The general procedure for the synthesis of 2-amino-4-methyl-5-nitropyridine and 4-methyl-3-nitropyridin-2-amine from 2-amino-4-methylpyridine was carried out as follows: commercially available 2-amino-4-methylpyridine (Fluka, purity >99%) was used as starting material according to the method previously described by Talik and Talik [29]. This was done as follows: 25 g of 2-amino-4-methylpyridine was dissolved in 125 cm3 concentrated sulfuric acid (Fluka, 96%). The reaction mixture was cooled to 0°C under strong stirring by adding ice mixed with sodium chloride. Subsequently, 37.5 cm3 of nitric acid (Chempur, 65%, density = 1.4 g/cm3) was slowly added, keeping the reaction temperature below 10°C. The reaction mixture was stirred under continuous cooling for 1.5 hours, followed by standing at room temperature for 1 hour. Next, the reaction mixture was sequentially heated in a water bath at 40°C for half an hour, at 60-70°C for 1 hour and in a boiling water bath for half an hour. After completion of the reaction, the mixture was cooled to room temperature, poured into ice water and adjusted to a weakly basic pH with ammonia. the solid product was collected by vacuum filtration. Steam distillation was utilized to separate the two nitro isomers (3-nitro and 5-nitro isomers). The more volatile 3-nitro isomer (I) was first distilled and concentrated and dried to give the pure product (10 g). The residual 5-nitro isomer (III) was collected by filtration and recrystallized from water (initial addition of sulfuric acid and activated carbon to dissolve the compound and remove impurities). After neutralization, filtration and drying, about 15 g of 5-nitroisomer (III) was obtained. 2-Amino-4-methyl-3,5-dinitropyridine (II) was prepared from 2-amino-4-methyl-5-nitropyridine (III) using a similar method (nitration and rearrangement to dinitropyridine). The residue was purified by crystallization in water to give 2-amino-4-methyl-3-nitropyridine (I) (yield: 27%, 10 g, melting point 134 °C), 2-amino-4-methyl-3,5-dinitropyridine (II) (yield: 80%, 10.4 g, melting point 197 °C) and 2-amino-4-methyl-5-nitropyridine (III) (yield: 40%, 15 g (yield: 40%, 15g, melting point 218°C). Melting points were determined using a Kfler apparatus and the chemical composition of the compounds was verified by Carlo Erba Analyzer (model 1104).
