Isoamyl Nitrite → 2-Bromo-5-fluorothioanisole

HRID 1513939Notes

Reaction equation

HRID 1513939 reaction equation
[Br:1][C:2]1[CH:8]=[CH:7][C:6]([F:9])=[CH:5][C:3]=1N.N(OCCC(C)C)=O.[CH3:18][S:19]SC>>[Br:1][C:2]1[CH:8]=[CH:7][C:6]([F:9])=[CH:5][C:3]=1[S:19][CH3:18]

Participants

4

Reactant 3

HCID 8053Isoamyl NitriteHCID 12232Dimethyl DisulfideHCID 27733172-Bromo-5-fluoroaniline

Product 1

HCID 117700132-Bromo-5-fluorothioanisoleYield 76%

Conditions

Temperature
75 °C

Procedure

Dissolve 2-bromo-5-fluoroaniline (25 g, 131 mmol) in methyldisulfide (220 mL) and heat to 75° C. under nitrogen. Add isoamyl nitrite (46 mL, 342 mmol) dropwise via an addition funnel trough a reflux condenser (˜1 drop/sec). Large exotherm may occur if addition is too fast. After addition is complete heat the reaction to 95° C. for 1 hour and cool to room temperature and concentrate in vacuo. Purify residue twice via silica gel chromatography eluting with hexanes to yield 22 g of 1-bromo-4-fluoro-2-methylsulfanyl-benzene (76%).

Workup

  1. additionLarge exotherm may occur if addition
  2. additionAfter addition
  3. temperatureis complete heat
  4. customthe reaction to 95° C. for 1 hour
  5. temperaturecool to room temperature
  6. concentrationconcentrate in vacuo
  7. washPurify residue twice via silica gel chromatography eluting with hexanes

Sources & evidence

ORD record
ord-2653373e833c49778344aa3fe3b3edab
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

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