8-Amino-5 -quinoxalinone

The formation of unsubstituted quinoxaline 1,4-dioxide in the Beirut reaction has been observed using a number of substrates benzoylacetalde-hyde and its enamines,395 vinyl acetate (Et2NH),396 acetylene (NEt3)397,398 propargyl alcohol, propiolic acid, and phenylacetylene (various amines).398 Some of these are unexceptional, but the apparent dephenylation in the case of the phenylacetylene is surprising. However, recently the reaction of benzofuroxan with diethylamine was reinvestigated399 (see Section V,E), and quinoxaline dioxide was found to be one of the major products from a complex sequence of oxidation and reduction reactions. It seems probable with phenylacetylene, and possible in other cases too, that the amines play more than a catalytic role in quinoxaline dioxide production. The amino-quinoxalinone 175 was reported, using vinyl acetate and morpholine.396... 

Aminopyrazines and 2-aminoquinoxalines, like their pyridine analogs, react with nitrous acid under aqueous conditions to give the 2(l//)-pyrazinones and 2(l//)-quinoxalinones. 2-Aminoquinoxalines are more readily hydrolyzed than typical heterocyclic amines and 2-amino-3-methylquinoxaline, for example, undergoes hydrolysis on heating at 100 °C with dilute sodium hydroxide (59JCS1132). 

A,A-Dibenzyl-2-(ethoxycarbonylmethyl)amino-4-(trifluoromethyl)aniline (27) underwent reductive debenzylation and spontaneous cyclization to 6-trifluoro-methyl-3,4-dihydro-2(17/)-quinoxalinone (28) [Pd(OH)2/C, EtOH, H2 (3 atm), 3 days 97%]. " °... 

Chloro-3- [(1 -ethoxycarbonyl-1 -methylethyl)amino] -4-nitrobenzene (61) gave 6-cbloro-3,3-dimetbyl-3,4-dibydro-2(lF/)-quinoxalinone (62) (TiCl3, AcONa,... 

The corresponding half-imidic esters have also been used to afford 3-amino-2(17/)-quinoxalinones. The following examples illustrate typical conditions and yields. 

In contrast, 4-methyl-1,2-benzenediamine (263) and the same synthon (261) gave an inseparable 70 30 mixture of 3-amino-7-methyl- (264) and 3-amino-6-methyl-2(177)-quinoxalinone (265) [EtOH, 25°C, >8 h 77% (mixture)] likewise analogous mixtures. 

Benzenediamine (270) and the nitrone, ethyl 2-amino-2-(oxidophenylimino) acetate (271) (the equivalent of ethyl carbamoylformate) gave 3-amino-2(177)-quinoxalinone (272) with loss of EtOH and A -phenylhydroxylamine (EtOH, trace AcOH, 20°C, h 45%). " ... 

Cyclohexanedione (322) and 2-amino-A -hydroxyacetamide (323) gave 1-hydroxy-5,6,7,8-tetrahydro-2(17/)-quinoxalinone (324) (Et0H-H20, minimal... 

Recent examples of this synthesis are of two types. The first involves condensation of the activated phenol, 2-amino-4,6-dinitrophenol (346a) with 2-dimethyl-amino-3,3-dimethyl-3//-azirine (346b) (in MeCN, 0°C- 20°C, A, 24 h) to afford a separable mixture of four products, one of which was 2-dimethylamino-3,3-dimethyl-5,7-dinitro-3,4-dihydroquinoxaline (346c) ( 20% yield) and another its hydrolysis product, 3,3-dimethyl-5,7-dinitro-3,4-dihydro-2(l//)-quinoxalinone (346d) ( 8%) the mechanism of such condensations has been discussed. ... 

Dimethoxy-1 -methyl-3-p-nitrostyryl-2( l//)-quinoxalinone gave 3-p-amino-phenethyl-6,7-dimethoxy-l-methyl-2(l//)-quinoxalinone (102) (H2, Pt02, AcOEt, 20°C 72% note incidental reduction of the nitro group). 

Amino-5(l/i)-quinoxalinone (123) gave 6,7-dichloro-5,8-quinoxalinequinone (124) (substrate sulfate, HCl, NaClOs, 0°C, 3 h >63% note additional chlorination). 

Amino-5,7-dimethoxy-3-phenyl-2(17/)-quinoxalinone (127) gave 6-methoxy-3-oxo-2-phenyl-3,4-dihydro-5,8-quinoxalinequinone (128) (NaI04, H2SO4, MeOH, H2O, 20°C, 3 min 87%). ... 

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%]." ... 

Amino-3-phenyl-3,4-dihydro-2(177)-quinoxalinone (181) and triphosgene gave 4-phenyl-47/-imidazo[l,5,4-< e]quinoxaline-2,5(l//, 6//)-dione (182) (EtsN, THF, 20°C, N2, until substrate gone by tic 65%) analogs Ukewise. ... 

Amino-3-phenyl-3,4-dihydro-2(l//)-quinoxalinone (194) gave 5-phenyl-2,3-dihydro-17/, 5//-pyrazino[l,2,3-tie]quinoxaline-2,3,6(77/)-trione (195) [(COCl)2,... 

Amino-5-hydroxy-2(l//)-quinoxalinone 3-Amino-l-hydroxy-2(l//)-quinoxalinone... 

Like oxalic acid, oxalic esters and o-phenyldiamines give 2,3(l/7,4/7)-quinox-alinediones that bear substituents according to those on the substrate such condensations appear to be assisted substantially by microwave irradiation.1036 The corresponding half-imidic esters have also been used to afford 3-amino-2(l/7)-quinoxalinones. The following examples illustrate typical conditions and yields. 

---