Hydrochloric Acid → 2-Iodo-5-(trifluoromethyl)benzaldehyde

HRID 1028551Notes

Reaction equation

HRID 1028551 reaction equation
[I:1][C:2]1[CH:9]=[CH:8][C:7]([C:10]([F:13])([F:12])[F:11])=[CH:6][C:3]=1[C:4]#N.CC(C[AlH]CC(C)C)C.Cl.CC[O:26]CC>C(Cl)Cl>[I:1][C:2]1[CH:9]=[CH:8][C:7]([C:10]([F:13])([F:12])[F:11])=[CH:6][C:3]=1[CH:4]=[O:26]

Participants

6

Reactant 4

HCID 313Hydrochloric Acid2×HCID 3283Diethyl EtherHCID 14487Diisobutylaluminum hydride2×HCID 533636442-Iodo-5-(trifluoromethyl)benzonitrile

Product 1

HCID 716509062-Iodo-5-(trifluoromethyl)benzaldehyde

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 2-iodo-5-(trifluoromethyl)benzonitrile (EXAMPLE 2, 42 g) in CH2Cl2 (300 mL) at −78° C. was added a solution of DIBAL in CH2Cl2 (175 mL, 1M) over 30 minutes. A precipitate formed. The reaction was warmed to 0° C. An additional 25 mL of the DIBAL solution was added dropwise over 30 minutes. The reaction was poured into 200 mL 2N aqueous HCl, diluted with ether and stirred 1 hour. TLC analysis indicates imine still present and an additional 100 mL 2N aqueous was added and the reaction stirred overnight. Imine was still present by TLC analysis and 200 mL 2N aqueous HCl was added and the mixture stirred 2 hours. The layers were separated and the aqueous layer back extracted with ether. The ether extracts were combined, washed with brine, dried over anhydrous MgSO4, filtered and concentrated. The product was purified by silica gel chromatography eluting with 95:5 hexanes/EtOAc to give 2-Iodo-5-(trifluoromethyl)benzaldehyde as a white solid. 1H NMR (500 MHz, CDCl3): δ 10.00 (s, 1H), 8.12 (s, 1H), 8.11 (d, J=8 Hz, 1H), 7.53 (dd, J=2 Hz, 8 Hz, 1H).

Workup

  1. customA precipitate formed
  2. additionan additional 100 mL 2N aqueous was added
  3. stirringthe reaction stirred overnight
  4. additionwas added
  5. stirringthe mixture stirred 2 hours
  6. customThe layers were separated
  7. extractionthe aqueous layer back extracted with ether
  8. washwashed with brine
  9. dry with materialdried over anhydrous MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe product was purified by silica gel chromatography
  13. washeluting with 95:5 hexanes/EtOAc

Sources & evidence

ORD record
ord-de46e3e5c1df48c79ef996ff7e8dce0d
Source dataset
uspto-grants-2014_05
Patent number
US08735435B2

Reaction notes

Loading…