Aminoquinoxalines and 2,3-Diaminoquinoxalines

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

The most common substrates for the preparation of aminoquinoxalines are the corresponding chloro compounds. 2-Aminoquinoxaline itself has 

3-Dichloro-6-nitroquinoxaline reacts with aziridine(ethyleneimine) in benzene solution at room temperature, in the presence of triethylamine as acid scavenger, to give the 2-aziridinyl derivative, the 6-nitro group thus selectively activating the 2-chloro substituent. Chlorine activation is also apparent in the substitution reactions of 2-chloroquinoxaline 1-oxide, which is converted into the 2-amino 1-oxide by treatment with aqueous or ethanolic ammonia at 60-80° and thus under much milder conditions than those used for the conversion of 2-chloroquinoxaline into 2-aminoquinoxaline. 

As alternatives to the chloro compounds for substrates in nucleophilic displacement reactions, phenoxy compounds and cyclic amides and cyclic thioamides have been used. It appears that 2-phenoxyquinoxaline is significantly less reactive than the corresponding cinnoline or phthalazine derivatives and only gives a negligible yield of 2-aminoquinoxaline when heated with ammonium acetate. However the phenoxyquinoxaline 1 is converted in high yield into the aminoquinoxaline 2 on treatment with this reagent.  

Quinoxaline-2-carboxamides have been used in the preparation of 2-aminoquinoxalines these derivatives are converted into the corresponding amines by treatment with sodium hypohalite under normal Hofmann-type conditions. 2-Aminoquinoxalines have been prepared by the reduction of aminoquinoxaline N-oxides with hydrogen and a Raney Ni catalyst, and 2-anilinoquinoxaline has been obtained from hydrolysis of 

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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... 

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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