Water → 3-Fluoro-4-formylbenzonitrile

Participants

Reaction Steps

The reaction was carried out under argon. 3-Fluoro-4-methylbenzonitrile (121 g, 895 mmol) and N,N-dimethylformamide dimethylacetal (245 g, 2.06 mol) were dissolved in DMF (1.8 liters) and stirred under reflux overnight. The content of the flask was then poured into water (2 liters), the mixture was extracted twice with ethyl acetate and the combined organic phases were washed with saturated sodium chloride solution. The organic phase was concentrated and the residue was redissolved in THF/water (1:1, 2.7 liters). Sodium periodate (503 g, 2.35 mol) was added, and the mixture was stirred at room temperature for one hour. The precipitate was then removed and the filtrate was recovered and extracted repeatedly with ethyl acetate. The combined organic phases were washed once with saturated sodium bicarbonate solution and once with saturated sodium chloride solution, dried and concentrated to give an oil. This oil was purified by column chromatography on silica gel (mobile phase: petroleum ether/dichloromethane 6:4, then 4:6, finally pure dichloromethane). The product fractions were concentrated. This gave 28.0 g (20% of theory) of the target compound as a white crystalline solid.

Provenance & Evidence