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

HRID 1707522Notes

Reaction equation

HRID 1707522 reaction equation
OS(O)(=O)=O.N([O-])=O.[Na+].C(O)(=O)C.N[C:15]1[C:22]([F:23])=[CH:21][C:18]([C:19]#[N:20])=[CH:17][C:16]=1[F:24].[BrH:25]>>[Br:25][C:15]1[C:22]([F:23])=[CH:21][C:18]([C:19]#[N:20])=[CH:17][C:16]=1[F:24]

Participants

6

Reactant 5

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

Product 1

HCID 147942904-Bromo-3,5-difluorobenzonitrile

Conditions

Temperature
40 °C

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.

Workup

  1. additionafter the addition it
  2. dissolutiondissolved completely
  3. stirringWhile stirring this solution on an ice water bath
  4. temperaturemaintaining the temperature at 20°-25° C.
  5. additionafter the addition
  6. stirringwas stirred at this temperature until the crystals
  7. dissolutionwere completely dissolved
  8. additionwas added dropwise for 2 hours
  9. stirringit was stirred on an ice water bath for 1 hour and at room temperature overnight
  10. customThe crystals formed
  11. filtrationwere filtered
  12. washafter washing the crystals in glacial acetic acid
  13. customthey were recrystallized from a mixture of acetone and methanol

Sources & evidence

ORD record
ord-80f863b243ce4abd909dc447ef412891
Source dataset
uspto-grants-1994_10
Patent number
US05354502

Reaction notes

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