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

HRID 892279Notes

Reaction equation

HRID 892279 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([CH3:9])[C:3]=1[OH:10].F[C:12]1[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[CH:14][CH:13]=1.C(=O)([O-])[O-].[K+].[K+].CN1C(=O)CCC1>C1(C)C=CC=CC=1>[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([CH3:9])[C:3]=1[O:10][C:12]1[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[CH:14][CH:13]=1

Participants

6

Reactant 4

HCID 106982,4,6-TrimethylphenolHCID 11430Potassium CarbonateHCID 13387N-methyl-2-pyrrolidoneHCID 145174-Fluorobenzonitrile

Product 1

HCID 222423224-(2,4,6-Trimethylphenoxy)benzonitrileYield 97%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
140 °C

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 hours 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 completely from the organic extract. Light brown oily residue was freeze-dried to afford 10.1 g (97% yield) of the desired product. 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.

Workup

  1. customInto a 250 mL three-necked, round-bottomed flask equipped with a magnetic stir-bar, nitrogen inlet, and a condenser
  2. temperatureThe reaction mixture was then heated
  3. filtrationThe dark solution was filtered while it
  4. temperaturewas warm
  5. additionthe filtrate was poured
  6. distillationinto distilled water containing 5% hydrochloric acid
  7. customThe solution was separated into organic layer and aqueous layer
  8. additionThe organic layer was diluted with dichloromethane
  9. customseparated
  10. customThe solvent was removed completely from the organic extract
  11. customLight brown oily residue was freeze-dried

Sources & evidence

ORD record
ord-694bfa08ce584005a22d369461be7cae
Source dataset
uspto-grants-2006_02
Patent number
US07005550B1

Reaction notes

Loading…