4-(Chloromethyl)benzoic acid

258278-55-6

1642-81-5

Example 1: Synthesis of 4-nitro-oxo-methyl-benzoic acid (I) a) Nitration of 4-chloromethyl-benzoic acid (III) 49.29 kg of 4-chloromethyl-benzoic acid (III) was dissolved in 92.9 L of acetonitrile and stirred for 20 minutes while a slow stream of nitrogen was passed. Subsequently, 93 mL of sulfuric acid was added and stirring was continued for 15 minutes. Under the same operating conditions, 13.65 kg of silver nitrate was slowly added. The reactor was protected from light and the reaction mixture was stirred for 15 minutes. After that, the mixture was heated to reflux for 7 hours and 15 minutes. After completion of the reaction, it was cooled to 20°C-25°C. b) Post-treatment 37.2 L of dimethylformamide (DMF) was added and stirred for 30 min, maintaining the temperature between 20°C-25°C. The silver salt was separated by filtration under nitrogen pressure through a filter pre-washed with 11 L of water and containing 9 kg of filter media. The filter cake was washed with 28 L DMF in three passes. The solid waste was washed twice with 9.3 L DMF. The cellulose in the filter was removed and washed with DMF until clarified, then rinsed with water. c) Precipitation and purification The liquid phase was combined and stabilized at a temperature between 20°C and 25°C. Slowly add 1486 L of water over a period of 1 hour, maintaining the temperature between 20°C-25°C. Continue stirring for 1 hour, maintaining the same temperature range. The precipitate was separated by filtration and the filter cake was washed with water until the pH of the eluate was similar to that of water. Finally, the filter cake was washed with 18.6 L of ethanol. The wet solid was dried under vacuum at not more than 40 °C until the moisture content (KF method) was ≤ 0.2%. 9.68 kg of 4-nitro-oxo-methyl-benzoic acid (I) was obtained in 90.2% yield, 99.35% HPLC purity, and 0.23% (IV).