Iodine → 4-Fluoro-2-iodo-5-methylaniline

HRID 1027992Notes

Reaction equation

HRID 1027992 reaction equation
[F:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[CH3:9].C(=O)(O)[O-].[Na+].[I:15]I>CO.O>[F:1][C:2]1[C:3]([CH3:9])=[CH:4][C:5]([NH2:6])=[C:7]([I:15])[CH:8]=1

Participants

6

Reactant 3

HCID 807IodineHCID 679814-Fluoro-m-toluidineHCID 516892Sodium Bicarbonate

Product 1

HCID 250673514-Fluoro-2-iodo-5-methylanilineYield 69%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Procedure

Into a solution of 4-fluoro-3-methylaniline (8.75 g, 70 mmol) in methanol (65 mL) and water (65 mL) was added sodium bicarbonate (5.88 g, 70 mmol) followed by portionwise addition of powdered I2 (17.78 g, 70 mmol). The mixture was stirred at room temperature overnight then treated with water (300 mL). The aqueous mixture was extracted with CH2Cl2 (3×200 mL). The organics were combined and washed with sat. aq. sodium thiosulfate, water, and brine. The mixture was dried over Na2SO4 and concentrated. The residue was purified by flash chromatography with 30-100% CH2Cl2/hexane to give 4-fluoro-2-iodo-5-methylaniline (12.1 g, 69%), which contained ˜10% of the undesired isomer (4-fluoro-2-iodo-3-methylaniline).

Workup

  1. extractionThe aqueous mixture was extracted with CH2Cl2 (3×200 mL)
  2. washwashed with sat. aq. sodium thiosulfate, water, and brine
  3. dry with materialThe mixture was dried over Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by flash chromatography with 30-100% CH2Cl2/hexane

Sources & evidence

ORD record
ord-8e21810e766f42c68dde7942b9df4d50
Source dataset
uspto-grants-2014_05
Patent number
US08735414B2

Reaction notes

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