Acetic Acid → 2-Chloro-4-(trifluoromethyl)benzaldehyde

HRID 252131Notes

Reaction equation

HRID 252131 reaction equation
[Cl:1][C:2]1[CH:9]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:7]=[CH:6][C:3]=1[C:4]#N.[H-].C([Al+]CC(C)C)C(C)C.C(O)(=[O:26])C.ClCCl>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:9]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:7]=[CH:6][C:3]=1[CH:4]=[O:26]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 6344DichloromethaneHCID 27364762-Chloro-4-(trifluoromethyl)benzonitrileHCID 21225700Diisobutylaluminumhydride

Product 1

HCID 130761442-Chloro-4-(trifluoromethyl)benzaldehydeYield 30%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Dissolve 2-chloro-4-trifluoromethylbenzonitrile (405 mg, 1.97 mmol) in anhydrous toluene (7 mL) and cool in a dry ice/ethanol bath. Add diisobutylaluminum hydride (DIBAL) (3.94 mL, 3.94 mmol, 1.0 M in toluene) slowly. Stir 30 min. Warm to room temperature, add acetic acid (2 mL) and wafer (10 mL) and stir for 2 hours. Extract the aqueous layer with ethyl acetate twice. Wash the organic layer with potassium sodium tartrate solution (Rochelle salt) twice. Dry (magnesium sulfate), filter, and concentrate to give a residue. Chromatograph the residue on silica gel eluting with a gradient of 100:0 to 1:1 hexanes:dichloromethane to give 2-chloro-4-trifluoromethylbenzaldehyde (123 mg, 30%). 1H NMR (400 MHz, CDCl3) δ 10.52 (s, 1H), 8.05 (d, 1H, J=8.0 Hz), 7.75 (s, 1H), 7.66 (d, 1H, J=8.0 Hz).

Workup

  1. temperaturecool in a dry ice/ethanol bath
  2. stirringstir for 2 hours
  3. extractionExtract the aqueous layer with ethyl acetate twice
  4. washWash the organic layer with potassium sodium tartrate solution (Rochelle salt) twice
  5. dry with materialDry (magnesium sulfate)
  6. filtrationfilter
  7. concentrationconcentrate
  8. customto give a residue

Sources & evidence

ORD record
ord-1eb9180f6d5c41d4a0ce4f7bfb4d4ccd
Source dataset
uspto-grants-2011_01
Patent number
US07868014B2

Reaction notes

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