For the large-scale synthesis of 1,2,3,5-tetrafluoro-4-nitrobenzene, a mixed solution of concentrated nitric acid (990 g) in concentrated sulfuric acid (973 mL) was first pre-cooled, and then the mixed solution was slowly added to a cold solution of 1,2,3,5-tetrafluorobenzene (973.1 g) dissolved in concentrated sulfuric acid (2,920 mL) at temperatures ranging from 0 °C to 10 °C, with the addition process being controlled to be completed within 1.5 The addition process was completed within 1.5 hours. After the addition was completed, the reaction temperature was maintained between 0 °C and 10 °C, and the yellow reaction solution was continued to be stirred for 1 hour until the analysis confirmed the completion of the reaction. Subsequently, the reaction solution was slowly poured into water (9730 g) that had been pre-cooled to below 25 °C, and dichloromethane (9730 mL) was added for extraction. After separation of the organic phase, it was washed twice with deionized water (10 L). The dichloromethane layer was concentrated to give a yellow oil. Finally, the oily substance was distilled under reduced pressure (2.5 mbar) at 70 °C to 75 °C to give a yellow oily product with 98% purity and 72.4% yield.
