4-broMo-3,5-difluorobenzonitrile

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

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

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

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: 24 g of sodium nitrite was added to 180 ml of concentrated sulfuric acid cooled to a temperature of at least 10° C. 38 ml of acetic acid was added to the mixture. 53 g of 4-cyano-2,6difluoroaniline was added gradually to keep the temperature of the solution between about 20°and 25° C. The mixture was stirred at 20°-25° C. for one hour. A solution was prepared by dissolving 60 g of copper (I) bromide in 180 ml of an aqueous 48% solution of hydrobromic acid. The mixture was added drop-wise to the solution and the solution was stirred at room temperature for 15 hours. Water was added to the solution, and the solution was extracted with chloroform and washed with water. The chloroform in the aqueous layer was distilled off and the residue was recrystallized from a solution mixture of methanol and acetone, to yield 25 g of 2-bromo-5-cyano-1,3-difluorobenzene. cooled to a temperature of at least 10° C between about 20°and 25° C A solution was prepared The mixture was added drop-wise to the solution the solution was stirred at room temperature for 15 hours the solution was extracted with chloroform washed with water The chloroform in the aqueous layer was distilled off the residue was recrystallized from a solution mixture of methanol and acetone

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

Procedure: 24 g of sodium nitrite was added to 180 ml of concentrated sulfuric acid cooled to a temperature of at least 10° C. 38 ml of acetic acid was added to the mixture. 53 g of 4-cyano-2,6difluoroaniline was added gradually to keep the temperature of the solution between about 20°and 25° C. The mixture was stirred at 20°-25° C. for one hour. A solution was prepared by dissolving 60 g of copper (I) bromide in 180 ml of an aqueous 48% solution of hydrobromic acid. The mixture was added drop-wise to the solution and the solution was stirred at room temperature for 15 hours. Water was added to the solution, and the solution was extracted with chloroform and washed with water. The chloroform in the aqueous layer was distilled off and the residue was recrystallized from a solution mixture of methanol and acetone, to yield 25 g of 2-bromo-5-cyano-1,3-difluorobenzene. cooled to a temperature of at least 10° C between about 20°and 25° C A solution was prepared The mixture was added drop-wise to the solution the solution was stirred at room temperature for 15 hours the solution was extracted with chloroform washed with water The chloroform in the aqueous layer was distilled off the residue was recrystallized from a solution mixture of methanol and acetone

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: 167 g (0.88 mol) of SnCl2 was added to 880 cm3 of diethyl ether, and dried HCl gas was absorbed to saturation at room temperature. 98 g (0.44 mol) of 4-bromo-3,5-difluorobenzonitrile was added all at once to this mixture, and after stirring for i hour, it was let stand overnight. The reactant was poured into 1,000 cm3 of water, and ether was distilled on a hot water bath at 50° C. The residue was extracted by adding chloroform, and after washing in water the chloroform was removed. The residue was distilled under reduced pressure (b. p. 96° C./73 mmHg) to obtain 88 g (0.40 mol) of 4-bromo-3,5-difluorobenzaldehyde. was absorbed to saturation at room temperature was distilled on a hot water bath at 50° C The residue was extracted by adding chloroform after washing in water the chloroform was removed The residue was distilled under reduced pressure (b. p. 96° C./73 mmHg)

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: While stirring 420 cm3 of concentrated H2SO4 on an ice water bath, 54 g (0.78 mol) of pulverized NaNO2 was added at a rate that maintained a temperature under 40° C., and after the addition it was stirred in a hot water bath at 50° C. until the crystals dissolved completely. While stirring this solution on an ice water bath, 700 cm3 of glacial acetic acid was added dropwise, then 108 g (0.7 mol) of 4-amino-3,5-difluorobenzonitrile was added at a rate maintaining the temperature at 20°-25° C., and after the addition was completed it was stirred at this temperature until the crystals were completely dissolved to prepare a diazonium salt solution. A solution with 143 g (1.0 mol) of CuBr dissolved in 420 cm3 of 47% HBr was stirred in an ice water bath while the previously prepared diazonium salt solution was added dropwise for 2 hours, and after the dropping was completed, it was stirred on an ice water bath for 1 hour and at room temperature overnight. The crystals formed were filtered, and after washing the crystals in glacial acetic acid, they were recrystallized from a mixture of acetone and methanol to obtain 98 g (0.44 mol) of 4-bromo-3,5-difluorobenzonitrile. after the addition it dissolved completely While stirring this solution on an ice water bath maintaining the temperature at 20°-25° C. after the addition was stirred at this temperature until the crystals were completely dissolved was added dropwise for 2 hours it was stirred on an ice water bath for 1 hour and at room temperature overnight The crystals formed were filtered after washing the crystals in glacial acetic acid they were recrystallized from a mixture of acetone and methanol

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

Procedure: 4 g of sodium nitride was added to 30 ml of concentrated sulfuric acid and chilled to a temperature of 10° C. and 38 ml of acetic acid was added thereto. 8.9 ml of 4-cyano-2,6-difluoroaniline was added gradually to maintain the solution at a temperature of 20° to 25° C. The reaction mixture was added dropwise to a solution a 10 g of copper (I) bromide dissolved in 30 ml of concentrated hydrobromic acid. After the dropwise addition was completed, the reaction mixture was stirred for one and one half hours at room temperature. Water was added to the reaction mixture, the reaction mixture was extracted with chloroform and washed with water. The organic layer was removed by distillation, and the residue was recrystallized with a mixture of methanol and acetone to yield 6.6 g of 2-bromo-5-cyano-1,3-difluorobenzene. was added to maintain the solution at a temperature of 20° to 25° C After the dropwise addition the reaction mixture was extracted with chloroform washed with water The organic layer was removed by distillation the residue was recrystallized with a mixture of methanol and acetone