Synthesis from 2 -quinoxalinone

Scheme 2.20 Synthesis of quinoxalinones from 2-oxo-2-aryl acetyl bromides 219...

Table 6.12 Synthesis of benzimidazoles from quinoxalinones and a-picoline via rearrangement...

A Reaction for the Synthesis of Benzimidazol-2-ones, Imidazo[5,4-h]- and Imidazo[4,5-c]pyridin-2-ones from Quinoxalinones and Their Aza-Analogues When Exposed to Enamines... 

Mamedov VA, Saifina DF, Gubaidullin AT, Saifina AF, Rizvanov IKh (2008a) An efficient one-step method for the synthesis of 2-(indohzin-2-yl)benzimidazoles from quinoxalinones and a-picoline via a novel rearrangement Tetrahedron Lett49(43) 6231-6233. doi 10.1016/j.tetlet 2008.08.032... 

Mamedov VA, Zhukova NA, Beschastnova TN, Zakirova El, Kad3TOva SF, Mironova EV, Nikonova AG, Latypov ShK, Litvinov lA (2012) An efficient metal-free synthesis of 2-(pyrazin-2-yl)benzimidazoles from quinoxalinones and diaminomaleonitrile via a novel rearrangement. Tetrahedron Lett 53(3) 292-296. doi 10.1016/j.tetlet.2011.11.013... 

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. 

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],... 

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>. 

Quinoxalinones result from the reaction of o-phenylenediamines and acetylenedicarboxylic acid, as exemplified by the synthesis of 3,6,7-trimethylquinoxalin-2-one (18) The corresponding condensation reactions with acetylenedicarboxylic acid esters yield 3-alkoxycarbonyl-methylenequinoxalin-2-ones, which on hydrolysis and rearrangement give... 

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). ... 

For the synthesis of 2(lH)-quinoxalones, Tennant has reported an intramolecular cyclisation reaction (scheme 2) of 2 -nitroacetoacetanilide 7 to 2(lH)-quinox-alinone-4-N-oxide 8 in aqueous sodium hydroxide. This method has been uskl ( also for the regioselective preparation of various substituted 2(lH)-quinoxalinone-4-oxides and extended with a reduction step to afford 6-halo-2(lH)-quinoxalinones (5.6) as intermediates for pharmaceutical and agricultural chemicals. The 2 -nitro-acetoacetanilides were obtained from the nitroanilines with diketene and mercuric acetate as catalyst in acetic acid or catalytic amounts of triethylamine in refluxing benzene. 

In 2010, Luo and coworkers reported a practical and highly efficient route to the synthesis of pharmaceutically interesting quinoxalinones (Luo et al. 2010). The key step involves an intramolecular palladium-catalyzed A-arylation reaction (Buchwald-Hartwig amination Janey 2007 Appukkuttan and Van der Eycken 2008) under microwave irradiation. The precursors to the quinoxalinone core were easily prepared from D,L-proline 309d in accordance with the mixed anhydride protocol followed by Boc group deprotection (Scheme 2.57). 

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... 

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