General procedure for the synthesis of 4-butyl-2-nitroaniline from 4-n-butylaniline: Acetic anhydride (27.0 mL, 286 mmol) was slowly added to 4-n-butylaniline (5.08 g, 34.0 mmol) under ice bath cooling. The ice bath was removed and the resulting viscous mixture was stirred at room temperature for 40 min and then cooled in the ice bath again. 70% w/w nitric acid (34 mL, 378 mmol) was slowly added through the addition funnel. After addition, the reaction mixture was poured into a 200 mL ice-water mixture and extracted twice with ethyl acetate (200 mL, followed by 100 mL). The organic phases were combined and washed sequentially with water (100 mL), saturated aqueous sodium bicarbonate (100 mL), brine (100 mL), dried over anhydrous sodium sulfate, filtered and concentrated, and dried under vacuum to give 7.38 g of dark orange oil. The oil was dissolved in dioxane (20 mL), 6 M aqueous hydrochloric acid (30.0 mL, 180 mmol) was added, a condenser was assembled and the reaction was heated to 80 °C for 3 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (150 mL) and neutralized with 1 M sodium hydroxide solution (230 mL). After partitioning, the aqueous phase was back-extracted with ethyl acetate (100 mL). The organic phases were combined, washed sequentially with water and brine (150 mL each), dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by fast chromatography on a BiotageTM fast 340 g silica gel column using a gradient elution of ethyl acetate/hexane (0-30%). The fractions containing the target product were combined and concentrated to give 4-butyl-2-nitroaniline (1.84 g, 28% yield).1H NMR (400 MHz, CDCl3) δ 7.92 (d, J = 1.9 Hz, 1H), 7.21 (dd, J = 8.5, 2.0 Hz, 1H), 6.74 (d, J = 8.5 Hz, 1H), 5.94 (s 2H), 2.61-2.44 (m, 2H), 1.65-1.49 (m, 2H), 1.34 (h, J = 7.3 Hz, 2H), 0.92 (t, J = 7.3 Hz, 3H).
