Synthesis
General procedure for the synthesis of 2-fluoro-4-nitrobenzonitrile from 2-fluoro-4-nitrobenzamide: A mixture of 2-fluoro-4-nitrobenzamide (0.83 g, 4.6 mmol) and phosphorus pentoxide/hexamethyldisiloxane in 1,2-dichloroethane (20 mL) was heated and refluxed for 4 hr at 100 °C under nitrogen atmosphere. Upon completion of the reaction, the mixture was cooled to room temperature and subsequently filtered through a silicone plug, washed first with hexane (200 mL) and then with 5% methanol/chloroform mixture (400 mL). The methanol/chloroform washings were combined and concentrated under reduced pressure to give 2-fluoro-4-nitrobenzonitrile (0.71 g, 95% yield) as a beige solid.1H NMR (DMSO-d6) data were as follows: δ 8.46 (dd, J = 9.5, 2.0 Hz, 1H), 8.37-8.22 (m, 2H).
References
[1] Journal of Heterocyclic Chemistry, 1997, vol. 34, # 4, p. 1163 - 1172
[2] Patent: US6344459, 2002, B1. Location in patent: Page column 70-71
[3] European Journal of Medicinal Chemistry, 2018, vol. 143, p. 1325 - 1344
[4] Journal of Medicinal Chemistry, 2001, vol. 44, # 23, p. 3856 - 3871
