Phenol → 5,5,8,8-Tetramethyl-5,6,7,8-tetrahydronaphthalen-2-ol

HRID 964509Notes

Reaction equation

HRID 964509 reaction equation
O1C=CC(=O)C=C1.[Cl-].[Cl-].[Cl-].[Al+3].[C:12]1([OH:18])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.Cl[C:20]([CH3:28])([CH2:22][CH2:23][C:24](Cl)([CH3:26])[CH3:25])[CH3:21]>ClCCl>[CH3:21][C:20]1([CH3:28])[CH2:22][CH2:23][C:24]([CH3:26])([CH3:25])[C:16]2[CH:17]=[C:12]([OH:18])[CH:13]=[CH:14][C:15]1=2

Participants

6

Reactant 4

HCID 996PhenolHCID 79684H-pyran-4-oneHCID 80360Hexane, 2,5-dichloro-2,5-dimethyl-HCID 6451240Aluminum(III) Chloride

Product 1

HCID 2687865,5,8,8-Tetramethyl-5,6,7,8-tetrahydronaphthalen-2-ol

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The title compound was synthesized in a manner similar to that of compound 101b except 3,4,5,6,7,8-hexahydro-2,2,5,5,8,8-hexamethylnaphtho(2,3-b)-1,2-pyran-4-one (structure 1) was employed as the starting ketone. The synthesis of the pyran-4-one is detailed here. Aluminum trichloride (25 g, 0.18M) was added in portions to a solution of phenol (49.5 g, 0.52M) and 2,5-dichloro-2,5-dimethylhexane (101.0 g, 0.55M) in dichloromethane (700 ml). The reaction mixture was allowed to stir at 25°-40° C. for 2 h, then the dark red mixture was poured onto ice. Aqueous work up (EtOAc extraction) gave 5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalen-2-ol as a white solid, which was recrystallized from hexane to give colorless needles (84.8 g, 0.42 moles, 80%): 1H NMR (400 MHz, CDCl3) δ 7.17 (d, 1H), 6.78 (d, 1H), 6.62 (dd, 1H), 4.55 (s, 1H), 1.65 (s, 4H), 1.25 (s, 12H). The hydroxynaphthalene (19.1g, 93.6 mmol) was treated dropwise with acetyl chloride (7.7 g, 98.2 mmol) in 1,2-dichloroethane (250ml) at 0° C. After completion of the addition, aluminum chloride (10 g, 75.2 mmol) was added in portions over 5 min. The mixture was refluxed for 10 h, then stirred at 25° C. for 8 h. GLC analysis indicated the desired keto-phenol was present in 98.6% purity. The reaction mixture was poured onto ice and aqueous work up (EtOAc extract) gave a brown-black solid, which was dissolved in hot methanol, filtered, and concentrated to give a brown viscous semi-solid. Flash chromatography (15% EtOAc/hexane) gave 1-(3-hydroxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)ethanone as a light yellow solid. Recrystallization from hexane afforded white crystals (15.2 g, 61.8 mmol, 66%): 1H NMR (400 MHz, CDCl3) δ 7.63 (s, 1H,), 6.9 (s, 1H), 2.61 (s, 3H), 1.67 (s, 4H), 1.29 (s, 6H), 1.27 (s, 6H).

Workup

  1. additionthe dark red mixture was poured onto ice
  2. extractionAqueous work up (EtOAc extraction)

Sources & evidence

ORD record
ord-ad28df2b6ff440049fa92c7a19cb21a8
Source dataset
uspto-grants-1998_06
Patent number
US05770383

Reaction notes

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