4-(tert-Butyl)-2-nitroaniline

Uses

4-(tert-Butyl)-2-nitroaniline is an organic compound commonly used in organic synthesis, especially as a synthetic intermediate in the pharmaceutical and dye industries.

Synthesis

General procedure for the synthesis of 4-tert-butyl-2-nitroaniline from N-(4-tert-butyl-2-nitrophenyl)acetamide: Methanol (13.5 L) and N-(4-tert-butyl-2-nitrophenyl)acetamide (7.0 kg, 29.6 mol) were added to the reactor. The mixture was stirred for 10 min, then a methanol solution of 30% sodium methanol (6.49 L, 35.5 mol) was slowly added at room temperature. The mixture was slowly heated to reflux and held at this temperature for 2 hours. Upon completion of the reaction, the methanol was vacuum distilled to dryness at 50-55°C and the solid was cooled to room temperature. The residue was stirred in water (35 L) for 1 h. The solid was collected by filtration, washed with water (14 L) and dried at 45-50 °C to give 5.3 kg of 4-tert-butyl-2-nitroaniline. The product was characterized by 1H NMR (400 MHz, CDCl3): δ 1.27 (s, 9H), 5.95 (br s, 2H), 6.76 (d, 1H), 7.43 (d, 1H), 8.08 (s, 1H).

References

[1] Journal of the American Chemical Society, 2012, vol. 134, # 3, p. 1528 - 1535
[2] Journal of Organic Chemistry, 1970, vol. 35, p. 917 - 923
[3] Journal of Medicinal Chemistry, 1995, vol. 38, # 25, p. 4906 - 4916
[4] Patent: WO2011/47315, 2011, A1. Location in patent: Page/Page column 51
[5] Patent: WO2013/114250, 2013, A1. Location in patent: Page/Page column 181