Preparation
Preparation by diazotization of 5-amino-3-bromo-2- hydroxyacetophenone, followed by hydrolysis of the obtained diazonium salt (49%).
Synthesis
GENERAL STEPS: A solution of commercially available 2-bromophenol (10.0 g, 57.8 mmol) in anhydrous dichloromethane (50 mL) was added to a round-bottomed flask, followed by dropwise addition of acetyl chloride (5.0 g, 63.6 mmol) and triethylamine (4.67 mL, 63.6 mmol). The reaction mixture was stirred at room temperature for 1 h. The solvent was removed by distillation under reduced pressure to give pure 2'-bromophenyl acetate (12.18 g, 56.6 mmol, 98% yield). The resulting ester was dissolved in 1,2-dichlorobenzene (100 mL) and aluminum trichloride (11.3 g, 84.9 mmol) was added. The reaction mixture was heated to 140 °C and stirred for 3 hours. Upon completion of the reaction, it was adjusted to slightly acidic (pH) by adding ice and 10% hydrochloric acid. The organic phase was separated and the aqueous phase was extracted with dichloromethane (3 x 50 mL). The organic phases were combined, dried with magnesium sulfate and filtered. Dichloromethane was removed by evaporation under reduced pressure. The crude product was treated with hexane (300 mL) and cooled at -20 °C to crystallize most of the para-substituted by-products, which were removed by filtration. The filtrate was filtered through a silica gel column and washed with hexane to remove 1,2-dichlorobenzene, followed by replacement of the eluent with dichloromethane-triethylamine (20:1). After separation by column chromatography, the eluate was evaporated under reduced pressure to afford the pure product 1-(3-bromo-2-hydroxyphenyl)ethanone (8) as a colorless oil (7.55 g, 35.1 mmol, 62% yield). The product was analyzed by IR, 1H NMR, 13C NMR and mass spectrometry to confirm the structure.
References
[1] Synthesis (Germany), 2016, vol. 48, # 1, p. 97 - 102
[2] Monatshefte fuer Chemie, 1965, vol. 96, p. 450 - 460
[3] Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 7, p. 909 - 913
[4] Organic Letters, 2016, vol. 18, # 15, p. 3766 - 3769
