Preparation of 4-bromo-2-methoxyaniline_Kain Industrial Additive

Background and overview^[1]

Bromoaniline is widely used in medicine and pesticides and is an important raw material for pharmaceuticals and pesticides. Since the experiments of para-chlorination of substituted phenolic hydroxyl groups with copper chloride were carried out in the early 1970s, no one has systematically studied the bromination situation of bromoaniline. At present, the preparation of brominated aniline has been relatively cumbersome in the industry. It is generally prepared by first protecting the amino group, then brominating, isolating, and finally deprotecting it; there are also methods by attaching amino groups or other functional groups to other substrates, but the preparation cost is high, the pollution is large, and the synthesis steps are long.

4-Bromo-2-methoxyaniline CAS number 57652-28-3, chemical formula C₉H₈BrFO₂. Molecular weight 247.06100. Density 1.534g/cm3, boiling point 291.6ºC at 760 mmHg), flash point 130.1ºC, refractive index 1.541, vapor pressure 0.00193mmHg at 25°C. 4-Bromo-2-methoxyaniline can be used as a pharmaceutical and chemical synthesis intermediate.

Preparation ^[1]

React the substrate with CuBr2 in a solvent, and then collect the bromoaniline from the reaction product. The solvent is selected from hydrochloric acid, tetrahydrofuran, acetonitrile, 1,4 with a weight concentration of 10 to 36%. Dioxane, ethanol, methylene chloride, toluene, N, N dimethylformamide or ionic liquid, such as 1 hexyl chloride 3 methylimidazole, 1 isobutyl chloride Base 3 methylimidazole, 1 pentyl 3 methylimidazole chloride; preferably hydrochloric acid, tetrahydrofuran or 1 hexyl 3 methylimidazole chloride with a weight concentration of 25 to 36%; in the solvent, The content of substrate is 0.01～0.1g/ml;

The brominated anilines are: 4 bromide 2 methyl aniline, 4 bromide 2 methoxy aniline, 4 bromide 2 fluorine aniline preparation, 4 bromide 2 trianiline Preparation of fluoromethylaniline, 4-bromide 2-nitroaniline, 4-bromide 3-methylaniline, 4-bromide 3-methoxyaniline, 4-bromide 3-fluoroaniline or 4-bromide 3 Trifluoromethylaniline, of which 4 bromide 2 methoxyaniline is prepared as follows: In a 500 ml reactor, add 150 ml of 1 hexyl 3 methylimidazole chloride and stir ultrasonically Evenly, add 67 grams (0.3 mol) CuBr2, stir evenly by ultrasonic, at this temperature, add 10.7 grams (0.1 mol) 2 methoxyaniline, stir for 1 hour, TLC tracking spots show that the raw material spots disappear.

Add 50 ml of ethyl acetate to extract twice, combine the ethyl acetate phases, wash twice with saturated brine, and dry the ethyl acetate phase over anhydrous Na2SO4. Further recover the solvent to most of it, add a small amount of petroleum ether, cool, and precipitate a red crystalline solid, which is filtered to obtain 19.2 grams of 4-bromo-2-methoxyaniline with a yield of 95% and a purity of 99% (HPLC).

(R1 represents -OCH3)

Main reference materials

[1] CN201110272053.5 Preparation method of bromoaniline