3.4- Dihydroquinoxaline-2-amines

Scheme 35 Synthesis of 3,4-dihydroquinoxalin-2-amine derivatives 196 and two representative 3D conformations of 196A (blue) and 196C (cyan)...

Quinoxalin-2-amine (14) can be synthesized by intramolecular cyclization of (2-aminophcnyl)-aminoacetonitrile (13) to form 3,4-dihydroquinoxalin-2-amine which is then dehydrogenated. The 3.4-dihydroquinoxalin-2-amine need not be isolated for conversion to quinoxalin-2-amine (14). since addition of hydrogen peroxide to the mixture in the presence of a catalytic amount of a transfer agent, such as iron(II) chloride, brings about the required dehydrogenation. ... 

Shobha, D., Chari, M.A., Mukkanti, K. and Kim, S.Y. 2012. Synthesis and anti-neuroin-flammatory activity studies of substituted 3,4-dihydroquinoxalin-2-amine derivatives. Tetrahedron Lett. 53(22) 2675-2679. 

H. Mofakham, Z. Hezarkhani, A. Shaabani, J. Mol. Cat. 2012, 360, 26-34. CeUulose-SOjH as a biodegradable solid acid catalyzed one-pot three-component Ugi reaction synthesis of a-amino amide, 3,4-dihydroquinoxalin-2-amine, 4H-benzo [f>][l,4]thiazin-2-amine and l,6-dihydropyrazine-2,3-dicarbo-nitrile derivatives. 

In 2008, Shaabani and coworkers reported an elegant and hitherto unknown reaction that affords 3,4-dihydroquinoxalin-2-amines 255 via the three-component condensation of 1,2-DAB 155a-c, n, q and ketones 197-199 or aldehydes 252, 253, and an isocyanide 254 in the presence of a catalytic amount of P-TSOH H2O in EtOH at room temperature in good to excellent yields (Scheme 2.32). 

Scheme 2.32 Synthesis of 3,4-dihydroquinoxalin-2-amines 255 from the MCRs of various diamines 155, ketones 197-199 or aldehydes 252, 253, and isocyanides 254...

The Shaabani method is a three-component condensation reaction of 1,2-DABs with diverse carbonyl compounds and isocyanides in the presence of a catalytic p-TsOH with the formation of highly substituted 3,4-dihydroquinoxalin-2-amines involving spiro-cyclic compounds. 

J, Liu Y, Li C, Jia X (2009a) CAN-catalyzed syntheses of 3,4-dihydroquinoxalin-2-amine derivatives based on isocyanides. Tetrahedron Lett 50(47) 6502-6505. doi 10.1016/j.tetlet. 

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... 

The A-acylimine-enamide tautomerism of methyl 2-acetamidoacrylate has been studied641 by means of ab initio calculations. A 13C NMR investigation has been undertaken to study the tautomerism between the hydrazone imine and diazenylen-amine forms of 3-(arylhydrazono)methyl-2-oxo-l,2-dihydroquinoxalines,642 and the effects of temperature and side-chain on the imine-enamine tautomerism in quinoxalinone and pyridopyrazinone systems have been studied.643 A detailed... 

Also included in Expt 8.44, is the preparation of 2,3-diphenylquinoxaline (114) and 3-benzyl-2-oxo-l,2-dihydroquinoxaline (115) from o-phenylenedi-amine and benzil or phenylpyruvic acid respectively. 

Dihydroquinoxalin-2(l//)-one oxime (2) in refluxing acetic anhydride yields iV-(2-quinoxa-line)acetamide (3) in 75% yield, and heating of 2 with palladium on charcoal in ethanolic solution gives quinoxalin-2-amine (4) in 82.5% yield. 

When benzofuroxan is reacted with the enamine (Me20=CHNMe2), the dihydroquinoxaline 1,4-dioxide 21 is obtained. In this case aromati-zation by elimination of amine is structurally precluded. It is suggested that dihydroquinoxalines are the common intermediates in these reactions. ... 

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... 

As distinct from 3-chloro-3-phenylpymvamides 227, 6-chloroacetylaminouracil 229 was refluxed with 1,2-DAB in the presence of triethyl amine (Bondock et aJ. 2011) to yield dihydroquinoxalin-2-ylamino derivative 230 as a mixture of quinoxalinyl-C(3)-CH2- and quinoxalinyl-C(3)=CH- tautomers (Sarg and El-Shaer 2014) (Scheme 2.24). 

The most likely mechanism to rationalize this transformation is illustrated in Scheme 3.80. In an acidic medium, iron could catalyze the reduction of the nitrophenylpyrrole 224 to its amine counterpart E giving ferric salts (or ferrous salts) which in turn would be able to oxidize alcohols into aldehydes. Condensation of these latter with the amine E gives the iminium salts F which spontaneously cyclize leading to the dihydroquinoxalines G as previously described. Finally, a... 

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