2-Bromo-5-methoxybenzaldehyde

White powder

A/e/ -anisaldehyde (6.06 g, 44.6 mmol, 1.0 equiv) was dissolved in AcOH (10 mL), BrAfter the N- bromosuccinimide (749 g) dissolved in dimethylformamide (2 L), it was added dropwise a m- anisaldehyde (m-anisaldehyde) 334.2 g.The reaction mixture was stirred for 3 hours and then poured into ice water (2 L) was produced a yellow solid.The reaction mixture was filtered and the resulting solid was dissolved in ethyl acetate.The resulting solution was washed in turn with water and aqueous NaCl solution and, MgSOThe compound was made according to a literature method (Tetrahedron 1999, 10120). The following optional recrystallization was developed. To a 1 L round-bottom flask equipped with overhead stirring, reflux condenser and thermocouple was charged 2-bromo-5- methoxybenzaldehyde (50.0 g) and 250 mL 2-propanol. The slurry was warmed to 45°C to give a clear, faint yellow solution. Water (250 mL) was then added via addition funnel over the course of 10 minutes while maintaining the internaltemperature above 42 °C. Note : A slurry forms upon addition of the first approximately 1/3 of the water charge. Once the addition was complete, heating was turned off and the slurry was cooled to ambient temperature (21 °C) over 1.5 h. After 2 h the slurry was filtered and the cake was subsequently washed with 2: 1 water:2- propanol (65 mL). After air drying for 0.5 h, the solid (57 g) was dried in a vacuum oven (35 °C, 4 mbar) for 16 h. 2-Bromo-5-methoxybenzaldehyde (46.77 g, 93.5 percent yield) was obtained as a white solid.Step 1 Stage A To a solution of m-anisaldehyde (55.4 g, 0.41 mol) in DMF (400 mL) was added a solution of N-bromosuccinimide (124.0 g, 0.69 mol) dropwise at room temperature. After the addition, the reaction solution was stirred at room temperature for 12 h, then poured into a mixture of ice and water and stirred for 10 min. The precipitate was collected by filtration and dissolved in ethyl acetate. The resulting To a solution of m-anisaldehyde (55.4 g, 0.41 mol) in DMF (400 mL) was added a solution of N-bromosuccinimide (124.0 g, 0.69 mol) dropwise at room temperature. After the addition, the reaction solution was stirred at room temperature for 12 h, then poured into a mixture of ice and water and stirred for 10 min. The precipitate was collected by filtration and dissolved in ethyl acetate. The resulting solution was washed with water (2×) and brine, dried over sodium sulfate and concentrated in vacuo to give compound 19 (76.4 g, 87percent) as an off-white solid: Bromine (2.75 mL, 8.58 g, 53.6 mmol) was added dropwise to a stirred solution of m-anisaldehyde(6.06 g, 44.6 mmol) in AcOH (10 mL) in 3 minutes to bring the solution to gentle reflux. After 24 hours the reaction mixture was poured into water (130 mL). The precipitate was filtered, washed with water and dissolved in EtOAc (60 mL). This solution was washed with water (50 mL), brine (50 mL), dried over Na2SO4 and concentrated on a rotary evaporator. The yellow residue was recrystallized from hexane to give bromobenzaldehyde SI-1c (8.05 g, 37.4 mmol, 84percent) as beige solid.To the solution of meta-anisaldehyde (3.03 g, 22.3 mmol) in AcOH (5.0 mL), Br2 (1.4 mL, 26.8 mmol, 1.2 eq.) was drop wisely added, andthe reaction mixture was stirred for 36 h at room temperature. Upon completion, the reactionwas quenched with a saturated solution of Na2SO3 (25 mL), then poured into water (10 mL), and extracted with EtOAc (3×25 mL). The combined organic layers were washed with water(3×20 mL) and brine (15 mL), dried (Na2SO4), and concentrated to give the desired 2-bromo--5-methoxybenzaldehyde (21, 3.99 g, 83 percent).(Z)-2-(2-Iodethenyl)-4-methoxybrombenzol (III):; 1. 2-Brom-5-methoxybenzaldehyde: Bromine (5.72 mL, l l l mmol) was added at room temperature to a solution of 3-methoxybenzaldehyde (11.8 mL, 97.0 mmol). After stirring for 48 h, the mixture was poured into water (650 mL) and the precipitated product was filtered of and extensively washed with water. After drying in vacuo aldehyde (16.7 g, 80 percent) was obtained as white solid. IH NMR (200 MHz, CDC13): δ = 3.85 (s, 3 H, 5- OCH3), 7.04 (dd, J = 8.8 Hz, 3.2 Hz, 1 H, 4-H), 7.42 (d, J = 3.2 Hz, 1 H, 6-H), 7.53 (d, J = 8.8 Hz, I H, 3-H), 10.32 (s, I H, 1-CHO); MS (7O eV, EI): m/z (percent):214.1/216.1 (100/87) [M+].Prepared according to the literature [1], starting with 3-methoxybenzaldehyde (61 mL, 0.5 mol) and bromine (26 mL, 0.5 mol) in CHScheme ClO; Br4.4.1 General procedure: In an oven dried Schlenk tube, were added alcohol 1 (69.0–199.5 mg, 0.5 mmol), CuI (10 molpercent)and 1, 10-Phenanthroline (20 molpercent) and K3PO4 (2 mmol) followed by the addition of dioxane (2mL) at room temperature under a nitrogen atmosphere. The stirred reaction mixture was heatedin an oil bath at 80 C for 24–48 h. Progress of the reaction was monitored by TLC till thereaction is completed. Then, the reaction mixture was cooled to room temperature, quenchedwith aqueous NH4Cl solution and then extracted with CH2Cl2 (3 10 mL). The organic layerwas washed with saturated NaCl solution, dried (Na2SO4), and filtered. Evaporation of thesolvent under reduced pressure and purification of the crude material by silica gel columnchromatography (petroleum ether/ethyl acetate) furnished the aldehyde/ketone 2 (58–92percent).General procedure: The benzyl alcohols substrates (1a–1p) (0.2mmol), FeClTo a solution of 2-bromo-5-hydroxybenzaldehyde (1000.0 mg, 4.975 mmol) in DMF (20 mL) were added methyl iodide (0.31 mL, 5.000 mmol) and potassium carbonate (1036.6 mg, 7.500 mmol). The reaction mixture was stirred at rt for 2.5 days. Water was added and the reaction mixture was extracted with hexanes-ether (1:1) solvent system. The combined organic phases were dried over NaGeneral procedure: A mixture of arene (0.5 mmol), I

Molecular Weight:215.04
XLogP3:2
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:213.96294
Monoisotopic Mass:213.96294
Topological Polar Surface Area:26.3
Heavy Atom Count:11
Complexity:138
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes