Hydrochloric Acid → 4-Chloro-2,6-difluorobenzaldehyde

HRID 1977854Notes

Reaction equation

HRID 1977854 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([Cl:9])[CH:5]=[C:6]([F:8])[CH:7]=1.C([Li])CCC.CCCCCC.CN(C)[CH:23]=[O:24].Cl>O1CCCC1.CCOCC>[Cl:9][C:4]1[CH:3]=[C:2]([F:1])[C:7]([CH:23]=[O:24])=[C:6]([F:8])[CH:5]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 8058HexaneHCID 137000Benzene, 1-chloro-3,5-difluoro-HCID 178418339Butyllithium

Product 1

HCID 27735124-Chloro-2,6-difluorobenzaldehydeYield 96%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3,5-difluoro-1-chlorobenzene (5.0 g, 34 mmol) in tetrahydrofuran (70 mL) at −78° C. was added a solution of n-butyllithium in hexane (12.1 mL, 2.5 M, 30 mmol). After stirring for 1 hour, dimethylformamide (5.2 mL, 67 mmol) was added, and the mixture was stirred for 1.5 hours. The mixture was warmed to ambient temperature, diluted with ether and poured into 150 mL of 0.5 M aqueous HCl. The aqueous phase was extracted 3× into ether, and the combined organic layers were dried over MgSO4, filtered and concentrated in vacuo, affording 5.72 g (96%) of 4-chloro-2,6-difluoro-benzaldehyde as a colorless solid. 1H NMR (400 MHz, CDCl3) δ10.27 (s, 1H), 7.04 (d, 2H, J=7.9 Hz) ppm.

Workup

  1. stirringthe mixture was stirred for 1.5 hours
  2. extractionThe aqueous phase was extracted 3× into ether
  3. dry with materialthe combined organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8ee255830c634050b0a70b256d77075b
Source dataset
uspto-grants-2001_05
Patent number
US06235764B1

Reaction notes

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