Sulfuric Acid → 4-Fluoro-2-(1-methylcyclohexyl)phenol

HRID 404594

Reaction equation

HRID 404594 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[CH3:9][C:10]1(O)[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1.S(=O)(=O)(O)O>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([C:10]2([CH3:9])[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)[CH:3]=1

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 97324-FluorophenolHCID 115501-Methylcyclohexanol

Product 1

HCID 593949974-Fluoro-2-(1-methylcyclohexyl)phenolYield 61.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-Fluorophenol (41.8 g, 373 mmol) and 1-methylcyclohexanol (63.8 g, 560 mmol) dissolved in 600 mL of dried CH2Cl2, were treated with concentrated sulfuric acid (98%, 22.3 mL, 418 mmol). The mixture was stirred at room temperature for 50 hours. The reaction mixture was then extracted by CH2C2 (250 mL×3). The organic layer was washed with saturated a.q NaHCO3, dried over MgSO4, and evaporated under vacuum. The residue was purified by column chromatography on silica gel to give 4-fluoro-2-(1-methylcyclohexyl)phenol as a dark green oil −47.6 g. 1H NMR (400 MHz, CDCl3) δ 7.00 (dd, J=3.2, 11.2 Hz, 1H), 6.76-6.71 (m, 1H), 6.62-6.59 (m, 1H), 5.27 (brs, 1H), 2.13-2.07 (m, 2H), 1.70-1.37 (m, 8H), 1.32 (s, 3H).

Workup

  1. extractionThe reaction mixture was then extracted by CH2C2 (250 mL×3)
  2. washThe organic layer was washed with saturated a.q NaHCO3
  3. dry with materialdried over MgSO4
  4. customevaporated under vacuum
  5. customThe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-4654fe6cc0214d05921755de7df50929
Source dataset
uspto-grants-2014_06
Patent number
US08748612B2

Linked notes

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