4-METHYL-3-(TRIFLUOROMETHYL)BROMOBENZENE synthesis

Yield: 85.9%

Reaction Conditions:

Stage #1:3-(trifluoromethyl)-4-methylaniline with hydrogen bromide;acetic acid in water at 30 - 95; for 0.5 h;Inert atmosphere;Large scale;
Stage #2: with sodium nitrite in water at 0; for 1 h;Inert atmosphere;Large scale;
Stage #3: with hydrogen bromide;copper(I) bromide in water at 65; for 1 h;Large scale;Concentration;Temperature;

Steps:

2 Example 2
Under nitrogen protection, Add 2642.3 g of 48% aqueous hydrogen bromide solution at room temperature. 1760.0g water and 880.0g acetic acid, Stirring, 880.0 g of 2-methyl-5-amino-benzotrifluoride (isoforms 0.037%, gas phase area normalized) were added dropwise at 30°C. After dropping, The temperature was raised to 95°C and stirred for 30 minutes to obtain a solution of hydrogen bromide salt.Cooling to 0°C, Add dropwise 1213.3g of 30% aqueous sodium nitrite solution at 0°C. The reaction was completed 1.0 h after the addition. The prepared diazonium salt was added dropwise to a previously prepared 360.4 g of cuprous bromide and 4997.0 g of a 48% aqueous solution of hydrogen bromide at 65C. A lot of nitrogen is released, Stirring is completed 1h, A 4-bromo-1-methyl-2-(trifluoromethyl)benzene solution was obtained.After the reaction is over, Cool down to 20°C and stir for 1.0h Resting, Layered, 1046.0g oil layer was added to 3661.0g water, 5.0% alkali hydroxide solution is alkalized to PH=7. After vapor distillation, 1032.0 g of pale yellow 4-bromo-1-methyl-2-(trifluoromethyl)benzene product was obtained. Yield 85.9%, The gas purity is 99.2%. Gas chromatography showed that the isomer content was less than 0.1%.

References:

Jinkai (Liaoning) Chemical Co., Ltd.;Wang Yanming;Wang Yongcan;Qin Long;Song Tongji;Chen Biwei CN107915570, 2018, A Location in patent:Paragraph 0057-0061; 0064-0067