Day: February 7, 2023

The thermolysis of polyazapentadienes. Part 2. Formation of quinoxalines from 5-aryl-1-phenyl-1,2,5-triazapentadienes was written by McNab, Hamish. And the article was included in Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999) in 1982.Application In Synthesis of 6-Chloroquinoxaline This article mentions the following:

Gas phase pyrolysis of RC₆H₄N:CHCH:NNHPh (I; R = p-Me, -OMe, -Cl, -Ac) at 600° and 10^-2 Torr gave the quinoxalines II (R = Me, OMe, Cl, Ac, R¹ = H) in 13-42% yield. Similarly, I (R = o-Me, -OMe, -Cl) gave II (R = H, R¹ = Me, OMe, Cl) but in lower yields; II (R = R¹ = H) was the major by-product due to ipso attack and elimination of the substituent. Meta-substituted I gave mixtures of 5- and 6-substituted quinoxalines on pyrolysis. The 5-isomer is dominant for compounds with meta-alkyl substituents whereas the 6-isomer is the major product for those with electron-withdrawing or -donating meta-substituents. In the experiment, the researchers used many compounds, for example, 6-Chloroquinoxaline (cas: 5448-43-1Application In Synthesis of 6-Chloroquinoxaline).

6-Chloroquinoxaline (cas: 5448-43-1) belongs to quinoxaline derivatives. Condensed heterocycles of quinoxalines have become attractive targets in synthetic and medicinal chemistry due to their significant biological activities. Quinoxaline-1,4-di-N-oxide derivatives have shown to improve the biological results and are endowed with anti-viral, anti-cancer, anti-bacterial, and anti-protozoal activities with application in many other therapeutic areas.Application In Synthesis of 6-Chloroquinoxaline

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Nitration of quinoxalines was written by Otomasu, Hirotaka;Nakajima, Shoichi. And the article was included in Chemical & Pharmaceutical Bulletin in 1958.Product Details of 6639-82-3 This article mentions the following:

Quinoxaline (I), its N-oxide, and its 2,3-Me₂ derivative resisted nitration even with concentrated H₂SO₄ and fuming HNO₃ (d. 1.52) at 100°. The presence of polar substituents in either ring facilitated nitration. The 6-MeO derivative (II) of I (0.43 g.) in 4 cc. concentrated H₂SO₄ at 0°, well stirred during the addition of 0.5 g. powd. KNO₃, the mixture kept 2 hrs. at room temperature, and poured on ice yielded 0.45 g. 5,6-O₂N(MeO) derivative (III) of I, m. 203° (Me₂CO), and this catalytically reduced (10% Pd-C) in MeOH gave the 5,6-H₂N(MeO) derivative (IV) of I, m. 96° (ligroine). The position of the NO₂ group in III was confirmed by the synthesis of IV from 4,2,3-H₂N(O₂N)₂C₆H₂OMe (V). V (5 g.) catalytically reduced (Pd-C) to 2,3,4-(H₂N)₃C₆H₂OMe, and this under H warmed 30 min. with 10 g. glyoxal bisulfite in 200 cc. hot H₂O, the mixture refluxed 1.5 hrs. on a water bath, evaporated in vacuo, made alk. with NaOH, and the resulting solid extracted with CHCl₃ yielded 1.2 g. IV, identical with the sample from III. No isomeric 5,8-H₂N(MeO) derivative (VI) of I was produced in this reaction. However, 4 g. 4,2,3-AcNH(O₂N)₂C₆H₂OMe in place of V similarly reduced and condensed with (CHO)₂ yielded 1.8 g. 5,8-AcNH(MeO) derivative of I, m. 149°, hydrolyzed by warming 1 hr. on a water bath with 20% NaOH and extracting the cooled mixture with CHCl₃ to give VI, m. 125° (C₆H₆). The 5-MeO derivative of I (0.5 g.) in 5 cc. concentrated H₂SO₄ warmed 15 min. at 60° with 1 g. KNO₃ and the mixture poured into 80 cc. ice water yielded 0.6 g. 5,6,8-MeO(O₂N)₂ derivative of I, m. 204-6° (MeOH), and no mono-O₂N derivative could be formed even at a lower temperature 3,2-Me(HO) derivative of I (5 g.) nitrated as was II yielded 5 g. 3,2,6-Me(HO)(O₂N) derivative (VII) of I, m. 270° (Me₂CO), but no nitration of the 2,3-Cl(Me) or 2,3-(EtO)Me derivatives of I took place under similar conditions. In an attempt to confirm the position of the NO₂ group in VII by synthesis, 1.5 g. 3,4-(H₂N)₂C₆H₃NO₂ (VIII) in 200 cc. MeOH was boiled 1 hr. with 1 g. AcCO₂H and the MeOH evaporated to yield 1.85 g. 3,2,7-Me(HO)(O₂N) derivative of I, m. 255° (MeOH), obviously different from VII. VII (1 g.) methylated with 4 cc. Me₂SO₄ in 20 cc. 20% NaOH yielded 0.55 g. 1,3-dimethyl-2-oxo-6-nitro-1,2-dihydroquinoxaline, m. 218° (Me₂CO), formed also (0.16 g.) from 0.2 g. 2,4-H₂N(O₂N)C₆H₃NHMe in 50 cc. MeOH condensed as was VIII with 0.2 g. AcCO₂H. This synthesis confirms the 6-position of NO₂ in VII. In the experiment, the researchers used many compounds, for example, 6-Methoxyquinoxaline (cas: 6639-82-3Product Details of 6639-82-3).

6-Methoxyquinoxaline (cas: 6639-82-3) belongs to quinoxaline derivatives. Quinoxaline derivatives are important constituents of pharmacologically active compounds, including antibacterial, antibiotic and antineoplastic, antifungal, anti-inflammatory and analgesic drugs. The parent substance of the group, quinoxaline, results when glyoxal is condensed with 1,2-diaminobenzene. Substituted derivatives arise when α-ketonic acids, α-chlorketones, α-aldehyde alcohols and α-ketone alcohols are used in place of diketones.Product Details of 6639-82-3

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Selective skeletal editing of polycyclic arenes using organophotoredox dearomative functionalization was written by Ji, Peng;Davies, Cassondra C.;Gao, Feng;Chen, Jing;Meng, Xiang;Houk, Kendall N.;Chen, Shuming;Wang, Wei. And the article was included in Nature Communications in 2022.Reference of 6639-82-3 This article mentions the following:

A general organophotoredox approach for the chemo- and regioselective dearomatization of structurally diverse polycyclic aromatics, including quinolines, isoquinolines, quinoxalines, naphthalenes, anthracenes and phenanthrenes was described. The success of the method for chemoselective oxidative rupture of aromatic moieties relies on precise manipulation of the electronic nature of the fused polycyclic arenes. Mechanistic studies show that the addition of a hydrogen atom transfer (HAT) agent helps favor the dearomatization pathway over the more thermodynamically downhill aromatization pathway. This strategy was applied to rapid synthesis of biol. valued targets and late-stage skeletal remodeling en route to complex structures. In the experiment, the researchers used many compounds, for example, 6-Methoxyquinoxaline (cas: 6639-82-3Reference of 6639-82-3).

6-Methoxyquinoxaline (cas: 6639-82-3) belongs to quinoxaline derivatives. Compounds possessing quinoxaline derivatives were bestowed with a variety of significant biological properties such as antiviral, antimalarial, anticancer, DNA intercalation, DNA duplex stabilization, and many others. They are well-known for application in organic light emitting devices, polymers and pharmaceutical agents. The quinoxaline-containing polymers are applicable in optical devices due to their thermal stability and low band gap.Reference of 6639-82-3

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Proton magnetic resonance spectra in aromatic systems. XIII. Heteroaromatic series. 5. 6-Substituted quinoxalines was written by Sasaki, Yoshio;Hatanaka, Minoru;Suzuki, Miyoko. And the article was included in Yakugaku Zasshi in 1969.Application In Synthesis of 6-Chloroquinoxaline This article mentions the following:

The chem. shifts of the ring 1H of 6-quinoxalines have been corrected for N anisotropy, N elec. field, and ring current effects. The corrected shifts have also been correlated with the substituent constants σπ, and those corresponding to the π-electron charge density-ρ-distributions were estimated, and converted to ρ values. In the experiment, the researchers used many compounds, for example, 6-Chloroquinoxaline (cas: 5448-43-1Application In Synthesis of 6-Chloroquinoxaline).

6-Chloroquinoxaline (cas: 5448-43-1) belongs to quinoxaline derivatives. Quinoxalines are important class of heterocyclic compounds, associated with wider pharmacological applications. Quinoxalines are used in the treatment of bacterial, cancer, and HIV infections. Moreover, varenicline, a clinical drug is used for treating nicotine addiction, also contains quinoxaline moiety.Application In Synthesis of 6-Chloroquinoxaline

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Studies on the thalleioquine reaction was written by Takada, Atsushi;Negishi, Haruo;Ueda, Takeo. And the article was included in Chemical & Pharmaceutical Bulletin in 1983.Application of 6639-82-3 This article mentions the following:

Two colored substances produced in the thalleioquine reaction using 6-methoxyquinoxaline as a model compound were isolated. The red substance was determined to be an 8,8′-biquinolinyl derivative (I), and the blue substance was found to be a super-stable radical compound In the experiment, the researchers used many compounds, for example, 6-Methoxyquinoxaline (cas: 6639-82-3Application of 6639-82-3).

6-Methoxyquinoxaline (cas: 6639-82-3) belongs to quinoxaline derivatives. Condensed heterocycles of quinoxalines have become attractive targets in synthetic and medicinal chemistry due to their significant biological activities. The parent substance of the group, quinoxaline, results when glyoxal is condensed with 1,2-diaminobenzene. Substituted derivatives arise when α-ketonic acids, α-chlorketones, α-aldehyde alcohols and α-ketone alcohols are used in place of diketones.Application of 6639-82-3

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Studies in the heterocyclic series. XVII. A new type of triazaphenothiazine heterocycle was written by Okafor, Charles O.. And the article was included in Journal of Heterocyclic Chemistry in 1980.Related Products of 5448-43-1 This article mentions the following:

The synthesis of derivatives of 1,4,6-benzo[b]triazaphenothiazine (I), a novel aza-analog of phenothiazine, is described. I was obtained by base-catalyzed condensation of 3-amino-2-mercaptopyridine with 2,3-dichloroquinoxaline in aqueous DMF. Several derivatives were also prepared by using the appropriately substituted aminomercaptopyridines and dichloroquinoxalines. Nitration with mixed nitric and sulfuric acids gave the corresponding 13-nitro derivatives The structures were elucidated by chem. evidence and by a study of their IR, UV, NMR and mass spectra. In the experiment, the researchers used many compounds, for example, 6-Chloroquinoxaline (cas: 5448-43-1Related Products of 5448-43-1).

6-Chloroquinoxaline (cas: 5448-43-1) belongs to quinoxaline derivatives. Compounds possessing quinoxaline derivatives were bestowed with a variety of significant biological properties such as antiviral, antimalarial, anticancer, DNA intercalation, DNA duplex stabilization, and many others. The antitumoral properties of quinoxaline compounds have been of interest. Recently, quinoxaline and its analogs have been investigated as the catalyst’s ligands.Related Products of 5448-43-1

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

The Nitration of 5-Methylquinoxalines in Mixed Acid was written by Marterer, Wolfgang;Prikoszovich, Walter;Wiss, Jacques;Prashad, Mahavir. And the article was included in Organic Process Research & Development in 2003.HPLC of Formula: 532934-95-5 This article mentions the following:

5-Methylquinoxalines are nitrated surprisingly efficiently at the 8 position following a simple nitration protocol with mixed acid at 40-50°. The implications of halogen functionalization at C-7 and modification of the mixed acid conditions on the relative rates of conversion and process safety are discussed. Competing side reactions for 7-halo-5-methylquinoxalines involve hydrolysis at C-7 and halogenation at C-6 or C-8. In the experiment, the researchers used many compounds, for example, 7-Bromo-5-methylquinoxaline (cas: 532934-95-5HPLC of Formula: 532934-95-5).

7-Bromo-5-methylquinoxaline (cas: 532934-95-5) belongs to quinoxaline derivatives. Compounds possessing quinoxaline derivatives were bestowed with a variety of significant biological properties such as antiviral, antimalarial, anticancer, DNA intercalation, DNA duplex stabilization, and many others. Quinoxaline and its analogues may also be formed by reduction of amino acids substituted 1,5-difluoro-2,4-dinitrobenzene (DFDNB),One study used 2-iodoxybenzoic acid (IBX) as a catalyst in the reaction of benzil with 1,2-diaminobenzene.HPLC of Formula: 532934-95-5

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Implications of Promiscuous Pim-1 Kinase Fragment Inhibitor Hydrophobic Interactions for Fragment-Based Drug Design was written by Good, Andrew C.;Liu, Jinyu;Hirth, Bradford;Asmussen, Gary;Xiang, Yibin;Biemann, Hans-Peter;Bishop, Kimberly A.;Fremgen, Trisha;Fitzgerald, Maria;Gladysheva, Tatiana;Jain, Annuradha;Jancsics, Katherine;Metz, Markus;Papoulis, Andrew;Skerlj, Renato;Stepp, J. David;Wei, Ronnie R.. And the article was included in Journal of Medicinal Chemistry in 2012.Application In Synthesis of 6-Bromoquinoxaline-2,3(1H,4H)-dione This article mentions the following:

We have studied the subtleties of fragment docking and binding using data generated in a Pim-1 kinase inhibitor program. Crystallog. and docking data analyses have been undertaken using inhibitor complexes derived from an inhouse surface plasmon resonance (SPR) fragment screen, a virtual needle screen, and a de novo designed fragment inhibitor hybrid. These investigations highlight that fragments that do not fill their binding pocket can exhibit promiscuous hydrophobic interactions due to the lack of steric constraints imposed on them by the boundaries of said pocket. As a result, docking modes that disagree with an observed crystal structure but maintain key crystallog. observed hydrogen bonds still have potential value in ligand design and optimization. This observation runs counter to the lore in fragment-based drug design that all fragment elaboration must be based on the parent crystal structure alone. In the experiment, the researchers used many compounds, for example, 6-Bromoquinoxaline-2,3(1H,4H)-dione (cas: 1910-90-3Application In Synthesis of 6-Bromoquinoxaline-2,3(1H,4H)-dione).

6-Bromoquinoxaline-2,3(1H,4H)-dione (cas: 1910-90-3) belongs to quinoxaline derivatives. Condensed heterocycles of quinoxalines have become attractive targets in synthetic and medicinal chemistry due to their significant biological activities. Quinoxaline and its analogues may also be formed by reduction of amino acids substituted 1,5-difluoro-2,4-dinitrobenzene (DFDNB),One study used 2-iodoxybenzoic acid (IBX) as a catalyst in the reaction of benzil with 1,2-diaminobenzene.Application In Synthesis of 6-Bromoquinoxaline-2,3(1H,4H)-dione

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

From simple quinoxalines to potent oxazolo[5,4-f]quinoxaline inhibitors of glycogen-synthase kinase 3 (GSK3) was written by Lassagne, Frederic;Dugueperoux, Camille;Roca, Carlos;Perez, Concepcion;Martinez, Ana;Baratte, Blandine;Robert, Thomas;Ruchaud, Sandrine;Bach, Stephane;Erb, William;Roisnel, Thierry;Mongin, Florence. And the article was included in Organic & Biomolecular Chemistry in 2020.HPLC of Formula: 166402-16-0 This article mentions the following:

2,7-Disubstituted oxazolo[5,4-f]quinoxalines were synthesized from 6-amino-2-chloroquinoxaline in four steps (iodination at C5, substitution of the chloro group, amidation and copper-catalyzed cyclization) affording 28 to 44% overall yields. 2,8-Disubstituted oxazolo[5,4-f]quinoxaline was similarly obtained from 6-amino-3-chloroquinoxaline (39% overall yield). For the synthesis of other oxazolo[5,4-f]quinoxalines, amidation was rather performed before substitution; moreover, time-consuming purification steps were avoided between the amines and the final products (38 to 54% overall yields). Finally, a more efficient method involving merging of the last two steps in a sequential process was developed to access more derivatives (37 to 65% overall yields). Most of the oxazolo[5,4-f]quinoxalines were evaluated for their activity on a panel of protein kinases, and a few 2,8-disubstituted derivatives proved to inhibit GSK3 kinase. While experiments showed an ATP-competitive inhibition on GSK3β, structure-activity relationships allowed us to identify 2-(3-pyridyl)-8-(thiomorpholino)oxazolo[5,4-f]quinoxaline as the most potent inhibitor with an IC₅₀ value of about 5 nM on GSK3α. In the experiment, the researchers used many compounds, for example, 3-Chloroquinoxalin-6-amine (cas: 166402-16-0HPLC of Formula: 166402-16-0).

3-Chloroquinoxalin-6-amine (cas: 166402-16-0) belongs to quinoxaline derivatives. Quinoxaline derivatives are important constituents of pharmacologically active compounds, including as well as for RNA synthesis inhibition, reactive dyes and pigments, azo dyes, flurox Cylin Dyes, Corrosion Inhibitors and Photovoltaic Polymers. Quinoxalines are used as dyes, pharmaceuticals, and antibiotics such as echinomycin, levomycin exhibiting antitumoral properties. Quinoxalines establish also the basis of anthelmintics and receptor antagonists.HPLC of Formula: 166402-16-0

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

New 6-Aminoquinoxaline Derivatives with Neuroprotective Effect on Dopaminergic Neurons in Cellular and Animal Parkinson Disease Models was written by Le Douaron, Gael;Ferrie, Laurent;Sepulveda-Diaz, Julia E.;Amar, Majid;Harfouche, Abha;Seon-Meniel, Blandine;Raisman-Vozari, Rita;Michel, Patrick P.;Figadere, Bruno. And the article was included in Journal of Medicinal Chemistry in 2016.Name: 3-Chloroquinoxalin-6-amine This article mentions the following:

Parkinson’s disease (PD) is a neurodegenerative disorder of aging characterized by motor symptoms that result from the loss of midbrain dopamine neurons and the disruption of dopamine-mediated neurotransmission. There is currently no curative treatment for this disorder. To discover druggable neuroprotective compounds for dopamine neurons, the authors have designed and synthesized a 2nd-generation of quinoxaline-derived mols. based on structure-activity relation studies, which led previously to the discovery of the authors’ 1st neuroprotective brain penetrant hit compound MPAQ (5c). Neuroprotection assessment in PD cellular models of the authors’ newly synthesized quinoxaline-derived compounds led to the selection of a better hit compound, PAQ (4c). Extensive in vitro characterization of 4c showed that its neuroprotective action is partially attributable to the activation of reticulum endoplasmic ryanodine receptor channels. Most interestingly, 4c was able to attenuate neurodegeneration in a mouse model of PD, making this compound an interesting drug candidate for the treatment of this disorder. In the experiment, the researchers used many compounds, for example, 3-Chloroquinoxalin-6-amine (cas: 166402-16-0Name: 3-Chloroquinoxalin-6-amine).

3-Chloroquinoxalin-6-amine (cas: 166402-16-0) belongs to quinoxaline derivatives. Quinoxaline is isomeric with other naphthyridines including quinazoline, phthalazine and cinnoline. Quinoxaline-1,4-di-N-oxide derivatives have shown to improve the biological results and are endowed with anti-viral, anti-cancer, anti-bacterial, and anti-protozoal activities with application in many other therapeutic areas.Name: 3-Chloroquinoxalin-6-amine

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider