Uses
2-Fluoro-3-nitrotoluene is a class of fluorinated aromatic compounds. Compared with fluorinated aromatic compounds, fluorinated aromatic compounds have excellent properties in the fields of medicine and pesticides, such as low dosage, low toxicity, high efficacy, and strong metabolic capacity, and are widely used.
Synthesis
Cesium fluoride (97.5 g, 642 mmol) was added to a solution of 2-chloro-1-methyl-3-nitrobenzene (73.4 g, 428 mmol) in dimethyl sulfoxide (DMSO, 185 mL) under nitrogen protection. The reaction mixture was stirred at 140 °C for 10 hours. Upon completion of the reaction, the mixture was slowly poured into 0.5 N hydrochloric acid and extracted twice with ethyl acetate. The organic phases were combined, washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was removed by concentration under reduced pressure to give the crude product. The crude product was purified by reduced pressure distillation (boiling point: 118-122 °C/15 mmHg) to give 2-fluoro-3-nitrotoluene (54.4 g, 82% yield) as a yellow oil.1H NMR (DMSO-d6, 270 MHz) δ (ppm): 7.96 (m, 1H), 7.73 (m, 1H), 7.34 (t, J = 8.2 Hz, 1H), 2.35 (t, J = 8.2 Hz, 1H), 2.35 (t, J = 8.2 Hz, 1H), 2.35 (t, J = 8.2 Hz, 1H). 1H), 2.35 (d, J = 2.4 Hz, 3H). Intersil C18 (ODS, 5 μm, 4.6 mm ID × 50 mm, GL Sciences) or SunFire C18 (ODS, 5 μm, 4.6 mm ID × 50 mm, Waters); mobile phases: water (A) containing 0.05% trifluoroacetic acid and acetonitrile (B) containing 0.05% trifluoroacetic acid; elution method: gradient elution ( Solvent B was raised from 10% to 95% in 3.5 min, then lowered to 10% in 1 min, holding 10% B for 0.5 min); Flow rate: 4.0 mL/min.
References
[1] Patent: EP1982982, 2008, A1. Location in patent: Page/Page column 196
[2] Patent: EP2172198, 2010, A1
[3] ACS Medicinal Chemistry Letters, 2013, vol. 4, # 11, p. 1059 - 1063
[4] Patent: KR101511396, 2015, B1. Location in patent: Paragraph 2861-2865
