Bis(4-fluorophenyl)methanol

white to yellowish crystalline flakes or powder

General procedure: NaBH4 (0.6mol) was added to a stirred solution of benzophenones (1.0 mol)in methanol (2 vol) portionwise at room temperature for 45 min. The mixture was stirred for 2–3 h at ambient temperature (completion of reaction was monitoredby TLC), and was diluted with water (750 ml), acidified with acetic acid to pH 4, and extracted with dichloromethane (2x400 ml). The organic layer was washed with water (200 ml) and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to get pure benzhydrol derivatives as a white to off-white solid in 93–97percent yield. To the benzhydrol derivatives (1.0 mol) in toluene (370 ml) was added concentrated HCl (35percent in H2O, 370 ml) and tetrabutylammonium bromide(0.01 mol) at room temperature under stirring. Stirring was continued at 40–45 °C for 6–7 h. After completion of the reaction as indicated by TLC, the mixture was cooled to room temperature. The organic layer was separated and concentrated under vacuum to obtain crude benzhydryl chloride derivatives as a light brown liquid in 95–97percent yield. To this benzhydryl chloride (0.96 mol) derivatives in toluene (380 ml) was added anhydrous piperazine (5.0 mol) at 60–70 °C for 45–60 min. The resulting mixture was heated under stirring at 90–100 °C for 8–10 h. The mixture was cooled after completion of the reaction. Water (380 ml) was added, and the organic layer was separated. The latter was washed with a 1:1 mixture of concentrated HCl/water(2x350 ml) and neutralized with 20percent NaOH solution (750 ml). The water layer was re-extracted into toluene (2x300 ml), dried over anhydrous sodium sulfate, and concentrated under vacuum to result pure diphenylmethylpiperazine compounds (2a–c) as a white to off-white solid with yields up to 88percent.A. In a reaction vessel equipped with a reflux condenser, 0.23 mol of 4, 4-difluorobenzophenone, 0.31 mol of lithium isobutoxide, 65percent of dimethylamine solution and 260 ml of dimethylamine solution were added, and the temperature of the solution was increased to 60 , refluxing reaction 5h;B, save the distillate temperature at 45 , vacuum distillation, steamed out of dimethylamine, the remaining solution by adding 300ml mass fraction of 35percent ethyl acetate solution, precipitation of oil;C, pour out the oil and then add 350ml mass fraction of 60percent cyclohexane solution, shake, precipitate solid, filter, 75percent acetonitrile solution in the recrystallization, mass fraction of 50percent dichloromethane solution washing , The mass fraction of 25percent triethylamine solution washing, anhydrous magnesium sulfate dehydrating agent dehydration, in colorless crystal two pairs of fluorophenyl methanol 45.03g, yield 89percent.Synthesis begins with the preparation of Grignard reagent 2 from aromatic bromide 1 with magnesium in ether. Fluorobenzaldehyde 3 is added at -18° C. to Grignard solution 2 to give fluorobenzhydrol 4. It should be noted that instead of using fluorobenzaldehyde 3, it is possible to use ethyl formate to condense 2 units of Grignard 2. This option is economically advantageous as fluorobenzaldehyde 3 is relatively expensive.I. Bis(4-fluorophenyl)methanol; [00290] To a solution of 1 -bromo-4-fluorobenzene (1.00 g, 5.71 mmol) in anhydrous mol) dropwise , 5.71 mmol) in y ( ) y g -78General procedure: 1-bromo-4-methylbenzene (12.6 g, 73.8 mmol, 1.0 equiv.) was dissolved in dry THF (75 mL) and cooledto -78 oC under N2. n-Butyl lithium (46.2 mL, 1.6 M solution in hexane, 73.8 mmol, 1.0 equiv.) was addeddropwise and the resulting suspension was stirred at-78 oC for 1 h. Methyl formate (2.22 g, 36.9 mmol, 0.5equiv.) in THF (15 mL) was then added dropwise over a period of 10 min, and the mixture was stirred at-78 oC for 1 h, then at room temperature for 3 h. Saturated ammonium chloride (aqueous, 100 mL) wasadded and the mixture was extracted with DCM (3100 mL). The combined organic layers were washedwith brine (230 mL), dried over anhydrous Na2SO4, and concentrated to 20 mL. The product was crashedout with 200 ml Hexanes and washed with hexanes l (3 × 20 mL). The pure desired product was obtainedas a white crystalline solid (Yield: 6.67 g, 85.2percent).To the reaction flask was added 1 mmol of 4-fluorobenzyl bromide, 1.2 mmol of 4-fluorobenzeneboronic acid, and anhydrous potassium carbonate2 mmol, PEG 2000 2.5 mmol, 0.01 mmol catalyst, 5 ml pure water, air at room temperatureThe reaction was stopped for 4 h, and the reaction was quenched with about 40 ml of ethyl acetate to give ethyl acetateMachine phase, add 2-3 tablespoons of anhydrous sodium sulfate for 4h in addition to water, filter steaming steam, using TLC methodThe product was isolated using (n-hexane: dichloromethane = 7: 1, v: v) as a developing solvent.Ethanol to give bis (4-fluorophenyl) methanol in a yield of 75percent.

Molecular Weight:220.21
XLogP3:2.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:220.06997126
Monoisotopic Mass:220.06997126
Topological Polar Surface Area:20.2
Heavy Atom Count:16
Complexity:184
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes