2.3- Diaminoquinoxalines

Although o-phenylenediamine and DISN react under neutral conditions to give a low yield of 2,3-diaminoquinoxaline, DAMN and DISN do not react at all under these eonditions and at elevated temperatures gross mixtures are obtained. Weakly basic or acidic catalysts promote the condensation, but the acyclic products 51 and 52 dominate the mixtures which usually result (Scheme 21) (74JOC1235). 

The curiously named fluorubine, 6,13-dihydropyrazino[2,3-f> 5,6-6 ]diquinoxaline (83), is a bright yellow compound prepared by condensation at 270 °C of 2,3-diaminoquinoxaline with 2,3-dichloroquinoxaline (03CB4039). The condensation can also be effected in dimethyl-formamide alternatively 2-amino-3-chloroquinoxaline will undergo self-condensation in the same solvent (63GEP1142981). 

Diethyl acetylenedicarboxylate with 2,3-diaminoquinoxaline (462) in methanol gave pyrazino[2,3-6]quinoxaline (463), which exists as the tautomer 464 in the solid state. In solution, NMR measurements show that a tautomeric mixture of both 463 and 464 is present.435... 

Quinoxaline (235) has been easily aminated in liquid ammonia with excess potassium amide and potassium permanganate as oxidant (82JHC1285). The ratio of monoamino to diamino products can be altered by varying the reaction time prior to addition of the oxidant (Scheme 78). When potassium permanganate was added 5-10 min after 235 was added to liquid ammonia containing potassium amide, the yield of 2-aminoquinoxaline (236) was 53% and 2,3-diaminoquinoxaline(237) was 23%. However, if the oxidant was not added until 30 min had elapsed, the yield of 236 was 4% and that of 237 was 57%. 

Substituted quinoxalines undergo some interesting reactions when treated with nucleophilic reagents. When 6-bromoquinoxaline is treated with potassium amide in liquid ammonia the main product is benzimidazole. Minor amounts of 2-amino- and 2,3-diaminoquinoxalines are also formed, but none of the expected 5- and 6-aminoquinoxalines are obtained (Scheme ) Similar treatment of 6-chloroquinoxaline gives a mixture of 2-amino-7-chloroquinoxaline and 6-chloro-2,3-diamino-quinoxaline. It has been suggested that the difference in behavior between the 6-bromo and 6-chloro compounds may be explained by the... 

Dichloroquinoxaline has been converted into a number of polycyclic derivatives by reaction with o-disubstituted benzenes. Thus reaction with o-phenylenediamines gives tetraazanaphthacenes (17), and the corresponding reaction with 2,3-diaminoquinoxaline gives fluorubin derivatives (18). Quinoxalino[2,3-h]benzothiazine derivatives (19) result from the reaction of dichloroquinoxaline and o-aminobenzenethiol and... 

The chemistry of 2-amino- and 2,3-diaminoquinoxalines has been previously reviewed by Simpson. ... 

A number of 2,3-diaminoquinoxalines have been prepared by heating a... 

Diaminoquinoxalines are obtained from the reaction of o-phenylenediamines with cyanogen in methanol containing a little aqueous sodium hydroxide solution." A variant on this procedure is first to prepare the oxaldiimido ester 7 from cyanogen and methanolic sodium methoxide and then to react the isolated ester with an o-phenylene-diamine (Scheme 5). " The latter method has been used with a wide range of nuclear-substituted diamines. 

Monoacylation of 2,3-diaminoquinoxalines has been achieved by reaction with an acid anhydride in THF. Under more vigorous conditions reaction of 2,3-diaminoquinoxalines with acid anhydrides results in ring closure to an imidazo[ ]quinoxaline. Similar ring closures have been carried out with aldehydes, acyl halides, formic acid, orthoesters, and urea. Polycyclic compounds have also been prepared from 2,3-diaminoquinoxaline by reaction with 1,-2-dicarbonyl compounds and 1,2-diamines, as illustrated in Scheme 7. 

Imidazo[4,5-h]quinoxalines have invariably been prepared from quinoxaline intermediates. Almost twenty years elapsed between the first reported synthesis of the ring system and the next publication containing an extensive study of the utility of reagents for converting 2,3-diaminoquinoxalines into 2-substituted imidazo[4,5-h]quinoxalines. ... 

Although the 1,3-diphenyl 2-oxo compound 63 is stable to acid hydrolysis, imidazo[4,5-h]quinoxaline itself undergoes very ready hydrolytic ring opening. Hot dilute hydrochloric acid gives 3-aminoquinoxalin-2-one (74), and hot alkali affords 2,3-diaminoquinoxaline (57). Similarly acid treatment of the 2-methyl N-oxides 72 and 73 provides the quinox-aline N-oxides 75 and 76, respectively. ... 

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