Uses
4-Bromo-2-(trifluoromethyl)benzonitrile is an intermediate for the synthesis of 4-Bromo-2-(trifluoromethyl)phenylacetic Acid (B688526), which is a useful intermediate for organic synthesis and other chemical processes.
Synthesis
The general procedure for the synthesis of 4-bromo-2-trifluoromethylbenzonitrile using 4-amino-2-trifluoromethylbenzonitrile as starting material was as follows: 4-amino-2-trifluoromethylbenzonitrile (1.02 g, 5.48 mmol) was dissolved in acetonitrile (30 mL) at 0 °C, and tert-butyl nitrite (0.95 mL, 7.19 mmol) was slowly added dropwise. The reaction mixture was stirred continuously at 0°C for 0.5 h. After that, copper (II) bromide (1.39 g, 6.22 mmol) was added, followed by slow warming of the reaction system to room temperature. The mixture was continued to be stirred at room temperature for 14 h. After completion of the reaction, the mixture was poured into brine and extracted with ethyl acetate (EtOAc). The organic layer was dried over anhydrous magnesium sulfate (MgSO4) and the solvent was removed by concentration under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate) to afford the target product 4-bromo-2-trifluoromethylbenzonitrile (1.13 g, 82% yield) as a yellow oil. The structure of the product was confirmed by 1H NMR (200 MHz, CDCl3), δ: 7.60-8.10 (3H, m).
References
[1] Patent: US2004/6134, 2004, A1
[2] Chemical and Pharmaceutical Bulletin, 2005, vol. 53, # 4, p. 402 - 409
[3] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 1, p. 422 - 434
[4] Organic Letters, 2017, vol. 19, # 10, p. 2518 - 2521
[5] Medicinal Chemistry Research, 2016, vol. 25, # 4, p. 539 - 552
