Phenylacetaldehyde → 2-Phenyl-1-[4-(trifluoromethyl)phenyl]ethan-1-one

HRID 2380659Notes

Reaction equation

HRID 2380659 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][CH:3]=1.C([Li])CCC.[C:17]1([CH2:23][CH:24]=[O:25])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C1COCC1.CCCCCC>[C:17]1([CH2:23][C:24]([C:2]2[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][CH:3]=2)=[O:25])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

6

Reactant 3

HCID 998PhenylacetaldehydeHCID 67872Benzene, 1-bromo-4-(trifluoromethyl)-HCID 178418339Butyllithium

Product 1

HCID 3182342-Phenyl-1-[4-(trifluoromethyl)phenyl]ethan-1-oneYield 24%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Procedure

To a solution of 45.0 g of 1-bromo-4-(trifluoromethyl)benzene in 300 mL of THF cooled to -78° C. was added 77.0 mL of 2.5M n-butyl lithium in hexane dropwise. An exothermic reaction to -55° C. was observed. The reaction was then stirred for 20 minutes after which time phenyl acetaldehyde (23.5 mL, 0.2 mol) was added dropwise. The reaction was then stirred for an additional hour with gradual warming to room temperature. The mixture was then partitioned between ether and water, dried over anhydrous magnesium sulfate and concentrated to 52.6 g of a yellow oil. The crude oil was dissolved in 600 mL of methylene chloride and 100 g of pyridinium dichromate was added in several portions over 20 minutes and the mixture was then stirred at room temperature overnight. The reaction was then diluted with ether and filtered through magnesium sulfate and concentrated. The crude product was dissolved in hot n-butyl chloride, insoluble material was filtered off and the mixture was cooled to 0° C. Filtration and drying of the precipitate afforded 12.7 g of the title compound as a white solid, mp 127°-128° C.

Workup

  1. customAn exothermic reaction to -55° C.
  2. additionwas added dropwise
  3. customThe mixture was then partitioned between ether and water
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated to 52.6 g of a yellow oil
  6. dissolutionThe crude oil was dissolved in 600 mL of methylene chloride
  7. addition100 g of pyridinium dichromate was added in several portions over 20 minutes
  8. stirringthe mixture was then stirred at room temperature overnight
  9. additionThe reaction was then diluted with ether
  10. filtrationfiltered through magnesium sulfate
  11. concentrationconcentrated
  12. dissolutionThe crude product was dissolved in hot n-butyl chloride
  13. filtrationinsoluble material was filtered off
  14. temperaturethe mixture was cooled to 0° C
  15. filtrationFiltration
  16. customdrying of the precipitate

Sources & evidence

ORD record
ord-d5fe1bd3a06c4650b4bd5f3af569fd88
Source dataset
uspto-grants-1994_11
Patent number
US05369121

Reaction notes

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