2'-Chloro-4',5'-difluoroacetophenone

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

Procedure: To 19.1 g (0.1 mol) of 2-chloro-4,5-difluoroacetophenone, 280.4 g (0.4 mol) of a 12% sodium hypochlorite aqueous solution was added, and the mixture was reacted under reflux for 4 hours. After cooling, concentrated hydrochloric acid was dropwise added thereto until the pH became 1. The formed white crystals were dissolved in methylene chloride and separated from the aqueous phase. The separated aqueous phase was extracted twice with methylene chloride, and the extracts were added to the oil phase. Then, the solvent was distilled off to obtain 16.4 g (yield: 85.1%) of 2-chloro-4,5-difluorobenzoic acid as white crystal. the mixture was reacted under reflux for 4 hours After cooling separated from the aqueous phase The separated aqueous phase was extracted twice with methylene chloride the extracts were added to the oil phase Then, the solvent was distilled off

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

Procedure: To 19.1 g (0.1 mol) of 2-chloro-4,5-difluoroacetophenone, 280.4 g (0.4 mol) of a 12% sodium hypochlorite aqueous solution was added, and the mixture was reacted under reflux for 4 hours. After cooling, concentrated hydrochloric acid was dropwise added thereto until the pH became 1. The formed white crystals were dissolved in methylene chloride and separated from the aqueous phase. The separated aqueous phase was extracted twice with methylene chloride, and the extracts were added to the oil phase. Then, the solvent was distilled off to obtain 16.4 g (yield: 85.1%) of 2-chloro-4,5-difluorobenzoic acid as white crystal. the mixture was reacted under reflux for 4 hours After cooling separated from the aqueous phase The separated aqueous phase was extracted twice with methylene chloride the extracts were added to the oil phase Then, the solvent was distilled off

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

Procedure: To 19.1 g (0.1 mol) of 2-chloro-4,5-difluoroacetophenone, 280.4 g (0.4 mol) of a 12% sodium hypochlorite aqueous solution was added, and the mixture was reacted under reflux for 4 hours. After cooling, concentrated hydrochloric acid was dropwise added thereto until the pH became 1. The formed white crystals were dissolved in methylene chloride and separated from the aqueous phase. The separated aqueous phase was extracted twice with methylene chloride, and the extracts were added to the oil phase. Then, the solvent was distilled off to obtain 16.4 g (yield: 85.1%) of 2-chloro-4,5-difluorobenzoic acid as white crystal. the mixture was reacted under reflux for 4 hours After cooling separated from the aqueous phase The separated aqueous phase was extracted twice with methylene chloride the extracts were added to the oil phase Then, the solvent was distilled off

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 23.6 g (0.3 mol) of acetyl chloride was added to a mixture comprising 29.7 g (0.2 mol) of 1-chloro-3,4-difluorobenzene and 40.0 g (0.3 mol) of aluminum chloride at a temperature of from 20° to 40° C. Then, the mixture was stirred at 120° C. for two hours. While still being hot, the mixture was poured on 250 g of ice, and the separated oil was extracted with ethylene chloride. The extract was neutralized and washed with water, and the solvent was distilled off under reduced pressure to obtain 31.2 g (yield: 82%) of 2-chloro-4,5-difluoroacetophenone. This compound was analyzed, and the analytical values were as follows. the separated oil was extracted with ethylene chloride washed with water the solvent was distilled off under reduced pressure

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

Procedure: According to the process disclosed in EP-A2-303,291, 2-chloro-4,5-difluorobenzoic acid is prepared by acylating 1-chloro-3,4-difluorobenzene to give 2-chloro-4,5-difluoroacetophenone with a yield of 82% of theory and then oxidizing with sodium hypochlorite to 2-chloro-4,5-difluorobenzoic acid in a yield of 85.1% of theory. The total yield of this process thus only amounts to about 70% of theory, relative to the 1-chloro-3,4-difluorobenzene as the starting material. It is further a disadvantage of this process that, according to the illustrative example, the acylation must be carried out at a temperature of 120° C. is prepared

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

Procedure: To 19.1 g (0.1 mol) of 2-chloro-4,5-difluoroacetophenone, 280.4 g (0.4 mol) of a 12% sodium hypochlorite aqueous solution was added, and the mixture was reacted under reflux for 4 hours. After cooling, concentrated hydrochloric acid was dropwise added thereto until the pH became 1. The formed white crystals were dissolved in methylene chloride and separated from the aqueous phase. The separated aqueous phase was extracted twice with methylene chloride, and the extracts were added to the oil phase. Then, the solvent was distilled off to obtain 16.4 g (yield: 85.1%) of 2-chloro-4,5-difluorobenzoic acid as white crystal. the mixture was reacted under reflux for 4 hours After cooling separated from the aqueous phase The separated aqueous phase was extracted twice with methylene chloride the extracts were added to the oil phase Then, the solvent was distilled off

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 23.6 g (0.3 mol) of acetyl chloride was added to a mixture comprising 29.7 g (0.2 mol) of 1-chloro-3,4-difluorobenzene and 40.0 g (0.3 mol) of aluminum chloride at a temperature of from 20° to 40° C. Then, the mixture was stirred at 120° C. for two hours. While still being hot, the mixture was poured on 250 g of ice, and the separated oil was extracted with ethylene chloride. The extract was neutralized and washed with water, and the solvent was distilled off under reduced pressure to obtain 31.2 g (yield: 82%) of 2-chloro-4,5-difluoroacetophenone. This compound was analyzed, and the analytical values were as follows. Boiling point: 65°-67° C./4-5 mmHg. the separated oil was extracted with ethylene chloride washed with water the solvent was distilled off under reduced pressure

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 23.6 g (0.3 mol) of acetyl chloride was added to a mixture comprising 29.7 g (0.2 mol) of 1-chloro-3,4-difluorobenzene and 40.0 g (0.3 mol) of aluminum chloride at a temperature of from 20° to 40° C. Then, the mixture was stirred at 120° C. for two hours. While still being hot, the mixture was poured on 250 g of ice, and the separated oil was extracted with ethylene chloride. The extract was neutralized and washed with water, and the solvent was distilled off under reduced pressure to obtain 31.2 g (yield: 82%) of 2-chloro-4,5-difluoroacetophenone. This compound was analyzed, and the analytical values were as follows. Boiling point: 65°-67° C./4-5 mmHg. the separated oil was extracted with ethylene chloride washed with water the solvent was distilled off under reduced pressure

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 23.6 g (0.3 mol) of acetyl chloride was added to a mixture comprising 29.7 g (0.2 mol) of 1-chloro-3,4-difluorobenzene and 40.0 g (0.3 mol) of aluminum chloride at a temperature of from 20° to 40° C. Then, the mixture was stirred at 120° C. for two hours. While still being hot, the mixture was poured on 250 g of ice, and the separated oil was extracted with ethylene chloride. The extract was neutralized and washed with water, and the solvent was distilled off under reduced pressure to obtain 31.2 g (yield: 82%) of 2-chloro-4,5-difluoroacetophenone. This compound was analyzed, and the analytical values were as follows. Boiling point: 65°-67° C./4-5 mmHg. the separated oil was extracted with ethylene chloride washed with water the solvent was distilled off under reduced pressure

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

Procedure: To 19.1 g (0.1 mol) of 2-chloro-4,5-difluoroacetophenone, 280.4 g (0.4 mol) of a 12% sodium hypochlorite aqueous solution was added, and the mixture was reacted under reflux for 4 hours. After cooling, concentrated hydrochloric acid was dropwise added thereto until the pH became 1. The formed white crystals were dissolved in methylene chloride and separated from the aqueous phase. The separated aqueous phase was extracted twice with methylene chloride, and the extracts were added to the oil phase. Then, the solvent was distilled off to obtain 16.4 g (yield: 85.1%) of 2-chloro-4,5-difluorobenzoic acid as white crystal. the mixture was reacted under reflux for 4 hours After cooling separated from the aqueous phase The separated aqueous phase was extracted twice with methylene chloride the extracts were added to the oil phase Then, the solvent was distilled off

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

Procedure: To 19.1 g (0.1 mol) of 2-chloro-4,5-difluoroacetophenone, 280.4 g (0.4 mol) of a 12% sodium hypochlorite aqueous solution was added, and the mixture was reacted under reflux for 4 hours. After cooling, concentrated hydrochloric acid was dropwise added thereto until the pH became 1. The formed white crystals were dissolved in methylene chloride and separated from the aqueous phase. The separated aqueous phase was extracted twice with methylene chloride, and the extracts were added to the oil phase. Then, the solvent was distilled off to obtain 16.4 g (yield: 85.1%) of 2-chloro-4,5-difluorobenzoic acid as white crystal. the mixture was reacted under reflux for 4 hours After cooling separated from the aqueous phase The separated aqueous phase was extracted twice with methylene chloride the extracts were added to the oil phase Then, the solvent was distilled off

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 23.6 g (0.3 mol) of acetyl chloride was added to a mixture comprising 29.7 g (0.2 mol) of 1-chloro-3,4-difluorobenzene and 40.0 g (0.3 mol) of aluminum chloride at a temperature of from 20° to 40° C. Then, the mixture was stirred at 120° C. for two hours. While still being hot, the mixture was poured on 250 g of ice, and the separated oil was extracted with ethylene chloride. The extract was neutralized and washed with water, and the solvent was distilled off under reduced pressure to obtain 31.2 g (yield: 82%) of 2-chloro-4,5-difluoroacetophenone. This compound was analyzed, and the analytical values were as follows. the separated oil was extracted with ethylene chloride washed with water the solvent was distilled off under reduced pressure