Quinoxaline, benzene ring oxidation

Quinoxaline 1,4-dioxide undergoes reaction with acetyl chloride and substitution occurs in the benzene ring to give 6-chloroquinoxaline 1 -oxide and, on increasing the reaction time, 3-chloroquinoxaline 1-oxide and 6,7-dichloroquinoxaline appear as additional products.A similar reaction is observed with 3-phenylquinoxalin-2(l//)-one 4-oxide and its 7-substituted derivatives, where ring substitution at position 6 again is accompanied by deoxygenation. 2-Chloroquinoxalinc 1-oxide (19) is obtained in 60% yield by treatment of quinoxaline 1,4-dioxide with benzenesulfony chloride and consequent neutralization of the benzenesulfonate initially formed,and in addition about 3% of 3-chloroquinoxaline 1-oxide is formed. 

Both these series of bicyclic compounds have been used as important starting materials for the preparation of pyrazines by the oxidative removal of the benzene ring from quinoxaline and by cleavage of the pyrimidine ring in pteridines. Both preparative procedures are discussed in detail in Sections 4 and 5. 

The Diels-Alder reaction of weio-tetraarylporphyrins with the pyrazine o-quino-dimethane mainly affords the oxidized compounds 55a-c instead of the expected chlorin adducts (Scheme 5.14). The bis-addition is site specific, occurring in opposite pyrrolic rings and leads to compounds 57 and 58. The novel polycyclic products 56a-c, 58a, and 58b result from the coupling reactions between the p-fused quinoxaline ring and one adjacent meso-atyl group. It should be pointed out that, in contrast to compounds 55a and 57a, there also occurs the combination between one of the orto-atoms of the carbon of the mew-aryl group and one of the carbon atoms of the benzene ring quinoxaline system in the fonnalion of compounds 56a and 58a. 

The 1,5-benzodiazepine 40 on irradiation in benzene under oxygen undergoes oxidative ring contraction to 2-benzoyl-3-methyl-quinoxaline.42 Similarly, photolysis of 7-chloro-2-methylamino-5-phenyl-3//-l,4-benzodiazepine-4-oxide (41) in benzene yields the N-benzoylquinoxaline 42. Related ring contractions of diazepines to reduced quinoxalines have also been observed.43... 

The greater stability of the pyrazine ring to oxidation compared with that of benzene enables pyrazinecarboxylic acids to be prepared by permanganate oxidation of either quinoxalines or phenazines. The pyrazine ring is more stable than the pyrimidine ring to acid and alkaline hydrolysis. Thus, pteridine is converted into 2-amino-3-formylpyrazine on treatment with dilute sulfuric acid and N-(3-formyl-2-pyrazinyl)formamidine oxime on treatment with sodium carbonate and hydroxylamine (Scheme 11).136 Aminopyrazines and... 

Condensation reactions using different fragments are very important for the synthesis of quinoxaline derivatives. Some of these condensation reactions lead, in the first step, to a partially saturated derivative of the heteroaromatic system which can be further oxidized with appropriate reagents. The most widely used method for the synthesis of the quinoxaline ring is the condensation of benzene-1,2-diamine with a two-carbon synthon. 

Oxidation of solutions of benzodiazepines in benzene or acetic acid with a high-pressure mercury arc in oxygen also causes oxidative ring contraction to give quinoxalines.49 Since hydrolytic cleavage is ruled out in this case a photolytic norcaradiene-type rearrangement of the intermediate ketone to a quinoxaline was suggested (Scheme 5). 

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