- Highly practical "ligand-free-like" copper-catalyzed N-arylation of azoles in lower nitrile solvents
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In lower nitrile solvents, the N-arylation of azoles with aryl halides was achieved efficiently in the presence of copper powder without any additional ligands. Thus, the first nitrile type of monodentate ligand-mediated, "ligand-free-like" copper-catalyzed N-arylation procedure was established.
- Zhu, Rui,Xing, Lixin,Wang, Xinyan,Cheng, Chuanjie,Su, Deyong,Hu, Yuefei
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- α-d-Galacturonic Acid as Natural Ligand for Selective Copper-Catalyzed N-Arylation of N-Containing Heterocycles
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The first application of α-d-galacturonic acid hydrate (GalA) is reported here, as a potential O-donor ligand. The C-N couplings of N-heterocycles with aryl halides or arylboronic acids could be readily conducted and exhibited good functional group tolerance with characters of selectivity. These N-Arylazoles allow rapid access to several pharmaceutical intermediates and can be easily transformed into a variety of other interesting scaffolds as well.
- Yuan, Chunling,Zhao, Yingdai,Zheng, Li
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- CuI heterogenized on thiosemicarbazide modified-multi walled carbon nanotubes (thiosemicarbazide-MWCNTs-CuI): Novel heterogeneous and reusable nanocatalyst in the C-N Ullmann coupling reactions
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Herein we described the synthesis of novel thiosemicarbazide-MWCNTs-CuI nanocatalyst by covalent grafting of thiosemicarbazide on carbon nanotubes surface and subsequent coordination with CuI catalyst. The formation of nanocatalyst was analyzed by Raman spectroscopy, energy dispersive spectroscopy (EDS), wavelength-dispersive X-ray spectroscopy (WDX) and ICP analysis. The morphology of the nanocatalyst was characterized using scanning and transmission electron microscopes (SEM and TEM). Additionally, the (thiosemicarbazide-MWCNTs-CuI) nanocatalyst was successfully employed in the N-arylation of indole, amines and imidazoles through intermolecular C(aryl)-N bond formation from the corresponding aryl halides (Ar–I, Ar–Br, Ar–Cl) with amines through Ullmann-type coupling reactions. Interestingly, the novel catalyst could be recovered and recycled five times.
- Veisi, Hojat,Metghalchi, Yalda,Hekmati, Malak,Samadzadeh, Shiva
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- Efficient iron-catalyzed N-arylation of aryl halides with amines
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(Chemical Equation Presented) A practical and promising protocol was developed for N-arylations of various amines with differently substituted aryl halides. The processes are efficiently promoted by the catalyst system involving the environmentally benign Fe2O3 and the universal ligand L-proline. The versatility, convenient operation, low cost, and environmental friendliness, in combination with the high yields, render this method viable for use in both laboratory research and larger industrial scales.
- Quo, Diliang,Huang, He,Xu, Jinyi,Jiang, Hualiang,Liu, Hong
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- A ligand-free copper-catalyzed strategy to the N-arylation of indazole using aryl bromides
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A simple and efficient strategy for the C–N cross-coupling of indazole with a variety of substituted aryl bromides is reported. Under the optimized conditions, a broad scope of N-arylated products were obtained in good to excellent yields (up to 87%) under the ligand-free conditions.
- Bai, Di-Xiang,Lim, Rachel Sin-Ee,Ng, Hui-Fen,Teo, Yong-Chua
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- Cooperatively assisted N-arylation using organic ionic base-Br?nsted acid combination under controlled microwave heating
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A new synthetic strategy is developed for the construction of C-N bond through the assistance of Br?nsted acid/[DBU][HOAc] without adding any metal catalyst. This is the first efficient SNAr methodology utilizing fluoro, chloro, bromo, and iodoarenes as coupling partners, which offers excellent yield up to 94% within a very short time.
- Singh, Rahul,Allam, Bharat Kumar,Raghuvanshi, Dushyant Singh,Singh, Krishna Nand
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- Efficient iron/copper co-catalyzed arylation of nitrogen nucleophiles
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(Chemical Equation Presented) An ideal pair: Various substituted aryl halides react under mild conditions with nitrogen heterocycles in the presence of catalytic amounts of [Fe(acac)3] (acac = acetylacetonate) and copper salts to give the corresponding cross-coupling products in high yields (see scheme). This cheap and environmentally friendly cocatalyst system is the first example of cooperative Fe/Cu catalysis in this type of N-C bond formation.
- Taillefer, Marc,Xia, Ning,Ouali, Armelle
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- Facile Synthesis of 1-Arylpyrazoles
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A convenient and transition-metal-free synthesis of 1-arylpyrazoles that involves the cycloaddition of 3-arylsydnones and acrylic acid is presented. The process proceeds smoothly to obtain the target products with moderate to high yields.
- Yang, Yiwen,Kuang, Chunxiang
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- Cooperative Au/Ag Dual-Catalyzed Cross-Dehydrogenative Biaryl Coupling: Reaction Development and Mechanistic Insight
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An operationally simple and highly selective Au/Ag bimetallic-catalyzed cross-dehydrogenative biaryl coupling between pyrazoles and fluoroarenes has been developed. With this reaction, a wide range of biheteroaryl products can be obtained in moderate to good yields with excellent functional group compatibility. The exact role of silver salts, previously overlooked in most gold-catalyzed transformations, has been carefully investigated in this biaryl coupling. Insightful experimental and theoretical studies indicate that silver acetate is the actual catalyst for C-H activation of electron-poor arenes, rather than the previously reported gold(I)-catalyzed process. An unprecedented Au/Ag dual catalysis is proposed, in which silver(I) is responsible for the activation of electron-poor fluoroarenes via a concerted metalation-deprotonation pathway, and gold(III) is responsible for the activation of electron-rich pyrazoles via an electrophilic aromatic substitution process. Kinetic studies reveal that ArFnAu(III)-mediated C-H activation of pyrazoles is most likely the rate-limiting step.
- Li, Weipeng,Yuan, Dandan,Wang, Guoqiang,Zhao, Yue,Xie, Jin,Li, Shuhua,Zhu, Chengjian
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- Copper ferrite nanoparticle-mediated N-arylation of heterocycles: A ligand-free reaction
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The synergistic effects of iron and copper in copper ferrite nanoparticles for the N-arylation of heterocycles with aryl halides were demonstrated. The magnetic nature of the catalyst facilitates its removal from the reaction medium for further use. Negligible leaching of Cu and Fe in consecutive cycles makes the catalyst economical and environmentally benign for C-N cross-coupling reactions.
- Panda, Niranjan,Jena, Ashis Kumar,Mohapatra, Sasmita,Rout, Smruti Ranjan
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- SBA-15-functionalized melamine-pyridine group-supported palladium(0) as an efficient heterogeneous and recyclable nanocatalyst for N-arylation of indoles through Ullmann-type coupling reactions
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SBA-15-functionalized melamine-pyridine group-supported palladium(0) was found to serve as a heterogeneous and recyclable nanocatalyst for N-arylation of indoles with aryl iodides under a low catalyst loading (0.3mol% of Pd) through Ullmann-type C£N coupling reactions. A variety of aryl iodides could be aminated to provide the N-arylated products in good to excellent yields without the need of an inert atmosphere. Also, this catalyst was found to be an efficient system for the N-arylation of other nitrogen-containing heterocycles with aryl iodides. The heterogeneous palladium catalyst could be recovered by simple filtration of the reaction solution and reused for six cycles without significant loss in its activity.
- Veisi, Hojat,Poor Heravi, Mohammad Reza,Hamelian, Mona
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- Highly efficient and reusable copper-catalyzed N-arylation of nitrogen-containing heterocycles with aryl halides
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CuO/AB was found to be a simple and efficient catalyst for the N-arylation of a variety of nitrogen-containing heterocycles, giving the products in excellent yields.
- Kim, A. Young,Lee, Hyun Ju,Park, Ji Chan,Kang, Hyunju,Yang, Haesik,Song, Hyunjoon,Park, Kang Hyun
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- Mild conditions for copper-catalysed N-arylation of pyrazoles
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Copper-catalysed N-arylation of pyrazoles with aryl or heteroaryl bromides or iodides, which can include functional substituents, was performed under the mildest conditions yet described, with excellent yields and selectivity, by the use as catalyst of a combination of cuprous oxide with a set of inexpensive, chelating oxime-type ligands not previously known to promote such reactions. Other original bi-, tri- or tetradentate ligands providing nitrogen and/or oxygen as chelating atoms were also successfully tested in this type of arylation. ( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004).
- Cristau, Henri-Jean,Cellier, Pascal P.,Spindler, Jean-Francis,Taillefer, Marc
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- Ruthenium- and rhodium-catalyzed direct carbonylation of the ortho C-H bond in the benzene ring of N-arylpyrazoles
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The direct carbonylation of C-H bonds in the benzene ring of N-phenylpyrazoles via catalysis by ruthenium or rhodium complexes is described. The reaction of N-phenylpyrazoles with carbon monoxide and ethylene in the presence of Ru3(CO)12 or Rh4(CO)12 resulted in the site-selective carbonylation of the ortho C-H bonds in the benzene ring to give the corresponding ethyl ketones. A variety of functional groups on the benzene ring can be tolerated. N-Phenylpyrazoles have higher reactivities than would be expected, based on the pKa values of the conjugate acid of pyrazole. The choice of solvent for this reaction is significant, and N, N-dimethylacetamide (DMA) gives the best result.
- Asaumi, Taku,Matsuo, Takuya,Fukuyama, Takahide,Ie, Yutaka,Kakiuchi, Fumitoshi,Chatani, Naoto
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- Mechanistic aspects of Submol % copper-catalyzed C-N cross-coupling
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Carbon-nitrogen bond formation can be catalyzed by copper in very low concentrations (≈100 ppm), with mechanistic features that are distinct from those in the high-concentration regime. The reaction was studied by initial rate kinetics, competitive Hammett studies, and DFT calculations. The deprotonation of the model nucleophile, pyrrole, is limited by mass transfer with the heterogeneous base. The positive reaction order in dimethylethylenediamine was explained by this reagent working not only as a ligand to Cu, but also as a facilitator for mass transfer. The selectivity-determining step in the competitive Hammett study is oxidative addition. Alternative mechanisms for this step, such as single-electron transfer, atom transfer, or σ-bond metathesis, can be excluded based on the observed Hammett behavior and DFT calculations. A dash of copper: The submol % copper catalyzed C-N bond formation has been studied by kinetic and DFT methods. DMEDA acts as a facilitator for mass transfer, as well as a ligand. Oxidative addition leads to a Cu III intermediate undergoing facile reductive elimination.
- Larsson, Per-Fredrik,Wallentin, Carl-Johan,Norrby, Per-Ola
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- Selective C-arylation of free (NH)-heteroarenes via catalytic C-H bond functionalization
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A new system for palladium-catalyzed arylation of a broad spectrum of free (NH)-heteroarenes has been developed (indole, pyrrole, pyrazole, 2-phenylimidazole, imidazole, benzimidazole, and purine). Remarkable selectivity has been achieved in the presence of MgO base, providing single C-arylation products, while no N-arylation and no bis-arylation products have been detected. In the case of free imidazole, exclusive C-4 arylation may be switched to exclusive 2-arylation by the addition of CuI to the Pd/Ph3P/MgO system. When free aryl-(NH)-azoles are desired, direct arylation eliminates three steps in comparison to standard methods, including N-protection, stoichiometric metalation or halogenation, and N-deprotection. Copyright
- Sezen, Bengue,Sames, Dalibor
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- Pyrrole-2-carbohydrazides as Ligands for Cu-Catalyzed Amination of Aryl Halides with Amines in Pure Water
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Pyrrole-2-carbohydrazides were synthesized and found to be novel and efficient ligands for the Cu-catalyzed amination of aryl halides with amines in pure water with high yields. A variety of aryl bromides or iodides could be aminated, promoted by the CuI/N'-phenyl-1H-pyrrole-2-carbohydrazide (L13) system, under microwave irradiation or conventional heating without the protection by an inert gas.
- Xie, Jianwei,Zhu, Xinhai,Huang, Manna,Meng, Fei,Chen, Weiwei,Wan, Yiqian
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- N-phenylation of azole derivatives by triphenylbismuth derivatives/cupric acetate
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Triphenylbismuth diacetate reacts with various N-H containing heteroarenes in the presence of a catalytic amount of copper diacetate to afford moderate to good yields of the N-phenylheteroarenes.
- Fedorov, Alexey Yu,Finet, Jean-Pierre
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- Anti-inflammatory effect of a new piperazine derivative: (4-methylpiperazin-1-yl)(1-phenyl-1H-pyrazol-4-yl)methanone
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Aims: This study investigates the anti-nociceptive and anti-inflammatory effects of new piperazine compound (LQFM182) as well as the toxicity acute in vitro. Main methods: To evaluate the anti-nociceptive activity, the acetic acid-induced abdominal writhing test, tail flick test and formalin-induced pain test were used. The anti-inflammatory activity was evaluated using the models of paw oedema and pleurisy induced by carrageenan and some inflammatory parameters were evaluated, including cell migration, myeloperoxidase enzyme activity and the levels of TNF-α and IL-1β cytokines in pleural exudate. The acute oral systemic toxicity of LQFM182 in mice was evaluated through the neutral red uptake (nru) assay. Key findings: LQFM182 (50, 100 or 200?mg/kg, p.o.) decreased the number of writhings induced by acetic acid in a dose-dependent manner, and an intermediate dose (100?mg/kg, p.o.) reduced the paw licking time of animals in the second phase of the formalin test. Furthermore, LQFM182 (100?mg/kg, p.o.) reduced oedema formation at all hours of the paw oedema induced by carrageenan test and in pleurisy test reduced cell migration from the reduction of polymorphonuclear cells, myeloperoxidase enzyme activity and the levels of pro-inflammatory cytokines IL-1β and TNF-α. Therefore, it was classified in GHS category 300?50??2000?mg/kg. Significance: Reduction of the TNF-α and IL-1β levels.
- Batista, Daniel C.,Silva, Daiany P. B.,Florentino, Iziara F.,Cardoso, Carina S.,Gon?alves, Merita P.,Valadares, Marize C.,Li?o, Luciano M.,Sanz, Germán,Vaz, Boniek G.,Costa, Elson A.,Menegatti, Ricardo
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- Ball milling of copper powder under dry and surfactant-assisted conditions—on the way towards Cu/Cu2O nanocatalyst
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Samples of copper powder was milled with varied grinding frequencies in the presence of various organic agents (oleylamine, ethylene glycol or dimethyl sulfoxide) or without additives. The effects of experimental conditions were investigated by X-ray diff
- Musza, Katalin,Szabados, Márton,ádám, Adél Anna,Kónya, Zoltán,Kukovecz, ákos,Sipos, Pál,Pálinkó, István
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- Novel choline analog 2-(4-((1-phenyl-1H-pyrazol-4-yl)methyl)piperazin-1-yl)ethan-1-ol produces sympathoinhibition, hypotension, and antihypertensive effects
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The search for new drugs remains an important focus for the safe and effective treatment of cardiovascular diseases. Previous evidence has shown that choline analogs can offer therapeutic benefit for cardiovascular complications. The current study investigates the effects of 2-(4-((1-phenyl-1H-pyrazol-4-yl)methyl)piperazin-1-yl)ethan-1-ol (LQFM032) on cardiovascular function and cholinergic-nitric oxide signaling. Synthesized LQFM032 (0.3, 0.6, or 1.2?mg/kg) was administered by intravenous and intracerebroventricular routes to evaluate the potential alteration of mean arterial pressure, heart rate, and renal sympathetic nerve activity of normotensive and hypertensive rats. Vascular function was further evaluated in isolated vessels, while pharmacological antagonists and computational studies of nitric oxide synthase and muscarinic receptors were performed to assess possible mechanisms of LQFM032 activity. The intravenous and intracerebroventricular administration of LQFM032 elicited a temporal reduction in mean arterial pressure, heart rate, and renal sympathetic nerve activity of rats. The cumulative addition of LQFM032 to isolated endothelium-intact aortic rings reduced vascular tension and elicited a concentration-dependent relaxation. Intravenous pretreatment with L-NAME (nitric oxide synthase inhibitor), atropine (nonselective muscarinic receptor antagonist), pirenzepine, and 4-DAMP (muscarinic M1 and M3 subtype receptor antagonist, respectively) attenuated the cardiovascular effects of LQFM032. These changes may be due to a direct regulation of muscarinic signaling as docking data shows an interaction of choline analog with M1 and M3 but not nitric oxide synthase. Together, these findings demonstrate sympathoinhibitory, hypotensive, and antihypertensive effects of LQFM032 and suggest the involvement of muscarinic receptors.
- Menegatti, Ricardo,Carvalho, Flávio S.,Li?o, Luciano M.,Villavicencio, Bianca,Verli, Hugo,Mour?o, Aline A.,Xavier, Carlos H.,Castro, Carlos H.,Pedrino, Gustavo R.,Franco, Octavio L.,Oliveira-Silva, Iransé,Ashpole, Nicole M.,Silva, Osmar Nascimento,Costa, Elson A.,Fajemiroye, James O.
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- Copper nanoparticle decorated organically modified montmorillonite (OMMT): An efficient catalyst for the N-arylation of indoles and similar heterocycles
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A highly active ligand-free and efficient copper nanoparticle decorated OMMT catalyzed N-arylation of NH-heterocycles, i.e. indole, imidazole, benzimidazole, pyrrole, carbazole has been demonstrated.
- Talukdar, Dhrubajyoti,Das, Gautam,Thakur, Suman,Karak, Niranjan,Thakur, Ashim J.
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- N-arylation of heterocycles catalyzed by activated-copper in pure water
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N-arylation Activated-copper powder is an efficient catalyst for the N-arylation of heterocycles with aryl halides and can be reused several times. The reactions can proceed smoothly in water by using LiOH as base and give the corresponding products in good yields. The protocol shows good tolerance toward various functional groups.
- Yang, Qichao,Wang, Yufang,Lin, Dong,Zhang, Mingjie
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- Anxiolytic-like effect of 2-(4-((1-phenyl-1H-pyrazol-4-yl)methyl)piperazin-1-yl)ethan-1-ol is mediated through the benzodiazepine and nicotinic pathways
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In this study, we proposed the design, synthesis of a new compound 2-(4-((1-phenyl-1H-pyrazol-4-yl)methyl)piperazin-1-yl)ethan-1-ol (LQFM032), and pharmacological evaluation of its anxiolytic-like effect. This new compound was subjected to pharmacological screening referred to as Irwin test, prior to sodium pentobarbital-induced sleep, open-field and wire tests. The anxiolytic-like effect of this compound was evaluated using elevated plus maze and light–dark box tests. In addition, the mnemonic activity was evaluated through step-down test. In sodium pentobarbital-induced sleep test, LQFM032 decreased latency and increased duration of sleep. In the open-field test, LQFM032 altered behavioral parameter, that suggested anxiolytic-like activity, as increased in crossings and time spent at the center of open field. In the plus maze test and light–dark box test, the LQFM032 showed anxiolytic-like activity, increased entries and time spent on open arms, and increased in number of transitions and time spent on light area, respectively. Those effects was antagonized by flumazenil but not with 1-(2-Methoxyphenyl)-4-(4-phthalimidobutyl)piperazine (NAN-190). The LQFM032 did not alter mnemonic activity. Moreover, the anxiolytic-like activity of LQFM032 was antagonized by mecamylamine. In summary, LQFM032 showed benzodiazepine and nicotinic pathways mediated anxiolytic-like activity without altering the mnemonic activity.
- Brito, Adriane F.,Fajemiroye, James O.,Neri, Hiasmin F. S.,Silva, Dayane M.,Silva, Daiany P. B.,Sanz, Germán,Vaz, Boniek G.,de Carvalho, Flávio S.,Ghedini, Paulo C.,Li?o, Luciano M.,Menegatti, Ricardo,Costa, Elson A.
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- Copper iodide as a recyclable catalyst for Buchwald N-arylation
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An experimentally simple, efficient, and inexpensive catalyst system was developed for the N-arylation of indole, substituted indoles, pyrazole, imidazole, benzamide, morpholine, benzimidazole, thiobenzamide, aniline, benzylaniline, octylaniline, heptylaniline, and cyclohexylaniline with aryl iodides and bromides by using CuI as catalyst, trans-1,2-diaminocyclohexane (L1) as ligand, K2CO3 as base, and water as solvent at 80 °C. The yields were excellent, and the catalytic system was recyclable up to four times without loss of catalytic activity. Arylated amines are green protocol that avoids hazardous and moisture-sensitive catalysts. The catalytic system can be recycled up to four times without loss of catalytic activity. Copyright
- Swapna, Kokkirala,Murthy, Sabbavarapu Narayana,Nageswar, Yadavalli Venkata Durga
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- Tamarix gallica leaf extract mediated novel route for green synthesis of CuO nanoparticles and their application for N-arylation of nitrogen-containing heterocycles under ligand-free conditions
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We report the green synthesis of CuO nanoparticles (CuO NPs) using Tamarix gallica leaf extract and their catalytic activity for N-arylation of nitrogen-containing heterocycles with aryl halides under ligand-free conditions. Tamarix gallica leaves are used as a bio-material for the first time as reducing agent. The green synthesized CuO NPs was characterized using the powder XRD, TEM, UV-vis and FT-IR. This method offers several advantages, viz. high yields, simple methodology, recyclability of the catalyst and a simple workup procedure.
- Nasrollahzadeh, Mahmoud,Sajadi, S. Mohammad,Maham, Mehdi
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- A Highly Active, Recyclable and Cost-Effective Magnetic Nanoparticles Supported Copper Catalyst for N-arylation Reaction
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Abstract: The immobilization of a copper complex by covalent anchoring of 2-hydroxybenzophenone on the surface of amine-functionalized magnetic nanoparticles was reported. The structure and morphology of the catalyst was characterized by different techniques such as Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), transmission electron micrograph (TEM), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), vibrating sample magnetometer (VSM) and inductively coupled plasma (ICP) spectroscopy. This efficient and cost effective catalyst was applied in the N-arylation reaction and the products were obtained in good to excellent yields in short reaction times. The cost-effective catalyst demonstrated high stability, which could be facilely separated from the reaction mixture by applying an external magnet and recycled at least four times with only a slight decrease in its activity. Graphic Abstract: [Figure not available: see fulltext.]
- Zahedi, Razieh,Asadi, Zahra,Firuzabadi, Fahimeh Dehghani
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- Ruthenium-catalysedmeta-selective CAr-H bond alkylationviaa deaminative strategy
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The use of aliphatic amines as alkylating reagents in organic synthesisviaC-N bond activation remains underdeveloped. We herein describe a novel ruthenium-catalysed and directing-group assisted protocol for the synthesis ofmeta-alkylated arenesviadual C-H and C-N activation. Bench-stable and easily handled redox-active Katritzky pyridinium salts derived from abundant amines and amino acid species were used as alkyl radical precursors. This catalytic reaction could accommodate a broad range of functional groups and provide access to variousmeta-alkylated products.
- Zhu, Ze-Fan,Chen, Guang-Le,Liu, Feng
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- Anti-inflammatory and antinociceptive activity profile of a new lead compound – LQFM219
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LQFM219 is a molecule designed from celecoxibe (COX-2 inhibitor) and darbufelone (inhibitor of COX-2 and 5-LOX) lead compounds through a molecular hybridisation strategy. Therefore, this work aimed to investigate the antinociceptive and anti-inflammatory activities of this new hybrid compound. The acute oral systemic toxicity of LQFM219 was evaluated via the neutral red uptake assay. Acetic acid-induced abdominal writhing and CFA-induced mechanical hyperalgesia were performed to evaluate the antinociceptive activity, and the anti-oedematogenic activity was studied by CFA-induced paw oedema and croton oil-induced ear oedema. Moreover, the acute anti-inflammatory activity was determined by carrageenan-induced pleurisy. In addition, cell migration, myeloperoxidase enzyme activity, and TNF-α and IL-1β levels were determined in pleural exudate. Moreover, a redox assay was conducted using electroanalytical and DPPH methods. The results demonstrated that LQFM219 was classified as GHS category 4, and it showed better free radical scavenger activity compared to BHT. Besides, LQFM219 decreased the number of writhings induced by acetic acid and the response to the mechanical stimulus in the CFA-induced mechanical hyperalgesia test. Furthermore, LQFM219 reduced oedema formation, cell migration, and IL-1β and TNF-α levels in the pleural cavity and inhibited myeloperoxidase enzyme activity. Thus, our study provides that the new pyrazole derivative, LQFM219, demonstrated low toxicity, antinociceptive and anti-inflammatory potential in vitro and in vivo.
- Cardoso, Carina S.,Costa, Elson A.,Florentino, Iziara F.,Leite, Jacqueline A.,Menegatti, Ricardo,Silva, Andreia L. P.,Valadares, Marize C.,Vaz, Boniek G.,da Silva, Artur C. G.,da Silva, Daiany P. B.,de S. Gil, Eric,Galv?o, Gustavo M.,Li?o, Luciano M.,Sabino, José R.,Sanz, Germán
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- Palladium-catalyzed acyloxylation of 2-substituted 1,2,3-triazoles via direct sp2 C-H bond activation
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The palladium-catalyzed acyloxylation of 2-substituted 1,2,3-triazoles with acids via direct sp2 C-H bond activation is described. This reaction is applied to a wide variety of 2-substituted 1,2,3-triazoles and exhibits excellent functional group tolerance. The route is found to be efficient for the preparation of 2-substituted 1,2,3-triazole derivatives.
- Wang, Zechao,Kuang, Chunxiang
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- Kinetic investigation of a ligand-accelerated sub-mol % copper-catalyzed C-N cross-coupling reaction
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Unique ligand acceleration: A kinetic investigation of the copper-catalyzed C-N cross-coupling in the sub-mol % range reveals an exceptional ligand dependence. Dimethylethylenediamine (DMEDA) is unique in promoting this reaction, and even at a ratio of >2000:1 relative to the catalyst, the reaction order is still positive in DMEDA. This discovery allowed the development of milder reaction conditions. The reaction order in copper becomes zero at very low concentration. Copyright
- Larsson, Per-Fredrik,Bolm, Carsten,Norrby, Per-Ola
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- Domino N-/C-Arylation via In Situ Generation of a Directing Group: Atom-Efficient Arylation Using Diaryliodonium Salts
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Both aryl components of diaryliodonium salts can be used in a domino one-pot reaction via in situ generation of a directing group. A number of heterocycles undergo N-arylation which is followed by ruthenium-catalyzed C-arylation. Notably the reaction extends well to unsymmetrical diaryliodonium salts with a number of highly selective examples shown.
- Teskey, Christopher J.,Sohel, Shariar M. A.,Bunting, Danielle L.,Modha, Sachin G.,Greaney, Michael F.
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- Anxiolytic- and antidepressant-like effects of new phenylpiperazine derivative LQFM005 and its hydroxylated metabolite in mice
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The current treatments available for anxiety and depression are only palliative. Full remission has remained elusive, characterizing unmet medical needs. In the scope of an academic drug discovery program, we describe here the design, synthesis, in vitro metabolism prediction and pharmacological characterization of a new piperazine compound, 1-(4-methoxyphenyl)?4-((1-phenyl-1H-pyrazol-4-yl)methyl)piperazine (LQFM005), and of its main putative metabolite, 4-(4-((4-(4-methoxyphenyl)piperazin-1-yl)methyl)? 1H-pyrazol-1-yl)phenol (LQFM235). The production of the metabolite was initially performed by in vitro biotransformation of LQFM005 using Aspergillus candidus and then by chemical synthesis. Oral administration of either 12 or 24 μmol/kg LQFM005 to mice did not affect spontaneous locomotor activity but increased the time spent in the center of the open field. Both LQFM005 and LQFM235 (24 μmol/kg) increased the time spent by the mice in the open arms of the elevated plus maze (EPM), a good indication of anxiolytic-like effect, and decreased the immobility time in the forced swimming test (FST), suggesting an antidepressant-like effect. The previous administration of WAY-100635 (a 5-HT1A antagonist) abolished the effects of LQFM005 in both EPM and FST. Binding experiments showed that LQFM005 and its metabolite bind to the 5-HT1A receptor with a moderate affinity (Ki around 5–9 μM). The two compounds are relatively safe, as indicated by cytotoxic assessment using the 3T3 fibroblast cell line and estimated LD50 around 600 mg/kg. In conclusion, oral administration of the newly synthesized phenylpiperazines produced anxiolytic- and antidepressant-like effects in behavioral tests, putatively in part through the activation of 5-HT1A receptors.
- Moreira, Lorrane Kelle da Silva,Silva, Rafaela Ribeiro,da Silva, Dayane Moreira,Mendes, Mirella Andrade Silva,de Brito, Adriane Ferreira,de Carvalho, Flávio Souza,Sanz, Germán,Rodrigues, Marcella Ferreira,da Silva, Artur Christian Garcia,Thomaz, Douglas Vieira,de Oliveira, Valéria,Vaz, Boniek Gontijo,Li?o, Luciano Morais,Valadares, Marize Campos,Gil, Eric de Souza,Costa, Elson Alves,No?l, Fran?ois,Menegatti, Ricardo
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- L-Proline N-oxide dihydrazides as an efficient ligand for cross-coupling reactions of aryl iodides and bromides with amines and phenols
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A novel catalytic system based on L-proline N-oxide/CuI was developed and applied to the cross-coupling reactions of various N- and O- nucleophilic reagents with aryl iodides and bromides. This strategy featured in the employment of an-proline derived dihydrazides N-oxide compound as the superior supporting ligand. By using this protocol, a variety of products, including N-arylimidazoles, N-arylpyrazoles, N-arylpyrroles, N-arylamines, and aryl ethers, were synthesized with up to 99% yield.
- Ding, Zhiqiang,Nie, Nan,Chen, Tian,Meng, Lingxin,Wang, Gongshu,Chen, Zhangpei,Hu, Jianshe
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supporting information
(2020/12/21)
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- Copper pyrithione (CuPT)-catalyzed/mediated amination and thioarylation of (hetero)aryl halides: A competition
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A facile method for the synthesis of N-arylheterocycles and di(hetero)aryl sulfides under mild condition is described. In these transformations, copper pyrithione (CuPT) was used as the copper catalyst for C─N coupling, while served as catalyst and coupled partner for C─S coupling with high yields and broad substrate tolerance. The S-arylation process was also utilized for the construction of valuable bioactive 2-sulfonylpyridine 1-oxide derivatives.
- Cao, Ningtao,Song, Bao,Xie, Jianwei,Zhang, Jie
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- NaBHT Generated in Situ from BHT and NaO tBu: Crystallographic Characterization and Applications in Buchwald-Hartwig Amination
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NaBHT is a valuable medium-strength base useful for many applications, particularly for Buchwald-Hartwig coupling. The structures of solvent-free NaBHT and its solvates with Et2O, THF, tBuOH, and a THF/tBuOH mixture were established using single-crystal X-ray diffraction. While [NaBHT·Et2O]2 adopts a dimeric structure and crystallizes in a monoclinic cell, [NaBHT·THF]3, [NaBHT·tBuOH]3, and [NaBHT·(THF-tBuOH)]3 prefer a trimeric structure and crystallize in cubic cells. Solvent-free [NaBHT]n is different from solvated NaBHT and from other known sodium phenolates. It is an inorganic polymer that crystallizes in an orthorhombic cell, with a NaO core spreading in the [1 0 0] direction. Agostic interactions of the tBu group hydrogens with Na, which were confirmed for all structures, may help explain the reductive properties of NaBHT. Further, interactions of BHT with tBuONa in solution and in the solid state were examined, reveraling that NaBHT does not need to be prepared from pyrophoric NaH or metallic Na every time. Instead, it can be generated efficiently in or ex situ using NaOtBu in solution or with only a stoichiometric amount of solvent to assist in bringing the reactants together. Application of this methodology was demonstrated with the efficient, solvent-free, and Pd-catalyzed C-N coupling with Pd(NHC) catalysts.
- Semeniuchenko, Volodymyr,Ovens, Jeffrey S.,Braje, Wilfried M.,Organ, Michael G.
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p. 3276 - 3290
(2021/10/12)
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- Photo-induced thiolate catalytic activation of inert Caryl-hetero bonds for radical borylation
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Substantial effort is currently being devoted to obtaining photoredox catalysts with high redox power. Yet, it remains challenging to apply the currently established methods to the activation of bonds with high bond dissociation energy and to substrates with high reduction potentials. Herein, we introduce a novel photocatalytic strategy for the activation of inert substituted arenes for aryl borylation by using thiolate as a catalyst. This catalytic system exhibits strong reducing ability and engages non-activated Caryl–F, Caryl–X, Caryl–O, Caryl–N, and Caryl–S bonds in productive radical borylation reactions, thus expanding the available aryl radical precursor scope. Despite its high reducing power, the method has a broad substrate scope and good functional-group tolerance. Spectroscopic investigations and control experiments suggest the formation of a charge-transfer complex as the key step to activate the substrates.
- K?nig, Burkhard,Wang, Hua,Wang, Shun
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supporting information
p. 1653 - 1665
(2021/06/17)
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- A post-synthetically modified metal-organic framework for copper catalyzed denitrative C-N coupling of nitroarenes under heterogeneous conditions
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Here we report, for the first time, the Ullmann C-N coupling reaction of nitroarenes which is achieved by using a copper containing metal-organic framework (MOF) catalyst under heterogenous conditions. The ready availability of nitroarenes and their low cost have made them ideal replacements for haloarenes as electrophilic coupling partners. Notably, the reaction protocol suppresses the by-product formation in the catalytic reaction. The catalyst has been designed and synthesized by two step post-synthesis functionalization of a MOF,viz.dabco MOF-1 with a -NH2functional group (DMOF-NH2). In the post-synthetic treatment, salicylaldehyde has been used for organic modification first and then copper(ii) was successfully incorporated onto the inner surface of the porous material. The hybrid porous solid thus obtained has been employed in the catalytic C-N coupling reaction of nitroarenes with a wide variety of amines under heterogeneous conditions, which displayed very high turnover frequencies (TOF) in catalytic reactions attesting its efficacy towards theN-arylation reaction.
- Maity, Tanmoy,Ghosh, Pameli,Das, Soma,Saha, Debraj,Koner, Subratanath
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p. 5568 - 5575
(2021/04/06)
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- Unveiling Potent Photooxidation Behavior of Catalytic Photoreductants
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We describe a photocatalytic system that reveals latent photooxidant behavior from one of the most reducing conventional photoredox catalysts, N-phenylphenothiazine (PTH). This aerobic photochemical reaction engages difficult to oxidize feedstocks, such as benzene, in C(sp2)-N coupling reactions through direct oxidation. Mechanistic studies are consistent with activation of PTH via photooxidation and with Lewis acid cocatalysts scavenging inhibitors inextricably formed in this process.
- Targos, Karina,Williams, Oliver P.,Wickens, Zachary K.
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supporting information
p. 4125 - 4132
(2021/04/07)
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- Cu(I)–N-heterocyclic carbene-catalyzed base free C–N bond formation of arylboronic acids with amines and azoles
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A new N-heterocyclic carbene (NHC) precursor of imidazolium chloride and its corresponding Cu(I)–NHC complex 1 was synthesized. The complex 1 was found to be a highly effective catalyst for Chan-Evans-Lam coupling of arylboronic acid with amines and azoles (including imidazole, pyrazole and triazole), without addition of base at room temperature. Various substituents on three substrates can be tolerated, giving the desired coupling products in good to excellent yields (62–94%). The method is practical and offers an alternative to the corresponding copper-catalyzed Chan-Evans-Lam process for the construction of C–N bonds.
- Zhang, Maoyuan,Xu, Zengbing,Shi, Dabin
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- Cu(OAc)2-porphyrins as an efficient catalytic system for base-free, nature mimicking Chan–Lam coupling in water
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The use of porphyrins as ligands in organic synthesis reveals the natural process, because these are the constituent motifs of catalysts in many bio-organic reactions. This article presents the synthesis of two N-pincer tetradentate porphyrins; tetrasodium meso-tetra(p-sulfonatophenyl)phorphyrin (H2TSTpSPP) and meso-tetra(m-carboxyphenyl)porphyrin (H2TmCPP), and study on their aptness for Cu-catalyzed C–N coupling reactions of arylboronic acids and amines (Chan–Lam coupling reaction) in water under external base free conditions. The porphyrins and Chan–Lam coupling products were well characterized by their spectral analysis. The high product yields, application of nature-inspired conditions, large extent of substrates, ease of making and handling the ligands, avoidance of base, and use of water as reaction media are the attractive attributes of this finding.
- Venkateswarlu, Katta,Rao, Kanusu Umamaheswara
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- Meta-dehydrogenative alkylation of arenes with ethers, ketones, and esters catalyzed by ruthenium
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A meta-dehydrogenative alkylation of arenes with cyclic ethers, ketones, and esters catalyzed by ruthenium is achieved in the presence of a di-tert-butyl peroxide (DTBP) oxidant. Interestingly, when quinoline and isoquinoline are employed as the directing group, or a chain ether as alkylation reagent, the system produces Minisci reaction products. Mechanistic study indicates that meta-dehydrogenative alkylation is a radical process initiated by DTBP with the assistance of a CAr-Ru bond ortho/para-directing effect.
- Li, Gang,Gao, Yuan,Jia, Chunqi,Wang, Shichong,Yan, Bingxu,Fang, Yu,Yang, Suling
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supporting information
p. 8758 - 8763
(2020/12/02)
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- PYRAZOLYL COMPOUNDS AND METHODS OF USE THEREOF
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Compounds having activity as chemotherapeutic agents are provided. The compounds have the following structure (I): or a pharmaceutically acceptable salt, stereoisomer, isotopic form or prodrug thereof, wherein R1a, R1b, R1c, R1d, L, and are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods for treating cancer (e.g., hematological cancers) are also provided.
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Paragraph 0690-0693
(2020/05/14)
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- N -Arylation of (hetero)arylamines using aryl sulfamates and carbamates via C-O bond activation enabled by a reusable and durable nickel(0) catalyst
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An effective and general aryl amination protocol has been developed using a magnetically recoverable Ni(0) based nanocatalyst. This new stable catalyst was prepared on Fe3O4@SiO2 modified by EDTA and investigated by FT-IR, EDX, TEM, XRD, DLS, FE-SEM, XPS, NMR, TGA, VSM, ICP and elemental analysis techniques. The reaction proceeded via carbon-oxygen bond cleavage of (hetero)aryl carbamates and sulfamates under simple and mild conditions without the use of any external ligands. This method demonstrated functional group tolerance in the N-arylation of various nitrogen-containing compounds as well as aliphatic amines, anilines, pyrroles, pyrazoles, imidazoles, indoles, and indazoles with good to excellent yields. Furthermore, the catalyst could be easily recovered by using an external magnetic field and directly reused at least six times without notable reduction in its activity. This journal is
- Dindarloo Inaloo, Iman,Majnooni, Sahar,Eslahi, Hassan,Esmaeilpour, Mohsen
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p. 13266 - 13278
(2020/10/07)
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- Design, synthesis and pharmacological assessment of new pyrazole compounds
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Aims: This study investigated the antinociceptive and anti-inflammatory effects of new pyrazole compounds LQFM011(5), LQFM043(6) and LQFM044(7) as well as the mechanisms of action and acute in vitro toxicity. Main methods: The antinociceptive activity was evaluated using the acetic acid-induced abdominal writhing test, formalin-induced pain test and the Randall–Selitto test. The anti-inflammatory activity was evaluated using models of paw oedema and pleurisy induced by carrageenan; cell migration, the levels of tumour necrosis factor α (TNF-α) and myeloperoxidase (MPO) enzyme activity were evaluated. In addition, the ability to inhibit phospholipase A2 (PLA2) in vitro and docking in PLA2 were used. Acute oral systemic toxicity in mice was evaluated through the neutral red uptake assay. Key findings: The synthesised compounds (5–7), delivered via gavage (p.o.) at 70, 140 or 280 μmol/kg, decreased the number of writhings induced by acetic acid; the three compounds (280 μmol/kg p.o.) reduced the paw licking time in the first and second phase of the formalin test and decreased the nociceptive threshold variation in the Randall–Selitto test. Furthermore, this dose reduced oedema formation, leucocyte migration (specifically through reduction in polymorphonuclear cell movement) and increased mononuclear cells. MPO activity and the levels of pro-inflammatory cytokines TNF-α were decreased. Evaluation of PLA2 inhibition via the docking simulation revealed more interactions of LQFM043R(6) and LQFM044(7), data that corroborated the half-maximal inhibitory concentration (IC50) of PLA2 inhibition in vitro. Therefore, LQFM011(5), LQFM043(6) and LQFM044(7) were classified with the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) as category 4.
- Costa, Elson A.,Florentino, Iziara F.,Li?o, Luciano M.,Menegatti, Ricardo,Oliveria, Jordana C.,Pazini, Francine,Sanz, Germán,Silva, Daiany P. B.,Valadares, Marize C.,Vaz, Boniek G.,Verli, Hugo,Villavicencio, Bianca,da Silva, Lidya C.,de Carvalho, Flávio S.,dos Santos, Fernanda Cristina Alcantara,dos Santos, Thaís Rosa Marques
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p. 915 - 928
(2020/07/21)
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- Design, synthesis, and evaluation of indeno[2,1-c]pyrazolones for use as inhibitors against hypoxia-inducible factor (HIF)-1 transcriptional activity
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HIF-1 is regarded as a promising target for the drugs used in cancer chemotherapy, and creating readily accessible templates for the development of synthetic drug candidates that could inhibit HIF-1 transcriptional activity is an important pursuit. In this study, indeno[2,1-c]pyrazolones were designed as readily available synthetic inhibitors of HIF-1 transcriptional activity. Nine compounds were synthesized in 4–5 steps from commercially available starting materials. In evaluations of the ability to inhibit the hypoxia-induced transcriptional activity of HIF-1, compound 3c showed a higher level compared with that of known inhibitor, YC-1. The compound 3c suppressed HIF-1α protein accumulation without affecting the levels of HIF-1α mRNA.
- Fuse, Shinichiro,Kadonosono, Tetsuya,Kizaka-Kondoh, Shinae,Kuchimaru, Takahiro,Nakamura, Hiroyuki,Sato, Shinichi,Suzuki, Kensuke,Ueda, Hiroki
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supporting information
(2019/11/26)
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- C?N Cross-Coupling Reactions Under Mild Conditions Using Singlet Di-Radical Nickel(II)-Complexes as Catalyst: N-Arylation and Quinazoline Synthesis
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Herein we report a cost-effective synthetic approach for C?N cross-coupling reactions of a broad array of nitrogen nucleophiles and aryl halides under mild conditions. These reactions are catalyzed by an inexpensive, air-stable, earth-abundant and easy-to-prepare singlet di-radical nickel(II)-catalyst containing two antiferromagnetically coupled single-electron oxidized diiminosemiquinonato type ligands. This protocol provides an alternative method for C?N cross-coupling reactions avoiding nickel(0)/nickel(II) or nickel(I)/nickel(III) redox processes via cooperative participation of metal and ligand-centered redox events. Besides a wide range of N-arylation reactions, by judicious choice of aryl halides and nitrogen nucleophiles the synthesis of a variety of polysubstituted quinazolines has been achieved in moderate to good yields under relatively mild reaction conditions. Our catalyst has been found to be almost equally effective in quinazoline synthesis via C?N cross-coupling of (i) 2-bromobenzylamine with benzamide, and (ii) 2-bromobenzylbromide with amidine. Control experiments and DFT studies were performed to improve the understanding of the cooperative participation of ligand and metal (nickel)-centered redox events during oxidative addition/reductive elimination processes of the catalytic cycle and to shed light on the plausible mechanistic pathway of the C?N cross-coupling reactions. (Figure presented.).
- Sikari, Rina,Sinha, Suman,Chakraborty, Gargi,Das, Siuli,van Leest, Nicolaas Petrus,Paul, Nanda D.
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supporting information
p. 4342 - 4353
(2019/08/21)
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- Iron-Catalyzed/Mediated C-N Bond Formation: Competition between Substrate Amination and Ligand Amination
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Iron catalyzed carbon-nitrogen bond formation reactions of a wide variety of nucleophiles and aryl halides using well-defined iron-complexes featuring redox noninnocent 2-(arylazo)-1,10-phenanthroline (L1) ligands are reported. Besides substrate centered C-N coupling, C-N bond formation reactions were also observed at the ortho- and para-positions of the phenyl ring of the coordinated azo-aromatic scaffolds affording new tetradentate ligands, 2-N-aryl-(2-arylazo)-1,10-phenanthroline (L2), and tridentate ligands, 4-N-aryl-(2-arylazo)-1,10-phenanthroline (L3), respectively. Control experiments and mechanistic studies reveal that the complex [FeL1Cl2] (1) undergoes in situ reduction during the catalytic reaction to produce the monoanionic complex [1]-, which then acts as the active catalyst. The metal (iron) and the coordinated ligand were found to work in a cooperative manner during the transfer processes involved in the fundamental steps of the catalytic cycle. Detailed experimental and theoretical (DFT) studies were performed to get insight into the competitive substrate versus ligand centered amination reactions.
- Sinha, Suman,Sikari, Rina,Sinha, Vivek,Jash, Upasona,Das, Siuli,Brand?o, Paula,Demeshko, Serhiy,Meyer, Franc,De Bruin, Bas,Paul, Nanda D.
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p. 1935 - 1948
(2019/01/25)
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- Ruthenium-Catalyzed ortho- And meta-H/D Exchange of Arenes
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Ruthenium-catalyzed aromatic H/D exchange in [D4]acetic acid has been developed. By using N-heteroarenes as directing groups, both ortho and meta positions are selectively deuterated with high levels of D incorporation. Moreover, this strategy provides an alternative way to achieve meta-C-H activation.
- Zhao, Liang-Liang,Liu, Wei,Zhang, Zengyu,Zhao, Hongyan,Wang, Qi,Yan, Xiaoyu
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supporting information
p. 10023 - 10027
(2019/12/24)
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- Nickel-catalyzed reductive defunctionalization of esters in the absence of an external reductant: Activation of C-O bonds
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The nickel-catalyzed reductive cleavage of esters in the absence of an external reductant, which involves the cleavage of an inert acyl C-O bond in O-Alkyl esters is reported. Various groups, such as N-containing heterocycles, esters, amides, and even arene rings can function as a directing group.
- Iyori, Yasuaki,Takahashi, Kenjiro,Yamazaki, Ken,Ano, Yusuke,Chatani, Naoto
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supporting information
p. 13610 - 13613
(2019/11/14)
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- Ruthenium-Catalyzed Reductive Cleavage of Unstrained Aryl-Aryl Bonds: Reaction Development and Mechanistic Study
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Cleavage of carbon-carbon bonds has been found in some important industrial processes, for example, petroleum cracking, and has inspired development of numerous synthetic methods. However, nonpolar unstrained C(aryl)-C(aryl) bonds remain one of the toughest bonds to be activated. As a detailed study of a fundamental reaction mode, here a full story is described about our development of a Ru-catalyzed reductive cleavage of unstrained C(aryl)-C(aryl) bonds. A wide range of biaryl compounds that contain directing groups (DGs) at 2,2′ positions can serve as effective substrates. Various heterocycles, such as pyridine, quinoline, pyrimidine, and pyrazole, can be employed as DGs. Besides hydrogen gas, other reagents, such as Hantzsch ester, silanes, and alcohols, can be employed as terminal reductants. The reaction is pH neutral and free of oxidants; thus a number of functional groups are tolerated. Notably, a one-pot C-C activation/C-C coupling has been realized. Computational and experimental mechanistic studies indicate that the reaction involves a ruthenium(II) monohydride-mediated C(aryl)-C(aryl) activation and the resting state of the catalyst is a η4-coordinated ruthenium(II) dichloride complex, which could inspire development of other transformations based on this reaction mode.
- Zhu, Jun,Chen, Peng-hao,Lu, Gang,Liu, Peng,Dong, Guangbin
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supporting information
p. 18630 - 18640
(2019/11/21)
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- Palladium-Catalyzed C-N Cross-Coupling of NH-Heteroarenes and Quaternary Ammonium Salts via C-N Bond Cleavage
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In this paper, we extend the substrate class of Buchwald-Hartwig amination to quaternary ammonium salts. In the presence of Pd(OAc)2 and t-BuXPhos, the coupling of aryl- or arylmethyltrimethylammonium triflates with NH-heteroarenes via C-N bond cleavage affords the desired N-aryl or N-arylmethyl heteroarenes in moderate to excellent yields.
- Chen, Hongyi,Yang, Hongqin,Li, Nutao,Xue, Xinghua,He, Ze,Zeng, Qingle
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p. 1679 - 1685
(2019/08/20)
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- Efficient N-arylation of azole compounds utilizing selective aryl-transfer TMP-iodonium(III) reagents
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It was determined that diaryliodonium(III) triflates bearing a trimethoxybenzene (TMP) auxiliary are more reactive than the reported selective aryl-transfer iodonium salts in the N-arylation of benzimidazoles and other types of azole compounds under catalytic conditions. The TMP-iodonium(III) salts can thus effectively facilitate the reaction at 50 °C or below, producing the corresponding N-arylated biaryls without the formation of TMP-derived coupling byproducts. Utilization of this TMP reagent under mild conditions would prevent the underlying problem of participation of the auxiliary group in the coupling reactions, which is observed while using the iodonium(III) salts that require elevated temperatures.
- Koseki, Daichi,Aoto, Erika,Shoji, Toshitaka,Watanabe, Kazuma,In, Yasuko,Kita, Yasuyuki,Dohi, Toshifumi
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p. 1281 - 1286
(2019/04/10)
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- Palladium catalyzed hydrodefluorination of fluoro-(hetero)arenes
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Palladium catalyzed hydrodefluorination was developed for fine-tuning the properties of fluoro-(hetero)aromatic compounds. The robust reaction can be set up in air, requires only commercially available components, and tolerates a variety of heterocycles and functionalities relevant to drug discovery. Given the prevalence of fluorine incorporation around metabolic hotspots, the corresponding deuterodefluorination reaction may prove useful for converting fluorinated libraries to deuterated analogues to suppress the oxidative metabolism by kinetic isotope effects.
- Gair, Joseph J.,Grey, Ronald L.,Giroux, Simon,Brodney, Michael A.
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supporting information
p. 2482 - 2487
(2019/04/10)
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- Methyl-α-d-glucopyranoside as Green Ligand for Selective Copper-Catalyzed N-Arylation
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In the selective N-arylation of amines or azoles with aryl halidesa-, methyl-α-d-glucopyranoside (MG) was found to function as a green ligand of copper powder. In addition, nitrogen heterocyclic amine compounds can also undergo the N-arylation coupling with heterocyclic aryl chlorides. This process allows access to a variety of aromatic amines and aryl azoles under mild reaction conditions, has good tolerance, and proceeds in moderate to high yield.
- Chen, Fengyang,Chen, Guoliang,Chen, Yuanguang,Du, Fangyu,Zhou, Qifan
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p. 4590 - 4600
(2019/12/11)
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- L -(-) -Quebrachitol as a Ligand for Selective Copper(0)-Catalyzed N-Arylation of Nitrogen-Containing Heterocycles
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l-(-)-Quebrachitol (QCT) has been found as a ligand of copper powder for selective N-arylation of nitrogen-containing heterocycles with aryl halides. Furthermore, another potential catalytic system (copper powder/QCT/t-BuOK) was successfully adapted to unactivated aryl chlorides.
- Zhou, Qifan,Du, Fangyu,Chen, Yuanguang,Fu, Yang,Sun, Wenjiao,Wu, Ying,Chen, Guoliang
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p. 8160 - 8167
(2019/06/28)
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- Copper(I)-USY as a Ligand-Free and Recyclable Catalyst for Ullmann-Type O-, N-, S-, and C-Arylation Reactions: Scope and Application to Total Synthesis
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The copper(I)-doped zeolite CuI-USY proved to be a versatile, efficient, and recyclable catalyst for various Ullmann-type coupling reactions. Easy to prepare and cheap, this catalytic material enables the arylation and heteroarylation of diverse O-, N-, S-, and C-nucleophiles under ligand-free conditions while exhibiting large functional group compatibility. The facility of this catalyst to promote C-O bond formation was further demonstrated with the total synthesis of 3-methylobovatol, a naturally occurring diaryl ether of biological relevance. From a mechanistic viewpoint, two competitive pathways depending on the nature of the nucleophile and consistent with the obtained results have been proposed.
- Garnier, Tony,Danel, Mathieu,Magné, Valentin,Pujol, Anthony,Bénéteau, Valérie,Pale, Patrick,Chassaing, Stefan
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p. 6408 - 6422
(2018/05/31)
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- Pyridazinone compounds and use thereof (by machine translation)
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The invention discloses a pyridazinone compounds, structure such as formula I shown: In the type of each substituent is as defined in the specification. The compounds of this invention have broad-spectrum antibacterial, insecticidal or acaricidal activity, the cucumber downy mildew, wheat powdery mildew, corn rust, rice blast, cucumber anthracnose and has excellent control effect. (by machine translation)
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Paragraph 0497
(2018/05/07)
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- Fipronil intermediate synthesis method
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The invention relates to a fipronil key intermediate 5-amino-1-(2,6-dichloro-4-trifluoromethyl-phenyl)-1H-pyrazole-3-carbonitrile synthesis method. 2, 6-dichloro-4-trifluoromethyl aniline and pyrazole-3-carbonitrile serve as reactive raw materials, copper acetate and glacial acetic acid serve as catalysts, t-BuONO (butyl nitrite) serves as an oxidizing agent, methanol serves as a solvent, and reaction is performed under the condition of argon. The method has the advantages of convenience in operation, fewer steps, easiness in acquiring the raw materials, less pollution, mild reaction conditions and the like.
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Paragraph 0004
(2018/05/16)
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- Dendrimer-encapsulated Cu(Π) nanoparticles immobilized on superparamagnetic Fe3O4@SiO2 nanoparticles as a novel recyclable catalyst for N-arylation of nitrogen heterocycles and green synthesis of 5-substituted 1H-tetrazoles
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In this study, dendrimer-encapsulated Cu(Π) nanoparticles immobilized on superparamagnetic Fe3O4@SiO2 nanoparticles were prepared via a multistep-synthesis. Then, the synthesized composite was fully characterized by various techniques such as fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), dynamic light scattering (DLS), UV-vis spectroscopy, energy dispersive X-ray analysis (EDX), thermogravimetric analysis (TGA) and vibration sample magnetometer (VSM). From the information gained by. FE-SEM and TEM studies it can be inferred that the particles are mostly spherical in shape and have an average size of 50?nm. Also, the amount of Cu is determined to be 0.51?mmol/g in the catalyst by inductively coupled plasma (ICP) analyzer. This magnetic nano-compound has been successfully applied as a highly efficient, magnetically recoverable and stable catalyst for N-arylation of nitrogen heterocycles with aryl halides (I, Br) and arylboronic acids without using external ligands or additives. The catalyst was also employed in a one-pot, three-component reaction for the efficient and green synthesis of 5-substituted 1H-tetrazoles using various aldehydes, hydroxylamine hydrochloride and sodium azide in water. The magnetic catalyst can be easily separated by an external magnet bar and is recycled seven times without significant loss of its activity.
- Esmaeilpour, Mohsen,Sardarian, Ali Reza,Firouzabadi, Habib
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- Cu(II) complex of phenylthiosemicarbazone: An in situ catalyst for formation of C-N bond between different N-based neucleophiles with arylboronic acids at room temperature
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We have reported here a new synthetic protocol for the formation of C-N bond catalyzed by a thiosemicarbazone complex of copper. This in situ complex has been found to be very effective for Chan-Lam C-N cross-coupling reaction of anilines and various imidazoles at room temperature. Pyrazole and 4-bromoindole were also activated for C-N bond formation by using this protocol at room temperature. This catalytic system gave good-to-excellent yield using a mixture of DMF and water as solvent in a 1:1 proportion.
- Gogoi, Nibedita,Borah, Geetika,Gogoi, Pradip K.
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- Chan-Evans-Lam Couplings with Copper Iminoarylsulfonate Complexes: Scope and Mechanism
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Copper(II) pyridyliminoarylsulfonate complexes with chloride or triflate counteranions were employed in Chan-Evans-Lam (CEL) couplings of N-nucleophiles and arylboronic acids. The complexes avoided typical side reactions in CEL couplings, and an excess of boronic acid was not required. Water was tolerated, and addition of neither base nor other additives was necessary. Primary amines, acyclic and cyclic secondary amines, anilines, aminophenol, imidazole, pyrazole, and phenyltetrazole can be quantitatively arylated at either 25 or 50 °C with 2.5 mol % of the catalyst. Reaction kinetics were investigated in detail. Kinetic and spectroscopic studies provide evidence for the formation of unproductive copper-substrate complexes. Formation of an aniline-phenylboronic acid adduct was responsible for the zero-order dependence of reaction rates on phenylboronic acid concentration. Kinetic evidence indicates that the order of reaction steps is transmetalation, nucleophile coordination, and oxidation. Couplings performed poorly with electron-deficient arylboronic acids, due to a slower Cu(II)/Cu(III) oxidation in the catalytic cycle. Photoredox catalysis partially resolved this problem, but addition of copper acetate as an external oxidant proved to be more efficient.
- Hardouin Duparc, Valérie,Bano, Guillaume L.,Schaper, Frank
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p. 7308 - 7325
(2018/07/05)
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- A N - aryl pyrazole compounds and N - aryl imidazole compound of preparation method
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The invention discloses a preparation method of an N-arylpyrazole compound and an N-arylimidazole compound. The method comprises the following steps: reacting at 20-120 DEG C for 6-48 hours by taking aryl halide and pyrazole or imidazole as substrates and copper salt as a catalyst in an organic solvent in the presence of alkali and a nitrogenous ligand under nitrogen protection; and after the reaction is finished, separating and purifying a reaction liquid to obtain the N-arylpyrazole compound or the N-arylimidazole compound. A product prepared by utilizing the method disclosed by the invention can not only be directly used, but also be used for other reactions as a substrate and has the advantages of moderation in adopted reaction condition, simple operation step and post-processing process, high yield and suitability for large-scale production.
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Paragraph 0064; 0065; 0066; 0067; 0068; 0069
(2017/10/05)
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- Palladium-catalyzed decarboxylative, decarbonylative and dehydrogenative C(sp2)-H acylation at room temperature
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Over the past few decades, an impressive array of C-H activation methodology has been developed for organic synthesis. However, due to the inherent inertness of the C-H bonds (e.g. ~110 kcal mol-1 for the cleavage of C(aryl)-H bonds) harsh reaction conditions have been realized to overcome high energetic transition states resulting in a limited substrate scope and functional group tolerance. Therefore, the development of mild C-H functionalization protocols is in high demand to exploit the full potential of the C-H activation strategy in the synthesis of a complex molecular framework. Although, electron-rich substrates undergo electrophilic metalation under relatively mild conditions, electron-deficient substrates proceed through a rate-limiting C-H insertion under forcing conditions at high temperature. In addition, a stoichiometric amount of toxic silver salt is frequently used in palladium catalysis to facilitate the C-H activation process which is not acceptable from the environmental and industrial standpoint. We report herein, a Pd(ii)-catalyzed decarboxylative C-H acylation of 2-arylpyridines with α-ketocarboxylic acids under mild conditions. The present protocol does not require stoichiometric silver(i) salts as additives and proceeds smoothly at ambient temperature. A novel decarbonylative C-H acylation reaction has also been accomplished using aryl glyoxals as acyl surrogates. Finally, a practical C-H acylation via a dehydrogenative pathway has been demonstrated using commercially available benzaldehydes and aqueous hydroperoxides. We also disclose that acetonitrile solvent is optimal for the acylation reaction at room temperature and has a prominent role in the reaction outcome. Control experiments suggest that the acylation reaction via decarboxylative, decarbonylative and dehydrogenative proceeds through a radical pathway. Thus we disclose a practical protocol for the sp2 C-H acylation reaction.
- Hossian, Asik,Manna, Manash Kumar,Manna, Kartic,Jana, Ranjan
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supporting information
p. 6592 - 6603
(2017/08/16)
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- Two copper titanium cyanine metal organic complex and its preparation method (by machine translation)
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Two copper titanium cyanine metal organic complex and its preparation method, relates to two complex and its preparation method, the invention discloses two novel copper titanium cyanine organic complex preparation method and its reaction univalence catalytic application. The method relates to metal organic chemical, coordination chemistry and the field of catalysis. In this invention the two kinds of metal organic complex is a 3 - alkoxy substituted neighbouring benzene two nitrile and 3 - aryloxy substituted the neighbouring benzene two nitrile are ligand, the copper salt reacted with two four-substituted copper phthalocyanine complex, the complex is in nuclear magnetic resonance, mass spectrometry, infrared, ultraviolet test characterization. The result shows that, two kinds of complex structure clearly. It is applied in univalence reaction catalytic application discovered in, this kind of complex catalytic univalence reaction time, mild reaction conditions, after treatment is simple, high catalytic activity, the good properties of high selectivity, is a great potential for the catalyst. (by machine translation)
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Paragraph 0010; 0014
(2017/08/28)
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- Teaching Old Compounds New Tricks: DDQ-Photocatalyzed C?H Amination of Arenes with Carbamates, Urea, and N-Heterocycles
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The C?H amination of benzene derivatives was achieved using DDQ as photocatalyst and BocNH2 as the amine source under aerobic conditions and visible light irradiation. Electron-deficient and electron-rich benzenes react as substrates with moderate to good product yields. The amine scope of the reaction comprises Boc-amine, carbamates, pyrazoles, sulfonimides and urea. Preliminary mechanistic investigations indicate arene oxidation by the triplet of DDQ to radical cations with different electrophilicity and a charge transfer complex between the amine and DDQ as intermediate of the reaction.
- Das, Somnath,Natarajan, Palani,K?nig, Burkhard
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supporting information
p. 18161 - 18165
(2017/12/28)
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- Chan-Lam-Type C-N Cross-Coupling Reactions under Base- and Ligand-Free CuI-Zeolite Catalysis
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Various representative copper(I)-exchanged zeolites were investigated for their catalytic potential in Chan-Lam cross-coupling reactions. CuI-USY appeared as the best catalyst and proved to efficiently promote C-N cross-coupling processes under attractive, simple, and practical conditions, namely refluxing in methanol under air and without any base.
- Garnier, Tony,Sakly, Randa,Danel, Mathieu,Chassaing, Stefan,Pale, Patrick
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supporting information
p. 1223 - 1230
(2017/03/11)
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- Ruthenium-Catalyzed meta-Selective C?H Mono- and Difluoromethylation of Arenes through ortho-Metalation Strategy
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The first example for the ruthenium-catalyzed ligand-directed meta-selective C?H mono- and difluoromethylation is developed, affording a variety of new meta-mono- and difluoromethylated 2-phenylpyridines, 2-phenylpyrimidines, and 1-phenylpyrazoles in moderate-to-good yields. This new transformation exhibits broad substrate scope, good functional group tolerance, and high efficiency, and offers a practical approach to synthesize mono- and difluoromethylated arenes. Mechanistic studies indicate that a reaction pathway involving palladium-initiated radical species is involved in the catalytic cycle. The new dual catalytic system consisting of compatible ruthenium(II) and palladium(0) complexes enables the key processes of C?H activation and mono-/difluoromethyl-radical formation to occur and achieves the meta-selective functionalization efficiently. In addition, the present protocol can also be extended to non-fluoromethylation.
- Li, Zhong-Yuan,Li, Liang,Li, Qi-Li,Jing, Kun,Xu, Hui,Wang, Guan-Wu
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supporting information
p. 3285 - 3290
(2017/03/16)
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- Sulfonato-imino copper(II) complexes: Fast and general Chan-Evans-Lam coupling of amines and anilines
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Sulfonato-imine copper complexes with either chloride or triflate counteranions were prepared in a one-step reaction followed by anion-exchange. They are highly active in Chan-Evans-Lam couplings under mild conditions with a variety of amines or anilines, in particular with sterically hindered substrates. No optimization of reaction conditions other than time and/or temperature is required.
- Hardouin Duparc,Schaper
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supporting information
p. 12766 - 12770
(2017/10/11)
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