Dimethylformamide → 4-Chloro-2-(trifluoromethyl)benzonitrile

HRID 252134Notes

Reaction equation

HRID 252134 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5](I)=[C:4]([C:9]([F:12])([F:11])[F:10])[CH:3]=1.[CH3:13][N:14](C)C=O>C1(C)C=CC=CC=1.[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:13]#[N:14])=[C:4]([C:9]([F:12])([F:11])[F:10])[CH:3]=1

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 27245244-Chloro-1-iodo-2-(trifluoromethyl)benzene

Product 1

HCID 27734954-Chloro-2-(trifluoromethyl)benzonitrileYield 63%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

Add 4-chloro-1-iodo-2-trifluromethylbenzene (1500 mg, 4.89 mmol), zinc cyanide (345 mg, 2.94 mmol), and tetrakis(triphenylphosphine)palladium(0) (564 mg, 0.488 mmol) to anhydrous N,N-dimethylformamide (40 mL). Heat to 80° C. overnight. Cool to room temperature, dilute with toluene, wash with 2 N ammonium hydroxide (3×), saturated aqueous sodium chloride, dry, filter, concentrate to give a residue. Chromatograph the residue on silica gel eluting with hexanes/dichloromethane, to give 4-chloro-2-trifluoromethylbenzonitrile (630 mg, 63%): 1H NMR (400 MHz, CDCl3) δ 7.81-7.78 (m, 2H), 7.67 (dd, 1H, J=8.4, 2.4 Hz).

Workup

  1. temperatureCool to room temperature
  2. washwash with 2 N ammonium hydroxide (3×), saturated aqueous sodium chloride
  3. customdry
  4. filtrationfilter
  5. concentrationconcentrate
  6. customto give a residue

Sources & evidence

ORD record
ord-7841bca62ba344c4970861f147139022
Source dataset
uspto-grants-2011_01
Patent number
US07868014B2

Reaction notes

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