Tetrahydroquinoxaline, from quinoxaline

The fusion of a benzene ring to pyrazine results in a considerable increase in the resistance to reduction and it is usually difficult to reduce quinoxalines beyond the tetrahydroquinoxa-line state (91). Two possible dihydroquinoxalines, viz. the 1,2- (92) and the 1,4- (93), are known, and 1,4-dihydroquinoxaline appears to be appreciably more stable than 1,4-dihydropyrazine (63JOC2488). Electrochemical reduction appears to follow a course anzdogous to the reduction of pyrazine, giving the 1,4-dihydro derivative which isomerizes to the 1,2- or 3,4-dihydroquinoxaline before subsequent reduction to 1,2,3,4-tetra-hydroquinoxaline (91). Quinoxaline itself is reduced directly to (91) with LiAlH4 and direct synthesis of (91) is also possible. Tetrahydroquinoxalines in which the benzenoid ring is reduced are well known but these are usually prepared from cyclohexane derivatives (Scheme 30). 

N-Substituted quinoxalines are obtained from N-substituted o-phenylenediamines. Thus methyl 2,3-dibromopropionate condenses with (V,A -bis(/7-toluenesulfonyl)-o-phenylenediamine to give l,4-bis(p-tolu-enesulfonyl)-2-methoxycarbonyl-1,2,3,4-tetrahydroquinoxaline (20).25 AVV -Disubstituted cyclohexane-1,2-diamines with suitable a/7-dihalides yield decahydroquinoxalines.26 Condensation of cyclohexane- 1,2-diones with glycine amide gives 2-oxo-5,6,7,8-tetrahydroquinoxalines.27... 

Sodium borohydride or sodium borohydride and trifluoroacetic acid reduce 5- or 6-sub-stituted quinoxalines to the 1,2,3,4-tetrahydro compounds 1.2,3,4-tetrahydroquinoxaline is also formed in the reduction of quinoxaline with bis(trifluoroacetoxy)boranc-tetrahydrofuran. The sodium borohydride reduction of 2,3-dimethylquinoxaline 1,4-dioxide in alcohols affords c 3-2,3-dimethyl-l,2,3,4-tetrahydroquinoxaline as the predominant product and identical to that obtained from the reduction of 2,3-dimethylquinoxaline with lithium aluminum hydride. ... 

Reduction of quinoxaline with sodium in THF at 20° yields a deep-purple solution from which 1,4-dihydroquinoxaline is isolated. Reduction with either sodium in refluxing alcohol or lithium aluminum hydride in ether gives 1,2,3,4-tetrahydroquinoxaline. Hydrogenation of quinoxaline over a 5% rhodium-on-alumina catalyst at 100° and 136 atm or over freshly prepared Raney nickel W-6 under similar conditions gives meso-(cis)-decahydroquinoxaline. ° However hydrogenation of quinoxaline over a palladium-on-charcoal catalyst at 180° and 50 atm gives dl-(/rans)-decahydroquinoxaline." ... 

Quinoxaline readily reacts with Grignard reagents. Addition of two molecular proportions of allylmagnesium bromide and of 3-(dimethylamino)propylmagnesium chloride, and hydrolysis of the initial adducts, gives the tetrahydroquinoxalines 2 and 3, respectively. The 1 1 adducts 4, 5, and 6 are obtained from the reaction of quinoxaline with diphenylcyclopropenone, diphenylcyclopropenethione, and methyl phenylhydrazonochloroacetate in the presence of triethylamine, respectively. In the latter case the presumed intermediate is the dipolar... 

Tetrahydroquinoxalines have also been prepared by cyclization of ortho-disubstituted benzenes. Thus high-temperature (200-210°) reaction of catechol with ethylenediamine gives 1,2,3,4-tetrahydro-quinoxaline tetrahydroquinoxalines have also been prepared from hexafluorobenzene. ° The reaction of N,N -ditosyl-o-phenylenediamine with a variety of 1,2-dibromo compounds " gives. 1,2,3,4-tetrahydro-quinoxalines, as illustrated in Scheme 3. 

Bovine superoxide dismutase and catalase were purchased from Sigma Chemical Co., glutathione peroxidase from Boehringer Mannheim and quinoxaline from Fluka AG. The synthesis of 6,7-dimethylperin and its 7,8-dihydro derivative has been described before. 6,7-Dimethyl-5,6,7,8-tetra-hydropterin was prepared by controlled potential electrolysis a 0.1 M phosphate buffer pH 7.0 at a glassy carbon or a mercury pool cathode. After complete electrolysis the tetrahydropterin was used in situ. 1,2,3,4-Tetrahydroquinoxaline was prepared by reducing quinoxaline in dry ether with lithium aluminium hydride or in ethanol with solid sodium. ... 

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