5.6.7.8- Tetrahydroquinoxaline, oxidation

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). 

Two 4-substituted 1,2,4-triazole 1-oxides, namely 2-(l -hydroxymethylene-2-oxo-l,2,3,4-tetrahydroquinoxaline-1-yl)-4-allyl-5-methylthio 1,2,4-triazole 1-oxide 530 (1984H695) and 4-hydroxy-l,2,4-triazole 1-oxide 531 (1995J CS(P1)243), (Scheme 157) derived from the parent species 528 (Scheme 156), have been described. The compounds were characterized by their H NMR and C NMR spectra. 

Tetrahydroquinoxaline was hydrogenated to the decahydro derivative over platinum oxide in acetic acid,—better—in an absolute ethanolic hydrogen chloride (eq. 12.87). In ethanolic aqueous hydrogen chloride or aqueous hydrochloric acid, considerable hydrogenolysis occurred to give a mixture of decahydroquinoxaline and A-cyclo-hexylethylenediamine, and also neutral substances (e.g., cyclohexanol) in the latter solvent.168... 

The method has also been applied to the synthesis of alkyl-substituted quinoxalin-2-amines. Thermal rearrangement of l-(2-aminophenyl)-4,5-dihydro-5-morpholino-l,2,3-triazoles 15 affords unstable 2-alkyl-l,2,3,4-tetrahydroquinoxalin-3-amines, which undergo deamination and consequent oxidation to afford 2-alkylquinoxalines 16. ... 

The synthesis of (quinoxaline-2,3-diyl)bis(aryldiazenes) 1 in high overall yields (77-84%) proceeds via reaction of benzene-1,2-diamine with l,2-dichloro-l,2-ethaiiebis(iV-arylhydra-zones) in the presence of tricthylamine and oxidation of the resultant 2,3-bis(arylhydrazono)-1,2,3,4-tetrahydroquinoxalines with iodobenzene bis(trinuoroacetate). ... 

The sodium tungstate catalyzed oxidation of 1,2,3,4-tetrahydroquinoxaline with 30% aqueous hydrogen peroxide solution in methanol gives quinoxaline. ... 

The hydrodimerization is also a useful method in the preparation of heterocycles [7,8], 6>-Bis(yS-bicarbethoxyvinylamino)benzene (III) thus yields by intramolecular reductive coupling 2,3-bis(dicarbethoxymethyl)-l,2,3,4-tetrahydroquinoxaline (IV), which on heating gives quinoxaline [7], as in Eq. (2). Compound IV may be anodically oxidized to the substituted quinoxaline [9],... 

The NBH reduction of 1,4-quinoxaline di-A -oxide (327) in alcohols has been shown to produce the d5-tetrahydroquinoxalines 328 as the predominant product. The product 328 was identical to that obtained from the reduction of 2,3-dimethylquinoxaline with LAH. ... 

Several examples of the successful lithium aluminum hydride reduction of l,2,3,4-tetrahydro-2-oxoquinoxalines to the corresponding tetrahydroquinoxalines have been recorded in the literature. " A moderate yield of 1,2,3,4-tetrahydroquinoxaline is obtained by reduction of 1,2,3,4-tetrahydro-2,3-dioxoquinoxaline with lithium aluminum hydride in N-ethylmorpholine. The anils 19 give the tetrahydroquinoxalines 20 on treatment with sodium borohydride. This reagent has also been used to reduce a number of 2,3-disubstituted quinoxaline di-iV-oxides to the corresponding cis-tetrahydro derivatives. The trans isomers can be prepared by first reducing the N-oxides with sodium dithionite to the parent quinoxalines, and then the further reduction of the quinoxalines so formed with sodium and ethanol. ... 

The replacement of 1,2-DAB 155a by 2,3-diaminomaleonitiile 468 in the reaction with cyclohexene oxides 466b, d led to the tetrahydroquinoxaline derivatives 469, according to Scheme 2.97 (Antoniotti and Dunach 2002). 

Scheme 2.97 Synthesis of tetrahydroquinoxaline derivatives 469 from cyclohexene oxides 466h, f and 2,3-diaminomaleonitrile 468...

Benkovic SJ, Bullard WP, Benkovic PA (1972) Models for tetrahydrofolic acid. HI. Hydrolytic interconversions of the tetrahydroquinoxaline analogs at the formate level of oxidation. J Am Chem Soc 94(21) 7542-7549. doi 10.1021/ja00776a043 Benkovic SJ, Barrows TH, Farina PR (1973) Models for the tetrahydrofolic acid. IV. Reactions of amines with formamidinium tetrahydroquinoxaline analogs. J Am Chem Soc 95(25) 8414-8420. doi 10.1021/ja00806a036... 

So there must be another explanation, why cytochrome b is not reduced. Figure 2 shows the values for the midpoint potentials of the components of the electron transport chain. From this it can clearly be seen that the difference between the potentials of both the dihydro/tetra-hydropterin and the dihydro/tetrahydroquinoxaline redox couples and that of cytochrome b, is too small for reduction to take place. On the other hand, the potential differences between the mediator couples and both the midpoint potentials of cytochrome c and cytochrome a/aa are large enough to drive the reduction. For the same reason, ascorbate alone cannot reduce cytochrome b (Figure ID). It had been shown earlier that the dihydro/-tetrahydropterin mediator system can be used for the oxidation of NADH, but naturally not for the reduction of NAD+. 

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