Benzenesulfonyl chloride → 1-(Benzenesulfonyl)-2-(2,6-difluorophenyl)benzimidazole

HRID 2182081Notes

Reaction equation

HRID 2182081 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[NH:10][C:11]2[CH:17]=[CH:16][CH:15]=[CH:14][C:12]=2[N:13]=1.[H-].[Na+].[C:20]1([S:26](Cl)(=[O:28])=[O:27])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C1COCC1.C(OC(=O)C)C>[C:20]1([S:26]([N:13]2[C:12]3[CH:14]=[CH:15][CH:16]=[CH:17][C:11]=3[N:10]=[C:9]2[C:3]2[C:4]([F:8])=[CH:5][CH:6]=[CH:7][C:2]=2[F:1])(=[O:28])=[O:27])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

6

Reactant 3

HCID 7369Benzenesulfonyl chlorideHCID 24758Sodium hydrideHCID 16536142-(2,6-difluorophenyl)-1H-benzimidazole

Product 1

HCID 4688601-(Benzenesulfonyl)-2-(2,6-difluorophenyl)benzimidazoleYield 83%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-(2,6-difluorophenyl)benzimidazole (Example 12) (0.31 g, 1.34 mmol) dissolved in THF (5 mL) was added to NaH (0.10 g, 190 M %). After 5 min, benzenesulfonyl chloride (0.25 mL, 0.35 g, 2.00 mmol, 150 M %) was added. After stirring for 2 h, the reaction was dissolved in ethylacetate, and washed with NaHCO3 (sat. aq.) and NaCl (sat. aq.). The combined washings were dried (Na2SO4), filtered, and concentrated. The product was purified by flash chromatography eluting with 2% MeOH/CH2Cl2 and then recrystallized from diethylether/hexane (3:1), to yield white powders of 1-benzenesulfonyl-2-(2,6-difluorophenyl)benzimidazole (0.41 g, (1.10 mmol, 83% yield). M.p. 104-106° C. 1H-NMR (300 MHz, CD2Cl2): δ 8.09 (m, 1H, PhSO2), 7.77 (m, 1H, PhSO2), 7.69 (m, 2H, PhSO2), 7.66-7.53 (m, 2H, H4,7), 7.51-7.39 (m, 4H, PhSO2, H3,5), 7.07 (m, 2H, H3′,5′).

Workup

  1. washwashed with NaHCO3 (sat. aq.) and NaCl (sat. aq.)
  2. dry with materialThe combined washings were dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe product was purified by flash chromatography
  6. washeluting with 2% MeOH/CH2Cl2
  7. customrecrystallized from diethylether/hexane (3:1)

Sources & evidence

ORD record
ord-bb8684bfdd054aa4bd6970fefe6fd9bc
Source dataset
uspto-grants-2005_05
Patent number
US06894068B2

Reaction notes

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