Quinoxalin-2-ones synthesis

Treatment of 4-substituted benzene-l,2-diamines with 6-hydroxy-6-(2,3,5-tri-C -benzoyl-)3-D-ri-bofuranosyl)-6/f-pyran-3(2//)-one leads to 6- and 7-substituted 2-()8-D-ribofuranosyl)quinox-alines and 7- and 8-substituted l-()8-D-ribofuranosyl)pyrrolo[l,2-a]quinoxalines the synthesis of a quinoxaline acyclo-C-nueleoside from benzene-1,2-diamine and a furanone glycoside... 

Ali lAI, Al-Masoudi lA, Hassan HG, Al-Masoudi NA (2007) Synthesis and anti-HIV activity of new homo acyclic nucleosides, l-(pent-4-enyl)quinoxalin-2-ones and 2-(pent-4-enyloxy) quinoxalines. Qiem Heterocyclic Comp 43 1052-1059. doi 10.1007/sl0593-007-0164-0 Ali lAI, Al-Masoudi lA, Aziz NM, Al-Masoudi NA (2008) New acyclic quinoxaline nucleosides. Synthesis and anti-hiv activity. Nucleosides, Nucleotides Nucleic Acids 27(2) 146-156. doi 10. 1080/15257770701795920... 

Scheme 4.48 Three-component condensation of Af-Boc-o-diaminobenzenes, ethyl glyoxylate and substituted tosyl isocyanates for the synthesis imidazo[l,5-a]quinoxalin -ones...

It should be pointed out that there is only one paper (Kanoktanapom et al. 1980) in which the formation of 2,3-few(benzimidazol-2-yl)quinoxa]ine 100a as a by product in the reaction of tetrachloropyridazine 98 and 1,2-DAB 5a in iV-methylpyrroldone at 115 °C for 17 h is described (Scheme 6.31). The yield of the main product of this reaction 5,6,7,8,13,14-hexaazapentaphene 99 obtained as a free base after treatment of the corresponding hydrochloride with aqueous sodium hydroxide is 15 %. The yield of the by-product-2,3-fcw(benzimidazol-2-yl)quinoxaline 100a has not been given in this paper. Therefore this method cannot be used, as a preparative one for the synthesis of 2,3-6 (benzimidazol-2-yl)quinoxalines. The synthesis of other heterocyclic systems with two benzimidazole fragments cannot be used either. 

Echinomycin (131) has been shown to be an antitumor agent and to have antiviral and antibacterial properties. Its structure elucidation represents a triumph for and mass spectral studies (75JA2497). It has been demonstrated that echinomycin functions by inhibiting RNA synthesis in organisms such as Staphylococcus aureus. Echinomycin, levomycin and actinoleutin are members of the quinoxaline-peptide antibiotic family and all contain one or more quinoxaline rings (67MI21402). 

This method is widely applicable to the unambiguous synthesis of quinoxalin-2-ones." It involves the intermediate preparation of a l,2,3,4-tetrahydro-2-oxoquinoxaline by the reductive ring closure of the o-nitrophenyl derivative of an a-aminoacid. These derivatives are formed readily from the aminoacid and an o-nitrohalogenobenzene. The final step of oxidation of the tetrahydro- to the dihydro-quinoxa-line is carried out with potassium permanganate or hydrogen peroxide. The preparation of 7-nitroquinoxalin-2-one illustrates the application of this synthesis ... 

Diphenol/thiophenol is one of the most important polymer precursors for synthesis of poly(aryl ethers) or poly-(aryl sulfides) in displacement polymerizations. Commonly used bisphenols are 4,4 -isopropylidene diphenol or bisphenol-A (BPA) due to their low price and easy availability. Other commercial bisphenols have also been reported [7,24,25]. Recently, synthesis of poly(aryl ethers) by the reaction of new bisphenol monomers with activated aromatic dihalides has been reported. The structures of the polymer precursors are described in Table 2. Poly(aryl ether phenylquinoxalines) have been synthesized by Connell et al. [26], by the reaction of bisphenols containing a preformed quinoxaline ring with... 

Many nitroquinoxalines have been prepared by primary synthesis (see Chapter 1), from halogeno quinoxalines (see Section 3.2.7), or by passenger introduction (e.g., on deoxidative alkylation of an M-oxide see Section 4.6.2.2). However, one major route and one minor preparative route remain, and they are illustrated in the following subsections. 

Selective transformations Selective styrene ring opening [103] One-pot domino process for regioselective synthesis of a-carbonyl furans [104] Tandem process for synthesis of quinoxalines [105] Atmospheric oxidation of toluene [106] Cyclohexane oxidation [107] Synthesis of imines from alcohols [108] Synthesis of 2-aminodiphenylamine [109] 9H-Fluorene oxidation [110] Dehydrogenation of ethane in the presence of C02 [111] Decomposition of methane [112] Carbon monoxide oxidation [113]... 

Scheme 7.69 Liquid-phase synthesis of quinoxalin-2-ones.

In a closely related study, Tung and Sun discussed the microwave-assisted liquid-phase synthesis of chiral quinoxalines [80], Various L-a-amino acid methyl ester hydrochlorides were coupled to MeOPEG-bound ortho-fluoronitrobenzene by the aforementioned ipso-fluoro displacement method. Reduction under microwave irradiation resulted in spontaneous synchronous intramolecular cyclization to the corresponding l,2,3,4-tetrahydroquinoxalin-2-ones (Scheme 7.71). Retention of the chiral moiety could not be monitored during the reaction, but after release of the desired products it was found that about 10% of the product had undergone racemization. 

Many more results were reported in the area of the isomeric [l,2,4]triazolo[4,3-tf]quinoxaline derivatives. With one exception, however, all these studies applied known recognized ring-closure techniques for the synthesis of novel derivatives, in many cases of biological importance (cf. Section 11.16.8.) In Table 15, these derivatives are summarized together with the literature references. 

Neochoritis C, Stephanidou-Stephanatou J, Tsoleridis CA (2009) Heterocyclizations via TosMIC-based multicomponent reactions a new approach to one-pot facile synthesis of substimted quinoxaline derivatives. Synlett 2009(02) 302-305... 

A simple, efficient, one-step synthesis of quinoxaline 1,4-dioxides from the reaction of benzofurazan oxide 179 with activated alkenes such as enamines was named the Beirut reaction in honor of the city of its discovery. Developments up to 1993 were surveyed by Haddadin and Issidorides <1993H(35)1503>, who first demonstrated this reaction. The benzofurazan oxide 179 (Scheme 52) also condenses with 1,3-diketones <1995M1217, 1996JHC1057, 1999CHE459, 2003EJM791, 2005H(65)1589>, /3-keto acid derivatives <1995H(41)2203,... 

Our approach was based on the observation that it is possible to perform SwAr reactions on solid support with amino acids using a solvent system comprised, in equal parts, of acetone and an aqueous 0.5 M NaHC03 solution at temperatures around 70-75°C. Application of this solvent system to the synthesis of quinoxalin-2-ones 6 from la and a-amino acids is described in Section 3.3.2. With respect to the synthesis of 1,5-ben-zodiazepin-2-ones 4, more than 40 examples of aliphatic and aromatic P-amino acids 35 were found to furnish the desired o-nitro anilines 36, about 80% of which were successfully carried on to eventually afford the ben-zodiazepinone products 4 (Scheme 6). In general, the anthranilic acids required slightly harsher conditions to drive the fluorine displacement to completion (75-80°C, 72 h vs. 70-75°C, 24 h for aliphatic P-amino acids). 

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