- In water organic synthesis: Introducing itaconic acid as a recyclable acidic promoter for efficient and scalable synthesis of quinoxaline derivatives at room temperature
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Substituted quinoxaline derivatives are traditionally synthesized by co-condensation of various starting materials. Herein, we describe a novel environmentally benign in water synthetic route for the synthesis of structurally and electronically diverse ninety quinoxalines with readily available substituted o-phenylenediamine and 1,2-diketones using cheap and biodegradable itaconic acid as a mild acid promotor in 1 hours. The reaction is performed at room temperature, which proceeds through cyclo-condensation reaction followed by obtaining the aforesaid nitrogen-containing heterocyclic adducts without performing the column chromatography up to 96% total yields. The simplicity, high efficiency, and reusable of the catalyst merits this reaction condition as “green synthesis” which enables it to be useful in synthetic transformations upto gram scale level.
- Tamuli, Kashyap J.,Nath, Shyamalendu,Bordoloi, Manobjyoti
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supporting information
p. 983 - 1002
(2021/02/27)
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- Synthesis, biological evaluation, and in silico studies of new acetylcholinesterase inhibitors based on quinoxaline scaffold
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A quinoxaline scaffold exhibits various bioactivities in pharmacotherapeutic interests. In this research, twelve quinoxaline derivatives were synthesized and evaluated as new acetyl-cholinesterase inhibitors. We found all compounds showed potent inhibitory activity against acetyl-cholinesterase (AChE) with IC50 values of 0.077 to 50.080 μM, along with promising predicted drug-likeness and blood–brain barrier (BBB) permeation. In addition, potent butyrylcholinesterase (BChE) inhibitory activity with IC50 values of 14.91 to 60.95 μM was observed in some compounds. Enzyme kinetic study revealed the most potent compound (6c) as a mixed-type AChE inhibitor. No cytotoxicity from the quinoxaline derivatives was noticed in the human neuroblastoma cell line (SHSY5Y). In silico study suggested the compounds preferred the peripheral anionic site (PAS) to the catalytic anionic site (CAS), which was different from AChE inhibitors (tacrine and galanthamine). We had proposed the molecular design guided for quinoxaline derivatives targeting the PAS site. Therefore, the quinoxaline derivatives could offer the lead for the newly developed candidate as potential acetylcholinesterase inhibitors.
- Khongkow, Pasarat,Lomlim, Luelak,Nualnoi, Teerapat,Saetang, Jirakrit,Suwanhom, Paptawan,Tipmanee, Varomyalin
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- Efficient and sustainable Co3O4 nanocages based nickel catalyst: A suitable platform for the synthesis of quinoxaline derivatives
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Engineered nanocages have emerged at the forefront of nanomaterial investigation as they possess tremendous potential to boost key chemical processes owing to their hollow architectures that can help in achieving high reactivity. With an intention to make profitable use of their morphological features guided chemical activity, we developed dispersable Co3O4 nanocages decorated with nickel nanoparticles for accessing a broad spectrum of pharmaceutically and biologically active N-heterocyclic quinoxaline nuclei using α-dicarbonyls and 1,2-diamines as precursor reagents. For designing Co3O4 nanocages, we employed a simple and scalable method involving Kirkendall effect in which thermal decomposition of Co3[Co(CN)6]2 was carried out thereafter, nanocages were loaded with Ni nanoparticles to obtain the final Ni@Co3O4 catalyst. Results revealed that Ni@Co3O4 catalyst possesses immense potential to accelerate condensation of diamines and di-carbonyls in absence of any additives under mild reaction conditions. The superior catalytic efficiency has been attributed to the hollow architecture of the nanocatalyst comprising of abundant catalytic sites. This protocol exhibits several remarkable attributes such as mild reaction conditions outstanding functional group tolerance, high yield, immense durability and reusability for six subsequent runs.
- Sharma, Aditi,Dixit, Ranjana,Sharma, Shivani,Dutta, Sriparna,Yadav, Sneha,Arora, Bhavya,Gawande, Manoj B.,Sharma, Rakesh K.
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- NaOH-Mediated Direct Synthesis of Quinoxalines from o-Nitroanilines and Alcohols via a Hydrogen-Transfer Strategy
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A NaOH-mediated sustainable synthesis of functionalized quinoxalines is disclosed via redox condensation of o-nitroamines with diols and α-hydroxy ketones. Under optimized conditions, various o-nitroamines and alcohols are well tolerated to generate the desired products in 44-99% yields without transition metals and external redox additives.
- Wang, Yan-Bing,Shi, Linlin,Zhang, Xiaojie,Fu, Lian-Rong,Hu, Weinan,Zhang, Wenjing,Zhu, Xinju,Hao, Xin-Qi,Song, Mao-Ping
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p. 947 - 958
(2021/01/14)
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- Iron-catalyzed one-pot synthesis of quinoxalines: Transfer hydrogenative condensation of 2-nitroanilines with vicinal diols
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Here, we report iron-catalyzed one-pot synthesis of quinoxalines via transfer hydrogenative condensation of 2-nitroanilines with vicinal diols. The tricarbonyl (η4-cyclopentadienone) iron complex, which is well known as the Kn?lker complex, catalyzed the oxidation of alcohols and the reduction of nitroarenes, and the corresponding carbonyl and 1,2-diaminobenzene intermediates were generated in situ. Trimethylamine N-oxide was used to activate the iron complex. Various unsymmetrical and symmetrical vicinal diols were applied for transfer hydrogenation, resulting in quinoxaline derivatives in 49-98% yields. A plausible mechanism was proposed based on a series of control experiments. The major advantages of this protocol are that no external redox reagents or additional base is needed and that water is liberated as the sole byproduct. This journal is
- Chun, Simin,Hong, Junhwa,Hong, Suckchang,Lee, Seok Beom,Oh, Dong-Chan,Putta, Ramachandra Reddy
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p. 18225 - 18230
(2021/06/03)
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- Hydrogen Auto-transfer Synthesis of Quinoxalines from o-Nitroanilines and Biomass-based Diols Catalyzed by MOF-derived N,P Co-doped Cobalt Catalysts
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A Co-based heterogeneous catalyst supported on N,P co-doped porous carbon (Co@NCP) is prepared via a facile in-situ doping-carbonization method. The Co@NCP composite features a large surface area, high pore volume, high-density and strong basic sites. Furthermore, doping of P atoms can regulate the electronic density of Co. Therefore, Co@NCP exhibits good performance for the synthesis of quinoxalines from o-nitroanilines and biomass-derived diols under alkali-free conditions.
- Sun, Kangkang,Li, Dandan,Lu, Guo-Ping,Cai, Chun
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p. 373 - 381
(2020/12/09)
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- Application of a reusable Co-based nanocatalyst in alcohol dehydrogenative coupling strategy: Synthesis of quinoxaline and imine scaffolds
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A nitrogen doped carbon supported cobalt catalyzed efficient synthesis of imines and quinoxaline motifs is reported. Co(OAc)2-Phen/Carbon-800 (Co-phen/C-800) showed the superior reactivity compared to other materials prepared at different temperature, in the synthesis of quinoxalines by the coupling between diamines and diols. Moreover, applying the transfer hydrogenation and acceptorless dehydrogenative coupling strategy, imines and quinoxaline derivatives were synthesized from the nitro compounds. The practical applicability of this protocol was demonstrated by the gram-scale synthesis and the reusability of the catalyst upto 8th cycle. Furthermore, several kinetic experiments were carried out to realize the probable mechanism.
- Panja, Dibyajyoti,Paul, Bhaskar,Balasubramaniam, Bhuvaneshwari,Gupta, Raju K.,Kundu, Sabuj
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- Nickel-Catalyzed Direct Synthesis of Quinoxalines from 2-Nitroanilines and Vicinal Diols: Identifying Nature of the Active Catalyst
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The inexpensive and simple NiBr2/1,10-phenanthroline system-catalyzed synthesis of a series of quinoxalines from both 2-nitroanilines and 1,2-diamines is demonstrated. The reusability test for this system was performed up to the seventh cycle, which afforded good yields of the desired product without losing its reactivity significantly. Notably, during the catalytic reaction, the formation of the heterogeneous Ni-particle was observed, which was characterized by PXRD, XPS, and TEM techniques.
- Shee, Sujan,Panja, Dibyajyoti,Kundu, Sabuj
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p. 2775 - 2784
(2020/03/13)
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- Cobalt complex catalyzed atom-economical synthesis of quinoxaline, quinoline and 2-alkylaminoquinoline derivatives
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A new phosphine-free Co(ii) complex-catalyzed synthesis of various quinoxalines via dehydrogenative coupling of vicinal diols with both o-phenylenediamines and 2-nitroanilines is reported. This complex was also effective for the synthesis of quinolines. The practical aspect of this catalytic system was revealed by the one-pot synthesis of 2-alkylaminoquinolines.
- Shee, Sujan,Ganguli, Kasturi,Jana, Kalipada,Kundu, Sabuj
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supporting information
p. 6883 - 6886
(2018/06/26)
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- Highly efficient synthesis of quinoxaline derivatives catalized by iridium complex
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A novel iridium complex was used to catalyze a mild reaction of phenylenediamine with propanediol that led to formation of quinoxaline derivatives with moderate to high yields. The reaction diemonstrated strong compatibility with substrates bearing various functional groups.
- Lv,Xie,Gu,Wu,Wan
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p. 2887 - 2890
(2017/03/22)
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- Ionic liquid functionalized cellulose as an efficient heterogeneous catalyst for the facile and green synthesis of benzoxazine, pyrazine and quinoxaline derivatives in aqueous media
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Immobilization of acidic ionic liquid, 1-methyl-3-(3-trimethoxysilylpropyl) imidazolium hydrogen sulfate on cellulose (Cell-[pmim]HSO4) as an efficient heterogenous catalyst for the simple and environmentally benign synthesis of benzoxazine, pyrazine and quinoxaline derivatives in aqueous media at room temperature is described. The catalyst was characterized by FTIR spectroscopy and X-ray diffraction pattern. This method provides several advantages such as mild reaction conditions, environmentally friendly catalyst, good to excellent yields and simple work-up procedure.
- Moghaddam, Sevil Vaghefi,Valizadeh, Hassan
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p. 1517 - 1524
(2016/07/06)
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- An experimental and theoretical study of intramolecular regioselective oxidations of 6-substituted 2,3-dimethylquinoxaline derivatives
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An experimental and theoretical study of the regioselective Riley oxidation was conducted on a series of 2,3-dimethyl-6-substituted-quinoxalines bearing EWG (NO2, CN, CF3, Cl, Br, F, COOH, COOMe, COPh) and EDG (2,3-dimethylquinoxaline, OMe, OH, NH2) substituents. The nitrogen lone pair of electrons of the symmetric benzopyrazine moiety initiates the oxidation and promotes nucleophilic competition between the two active sites to give carbaldehyde regioisomers a and b. The mesomeric effect provides the dominant contribution to the regioselectivity. The compounds were characterized by NMR, measuring the 1H, 13C, pfg-HSQC, pfg-HMBC, and 15N, 1H correlation signals established by pfg-HMQC. The nucleophilic reactivity of nitrogen was evaluated by 1H NMR titration and analyzed using Perrin linearization to determine the reactivity ratio, ΔK, of the N4 and N1 nitrogen atoms. The structures were optimized using density functional theory at the ωB97XD/6-311G++(d,p) level of theory. The highest occupied molecular orbitals modeled using the HF/6-311G++(d,p) functionals revealed an asymmetric electron density that confirmed the asymmetric nucleophilicity of the nitrogen centers. These values agreed with the experimentally measured ΔK ratios. The PM6 theoretical calculations of the heats of formation of the mesomeric forms and intermediates of (2,3-dimethyl-6-substituted-quinoxalines)-SeO2 allowed us to identify the reaction routes that minimized energy expenditures. The regioselectivities were explained in terms of the energetic diagrams of the regioisomers. All compounds evaluated indicated a preference toward forming regioisomer b, except for the derivative bearing the EDG substituent (2,3-dimethylquinoxaline) which displayed a preference for regioisomer a.
- Peralta-Cruz, Javier,Díaz-Fernández, Mónica,ávila-Castro, Alberto,Ortegón-Reyna, David,Ariza-Castolo, Armando
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p. 5501 - 5515
(2016/07/06)
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- Aqueous hydrofluoric acid catalyzed facile synthesis of 2,3,6-substituted quinoxalines
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A versatile synthetic route for the preparation of 2,3,6-trisubstituted quinoxalines in excellent yield is developed from θ-diamines and 1,2-dicarbonyl compounds in which aqueous hydrofluoric acid was employed as the medium and catalyst. Other salient features of this protocol include milder conditions, absence of coupling agents, and easy workup procedures.
- Chandra Shekhar,Ravi Kumar,Sathaiah,Raju,Srinivas,Shanthan Rao,Narsaiah
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p. 1504 - 1508
(2015/04/27)
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- One-pot synthesis of quinoxalines from reductive coupling of 2-nitroanilines and 1,2-diketones using indium
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The one-pot reduction-cyclization of 2-nitroanilines and 1,2-diketones to give quinoxalines was investigated. Using indium and an appropriate acid such as acetic acid or indium(III) chloride, various quinoxaline derivatives including 2,3-dialkylquinoxalines, 2,3-diphenylquinoxalines, 2,3-di-2-thiophenylquinoxalines, 2,3-di(pyridin-2-yl)quinoxalines, and dibenzo[a,c]phenazines were synthesized in moderate to excellent yield.
- Go, Ahra,Lee, Geunsoo,Kim, Jaeho,Bae, Seolhee,Lee, Byung Min,Kim, Byeong Hyo
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p. 1215 - 1226
(2015/03/04)
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- Efficient synthesis of quinoxalines from 2-nitroanilines and vicinal diols via a rutheniumcatalyzed hydrogen transfer strategy
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Via a ruthenium-catalyzed hydrogen transfer strategy, we have demonstrated a one-pot method for efficient synthesis of quinoxalines from 2-nitroanilines and biomass-derived vicinal diols for the first time. In such a synthetic protocol, the diols and the nitro group serve as the hydrogen suppliers and acceptors, respectively. Hence, there is no need for the use of external reducing agents. Moreover, it has the advantages of operational simplicity, broad substrate scope and the use of renewable reactants, offering an important basis for accessing various quinoxaline derivatives.
- Xie, Feng,Zhang, Min,Jiang, Huanfeng,Chen, Mengmeng,Lv, Wan,Zheng, Aibin,Jian, Xiujuan
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supporting information
p. 279 - 284
(2018/04/16)
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- A green synthesis of quinoxalines and 2,3-dihydropyrazines
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Quinoxaline and dihydropyrazine derivatives were obtained in high yields by simple addition of 1,2-diamines and 1,2-dicarbonyl compounds in water. In some cases, the products spontaneously precipitated from the reaction mixture, making it possible to recover and reuse the mother liquor for further condensations. The very mild reaction conditions, the high yields of the products, and the absence of any catalyst make this methodology an efficient and green route to quinoxalines and dihydropyrazines. Georg Thieme Verlag Stuttgart New York.
- Delpivo, Camilla,Micheletti, Gabriele,Boga, Carla
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p. 1546 - 1552
(2013/06/27)
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- Microwave-assisted solvent-free synthesis and in vitro antibacterial screening of quinoxalines and pyrido[2, 3b]pyrazines
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We report herein the microwave assisted synthesis, without solvents and catalysts, of 6-substituted quinoxalines and 7-substituted pyrido[2,3b] pyrazines. The compounds were obtained in good yields and short reaction times using the mentioned procedure and two new structures are reported. A complete 1H-and 13C-NMR assignment was performed using 1D and 2D-NMR. Additionally, an in vitro screening was performed on Gram-positive and Gram-negative bacteria using amoxicillin as positive reference. Compounds bearing a pyridyl group tended to have higher antibacterial activity, but the best activity against Bacillus subtilis and Proteus mirabilis was observed with quinoxaline derivatives.
- Morales-Castellanos, J. Jesus,Ramirez-Hernandez, Karina,Gomez-Flores, Nancy S.,Rodas-Suarez, Oscar R.,Peralta-Cruz, Javier
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experimental part
p. 5164 - 5176
(2012/09/07)
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- Sustainable approach to tandem catalysis: Expedient access to quinoxalines and pyrido[2,3-b]pyrazines from α-hydroxyketones via microwave-induced [(NH4)6Mo7O24·4H 2O - PEG 300] polar paste catalyst system
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[(NH4)6Mo7O24·4H 2O-PEG 300] is introduced as a polar paste catalyst system for tandem synthesis of quinoxalines and pyrido[2,3-b]pyrazines under open-vessel focused microwave irradiation. Low conversions were obtained when catalyst or PEG was used individually. Accordingly, a convenient combination of catalyst and PEG mostly led to quantitative yield of products within 15 min microwave irradiation with good turnover frequency values (11-20 h-1) taking a tandem process into consideration. The salient features of this environmentally benign method are fast conversions, high product selectivity and the use of a low-cost, readily available, nontoxic, catalyst and medium.
- Aghapoor, Kioumars,Mohsenzadeh, Farshid,Mohebi Morad, Mina,Darabi, Hossein Reza
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p. 764 - 767
(2012/10/29)
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- Heterogeneous SnCl2/SiO2 versus homogeneous SnCl 2 acid catalysis in the benzo[N,N]-heterocyclic condensation
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The scope of homogeneous Lewis acid-catalyzed benzo[N,N]-heterocyclic condensation was expanded to include the use of various metal salts not reported in the literature and SnCl2·2H2O was finally selected. Among various solid supports activated with SnCl2, heterogeneous SnCl2/SiO2 proved to be the most effective and significantly higher conversions were achieved compared to SnCl 2·2H2O itself. The results of TG-DTA and BET indicated that dispersed SnCl2 coordinates with surface hydroxyl groups of silica leading to formation of stable Lewis acid sites. Low catalyst loading, operational simplicity, practicability and applicability to various substrates render this eco-friendly approach as an interesting alternative to previously applied procedures.
- Darabi, Hossein Reza,Aghapoor, Kioumars,Mohsenzadeh, Farshid,Jalali, Mohammad Reza,Talebian, Shiva,Ebadi-Nia, Leila,Khatamifar, Ehsan,Aghaee, Ali
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experimental part
p. 213 - 218
(2011/11/06)
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- Vitamin B1 as a metal-ion-free natural catalyst for sustainable quinoxaline ring condensation under sonochemical conditions
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The role of vitamin B1 as a catalyst is investigated for the quinoxaline ring condensation under various mild reaction conditions. The results revealed that the combination of vitamin B1 and ultrasonic irradiation promotes the reaction more efficiently. The salient features of this environmentally benign method are fast conversions, excellent yields for a wide range of substrates, and the use of a low-cost, readily available, nontoxic, and metal-ion-free natural catalyst. The wide range of turnover frequency values (6-400 h-1) shows that the reaction rate is highly dependent on the nature of the functional groups on the aromatic ring of substrates. Moreover, a plausible mechanism for the catalytic action of vitamin B1 has been introduced.
- Aghapoor, Kioumars,Mohsenzadeh, Farshid,Talebian, Shiva,Tehrani, Mohammad Jafar,Balavar, Yadollah,Khanalizadeh, Golriz,Darabi, Hossein Reza
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experimental part
p. 619 - 624
(2012/01/15)
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- Asymmetric hydrogenation of 2-and 2,3-substituted ouinoxalines with chiral cationic ruthenium diamine catalysts
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The enantioselective hydrogenation of 2-alkyl- and 2-aryl-subsituted quinoxalines and 2,3-disubstituted quinoxalines was developed by using the cationic Ru(η6-cymene)(monosulfonylated diamine)(BArF) system in high yields with up to 99% ee. The counteranion was found to be critically important for the high enantioselectivity and/or diastereoselectivity.
- Qin, Jie,Chen, Fei,Ding, Ziyuan,He, Yan-Mei,Xu, Lijin,Fan, Qing-Hua
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supporting information; experimental part
p. 6568 - 6571
(2012/02/13)
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- Zirconium(IV) chloride as versatile catalyst for the expeditious synthesis of quinoxalines and pyrido[2,3-b]pyrazines under ambient conditions
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Among the various transition metal chlorides, zirconium(IV) chloride was found to be an efficient catalyst for the rapid synthesis of a wide range of 2,3-dialkyl- and 2,3-diaryl-quinoxaline and pyrido[2,3-b]pyrazine derivatives in excellent yields at room temperature. The remarkable features of this catalytic process are the mild reaction conditions, quantitative yields, short reaction times, high conversions, tolerability of various functional groups, clean reaction profiles, and operational simplicity. Graphical Abstract: Among the various transition metal chlorides, zirconium(IV) chloride was found to be an efficient catalyst for the rapid synthesis of a wide range of 2,3-dialkyl- and 2,3-diaryl-quinoxaline and pyrido[2,3-b]pyrazine derivatives in excellent yields at room temperature. The remarkable features of this catalytic process are the mild reaction conditions, quantitative yields, short reaction times, high conversions, tolerability of various functional groups, clean reaction profiles, and operational simplicity.
- Aghapoor, Kioumars,Darabi, Hossein Reza,Mohsenzadeh, Farshid,Balavar, Yadollah,Daneshyar, Hesam
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experimental part
p. 49 - 53
(2011/12/14)
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- Magnetic Fe3O4 nanoparticles as new, efficient, and reusable catalysts for the synthesis of quinoxalines in water
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A novel, environmentally friendly procedure has been developed for the synthesis of quinoxaline derivatives in the presence of magnetic Fe 3O4 nanoparticles. The reaction between 1,2-diamines and 1,2-dicarbonyl compounds was carried out in water to afford quinoxaline derivatives in high yield. The catalyst can be recovered by the use of an external magnet and reused for five cycles with almost consistent activity. CSIRO 2010.
- Lue, Hong-Yan,Yang, Shu-Hong,Deng, Jia,Zhang, Zhan-Hui
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experimental part
p. 1290 - 1296
(2011/04/15)
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- Room temperature facile synthesis of quinoxalines catalyzed by amidosulfonic acid
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(Chemical Equation Presented) Amidosulfonic acid NH2-SO 3H catalyzed direct condensations of o-phenylenediamines with α-diketones at room temperature in organic solvents to afford quinoxalines in excellent yields. The amidosulfonic acid as a solid acid catalyst in this preparation was efficient and recoverable.
- Li, Zhenjiang,Li, Weisi,Sun, Yingjie,Huang, He,Ouyang, Pingkai
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p. 285 - 288
(2008/09/19)
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- Efficient route to quinoxalines catalyzed by sulfamic acid in tap water suspension
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Quinoxalines were synthesized via direct condensations of o-phenylenediamines with α-diketones promoted by sulfamic acid at room temperature in tap water suspension in high yields and by simple work-up.
- Li, Zhenjiang,Li, Weisi,Ren, Xinghua,Sun, Yingjie,Shi, Yuhu,Ouyang, Pingkai
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p. 125 - 130
(2008/02/12)
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