Methanesulfonic Acid → 1,2-Difluoro-4-(methylsulfonyl)benzene

HRID 1931558Notes

Reaction equation

HRID 1931558 reaction equation
S(Cl)(Cl)=O.[CH3:5][S:6]([OH:9])(=O)=[O:7].[F:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[F:17].FC(F)(F)S(O)(=O)=O>>[F:10][C:11]1[CH:16]=[CH:15][C:14]([S:6]([CH3:5])(=[O:9])=[O:7])=[CH:13][C:12]=1[F:17]

Participants

5

Reactant 4

HCID 6395Methanesulfonic AcidHCID 97061,2-DifluorobenzeneHCID 24386Thionyl ChlorideHCID 62406Trifluoromethanesulfonic acid

Product 1

HCID 27827431,2-Difluoro-4-(methylsulfonyl)benzeneYield 59%

Conditions

Temperature
80 °C

Procedure

A mixture of thionyl chloride (12.73 mL, 0.175 mol) and methanesulfonic acid (28.4 mL, 0.438 mol) was heated at reflux overnight and then cooled to 80° C. 1,2-Difluorobenzene (8.64 mL, 88 mmol) was and trifluoromethanesulfonic acid (0.675 mL, 8.8 mmol) were added dropwise. The reaction mixture was then heated at 120° C. for 3 h, cooled to room temperature and poured into ice-water (200 mL). The mixture was extracted three times with ethyl acetate and the combined organic extracts were dried (sodium sulfate), filtered, evaporated, and purified by flash chromatography, eluting with 15% ethyl acetate/hexanes, to give 1,2-difluoro-4-methanesulfonyl-benzene (9.98 g, 59%) as a white solid. 1H NMR (300 MHz, CDCl3) δ 3.27 (s, 3H), 7.70-7.84 (m, 2H), 8.02-8.09 (m, 1H).

Workup

  1. temperaturewas heated
  2. temperatureat reflux overnight
  3. temperatureThe reaction mixture was then heated at 120° C. for 3 h
  4. temperaturecooled to room temperature
  5. extractionThe mixture was extracted three times with ethyl acetate
  6. dry with materialthe combined organic extracts were dried (sodium sulfate)
  7. filtrationfiltered
  8. customevaporated
  9. custompurified by flash chromatography
  10. washeluting with 15% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-15c5a20739dc43c78adbe48c986e6ad6
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

Loading…