Sulfuric Acid → 4-(Difluoromethoxy)-2-iodophenol

HRID 1401998Notes

Reaction equation

HRID 1401998 reaction equation
[I:1]N1C(=O)CCC1=O.[F:9][CH:10]([F:19])[O:11][C:12]1[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=1.S(=O)(=O)(O)O>C(O)(=O)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.O>[F:9][CH:10]([F:19])[O:11][C:12]1[CH:13]=[CH:14][C:15]([OH:18])=[C:16]([I:1])[CH:17]=1

Participants

7

Reactant 3

HCID 1118Sulfuric AcidHCID 120273N-Iodosuccinimide2×HCID 27741244-(Difluoromethoxy)phenol

Product 1

HCID 594365464-(Difluoromethoxy)-2-iodophenolYield 42%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 311Citric AcidSolventHCID 962WaterSolvent

Procedure

To a suspension of N-iodosuccinimide (1.12 g, 0.005 mol) in acetic acid (15.0 mL) was added 4-(difluoromethoxy)phenol (0.8 g, 0.005 mol) under nitrogen. Sulfuric acid (0.147 g, 0.0015 mol) was added and the resulting dark brown suspension was stirred at room temperature for 4 hours before the addition of N-iodosuccinimide (0.6 g, 0.0025 mol). The mixture was stirred for 16 hours before diluting with citric acid (1.0 M aqueous solution, 20.0 mL) and water (20.0 mL). The aqueous layer was extracted with dichloromethane (2×30.0 mL). Combined organic layers were dried over sodium sulphate, filtered and concentrated in vacuo to afford a dark purple oil. This was concentrated in vacuo from toluene (3×20.0 mL) to afford a brown oil. The aqueous layer was concentrated in vacuo. Both organic and aqueous crude residues were purified by flash column chromatography on the ISCO™ (40 g SiO2) eluting with ethyl acetate:heptane (gradient 0:1 to 1:1, by volume) to afford the title compound as a yellow oil, 0.604 g, 42% yield.

Workup

  1. extractionThe aqueous layer was extracted with dichloromethane (2×30.0 mL)
  2. dry with materialCombined organic layers were dried over sodium sulphate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto afford a dark purple oil
  6. concentrationThis was concentrated in vacuo from toluene (3×20.0 mL)
  7. customto afford a brown oil
  8. concentrationThe aqueous layer was concentrated in vacuo
  9. customBoth organic and aqueous crude residues were purified by flash column chromatography on the ISCO™ (40 g SiO2)
  10. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-312242b697d945d0ad77c840d28e9223
Source dataset
uspto-grants-2014_12
Patent number
US08907101B2

Reaction notes

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