Preparation method of 2-chloro-5-nitrobenzoic acid_Kain Industrial Additive

Background and overview^[1]

The method for preparing 2-chloro-5-nitrobenzoic acid in the prior art is to use the method of refining o-chlorobenzoic acid after nitration, but due to the nitration, more 2-chloro-3-nitrobenzoic acid is produced. For isomers, it is difficult to achieve higher purity using conventional purification methods. Generally, it can only be controlled at around 99.0%, which cannot meet the needs of use.

Preparation^[1-2]

Method 1: A production process of 2-chloro-5-nitrobenzoic acid, the steps are as follows:

(1) Nitrification: Put concentrated sulfuric acid and o-chlorobenzoic acid into the nitrification kettle at a weight ratio of 3.5:1, add the reaction amount of nitric acid dropwise, control the temperature at 30°C, after the dropwise addition is completed, keep it warm for more than 2 hours, and take a thin sample After checking by layer chromatography that there is no residual o-chlorobenzoic acid, the material is discharged into the water separation kettle. The 2-chloro-5-nitrobenzoic acid and 2-chloro-3-nitrobenzoic acid generated by the reaction crystallize and separate out, and the crude product is obtained after centrifugal filtration;

(2) Alkali dissolution: Put the crude product into the alkali solution kettle, add water 3.5 times the weight of the crude product, stir and raise the temperature to 60°C, add liquid caustic soda dropwise until pH=7.5, 2-chloro-5-nitrobenzoic acid Dissolve with 2-chloro-3-nitrobenzoic acid and react with NaOH to generate sodium 2-chloro-5-nitrobenzoate and sodium 2-chloro-3-nitrobenzoate; add an appropriate amount of activated carbon and press filter for decolorization to obtain the filtrate;

(3) Acid precipitation: Put the filtrate into the acid precipitation kettle, add nitric acid solution with a mass concentration of 50% dropwise to pH = 2, raise the temperature to boiling, keep it for at least 1 hour and then naturally cool to 38°C, 2-chloro- 5-Nitrobenzoic acid is precipitated, centrifuged, washed with water, and dried with a double cone vacuum dryer at 0.06MP and 80°C to obtain a finished product; the chromatographic purity of the finished product is 99.5% and the yield is 85%.

Method 2: A method for preparing 2-chloro-5-nitrobenzoic acid, including the following steps: adding The mass ratio of concentrated nitric acid and SO3 is 20% fuming sulfuric acid with a mass ratio of 1 to 3, and the temperature of the solution is controlled below 10°C during the mixing process. Add 2-chlorotrichlorotoluene to the obtained sulfuric acid and nitric acid mixture within about 2.5 hours (the mass ratio of 2-chlorotrichlorotoluene to concentrated nitric acid and oleum mixture with 20% SO3 is 1:4) to control the reaction. The liquid temperature is between 0 and 10°C. After the dropwise addition is completed, the temperature is maintained and stirring is continued for 2 hours to complete the reaction. The reaction solution was then poured into ice water and solid precipitation was immediately observed. Dichloromethane was added to the mixture for extraction, and the organic phase was washed with saturated NaHCO3 solution, then dried over magnesium sulfate, filtered and evaporated to dryness. 2-Chloro-5-nitrotrichlorotoluene was obtained (GC titer = 99.6%, molar yield 98%). Take concentrated sulfuric acid with a mass fraction of 96%, add water to adjust the acid concentration to 85wt%. Adjust the temperature of the acid to approximately 60°C and begin adding purified 2-chloro-5-nitrotrichlorotoluene portionwise. The temperature was then adjusted to 90°C and a gradual formation of solid product dispersed in the mixture was noted. This temperature was maintained for about 3 hours, then the reaction mixture was cooled to about 50°C and diluted with water, and the product was extracted with ethyl acetate at room temperature. The phases were separated and the organic phase was washed with water. Finally, the solvent was evaporated to give 2-chloro-5-nitrobenzoic acid (titer by HPLC = 98.5%, molar yield 94%).

Main reference materials

[1] CN201110174759.8 A production process of 2-chloro-5-nitrobenzoic acid

[2] CN201610769451.0 Preparation method of 2?chloro?5?nitrobenzoic acid