Piperazine → [3-(Methylsulphanylmethyl)phenyl]piperazine

HRID 1266162Notes

Reaction equation

HRID 1266162 reaction equation
I[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][S:9][CH3:10])[CH:3]=1.CC(C)([O-])C.[Na+].[NH:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1>C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C1(C)C=CC=CC=1>[CH3:10][S:9][CH2:8][C:4]1[CH:3]=[C:2]([N:17]2[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]2)[CH:7]=[CH:6][CH:5]=1

Participants

6

Reactant 3

HCID 4837PiperazineHCID 109452871-Iodo-3-(methylsulphanylmethyl)benzeneHCID 23676156Sodium t-butoxide

Product 1

HCID 18549162[3-(Methylsulphanylmethyl)phenyl]piperazineYield 31.8%

Reagents, catalysts & solvents 2

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
900 °C

Procedure

A mixture of 2.5 g of 1-iodo-3-(methylsulphanylmethyl)benzene, 1.3 g of sodium tert-butoxide, 0.35 mg of [1,1′-bis(diphenylphosphino)ferrocenyl]palladium chloride, 0.79 g of 1,1′-bis(diphenylphosphino)ferrocene, 4 g of piperazine and 100 cm3 of toluene was heated at 900° C. under a nitrogen stream for 24 hours. The reaction mixture was cooled to room temperature and filtered through sintered glass. The filtrate was washed with 250 cm3 of dichloromethane and then concentrated to dryness under reduced pressure (2.7 kPa). The residue obtained was purified by silica gel column chromatography (particle size 0.04-0.06 mm, diameter 4 cm, height 20 cm) under a pressure of 0.5 bar of nitrogen with a mixture of dichloromethane and methanol (90/10 by volume) and then a mixture of dichloromethane and methanol (85/15 by volume) as eluents, 100-cm3 fractions were collected. Fractions 29 to 36 were combined and concentrated to dryness under reduced pressure (2.7 kPa). The oil obtained was distilled in a bulb oven (B.p.=160° C. approximately under a pressure of 0.1 mm of mercury). 0.67 g of 4-[3-(methylsulphanylmethyl)phenyl]piperazine was obtained in the form of a colorless oil.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered through sintered glass
  3. washThe filtrate was washed with 250 cm3 of dichloromethane
  4. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  5. customThe residue obtained
  6. customwas purified by silica gel column chromatography (particle size 0.04-0.06 mm, diameter 4 cm, height 20 cm) under a pressure of 0.5 bar of nitrogen with a mixture of dichloromethane and methanol (90/10 by volume)
  7. additiona mixture of dichloromethane and methanol (85/15 by volume) as eluents
  8. custom100-cm3 fractions were collected
  9. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  10. customThe oil obtained
  11. distillationwas distilled in a bulb oven (B.p.=160° C. approximately under a pressure of 0.1 mm of mercury)

Sources & evidence

ORD record
ord-ea71301e869f49cfa01e1a3f1be68583
Source dataset
uspto-grants-2003_04
Patent number
US06548506B2

Reaction notes

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