Synthesis
The general procedure for the synthesis of 2-bromo-5-chlorobenzonitrile using 3-chlorobenzonitrile as starting material was as follows: sulfuric acid (24 mL) was slowly added to a solution of 3-chlorobenzonitrile (50 g, 360 mmol) in trifluoroacetic acid (180 mL), followed by the addition of 1,3-dibromo-5,5-dimethyl-acetonitriles (67 g, 234 mmol) in batches over an 8-min period. During the reaction, the temperature was raised to 31 °C and then controlled at 24 °C by cooling. After 6 h of reaction, the non-homogeneous reaction mixture was cooled to 10 °C and quenched by the addition of water (250 mL).After 10 min, the reaction mixture was filtered and the filter cake was washed twice sequentially with water (250 mL and 100 mL) to give the final white solid product 2-bromo-5-chlorobenzonitrile (52.4 g, 63% yield). The structure of the product was confirmed by 1H NMR (CDCl3, 400 MHz) δ 7.64-7.62 (m, 2H), 7.44 (dd, J = 8.6, 2.5 Hz, 1H) and 13C NMR (CDCl3, 100 MHz) δ 134.2, 134.1, 133.9, 133.8, 123.3, 117.2, 115.8.
References
[1] Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 9, p. 3026 - 3035
[2] Tetrahedron, 2004, vol. 60, # 50, p. 11367 - 11374
[3] Organic Letters, 2006, vol. 8, # 18, p. 3903 - 3906
[4] Patent: US2004/181070, 2004, A1. Location in patent: Page 11
