Uses
3-Aminofuran-4-carboxylic acid is a carboxylic acid organic compound and an important intermediate in the synthesis of compounds such as furazan, oxyfuran, and pyrrolifuran.
Synthesis
To a stirred suspension of ethyl cyanoacetate (28.3 g, 0.25 mol, 1.0 eq.) and sodium nitrite (17.3 g, 0.25 mol, 1.0 eq.) in a mixture of ethanol (17 mL) and water (200 mL) was added 85% phosphoric acid (10 mL) slowly and dropwise at 10-15°C with continuous stirring for 12 hours. Upon completion of the reaction, the reaction mixture was treated sequentially with sodium hydroxide (4 x 10 g, 1 mol, 4.0 eq.) and potassium hydroxide (2 x 14 g, 0.5 mol, 2.0 eq.). Hydroxylamine hydrochloride (NH2OH-HCl, 69.5 g, 1.0 mol, 4.0 eq.) was slowly added to the resulting solution at room temperature, followed by heating the reaction mixture to 95 °C and stirring for 2 hours. After completion of the reaction, it was cooled to room temperature and quenched with concentrated hydrochloric acid. The mixture was cooled to 0 °C and allowed to stand for 12 h to precipitate, the precipitate was collected by filtration and dried. The filtrate was extracted with ether (3 x 30 mL), the organic phases were combined and concentrated under reduced pressure. The concentrated residue was combined with the previously obtained precipitate and recrystallized from hot water to afford the target compound 4-amino-1,2,5-oxadiazole-3-carboxylic acid (21.3 g, 0.165 mol, 66% yield) as a white solid. The product was characterized by 1H-NMR (300 MHz, DMSO-d6), 13C-NMR (75 MHz, DMSO-d6) and HRMS (ESI), and the data were consistent with the expected structure.
