2,5-Difluorobenzaldehyde → 1-(2,5-Difluorophenyl)ethan-1-one

HRID 2299177Notes

Reaction equation

HRID 2299177 reaction equation
[F:1][C:2]1[CH:9]=[CH:8][C:7]([F:10])=[CH:6][C:3]=1[CH:4]=[O:5].[CH3:11]Br.[Mg]>O1CCCC1>[F:1][C:2]1[CH:9]=[CH:8][C:7]([F:10])=[CH:6][C:3]=1[C:4](=[O:5])[CH3:11]

Participants

4

Reactant 2

HCID 1376632,5-DifluorobenzaldehydeHCID 86584079Magnesium methylbromide

Product 1

HCID 747941-(2,5-Difluorophenyl)ethan-1-oneYield 84%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 2,5-difluorobenzaldehyde (24.6 g) in tetrahydrofuran (100 ml) was added dropwise to an ice-cooled solution (207 ml) of 0.92N magnesium methylbromide in tetrahydrofuran. The resulting solution was stirred at room temperature for 1.5 hours, and the organic phase was washed in an aqueous saturated sodium chloride solution and dried over anhydrous magnesium sulfate, to subsequently distill off the solvents under reduced pressure. To the residue were added anhydrous dichloromethane (500 ml), sodium acetate (14.2 g) and pyridinium chlorochromate (55.94 g), prior to stirring at room temperature for 10 hours. To the resulting mixture was added an aqueous saturated sodium hydrogen carbonate solution, prior to extraction in ethyl acetate three times. The organic phase was washed in water and in an aqueous saturated sodium chloride solution and dried over anhydrous magnesium sulfate, to distill off the solvents under reduced pressure. The residue was purified by silica gel column chromatography (developing solvent:hexane:ethyl acetate=85:15), to recover 2′,5′-difluoroacetophenone (22.73 g; yield of 84%). By 1H-NMR (90 MHz, CDCl3), the compound has the peaks shown below.

Workup

  1. washthe organic phase was washed in an aqueous saturated sodium chloride solution
  2. dry with materialdried over anhydrous magnesium sulfate
  3. distillationto subsequently distill off the solvents under reduced pressure
  4. additionTo the residue were added anhydrous dichloromethane (500 ml), sodium acetate (14.2 g) and pyridinium chlorochromate (55.94 g)
  5. stirringto stirring at room temperature for 10 hours
  6. additionTo the resulting mixture was added an aqueous saturated sodium hydrogen carbonate solution
  7. extractionto extraction in ethyl acetate three times
  8. washThe organic phase was washed in water and in an aqueous saturated sodium chloride solution
  9. dry with materialdried over anhydrous magnesium sulfate
  10. distillationto distill off the solvents under reduced pressure
  11. customThe residue was purified by silica gel column chromatography (developing solvent:hexane:ethyl acetate=85:15)

Sources & evidence

ORD record
ord-1f60a90dd29d4c00a0fb19d1b3ad3e96
Source dataset
uspto-grants-2002_12
Patent number
US06495592B1

Reaction notes

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