5,6,7,8-Tetrahydroquinoxalines

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). 

Quinoxalines undergo facile addition reactions with nucleophilic reagents. The reaction of quinoxaline with allylmagnesium bromide gives, after hydrolysis of the initial adduct, 86% of 2,3-diallyl-l,2,3,4-tetrahydroquinoxaline. Quinoxaline is more reactive to this nucleophile than related aza-heterocyclic compounds, and the observed order of reactivity is pyridine < quinoline isoquinoline < phenan-thridine acridine < quinoxaline. ... 

Hydrogenation of quinoxaline, or 1,2,3,4-tetrahydroquinoxaline, over a 5% rhodium-on-alumina catalyst at 100°C and 136 atm, or over... 

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]

EthoxycarbonylaIlylamino)nitrobenzene (53) gave 2-ethoxycarbonyl-methyl-l,2,3,4-tetrahydroquinoxaline (54) (Fe, AcOH, N2, reflux, 30 min ... 

Dibenzyl-2,2-dimethyl-2,3-dihydrobenzimidazole (429) gave 1,4-dibenzyl-2,2-dimethyl-3-phenyl-l,2,3,4-tetrahydroquinoxaline (430) (neat, 200°C, sealed, h 11% after separation from benzaldehyde mechanism pro-... 

Diphenyl-5a,6,7,8,9,9a-hexahydro- 17/-benzodiazepine (448) underwent vapor-phase pyrolysis ( 750°C but no further details) to give 2-phenyl-5,6,7,8-tetrahydroquinoxaline (449) (46%) and 2,4-diphenyl-5,6,7,8-tetrahy-droquinoxaline (450) (4%). ... 

Each quaternary 1 -(2-hydroxyethyl)-2,3-dihydro-1,4-ethanoquinoxalin-1 -ium halide (553, X = Cl, Br, or I) underwent thermolysis to give the corresponding 1 -(2-halogenoethyl)-4-(2-hydroxyethyl)-1,2,3,4-tetrahydroquinoxaline... 

Quinoxaline gave l,4-diethyl-l,2,3,4-tetrahydroquinoxaline by indirect reductive alkylation (AcOH, KBHai, <15°C, 1 h, then reflux, 6h 87% presumably by nuclear reduction, A-acylation, and further reduction of the acetyl groups ). ... 

Methylquinoxaline with phenyUithium gave a separable mixture of 2-methyl-3-phenylquinoxaline (45), 2-methyl-3-phenyl-3,4-dihydroquinoxaline (46), and 2-methyl-2,3-diphenyl-1,2,3,4-tetrahydroquinoxaline (47) [PhLi (made in situ), Et20, <20°C, 90 min 20%, 45%, and 35%, respectively). 

Dibromo-5,6,7,8-tetrafluoroquinoxaline (187) gave 5,6,7,8-tetrafluoroqui-noxaline (186) [H2, Pd/CaCOs (deactivated. Lindlar s catalyst), EtsN CH2CI2, 3 days 44%] or 5,6,7,8-tetrafluoro-l,2,3,4-tetrahydroquinoxaline (188) (H2, Pd/C, EtsN, CH2CI2, 2.5 days >95%) note the selective dehalogenation in both procedures. ... 

Ethyl 6-hydroxy-5,6,7,8-tetrahydro-5-quinoxalinecarboxylate (94) gave a separable mixture of ethyl 5,6,7,8-tetrahydro-5-quinoxahnecarboxylate (95) and 5-hydroxymethyl-5,6,7,8-tetrahydroquinoxaline (96) pSfaBEU (1 mol), Et20, 20°C, 4 h 11% and 69%, respectively when an excess of NaBH4 was used, only product 96 was isolated]. ... 

Nevertheless, two important reactions are exemplified here. l-Benzenesulfonyl-4-[6-(6-methoxy-4-methylquinolin-8-ylamino)hexyl]-l,2,3,4-tetrahydroquinoxaline (72, R = S02Ph) gave l-[6-(6-methoxy-4-methylqui-nolin-8-ylamino)hexyl]-l,2,3,4-tetrahydroquinoxaline (72, R = H) (98% H2SO4, 20°C, 12 h 92%). ... 

Methyl-1,2,3,4-tetrahydroquinoxaline (161) gave 1-methyl-4-[A -phenyl(thio-carbamoyl)]-l,2,3,4-tetrahydroquinoxaline (162) (PhNCS, CH2CI2, reflux, 1 h 30%). ... 

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%). ... 

Although 1- and/or 4-acylated hydroquinoxalines might not be considered as regular quinoxalone ketones, they are included here for pragmatic reasons. Examination of the NMR chemical shifts for H5 and H8 in l,4-diacyl-l,2,3,4-tetrahydroquinoxalines (197, R = Me, Et, Ph, etc.) indicated that the endo-exo conformation (shown) predominated in most such compounds at ambient temperatures. " However, this was disturbed in l,4-dibenzoyl-6,7-dimethyl-l,2,3,4-tetra-hydroquinoxaline (198), which showed a predominance of the exo-exo conformation (shown) below the coalescence temperature. ... 

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