Acetic Acid → 4-Bromo-3,5-difluorobenzonitrile

HRID 1086396Notes

Reaction equation

HRID 1086396 reaction equation
N([O-])=O.[Na+].S(=O)(=O)(O)O.C(O)(=O)C.[C:14]([C:16]1[CH:22]=[C:21]([F:23])[C:19](N)=[C:18]([F:24])[CH:17]=1)#[N:15].[BrH:25]>[Cu]Br.O>[Br:25][C:19]1[C:21]([F:23])=[CH:22][C:16]([C:14]#[N:15])=[CH:17][C:18]=1[F:24]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 260Hydrogen BromideHCID 1118Sulfuric AcidHCID 2804674-Amino-3,5-difluorobenzonitrileHCID 23668193Sodium Nitrite

Product 1

HCID 147942904-Bromo-3,5-difluorobenzonitrile

Reagents, catalysts & solvents 2

HCID 24593copper(I) bromideCatalystHCID 962WaterSolvent

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.

Workup

  1. temperaturecooled to a temperature of at least 10° C
  2. custombetween about 20°and 25° C
  3. customA solution was prepared
  4. additionThe mixture was added drop-wise to the solution
  5. stirringthe solution was stirred at room temperature for 15 hours
  6. extractionthe solution was extracted with chloroform
  7. washwashed with water
  8. distillationThe chloroform in the aqueous layer was distilled off
  9. customthe residue was recrystallized from a solution mixture of methanol and acetone

Sources & evidence

ORD record
ord-89731dcb29fb4002832743abd203fab7
Source dataset
uspto-grants-1991_07
Patent number
US05030382

Reaction notes

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