2.3- Disubstituted quinoxalines

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. 

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... 

Dimethylquinoxaline has a pKa of 2.08, and thus in general +M-substitutents at the 6-position are found to increase basicity, and —M-substituents have the reverse effect. The basicities of a series of 2,3-disubstituted quinoxalines have also been determined by potentiometric titration.243... 

The reaction between aromatic 1,2-diamines and 1,2-diketones affords 2,3-disubstituted quinoxaline derivatives (see table below) " however, a number of hindered a-ketones fail to react. " Unsymmetrical diketones give mixtures of isomers whose ratio varies with the acidity of the medium in some examples. A mechanistic study of quinoxaline formation from benzene-1,2-diamine and benzil has been described." ... 

In the reaction between benzene-1,2-diamine and a-methylsulfinyl ketones, mono and 2,3-disubstituted quinoxalines are formed under neutral conditions the corresponding 0,S-acetals as formed by Pummerer rearrangement are putative intermediates. 

Loss of nitrogen and a proton shift in a-azidocarbonyl compounds upon pyrolysis gives a-iminocarbonyl compounds which condense with benzene-1,2-diamine in situ to afford 2,3-disubstituted quinoxalines. 

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

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... 

Disubstituted quinoxalines are not toxic to bees, so that, with the exception of a few more sensitive apple species, preparations can also be used in the blossoming period. 

Photochemical decomposition of 2-azido-l-methoxyphenazine forms singlet and triplet nitrenes, which are trapped with the azide leading in acetonitrile at —20°C to the dimeric product 3-[3-[[(l-methoxy-2-phenazinyl)imino]methoxymethyl]-2-quinoxalinyl]-2-propenenitrile <9lJOC6993>. Higher reaction temperatures result in the additional formation of aminophenazines and other 2,3-disubstituted quinoxalines <87J0C1245>. 

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. ... 

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... 

Cyclic derivatives have also been prepared from quinoxaline-2,3-dithiones by reaction with phosgene (COClj), thiophosgene (CSCI2), and thionyl chloride (SOCI2). 2,3-Disubstituted quinoxalines result from the reaction of the dithiones with isocyanates, isothiocyanates, and imidoyl chlorides (e.g., PhCCl=NMe). Derivatives of quinoxaline-2,3-dithiones incorporating arsenic, antimony, and tin have been prepared for example, with BujSnCl the 2,3-disubstituted quinoxaline 22 is obtained, and... 

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. ... 

A convenient synthetic method for 2,3-disubstituted quinoxalines 692 was described by heating aryl or alkyl acyloins with o-phenylenediamine in dry media under MWI for 3-6 min the products were obtained in 20-94% yields (Scheme 133) (98SC193). The condensation of the ot-dicarbonyl compounds with o-phenylenedia-mine was catalyzed by PTSA without a solvent under focused MWI. Thus, cam-phorquinone, 1,2,3-triketo-hydrindane hydrate, o-quinones, phenanthrenequinone, and acenaphthenequinone gave easily the corresponding quinoxalines within 15 s to 4 min (95SC2319). 

Yadav JS, Reddy S et al (2008) Bismuth(lll)-catalyzed rapid synthesis of 2,3-disubstituted quinoxalines in water. Synthesis 23 3787-3792... 

Bardajee GR (2013) Zr0Clj.8H20 in water an efficient catalyst for rapid one-pot synthesis of pyridopyrazines, pyrazines and 2,3-disubstituted quinoxalines. Comptes Rendus Chimie 16 872 877... 

Zhang, Z. Du, H. A Highly cis-Selective and Enantioselective Metal-Free Hydrogenation of 2,3-Disubstituted Quinoxalines. Angew. Chem. Int. Ed. 2015,54,623-626. 

The synthesis of 2,3-disubstituted quinoxalines 467a-c was achieved in yields of 53-70 % using 1,2-DAB 155a and internal epoxides 466a-c (R = -Pr, = m-Bu ... 

In a similar way, Chen et al. reported DlB-catalyzed an efficient synthesis of 2,3-disubstituted quinoxalines 140. In a one-pot method, internal alkynes 138 and o-phenylenediamines 139 were treated with a mild and inexpensive DIB to afford quinoxalines in good yields (Scheme 31). Among the prepared series of quinoxaline derivatives, one of the trimethoxy-substituted compounds 141 was foxmd to exhibit promising activity against leukemia cancer cell line. Using this simple and one-pot procedure, various therapeutically important quinoxalines can be prepared [47]. 

Zirconium Schiff-base complex modified SBA-15 (Zr-SBA-15) was used as catalyst in the synthesis of quinoxaline-based heterocycles such as pyridopyrazine, pyrazine, and quinoxaline derivatives [156]. 2,3-Disubstituted quinoxalines among others were prepared, in water media, in good-to-excellent yields. The Zr/SBA-15 catalyst showed an excellent reusability over seven successive runs xmder optimized conditions. 

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