Synthesis
General procedure for the synthesis of 2-amino-6-chlorophenol from 2-chloro-6-nitrophenol: 2-chloro-6-nitrophenol (1.05 g, 6.03 mmol) was mixed with tin powder (2.32 g, 19.5 mmol) in glacial acetic acid, and the reaction was stirred for 18 hours at 80 °C. After completion of the reaction, the reaction mixture was diluted with deionized water (120 mL) and filtered to remove insoluble material. The filtrate was extracted with ethyl acetate (1 x 100 mL, followed by 2 x 50 mL). The organic phases were combined, washed with saturated saline (3 × 50 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Purification by rapid column chromatography on silica gel (eluent ratio 2:1 hexane:ethyl acetate) afforded 2-amino-6-chlorophenol as a brown to white crystalline solid (476 mg, 55% yield).1H-NMR (500 MHz, CDCl3) δ 6.73 (dd, J = 1.7, 8.1 Hz, 1H), 6.69 (t, J = 7.8 Hz, 1H ), 6.62 (dd, J = 1.7, 7.7 Hz, 1H), 5.46 (br s, 1H), 3.84 (br s, 2H); 13C-NMR (125 MHz, CDCl3) δ 139.32, 135.73, 121.28, 119.87, 118.31, 114.42; ESI-MS m/z 144 [M +H]+, calculated value of 144 for the molecular formula C6H7ClNO.
References
[1] Liebigs Annalen der Chemie, 1994, # 3, p. 269 - 276
[2] Journal of the Iranian Chemical Society, 2018, vol. 15, # 2, p. 281 - 291
[3] Journal of Medicinal Chemistry, 2011, vol. 54, # 23, p. 7974 - 7985
[4] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 15, p. 3521 - 3525
[5] Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 15, p. 3441 - 3449
