1-(3-Bromo-4-hydroxyphenyl)ethanone

Intermediate 15. l-(3-bromo-4-hydroxyphenyl)ethanone (15)15; [0180] To a solution of 4-hydroxyacetophenone (6.8 g, 0.05 mol, 1 eq) in 60percent acetic acid (50 mL), was added a solution of bromine (2.6 mL, 0.05 mol, 1 eq) in 80percent acetic acid (20 mL). After stirring at room temperature for 30 min, the reaction mixture was poured into 100 mL of cold water. The solid was filtered and the filtrate was further diluted with 500 mL of cold water. The white precipitate was collected by filtration, washed with water and dried under vacuum to afford 4.2 g (39percent) of l-(3- bromo-4-hydroxyphenyl)ethanone (15) as white solid. Intermediate 17: l-(3-bromo-4-hydroxyphenyDethanone (17)17[0162] To a solution of 4-hydroxyacetophenone (6.8 g, 0.05 mol, 1 eq) in 60percent acetic acid (50 niL), was added a solution of bromine (2.6 mL, 0.05 mol, 1 eq) in 80percent acetic acid (20 mL). After stirring at rt for 30 min, the reaction mixture was poured into 100 mL of cold water. The solid was filtered and the filtrate was further diluted with 500 mL of cold water. The white precipitate was collected by filtration, washed with water and dried under vacuum to afford 4.2 g (39 percent) of l-(3-bromo-4- hydroxyphenyl)ethanone (17) as white solid. General procedure: A mixture of substrate 1 (2.0 mmol), Co(OAc)24H2O (40 mg, 0.16 mmol) andNaOH (160 mg, 4.0 mmol) in EG (9.0 ml) was stirred with molecular oxygen(1 atm) being bubbled, under 100 C for specified time. After completion ofreaction, diluted hydrochloric acid (15 ml, 2 percent) and chloroform (15 ml) weresuccessively added to the reaction mixture. The organic layer was separated, and theaqueous phase was extracted with chloroform (15 ml 9 2). The combined organicphase was dried over anhydrous sodium sulfate and concentrated to give a residue, which was purified by column chromatography on silica gel (eluents: petroleumether:ethyl acetate = 10:1) providing the desired products 2.2-Bromophenol (1.16 mL, 10.0 mmol) was dissolved in carbon disulfide (10 mL) that had been cooled in an ice-salt bath under stirring. Anhydrous aluminum chloride (2.7 g, 20.0 mmol) was added in portions and then acetyl chloride (0.754 mL, 11.0 mmol) was added to the mixture. The mixture was stirred for one hour, refluxed overnight and then a mixture of 1 M hydrochloric acid and ice was added. The mixture was extracted with DCM (x3) and the combined extracts were dried and concentrated. Chromatographed of the residue over 30 g of silica gel (20percent ethyl acetate/hexane, 40percent ethyl ACETATE/HEXANE) gave 3-bromo-4- hydroxyacetophenone (2.28 g, 53percent).1-methyl-3-cyanoquinoline salt as a photosensitizer, Cobalt oxime complex 2 as a cobalt catalyst, 5mL acetonitrile was added2.69 mg (1 × 10 -2 mmol) photosensitizer and 2.80 mg (6 × 10 -3 mmol) cobalt catalyst, Replacing the atmosphere with Ar atmosphereAnd then0.2 mmol of 3'-bromoacetophenone (R1 is COCH3, R3 is Br, R2, R4 are independently H) and 2 mmol of H2O. Room temperature, high pressureMercury lamp irradiation 5h. After the reaction was completed, the H2 production was detected by GC (TCD) and the conversion of benzene by GC (FID), And then separated by column. 1H NMR and MS identified products were 3'-bromo-2-hydroxyacetophenone, 3'-bromo-4-hydroxyacetophenone and 3'-bromo-6-hydroxyacetophenone. The conversion of 3'-bromoacetophenone was 32percent, the yield of coupling products was 2percent, 15percent and 15percent, respectively, and the yield of H2 was 8percent.40.05 g (0.24 mol) of potassium bromate and 100 ml of water were placed in a 500 ml four-necked flask, and a mixed solution of 27.24 g(0.2 mol) of p-hydroxyacetophenone and 80 g of methanol was placed in a 500 ml four-necked flask and stirred under stirring. 312 g of a 20% by weight sodium hydrogen sulfite solution was added. The dropping temperature was controlled not to exceed 70 C, the dropping time was about 3 hours, and the reaction was kept for 2 hours after the dropwise addition. It was cooled to room temperature, filtered off with suction, washed with water, and recrystallized from methanol to give 36.3 g beige solid, yield 84.5%, melting point (m.p.) = 82 ~ 85C.Intermediate 15. l-(3-bromo-4-hydroxyphenyl)ethanone (15)15; [0180] To a solution of 4-hydroxyacetophenone (6.8 g, 0.05 mol, 1 eq) in 60% acetic acid (50 mL), was added a solution of bromine (2.6 mL, 0.05 mol, 1 eq) in 80% acetic acid (20 mL). After stirring at room temperature for 30 min, the reaction mixture was poured into 100 mL of cold water. The solid was filtered and the filtrate was further diluted with 500 mL of cold water. The white precipitate was collected by filtration, washed with water and dried under vacuum to afford 4.2 g (39%) of l-(3- bromo-4-hydroxyphenyl)ethanone (15) as white solid. 1HNMR (CDCl3, 400MHz): delta 8.15 (s, 1H), 7.86 (d, 1H), 7.18 (d, 1H), 5.96 (s, 1H), 2.56 (s, 3H). MS (ES-API): M+l = 216.9. HPLC (Method B) tR = 2.48 min.Intermediate 17: l-(3-bromo-4-hydroxyphenyDethanone (17)17[0162] To a solution of 4-hydroxyacetophenone (6.8 g, 0.05 mol, 1 eq) in 60% acetic acid (50 niL), was added a solution of bromine (2.6 mL, 0.05 mol, 1 eq) in 80% acetic acid (20 mL). After stirring at rt for 30 min, the reaction mixture was poured into 100 mL of cold water. The solid was filtered and the filtrate was further diluted with 500 mL of cold water. The white precipitate was collected by filtration, washed with water and dried under vacuum to afford 4.2 g (39 %) of l-(3-bromo-4- hydroxyphenyl)ethanone (17) as white solid. 1HNMR (CDCl3, 400MHz): delta 8.15 (s, IH), 7.86 (d, IH), 7.18 (d, IH), 5.96 (s, IH), 2.56 (s, 3H). MS (ES-API): M+l = 216.9. HPLC (Method B) tR = 2.48 min.1-(3-Bromo-4-hydroxy-phenyl)-ethanone A solution of 4-hydroxyacetophenone (13.6 g, 0.1 mol) in 65% acetic acid (100 mL) was treated with bromine (5.1 mL, 0.1 mol) dissolved in 80% acetic acid (50 mL) at room temperature. After addition of bromine the solution was further stirred at room temperature for 30 min and poured into 200 mL of cold water. The side product formed was filtered off and the filtrate was further diluted with 1 L of cold water. The white precipitate formed was filtered, washed several times with water and dried under vacuum. Yield: (10.4 g, 35%). 1H NMR(CDCl3) delta2.57 (s, 3H), 6.46 (s, 1H), 7.08 (d, 1H), 7.85 (d, 1H), 8.21 (s, 1H). MS 216 (M+H), C8H7O2BrStep 3 To the above product (84.1 g, 0.367 mol) were added acetic acid (700 ml) and then hydrobromic acid (300 g), followed by refluxing the mixture for 50 hours, thereafter adding water (1 l) and collecting deposited crystals to obtain 3-bromo-4-hydroxyacetophenone (74.6 g) (m.p.: 111.2~113.0 C.).General procedure: Reference production example 20. (0834) 18 g of aluminum trichloride was added to a mixture of 8.9 g of the above 2-methylphenyl propionate described in Reference production example 19 and 100 mL of nitromethane at 0C and the mixture was heated to 50C. After the mixture was stirred for 12 hr, the reaction mixture was poured into 50 ml of ice water and then extracted with chloroform. The organic phase was washed with water, dried by magnesium sulfate anhydride, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to obtain 7.6 g of 1-(4-hydroxy-3-methyl-phenyl)propan-1-one. 1-(4-hydroxy-3-methyl-phenyl)propan-1-one 1H-NMR (CDCl3) delta: 7.81-7.79 (1H, m), 7.75 (1H, dd, J = 8.47, 2.18 Hz), 6.84 (1H, d, J = 8.47 Hz), 6.24 (1H, br s), 2.96 (2H, q, J = 7.33 Hz), 2.29 (3H, s), 1.21 (3H, t, J = 7.33 Hz).1-methyl-3-cyanoquinoline salt as a photosensitizer, Cobalt oxime complex 2 as a cobalt catalyst, 5mL acetonitrile was added2.69 mg (1 × 10 -2 mmol) photosensitizer and 2.80 mg (6 × 10 -3 mmol) cobalt catalyst, Replacing the atmosphere with Ar atmosphereAnd then0.2 mmol of 3'-bromoacetophenone (R1 is COCH3, R3 is Br, R2, R4 are independently H) and 2 mmol of H2O. Room temperature, high pressureMercury lamp irradiation 5h. After the reaction was completed, the H2 production was detected by GC (TCD) and the conversion of benzene by GC (FID), And then separated by column. 1H NMR and MS identified products were 3'-bromo-2-hydroxyacetophenone, 3'-bromo-4-hydroxyacetophenone and 3'-bromo-6-hydroxyacetophenone. The conversion of 3'-bromoacetophenone was 32%, the yield of coupling products was 2%, 15% and 15%, respectively, and the yield of H2 was 8%.

Molecular Weight:215.04
XLogP3:2.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:213.96294
Monoisotopic Mass:213.96294
Topological Polar Surface Area:37.3
Heavy Atom Count:11
Complexity:158
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes