Sulfuric Acid → 2,5-Difluoro-4-formylbenzonitrile

Participants

Reaction Steps

n-Butyllithium solution (1.6 M in hexanes, 8.75 mL, 14 mmol) was added dropwise to a solution of methyl methylthiomethyl sulfoxide (1.58 g, 12.7 mmol) in THF (25 mL) at −78° C. After 30 minutes at −78° C., 2,4,5-trifluorobenzonitrile (commercial, 1 g, 6.35 mmol) was added dropwise. The solution was then allowed to warm to room temperature, and stirred for 18 hours under a nitrogen atmosphere. The deep red reaction mixture was poured into water (75 mL), and extracted with EtOAc (2×75 mL). The combined organics were dried over magnesium sulphate and evaporated to yield a brown oil. The oil was redissolved in THF (15 mL) and concentrated sulphuric acid (4.1 mL, 77.2 mmol) and water (4 mL) were added. After stirring for 5 hours the reaction was quenched with saturated aqueous sodium bicarbonate (30 mL) and extracted with EtOAc (2×50 mL). The combined organic extracts were dried over magnesium sulphate, and evaporated to yield a brown oil, which was purified by silica gel chromatography eluting with 50% heptane in DCM to afford the title compound as a yellow oil (280 mg, 26%).

Provenance & Evidence