2.3- Disubstituted quinoxaline 1,4-dioxides

BFO reacted readily with 1,3-diketones to give 2,3-disubstituted quinoxaline 1,4-dioxides. In the case of unsymmetrical 1,3-diketones, mixtures of isomeric quinoxaline dioxides were obtained, and the ratio of isomers was influenced by the steric bulk of the carbonyl substituent. When BFO 1 was combined with 1,3-diketone compounds 18 in the presence of triethylamine, the isomeric quinoxaline 1,4-dioxides 19 and 20 were obtained. When R = Me, 19 was the only product observed. As the steric bulk of R increased, increasing amounts of isomer 20 were observed. When R = tBu, 20 was the only product detected in the reaction. 

Benzothiazole-2-acetonitrile reacts with benzofuroxan to give a 2,3-disubstituted quinoxaline 1,4-dioxide, 7. ... 

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... 

Trimethyl phosphite selectively reduces 2,3-disubstituted quinoxaline 1,4-dioxides (51) to the corresponding monoxides in high yield, whereas methods previously used led to mixtures of monoxides and quinoxalines. In unsymmetrically substituted... 

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>. 

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... 

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 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>. 

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... 

Enamines react with benzofuroxan and its derivatives under mild reaction conditions to form quinoxaline 1,4-dioxides.The reaction formally involves a 1,4-cycloaddition, followed by steps leading to a fully heteroaromatic system which arises by elimination of the amine component of the enamine participant. This elimination requires that the enamine possesses a hydrogen atom at the j8-carbon atom. A variety of enamines react satisfactorily, but the less reactive morpholine enamines give higher yields and more easily isolable products. The reaction between benzofuroxan and its 5(6)-monosubstituted or 5,6-disubstituted analogs proceeds much more easily than with 4(7)-monosubstituted or 4,7-disubstituted derivatives. 

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