6- Substituted quinoxalines oxidation

Substituted quinoxalines afford mono-A -oxides, presumably the 1-oxides, and are resistant to further oxidation, though 5-methoxyquinoxaline is exceptional in forming a 1,4-dioxide. In the case of 6-substituted quinoxalines, as the substituent becomes more electron attracting, the yields of 1,4-dioxide decrease but more of the corresponding 2,3-dioxo compound (41) is formed. ... 

A series of quinoxaline oxides 70 and 72 was obtained by the classical Beimt reaction of the substituted benzofuroxanes 71 and the 1,3-diketones, /3-ketoesters, amides, or l-(alkyl/phenyl) 4,4,4-trifluoromethyl-/3-diace-tones (Scheme 16) <1999CHE459, 2004BMC3711>. 

Peracetic acid oxidation of 2-carbamoylquinoxaline (94) at 20°-25° gives the monoxides 95 and 96, and at higher temperatures the 1,4-dioxide (97) is isolated in 50% yield, together with a small amount of the 1,4-dioxide of 2-amino-3-quinoxalinone.m However, Hayashi and co-workers report the isolation of only 96 from 94 using monoperphthalic acid in ether <10°.109 In their attempt to correlate the nature of 2-substitution with the formation of 1- versus 4-oxides, they examined the behavior of some 2-alkyl substituted quinoxalines 113,114 2-ethylquin-oxaline gives the 1- and 4-oxides and the 1,4-dioxide, 2-isopropylquin-oxaline yields the 4-oxide and the 1,4-dioxide however, 2-f-butylquin-oxaline only furnishes the 4-oxide because of steric hindrance.114 The N-oxidation of 2-phenyl- and 2-alkyl-3-phenyl-quinoxalines with monoperphthalic acid furnishes the products shown in Table 1.114... 

The synthesis of quinoxaline A-oxides from benzofurazan 1-oxides, and by N-oxidation of the corresponding substituted quinoxaline derivatives, has already been discussed (Sections II,D and III,C, respectively). 

Hayashi and his co-workers investigated the reactions of 2-substituted quinoxaline 4-oxides with ketones.210-212 2-Phenylquinoxaline 4-oxide (193) yields 2-phenyl-3-phenacylquinoxaline 4-oxide (203) with acetophenone and sodamide. However, 2-cyanoquinoxaline 4-oxide under these conditions yields cu-(3,4-dihydro-3-oxo-2-quinoxalinyl)aceto-phenone (204) by displacement of the cyano group by the ketone carbanion and rearrangement of the N-oxide.212... 

The UV spectra of substituted quinoxaline A-oxides 250 have been calculated and also observed experimentally,249 and the effect of solvent... 

Ring expansion has also been observed in the transformation of certain 1-cyano- and 1-phenylisoquinoline 2-oxides to the corresponding benz[/]-l,3-oxazepines,163 of phenyl-substituted quinoxaline 1-oxides to the substituted benz[d]-l,3,6-oxadiazepines,161 164 and of 4-phenylquinazoline 3-oxide (190) to 2-phenylbenz[/]-l,3,5-oxadiazepine (191).165... 

Intermediate 6-substituted quinoxalin-2(l//)-one 4-oxides can be converted into 6-substituted 3-methylquinoxalin-2(l//)-one 4-oxidcs in a one-pot reaction involving dehydration, deacetylation and decarboxylation using ethyl acetoacetate. ... 

The method has also been applied to the synthesis of alkyl-substituted quinoxalin-2-amines. Thermal rearrangement of l-(2-aminophenyl)-4,5-dihydro-5-morpholino-l,2,3-triazoles 15 affords unstable 2-alkyl-l,2,3,4-tetrahydroquinoxalin-3-amines, which undergo deamination and consequent oxidation to afford 2-alkylquinoxalines 16. ... 

A convenient preparation of quinoxalin-2(l//)-ones involves the reaction of benzene-1,2-diamine with chloroacetic acid and oxidation of the resulting dihydro compound,or more generally, 3-substituted quinoxalin-2(l//)-ones are prepared through reaction with appropriately... 

Mild oxidation of 3-substituted quinoxalin-2-ones, formed by reaction of quinoxalin-2(l//)-ones and Grignard reagents, with potassium hexacyanoferrate(III) or hydrogen peroxide gives aromatic systems. ... 

Alkyl- and alkoxy-substituted quinoxalines are readily oxidized using 60-90% hydrogen peroxide in acetic acid. although quinoxaline itself may give rise to quinoxaline-2,3-dione under these conditions.It has been reported that, although uncommon, an explosion hazard exists using this procedure. ... 

The deoxycyanation of 2-substituted quinoxaline 4-oxides 22 with cyanotrimethylsilane in the presence of l,8-diazabicyclo[5.4.0]undec-7-ene gives the corresponding 3-substituted quinoxa-line-2-carbonitriles 23.- ... 

Treatment of 2-oxo-l,2-dihydroquinoxaline-3-carbonitrile 4-oxide (1) with aniline, N-methylaniline, or cyclohexylamine results in a displacement of the cyano group and deoxygenation to give 3-substituted quinoxalin-2(127)-ones 2. 

The hydrodimerization is also a useful method in the preparation of heterocycles [7,8], 6>-Bis(yS-bicarbethoxyvinylamino)benzene (III) thus yields by intramolecular reductive coupling 2,3-bis(dicarbethoxymethyl)-l,2,3,4-tetrahydroquinoxaline (IV), which on heating gives quinoxaline [7], as in Eq. (2). Compound IV may be anodically oxidized to the substituted quinoxaline [9],... 

Quinoxaline -oxides substituted in the 2,3-position undergo facile nucleophilic displacement. Numerous reactions have been investigated in the search to prepare derivatives which are active... 

A study of the H chemical shifts of 2,3,6-trimethylquinoxaIine in carbon tetrachloride, trifluoroacetic acid, and fluorosulfonic acid indicated that the carbocyclic ring participates in the positive charge distribution to the extent of about 25-30% in the mono-protonated species and 15-20% in the d/-protonated quinoxaline. 2,3-Diphenyl-quinoxaline forms a stable monocation in trifluoroacetic acid, as indicated by the downfield hydrogen signals in this solvent, compared to those in CH Clj. The NMR spectra of quinoxaline i-oxide, 1,4-dioxide and the A-oxides of 2- and 3-substituted quinoxalines have been reported. Analysis of the chemical shift values of quinoxaline-... 

Fuchs, T., Gates, K.S., Kwang, J.T., and Greenberg, M.M., 1999, Photosensitization of guanine specific DNA damage by a cyano-substituted quinoxaline di-V-oxide, Chem. Res. Toxicol. 12, 1190-1194. 

Numerous 3-substituted 2-cyanopyrazines and quinoxalines are synthesized by reaction of the corresponding 3-substituted iV-oxides with TMS-CN in the presence of triethylamine (Section... 

Benzofuroxan (5) reacts under mild conditions with an enamine or with an aldehyde or ketone in the presence of ammonia or an amine to form mono- or disubstituted quinoxaline dioxides (151). Dark red dihydro-quinoxaline dioxides (e.g., 152) may be formed when an enamine is used which does not possess an a-hydrogen atom for elimination.381 2-Amino-substituted quinoxaline dioxides have been produced using (a) an ynamine [providing tertiary amines (153)],382 (b) chloroacetaldehyde and a primary amine [producing secondary amines (154)],9 and (c) some nitriles, e.g., malononitrile (to give the primary amine 155).382 The last reaction, however, is by no means a general one, since benzimidazoles are also produced from these substrates (see below). l-Hydroxyquinoxalin-2-one 4-oxides (156) can also be formed in several ways using (a) an a-substituted /1-ketoester (157)... 

Suter W, Rosselet A, Knusel F, Mode of action of quindoxin and substituted quinoxaline-di-N-oxides on Escherichia coli, Antimicrob. Agents Chemother. 1978 13 770-783. 

Substituted quinoxalines can be also prepared by a one-pot process commencing from hydroxy ketones using a Mn02 (Raw et al. 2004), FeCla/morphoIine (Song et al. 2012), and silica gel (Jeena and Robinson 2014)-mediated tandem oxidation process (Table 2.1). 

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