Quinoxaline oxidation

Note Only a few simple examples of the metal complexes formed by quinoxaline oxides and dioxides are given here. 

A series of quinoxaline oxides 70 and 72 was obtained by the classical Beimt reaction of the substituted benzofuroxanes 71 and the 1,3-diketones, /3-ketoesters, amides, or l-(alkyl/phenyl) 4,4,4-trifluoromethyl-/3-diace-tones (Scheme 16) <1999CHE459, 2004BMC3711>. 

D. Preparation of Quinoxaline -Oxides from Benzofurazan 1-Oxides and o-Quinone Dioximes... 

Quinoxaline -oxides substituted in the 2,3-position undergo facile nucleophilic displacement. Numerous reactions have been investigated in the search to prepare derivatives which are active... 

Less common methods of synthesis include nitrosation of suitable alkenes in acetonitrile solution (see Section 3.02.8.1.3(ii)) <84TLI319>, cyclization of iV-alkoxy ureas <87S1058>, and specific approaches to benzimidazole oxides from quinoxaline oxides, and to imidazole oxides from oxa-diazine and pyrazine oxides <93CHE127>. 

Benzofuroxans into Quinoxaline Oxides and Benzimidazole Oxides. . . 306... 

The authentic quinoxaline -oxide (108) is prepared from quinoxaline 1,4-dioxide by the following route ... 

The ease of oxidation varies considerably with the nature and number of ring substituents thus, although simple alkyl derivatives of pyrazine, quinoxaline and phenazine are easily oxidized by peracetic acid generated in situ from hydrogen peroxide and acetic acid, some difficulties are encountered. With unsymmetrical substrates there is inevitably the selectivity problem. Thus, methylpyrazine on oxidation with peracetic acid yields mixtures of the 1-and 4-oxides (42) and (43) (59YZ1275). In favourable circumstances, such product mixtures may be separated by fractional crystallization. Simple alkyl derivatives of quinoxalines are... 

Cerium(IV) ammonium nitrate in methanol has been used to oxidize phenazine to the mono-N-oxide (41) in good yield (75JCS(P1)1398), but no other reports on the application of this reagent to the pyrazine or quinoxaline series have appeared. 

Many pyrazine and quinoxaline syntheses yield mono- or di-N-oxides (76H(4)769). The condensation of a-aminooximes with 1,2-diketones results in the direct formation of pyrazine mono-N-oxides. The a-aminooximes themselves are not easily prepared but 2-amino-2-deoxy sugars readily form the oximes, which have been condensed with glyoxal to yield the pyrazine 4-oxides (Scheme 18) (72JOC2635, 80JOC1693). 

Quinoxaline mono-N-oxides are also available by a direct synthesis from n-nitroaniline derivatives. Condensation of acetyl chloride derivatives with o-nitroaniline followed by treatment with sodium ethoxide in ethanol yields the mono-N-oxides in good yields (Scheme 20) (64JCS2666). 

Quinoxaline and phenazine di-fV-oxides are also directly available by the Beirut reaction (see Section 2.14.3.2). 

Pyrazine and quinoxaline fV-oxides generally undergo similar reactions to their monoazine counterparts. In the case of pyridine fV-oxide the ring is activated both towards electrophilic and nucleophilic substitution reactions however, pyrazine fV-oxides are generally less susceptible to electrophilic attack and little work has been reported in this area. Nucleophilic activation generally appears to be more useful and a variety of nucleophilic substitution reactions have been exploited in the pyrazine, quinoxaline and phenazine series. 

Treatment of both pyrazine 1-oxide and quinoxaline 1-oxide with POCI3 results in the formation of the corresponding chlorinated derivatives (SO) and (SI). However, in the case of quinoxaline 1-oxide the 2-chloroquinoxaline is accompanied by 6-chloroquinoxaline (S2) (67YZ942). 

Other reactions with their counterparts in the pyridine series are also well known. Thus, 2,3-dimethylpyrazine 1,4-dioxide reacts with acetic anhydride to yield 2,3-bis(acetoxy-methyl)pyrazine (S3) in good yield (72KGS1275). Pyrazine 1-oxide also reacts directly with acetic anhydride to yield 2(ljH)-pyrazinone by way of the intermediate acetate (Scheme 22). The corresponding reaction in the quinoxaline series is not so well defined and at least three products result (Scheme 23) (67YZ942). 

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