2-Carboxy-6-methylpyrazine

Methylpyrazine. 2-Methylpyrazine has been prepared by decarboxylation of 2from glucose with 25% aqueous ammonia at 100° (33) by dehydrogenation of 2-methylpiperazine (or Mbutyl-2-methylpiperazine) over copper chromite at elevated temperatures (470, 471) (Section 11.6) and in high yield by dehydrogenation of methylpiperazine over catalysts containing CuO, Cr Os, or MnOi at 350-370° (469). Other catalysts have also been used for this dehydrogenation (471,562). 

Carboxy-5-methylpyazine (9.7 g) in dry dioxan (114 ml) and tributylamine (17.7 ml) was treated with ethyl chloroformate (7.5 ml), keeping the temperature at 0-5°C. After 10 min, dioxan (190 ml) saturated with ammonia was added. The mixture was stirred for 3 h at room temperature, then dioxin was distilled off, and the residue was taken up tin saturated aqueous sodium bicarbonate (20 ml). The mixture was filtered and the product washed with water to give 2-carbamoyl-5-methylpyrazine (9.2 g), melting point 204°-206°C. 

Carbamoyl-5-methylpyrazine 4-oxide (5.0 g) was added to 10% by weight sodium hydroxide (50 ml) and then refluxed for 30 min. The reaction mixture was acidified with dilute hydrochloric acid and extracted in a continuous extractor with ethyl acetate. The ethyl acetate extract was concentrated to small volume and gave, after filtration 2-carboxy-5-methylpyrazine 4-oxide (3.2 g), melting point 178°-180°C. 

Amino-3-cyano-5-methylpyrazine 1,4-dioxide (91) refluxed for several minutes with acetic anhydride formed 3-acetamido-2-cyano-5-hydroxy-6-methylpyrazine 1-oxide (92) (24%) (532) and 2-acetoxymethyl-5-methylpyrazine 1,4-dioxide refluxed with acetic anhydride afforded a mixture of2,5-di(acetoxymethyl)pyrazine 1-oxide, with some 2,5-diacetoxymethylpyrazine and a monoxide of 2-acetoxy-methyl-5-methylpyrazine (625). 2-Formylpyrazine hydrate 1,4-dioxide with aqueous sodium hydroxide or bicarbonate at < 37° in an unusual reaction gave 3-carboxy-pyrazine 1-oxide mixed with 5 [Pg.188]

Alkylpyrazines with other substituents have been oxidized to carboxylic acids as follows 2-acetamido-6-methylpyrazine was oxidized in aqueous magnesium sulfate with potassium permanganate to 2-acetamido-6aqueous potassium permanganate at room temperature to 2-carboxy-3-chloropyrazine, which was also obtained by oxidation of 2-chloro-3-methylpyrazine with selenium dioxide in boiling aqueous pyridine (947). Oxidations of 2-methoxy-3-methyl-... 

Dicarboxy-5,6-dimethylpyrazine, heated with acetic anhydride, also gave the anhydride which with methanol gave 2-carboxy-3-methoxycarbonyl-5,6-dimethylpyrazine (654). 2,3-Dicarboxy-5-methylpyrazine anhydride was prepared similarly and on methanolysis and decarboxylation it gave 2-methyl-5(and 6)-methoxycarbonylpyrazines (1327). 

Amides have also been prepared from carboxylic acids as follows a mixture of 2-carboxypyrazine and triethylamine in methylene chloride treated with ethyl chloroformate and then morpholine gave 2-(A-morpholinocarbonyl)pyrazine (1351) 2-carboxy-5(and 6)-methylpyrazine in dioxane with tributylamine and ethyl chloroformate and then treated with ammonia gave 2-carbamoyl-5(and 6)-methylpyrazine (673), and 2-carbamoyl-5(and 6)-ethylpyrazine were prepared... 

All tables include relevant C-alkyl derivatives of the type of pyrazine listed. For example, Table A.2 (aminopyrazines) contains aminopyrazines and A -substituted analogues, as well as C-alkyl derivatives and Table A.21 (carboxy halogenopyrazines) lists 2,6-dichloro-3 -cyano-5 -methylpyrazine. 

A series of bidentate N N, N 0, and 0 0 ligands for iron were tested. 5-Carboxy-2-methylpyrazine-N-oxide (7) proved to give the most selective catalyst (78% based on H2OJ. 

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