Preparation of 5-Chloro-2-nitroaniline

2-Nitro-5-chloroaniline is an important pharmaceutical and veterinary drug intermediate. It has been applied in the upgraded product of veterinary drug albendazole-fenbendazole, and has a broad market prospect.

Preparation

1. Synthesis of 2,4-Dichloronitrobenzene

Add 0.714 mol of concentrated sulfuric acid to a 250 mL flask, and then slowly add 0.701 mol of 95% nitric acid dropwise, and set aside after cooling. Add 0.68mol m-dichlorobenzene to a 250mL three-necked flask, lower the temperature in the ice bath to below 20°C, slowly add the above mixed acid dropwise, pay attention to control the reaction temperature between 35～45°C, and continue to react at 45°C for 1h after the addition is complete . The acid layer is separated by standing, and the obtained product is washed with water and alkali to obtain crude 2,4-dichloronitrobenzene. Add the crude product to 200mL of 95% ethanol and heat it to dissolve, then stir and lower the temperature to 10°C. A large number of needle-like crystals are formed. After filtration and drying, 105g of product is obtained. After the mother liquor is concentrated, the crystallization is continued to obtain 14g of product. The total yield is 91.1%. 

2. Synthesis of 2-nitro-5-chloroaniline

Add 2.46mol of 2,4-dichloronitrobenzene, 7.72mol of toluene to a 3L autoclave, seal the autoclave, replace the air with nitrogen, then pass in 14.1mol of liquid ammonia, increase the temperature to 160℃, continue the reaction for 8h, and then lower the temperature to 40℃, drain the excess ammonia gas, open the kettle, add the obtained solid-liquid mixture to 800mL of water, continue to cool to 10℃, filter, add the resulting filter cake to the water, continue beating and filtering, the obtained solid is crystallized with methanol to obtain 388g pure The yield is 91.2%, the purity of the liquid phase external standard is 99.5%, and the melting point is 126～129℃.