4-Bromo-3-nitrophenol

brown solid

General procedure: To a mixture of anilines or phenols (0.7 mmol) the brominatingagent (1) (0.72 g, 0.7 mmol) in dichloromethane(30 ml)-methanol (15 ml) was added. The reactionmixture was stirred at room temperature until decolorizationof the orange solution took place. The progress of thereaction was monitored by TLC (eluent: n-hexane/ethylacetate, 7:3). After completion of the reaction, the solventwas evaporated and diethyl ether (10 ml) was added to theresidue. The supernatant was decanted and the insolubleresidue was washed by ether (3 × 10 ml). The combinedether extracts were dried on magnesium sulfate and also evaporated under vacuum to afford monobromo anilines ormonobromo phenols which was purified by flash columnchromatography over silica gel (n-hexane/ethyl acetate, 7:3).A solution of boron tribromide (250 mmol) in dichloromethane (200 mL) was added drop wise over 1 h to a solution of the nitrobromide (100 mmol) in dichloromethane (250 mL) at -78° C. A solution of boron tribromide (250 mmol) in dichloromethane (200 mL) was added drop wise over 1 h to a solution of the nitrobromide (100 mmol) in dichloromethane (250 mL) at -78 Step 1 . Synthesis of 4-bromo-3-nitrophenol (C3). 1 -Bromo-4-nnethoxy- 2-nitrobenzene (170 g, 0.73 mol) was dissolved in dichloromethane (1 .5 L) in a 5-liter, 3-necked flat-bottomed flask equipped with a thermometer, pressure-equalizing dropping funnel and exhaust gas scrubber (1 M aqueous sodium hydroxide). The solution was cooled to -78 °C under argon. Boron tribromide (176 ml_, 1 .86 mol) was dissolved in cold dichloromethane (1 .6 L, 0 °C); this was added to the cooled reaction via the dropping funnel over 2 hours. An exotherm brought the temperature to -55 °C. At the completion of the addition, the cooling bath was removed and the reaction was allowed to warm to RT and stir for 48 hours.The reaction mixture was added to cold water (2.0 L, ice/water bath) over 4 hours via a dropping funnel, maintaining the internal temperature below 20 °C. A scrubber (1 M aqueous sodium hydroxide) was used to prevent release of the HBr gas that was formed. The quenched mixture was stirred at RT for an additional hour, at which time the phases were separated and the aqueous layer was extracted with EtOAc (2.0 L); the combined organic layers (dichloromethane and EtOAc) were washed with saturated aqueous sodium bicarbonate solution (2 x 1 .2 L; lower phase was the organic layer), then with brine (1 L, lower phase was the aqueous layer), dried over magnesium sulfate and concentrated in vacuo. The residue was suspended in dichloromethane (320 ml_) and slurried overnight, and the solid was collected by filtration. The solid was dissolved in aqueous sodium hydroxide solution (2.0 M, 500 mL) and extracted with dichloromethane (500 mL). The dichloromethane layer was then extracted with aqueous sodium hydroxide solution (250 mL), and the combined aqueous layers were acidified to pH 2 with aqueous HCI (1 .0 M, 790 mL). The precipitated phenol was filtered and dried under vacuum at 40 °C for 18 hours to provide C3 as a solid. Yield: 125.5 g, 0.5757 mol, 79percent. To a solution of 1-bromo-4-methoxy-2-nitrobenzene (20 g, 82 mmol) in DCM (800 mL) was added dropwise BBr3 (19 mL, 207 mmol) in DCM (120 mL). The resulting mixture was heated to reflux overnight. The mixture was cooled in ice-water and was diluted by addition of water. Then the mixture was washed with saturated NaHCO3 and brine. The organic phase was dried over Na2SO4, concentrated under reduced pressure to give a residue, which was purified by column chromatography on silica gel to provide 4-bromo-3-nitrophenol (6 g, 31percent) as a solid: ‘H NMR (CDC13): 3 7.57 (d, J = 8.8 Hz, 1H), 7.35 (d, J= 2.6 Hz, 1H), 6.94 (dd, J= 2.9, 8.6 Hz, 1H), 5.90 (br., 1H).(1) diazotization reaction: take 12g3_ amino-4-nitrophenol, Dissolved in 64 g of hydrobromic acid at a concentration of 40 wtpercentLiquid, cooled to 0-10 ° C.36 g of a 20percent by weight aqueous solution of sodium nitrite was added dropwise at this temperature. Thermal insulation reaction 1h.The resulting yellow liquid was an aqueous solution of 3-nitrophenol-4-diazonium salt, which was used directly in the next reaction.(2) Bromination reaction:Take 1.2g cuprous bromide, dissolved in 27g concentration of 40wtpercent hydrobromic acid solution.After the temperature was raised to 40-45 ° C, the reaction solution obtained in step (1) was added dropwise. After the addition was completed, the reaction 1h Thermal insulation. Cool to 20-25 ° C, precipitated solid. The product is filtered off and the solid washed with a little water and dried.13.1 g of 3-nitro-4-bromophenol were obtained.Content of 95percent.Benzyl bromide (131 mmol) and potassium carbonate (130 mmol) were added to a solution of the nitrophenol (87.0 mmol) in 2/1 acetonitrile/acetone (840 mL). The reaction mixture was heated at reflux for 17 h and was concentrated to dryness. The residue was suspended in ethyl acetate (756 mL), filtered, and the organic layer was washed with water (567 mL), 1 M hydrochloric acid (2*567 mL), and brine (567 mL). The organic layer was dried (magnesium sulfate) and concentrated to the benzyl ether in 78percent yield.Benzyl bromide (131 mmol) and potassium carbonate (130 mmol) were added to a solution of the nitrophenol (87.0 mmol) in 2/1 acetonitrile/acetone (840 mL). The reaction mixture was heated at reflux for 17 h and was concentrated to dryness. The residue was suspended in ethyl acetate (756 mL), filtered, and the organic layer was washed with water (567 mL), 1 M hydrochloric acid (2 x 567 mL), and brine (567 mL). The organic layer was dried (magnesium sulfate) and concentrated to the benzyl ether in 78percent yield.A. Preparation of 5-benzyloxy-2-bromonitrobenzene A. 2-Bromo-5-benzyloxy-nitrobenzene To a solution of 6.2 g (28.4 mmol) of To a mixture of General procedure: A reaction mixture of (4-cyanophenyl)boronic acid 5 (150 mg, 1.02 mmol, 1.0 equiv.), 4-bromo-2-chloro-6-methylphenol 6s (271 mg, 1.22 mmol, 1.2 equiv.) and potassium carbonate (353 mg, 2.55 mmol, 2.5 equiv.) in PEG400/H20 (4 mL/4 mL) was stirred at room temperaturefor 15 min, and then PdCl2 (1.8 mg, 0.01 mmol, 0.01 equiv.) wasadded to it. Stirring was continued for an additional 15 h until completeconsumption of starting material as judged by TLC. Then the reactionmixture was poured into water (20 mL) and extracted with ethyl acetate(10 mL * 4). The organic layers were washed with brine, dried overanhydrous Na2SO4, filtered and condensed. The residue was then purifiedvia flash chromatography on silica gel, eluting with EtOAc/petroleumethe to 7s as white solid in 54% yield.60 mmol of tributylvinyltin, 50 mmol of 50mmol tetravinylsilicon, 50mmol60mmol vinyl chlorideZinc, 50mmol

Molecular Weight:218.00
XLogP3:2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Exact Mass:216.93746
Monoisotopic Mass:216.93746
Topological Polar Surface Area:66
Heavy Atom Count:11
Complexity:158
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes