1- -quinoxalinone, 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). 

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. ... 

Most tautomeric quinoxalinones have been made either by primary synthesis (see Chapter 1) or by direct or indirect hydrolysis of halogenoquinoxalines (see Section 3.2.2). The remaining preparative routes are illustrated in the following classified examples. 

The kinetics for alkaline hydrolysis of 2-(o-, m-, or -nitrophenoxy)quinoxaline to 2(171)-quinoxalinone have been measured in some detail. 6,7-Dimethoxy-2-phenylquinoxaline (17) gave 2-phenyl-6,7(l//,4//)-quinoxaline-dione (18) (48% HBr, reflux, 23 h 53% as hydrobromide). 

Note There appear to be no recent examples of this reaction with simple alkoxy substrates (perhaps because normal aliphatic ethers need quite vigorous treatment, such as boiling hydriodic acid), but so-called isopropylidenedioxy derivatives (that undergo facile hydrolysis) have been used in this way. l-[2,3-(Isopropylidenedioxy)propyl]-3-methyl-2(17/)-quinoxalinone (165) gave l-(2,3-dihydroxypropyl)-3-methyl-2(l//)-quinoxahnone (70% AcOH, reflux, 2 h 35% homologs likewise). ... 

These ethers, both nuclear and extranuclear, undergo a few useful reactions, including hydrolysis to corresponding quinoxalinones or hydroxyquinoxalines, which has been covered in Sections 4.1.1 and 4.3.1, respectively. The other reactions are illustrated in the following classified examples. 

Note Perhaps because so many halogenoquinoxalines are themselves derived from quinoxalinones, the reverse process of hydrolysis is seldom reported the examples are all special cases in which a passenger group would complicate or preclude a straightforward acidic or alkaline hydrolysis. 

Numerous 2(177)-quinoxalinones and their 1-methyl derivatives were prepared by multistep manipulation starting from anilines <2005H(65)2741>. A considerable interest attaches to reaction of 2,3-furandiones 190 with 1,2-diaminobenzenes to produce 2(l//)-quinoxalinones 191, which can be converted into 3-phenacyl quinoxalinones by alkaline hydrolysis (Scheme 58) <2005H(65)2161>. 

During the last few years, numerous quaternary salts of quinoxalines have been prepared, and their reactions studied. 2-Methylquinoxaline and some of its 6,7-substituted derivatives (101) form 4-methyl-quinoxalinium methosulfates and perchlorates (102).116 On hydrolysis of these salts, the quinoxalinones (103) are formed. Similarly 2,3-dimethyl-... 

Attempted cyclization of 233 with alkali afforded 234 in addition to 238, resulting from the elimination of one molecule of water from the hydrazone residue and the quinoxalinone ring and simultaneous hydrolysis of the ester group. This indicated the presence of two competitive reactions under conditions of cyclization. The structure of 234 was proved by its preparation by hydrolysis of 235. The latter was prepared by the reaction of aldehyde 237 with the phosphorane. The structures were confirmed by studying their H-NMR and mass spectra. 

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... 

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. ... 

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. ... 

Irradiation of the diazepine N-oxide 8 gives a mixture of the 1,2-dihydroquinoxaline (10) and the oxadiazocine 11 through an intermediate oxaziridine (9). The dihydroquinoxaline undergoes acid hydrolysis to the quinoxalinone 12. It was subsequently shown that quinoxalinones of type 12 undergo ready reaction with ammonia or primary or secondary amines, in the presence of titanium tetrachloride, to give 3-amino- or... 

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