Tetrahydroquinoxalin-2-one

Amino-1,2,3,4-tetrahydroquinoxalin-2-ones (83) [obtained by reduction of AT-(2,6-dinitrophenyl)-cr-amino acids] undergo ring closure... 

A closely related study led to microwave-assisted liquid-phase synthesis of chiral quinoxalmes [81]. A variety of L-a-amino acid methyl ester hydrochlorides were coupled to MeO-PEG-bound ortho-fluoronitrobenzene by the already described ipso-fluoro displacement. Reduction under the action of microwave irradiation resulted in spontaneous synchronous intramolecular cyclization to the corresponding 1,2,3,4-tetrahydroquinoxalin-2 -ones. 

Cyclization of 4-cinnamoyl-l,2,3,4-tetrahydroquinoxalin-2-one (416) by treatment with AICI3 yielded l,2,3,5-tetrahydropyrido[l,2,3-[Pg.319]

Pyrolysis of 2-substituted l,3-dibenzyl-2-methylbenzimidazoles at 200°C results in ring expansion to afford the tetrahydroquinoxalines 180 (Equation 29) <1996TL3355>. The reaction was suggested to proceed by an ionic mechanism rather than a radical one. 

Lee, J. Murray, W. V. Rivero, R. A. Solid Phase Synthesis of 3,4-Disubsti-tuted-7-carbamoyl-l,2,3,4-tetrahydroquinoxalin-2-ones, J. Org. Chem. 

Ethoxycarbonyl-l,2,3,4-tetrahydroquinoxalin-2-ones (86) are obtained either by sodium dithionite reduction of the corresponding quin-oxalinone esters or by direct synthesis from o-phenylenediamines and bromomalonic ester (85).102... 

The oxidation of quinoxaline derivatives of 2//-pyrido[l, 2-a]pyrimidin-2-one 70 and 291 with 30% hydrogen peroxide in acetic acid at 100°C gave 2,3-dioxo-l,2,3,4-tetrahydroquinoxaline 292 in good yield (80CPB3537). 

Although benzopiperazinones (l,2,3,4-tetrahydroquinoxalin-2-ones) are structurally related to benzodiazepines, their use in drug discovery is less well established. Examples of biological activity of benzopiperazinones include their action as inhibitors of aldose reductase [208], as partial agonists of the y-aminobutyric acid (GABA)/benzodiazepine receptor complex [209, 210], and as angiotensin II receptor antagonists [211]. In addition, derivatives with antiviral acti vity associated vfith HIV have been reported [212, 213]. 

Ethoxycarbonylmethylene-l,2,3,4-tetrahydroquinoxalin-2-one (33) has been used as an intermediate to synthesize the isoxazolo- and triazoloquinoxalines 52 and 53. On heating the quinoxalinylpropionic ester (54) in diphenyl ether, ring closure to the furoquinoxaline (55) occurs. 

Alkylation of tetrahydroquinoxalines cannot be stopped at the monoalkylation stage however treatment of tetrahydroquinoxalines with ben-zenesulfonyl chloride, at a low temperature, gives monophenylsulfonyl derivatives. These on alkylation and subsequent acid hydrolysis of the protecting group yield l-alkyl-l,2,3,4-tetrahydroquinoxalines. " An alternative approach involves the alkylation of tetrahydroquinoxalin-2-ones and subsequent reductive removal of the carbonyl function (Scheme... 

Tetrahydroquinoxalines such as the ester (20, R = H) have been studied as model compounds for tetrahydrofolic acid. The latter has a vital role in one-carbon metabolism. On treating the ester with formaldehyde, in aqueous dioxan, the fused imidazoline 40 is isolated. Compound 40 undergoes acid-catalyzed rearrangement to the diazepine 42. Using a suitably blocked ester (20, R = Me), it has been possible to isolate the formaldehyde condensation product 41, formed by interaction with nitrogens 4 and 10. It is suggested that a compound of this type is formed prior to the imidazoline 40. ... 

Synthetic routes to cis- and trans-decahydroquinoxaline have been carefully evaluated the best route to ds-decahydroquinoxaline is shown in Scheme 8. Condensation of 1,2-cyclohexanedione with glycine amide gives 5,6,7,8-tetrahydroquinoxalin-2-one (48), and this on reduction with... 

Substituted tetrahydroquinoxalin-2-ones have been prepared on the RAM support 7c [303] by first coupling 4-fluoro-3-nitrobenzoic acid to the support in the presence of HATU using a procedure comparable to that described earlier followed by displacement of fluorine by an a-aminoester. Reduction of the nitro group useing tin (II) chloride lead to ring closure (Scheme 13) and further alkylation was followed by TFA-induced cleavage. 

Alkylation of o-(A-sulfonylamino)phenyimino derivatives of indol-2-one and cyclohepta[c]furan 211 with phenacyl bromides 212 is accompanied by cyclization to tetrahydroquinoxalines 213 with spiro-fused oxoindole or cyclohepta[c]furan fragments (Scheme 2.16) (Kurbatov et al. 2004). In these cases, only one carbon atom is supplied by the phenacyl bromides for the construction of the pyrazine. 

Diethyl (7 ,/ )-oxirane-2,3-dicarboxylate was obtained from diethyl 2R, 31 )-(+)-tartrate with 1,2-DABs at elevated temperature under argon to give optically active tetrahydroquinoxalin-2-ones 473 in good yields (Scheme 2.99) (Woydowski et al. 1998). Note that for 1,2-DABs, and derivatives with electron-donating substituents, refluxing in ethanol is sufficient, whereas for 4-nitro-1,2-DAB, 155n, heating without a solvent at 155 °C is required (Woydowski et al. 1998). 

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