Background and overview of two preparation methods of 3,5-difluorophenylboronic acid
3,5-Difluorophenylboronic acid is a fluorine-containing phenylboronic acid, which is a yellow solid. Fluorine-containing phenylboronic acid is a kind of organic synthesis, pharmaceutical, and chemical intermediates that are relatively stable in the air, insensitive to moisture, can be stored for a long time, and have high reactivity. The Suzuki coupling reaction of fluorobenzene boronic acid and halogenated aromatic hydrocarbons has good position selectivity and stereoselectivity. Various chemical functional groups do not change during the reaction. The reaction conditions are mild and the yield is high. It forms C—C bonds. important way.
Two preparation methods of 3,5-difluorophenylboronic acid
Two preparation methods of 3,5-difluorophenylboronic acid reported 1.
Add 62g (2.6mol) of magnesium chips and 750ml of tetrahydrofuran into a 5L three-neck flask, install a spherical condenser tube with a drying tube and a dropping funnel, and add dropwise 482.5g (2.5mol) of 3,5-difluorobenzene. and 1500ml tetrahydrofuran (confirm that the reaction has been initiated). After the addition, heat and reflux for 0.5 hours. Ventilate nitrogen to maintain positive pressure. Start stirring. Cool to about -50°C in a low-temperature bath. Add 850g (3.7mol) of triisobutyl borate – dropwise. 500ml tetrahydrofuran solution, when the reaction solution is lower than -50℃, it takes about 1.5 hours. After the addition, stir in the bath for 5 minutes, then stir to room temperature, leave it overnight, add 500ml concentrated hydrochloric acid (analytical grade, the same below)-1000ml water Hydrolyze and stir for 1 hour; then add 2L of ethyl acetate, separate the liquids, and wash with saturated brine until neutral; evaporate the solvent under reduced pressure in a water bath, cool to room temperature, and filter with suction to obtain 3,5-difluorophenylboronic acid. Yield: 296g (75% of theoretical value), melting point: 210°C.
Two preparation methods of 3,5-difluorophenylboronic acid reported 2.
Add 12.6g of fully dry magnesium and 100ml of THF into the reactor under nitrogen atmosphere, and heat to 48°C. 100.0 g of the compound (T1) dissolved in 500 ml of THF was slowly added dropwise thereto within a temperature range of 45°C to 55°C, and the mixture was stirred for another 120 minutes. 300 ml of THF and 80.8 g of trimethyl borate were added to another reactor, and stirred at -70°C. The THF solution of Grignard reagent obtained previously was slowly added dropwise thereto in the temperature range of -70°C to -60°C, and the mixture was further stirred at 0°C for 120 minutes. The obtained reaction mixture was poured into a container containing 3000 ml of 1N hydrochloric acid and 3000 ml of ethyl acetate cooled at 0°C, and mixed. Thereafter, the mixture was allowed to stand to separate into an organic layer and an aqueous layer, and the extraction operation was performed. The obtained organic layer was separated, washed with brine, and dried over anhydrous magnesium sulfate. Thereafter, the solvent was distilled off under reduced pressure to obtain 52.5 g of 3,5-difluorophenylboronic acid (T7). The obtained compound (T7) was a yellow solid.
References
[1][Chinese invention] CN200810117605.3 Method for synthesizing mica from terminal difluoromethoxy liquid crystal compounds
[2][China invention, China invention authorization] CN200880002823.0 Liquid crystal compounds, liquid crystal compositions and sodium trithiocarbonate liquid crystal display elements
