of molecules that have high potency in vitro against P. falciparum malaria and low cytotoxicity. They possessed attractive pharmaceutical properties, including low molecular weight, high ligand efficiency, high solubility, synthetic tractability and low in vitro clearance in human liver microsomes.
Discovery of dihydropyrazino-benzimidazole derivatives as metabotropic glutamate receptor-2 (mGluR2) positive allosteric modulators (PAMs)
Szabó, Gy?rgy,Kolok, Sándor,Orgován, Zoltán,Vastag, Mónika,Béni, Zoltán,Kóti, János,Sághy, Katalin,Lévay, Gy?rgy I.,Greiner, István,Keser?, Gy?rgy M.
, (2019/12/30)
A scaffold hopping strategy converted the known 1-[(1-methyl-1H-imidazol-2-yl)methyl]-4-phenylpiperidine core (1 and 2) by cyclization to a fused [6 + 5+6] membered heterocyclic mGluR2 PAM scaffold. Pharmacophore guided structure?activity relationship (SAR) studies resulted in a series of potent and metabolically stable mGluR2 PAMs. A representative optimized compound (95) having the most balanced profile, demonstrated efficacy in the PCP-induced hyper-locomotion model in mice that revealed the new chemotype being a promising PAM lead targeting mGluR2 receptors and providing support for further translational studies.
A green and practical reduction of N-(4-chlorophenyl)-2-nitroaniline and its derivatives to corresponding N-substituted-benzene-1,2-diamines using thiourea dioxide
Cui, Jian-Lan,Wang, Ning,Wang, Xiao,Yu, Si-Yuan,Zhong, Cong-Shan
supporting information, (2020/01/22)
A new effective approach for synthesizing diverse N-substituted-benzene-1,2-diamines is reported. The treatment of N-substituted-2-nitroanilines with thiourea dioxide in the presence of sodium hydroxide efficiently formed the corresponding N-substituted-benzene-1,2-diamines, including N-(4-chlorophenyl)benzene-1,2-diamine with a good yield of 94%. The by-product is environmentally-friendly urea and is easy to separate from the product by filtration procedure that enhances the convenience of the approach.
Green synthesis of N-(2-hydroxyethyl)anilines by the selective alkylation reaction in H2O
Guo, Hui,Hao, Jia,Sun, Tingting,Wang, Zuoyao,Cao, Jian,Zhang, Guobao
, p. 1 - 6 (2020/07/21)
Based on our previous work, a safer and more sustainable protocol for the synthesis of N-(2-Hydroxyethyl)anilines has been developed. The synthesis included the selective alkylation reaction of aniline with 2-chloroethanol in H2O, eliminating the need for any catalysts and solvents during synthesis. Comparing with our previous work, the salient features of this methodology are eco-friendliness, economic benefit, and the ease of obtaining target compounds. The selective alkylation reaction in H2O is amenable to scale-up for the synthesis of N-(2-Hydroxyethyl)anilines.
Synthesis of o-Nitroarylamines via Ipso Nucleophilic Substitution of Sulfonic Acids
Manne, Srinivasa Rao,Chandra, Jyoti,Mandal, Bhubaneswar
supporting information, p. 636 - 639 (2019/01/21)
A mild, efficient, and eco-friendly method for the synthesis of o-nitroarylamine from o-nitroaryl sulfonic acid via ipso nucleophilic aryl substitution by amine is described. The products have been obtained with good yields at room temperature without the assistance of any metal, activating agent, or toxic oxidant. This method is useful for racemization-free synthesis of N-aryl amino acid esters.
Regulating Cofactor Balance In Vivo with a Synthetic Flavin Analogue
Tan, Zhuotao,Zhu, Chenjie,Fu, Jingwen,Zhang, Xiaowang,Li, Ming,Zhuang, Wei,Ying, Hanjie
supporting information, p. 16464 - 16468 (2018/11/23)
A novel strategy to regulate cofactor balance in vivo for whole-cell biotransformation using a synthetic flavin analogue is reported. High efficiency, easy operation, and good applicability were observed for this system. Confocal laser scanning microscopy was employed to verify that the synthetic flavin analogue can directly permeate into Escherichia coli cells without modifying the cell membrane. This work provides a promising intracellular redox regulatory approach to construct more efficient cell factories.
CHEMICAL REGENERATION METHOD OF OXIDIZED COENZYME NAD (P)+
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Paragraph 0053, (2017/07/06)
It discloses a chemical regeneration method of oxidized coenzyme NAD(P)+ which is under an oxygen or air atmosphere condition, adding a catalytic amount of bridged flavin, and oxidizing NAD(P)H to obtain NAD(P)+. The catalyst for regeneration of cofactor is cheap and easily available small organic molecule having no noble metal; this regeneration system can regenerate NADH and NADPH; this regeneration system has a wide pH range and temperature range, being applicable to various oxidation reactions catalyzed by nicotinamide-dependent oxidoreductase.
Preparation method of N-(2-nitrophenyl)ethanolamine
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Paragraph 0026; 0027; 0028; 0029; 0030; 0031, (2017/02/28)
The invention relates to a preparation method of N-(2-nitrophenyl)ethanolamine. The purpose of the invention is to provide the preparation method of N-(2-nitrophenyl)ethanolamine, with the advantages of high yield, high purity, mild production technology and few three wastes. The method comprises the following steps: carrying a heating reaction on o-chloronitrobenzene and ethanolamine in an organic solvent under the action of a catalyst, crystallizing the above prepared product in a solvent, filtering obtained crystals, and drying to obtain the product. The method allows the total yield to reach 95% or above, and has the advantages of few three wastes, simple process, small consumption of raw materials due to recovery of the solvents, and good practicality, and industrial test shows that the method is suitable for industrial production. The N-(2-nitrophenyl)ethanolamine product prepared through the method has the advantages of high purity and good quality, and the preparation method also has the advantages of mild production technology and few three wastes, and fills the technical gap in the domestic synthesis of N-(2-nitrophenyl)ethanolamine.
"All-water" one-pot diverse synthesis of 1,2-disubstituted benzimidazoles: Hydrogen bond driven 'synergistic electrophile-nucleophile dual activation' by water
Kommi, Damodara N.,Jadhavar, Pradeep S.,Kumar, Dinesh,Chakraborti, Asit K.
, p. 798 - 810 (2013/04/24)
A new "all-water" tandem arylaminoarylation/arylaminoalkylation- reduction-cyclisation route is reported for one-pot diversity oriented synthesis of regiodefined 1,2-disubstituted benzimidazoles. Water plays a crucial and indispensable role through hydrogen bond driven 'synergistic electrophile-nucleophile dual activation' in the formation of N-mono-aryl/aryl alkyl/alkyl/cycloalkyl o-nitroanilines under metal and base-free conditions to replace the transition metal-based C-N bond formation (aryl amination) chemistry and underlines the origin of regiodefined installation of the diverse selection of aryl, aryl alkyl, and alkyl/cycloalkyl groups as substituents on the benzimidazole scaffold to form the 1,2-disubstituted benzimidazoles. The influence of the hydrogen bond effect of water in promoting the arylaminoarylation reaction under base and metal-free conditions has been realized through observation of inferior yields in D2O compared to that obtained in water during the reaction of o-fluoronitrobenzene with aniline separately performed in water and D2O under similar experimental conditions. Water also provides assistance in promoting the subsequent nitro reduction and in the final cyclocondensation steps. The role of water in promoting the cyclocondensation reaction through hydrogen bonds is realized by the differential product yields during the reaction of mono-N-phenyl-o- phenylenediamine with benzaldehyde performed separately in water and D 2O. The better hydrogen bond donor and hydrogen bond acceptor abilities of water compared to those of the organic solvents are the contributing/deciding factors for making the new water-assisted tandem arylaminoarylation/arylaminoalkylation-reduction-cyclisation strategy for the diversified synthesis of the regiodefined 1,2-disubstituted benzimidazoles effective in an aqueous medium, making it represent a true "all-water chemistry."
