Synthesis
The general procedure for the synthesis of 2-isopropyl-5-nitroaniline from 2-isopropylaniline was as follows: 70% HNO3 (5.1 mL, 84.76 mmol, 1.2 eq.) was slowly added dropwise to a solution of 2-isopropylaniline (10 mL, 9.55 g, 70.63 mmol, 1 eq.) dissolved in 70 mL of concentrated hydrochloric acid. The reaction mixture was stirred at 0 °C for 30 min and then poured into ice water to terminate the reaction. The aqueous phase was extracted with EtOAc (2 x 150 mL) and the combined organic layers were washed with saturated NaHCO3 solution. The organic phase was concentrated by evaporation and the residue was purified by silica gel column chromatography using EtOAc/hexane (3/7) as eluent to give 2 g of the target product (16% yield) as a dark red oil. The product was characterized by 1H NMR (CDCl3, 300 MHz): δ 7.60 (dd, J = 8.1, 2.7 Hz, 1H), 7.50 (d, J = 2.7 Hz, 1H), 7.23 (d, J = 8.7 Hz, 1H), 2.91 (sept, J = 6.6 Hz, 1H), 1.28 (d, J = 6.9 Hz, 6H); Mass spectrum (m/z): 181 (M + H)+.
References
[1] European Journal of Organic Chemistry, 2009, # 5, p. 687 - 698
[2] Patent: EP2116523, 2009, A1. Location in patent: Page/Page column 13; 34
[3] Patent: US2012/22092, 2012, A1. Location in patent: Page/Page column 45
[4] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 3, p. 668 - 671
[5] Patent: WO2010/71885, 2010, A1. Location in patent: Page/Page column 452-453
