Synthesis
Example 6 Synthesis of 1-(2,4-difluorophenyl)propan-2-one
Under stirring and ice bath cooling conditions, 132.0 g (1.32 mol) of concentrated sulfuric acid was slowly added to 375 ml of water for dilution, keeping the reaction temperature at 10-15 °C. Subsequently, 0.60 mol of 2,4-difluoroaniline was added to the diluted sulfuric acid solution to form a suspension. 104.6 g (0.606 mol) of 40% sodium nitrite aqueous solution was slowly added dropwise to the suspension at 0-3 °C for 45 min.
In another reactor, a mixture comprising 6.0 g of copper sulfate pentahydrate, 180 ml of water, 0.9 g of concentrated sulfuric acid and 91.2 g (0.90 mol) of isopropyl acetate was prepared. The diazonium salt solution prepared above and 50.4 g of 20% aqueous sodium sulfite solution were added slowly into the mixture simultaneously, the reaction temperature was maintained at 10-15 °C during the addition process, and the dropwise addition time was controlled to be within 2 hours. After addition, the reaction mixture was continued to be stirred for 1 hour.
Upon completion of the reaction, two extractions were carried out with toluene and the organic layers were combined. The organic layer was washed with dilute sodium bicarbonate solution to neutralize the acid. Subsequently, the solvent was removed by distillation under reduced pressure to give the crude product. The crude product was subjected to decompression distillation at 75-80 °C/5 mbar to afford 85.8 g of light yellow liquid 1-(2,4-difluorophenyl)propan-2-one in 82.9% yield.
