Synthesis
The general procedure for the synthesis of pyridine-3,5-diamine from pyridine-3,5-dicarboxamide by a modified Hofmann rearrangement reaction is as follows:[39] Pyridine-3,5-dicarboxamide (3.54 g, 21.4 mmol) was dissolved in 4 M NaOH aqueous solution (18 mL). A solution of bromine (2.65 mL, 8.27 g, 51.9 mmol Br2) in 4M aqueous NaOH solution (53 mL) was added slowly and dropwise over 15 min at 0 °C. The reaction mixture was stirred at room temperature for 1 hour until a clarified yellow solution was formed, followed by heating at 75 °C for 6 hours. Upon completion of the reaction, the dark brown solution was washed with ether (50 mL) to remove by-products and then extracted with ethyl acetate (150 mL) for 3 consecutive days. Finally, concentration by vacuum evaporation afforded pyridine-3,5-diamine (1.43 g, 13.0 mmol, 61% yield) as a greenish brown solid (Rf = 0.14, unfolding agent CH2Cl2/MeOH 10:1).
References
[1] Synthesis (Germany), 2014, vol. 46, # 9, p. 1243 - 1253
