2- -1,2-dihydroquinoxaline oxidation

In spite of the usefulness of the Beirut reaction, mechanistically it is not well understood. It has been suggested that the first step involves the nucleophilic attack by the enolate or the enamine at N-3 of the benzofuroxan to yield an intermediate iV-oxide (Scheme 50) which subsequently undergoes tautomerism to an hydroxylamino derivative. This intermediate then cyclizes to the dihydroquinoxaline 1,4-dioxide. This suggestion has not been proven, and indeed there is evidence that benzofuroxan is in equilibrium with 1,2-dinitrosobenzene... 

Diiodoquinoxaline (53) and malononitrile gave the expected product (54) that was characterized as its oxidized counterpart, 5,8-bis(dicyanomethy-lene)-5,8-dihydroquinoxaline (55), confirmed in stmcture by X-ray analysis... 

A mixture of 2-methyl-3-methylene-7-nitro-4-phenyl-3,4-dihydroquinoxaline (97) and its quaternary perchlorate, 2,3-dimethyl-6-nitro-l-phenylquinoxali-nium perchlorate (98), underwent oxidative coupling to give l,2-bis(3-methyl-6-nitro-1 -phenyl-1,2-dihydroquinoxalin-2-ylidene)ethane (99) [Cu-(OAc)2, AcOH-MeCN, 95°C, 20 min 60%] many such condensations... 

Haddadin and Issidorides first reported an elegant method for the synthesis of quinoxaline 1,4-dioxides (47) from the reaction of benzofurazan 1-oxide (46) and an enamine or an active methylene compound, such as a /J-diketone or a /J-ketoester, in the presence of base.46 47 Quinoxaline 1,4-dioxide formation formally involves loss of secondary amine in the enamine reaction and loss of water when an active methylene compound of the type R CH2CORJ is used. This reaction is now commonly referred to as the Beirut reaction. The isolation of the dihydroquinoxaline 1,4-dioxide 48 from the reaction of 46 and NJV-dimethylisobutenylamine (Me2C=CHNMe2), which is unable to aromatize by amine loss, suggests that 2,3-dihydroquinoxalines are likely intermediates in all these reactions.48... 

Dihydroquinoxalin-2-one exhibits two successive one-electron oxidation steps in DMF-Bu4NC104.315 Anodic dehydrogenation occurs presumably through an ECE mechanism. 

Benzene-1,2-diamine undergoes reaction with halomethyl phenyl ketones to give 3-aryl-l,2-di-hydroquinoxalines 1, ° or after oxidation 2-arylquinoxalines 2. ° 1,2-Dihydroquinoxalines can be readily oxidized with different reagents. 

Ouino.xaline di-.Af-oxides are not formed in the reaction of benzofuroxan v/ith malonic acid or malonales however, benzofuroxan reacts smoothly with ethyl cyanoacetate in the presence of a strong base such as l,5-diazabicyclo[4.3.0]non-5-ene (DBN) or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) with the elimination of alcohol to give 3-hydroxyquinoxaline-2-carbonitrile 1,4-dioxide. According to spectroscopic studies, the tautomeric equilibrium is shifted towards l-hydroxy-2-oxo-l,2-dihydroquinoxalin-3-carbonitrile 4-oxide. 

For exchange of a formyl substituent, see Houben-Weyl, Vol. 7/1, p 490. On being heated with 20% aqueous potassium hydroxide, 2-oxO-l,2-dihydroquinoxaline-3-carbonitrile 4-oxide yields quantitatively quinoxaline-2,3-dione 1-oxide. 

Treatment of 2-oxo-l,2-dihydroquinoxaline-3-carbonitrile 4-oxide (1) with aniline, N-methylaniline, or cyclohexylamine results in a displacement of the cyano group and deoxygenation to give 3-substituted quinoxalin-2(127)-ones 2. 

This melts at 226° C., forms an ammonium salt, decomposing at 200° C., and a benzoyl derivative, M.pt. 284° C. In the preparation of the glycine-amide, longer heating, or recrystallisation from an excess of alkali, causes it to change to the quinoxaline. If the latter in sodium hydroxide solution is allowed to stand for several days at 30° C. with an excess of ethylene oxide, the mixture being occasionally shaken, S-hydroiryethyl-amino-6-arsino-l i-dihydroquinoxaline is fomred. 

N-H stretching. The H NMR spectrum, in deuterated acetone, shows a methylene singlet at 5 4.44 and a broad band at 5 5.3 due to N-H absorption, which disappears on addition of D2O. 3-Aryl-l,2-dihydro-quinoxalines give monoacetyl derivatives on treatment with acetic anhydride and are oxidized to the corresponding quinoxalines with ben-zoquinone, ferric chloride, or m-nitrobenzoic acid. Other 1,2-dihydroquinoxalines have been prepared from o-phenylenediamine as illustrated in Scheme 2. 

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... 

Kumar and Pawar 2004 Gu et al. 2005) formed by reaction with the carbonyl group only, or with dihydroquinoxaline derivatives (Das et al. 2007 Chou et al. 2011). Thus, these reactions are usually carried out in the presence of oxidants or under conditions that promote oxidation (Wu and Ede 2001 Singh et al. 2004 Das et al. 2007 Madhav et al. 2009 Meshram et al. 2010 Chou et al. 2011). 

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