2-BROMO-1-(3,4-DIMETHOXYPHENYL)ETHANONE

Off-White Solid

To a stirred solution of 1 -(3, 4-dimethoxyphenyl)ethanone (1 .0 g, 5.55 mmol) in dichloromethane (6 mL) and methanol (3 mL) was added benzyltrimethylammonium tribromide (2.16 g, 5.55 mmol). After16 h, the mixture was diluted with dichloromethane (80 mL) and water (40 mL), the organic layer wasseparated, and the water phase was extracted with dichloromethane (80 mL x 2). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated to give 2-bromo-1 -(3, 4-dimethoxyphenyl)ethanone (1.20 g, 4.63 mmol, 83 percent) as a brown solid. 1H NMR (400 MHz, ODd3) O 7.63 (s, 1 H), 7.57 (d, J2.1 Hz, 1 H), 6.94 (d, J8.4 Hz, 1 H), 4.43 (s, 2H), 3.98 (d, J8.4 Hz, 6H).General procedure: A mixture of substituted arylethanones 14a-i (10 mmol), N-bromosuccinimide (1.4 g, 12 mmol) and p-toluenesulphonic acid (2.8 g, 15 mmol) in acetonitrile (50 mL) was stirred at 85 °C for 4 h. After completion of reaction (indicated by TLC), the reaction mass was allowed to reach ambient temperature and evaporated excess of acetonitrile under reduced pressure. The residue so obtained was mixed in water, extracted with ethyl acetate (2 × 50 mL). The organic layer was dried over anhydrous NaStep 1. 2-Bromo-1-(3, 4-dimethoxy-phenyl)-ethanone. To a 0° C. solution of 3, 4-dimethoxyacetophenone (5.00 g, 27.8 mmol) in diethyl ether (200 mL) and CHClTo a stirred solution of 1-(3, 4-Dimethoxy-phenyl)-ethanone (7) (20 g, 0.111 mol) in chloroform (200 mL) at RT added bromine solution (18.8 g, 0.111 mol) in chloroform 90 mL) over 1 h, reaction maintained at RT for 2 h, after completion of reaction by TLC, the reaction mixture quenched in to saturated sodium bicarbonate solution (300 mL) and extracted with chloroform (2 X 150 mL), organic layers combined and washed with DM water (300 mL) and dried over sodium sulfate and concentrated, co distilled with hexane (2 X 100 mL), charged methanol (50 mL) and stirred for 10 min, filtered solid (8) 20 g (70percent); mp 79-81° C; IR (KBr, Cm-1): 3570, 2779, 1684, 1266; Mass for C10H11BrO3 [M+1] 259.0; 1H NMR (400MHz, DMSO) (δ ppm): 3.84 (3H, s), 3.88 (3H, s), 4.21 (2H, s), 7.07 (1H, d, J = 8.4 Hz), 7.43 (1H, s), 7.71 (1H, dd, J1 = 1.46 Hz, J2 = 1.48 Hz); 13C NMR (100 MHz, DMSO) (δ ppm); 33.87, 55.91, 56.16, 111.1, 111.2, 124.1, 127.0, 149.0, 153.9, 190.5.Compound 2(27.78 mmol, 5.00 g, 1 eq) was dissolved in 90 mL of chloroform / ethyl acetate (1: 1 by volume)In the mixed solution, Copper bromide (55.56 mmol, 12.41 g, 2 eq) was added with stirring at room temperature, Heated to 65 reflux 16 h, TLC monitors the progress of the reaction.After the reaction (the reaction liquid is blue-black, The bottom of a large number of white solid precipitation), Cooling continue stirring 0.5 h, Filter, add appropriate amount of methylene chloride to the residue to continue filtration, The combined filtrates, Dried to 6.21 g of crude product (blue black solid), The crude product was isolated and purified by silica gel column chromatography (200-300 mesh) (ethyl acetate-petroleum 0: 100 →2: 98 → 5: 95 → 10: 80 → 20: 80 → 30: 70)Finally, compound 3 (4.53 g) was obtained, Yellow-brown solid, Yield 63.4percent.Step 12-bromo-1 -(3, 4-dimethoxyphenyl)eth3, 4-dimethoxyacetophenone (1 .00 g, 5.55 mmol) was dissolved in a 1 :1 mixture of ethanol and chloroform (60 ml_). Pyridinium tribromide (4.46 g, 13.9 mmol) was added and the mixture was stirred at 50°C for 16 h. The reaction was cooled to RT and solvents removed in vacuo to give a sticky orange solid, which was then dissolved in H3, 4-Dimethoxyacetophenone (10 g, 55 mmol) in CHCl3 (100 mL) was stirred in a round-bottom flask, while Br2 (10.6 g, 66 mmol) was added drop-wise over 1 h; the mixture was then stirred then for 16 h at r.t. The solvent was then removed in vacuo to give an oil; addition of EtOH (40 mL) and cooling to -15 °C gave a cream-white precipitate that was filtered off, washed with EtOH (2 9 20 mL), and dried in vacuo. Yield = 7.0 g (49 percent). 1H NMR (300 MHz, CDCl3): δPreparation example 64

Molecular Weight:259.10
XLogP3:2.6
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:4
Exact Mass:257.98916
Monoisotopic Mass:257.98916
Topological Polar Surface Area:35.5
Heavy Atom Count:14
Complexity:196
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes