Water → 5-Bromo-2-methanesulfonylpyridine

HRID 423515Notes

Reaction equation

HRID 423515 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=1.[CH3:9][S-].[Na+].O.O[O:14][S:15]([O-:17])=O.[K+]>CN(C=O)C.CC(C)=O>[Br:8][C:5]1[CH:6]=[CH:7][C:2]([S:15]([CH3:9])(=[O:17])=[O:14])=[N:3][CH:4]=1

Participants

7

Reactant 4

HCID 962Water3×HCID 693532,5-DibromopyridineHCID 4378561Sodium methanethiolateHCID 23707502Potassium hydroxy sulfite

Product 1

HCID 134334245-Bromo-2-methanesulfonylpyridineYield 54%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 2,5-dibromopyridine (1.0 g, 4.22 mmol) in DMF (15 mL) was treated with sodium thiomethoxide (0.69 g, 95%, 9.29 mmol) at ambient temperature. The reaction mixture was stirred for 30 minutes, was diluted water and then extracted with ether. The combined organic extract was washed with brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give crude sulfide as a colorless oil. The crude sulfide was dissolved in acetone (120 mL) and was treated with water (50 mL) followed by Oxone® (7.80 g, 12.7 mmol). The reaction mixture was stirred at ambient temperature for 2 h. After more water was added, the mixture was extracted with ether (200 mL) and EtOAc (150 mL). The organic layers were combined and washed with water and brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give the crude product as a light brown oil. The crude product was purified by chromatography on ISCO silica gel column eluted with a 0 to 45% EtOAc:hexane gradient to give 0.54 g (54% from 2,5-dibromopyridine) of 5-bromo-2-(methylsulfonyl)pyridine as a white solid. 1H NMR (400 MHz, CDCl3): δ 8.78 (d, 1H, J=2.2 Hz), 8.10 (dd, 1H, Ja=8.3 Hz, Jb=2.2 Hz), 7.98 (d, 1H, J=8.3 Hz), 3.22 (s, 3H); LRMS (ESI), m/z 236/238 (M+H).

Workup

  1. extractionextracted with ether
  2. extractionThe combined organic extract
  3. washwas washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated
  7. customto give crude sulfide as a colorless oil
  8. stirringThe reaction mixture was stirred at ambient temperature for 2 h
  9. extractionthe mixture was extracted with ether (200 mL) and EtOAc (150 mL)
  10. washwashed with water and brine
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. concentrationthe filtrate was concentrated
  14. customto give the crude product as a light brown oil
  15. customThe crude product was purified by chromatography on ISCO silica gel column
  16. washeluted with a 0 to 45% EtOAc

Sources & evidence

ORD record
ord-826731d2f89c43c7ab766035d21298a3
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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