Background and overview of two preparation methods of 3-fluorophenylboronic acid
3-Fluorophenylboronic acid is a white solid and an important pharmaceutical and chemical intermediate. It is widely used in organic and pharmaceutical synthesis. In addition to its important application in Suzuki coupling reactions, it also has other applications: for example, it is used as a catalyst to catalyze the condensation reaction of carboxylic acids and amines, to catalyze the reduction of carboxylic acids to alcohols; and to react with α, β-unsaturated compounds1,4 -Conjugate addition reaction to synthesize β-aryl substituted carbonyl compounds, etc. Most of these reactions of large aminopyridines use relatively non-toxic and cheap common reagents, with mild reaction conditions, high yields and good stereoselectivity. In recent years, with the continuous development of liquid crystal display technology, the demand for fluorine-containing liquid crystal display materials has continued to increase, and fluorobenzene boric acid is a key intermediate for the synthesis of fluorine-containing liquid crystal display materials.
Two preparation methods of 3-fluorophenylboronic acid reported
Two preparation methods of 3-fluorophenylboronic acid reported one,
The material ratio of 3-fluorobromobenzene:magnesium:trimethylborate is 1.0:1.1:1.5. The total mass amount of solvent 2-methyltetrahydrofuran is 7 times the mass of 3-fluorobromobenzene.
Add 2.6g of magnesium chips (0.11mol), 1 to 2 grains of iodine, and 30g of 2-methyltetrahydrofuran into a 250mL four-neck bottle with a reflux condenser and a constant-pressure dropping funnel, and place it under N2 protection at 40°C. A small amount of 17.5g (0.10 mol) of 3-fluorobromobenzene and 22.5g of 2-methyltetrahydrofuran solution was added dropwise. After stirring to initiate the reaction, the remaining 3-fluorobromobenzene solution was added dropwise. After the dropwise addition is completed, react at this temperature for 3 hours to prepare a solution of 3-fluorophenylmagnesium bromide in 2-methyltetrahydrofuran.
Take another 500mL four-neck bottle, add 15.6g (0.153mol) trimethyl borate and 90.0g 2-tetrahydrofuran, cool to -20°C under N2 protection, add the above Grignard reagent solution dropwise, and keep warm after the dropwise addition. Reaction takes 3 hours. At this temperature, add 100 mL of 8% hydrochloric acid and perform a hydrolysis reaction for 2 hours. Separate the organic phase. Extract the aqueous layer with 2-methyltetrahydrofuran and wash it with saturated brine until neutral. Combine the organic phases and wash with anhydrous sulfuric acid. Dry over sodium, recover the solvent under reduced pressure, and recrystallize the crude product with 1,2-dichloroethane to obtain 11.7g of 3-fluorophenylboronic acid, white needle-like crystals, with a yield of 83.7%, an HPLC purity of 99.6%, and a melting point of 217.6 ~218.3℃.
Two preparation methods of 3-fluorophenylboronic acid report 2,
A solution of 1-bromo-3-fluorobenzene (0.05M) in dry ether (130ml) was stirred at -78°C. Under a dry nitrogen atmosphere, n-butyllithium (0.52 M, 2.5 M solution in hexane) was added dropwise at a rate such that the temperature of the reaction mixture did not exceed -73 °C. (Addition takes approximately 15 minutes). The reaction mixture was stirred for 20 minutes, then triisopropyl borate (0.1 M) was added at a rate such that the temperature of the reaction mixture did not exceed -65 °C. The reaction mixture was stirred for 60 minutes, then warmed to room temperature and poured into diethyl ether (100 ml) and dilute aqueous hydrochloric acid (150 ml, prepared by diluting ten times concentrated aqueous hydrochloric acid). The aqueous layer was separated and extracted with diethyl ether (100ml). The combined ether layers were washed with water (5 ml of 7-pentahydroxycobalt dicarbonate), dried (Na2SO4) and evaporated. After removal of the mother liquor, the residue was triturated with hexanes (40 ml) to yield, which was used without further purification.
References
[1][Chinese invention] CN200910153604.9 Preparation method of fluorine-containing phenylboronic acid
[2]From U.S., 6069157, 30 May 2000
