Day: January 6, 2023

Quinoxaline derivatives. V. Some reactions of 2-cyano-3-hydroxyquinoxaline 1-oxide was written by Ahmad, Yusuf;Habib, M. S.;Iqbal, M.;Ziauddin. And the article was included in Bulletin of the Chemical Society of Japan in 1965.SDS of cas: 1910-90-3 This article mentions the following:

As has been reported the title compound (I, R = H), with a CN group and a N-oxide side by side, has unusual properties (Pachter and Kloetzel, CA 47, 10542b) and was unchanged on refluxing with PCl₃. Deoxygenation by reduction with Na dithionate in HOAc or EtOH, Zn and HCl, or catalytically with H over Pd-C was accompanied by loss of the CN group and gave in each case II (R = R¹ = R² = H). I refluxed with PhNH₂ 4 hrs., cooled, and diluted with petr. ether gave 90% II (R = R¹ = H, R² = NHPh), m. 247-8° (EtOH). Similarly with excess MeNHPh, I (R = H) gave 40% II (R = R¹ = H, R² = NMePh), m. 180-2° (EtOH), which was refluxed with Me₂SO₄ in the presence of anhydrous K₂CO₃ and Me₂CO to give 50% II (R = H, R¹ = Me, R² = NMePh), m. 145-6°, the ir spectrum and mixed m.p. of which were identical with a sample prepared by the method of Clark-Lewis (CA 51, 10537g). Similarly, I (R = H) with cyclohexylamine gave 90% II (R = R¹ = H, R² = cyclohexylamino), m. 246° (EtOH). I (R = Cl) or I (R = EtO) with PhNH₂ gave in good yield II (R = Cl, R¹ = H, R² = NHPh), m. 318-19° (glacial HOAc), or II (R = EtO, R¹ = H, R² = NHPh), m. 260-1° (EtOH), resp. I (R = H) or III refluxed in fuming HBr 2 hrs. and the mixture cooled and diluted with H₂O gave 30% IV (R = R¹ = H), m. >350° (HCONMe₂-EtOH). By this treatment, I (R = H) with Ph in place of CN, was deoxygenated quant. to II (R = R¹ = H, R² = Ph) (unpublished work). Ir spectra of IV (R = R¹ = H) and an authentic sample prepared by the method of Curd, et al. (CA 44, 3501e) were identical. The following sequence is suggested for this reaction: I(R = H ) → III → III(with CO₂H in place of CONH₂) which by decarboxylation gave 3-hydroxyquinoxaline 1-oxide, which by rearrangement gave 2,3-dihydroxyquinoxaline (loc. cit.), then bromination by Br formed by the action of part of the N-oxide on HBr or by aerial oxidation of HBr. In contrast, I (R = H) was unchanged by refluxing 8 hrs. with a 1:1 mixture of concentrated HCl and HOAc, or by heating under reflux with AcCl in a sealed tube at 100° 72 hrs. III, heated with a 1:1 mixture of HCl and HOAc, gave 2,3-dihydroxyquinoxaline. A mixture of this with fuming HBr refluxed 8 hrs. gave 20% monobromo derivative, m. >350° (HCONMe₂-EtOH), which was identical in ir spectrum with IV (R = R¹ = H) prepared from I (R = H) or III. Also the addition of a calculated amount aqueous KBrO₃ to a solution of 2,3-dihydroxyquinoxaline in hot, fuming HBr precipitated at once a quant. yield of monobromo derivative, m. >350° (HCONMe₂-EtOH), identical in ir spectrum with IV (R = R¹ = H) prepared from I (R = H) or III. Either of these monobromo derivatives refluxed 3 hrs. with anhydrous K₂CO₃ and Me₂SO₄ in Me₂CO, the mixture filtered, and the filtrate concentrated gave a good yield of IV (R = R¹ = Me), m 205-6° (EtOH), the ir spectrum and mixed m.p. of which were identical with a sample prepared by the methylation of IV (R = Me, R¹ = H) with Me2₂SO₄ and aqueous NaOH. Curd, et al. (loc. cit.) recorded its m.p. as 205-6°. Hydrogenation of 4-bromo-2-methylamino-1-nitrobenzene in EtOH over Pd-C gave 4-bromo-2-methylaminoaniline, which, refluxed in EtOH solution with Et oxalate 3.5 hrs. gave IV (R = Me, R¹ = H), m. 325-7° (HOAc). In the experiment, the researchers used many compounds, for example, 6-Bromoquinoxaline-2,3(1H,4H)-dione (cas: 1910-90-3SDS of cas: 1910-90-3).

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. The antitumoral properties of quinoxaline compounds have been of interest. Recently, quinoxaline and its analogs have been investigated as the catalyst’s ligands.SDS of cas: 1910-90-3

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Quinoxaline N-oxides. I. The oxidation of quinoxaline and its Bz-substituted derivatives was written by Landquist, Justus K.. And the article was included in Journal of the Chemical Society in 1953.Formula: C8H5ClN2 This article mentions the following:

Quinoxaline (I) and its Bz-substituted-alkyl, alkoxy, halo, and acylamino derivatives are oxidized to 1- and 1,4-dioxides by organic peroxy acids. Resistance to N-oxidation is encountered in 5- and 8-substituted I. Reduction of 2,3-(O₂N)₂C₆H₃OEt with H and Raney Ni gave 3,1,2-EtOC₆H₃(NH₂)₂, oil (picrate, m. 210-12°). 2,4-Br(O₂N)C₆H₃Me nitrated with HNO₃ and H₂SO₄ at 40-5° gave 2,4,5-Br(O₂N)₂C₆H₂Me, m. 94-5°, which, treated with NH₃ in alc. 5 h. at 120° and then reduced with Zn dust and NaOH in EtOH, yielded the 4,5-(H₂N)₂ analog, m. 140-1°. The following general procedure for preparation of I derivatives was used: (CHO.NaHSO₃)₂, an ο-phenylenediamine, and H₂O were stirred 3 h. at 60°, then made alk. with KOH, and the I derivative was filtered off. The following derivatives were prepared (substituent, m.p., m.p. of 1-oxide, m.p. of 1,4-dioxide): 5-Me, 20-1°, b₁₅, 120°, 131-2°, 192-4°; 5-EtO, 63-4°, b₁₈ 165-6°, 114-16°, -; 5-Cl (II), 60-2°, 177-9°, -; 6-iodo, 114-15°, -, -; 6-NC (III), 176-8°, -, -; 6,7-Me₂, 100-1°, -, 220°; 6,7-benzo, 125-6°, -, -; 6,7-ClMe (IV), 120-2°, 166-8°, 227°; 6,7-BrMe (V), 127-8°, 167-8°, 222-4°; 6,7-Cl₂ (VI), 210°, -, 206-8°; 5,8-Cl₂ (VII), 205-7°, -, -; 6-Br (VIII)(prepared by the Sandmeyer reaction from the 6-NH₂ compound), 48-9°, b₁₈ 146-9°, -, 223-5°; 6-AcNH (prepared from the 6-NH₂ compound with Ac₂O), 196.5°, -, 245-7°; 5-AcNH, -, 175-8°, 230-2° (insufficient for anal.). The following N-oxides were also prepared (substituent, m.p. 1-oxide, m.p. 1,4-dioxide): 6-Me (IX), -, 218-19°; 5,6-benzo, 158-9°, 215-16°; 5,6:7,8-dibenzo, 243-4°, -; 5-MeO, -, 222°; 6-MeO, -, 227-8°; 6-EtO, -, 192-4°; 5,6-(MeO)₂, 138-40°, 220-2°; 6,7-(MeO)₂, -, 264-5°; 2-Cl, 150-2°, -; 6-Cl (X), 151-2°, 211-12°. I is oxidized with equimolar AcO₂H to quinoxaline 1-oxide, m. 122-3° (XI) while excess peroxy acid yields quinoxaline 1,4-dioxide, m. 241-3° (XII). Simultaneous with N-oxide formation there were obtained 2,3-dihydroxyquinoxalines which are listed below: (substituent, % yield, m.p.): IX, 1, 112°; II, 30, 142-3°; X, 15-30, 144°; VIII, 28, 132°; VII, 65, 160-1°; VI, 43, 170-70.5°; IV, 10, 172-3°; V, 12-6, 160-1°; III, 50, -; 6-O₂N, 60, 150°. XI and MeI in MeCN set aside in the dark 36 h., precipitated 1-methylquinoxalinium iodide 4-oxide, m. 188-9°. XI was added cautiously to POCl₃, and the mixture boiled 15 min. after the reaction subsided, poured on ice, made alk. with KOH, extracted with Et₂O, and concentrated to yield 2-chloroquinoxaline, m. 46-8°. Under similar conditions XII yielded 2,3-dichloroquinoxaline; 5-methylquinoxaline 1-oxide gave 2-chloro-5-methylquinoxaline, m. 95°; and 5,6-benzoquinoxaline 1-oxide yielded 2-chloro-5,6-benzoquinoxaline, m. 120.5°. 2-C₁₀H₇NHCH₂CO₂Et dissolved treated in EtOH with PhN₂Cl yielded 1,2-Ph₂NC₁₀H₆NHCH₂CO₂Et, m. 135-6°, hydrogenated with Raney Ni at 60° and 50 atm. to 1,2,3,4-tetrahydro-2-oxo-7,8-benzoquinoxaline (XIII), m. 197-8°. XIII with alk. H₂O₂ gave 2-hydroxy-7,8-benzoquinoxaline, isolated as the hydrate, m. 275-5.5°, which was converted with POCl₃ into 2-chloro-7,8-benzoquinoxaline, m. 128-9°. N-(6-nitro-o-tolyl)glycine in EtOH hydrogenated over Raney Ni at 60° and 60 atm. yielded 1,2,3,4-tetrahydro-5-methyl-2-oxoquinoxaline, m. 177-80°, readily oxidized to 2-hydroxy-5-methylquinoxaline, m. 282-3°. 2-Chloro-7,8-benzoquinoxaline and piperidine refluxed 1.5 h. gave 2-piperidino-7,8-benzoquinoxaline, m. 101.5-2.5°. 2-Piperidino-5,6-benzoquinoxaline, m. 124-5°, was similarly prepared Cl slowly passed 1 h. into 5,6-benzoquinoxaline in glacial HOAc, and the solution filtered and diluted with H₂O yielded, on purification, dichloro-5,6-benzoquinoxaline, m. 187-8°. Methylation of 2,3-dihydroxy-6-nitroquinoxaline with Me₂SO₄ gave 3-hydroxy-1-methyl-6(or 7)-nitro-2(1H)-quinoxalinone, m. 344°. 6(or 7)-Cyano-3-hydroxy-1-methyl-2(1H)-quinoxalinone, m. 353-4°, is similarly prepared In the experiment, the researchers used many compounds, for example, 6-Chloroquinoxaline (cas: 5448-43-1Formula: C8H5ClN2).

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 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.Formula: C8H5ClN2

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Proton resonance spectra of heterocycles. VIII. Substituent effects on coupling constants in bicyclic heteroaromatic compounds and the prediction of chemical shifts from coupling constants was written by Katritzky, A. R.;Takeuchi, Y.. And the article was included in Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999) in 1972.Product Details of 5448-43-1 This article mentions the following:

Substituents affect coupling constants in bicyclic heteroaromatic compounds e.g., substituted 2,1,3-selenadiazole, benzofuroxan, quinazoline, quinoline; they increase 3Jαβ and 4Jαε, slightly decrease 4Jαγ and 5Jαδ, and have little effect on 3Jβγ. The regularities discussed allowed prediction of J in substituted systems. Ortho-substituent effects on chem. shifts relate to the corresponding 3J values in the unsubstituted compound, reflecting the dependence of both on partial bond fixation. In the experiment, the researchers used many compounds, for example, 6-Chloroquinoxaline (cas: 5448-43-1Product Details of 5448-43-1).

6-Chloroquinoxaline (cas: 5448-43-1) 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. The antitumoral properties of quinoxaline compounds have been of interest. Recently, quinoxaline and its analogs have been investigated as the catalyst’s ligands.Product Details of 5448-43-1

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Syntheses of 2-mono- and 2,3-disubstituted quinoxalines was written by Gowenlock, A. H.;Newbold, G. T.;Spring, F. S.. And the article was included in Journal of the Chemical Society in 1945.Name: Ethyl 3-chloroquinoxaline-2-carboxylate This article mentions the following:

For the preparation of 2,3-pyrazinedicarboxylic acids carrying certain substituents at the 5- and 5,6-positions, 2-mono- and 2,3-disubstituted quinoxalines have been synthesized. Most of these syntheses depend upon transformations of the readily available Et 2-hydroxy-3-quinoxalinecarboxylate (I). o-C₆H₄(NH₂)₂ (10.8 g.) and 17.4 g. Et ketomalonate in absolute EtOH, refluxed 1 hr., give about 18 g. of I, m. 175.5°-6.5°. Hydrolysis with 3 N NaOH on the steam bath for 30 min. gives 95% of 2-hydroxy-3-quinoxalinecarboxylic acid (II), m. 263-5° (decomposition); at 265°, II yields 72% of 2-hydroxyquinoxaline (III), sublimes at 200°/0.5 mm., m. 271°. III was also prepared in 57% yield from 2.7 g. o-C₆H₄(NH₂)₂ and 3.8 g. EtO₂CCHO in EtOH (refluxing 30 min.). I (10.9 g.) and 50 cc. POCl₃, heated at 110-20° for 10 min., give 90% of Et 2-chloro-3-quinoxalinecarboxylate (IV), m. 42.5° (after sublimation at 60°/6 × 10^-3 mm.); it gradually turns pink in the air and is best stored as the EtOH solution at 0°. Hydrolysis of IV by refluxing with 3 N NaOH for 30 min. gives II; 2 g. of IV and 0.5 g. Na₂CO₃ in 50 cc. 80% MeOH, refluxed 4 hrs., give 1.8 g. of 2-chloro-3-quinoxalinecarboxylic acid (V), pale yellow, m. 146-7° (decomposition); V results also on hydrolysis of IV with aqueous MeOH-NaCN. V in anhydrous EtOH, treated at 0° with dry NH₃ for 4 hrs., gives 85% of the amide, m. 214-15°; it results in small yields from IV and concentrated NH₄OH in 80% MeOH at room temperature IV (4 g.) and 120 cc. EtOH-NH₃ (saturated at 0°), heated 5 hrs. at 150-60°, give 77% of 2-amino-3-quinoxalinecarboxamide, bright yellow, m. 263-4°; refluxed with 10% NaOH for 3 hrs., it yields 2-amino-3-quinoxalinecarboxylic acid (VI), m. 212-13° (decomposition); with MeOH and dry HCl, this yields the HCl salt, light yellow, m. 188-9° (decomposition), of the Me ester, yellow, m. 218-19°. V and glass wool, heated at 0.1 mm. to 160°, give 2-chloroquinoxaline (VII), pale yellow, b_0.5 80°, m. 46-7°; this also results in 85% yield from III and POCl₃ (refluxed 20 min.) and in 18% yield by refluxing II with POCl₃ for 30 min.; a HCl salt seps. from the solution in 10 N HCl. VII and EtOH-NH₃, heated at 150° for 7 hrs., give. 86% of 2-aminoquinoxaline, m. 155-7°, sublimes 130-40°/10^-3 mm.; it also results in 38% yield on heating VI at 250° for 3 min. IV and EtONa in EtOH, refluxed 2 hrs., give 80% of the Et ester, m. 25°, of 2-ethoxy-3-quinoxaline-carboxylic acid (VIII), m. 120-1° (70% yield on hydrolysis of the ester). VIII, heated at 180°, yields 94% of 2-ethoxyquinoxaline, m. 56-8°; it also results in 81% yield from VII and EtONa in EtOH (refluxed 1 hr.). 2,3-Dichloroquinoxaline (IX) and EtONa in EtOH, refluxed 3.5 hrs., give 80% of 2,3-diethoxyquinoxaline, m. 78°; it is not affected by boiling with 0.2 N aqueous EtOH-KOH for 1 hr. but 0.2 g. and 5 cc. HCl (d. 1.19) in 50 cc. EtOH (refluxed 1 hr.) give 2,3-dihydroxyquinoxaline; the 0.1 N NaOH solution exhibits absorption maximum at 3160, 3260, and 3410 A. (ε 12,200, 14,400, and 10,500). IX and EtOH-NH₃, heated 6 hrs. at 150°, give 47% of 2,3-diaminoquinoxaline, m. 328-30° (decomposition). In the experiment, the researchers used many compounds, for example, Ethyl 3-chloroquinoxaline-2-carboxylate (cas: 49679-45-0Name: Ethyl 3-chloroquinoxaline-2-carboxylate).

Ethyl 3-chloroquinoxaline-2-carboxylate (cas: 49679-45-0) belongs to quinoxaline derivatives. Quinoxalines have received a significant amount of attention due to their potential use in fighting various pathophysiological conditions like epilepsy, Parkinson’s, and Alzheimer’s diseases. 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.Name: Ethyl 3-chloroquinoxaline-2-carboxylate

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Electrocatalytic Minisci Acylation Reaction of N-Heteroarenes Mediated by NH₄I was written by Wang, Qing-Qing;Xu, Kun;Jiang, Yang-Ye;Liu, Yong-Guo;Sun, Bao-Guo;Zeng, Cheng-Chu. And the article was included in Organic Letters in 2017.Name: 6-Chloroquinoxaline This article mentions the following:

Electron-deficient aromatic nitrogen heterocycles, particularly pyrazines and quinoxalines, underwent chemoselective and green electrochem. Minisci acylations with α-ketoacids such as pyruvic acid mediated by NH₄I, LiClO₄, and hexafluoroisopropanol in MeCN to give heteroaryl ketones such as 2-acetylquinoxaline in 18-65% yields. Cyclic voltammetry and control experiments were used to delineate the mechanism of the Minisci acylation; I₂ formed in situ likely reacts with carboxylate anions to yield acyl hypoiodites which then undergo decarboxylation to acyl radicals. In the experiment, the researchers used many compounds, for example, 6-Chloroquinoxaline (cas: 5448-43-1Name: 6-Chloroquinoxaline).

6-Chloroquinoxaline (cas: 5448-43-1) belongs to quinoxaline derivatives. Quinoxaline is isomeric with other naphthyridines including quinazoline, phthalazine and cinnoline. Modifying quinoxaline structure it is possible to obtain a wide variety of biomedical applications, namely antimicrobial activities and chronic and metabolic diseases treatment.Name: 6-Chloroquinoxaline

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider