Toluene → 4-(4-Fluorophenyl)benzonitrile

HRID 2407025Notes

Reaction equation

HRID 2407025 reaction equation
Br[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1.[F:10][C:11]1[CH:16]=[CH:15][C:14](B(O)O)=[CH:13][CH:12]=1.C1(C)C=CC=CC=1.[F-].[K+]>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.O>[F:10][C:11]1[CH:16]=[CH:15][C:14]([C:2]2[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=2)=[CH:13][CH:12]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 12162Benzonitrile, 4-bromo-HCID 2856454-Fluorophenylboronic acidHCID 522689Potassium Fluoride

Product 1

HCID 13930404-(4-Fluorophenyl)benzonitrileYield 96.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Procedure

To a solution of 4-bromobenzonitrile (4.0 g, 22 mmol) and 4-fluorophenylboronic acid (4.6 g, 32 mmol) in 4:1 toluene:water (100 mL) were added potassium fluoride (3.8 g, 66 mmol) and Pd(PPh3)4 (2.5 g, 2.2 mmol). The resulting mixture was stirred at reflux for 12 h. The mixture was cooled to room temperature and extracted with ethyl acetate (30 mL*3). The combined organic layers were washed with water, brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification of the crude residue by silica gel chromatography gave 4′-fluorobiphenyl-4-carbonitrile (4.2 g) as a colorless solid. 1H NMR (400 MHz, CD3OD) δ 7.69 (s, 4H), 7.63-7.60 (m, 2H), 7.15-7.10 (m, 2H).

Workup

  1. temperatureat reflux for 12 h
  2. extractionextracted with ethyl acetate (30 mL*3)
  3. washThe combined organic layers were washed with water, brine
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customPurification of the crude residue by silica gel chromatography

Sources & evidence

ORD record
ord-4cc8e04a1b8b4c8c9d54b8aeac977133
Source dataset
uspto-grants-2014_08
Patent number
US08809342B2

Reaction notes

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