Water → 2-Fluoro-6-(4-methylphenylthio)benzonitrile

HRID 432300Notes

Reaction equation

HRID 432300 reaction equation
F[C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([F:10])[C:3]=1[C:4]#[N:5].[CH3:11][C:12]1[CH:17]=[CH:16][C:15]([SH:18])=[CH:14][CH:13]=1.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O.C(OCC)(=O)C>[F:10][C:6]1[CH:7]=[CH:8][CH:9]=[C:2]([S:18][C:15]2[CH:16]=[CH:17][C:12]([CH3:11])=[CH:13][CH:14]=2)[C:3]=1[C:4]#[N:5]

Participants

7

Reactant 4

HCID 962WaterHCID 78114-MethylbenzenethiolHCID 11430Potassium CarbonateHCID 746952,6-Difluorobenzonitrile

Product 1

HCID 27374012-Fluoro-6-(4-methylphenylthio)benzonitrileYield 37%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 2,6-difluorobenzonitrile (5.18 g, 37.26 mmol) in dimethylformamide (100 mL) was treated with p-thiocresol (4.628 g, 37.26 mmol) and potassium carbonate (10.28 g, 74.52 mmol). The reaction mixture was stirred for 24 h under a nitrogen atmosphere. Water (150 mL) and ethyl acetate (250 mL) were added to the reaction mixture. The layers were partitioned and the aqueous layer was extracted with ethyl acetate (500 mL). The combined organic layers were washed with water (1 L), dried over magnesium sulfate, filtered and evaporated under reduced pressure. The crude product was purified by flash chromatography on silica gel, eluting 7:1 heptane:ethyl acetate. The column afforded 3.341 g (37%) of 2-fluoro-6-[(4-methylphenyl)sulfanyl]benzonitrile. 1H NMR (DMSO-d6, 400 MHz) δ 7.66-7.61 (m, 1H), 7.47-7.45 (m, 2H), 7.36-7.32 (m, 3H), 6.83-6.79 (m, 1H), 2.36 (s, 3H); HPLC Waters 2690 Alliance HPLC (Symmetry Shield RP18 3.5 μm, 2.1×50 mm; 5%-95% acetonitrile-0.1 M ammonium acetate over 15 min, 0.5 mL/min) Rt 8.04 min (93%).

Workup

  1. customThe layers were partitioned
  2. extractionthe aqueous layer was extracted with ethyl acetate (500 mL)
  3. washThe combined organic layers were washed with water (1 L)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customThe crude product was purified by flash chromatography on silica gel
  8. washeluting 7:1 heptane

Sources & evidence

ORD record
ord-5bd12ea2126a43c595a5425eaf0e8831
Source dataset
uspto-grants-2003_12
Patent number
US06660744B1

Reaction notes

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