Quinoxalinones preparation

Acetamido-5-methoxy-1,2-benzenediamine (prepared in situ by reduction of 1 -acetamido-2-methoxy-4,5-dinotrobenzene) gave 6-acetamido-7-methoxy-quinoxaline (104) (OHCCHO-2NaHS03 H20, 70°C, 2 h 96%). 4-Acetamido-2,3-diaminophenol (105) (prepared in situ by reduction of the 2,3-dinitro analog) gave 8-acetamido-5(l//)-quinoxalinone (106) (OHCCHO-2NaHS03-H20, reflux, Nji, 2 h 79%). °... 

Benzenediamine (358) and 5-(l,2-dihydroxyethyl)tetrahydro-2,3,4-furane-trione (359) (prepared in situ by oxidation of ascorbic acid with p-benzoqui-none) gave either 3-(2,3,4-trihydroxybutyryl)-2(17i)-quinoxalinone (360)... 

Methoxycarbonylmethyl-1 -methyl-2( 177)-quinoxalinone gave 3-[a-methoxy-carbonyl-a-(p-tolylhydrazono)methyl]-l-methyl-2(177)-quinoxalinone (171) [ i-MeCcH4N20Ac (prepared in situ), ACOH-H2O, 20°C 95°C, 1 h 36%] " analogous esters likewise." " ... 

Most tautomeric quinoxalinones have been made either by primary synthesis (see Chapter 1) or by direct or indirect hydrolysis of halogenoquinoxalines (see Section 3.2.2). The remaining preparative routes are illustrated in the following classified examples. 

The extranuclear C-nitrosoquinoxalines are typified by 3-(a-methoxycarbonyl-a-nitrosomethyl)-2(l/i)-quinoxalmone (66), made by nitrosation of 3-(methoxy-carbonylmethyl)-2(l/f)-quinoxalmone (65) [AcOH, CI3CO2H, C5H11ONO, 20°C, 3 h 91% spectra suggest that the hydroxyimino tautomer (67) may predominate] and was subsequently reduced to afford 3-(a-amino-a-methoxycarbonylmethyl)-2(l//)-quinoxafinone (68) (PtOa, H2, 1 atm, THF, EtOH, 20°C, 4 h 59%) also by 3-[a-(4-amino-5-methyl-4//-l,2,4-triazol-3-yl)-a-nitrosomethyl]-2(l//)-quinoxa-linone (69, R = NO), prepared by nitrosation of 3-(4-amino-5-methyl-4//-1,2,4-triazol-3-ylmethyl)-2(177)-quinoxalinone (69, R = H) [NaN02 ( 1.25 equiv), AcOH, H2O, no further details 79%]." ... 

Numerous 2(177)-quinoxalinones and their 1-methyl derivatives were prepared by multistep manipulation starting from anilines <2005H(65)2741>. A considerable interest attaches to reaction of 2,3-furandiones 190 with 1,2-diaminobenzenes to produce 2(l//)-quinoxalinones 191, which can be converted into 3-phenacyl quinoxalinones by alkaline hydrolysis (Scheme 58) <2005H(65)2161>. 

The most convenient synthesis of halogenopyrazines and -quinoxalines is by halogenation of pyrazinones and quinoxalinones with phosphoryl or other acid halides for example, 5-hydroxy-2-pyrazinecarboxylic acid, rather than 5(477)-pyrazinone-2-carboxylic acid, is chlorinated with phosphorus pentachloride/phosphoryl chloride to afford a 63% yield of 5-chloro-2-pyrazinecarbonyl chloride <1994SL814>. Sato and Narita provided an improved synthesis of various halogenopyrazines in which 2(l//)-pyrazinones were activated with chlorotrimethylsilane to give silyl ethers (Section 8.03.7.3). This procedure is most effective for synthesis of bromopyrazines whose overall yields are 62-81% <1999JHC783>. Bromopyrazine is directly prepared by treatment of 2-(l//)-pyrazinone with phosphoryl... 

Quinoxalinethione is conveniently prepared by treatment of quinoxalinone with Lawesson s reagent <1997H(44)357>. 

During the last few years, numerous quaternary salts of quinoxalines have been prepared, and their reactions studied. 2-Methylquinoxaline and some of its 6,7-substituted derivatives (101) form 4-methyl-quinoxalinium methosulfates and perchlorates (102).116 On hydrolysis of these salts, the quinoxalinones (103) are formed. Similarly 2,3-dimethyl-... 

Quinoxaline glycosides have been prepared from 2-quinoxalinone and its 3-methyl derivative and from 2-quinoxalinethione and its 3-methyl derivitive.233-232... 

The preparation of a quinoxalinylthiophosphate (121) in biphasic systems from 2-quinoxalinone and ClPS(OEt)2 with TBAB-NaOH has been recently described by Gore et o/.187 the reaction was catalyzed with ammonium salts and with N-methylimidazole. 

Diazines other than diketopiperazines can also be prepared on insoluble supports (Table 15.31 see also Figure 3.13 [382]). Most strategies are based on intramolecular nucleophilic substitutions or acylations. Several examples of the solid-phase preparation of quinoxalinones have been reported. In most cases, the compounds have been prepared from support-bound 2-fluoronitrobenzenes according to the strategies outlined in Figure 15.18. Alternatively, a-amino acid esters bound to polystyrene as IV-benzyl derivatives can be N-arylated with 2-fluoronitrobenzene. Reduction of the resulting 2-nitroaniline leads to the formation of quinoxalinones [383]. 1,4-Diazines have been chemically modified by N- or C-alkylation on insoluble supports (Entries 9 and 10, Table 15.31). 

Photocycloadditions to the carbon-nitrogen double bond are in general less common, although this year an exceptional number of such transformations have been reported. The quinoxalinones (150), for example, are converted in this way into the azetidines (151) by addition to electron-poor alkenes (152). Azetidines have also been prepared from 3-aryl-2-isoxazonines. ... 

These compounds are divided into two main types. The first has the quinoxaline ring fused to the 2 and 3 positions of the furanone ring, whereas the other type has that ring fused to the 3 and 4 positions. These compounds were prepared from quinoxalinones or quinoxalines obtained from the reaction of furantriones with one or two molar equivalents of o-diamines... 

Attempted cyclization of 233 with alkali afforded 234 in addition to 238, resulting from the elimination of one molecule of water from the hydrazone residue and the quinoxalinone ring and simultaneous hydrolysis of the ester group. This indicated the presence of two competitive reactions under conditions of cyclization. The structure of 234 was proved by its preparation by hydrolysis of 235. The latter was prepared by the reaction of aldehyde 237 with the phosphorane. The structures were confirmed by studying their H-NMR and mass spectra. 

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