1-Chloro-4-(chloromethyl)benzene → 3-(4-Chlorophenyl)-1,1,1-trifluoropropan-2-one

HRID 1030782Notes

Reaction equation

HRID 1030782 reaction equation
[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6]Cl)=[CH:4][CH:3]=1.[Mg].[F:11][C:12]([F:19])([F:18])[C:13](OCC)=[O:14].CC(C)=O.C(=O)=O>CCOCC>[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][C:13](=[O:14])[C:12]([F:19])([F:18])[F:11])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 77231-Chloro-4-(chloromethyl)benzeneHCID 9794Ethyl trifluoroacetateHCID 5462224MagnesiumHCID 18522661Acetone cardice

Product 1

HCID 151139833-(4-Chlorophenyl)-1,1,1-trifluoropropan-2-oneYield 47.4%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent3×

Conditions

Temperature
-10 °C

Procedure

A solution of p-chlorobenzyl chloride (80.5 g, 0.5 mol) in anhydrous ether (150 mL) is slowly added to a vigorously stirred slurry of magnesium turnings (12.5 g, 0.5 mol) in ether (50 mL) over 45 minutes such that the reaction mixture maintains a moderate reflux. The solution is then refluxed for 30 minutes and cooled in an ice bath. The Grignard reagent is then added to a solution of ethyl tri-fluoroacetate (71.04 g, 0.5 mol) in ether (150 mL) at -60° to -70° C. (acetone-dry ice bath) over 45 minutes. The cooling bath is removed and the reaction mixture is allowed to warm to -10° C. whereupon a solid precipitates out. The reaction mixture is cautiously decomposed with saturated NH4Cl and then acidified with 10% HCl. The ether layer is separated, washed with water and saturated NaCl and dried (MgSO4). Evaporation and vacuum distillation gives the title product as a clear liquid (52.8 g): bp 72°-74° C. (34 mm); IR (neat) 1762 cm-1 ; 1H NMR (CDCl3) δ4.00 (s, 2H, CH2), 7.15 and 7.35 (d, J=8.4 Hz, 4H, ArH); 19F NMR δ-79.1; 13C NMR; δ42.2 (CH2) 116.7 (q 1JCF =292.5 Hz, CF3), 129.1 (C-2'); 131.0 (C-3'), 132.6 (C-1'), 134.0 (C-4'), 188.5 (q, 2JCF =35.5 Hz, CO).

Workup

  1. temperatureThe solution is then refluxed for 30 minutes
  2. temperaturecooled in an ice bath
  3. customThe cooling bath is removed
  4. customprecipitates out
  5. customThe ether layer is separated
  6. washwashed with water and saturated NaCl
  7. dry with materialdried (MgSO4)
  8. customEvaporation and vacuum distillation

Sources & evidence

ORD record
ord-f1b261758ebf4bdf9238f53d85683cfd
Source dataset
uspto-grants-1992_04
Patent number
US05106985

Reaction notes

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