Reaction #43896

Reaction equation

KBr

2,4,6-trimethylphenol

4-fluorobenzonitrile

potassium carbonate

→

4-(2,4,6-Trimethylphenoxy)benzonitrile

Yield 97.0%

Solvents

toluene

NMP

Conditions

Workup

1. 1
   OtherInto a 250 mL three-necked, round-bottomed flask equipped with a magnetic stir-bar, nitrogen inlet, and a condenser
2. 2
   TemperatureThe reaction mixture was then heated
3. 3
   FiltrationThe dark solution was filtered while it
4. 4
   Temperaturewas warm
5. 5
   workup.ADDITIONthe filtrate was poured
6. 6
   workup.DISTILLATIONinto distilled water containing 5% hydrochloric acid
7. 7
   OtherThe solution was separated into organic layer and aqueous layer
8. 8
   workup.ADDITIONThe organic layer was diluted with dichloromethane
9. 9
   Otherseparated
10. 10
    OtherThe solvent was removed to dryness
11. 11
    OtherLight brown oily residue was freeze-dried
12. 12
    Otherto afford 10.1 g (97% yield)

Procedure

Into a 250 mL three-necked, round-bottomed flask equipped with a magnetic stir-bar, nitrogen inlet, and a condenser, 2,4,6-trimethylphenol (6.00 g, 44.1 mmol), 4-fluorobenzonitrile (5.34 g, 44.1 mmol), potassium carbonate (7.30 g, 52.8 mmol), and a mixture of NMP (100 mL) and toluene (60 mL) were placed. The reaction mixture was then heated and maintained around 140° C. for 8 h with vigorous nitrogen flow. The dark solution was filtered while it was warm and the filtrate was poured into distilled water containing 5% hydrochloric acid. The solution was separated into organic layer and aqueous layer. The organic layer was diluted with dichloromethane and separated. The solvent was removed to dryness. Light brown oily residue was freeze-dried to afford 10.1 g (97% yield): Anal. Calcd. for C16H15NO: C, 80.98%; H, 6.37%; N, 5.90%; O, 6.74%. Found: C, 80.31%; H, 6.37%; N, 5.75%; O, 6.46%. FT-IR (KBr, cm−1): 2226 (C≡N stretch). Mass spectrum (m/e): 237 (M+, 100% relative abundance), 222, 204, 194. 1H NMR (CDCl3, ppm) δ 2.05 (s, 6H, CH3), 2.30 (s, 3H, CH3), 6.81-6.84 (d, 2H, Ar), 6.91 (s, 2H, Ar), 7.53-7.56 (d, 2H, Ar). 13C NMR (CDCl3, ppm) δ 16.10, 20.79, 115.48, 129.07, 129.15, 129.88, 130.48, 134.25, 147.84, 150.03, 161.44.

Source