939-83-3

Light yellow crystalline

Tetrahedron Letters, 25, p. 4971, 1984 DOI: 10.1016/S0040-4039(01)91273-0

Using 2-bromo-4-nitrotoluene (250.0 g, 1.16 mol) and zinc cyanide (135.0 g, 1.16 mol) as raw materials, both were mixed with tetrakis(triphenylphosphine)palladium (25 g, 0.02 mol) in anhydrous N,N-dimethylformamide (1500 mL) under nitrogen protection. The reaction mixture was stirred at 80°C for 24 hours. The progress of the reaction was monitored by thin layer chromatography (TLC, unfolding reagent ratio of petroleum ether:ethyl acetate = 10:1), and after confirming the completion of the reaction, the mixture was poured into toluene (1500 mL) and washed with 2N ammonia (800 mL x 2). The aqueous layer was back-extracted with toluene (800 mL x 2). The organic layers were combined, washed with saturated saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the crude product. The crude product was purified by column chromatography (first eluted with petroleum ether, then with a mixed solvent of petroleum ether:ethyl acetate=10:1) to give 2-methyl-5-nitrobenzonitrile (25.5 g, 42% yield) as a gray solid and recovered unreacted 2-bromo-4-nitrotoluene (170 g) as a yellow solid. The product was characterized by 1H NMR (300 MHz, CDCl3): δ 8.46-8.47 (d, J=3.0 Hz, 1H), 8.31-8.34 (dd, J=9.0 Hz, 1H), 7.53-7.56 (d, J=9.0 Hz, 1H), 2.68 (s, 3H).

[1] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 23, p. 6273 - 6278
[2] Patent: WO2006/117669, 2006, A1. Location in patent: Page/Page column 41; 113