2.3- Disubstituted quinoxalines oxidation

Several recent general papers on the properties of quinoxaline N-oxides have reported studies on the crystal structures of quinoxaline 1,4-dioxide,380 its 2,3-dimethyl derivative,380 ethyl 7-chloro-3-methyl-2-quinoxalinecarboxylate 1,4-dioxide,40 and N-(2-hydroxyethyl)-3-methyl-2-quinoxalinecarboxamide 1,4-dioxide 931 the NMR spectral data of quinoxaline 1,4-dioxide for comparison with those of related dioxides 348 the NMR data for biologically active quinoxalinecarboxamide dioxides 381 thermochemical data for several quinoxaline dioxides 183 and polaro-graphic or cyclic voltammetric data for 2,3-disubstituted quinoxaline dioxides.239 894... 

The regiospecific oxidative nitration of 3,4-dihydro-6,7-disubstituted quinoxalin-2(l//)-ones utilizing fuming nitric acid in trifluoroacetic acid gives 5-nitro-6,7-disubstituted quinoxa-line-2,3(l/f,4/f)-diones in good yields. 

Mono- or 2,3-Disubstituted Quinoxaline 4-Oxides General Procedure ... 

Azidoquinoxaline undergoes ring contraction to l-hydroxybenzimidazole-2-carbonitrile." On photolysis in methanol, 2,3-disubstituted quinoxaline 1,4-oxides undergo rearrangement to 1,3-disubstituted benzimidazolones. -" ... 

Deoxygenation. Hexachlorodisilane is useful for deoxygenation of nitrones and various N-oxides in good yields under exceptionally mild conditions (25° or below).1 It is recommended for deoxygenation of 2,3-disubstituted quinoxaline 1,4-dioxides under mild conditions yet at reasonable rates.2... 

The major reactions in this section are those involving an V-oxide oxygen. Deoxygenation of 2,3-disubstituted quinoxaline 1,4-dioxides is achieved under mild conditions by treating with hexa-chlorodisilane, TMS-1, TFAA-sodium iodide, or titanium tetrachloride-zinc dust <81H(i6)4ii>. Quinoxaline and phenazine V,A( -dioxides are also deoxygenated under mild conditions by sodium hypophosphite catalyzed by Pd/C or by treatment with sodium iodide in the presence of pyri-dine/sulfur trioxide complex <83JHC1735>. Deoxygenation of 6-chloro-2(l//)-quinoxalinone 4-oxide is effected particularly by sodium borohydride or sodium hydrosulfite <85H(23)143>. 

Bis-deoxygenation of 2,3-disubstituted quinoxaline di-A -oxides has been performed under very mild conditions with a variety of reagents, such as hex-achlorodisilane or trifluoroacetic anhydride plus sodium iodide. ... 

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)... 

The results of oxidizing other 2,3-disubstituted quinoxalines are broadly predictable from what is known about the oxidation of the monosubstituted compounds. Thus 1,4-dioxides can be prepared from 2-methyl- and 2-ethyl-3-phenylquinoxalines, but a considerable amount of... 

Several examples of the successful lithium aluminum hydride reduction of l,2,3,4-tetrahydro-2-oxoquinoxalines to the corresponding tetrahydroquinoxalines have been recorded in the literature. " A moderate yield of 1,2,3,4-tetrahydroquinoxaline is obtained by reduction of 1,2,3,4-tetrahydro-2,3-dioxoquinoxaline with lithium aluminum hydride in N-ethylmorpholine. The anils 19 give the tetrahydroquinoxalines 20 on treatment with sodium borohydride. This reagent has also been used to reduce a number of 2,3-disubstituted quinoxaline di-iV-oxides to the corresponding cis-tetrahydro derivatives. The trans isomers can be prepared by first reducing the N-oxides with sodium dithionite to the parent quinoxalines, and then the further reduction of the quinoxalines so formed with sodium and ethanol. ... 

The second class of benzo-fused heterocycles accessible from benzofuroxans are benzimidazole oxides. In this case only one carbon from the co-reactant is incorporated in the product. With primary nitroalkanes 2-substituted l-hydroxybenzimidazole-3-oxides (46) are formed via displacement of nitrite, and / -sulfones behave similarly. The nitrile group of a-cyanoacetamides is likewise eliminated to alford 2-amide derivatives (46 R = CONRjX and the corresponding esters are formed in addition to the expected quinoxaline dioxides from acetoacetate esters. Under similar conditions secondary nitroalkyl compounds afford 2,2-disubstituted 2//-benzimidazole-1,3-dioxides (47). Benzimidazoles can also result from reaction of benzofuroxans with phosphorus ylides <86T3631>, nitrones (85H(23)1625>, and diazo compounds <75TL3577>. 

Oxidation of the parent base with hydrogen peroxide in formic acid gives a high yield of mono-N-oxide and a little di-N-oxide N-Oxidation is assumed to proceed preferentially at the less hindered 4-nitrogen. A number of substituted benzo[/]quinoxaline 4-oxides have been prepared, the majority by oxidation of the appropriate benzo[/]quinoxaline with peracids. " Treatment of benzo[/]quinoxaline 4-oxide with phosphoryl chloride gives mainly 3-chlorobenzo[/]quinoxaline. An isomeric mono-chloride, m.p. 104-104.5°, is also isolated from this reaction which is shown by independent synthesis not to be the 2-chloro derivative. A dichloro derivative, m.p. 187-188°, of unknown structure is obtained by treatment of the parent base with chlorine in glacial acetic acid. A disubstitution product of unknown orientation and m.p. 288° is obtained by nitration of... 

Ring contraction also occurs in irradiation of quinoxaline di-A-oxide of the type 10, the product of the reaction being a 1,3-disubstituted benzimidazolone 11 (Scheme 6.6) (Jarrer et al. 1976). 

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