Piperazine → 4-[(Piperazin-1-yl)methyl]benzonitrile

HRID 2119359Notes

Reaction equation

HRID 2119359 reaction equation
[NH:1]1[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.Cl.CCO.Br[CH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]#[N:20])=[CH:15][CH:14]=1>CCO>[C:19]([C:16]1[CH:17]=[CH:18][C:13]([CH2:12][N:1]2[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]2)=[CH:14][CH:15]=1)#[N:20]

Participants

5

Reactant 3

HCID 4837PiperazineHCID 869964-(Bromomethyl)benzonitrileHCID 21887872Ethanol hydrochloride

Product 1

HCID 20608924-[(Piperazin-1-yl)methyl]benzonitrile

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of piperazine (5.17 g, 60 mmol, 2 equiv) in EtOH (40 mL) was added 1 M HCl-EtOH (60 mL) dropwise over 1 h and the suspension was heated to 70° C. for 1 h. α-Bromo-p-tolunitrile (5.88 g, 30 mmol, 1 equiv) was added and the reaction was heated to reflux for 16 h. After cooling the solvent was removed by rotary evaporation and the residue was partitioned between CH2Cl2 (70 mL) and 2N aqueous KOH (70 mL) and the combined organic phase was washed with saturated aqueous NaCl (100 mL) and dried (MgSO4). Chromatography (SiO2, 20% CH3OH-5% Et3N-CH2Cl2) afforded the monoalkylated material (2.6 g, 6.0 g theoretical, 43%) as an amber oil.

Workup

  1. additionwas added
  2. temperaturethe reaction was heated
  3. temperatureto reflux for 16 h
  4. temperatureAfter cooling the solvent
  5. customwas removed by rotary evaporation
  6. customthe residue was partitioned between CH2Cl2 (70 mL) and 2N aqueous KOH (70 mL)
  7. washthe combined organic phase was washed with saturated aqueous NaCl (100 mL)
  8. dry with materialdried (MgSO4)
  9. customChromatography (SiO2, 20% CH3OH-5% Et3N-CH2Cl2) afforded the monoalkylated material (2.6 g, 6.0 g theoretical, 43%) as an amber oil

Sources & evidence

ORD record
ord-548f5bea9ca446768e162c4100be0282
Source dataset
uspto-grants-2004_02
Patent number
US06686353B1

Reaction notes

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