Nitric Acid → 2-Amino-4-methyl-5-nitropyridine

Participants

Reaction Conditions

Reaction Steps

Concentrated sulfuric acid (120 mL) was cooled in an ice bath at 0° C. 2-Amino-4-methylpyridine (25.0 g, 230=mol) was added portionwise. A mixture of concentrated sulfuric acid (18 mL) and concentrated nitric acid (17.5 mL) was added with addition funnel over 1 h, maintaining the temperature at 0° C. The reaction mixture was then warmed to room temperature over 4 h. After 15 h, the reaction mixture was heated at 60° C. for 1 h, and then at 100° C. for 1 h. The reaction mixture was poured over ice and adjusted to pH 4-5 with 6 N aqueous sodium hydroxide. The 3-regioisomer was removed by steam distillation (9.11 g, 26%). The remaining residue was extracted with methylene chloride and dried over sodium sulfate, and the solvent was evaporated. The dark yellow solid was crystallized from acetonitrile and methanol to give 2-amino-4-methyl-5-nitropyridine (9.53 g, 27%) as a dark yellow solid: 1H NMR (300 MHz, CD3OD) δ2.53 (3H, s), 6.39 (1H, s), 8.76 (1H, s).

Provenance & Evidence