Pyrazine dioxide, 2,5-dimethyl

Pyrazine, 2,5-dichloro-3,6-difluoro-synthesis, 3, 190-191 Pyrazine, dihydro-, 3, 177 Pyrazine, 1,2-dihydro-oxidation, 3, 178 reduction, 3, 177 Pyrazine, 1,4-dihydro-antiaromaticity, 3, 177-178 synthesis, 3, 177 Pyrazine, 2,3-dihydro-oxidation, 3, 178 Pyrazine, 2,5-dihydro-synthesis, 3, 178 Pyrazine, 3,6-dihydro-synthesis, 3, 184 Pyrazine, 2,5-dihydroxy-oxidation, 3, 175 Pyrazine, 2,3-dimethyl-1,4-dioxide... 

The simple phenyl-substituted pyrazines do undergo nitration in the phenyl ring for example, 2-phenylpyrazine yields the 4-nitrophenyl derivative (mixed acid), although 5-phenyl-2-pyrazinone forms the 3-nitropyra-zinone under similar conditions (75MI1). However, 2,5-dimethyl-3,6-diphenylpyrazine and its /V,A -dioxide are both reported to be nitrated to give the bis-(3-nitrophenyl) products (55JCS3094). 

Pyrazinecarboxylic acid has been obtained by selenious acid oxidation in pyridine of methylpyrazine or aqueous permanganate oxidation of ethylpyrazine, in yields of 64 and 48%, respectively.171,218 It has also been obtained in 70% yield by partial decarboxylation of pyrazine-2,3-dicarboxylic acid on heating in vacuo at 210°.219 Aqueous permanganate oxidation of 2,5-distyrylpyrazine gives the 2,5-dicarboxylic acid.220 Pyrazine-2,5-dicarboxylic acid has also been prepared in 45% yield by direct carboxylation of pyrazine with carbon dioxide at 50 atm pressure at 250° for 3 hours in the presence of a potassium carbonate and calcium fluoride catalyst.221 Pyrazine-tricarboxylic acid (57), obtainable in only very poor yields by oxidation of 2,5-dimethyl-3-ethylpyrazine, is prepared in 87% yield by alkaline permanganate oxidation of 2-(D-arabo)tetrahydroxybutyl-quinoxaline (56).222 Decarboxylation of the tricarboxylic acid by... 

Alkaline hydrolysis of the di-A-oxide of 2,5-dichloro-3,6-dimethyl-pyrazine (215) readily yields the monohydroxamic acid (216), but the second chlorine atom is inert. Both chlorine atoms in compound 215 may be displaced by ethoxide or benzyloxide ion. Acid treatment of the dibenzyloxy-1,4-dioxide (217) yields compound 218 which with... 

Gastaldi (286) first described this synthesis, in which an a-hydroxyimino ketone was treated with aqueous sodium bisulfite saturated with sulfur dioxide, and the bisulfite compound treated with potassium cyanide followed by hydrolysis with hydrochloric acid. By this procedure, Gastaldi prepared 2,5-dicyano-3,6-dimethyl-pyrazine from hydroxyiminoacetone, and 2,5-dicyano-3,6-diphenylpyrazine and some 3-cyano-2,5-diphenylpyrazine from hydroxyiminoacetophenone. He proposed a reaction mechanism involving the intermediate compounds (21) and (22). Sharp and Spring (287) used the same procedure to prepare 2,5-dicyano-3,6-diethyl-pyrazine from ethyl hydroxyiminomethyl ketone. 

The first lithiopyrazine derivative was prepared by Hirschberg et al. (1015) from 3-iodo-2,5-dimethylpyrazine and butyllithium in ether subsequent reaction with (a) carbon dioxide gave 3-carboxy-2,5-dimethylpyrazine, and (b) several aromatic aldehydes gave the carbinols (62, R = H, p-methoxy, m-nitro) (1015). Similar reactions were observed when 2-formylpyridine and 2-acetylpyridine (1016) were used as the carbonyl compounds, but with acetaldehyde attempted reactions were unsuccessful (1015). A patent also describes the preparation of many carbinols from 2,5-disubstituted 3-iodopyrazines (164). The lithio reagent derived from 3-iodo-2,5-dimethylpyrazine (with butyllithium in hexane) with 2-nitrobenzaldehyde gave 2,5-dimethyl-3[ 1 -hydroxy-1 (2"-nitrophenyl)methyl] pyrazine (1017). 

Bauer and Hirsch (764) found that 2,5-dimethylpyrazine 1-oxide refiuxed for 2 hours with propane-1-thiol in acetic anhydride gave 2,5-dimethyl-3-propylthio-pyrazine (5), and 2,5-dimethylpyrazine 1,4-dioxide similarly treated gave 2,5-dimethyl-3,6-dipropylthiopyrazine, but attempted reactions with benzenesulfonyl chloride instead of acetic anhydride (as in the pyridine series) were unsuccessful. 

The Vilsmeier reaction on 2-methylpyrazine has been described in Section IV.2C(7) (717), and King s reaction on 2-methyl(and 23-dimethyl)pyrazine 1,4-dioxide has been described in Section IV.3C(7) (763). Pyrazine with A, jV-dimethyl-acetamide, ammonium peroxydisulfate, and ferrous sulfate gave 2-(A -acetyl-iV-methylaminomethyl)pyrazine (1188). 

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