Pyrazine-2-carbaldehyde

Chemical Properties

brown liquid

Synthesis

General procedure for the synthesis of pyrazine-2-carbaldehyde from methyl pyrazine-2-carboxylate: 1. Suspend methyl pyrazine-2-carboxylate (20 g, 145 mmol) in anhydrous THF (300.0 mL) and cool to -78°C. 2. Slowly add a solution of lithium aluminum hydride in THF (73.8 mL, 73.8 mmol), keeping the reaction temperature below -72 °C. 3. After addition, continue to stir the reaction mixture at -78 °C for 20 min. 4. the reaction was quenched with glacial acetic acid (20.0 mL) and the mixture was subsequently warmed to room temperature. 5. The volatiles were removed by evaporation and the residue was dissolved in 3N hydrochloric acid (116 mL) and extracted with DCM. 6. The organic phases were combined, washed with saturated aqueous sodium bicarbonate and the solvent was evaporated. 7. The residue was purified by silica gel chromatography, eluting sequentially with DCM/diethyl ether (100:0, 80:20, 0:100) to give pyrazine-2-carbaldehyde (15.67 g, 100%). 8. The resulting pyrazine-2-carbaldehyde was immediately dissolved in chloroform (200 mL) cooled to 0 °C, hydroxylamine monohydrochloride (11.02 g, 159.5 mmol) and triethylamine (24.2 mL, 117.4 mmol) were added. 9. The reaction mixture was stirred at ambient temperature for 0.5 hours, followed by evaporation to remove the solvent. 10. The residue was suspended in diethyl ether (500 mL) and filtered to remove insoluble material. 11. The filtrate was evaporated and the residue was purified by silica gel chromatography, eluting sequentially with DCM/diethyl ether (100:0, 80:20, 0:100) to give the title compound (5.5 g, 31%) as a solid. NMR (DMSO-d6): δ 8.15 (s, 1H), 8.62 (dd, 2H), 8.99 (s, 1H).

References

[1] Patent: WO2005/40159, 2005, A1. Location in patent: Page/Page column 212-213
[2] Tetrahedron Letters, 2009, vol. 50, # 28, p. 4030 - 4032
[3] Inorganic Chemistry, 2013, vol. 52, # 11, p. 6481 - 6501
[4] Chemical Communications, 2007, # 38, p. 3957 - 3959
[5] Journal of the American Chemical Society, 1990, vol. 112, # 17, p. 6248 - 6254