Acetic Acid → 3-Bromo-2,5-difluorobenzaldehyde

HRID 1607181Notes

Reaction equation

HRID 1607181 reaction equation
N[C:2]1[C:9]([F:10])=[CH:8][C:5]([CH:6]=[O:7])=[C:4]([F:11])[C:3]=1[Br:12].CC(O)=O.[PH2](O)=O.N([O-])=O.[Na+]>O>[Br:12][C:3]1[C:4]([F:11])=[C:5]([CH:8]=[C:9]([F:10])[CH:2]=1)[CH:6]=[O:7]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 4124402Phosphinic AcidHCID 146210204-Amino-3-bromo-2,5-difluorobenzaldehydeHCID 23668193Sodium Nitrite

Product 1

HCID 146210213-Bromo-2,5-difluorobenzaldehydeYield 88.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 16 g of 4-amino-3-bromo-2,5-difluorobenzaldehyde and 375 mL of AcOH is stirred until homogenous and 188 mL of 50-52% aqueous hypophosphorous acid is added. Next a solution of 6.8 g of NaNO2 in 38 mL of H2O is added dropwise over 15 minutes with ice cooling to maintain a temperature of 15°-20° C. The ice bath is removed and stirring continued for 1 hour. the reaction mixture is poured into 1 L of ice/H2O and extracted with 3×300 mL of CH2Cl2. The CH2Cl2 extracts are washed with H2O, 2×10% NaOH, and 2×H2O (250 mL each), dried with Na2SO4 and concentrated in vacuo to give 13.32 g (80% yield) of 3-bromo-2,5-difluorobenzaldehyde, m.p. 36°-38° C. Recrystallization from Et2O/hexane furnishes the title compound melting at 37°-40° C. with M+1 ions at 221 and 223 in the mass spectrum.

Workup

  1. additionis added
  2. temperatureto maintain a temperature of 15°-20° C
  3. customThe ice bath is removed
  4. additionthe reaction mixture is poured into 1 L of ice/H2O
  5. extractionextracted with 3×300 mL of CH2Cl2
  6. washThe CH2Cl2 extracts are washed with H2O, 2×10% NaOH, and 2×H2O (250 mL each)
  7. dry with materialdried with Na2SO4
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3204ef27c85c49c2a11d5c1cde2cf753
Source dataset
uspto-grants-1989_09
Patent number
US04863959

Reaction notes

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