Preparation of 3′-bromo-4′-methylacetophenone_Kain Industrial Additive

Background and overview^[1]

3′-Bromo-4′-methylacetophenone is a bromide of acetophenone derivatives. This type of compound is a very important chemical intermediate in medicines, pesticides, dyes, and spices. It has a wide range of applications in other industries, and it can further prepare various target compounds through Suzuki coupling reaction.

Preparation^[1-2]

Report 1,

Put 40.05g (0.24mol) potassium bromate and 100ml water into a 500ml four-neck bottle, and then put the mixed solution of 26.84g (0.2mol) p-methylacetophenone and 90g methanol into the 500ml four-neck bottle. 312g of sodium bisulfite solution with a mass percentage concentration of 20% was added dropwise under stirring conditions. Control the dripping temperature to not exceed 55°C, the dripping time is about 3 hours, and the insulation reaction is 2 hours after the dripping is completed. Cool to room temperature, filter with suction, wash with water, and recrystallize with petroleum ether to obtain 34.95g of light brown solid 3′-bromo-4′-methylacetophenone, yield 82%, melting point (m.p.) = 42~46°C.

Report 2,

Add a solution of 97g (723mol) 4-methylacetophenone in 100ml methylene chloride to 237g (1.78mol) AlCl₃In a suspension in 700 ml of methylene chloride. The reaction mixture was then stirred at this temperature for 10 min, and then 40.0 ml (125 g, 0.781 mol, 8% excess) of bromine was added dropwise over 1 h. The resulting mixture was stirred at room temperature overnight and then poured onto 2000 cm³ of ice. The organic layer was separated, and the aqueous layer was extracted with 3x150ml methylene chloride. The combined organic extracts were washed with aqueous K₂CO₃, dried with K₂CO₃, and passed through Short pads of silica gel 60 (40-63μm) are then evaporated to dryness. The crude product was distilled under vacuum to yield 143 g (93%) of a colorless liquid (boiling point 125-132°C/8 mm Hg), which solidified completely on standing at room temperature. Anal. Calculated for C9H9BrO: C, 50.73; H, 4.26. Found: C, 50.89; H, 4.12. ¹H NMR (CDCl₃): δ8.09(s,1H,2-H),7.77(d,J＝7.8Hz,1H,6-H) ,7.31(d,J=7.8Hz, 1H,5-H),2.56(s,3H,COMe),2.44(s,3H,4-Me).