2-Bromo-1-fluoro-4-methylbenzene

colorless to light yellow liqui

(b) EXAMPLE 4 EXAMPLE 5 EXAMPLE 3 (a) A solution of potassium nitrate (2.46g; 0.024 mol) in concentrated sulfuric acid (36 ml) was added dropwise at a temperature below 5C to a solution of 3-bromo-4- fluorotoluene (2.52 mL; 0.02 mol) in concentrated sulfuric acid (4 ml). The mixture was stirred at 5C for 2 hours, then, poured onto ice water. The obtained precipitatewas filtered and dried yielding 3.94g (84%) of intermediate 492.2-bromo-4-(bromomethyl)-1-fluorobenzole Referential Production of 3-Bromo-4-fluorobenzylbromide 3-Bromo-4-fluorotoluene (9.36 g; 49.5 mmol) was dissolved in carbon tetrachloride (100 ml), and N-bromosuccinimide (8.82 g; 49.6 mmol) and benzoyl peroxide (200 mg) were added thereto. The mixture was heated under reflux for 1 hour, and then cooled. Insoluble matter was filtered off, followed by washing with carbon tetrachloride. The filtrate was concentrated under reduced pressure, and n-hexane (120 ml) was added thereto. The mixture was left to stand, and insoluble matter was filtered off, followed by washing with n-hexane. The filtrate was evaporated, to thereby yield 13.04 g of a mixture of the target-compound, the starting compound, and the dibromo compound (yield based on the weight of the mixture: 98.2%). 1H-NMR (CDCl3, ppm); 4.42 (2H, s), 7.09 (1H, t, J=8.37 Hz), 7.30 (1H, m), 7.60 (1H, dd, J=6.46 Hz, 1.89 Hz), To a solution of diisopropylamine (590 mg, 5.8 mmol, 1.1 eq) in dry THF (15 mL) at - 78C was added n-BuLi (2.6 mL, 5.8 mmol, 1.2 eq) dropwise. The solution was stirred at -78C for 30 min, then a solution of 2-bromo-l-fiuoro-4-methyl-benzene (lg, 5.3 mmol, 1.0 eq) in dry THF (5 mL) was added dropwise. After stirring for a further 1.5 h at -78C, C02 gas was bubbled into the solution. The reaction was warmed to room temperature and allowed to stir for a further lh. The reaction was then quenched by addition of aqueous NH4CI and the THF removed under reduced pressure. The aqueous residue was acidified to pH 5 and the solid that formed collected by filtration, washed with water and dried to give the title compound as a solid (700 mg, 58 %). 1H NMR (400 MHz, DMSO-d6) ' 7.78 (dd, J = 6.0, 2.2 Hz, 1H), 7.66 (dd, J = 6.4, 2.2 Hz, 1H), 2.33 (s, 3H)Step A. 3 -Bromo-2-fluoro-5 -methylbenzoic acidTo a solution of diisopropylamine (3.6 mL, 25 mmol) in THF (60 mL) was added n-BuLi (2.6 molar, 8.95 mL, 23.3 mmol) at 0 C, it was stirred at the same temperature for 20 minutes. The mixture was cooled to -78 C and 2-bromo-i-fluoro-4-methylbenzene (4.0 g, 21 mmol) in THF (20 mL) was added. The mixture was stirred at -78 C for 25 minutes, then dry-ice was added to the reaction. The mixture was stirred at -78C for 1 h and at RT for 30 minutes. THF was almostremoved and it was diluted with CH2C12 and iN aq. NaOH. The mixture was extracted with CH2C12. The aqueous layer was acidified with iN aq. HC1 to pH 1, and it was extracted with EtOAc. The extract was washed with water and brine, and dried over Na2504, filtered, and concentrated in vacuo to give the title compound.MS (ESI) mlz = 233, 235 (M+H)To a solution of diisopropylamine (3.6 mL, 25 mmol) in THF (60 mL) was added n-BuLi (2.6 molar, 8.95 mL, 23.3 mmol) at 0 C. This was stirred at the same temperature for 20 minutes. The mixture was cooled to -78 C and 2-bromo-l-fluoro-4-methylbenzene (4.0 g, 21 mmol) in THF (20 mL) was added. The mixture was stirred at -78 C for 25 min, then dry-ice was added to the reaction. The mixture was stirred at -78C for 1 h and at RT for 30 min. THF was almost removed and it was diluted with CH2CI2 and IN aq. NaOH. The mixture was extracted with CH2CI2. The aqueous layer was acidified with added IN aq. HC1 to pH 1, and it was extracted with EtOAc. The extract was washed with water and brine, and dried over Na2S04, filtered, and concentrated in vacuo to give the title compound. MS (ESI) m/z = 233, 235 (M+H)EXAMPLE 7 855 g of 2-bromo-4-methylbenzenediazonium tetrafluoborate are introduced in 85 g of 1, 3, 5-triisopropylbenzene at 125 to 130 C. in the course of 10 hours. After completion of the introduction, the mixture is maintained at 125 to 130 C. for a further 1 hour (completion of evolution of gas). Subsequently, volatile components are distlled off in vacuo. The distillate is neutralized with calcium oxide and purified by rectification. 474.5 g of EXAMPLE 6 143 g of 2-bromo-4-methylbenzenediazonium tetrafluoborate (prepared in accordance with Examples 2-5) are introduced into 80 g of paraffin oil at 120 to 125 C. in the course of 5 hours. The gas evolved (boron trifluoride and nitrogen) is passed through a washer which contains 100.0 g of i-butanol at 0 C. After completion of the introduction, the reaction mixture is then stirred for approximately a further 1 hour at 125 to 130 C. Subsequently, volatile components are distilled off in vacuo. The distillate is treated with 1 g of calcium oxide and filtered. In this manner, 88.2 g of General procedure: A sealed tube equipped with a magnetic stir bar was charged with the corresponding 1-bromo -2-fluoro (or chloro) benzene/ 1-fluoro-2-iodobenzene (1 mmol), amino phenol (1 mmol), Pd(OAc)2 (5 mol%), xantphos (5 mol%) and DBU (2.5 mmol). The tube was purged with argon. Then DMF (10 V) was added followed by the addition of Co2(CO)8 (0.25 mmol). The tube was closed with seal plug instantly. The reaction tube was placed in a pre heated oil bath at 150 0C for 16 h. On completion, the reaction mixture was cooled to room temperature, added water and ethyl acetate (1:1). Precipitated solid was filtered through a Celite bed. The bed was washed thoroughly with ethyl acetate. Organic layer was separated. Aqueous layer extracted with EtOAc. The combined organic layers were washed with water, brine, dried over anhydrous sodium sulphate. Organic layer was concentrated under reduced pressure and purified by flash column chromatography on silica gel (230-400 mesh) with ethyl acetate and petroleum ether as eluent to afford the corresponding dibenzoxazepinones.

Used as medicine, pesticide, liquid crystal material intermediate

Molecular Weight:189.02
XLogP3:3.1
Hydrogen Bond Acceptor Count:1
Exact Mass:187.96369
Monoisotopic Mass:187.96369
Heavy Atom Count:9
Complexity:94.9
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes