3-Bromo-4-hydroxybenzaldehyde

General procedure: a mixture of substrate 1a(1 mmol), cobalt salt (nOxidation reactions were conducted in a 10-ml two-necked flask equipped with a condenser and a thermometer. A balloon filled with oxygen was connected to the top of the condenser. All reactions were conducted at atmospheric pressure and stirred with an electromagnetic stirrer at a constant rate. In a typical process, a mixture of NaOH (10.9 mmol) and methanol (2.0 ml) was introduced into the flask. The mixture was vigorously stirred at room temperature. When the NaOH had completely dissolved, 2-bromo-p-cresol (3.62 mmol) was added and the mixture was stirred for half an hour to ensure the substrate had been converted into its sodium salt. Cobaltous chloride, NHPI, and salen-Cu(II) complex were then quickly added. Chilled water was circulated through the condenser to minimize loss of the solvent. The mixture was heated to the desired temperature (65 °C), then the oxygen from the balloon was introduced, and controlled by use of a triple valve. After a specific time, the introduction of oxygen was stopped and the reaction mixture was left to cool to room temperature.Example 8: (E)-5-[2-(1H-Indazol-3-yl)vinyl]-2-(2-morpholinoethoxy)benzamide (Compound 8) Step 1 A solution of 4-hydroxybenzaldehyde (10.0 g, 81.9 mmol) in chloroform (100 mL) was added with bromine (4.30 mL, 83.5 mmol), followed by stirring at room temperature for 2 hours. The reaction mixture was added with water (100 mL), and the solvent of the organic layer was evaporated under reduced pressure to obtain 3-bromo-4-hydroxybenzaldehyde as a pale yellow solid (quantitative yield). Example 34: (E)-3-{2-[3-bromo-4-(2-morpholinoethoxy)phenyl]vinyl}-1H-indazole (Compound 34); Step 1; A chloroform (100 mL) solution of 4-hydroxybenzaldehyde (10.0 g, 81.9 mmol) was added with bromine (4.30 mL, 83.5 mmol), follwed by stirring at room temperature for 2 hours. The reaction mixture was added with water (100 mL), and the organic layer was concentrated under reduced pressure to obtain 3-bromo-4-hydroxybenzaldehyde (quantitative yield) as pale yellow solid. (1) In a 4000 mL reaction vessel, Nitrogen protection, first add 1000.0g of chloroform, Another 500 g of 4-hydroxybenzaldehyde was added.The stirring condition is lowered to 0 to 5°C.The temperature was controlled at 10-15°C and 690.5 g of bromine was added dropwise.After the completion of the dropwise addition, the reaction temperature is maintained at 10-15°C.The generated hydrogen bromide gas can recover 20.0percent hydrogen bromide solution through falling film absorption.The raw materials in the control should be completely stopped after the reaction.Add water to quench the reaction, add sodium bicarbonate to adjust the pH to neutral, extract, concentrate, Recrystallization gave intermediate 3-bromo-4-hydroxybenzaldehyde 744.1 g, Yield: 91.0percent;A mixture of 64 4-hydroxybenzaldehyde (100.0g, 0.82mol) and 17 iodine (5.2g, 21mmol) in 18 dichloromethane (500mL) was stirred at−5°C for 15min, then a solution of 65 bromine (138.0g, 0.86mol) in dichloromethane (300mL) was slowly added dropwise to maintain the reactive temperature below 0°C. After the completion of the addition, the mixture was reacted at room temperature for 24h, then diluted with 0.9percent sodium bisulfite (1000mL) and stirred for 30min. The formed precipitate was collected by filtration, washed with water (100mL) and dried to give 19 3-bromo-4-hydroxybenzaldehyde (133.0g, yield 81.1percent) as an off-white solid, which was used directly in the next step. MS (ESI) m/z: 198.9, 200.9 [M−H]A solution of bromine (0.42 ml, 8.18 mmol) in chloroform (10 ml) was added drop-wise to a solution of 4- hydroxybenzaldehyde (1.0 g, 8.18 mmol) in chloroform (25 ml) at 40 General procedure: The general method for ultrasonically assisted brominationreaction is almost similar to conventional reaction as mentionedabove. A centimolar (0.01 mol) organic substrate (phenols, anilines, or acetanilides), 0.001 mol potassium halide(KBr), about 50 mg of dilute KHSO4, and hypervalent Cr(VI) reagent (IQCC or IQDC) were suspended in about30 mL solvent (DCE or ACN) in a previously cleaned roundbottom(R.B) flask placed in a sonicator. The reaction mixtureis sonicated at room temperature about 30–40 min. Progressof the reaction was monitored by TLC technique. Workupprocedure after completion of the reaction mixture is similarto the one described previously.To a stirred solution of 4-hydroxybenzaldehyde *8.0 g, 64.20 mmol) in chloroform (400 mL) at 40° C. was added portionwise a solution of bromine (3.3 mL) in chloroform (10 mL). General procedure: Phenol (1 mmol, 10 mL) dissolved in 1M PEG-600, isoquinolinium dichromate (IQDC) or isoquinolinium chlorochromate (IQCC) reagent, and tetrabutylammonium halide (TBAX) (1.1 mmol each) were taken in a reaction flask and refluxed with constant stirring at about 25 to 30 C, till the completion of reaction, as as certainedby thin layer chromatography. Then the contents of reaction were diluted with ethyl acetate (10 mL) and separated from aqueous layer. Organic layer was then washed two to three time swith 5 mL water and separated. Finally, the resultant mass is dried over sodium sulphate. The anhydrous ethyl acetate layerwas separated under reduced pressure to give crude product, which was further purified by column chromatography (silicagel, 100-200 mesh) using EtOAc-hexane (3:7). For the separation and recyclization of PEG, aqueous mother liquor (reaction mixture of PEG-600 and water) was treated with ether because PEG is insoluble in ether. The aqueous layer obtained after the removal of ether, was then distilled directly at 100 C to remove water and recover PEG-600. The recovered PEG-600 could be reused for consecutive runs.Adapting the procedure reported by S. Kelly et al., Helv. Chim. Acta., 1989, 72, 594. [0550] To a ice-cooled solution of 4-hydroxybenzaldehyde (30.0 g, 245.67 mmol) in glacial AcOH (120 mL) was added bromine (12.6 mL, 257.61 mmol). The mixture was stirred at room temperature overnight, diluted with water (600 mL) and extracted with DCM (3.x.120 mL). The combined organic fractions were washed with water (600 mL), dilute sodium hydrogen carbonate solution (2.x.600 mL) and brine (600 mL). The organic layer was dried (Na2SO4) and concentrated in vacuo to give a brown residue. Recrystallisation from toluene gave OBS01057 as a pink-brown crystalline solid (26.3 g, 53percent). TLC [SiO2, EtOAc-n-hexane (1:1)] Rf=0.6; m.p. 124-126° C. [Lit. (CHCl3): 125-126° C.]; 1H-NMR (400 MHz, CDCl3) 6.31 (1H, s, OH), 7.15 (1H, d, J=8.8), 7.77 (1H, dd, J=8.8, 2), 8.04 (1H, d, J=2), 9.83 (1H, s, CHO).Synthesis of 3-(2'-Benzyloxy-di-tert-butyl-6-hydroxy-3-biphenylyl)acrylic Acid; [0166] (a) Preparation of 3-Bromo-4-hydroxybenzaldehyde:; [0167] 15 g (123 mmol) of 4-hydroxybenzaldehyde, 687 mg (12.3 mmol) of iron powder, 200 ml of dichloromethane and 10 ml of THF were introduced into a 500 ml three-necked flask under nitrogen atmosphere. The mixture was cooled to 0[deg.] C., 19.60 g (123 mmol) of bromine were added dropwise and this mixture was stirred at room temperature for one hour. Saturated sodium thiosulfate solution was added, the dichloromethane was evaporated off, the residue was extracted with ethyl acetate, the organic phase was separated out after settling had taken place, washed with water to neutral pH and dried over magnesium sulfate, and the solvents were evaporated off. The residue obtained was purified by chromatography on a column of silica eluted with an eluting system composed of 80percent heptane and 20percent dichloromethane. After evaporation of the solvents, 9.7 g (39percent) of a white cottony powder having a melting point of 121[deg.]-124[deg.] C. were collected.General procedure: A mixture of alcohol (5.0 mmol), Cu(OAc)General procedure: BiCl

Molecular Weight:201.02
XLogP3:2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:199.94729
Monoisotopic Mass:199.94729
Topological Polar Surface Area:37.3
Heavy Atom Count:10
Complexity:127
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes