1-(3-chloro-2-hydroxyphenyl)propan-1-one

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3′-Chloro-2′-hydroxypropiophenone (10 g, 54.3 mmol) and potassium carbonate (17.5 g) in 70 ml of acetone are admixed with 7 ml of dimethyl sulphate. The reaction mixture is boiled at reflux for three hours. After it has cooled to room temperature, the batch is subjected to suction filtration through Celite and the filter cake is washed with diethyl ether. After the solvent has been removed on a rotary evaporator, the yellow oil which remains is diluted with 200 ml of diethyl ether and the organic phase is washed with 0.2 M aqueous sodium hydroxide solution (100 ml) and brine (100 ml). The organic phase is dried over sodium sulphate and the solvent is removed on a rotary evaporator. This leaves the desired title compound as a colourless oil (98% yield). at reflux for three hours the batch is subjected to suction filtration through Celite the filter cake is washed with diethyl ether After the solvent has been removed on a rotary evaporator the yellow oil which remains is diluted with 200 ml of diethyl ether the organic phase is washed with 0.2 M aqueous sodium hydroxide solution (100 ml) and brine (100 ml) The organic phase is dried over sodium sulphate the solvent is removed on a rotary evaporator

Conditions: temp:115.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Anhydrous aluminum trichloride (130 g, 0.974 mol) in 150 ml of dry o-dichlorobenzene is cooled to 10° C. and 2-chlorophenyl propionate (100 g, 0.543 mol) is added slowly dropwise to this reaction mixture (15 minutes). The flask with the mixture is heated slowly in an oil bath to 110-120° C. At this temperature, HCl begins to evolve. The temperature is then raised slowly to 130-140° C. and the reaction mixture is held within this temperature range for three hours. After the oil bath has been removed and the batch has cooled, the excess aluminum chloride is broken down by addition of 350 g of crushed ice, followed by the addition of 50 ml of concentrated hydrochloric acid. After the reaction mixture has cooled, ethyl acetate (500 ml) is added. The organic phase is separated off and washed with saturated sodium hydrogen carbonate solution (500 ml) and brine (500 ml). After the organic phase has been dried and the solvent has been removed on a rotary evaporator, the residue is purified by chromatography on silica gel (eluent: toluene). This isolates 10 g (10%) of the desired compound and also 40 g (40%) of the corresponding regioisomer, 5′-chloro-3′-hydroxy propiophenone. The temperature is then raised slowly to 130-140° C. After the oil bath has been removed the batch has cooled the excess aluminum chloride is broken down by addition of 350 g of crushed ice followed by the addition of 50 ml of concentrated hydrochloric acid After the reaction mixture has cooled ethyl acetate (500 ml) is added The organic phase is separated off washed with saturated sodium hydrogen carbonate solution (500 ml) and brine (500 ml) After the organic phase has been dried the solvent has been removed on a rotary evaporator the residue is purified by chromatography on silica gel (eluent: toluene)