Aminoquinoxalines hydrolysis

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). 

Aminoquinoxaline 1-methiodide (65) is slowly formed when 2-aminoquinoxaline is treated with excess of methyl iodide in methanol at room temperature. Decomposition of the 1-methiodide with cold aqueous sodium hydroxide solution gives l-methylquinoxalin-2 one-imine (66) and this on hydrolysis yields l-methylquinoxalin-2-one. ... 

Note Such deacylations have been done by acidic or alkaline hydrolysis to give primary or secondary aminoquinoxalines, both nuclear and extranuclear. Treatment with hydrazine should also achieve deacylation, but there appear to be no recent examples. 

Note. Hydrolysis can give nuclear or extranuclear primary aminoquinoxalines (no recent examples) reduction can give secondary aminoquinoxalines. 

Hydrolysis of 3-methylquinoxalin-2-amine with dilute sodium hydroxide on heating at 100 C affords 3-methylquinoxalin-2(l/f)-one, and of quinoxaline-2,3-diamine in dilute hydrochloric acid yields 3-aminoquinoxalin-2(l f)-one. ... 

There have been several reports of the hydrolysis of 2-aminoquinoxalines to quinoxalinones. For example, 2,3-diamino-quinoxaline is very readily hydrolyzed (2.5 M HCI, 100°, 5 min) to 3-aminoquinoxalin-2-one, and treatment of 2-amino-3-phenylquinoxaline with nitrous acid furnishes 3-phenylquinoxalin-2-one in excellent yield. ... 

Various 3-substituted aminoquinoxaline-2-thiones have been prepared from quinoxaline-2,3-dithione. For example, treatment of the dithione with methylamine yields 3-methylaminoquinoxaline-2-thione, and the corresponding reaction with hydrazine hydrate yields 3-hydrazino-quinoxaline-2-thione. The latter compound is also obtained by treatment of 2,3-dichloroquinoxaline with thiourea and then with hydrazine hydrate. When 2-chloroquinoxaline 1-oxide is heated with thiourea in methanol at room temperature, an unidentified solid m.p. 184-185° is obtained alkaline hydrolysis of methanol-soluble products gives quinoxaline-2-thione in 41% yield. A method of some general applicability is illustrated by the preparation of the thioxo compound 4 from o-anilinoaniline (3). °... 

The reaction of 3-aminoquinoxaline-2-thiones (6) with a-halo ketones such as chloroacetone and co-bromoacetophenone yields quinoxalino-thiazines (7), and hydrolysis of the thiazines in an alkaline medium gives... 

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... 

There is evidence that in the acid hydrolysis of the 2,3-dicycloalkyl-aminoquinoxalines to the corresponding substituted quinoxalinones, the ease of hydrolysis is in the order morpholino>piperidino>pyrrolidinyl. Thus 2-morpholino-3-pyrrolidinylquinoxaline (10) can be selectively hydrolyzed to 3-pyrrolidinylquinoxalin-2-one (11). The hydrolysis of 2,3-dicycloaminoquinoxalines proceeds much more readily than is the case with the corresponding 2,4-disubstituted quinazolines, presumably because of the steric hindrance in the quinoxaline derivatives. ... 

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. ... 

---