Chemical Properties
white crystalline
Uses
4-Bromo-2-hydroxybenzonitrile is a benzonitrile derivative containing hydroxyl and bromine atom substituents at the 2 and 4 positions. The substance can be used to prepare indole derivatives or small molecule inhibitors (plasma kinin releasing enzyme inhibitors).
Synthesis
General procedure for the synthesis of 4-bromo-2-hydroxybenzonitrile from 4-bromo-2-fluorobenzonitrile: 2-fluoro-5-bromobenzonitrile (30 g, 152.3 mmol), potassium acetate (222.4 g, 228.5 mmol), and 18-crown-6 ether (60.4 g, 228.5 mmol) were dissolved in acetonitrile (400 mL) and heated and refluxed for 36 hours. After completion of the reaction, the mixture was cooled to room temperature, 2.5 N NaOH solution (200 mL) was added and stirred overnight at room temperature. The reaction mixture was extracted with ether and the organic layer was discarded. The aqueous layer was acidified with 6 N HCl and extracted with ethyl acetate. The organic layers were combined, dried with anhydrous magnesium sulfate and concentrated under reduced pressure. The crude product was purified by fast column chromatography (40% ethyl acetate/hexane) to afford 4-bromo-2-hydroxybenzonitrile as a light yellow foamy solid (24.45 g, 81% yield). NMR hydrogen spectrum (300 MHz, DMSO-d6): δ 7.13 (dd, J = 1.7, 8.3 Hz, 1H), 7.17 (d, J = 1.7 Hz, 1H), 7.61 (d, J = 8.3 Hz, 1H).
References
[1] Synthetic Communications, 2004, vol. 34, # 5, p. 751 - 758
[2] Heterocyclic Communications, 2011, vol. 17, # 1-2, p. 10 - 16
[3] Patent: US2004/14723, 2004, A1. Location in patent: Page/Page column 7
[4] Patent: EP2632465, 2015, B1. Location in patent: Paragraph 0416
[5] Patent: WO2008/25509, 2008, A1
