Quinoxalinones derived from

Other synthetic routes to pyrazinones and quinoxalinones are from the halo compounds, by dealkylation of ethers (8lJCS(Pl)3111> or by diazotization of the corresponding amines, but since the halo derivatives are normally derived from the hydroxy compounds, and the amines from the halo derivatives, direct synthesis seems to represent the most practical approach. 

Note Perhaps because so many halogenoquinoxalines are themselves derived from quinoxalinones, the reverse process of hydrolysis is seldom reported the examples are all special cases in which a passenger group would complicate or preclude a straightforward acidic or alkaline hydrolysis. 

Cyclocondensation between l,2-dihydroquinoxalin-2-ones and l,2,4-triazine-3,5-dione derivatives involves the carbonyl group of the 1,2,4-triazinedione and not the carbonyl group of the quinoxalinones <04JHC597>. New examples of the synthesis of pyridine and 2,2 -bipyridine derivatives from a variety of substituted 1,2,4-triazines through Diels-Alder reactions have been described <04T8893>. 

Hekmatshoar and coworkers synthesized benzo-A -heterocycles using nano-CuO as the heterogeneous catalyst (Sadjadi et al., 2010). Several benzoxazinone, benzothiazinone, and quinoxalinone derivatives were rapidly assembled in good to excellent yields from the aromatic amines and acetylenedicarboxylic acid esters (Scheme 4.49). The water-resistant catalysts were environmentally benign, and could be easily synthesized, stored, and recycled. 

In 2006, Lectka and coworkers reported an asymmetric inverse electron demand hetero-Diels-Alder reaction (HDAR) of acyl chlorides (Bekele et al. 2006 Wolfer et al. 2006) and o-benzoquinone diimides to deliver chiral quinoxalinones (Abraham et al. 2006). In spite of perfect ee values observed by the catalysis of Lewis bases derived from cinchona alkaloids, the reaction conditions were somewhat harsh and metal triflates had to be used as co-catalysts to activate the electrophilic o-benzoquinone diimides (Abraham et al. 2006 Pauli et al. 2(X)8). 

The l/f-pyrrole-2,3-diones 494 easily available from the reactions of 4-(4-methylbenzoyl)-5-(4-methylphenyl)-2,3-furandione 492a and 4-(3,4-dimethoxybenzoyl)-5-(3,4-dimethoxyphenyl)-2,3-furandione 492b with the N, A-disubstituted urea derivatives 493 were performed with 1,2-DABs 155a, b and lead to 2(l/f)-quinoxalinone derivatives 495 in 61-74 % yields (Koca and Yildirim 2012) (Scheme 2.110). 

Ager IR, Barnes AC, Danswan GW, Hairsine PW, Kay DP, Kennewell PD, Matharu SS, Miller P, Robson P, Rowlands DA, Tully WR, Westwood R (1988) Synthesis and oral antiallergic activity of carboxylic acids derived from imidazo[2,l-c][l,4]benzoxazines, imidazo[l,2-tj] quinolines, imidazo[l,2-a]quinoxalines, imidazo[l,2-a]quinoxalinones, pyirolo[l,2-tj]quinox-alinones, pyrrolo[2,3-a]quinoxalinones, and imidazo[2,l-f>]benzothiazoles. J Med Chem 31 (6) 1098-1115. doi 10.1021/jm00401a009... 

At least two derivatives of pyran have been used for the primary synthesis of quinoxalines. Thus o-phenylenediamine (390) and 6-(p-methoxyphenyl)-6-methyl-5,6-dihydro-2//-pyran-2,5-dione (391) in methylene chloride at 20°C open to the air for 48 h gave 3-[2-hydroxy-2-(p-methoxyphenyl)propionyl]methyl-3,4-dihydro-2(1 //)-quinoxalinone (392) (as a mixture of two stereoisomers) in 92% yield 488 the 3,4,4a,5,6,7,8,8a-octahydro analog was made similarly from 1,2-diaminocyclohex-ane (91% of two separable stereoisomers).488... 

Kwakman et al. [65] described the synthesis of a new dansyl derivative for carboxylic acids. The label, N- (bromoacetyl)-A -[5-(dimethylamino)naphthalene-l-sulfonyl]-piperazine, reacted with both aliphatic and aromatic carboxylic acids in less than 30 min. Excess reagent was converted to a relatively polar compound and subsequently separated from the derivatives on a silica cartridge. A separation of carboxylic acid enantiomers was performed after labeling with either of three chiral labels and the applicability of the method was demonstrated by determinations of racemic ibuprofen in rat plasma and human urine [66], Other examples of labels used to derivatize carboxylic acids are 3-aminoperylene [67], various coumarin compounds [68], 9-anthracenemethanol [69], 6,7-dimethoxy-l-methyl-2(lH)-quinoxalinone-3-propionylcarboxylic acid hydrazide (quinoxalinone) [70], and a quinolizinocoumarin derivative termed Lumarin 4 [71],... 

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>. 

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

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). 

Quinoxalinones have been suggested for the chromatography of keto acids [184,185]. They are produced by reaction with aromatic o-diamines, as shown in Scheme 4.21 (p. 77). A solution of 60 mmol of sublimed o-phenylenediamine in 100 ml of 10% acetic acid was mixed with a solution of 30 mmol of the keto acid in 30 ml of water. The precipitated quinoxalinone was filtered after 15 min, washed with water, dried and crystallized from methanol. Prior to the GC analysis proper, it had to be converted into a silyl derivative 5—50 /ul of about a 1% solution of quinoxalinone in dry pyridine was mixed with 20 jul of a pyridine solution of the internal standard (6-methyl-2-naphthol, p-nitrophenyl phenyl ether). A 200-/lz1 volume of BSA and 50 of pyridine were added. As the silylation proceeded very quickly, the reaction mixture could be injected immediately. 

Chloroquinoxaline undergoes facile nucleophilic displacement reactions with amines and aryloxides to give the corresponding 2-substituted quinoxalines. With diamines, besides the 2-amino derivatives, bis(quinoxalinyl)alkylenediamines are produced. When 2-chloro-quinoxaline is treated with a sodium aryloxide in an excess of the corresponding phenol, a mixture of the expected 2-aryloxyquinoxaline and the corresponding benzofuro[2,3-6]quinoxaline (144) is obtained. 2-Aryloxyquinoxalines are readily cyclized with polyphosphoric acid to benzofuro[2,3-6]quinoxalines. 2-Arylfuro[2,3-h]quinoxalines (146) result from cyclization of 2-phenacyl-3-quinoxalinones (145). ... 

N-oxides of this type are accessible from o-nitroaniline-based syntheses (see earlier section). l,2-Dihydro-2-oxoquinoxaline 4-oxide (64) and its N-methyl derivative (65) condense with compoimds containing an active methylene group in the presence of piperidine, yielding 3-alkylated quinoxalinones (66). The oxide 64, when warmed with aqueous potassium cyanide, affords 3-cyano-l,2-dihydro-2-oxoquinoxaline, whereas oxide 65 gives l,2-dihydro-3-hydroxy-2-oxo-l-methylquinoxaline. ... 

The chemistry of quinoxalin-2-ones and quinoxaline-2,3-diones (2-hydroxy- and 2,3-dihydroxyquinoxalines) has been previously reviewed by Simpson. Quinoxalin-2-ones are very easily prepared from condensation of o-phenylenediamines and a-keto acids and because of their ease of preparation, they have been used as characterizing derivatives for a-keto acids. There are widespread references in the patent literature to the preparation of quinoxalinones for potential pharmaceutical and horticultural applications and also for the formation of polymers. 

Miscellaneous Reactions. Palladium dba has been employed as a catalyst for effecting various annulation reactions. Mediumsized nitrogen heterocycles have been prepared from allenes and amino alkenyl hahdes in the presence of a Pd(dba)2/PPh3 catalyst system. 1,3-Dienes can be converted to benzofuran derivatives upon reaction with o-iodoacetoxy arenes and this reaction has been applied in the synthesis of new coumarins. Dihydro-quinoxalines and quinoxalinones have been obtained via reductive annulation of nitro enamines (eq 26). ... 

As can be seen from the above data (Sect. 6.4.1), the rearrangement proceeds very well with different aroyl- and alkanoyl- derivatives of quinoxalinones and as a... 

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