Tetrahydrofuran → 3-phenyl-4'-thiomethylpropiophenone

HRID 480079Notes

Reaction equation

HRID 480079 reaction equation
[CH3:1][S:2][C:3]1[CH:10]=[CH:9][C:6]([C:7]#N)=[CH:5][CH:4]=1.[CH2:11]([Mg]Cl)[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C1C[O:24]CC1>>[CH3:1][S:2][C:3]1[CH:10]=[CH:9][C:6]([C:7](=[O:24])[CH2:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:5][CH:4]=1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 5909604-(Methylthio)benzonitrileHCID 178418865HCID 178418865, compound

Product 1

HCID 113458823-phenyl-4'-thiomethylpropiophenoneYield 96%

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 4-(methylthio)benzonitrile (25.0 g, 0.17 mol) in THF (100 mL) under N2 atmosphere was added phenethylmagnesium chloride (1.0 M in THF, 210 mL, 0.21 mol). The solution was heated to reflux for 4 hours, cooled to 0° C., and quenched carefully with water (10 mL). The resulting slurry was treated with 6 N hydrochloric acid (200 mL) and stirred at room temperature overnight. The THF was evaporated from the mixture, and the residue was extracted with EtOAc (2×300 mL). The combined organic extracts were washed with 2M NA2CO3, dried over Na2SO4, filtered, and concentrated to give a solid material. Recrystallization from EtOAc-Hex (1:4) afforded the title compound (41.5 g, 96%) as greenish plates. mp 105° C. 1H NMR (300 MHz, CDCl3) δ 7.85 (d, J=8.5 Hz, 2H), 7.32-7.19 (m, 7H), 3.24 (t, J=6.8 Hz, 2H), 3.06 (t, J=6.8 Hz, 2H), 2.50 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 198.2, 145.8, 141.3, 133.2, 128.48, 128.42, 128.38, 126.1, 125.0,40.2,30.2, 14.7; mass spectrum (API-TIS) m/z 257 (M+H).

Workup

  1. temperatureThe solution was heated
  2. temperatureto reflux for 4 hours
  3. customquenched carefully with water (10 mL)
  4. additionThe resulting slurry was treated with 6 N hydrochloric acid (200 mL)
  5. customThe THF was evaporated from the mixture
  6. extractionthe residue was extracted with EtOAc (2×300 mL)
  7. washThe combined organic extracts were washed with 2M NA2CO3
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto give a solid material
  12. customRecrystallization from EtOAc-Hex (1:4)

Sources & evidence

ORD record
ord-64a6a6ed40374bb28d9e540056e981ba
Source dataset
uspto-grants-2003_11
Patent number
US06649629B2

Reaction notes

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