Quinoxalines A-oxidation

Quinoxaline A-oxides undergo rearrangement under a variety of conditions. Thus on treatment of 2-ethoxy- and 2-methoxy-quinoxa-line 4-oxide with hydrochloric acid, rearrangement and hydrolysis occurs to give quinoxaline-2,3-dione. A possible intramolecular mechanism of rearrangement is shown in Scheme 7. Reaction of 2,3-... 

Protonation of pyrazine A-oxides takes place at the unsubstituted ring nitrogen as revealed by examination of their UV spectra and ionization constants in water. The same holds for unsubstituted quinoxaline A-oxide and the 3-amino derivative. Pyrazine and quinoxaline di-A-oxides are protonated at one A-oxide oxygen atom (74KGS1554). 

Such direct cyclizations usually occur in basic media to afford quinoxaline A-oxides. For success, C2 in the ethyl group needs to be a carbonyl entity or to be suitably activated. The following examples illustrate this valuable route to such A-oxides (and thence to quinoxalines see Section 4.6.2.1). 

Quinoxaline A-oxides have marked biological effects for example, N- 2-hydroxyethyl)-3-methyl-2-quinoxahnecarboxamide 1,4-dioxide (Olaquindox BA-YO-N-OX) is marketed as a growth-promoting feed additive for stock " ... 

Several recent general papers on the properties of quinoxaline A -oxides have... 

Some aspects of the deoxidative C-substitution of quinoxaline N-oxides (see Section 4.6.2.2 for cross-references) and the photoinduced rearrangement of quinoxaline dioxides into quinoxalinediones (see Section 4.5.1) have been discussed already. The remaining reactions of quinoxaline A -oxides are covered in the following subsections. 

Some minor reactions of quinoxaline A -oxides are illustrated in the following classified examples. 

The only publication on the angularly condensed benzologues, pyrimido[2,l-tf]quinoxalines, describes the synthesis of 161 by formation of both the pyrimido and the pyrazino ring from [6+0] atom fragments. Compound 160, the targeted cyclocondensation product of the propanediamine derivative 159, spontaneously cyclized to the pyri-mido[2,l- ]quinoxaline A-oxide 161 (Equation 17) <2002S2687>. 

Deoxygenation of quinoxaline A -oxides or A, A -dioxides has been realized with sodium dithionite <199681477, 2005AF754>. 

A particular class of quinoxaline A-oxides can be synthesized by a reaction sequence starting from condensation of anilines with a-oximino ketones (Scheme 50) <1998S1769>. The key step is oxidation of the oxime to an a-acetoxy nitroso group, which behaves as an electrophile leading to the formation of the quinoxaline ring. 

Catalytic hydrogenation of iV-(o-nitrophenyl)aminoacetonitriles 192 with palladium(ll) oxide hydrate gives high yields of quinoxaline A -oxides 193 through condensing the reduced hydroxylamine intermediate with nitrile (Equation 31) <2001EJ0987>. 

Cyclization of cr-aryl-o-nitroacetanilides 56 to quinoxaline A-oxides has been reported independently by three groups.66-68 Thus treatment with ethanolic sodium ethoxide of 56 (R=R =H R2=Ph), synthesized from o-nitroaniline and PhCH2COCl, gives l,2-dihydro-2-oxo-3-phenyl-quinoxaline 4-oxide (57 R=R =H, R =Ph). 

The synthesis of quinoxaline A-oxides from benzofurazan 1-oxides, and by N-oxidation of the corresponding substituted quinoxaline derivatives, has already been discussed (Sections II,D and III,C, respectively). 

There are several reports of the deoxygenative halogenation of quinoxaline A-oxides. Thus, 3-(o-hydroxyphenyl)quinoxaline 1-oxide with sulfuryl chloride furnishes 2-chloro-3-(o-hydroxyphenyl) quinoxaline,51 and 2,3-diphenylquinoxaline 1-oxide with phosphoryl... 

The UV spectra of substituted quinoxaline A-oxides 250 have been calculated and also observed experimentally,249 and the effect of solvent... 

A nitrogen common to two rings was obtained by cycloaddition of phenyl isocyanate to 3-picoline TV-oxide.126 Isomeric products 37 and 38 were obtained, the first predominating. Phosgene, acting on an amino-quinoxaline A-oxide, gave a comparable fused ring system.127 Hamana... 

Related 1,3-oxazepines have been obtained from irradiation of many other heterocyclic A-oxides including pyridine A-oxides, isoquinoline A-oxides, quinoxaline A-oxides, quinazoline A-oxides, phenanthridine A-oxides, benzophenazine A-oxides, and acridine A-oxides.4 However, the reported yields are variable and have generally been higher for phenyl and other aryl-substituted derivatives. 

In quinoxaline A -oxides, ring substituents show enhanced reactivity towards nucleophilic substitution relative to the unoxidized compounds, in particular in the position a to the 7V-oxide moiety. 

The synthesis of quinoxaline A-oxides by intramolecular cyclization was first reported by Tennant. ... 

From Benzofuroxan to Quinoxaline A -Oxides or Quinoxaline Di-A -Oxides (the Beirut Reaction)... 

Quinoxaline A -oxide is resistant to nitration with concentrated sulfuric acid and fuming nitric acid at 100... 

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