1126-00-7Relevant articles and documents
Highly practical "ligand-free-like" copper-catalyzed N-arylation of azoles in lower nitrile solvents
Zhu, Rui,Xing, Lixin,Wang, Xinyan,Cheng, Chuanjie,Su, Deyong,Hu, Yuefei
, p. 1253 - 1257 (2008)
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.
CuI heterogenized on thiosemicarbazide modified-multi walled carbon nanotubes (thiosemicarbazide-MWCNTs-CuI): Novel heterogeneous and reusable nanocatalyst in the C-N Ullmann coupling reactions
Veisi, Hojat,Metghalchi, Yalda,Hekmati, Malak,Samadzadeh, Shiva
, (2017)
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.
A ligand-free copper-catalyzed strategy to the N-arylation of indazole using aryl bromides
Bai, Di-Xiang,Lim, Rachel Sin-Ee,Ng, Hui-Fen,Teo, Yong-Chua
, p. 1398 - 1405 (2021)
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.
Efficient iron/copper co-catalyzed arylation of nitrogen nucleophiles
Taillefer, Marc,Xia, Ning,Ouali, Armelle
, p. 934 - 936 (2007)
(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.
Cooperative Au/Ag Dual-Catalyzed Cross-Dehydrogenative Biaryl Coupling: Reaction Development and Mechanistic Insight
Li, Weipeng,Yuan, Dandan,Wang, Guoqiang,Zhao, Yue,Xie, Jin,Li, Shuhua,Zhu, Chengjian
, p. 3187 - 3197 (2019)
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.
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
Veisi, Hojat,Poor Heravi, Mohammad Reza,Hamelian, Mona
, p. 334 - 337 (2015)
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.
Mild conditions for copper-catalysed N-arylation of pyrazoles
Cristau, Henri-Jean,Cellier, Pascal P.,Spindler, Jean-Francis,Taillefer, Marc
, p. 695 - 709 (2004)
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).
Mechanistic aspects of Submol % copper-catalyzed C-N cross-coupling
Larsson, Per-Fredrik,Wallentin, Carl-Johan,Norrby, Per-Ola
, p. 1277 - 1282 (2014)
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.
Pyrrole-2-carbohydrazides as Ligands for Cu-Catalyzed Amination of Aryl Halides with Amines in Pure Water
Xie, Jianwei,Zhu, Xinhai,Huang, Manna,Meng, Fei,Chen, Weiwei,Wan, Yiqian
, p. 3219 - 3223 (2010)
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.
Anti-inflammatory effect of a new piperazine derivative: (4-methylpiperazin-1-yl)(1-phenyl-1H-pyrazol-4-yl)methanone
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
, p. 217 - 226 (2018)
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.
Novel choline analog 2-(4-((1-phenyl-1H-pyrazol-4-yl)methyl)piperazin-1-yl)ethan-1-ol produces sympathoinhibition, hypotension, and antihypertensive effects
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.
, p. 1071 - 1083 (2019)
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.
N-arylation of heterocycles catalyzed by activated-copper in pure water
Yang, Qichao,Wang, Yufang,Lin, Dong,Zhang, Mingjie
, p. 1994 - 1997 (2013)
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.
Copper iodide as a recyclable catalyst for Buchwald N-arylation
Swapna, Kokkirala,Murthy, Sabbavarapu Narayana,Nageswar, Yadavalli Venkata Durga
, p. 6678 - 6684 (2010)
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
A Highly Active, Recyclable and Cost-Effective Magnetic Nanoparticles Supported Copper Catalyst for N-arylation Reaction
Zahedi, Razieh,Asadi, Zahra,Firuzabadi, Fahimeh Dehghani
, p. 65 - 73 (2020)
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.]
Anti-inflammatory and antinociceptive activity profile of a new lead compound – LQFM219
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
, (2020)
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.
Kinetic investigation of a ligand-accelerated sub-mol % copper-catalyzed C-N cross-coupling reaction
Larsson, Per-Fredrik,Bolm, Carsten,Norrby, Per-Ola
, p. 13613 - 13616 (2010)
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
Anxiolytic- and antidepressant-like effects of new phenylpiperazine derivative LQFM005 and its hydroxylated metabolite in mice
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
, (2021/09/28)
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.
Unveiling Potent Photooxidation Behavior of Catalytic Photoreductants
Targos, Karina,Williams, Oliver P.,Wickens, Zachary K.
supporting information, p. 4125 - 4132 (2021/04/07)
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.
Copper pyrithione (CuPT)-catalyzed/mediated amination and thioarylation of (hetero)aryl halides: A competition
Cao, Ningtao,Song, Bao,Xie, Jianwei,Zhang, Jie
, (2021/11/08)
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.
