Preparation method of 4-tolueneboric acid_Industrial additives

Overview of the preparation method of 4-tolueneboronic acid

4-Tolueneboronic acid is an important chemical raw material for the synthesis of medicines and electronic materials. Its preparation is generally completed through the intermediate compound 4-bromo-2,6-difluorotoluene. The main synthesis steps are: using 4-bromo-2,6-difluorobenzyl alcohol as the starting material, first carrying out the sulfonyl addition of the hydroxyl group reaction, and then hydrogenolysis of the sulfonate ester with lithium alkylborohydride to prepare the intermediate compound 4-tolueneboronic acid in two steps.

Preparation method of 4-tolueneboronic acid Preparation method

1. In an inert gas environment, use 1-bromo-3,5-difluorobenzene to react with lithium diisopropylamine at -78°C for 12 hours, then add methyl iodide, and adjust the pH value of the solution with 1N dilute acid is 6-7, add an organic solvent for extraction, concentrate the solvent, and distill under reduced pressure to generate 4-bromo-2,6-difluorotoluene;

2. Under an inert gas environment, use 4-bromo-2,6-difluorotoluene and n-butyllithium to react at -78°C for 12 hours, add triisopropylborate, and adjust the solution with dilute acid The pH value is 5-6. Add an organic solvent for extraction. After concentrating the solvent, add n-hexane for rinsing to obtain the target compound 3,5-difluoro-4-methylphenylboronic acid.

The preparation method of 4-tolueneboronic acid. The specific preparation steps are:

1. Preparation of 4-bromo-2,6-difluorotoluene:

Under nitrogen protection, add 834g, 4.34mol 1-bromo-3,5-difluorobenzene and 2L anhydrous tetradimethoxypyridine hydrofuran into the 5L reaction bottle, cool to -78°C, and add slowly dropwise 2795mL diisopropylamide lithium 4.77mol, 1.7N in hexanes, react at -78°C for 3h, then slowly add 613.35g methyl iodide 4.32mol dropwise, the reaction system rises to room temperature, react at room temperature for 12h, adjust the solution with 1N acid The pH value is 6, add ethyl acetate for extraction, use a rotary evaporator to evaporate all the solvent at a water temperature of 35oC, and then distill under reduced pressure at 102oC/2mmHg to generate 4-bromo-2,6-difluorotoluene;

Preparation of 2, 4-tolueneboronic acid:

Under nitrogen protection, add 69g, 0.33mol 4-bromo-2,6-difluorotoluene and 500mL anhydrous tetrahydrofuran into a 3L reaction bottle, cool to -78°C, slowly add 141mL n-butyllithium 0.37mol dropwise, 2.6N in hexanes, after adding, react at 78°C for 3 hours, then dropwise add 65.82g of triisopropylboric acid with a purity of 99% and 0.35mol of methylboric acid, and let the reaction system slowly rise to room temperature. This process takes 12 hours. Adjust the pH value of the solution to 5 with 1N hydrochloric acid, add ethyl acetate for extraction, evaporate all the solvents using a rotary evaporator at a water temperature of 35°C, add n-hexane and rinse at room temperature for 3 hours to obtain 41g of the target compound 4-tolueneboronic acid.

Reference materials

[1] Tang Yongjun, Mo Shan. A method for preparing 4-tolueneboronic acid:, 2014.

TAG: 4-tolueneboronic acid, preparation method of 4-tolueneboronic acid

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