General procedure for the synthesis of 5-chloro-1-methyl-4-nitroimidazole from 5-chloro-1-methylimidazole: A mixed solution of 1-methyl-5-chloroimidazole (57.0 g, 0.50 mol) and dilute nitric acid (690 mL, 1.15 mol) was concentrated to dryness. The resulting light yellow oil (131.40 g) was slowly added dropwise to 214 mL of pre-cooled concentrated sulfuric acid over 85 minutes under nitrogen protection. Subsequently, the reaction mixture was stirred at 100 °C for 2 h under nitrogen atmosphere. Upon completion of the reaction, the reaction solution was slowly poured into 21 mL of ice water and precipitate was precipitated and collected by filtration. The precipitate was washed to neutrality with ice water to give 1-methyl-5-chloro-4-nitroimidazole (45.3 g, 62% yield) in white crystalline form. The melting point of the product was 147.5-148.9 °C. 1H NMR (400 MHz, d6-DMSO): δ= 7.50 (s, 1H, 2-H), 3.72 (s, 3H, CH3). 13C NMR (100 MHz, d6-DMSO): δ= 142.4 (C-4), 134.6 (C-2), 119.6 (C-5). 32.9 (CH3).
