Pyrazinedicarboxylic Acid

Submitted by Reuben G. Jones and Keith C. McLaughlin. Checked by H. R. Snyder and R. E. Heckert. 

Quinoxaline. One hundred thirty-five grams (1.25 moles) of fl-phenylenediamine 1 is dissolved in 2 1. of water, and the solution is heated to 70°. With stirring, a solution of 344 g. (1.29 moles) of glyoxal-sodium bisulfite 2 (Note 1) in 1.5 1. of hot water (about 80°) is added to the o-phenylenediamine solution. The mixture is allowed to stand for 15 minutes and then is cooled to about room temperature and 500 g. of sodium carbonate monohydrate (Note 2) is added. The quinoxaline separates as an oil or as a crystalline solid if the mixture is sufficiently cool. The 

3-Pyrazinedicarboxylic acid. A 12-1. three-necked flask is provided with an efficient mechanical stirrer, a reflux condenser, and a 1-1. dropping funnel. In the flask are placed 4 1. of hot (about 90°) water and 145 g. (1.12 moles) of quinoxaline. With rapid stirring a saturated aqueous solution of 1050 g. (6.6 moles) of potassium permanganate (Note 4) is added through the dropping funnel in a thin stream. The rate of addition of the permanganate solution is adjusted so that the reaction mixture boils gently. The addition requires about 1.5 hours. 

The reaction mixture is cooled somewhat (Note 5) and filtered through a large Buchner funnel. The manganese dioxide cake is removed from the funnel and stirred to a smooth paste with 1 1. of fresh water. The slurry is filtered, and the washing is repeated. The total filtrate, about 10 1., is evaporated under reduced pressure on the steam bath to a volume of approximately 3 1. (Note 6). The solution is swirled or stirred gently while 550 ml. (6.6 moles) of 36% hydrochloric acid is cautiously added (Note 7). Evaporation under reduced pressure is then continued until a moist cake of solid potassium chloride and 2,3-pyrazinedicar-boxylic add remains in the flask (Note 8). 

The moist cake is scraped from the flask and allowed to dry in a 16-in. porcelain evaporating dish until the odor of hydrochloric acid is faint (about 24 hours, but this time can be reduced to about 8 hours if a gentle stream of air is directed onto the solid). The solid material is returned to the dried flask and mixed thoroughly with about 200 ml. of water. Two liters of acetone is added, and the mixture is boiled under reflux for 15 minutes, then cooled to room temperature and filtered through a 6-in. Buchner funnel. The solid on the filter is returned to the flask, treated with 100 ml. of water, and extracted with 1 1. of boiling acetone as before 

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Quinoxaline gave 2,3-pyrazinedicarboxylic acid (Q3, H2SO4, Mn catalyst >15%- KMnQ4, H2Q, 95°C, 3h ... 

A solubility study coupled with IR and titrameric measurements and ab initio molecular orbital calculations was performed on 2,3-pyrazinedicarboxylic acid <2000JST(526)191>, demonstrating that the dicarboxylic acid exists in the solid as such and not in a zwitterionic form. In addition, one internal and one external 0---0=C hydrogen bond per molecule were proposed. 

Azirines are dimerized under various conditions to dihydropyrazines or their dehydrogenated products, namely pyrazines (Section 8.03.9.5). Quinoxalines are oxidized with potassium permanganate to afford 2,3-pyrazinedicarboxylic acids, and pteridines are hydrolyzed to give 3-amino-2-pyrazinecarboxylic acid derivatives. Condensation of 3,4-diamino-l,2,5-thiadiazole 176 with a-diketones produces l,2,5-thiadiazolo[3,4- Jpyrazines 177, which are reduced to provide 2,3-diaminopyrazines 178 (Scheme 51) <1997JCM250>. 

Propionitrile, 51 -Propylacetylene, 17 2,3-Pyrazinedicarboxylic acid, 86 Pyridine, 3-amino, 3 Pyridine, 5-ethyl-2-methyl, 41 Pyruvic aldehyde-sodium bisulfite, 88... 

Quinoxaline has been prepared by the reaction of glyoxal with o-phenylenediamine, and 2-methylquinoxaline by the reaction of pyruvic aldehyde or isonitrosoacetone with < -phenylenedi-amine. 2,3-Pyrazinedicarboxylic acid has been prepared only by the permanganate oxidation of quinoxaline. 2-Methyl-5,6-pyrazinedicarboxylic acid has been prepared from 2-methyl-quinoxaline in the same way. - ... 

Dichloro-2,3-pyrazinedicarboxylic acid (103, R = Cl) gave 5-amino-6-chloro-2,3-pyrazinedicarboxylic acid (103, R = NH2) [NH3 (liquid), 130°C, autoclave, 24 h 88% dangerously close to the critical temperature of ammonia ].947... 

Methyl-2,3-pyrazinedicarbonitrile (13) gave 5-methyl-2,3-pyrazinedicarboxylic acid (14) (NaOH, H20—EtOH, reflux, 2 h 60% a little HCN due to a side reaction).477... 

Pyrazinedicarboxylic acid (23, R = C02H) gave 2-pyrazinecarboxylic acid (23, R = H) (AcOH—H2S04, reflux, 2 h 85%).143... 

Methyl-2,3-pyrazinedicarboxylic acid (24, Q = R = C02H) gave a mixture of 5-methyl-2-pyrazinecarboxylic acid (24, Q = H, R = C02H) and 6-methyl-2-pyrazinecarboxylic acid (24, Q = C02H, R = H), in which the former predominated (sublimed at 185°C under reduced pressure 72% before separation as derivatives).477... 

Acetamido-2,3-pyrazinedicarboxylic acid 2-Acetamidopyrazine 1,4-dioxide 2-Acetamidopyrazine 1-oxide... 

Phenyl-2-pyrazinecarboxylic acid 5-Phenyl-2,3-pyrazinediamine 5-Phenyl-2,3-pyrazinedicarbonitrile 5-Phenyl-2,3-pyrazinedicarboximide 5-Phenyl-2,3-pyrazinedicarboxylic acid 5- Phenyl-2,3(1 H, 4//)-pyrazinedione 2-Phenylpyrazine 1,4-dioxide 2-Phenylpyrazine 1-oxide... 

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