Water → 4-[(4-Bromophenyl)(tetrahydro-4H-thiopyran-4-ylidene)methyl]phenol

HRID 229154

Reaction equation

HRID 229154 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=2)=O)=[CH:4][CH:3]=1.[S:17]1[CH2:22][CH2:21][C:20](=O)[CH2:19][CH2:18]1.O.C([O-])([O-])=O.[K+].[K+]>C1COCC1.Cl[Ti](Cl)(Cl)Cl.[Zn]>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[C:20]2[CH2:21][CH2:22][S:17][CH2:18][CH2:19]2)[C:10]2[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=2)=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 66173Tetrahydrothiopyran-4-oneHCID 4570728(4-Bromophenyl)(4-hydroxyphenyl)methanone

Product 1

HCID 686544294-[(4-Bromophenyl)(tetrahydro-4H-thiopyran-4-ylidene)methyl]phenolYield 71%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 24193Titanium TetrachlorideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

In a 3-neck round-bottomed flask equipped with a condenser and a nitrogen inlet, TiCl4 (0.51 mL, 4.67 mmol) was slowly added to a suspension of zinc powder (0.63 g, 9.60 mmol) in anhydrous THF (13 mL) at room temperature. The reaction was heated at reflux for 2.5 h. The reaction was taken out of the oil bath then a solution of (4-bromophenyl)(4-hydroxyphenyl)methanone (2) (0.35 g, 1.26 mmol) and tetrahydrothiopyran-4-one (0.44 g, 3.79 mmol) in anhydrous THF (13 mL) was added and the reaction mixture was heated at reflux for 2 h. The reaction mixture was cooled to room temperature and water (10 mL) added, via syringe, followed by addition of 10% aqueous K2CO3 (10 mL). The reaction mixture was filtered through a pad of Celite and the pad was washed with EtOAc. The filtrate was transferred to a separatory funnel and the layers were separated. The organic layer was washed with brine, dried (MgSO4), filtered, and the filtrate was concentrated to give an oil. The crude product was purified by flash column chromatography on silica gel using a hexanes:EtOAc gradient (100:0 to 75:25) to give compound 36 as a white powder (0.323 g, 71%). 1H NMR (400 MHz, DMSO-d6): δ 2.38-2.41 (m, 2H), 2.45-2.47 (m, 2H), 2.62-2.66 (m, 4H), 6.67 (d, J=8.5 Hz, 2H), 6.86 (d, J=8.5 Hz, 2H), 7.01 (d, J=8.2 Hz, 2H), 7.47 (d, J=8.3 Hz, 2H), 9.39 (s, 1H).

Workup

  1. customIn a 3-neck round-bottomed flask equipped with a condenser and a nitrogen inlet
  2. temperatureThe reaction was heated
  3. temperatureat reflux for 2.5 h
  4. temperaturethe reaction mixture was heated
  5. temperatureat reflux for 2 h
  6. filtrationThe reaction mixture was filtered through a pad of Celite
  7. washthe pad was washed with EtOAc
  8. customThe filtrate was transferred to a separatory funnel
  9. customthe layers were separated
  10. washThe organic layer was washed with brine
  11. dry with materialdried (MgSO4)
  12. filtrationfiltered
  13. concentrationthe filtrate was concentrated
  14. customto give an oil
  15. customThe crude product was purified by flash column chromatography on silica gel using a hexanes

Sources & evidence

ORD record
ord-7a9c9a4d441149018bc795e02b8efb77
Source dataset
uspto-grants-2009_07
Patent number
US07560589B2

Linked notes

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