Quinoxalines, tetrahydro

Except for the tetrahydrobiaryls derived from acridine and from quinoxaline, the postulated intermediate tetrahydrobipyridines have not been isolated but such compounds may be too unstable under the conditions of the reaction to permit their isolation. Evidence is, therefore, still lacking for the last two steps of dehydrogenation and desorption from the catalyst. Dehydrogenation could conceivably occur while the tetrahydro derivative is still adsorbed on the catalyst,... 

This method is widely applicable to the unambiguous synthesis of quinoxalin-2-ones." It involves the intermediate preparation of a l,2,3,4-tetrahydro-2-oxoquinoxaline by the reductive ring closure of the o-nitrophenyl derivative of an a-aminoacid. These derivatives are formed readily from the aminoacid and an o-nitrohalogenobenzene. The final step of oxidation of the tetrahydro- to the dihydro-quinoxa-line is carried out with potassium permanganate or hydrogen peroxide. The preparation of 7-nitroquinoxalin-2-one illustrates the application of this synthesis ... 

Tetrahydro derivatives are formed when either quinoxaline or 6-chloroquinoxaline is reduced with lithium aluminum hydride in ethereal solution. Similar reduction of 2,3-dimethylquinoxaline gives the meso-(cts)-1,2,3,4-tetrahydro derivative. This is shown to be a stereospecific reduction since lithium aluminum hydride does not isomerize the dl-(trans)-compound. Low temperature, platinum catalyzed, hydrogenation of 2,3-dimethylquinoxaline in benzene also gives meso (cis) -l,2,3,4-tetrahydro-2,3-dimethylquinoxaline. ... 

Catalytic hydrogenation of 5-oxy-7,8,9,10-tetrahydro-6a//-pyrido[l,2-a]quinoxalin-6-ylamines 352 over Pearlman s catalyst under 5 atm of H2 in MeOH for 5-7 days at room temperature gave 6,6u,7,8,9,10-hexahydro-5//-pyrido[ 1,2-u]quinoxalines (01EJOC987). 

A sulfoxide was obtained by oxidation of 8-[(4-trifluoromethylmercapto-phenyl)methoxy] derivative 358 with 36% H2O2 in AcOH (98MIP7) and by oxidation of l-[2-(4-thiomorfolin-l-yl)acetyl]-7-(3-methoxyphenyl)-A-methyl-A- [3,5-bis(trifluoromethyl)phenyl]ethyl -5-oxo-1,2,3,5-tetrahydro-pyrido[l,2,3-i/ ]quinoxaline-6-carboxamide with 3-chloroperbenzoic acid (01MIP12). A 7-[(4-fluorophenylsulfonyl)methyl] derivative was obtained by oxidation of a 7-[(4-fluorophenylsulfanyl)methyl]perhydropyrido[l,2-u] prazine with 3-chloroperbenzoic acid in CHCI3 (01EUP1074257). 

Ester group of l-(ethoxycarbonylmethyl)-7-aryl-5-oxo-1,2,3,5-tetrahydro-pyrido[l,2,3-i/e]quinoxaline-6-carboxamides was hydrolyzed and the 1-carboxymethyl moiety was converted to an aminocarbonylmethyl group with 1-methylpiperazine (01MIP12). Bromo atom of l-(2-bromoacetyl) derivatives was substituted by different amines. An amino group in the side chain attached to the position 1 of 7-aryl-5-oxo-l,2,3,5-tetrahydropyr-ido[l,2,3-i/e]quinoxaline-6-carboxamides was acylated, and terc-butoxycarbonyl protecting group of amino group was eliminated. 

Perhydropyrido[l, 2-a]pyrazine-1,6-diones and 6a,7,8,9-tetrahydro-5//-pyrido[l,2-a]quinoxaline-6,10-diones were formed when their precursors bond to a resin were cleaved by an acid (01MIP4). 

Treatment of bis-lactim ether 420 with BuLi, then with cw-l,4-dichloro-2-butene in the presence of Nal afforded 3,4,9,9n-tetrahydro-6//-pyrido[l,2-fl]pyrazin-4-one (421) with 96% diastereomeric excess (97TA1855). Reaction of l,2-diphenyl-6-methyl-quinoxaline with 1,4-dichlorobutane in THF in the presence of Na at —78°C afforded a 3 1 mixture of 4a,5-diphenyl-9-methyl-l,2,3,4-tetrahydro-4a//-pyrido[l,2-n]quinoxaline and 4-(4-chlorobutyl)-2,3-diphenyl-6-methyl-1,4-dihydroquinoxaline (98JHC1349). 

Quinoxaline with allyltributyltin and 2,2,2-trichloroethyl chloroformate (CICO2-CH2CCI3) gave bis(2,2,2-trichloroethyl) 2,3-diallyl-l,2,3,4-tetrahydro-l,4-quinoxalinedicarboxylate (17) (CH2CI2, 0°C, 3 h 30%) and a separable byproduct, bis(2,2,2-trichloroethyl) 2-aUyl-3-hydroxy-l,2,3,4-tetrahydro-l,4-quinoxalinedicarboxylate (18) (18%). ... 

Imidazolidin-2-ylideneamino)quinoxaline gave its 1,2,3,4-tetrahydro derivative (209) [H2 (3 atm), Pt02, MeOH no other details). ... 

In a different way, by involving the Al-(substimted alkyl) substituent, 1-phena-cylquinoxalinium bromide (226) and acrylonitrile gave l-benzoylpyrrolo[l,2-fl]quinoxaline-3-carbonitrile (228), presumably via the tetrahydro derivative (227) (Mn02, EtsN, Me2NCHO, 85°C, 4h 48%) several analogs were... 

Amino-4-methyl-4,6,7,8-tetrahydro-2-quinoxalinecarbonitrile (159) gave 4-methyl-3-[(A(-phenylcarbamoyl)imino]-3,4,5,6,7,8-hexahydro-2-quinoxaline-carbonitrile (160) (authors formulations) (PhNCO, CHCI3, 20°C, 24 h 55% several analogs likewise). 

Benzylamino)methyl-l,2,3,4-tetrahydroquinoxaline (189) and diethyl oxalate gave 2-benzyM,4a,5,6-tetrahydro-l//-pyrido[l,2-fl]quinoxaline-l,2(3//)-dione (190) (neat reactants, 95°C, 20 h 46%). ... 

Amino-2-quinoxalinecarbonitriles (96, R = CN) gave 3-amino-2-quinoxaline-carboxamide (96, R = CONH2) (KOH, H2O2, HjO, EtOH, 40°C, 2 h 72%) the corresponding 5,6,7,8-tetrahydro substrate likewise gave 3-amino-5,6,7,8-tetrahydro-2-quinoxalinecarboxamide (97, R = NH2) (KOH,... 

Bis(o-formylphenoxymethyl)quinoxaline (185, X = Y = 0) gave the macro-cyclic double Schiff base (185, X + Y = NCH2CH2CH2N) (named in Chemical Abstracts as a tetrahydro-9//-benzo[g]quinoxalino[2,3-u][l,6,10,14] benzodioxadiazacycloheptadecine) (H2NCH2CH2CH2NH2, large excess... 

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