Ammonia → 5-amino-2-butyl-1-(2-methylpropyl)-1H-imidazole-4-carbonitrile

Participants

Reaction Steps

Dry ammonia was bubbled through a stirred solution of aminomalononitrile p-toluenesulfonate (25.0 g, 98.7 mmol) in anhydrous acetonitrile (1 L). The reaction warmed slightly, and precipitate formed. The precipitate was removed by filtration, and the filtrate was concentrated to a volume of about 500 mL. Trimethyl orthovalerate (17.0 mL, 98.7 mmol) was added, and the resulting solution was heated at reflux for 30 minutes and then allowed to cool to room temperature. Isobutylamine (9.8 mL, 99 mmol) was added, and the reaction was complete in minutes as evidenced by thin layer chromatography (TLC). The volatiles were removed under reduced pressure, and the residue was dissolved in ethyl acetate (400 mL). The resulting solution was washed sequentially with aqueous sodium hydroxide (75 mL of 2 M), water, and brine; dried over magnesium sulfate, and concentrated under reduced pressure to provide a dark solid. The crude product was purified by column chromatography on silica gel (eluting with 50/50 ethyl acetate/hexane) to provide 13.50 g (62%) of 5-amino-2-butyl-1-(2-methylpropyl)-1H-imidazole-4-carbonitrile as a brown solid.

Provenance & Evidence