preparation method of 2-bromo-6-nitrotoluene_kain industrial additive

background and overview^[1][2]

2-bromo-6-nitrotoluene can be used as a pharmaceutical synthesis intermediate.

preparation^[1]

2-bromo-6-nitrotoluene is prepared as follows:

① preparation of 3-nitro-4-methylbenzenesulfonic acid: place 100kg p-toluenesulfonic acid and 319kg concentrated sulfuric acid into the reaction kettle, stir for 1.5 hours, and slowly add 65% concentrated nitric acid while stirring 61.8kg, keep the temperature at 30-40°c during stirring. after adding, keep stirring at 30-40°c for 1 hour to obtain the reaction mixture; then pour the reaction mixture into a mixture of 100kg ice and 200l water, and use dichloromethane to extract with 2×500l, combine the dichloromethane layers, wash with 2×500l of water, dry the organic phase with 10kg of anhydrous magnesium sulfate, evaporate the solvent under reduced pressure to obtain 115kg of 3-nitro-4-methylbenzenesulfonic acid as a light yellow oil. yield 92%;

② preparation of 3-nitro-4-methyl-5-bromobenzenesulfonic acid: add 115kg of 3-nitro-4-methylbenzenesulfonic acid in step ① to 230l of glacial acetic acid, and heat to 70°c , add 69kg liquid bromine dropwise, keep the temperature at 70°c for 12 hours, cool to room temperature, add 600l ice water, stir, filter, wash with 2×230l cold water, and dry to obtain 3-nitro-4-methyl-5-bromobenzene sulfonic acid 130kg, yield 84%;

③ preparation of 2-bromo-6-nitrotoluene: add 130kg of 3-nitro-4-methyl-5-bromobenzenesulfonic acid in step ②, 39kg of sodium acetate, and 58.5kg of 40% sulfuric acid into 390l for purification in water, react at 90°c for 24 hours, cool to 5°c, suction filter, wash the filter cake fully with 2×300l cold water, and dry under reduced pressure to obtain 85.7kg of light yellow 2-bromo-6-nitrotoluene, with a yield of 90%;

application

2-bromo-6-nitrotoluene can be used as a pharmaceutical synthesis intermediate, such as the preparation of 2-nitro-6-trichloromethyltoluene:

dissolve 85.7kg 2-bromo-6-nitrotoluene in 900l dry tetrahydrofuran solution, cool to 0°c under nitrogen protection, then add 180l of 1.6m n-butyllithium hexane solution dropwise, and control the dropping speed. as long as the internal temperature does not rise more than 10°c, after the dropwise addition is completed, keep stirring at this temperature for 2.5 hours at 5°c to obtain a mixed solution;

main reference materials

[1]cn201110432682.x a kind of synthesis method of 2-methyl-3-trifluoromethylaniline