Pyrazine chemistry. IV. Bromination of 2-amino-3-carbomethoxypyrazine was written by Ellingson, R. C.;Henry, R. L.. And the article was included in Journal of the American Chemical Society in 1949.Quality Control of 5-Aminopyrazine-2-carboxamide This article mentions the following:
The structure of the product obtained on bromination of 2-amino-3-carbomethoxypyrazine (I) was established as 2-amino-3-carbomethoxy-5-bromopyrazine (II). I (15.3 g.) in 60 cc. warm AcOH treated dropwise with 5.4 cc. Br and 450 cc. water added after 10 min. yielded 21 g. (90.5%) II, light-yellow solid, m. 175.3-5.9°. I (61.2 g.) in 330 cc. AcOH was brominated with 21.6 cc. Br, 2 l. water and 210 g. NaOH in 400 cc. water added after 30 min., and the solution boiled 15 min., treated with C, filtered, and cooled, yielding 90.5 g. Na 3-amino-6-bromopyrazinoate (C.A. numbering) which, when dissolved in 2400 cc. warm water, acidified with 60 cc. 40% HBr, and cooled, yielded 64 g. light-brown crystals of 3-amino-6-bromopyrazinoic acid (III), m. 185-6° (decomposition) (from water). A suspension of 59.6 g. crude III in 600 cc. dry tetrahydronaphthalene was refluxed 30 min., treated (hot) with C, the filtrate was chilled, and the crystals which separated were washed in petr. ether, yielding 38.4 g. 2-amino-5-bromopyrazine (IV), m. 113.6° (corrected). IV (4.0 g.), 2 g. CuCN, 3.0 g. KCN, 14.0 cc. water, and 6.0 cc. EtOH sealed in a Carius tube were heated at 170° for 16 h., then rinsed out with 400 cc. water, the suspension acidified with HCl, boiled to remove the HCN, and the Cu removed with H2S; the cooled filtrate deposited 1.55 g. of a mixture of the amide and 6-aminopyrazinoic acid (V). The mixture was suspended in 50 cc. of 2% NaOH; the insoluble fraction (0.7 g.), 2-amino-5-carbamylpyrazine, m. 277-9° (from water). The alk. filtrate acidified with HCl gave 0.55 g. V, m. 278° (from water). Br (15.2 cc.) was added dropwise (temperature kept below 0°) to 15.3 g. I in 57 cc. 48% HBr, then 17.4 g. NaNO2 in 30 cc. water (temperature below 0°), and finally 38 g. NaOH in 100 cc. water; next day 5.6 g. light-brown solid was collected and an addnl. 3.8 g. was obtained by extraction with EtOAc. Crystallization from 100 cc. water and 32 cc. EtOH gave 7.4 g. 2-bromo-3-carbomethoxypyrazine (VI), m. 44° (corrected). VI (3 g.), 2.5 g. CuCN, 1 g. KCN, 7 cc. EtOH, and 12 cc. water sealed in a Carius tube were heated 16 h. at 125°, the filtered suspension made alk., boiled 1 h., 10 cc. of a 25% solution of BaCl2 added, the Ba salt collected, the Ba removed with H2SO4, and the filtrate concentrated to give (on cooling) tan crystals (VII), m. 171-5° (decomposition). VII (0.55 g.) in 5 cc. MeOH and 5 cc. H2SO4 was refluxed 15 h., the mixture diluted with water, made alk. with Na2CO3, extracted with EtOAc, and the extract dried, filtered, and evaporated to dryness, yielding 0.4 g. 2,3-dicarbomethoxypyrazine (VIII), m. 55-6°. To 29 cc. 48% HBr (cooled, ice-NaCl) were added consecutively 8.7 g. IV, 7.6 cc. Br, 8.7 g. NaNO2 in 15 cc. water, and 19 g. NaOH in 50 cc. water to give 7.8 g. 2,5-dibromopyrazine (IX), m. 47-8° (from water-EtOH, 2:1). 2,5-Dicarbomethoxypyrazine, prepared from IX by a method similar to that used for the preparation of VIII, m. 169.5-70.1° (from MeOH). In the experiment, the researchers used many compounds, for example, 5-Aminopyrazine-2-carboxamide (cas: 89323-09-1Quality Control of 5-Aminopyrazine-2-carboxamide).
5-Aminopyrazine-2-carboxamide (cas: 89323-09-1) belongs to pyrazine derivatives. Pyrazines are volatile compounds that are used in the cosmetic, food, flavor, and fragrance industries. A number of pyrazine-based derivatives were used as dyes or fluorescent probes.Quality Control of 5-Aminopyrazine-2-carboxamide