Synthesis
General procedure for the synthesis of 3-bromo-4-methylbenzonitrile from 4-methylbenzonitrile: 4-methylbenzonitrile (168 g, 1.46 mol) was dissolved in a mixed solution of H2SO4/H2O (800 mL, 1:1, v/v/v) at 10 °C and N-bromosuccinimide (NBS, 256 g, 1.43 mol) was added slowly. The reaction mixture was stirred under light-avoiding conditions for 48 hours. After completion of the reaction, the mixture was filtered and the filter cake was collected. The filter cake was dissolved in ethyl acetate (1000 mL) and the organic layer was washed sequentially with water and saturated saline. Subsequently, it was neutralized with NaOH solution to pH=7 and washed again with saturated saline. The organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure to give 3-bromo-4-methylbenzonitrile (276.5 g, 89% yield) as a yellow solid.
References
[1] Journal of Organic Chemistry USSR (English Translation), 1988, vol. 24, # 2, p. 217 - 223
[2] Zhurnal Organicheskoi Khimii, 1988, vol. 24, # 2, p. 248 - 255
[3] Patent: WO2011/22337, 2011, A1. Location in patent: Page/Page column 103-104
[4] Synlett, 2007, # 14, p. 2179 - 2184
[5] Organic Letters, 2006, vol. 8, # 4, p. 645 - 647
