Cyclohexanone → 4-[(4-Bromo-3-methylphenyl)(cyclohexylidene)methyl]phenol

HRID 229179Notes

Reaction equation

HRID 229179 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][C:3]=1[CH3:17].[C:18]1(=O)[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1>C1COCC1.[Ti](Cl)(Cl)(Cl)Cl.[Zn]>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[C:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)[C:10]2[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=2)=[CH:4][C:3]=1[CH3:17]

Participants

6

Reactant 2

HCID 7967CyclohexanoneHCID 68654843(4-Bromo-3-methylphenyl)(4-hydroxyphenyl)methanone

Product 1

HCID 686545224-[(4-Bromo-3-methylphenyl)(cyclohexylidene)methyl]phenolYield 85%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 24193Titanium TetrachlorideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

Titanium tetrachloride (2.70 mL, 24.5 mmol) was added dropwise to a suspension of zinc powder (3.24 g, 49.5 mmol) in anhydrous THF (60 mL) at RT. After refluxing for 1 h, a mixture of 66 (1.78 g, 6.11 mmol) and cyclohexanone (1.80 g, 18.3 mmol) dissolved in THF (20 mL) was added dropwise. Refluxing was continued for 30 min. The reaction mixture was cooled to RT and filtered through Celite. Water (250 mL) was added and the mixture was extracted with Et2O (3×100 mL). The combined ethereal extracts were washed with water (200 mL), brine (200 mL), and dried over MgSO4. Concentration followed by flash chromatography (20:1 to 5:1 hexanes:EtOAc) afforded 1.85 g (85%) of 67 as an orange solid. 1H NMR (400 MHz, CDCl3): δ 1.58 (m, 6H), 2.20 (m, 4H), 2.32 (s, 3H), 5.95 (br s, 1H), 6.73 (d, J=8.4 Hz, 2H), 6.79 (dd, J=8.1 Hz, 2.0 Hz, 1H), 6.95 (m, 3H), 7.40 (d, J=8.1 Hz, 1H).

Workup

  1. temperatureAfter refluxing for 1 h
  2. additionwas added dropwise
  3. temperatureRefluxing
  4. filtrationfiltered through Celite
  5. additionWater (250 mL) was added
  6. extractionthe mixture was extracted with Et2O (3×100 mL)
  7. washThe combined ethereal extracts were washed with water (200 mL), brine (200 mL)
  8. dry with materialdried over MgSO4
  9. concentrationConcentration

Sources & evidence

ORD record
ord-d5899242af304aa981aed3fababa5a74
Source dataset
uspto-grants-2009_07
Patent number
US07560589B2

Reaction notes

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