Reduction of quinoxalines

The redox behavior of aminonaphthoquinones has been investigated by Matsuoka and co-workers.11 Reduction of quinoxaline quinone (40) by sodium dithionite in aqueous sodium hydroxide gives the corresponding leuco dye (41) which absorbs at 445nm. Compound 40 shows quinone-... 

The cathodic reduction of quinoxaline or 4-methylcinnoline in the presence of acetic anhydride affords diacetylated products [264] as depicted in Scheme 146 for quinoxaline. 

Reduction of quinoxalines was carried out by catalytic hydrogenation [491, 492,493,494], with sodium borohydride [490] or with lithium aluminum hydride [476] to different stages of saturation. 

Reduction of quinoxaline with sodium in tetrahydrofuran (THF) at 20° yields 1,4-dihydroquinoxaline (26%).91 A 1,4-dihydroquinoxaline (75) is also the first product of reduction of 2-phenylquinoxaline (74), but 75 readily rearranges to the thermodynamically more stable 1,2-dihydro isomer (76).92... 

The reduction of quinoxalines was discussed in Part I1 newer investigations have confirmed the general scheme.312,313 The quaternized compound,... 

In aqueous alkaline solution a dimeric product is formed on reduction of quinoxaline besides the 1,4-dihydro compound on acidification it dissociates.173... 

The reduction of quinoxaline derivatives or quaternized quinoxalines by titanium(lll) chloride leads to di- or tetrahydro compounds. Several reductions of quinoxalines to 1,2,3,4-tetrahy-droquinoxalines with hydrogen and a metal catalyst at room temperatures and pressure not exceeding 3 atmospheres have been described, the yields of which are sometimes strongly solvent dependent. At higher temperatures and pressures decahydroquinoxalines may be reaction products. ... 

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 with concomitant A, Af -dialkylation is achieved by the action of potassium borohydride in the presense of carboxylic acids. Similarly, reduction of quinoxalines with sodium borohydride or sodium cyanoborohydride in the presence of benzyl chloroformate gives A -benzyloxycarbonyl- or /V,jV -bis(benzyloxycarbonyl)tetrahydro derivatives. ... 

Reduction of quinoxaline and its derivatives with sodium in tetrahydrofuran or ethanol affords l,4-dihydroquinoxalines. ... 

Upon reduction of quinoxaline with 5 M sulfuric acid and zinc, some ring cleavage of the intermediate dihydro compound occurs and, in addition to tetrahydroquinoxaline, benzene-1,2-diamine and acetaldehyde are formed. 

Reduction of quinoxaline in DMF in the presence of acetic anhydride [308] produces... 

Reduction of quinoxaline with lithium aluminum hydride in ether yields 43% of 1,2,3,4-tetrahydroquinoxaline (81), also obtained in 20% yield by reduction with sodium in refluxing alcohol. Both sodium borohydride in acetic acid, and hydrogen and platinum, have been used to reduce 6-substituted quinoxalines to the 1,2,3,4-tetrahydro compounds. Quinoxaline and its 2-methyl derivative undergo reductive formylation when treated with formic acid in formamide 1,4-diformyl-... 

Dihydro-, 1,4-dihydro-, 1,2,3,4-tetrahydro-, and decahydroquinox-alines are known (Chapter XVIII). Thus reduction of quinoxaline with lithium aluminum hydride yields 1,2,3,4-tetrahydroquinoxaline (Chapter II). Quinoxaline also adds two molecular proportions of Grignard reagent to give a 2,3-disubstituted 1,2,3,4-tetrahydroquinoxaline (Chapter II). It also undergoes cycloaddition reactions with reagents such as diphenylcyc-lopropenone to form 1 1 molecular adducts (Chapter II). 

The polarographic reduction of quinoxaline and its derivatives has been studied by a number of workers. Half-wave electrode potentials are pH dependent and over the pH range of 1 to 10, Ei has been reported to vary from —0.254 to -0.863 The half-wave electrode potential in anhydrous dimethylformamide is — l.bOV for quinoxaline, —1.06 V for cinnoline, —1.41V for phthalazine, and —1.22 V for quinazoline. The benzodiazines are more easily reduced than the corresponding diazines, thus pyrazine has a half-wave electrode potential of -1.57V. Pyridine with a half-wave potential of —2.15 V is still more difficult to reduce. The reversible reduction potential of quinoxaline as determined by cyclic voltammetry is -1.097 V. The observed energy differences between azine and radical anion are well correlated with the results of CNDO and SCF iT-electron calculations. 

Detailed study of the electrochemical reduction of quinoxaline in aqueous media has revealed that 1,2,3,4-tetrahydroquinoxaline is formed via a sequence involving 1,4-dihydroquinoxaline and acid-catalyzed rearrangement of the 1,4-dihydro derivative to 1,2-dihydroquinoxaline (Scheme... 

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." ... 

Reduction of quinoxaline with sodium in tetrahydrofuran, or elec-trochemically in an alkaline medium, gives 1,4-dihydroquinoxaline. This is described as a white, insoluble compound of m.p. 158-159°, and it is thought to be a 1,4- rather than a 1,2-dihydro compound because reaction with methyl magnesium iodide shows that it contains approximately 1.8 atoms of active hydrogen per molecule. 

Tetrahydroquinoxalines are prepared either by the reduction of quinoxalines or by the cyclization of ortho-disubstituted benzenes. The lithium aluminum hydride reduction of quinoxaline itself gives 1,2,3,4-tetrahydroquinoxaline, and reduction of the 2,3-dimethyl derivative has been shown to occur stereospecifically to give cis-l,2,3,4-tetrahydro-2,3-dimethylquinoxaline (m.p. 113-114°). ° Sodium and ethanol reduction of... 

There are numerous papers describing the reduction of quinoxalines to... 

Reduction of quinoxaline with potassium borohydride in acetic acid gives an excellent yield of l,4-diethyl-l,2,3,4-tetrahydroquinoxaline phthalazine reacts similarly, and other carboxylic acids can be used. ... 

The reduction of quinoxaline (29) with Eu, or Ti in I.2M-HCIO4 yields the strongly absorbing quinoxalinium radical (QH-), which under favour-... 

Recently, the first example of asymmetric hydrogenation of thiophenes and benzothiophenes was reported by Glorius and coworkers (Scheme 3.12) [31]. High levels of reactivities (up to 99%) and enantioselectivities (up to 98% ee) were achieved by in situ generation of the catalyst from 23 and [Ru(COD)(2-methylallyl)2]. Qrmpared to the reduction of quinoxalines and benzofurans. 

Recently, Chen et al. reported a novel hydrogenation of quinoxalines 357 via the convergent disproportionation reaction of dihydroquinoxalines 359 under a ruthe-nium/Br0nsted acid relay catalysis system (Scheme 2.95) [130a]. This transformation was initiated by the reduction of quinoxalines to dihydroquinoxalines 359 under the catalysis of [Rul/i-cymene) ] 360 the active intermediate then underwent phosphoric acid-catalyzed self-transfer hydrogenation to afford primary starting material 357... 

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