Hydrochloric Acid → 1-(3-Chlorophenyl)-4-(3-chloropropyl)-piperazine

HRID 851694Notes

Reaction equation

HRID 851694 reaction equation
[OH-].[Na+].Cl.ClC1C=C(N2CCNCC2)C=CC=1.BrCCCCl.Cl.Cl.[Cl:24][CH2:25][CH2:26][CH2:27][N:28]1[CH2:33][CH2:32][N:31]([C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([Cl:40])[CH:35]=2)[CH2:30][CH2:29]1>CC(C)=O.O>[Cl:24][CH2:25][CH2:26][CH2:27][N:28]1[CH2:33][CH2:32][N:31]([C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([Cl:40])[CH:35]=2)[CH2:30][CH2:29]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 80061-Bromo-3-chloropropaneHCID 14798Sodium Hydroxide2×HCID 256811-(3-Chlorophenyl)piperazine monohydrochlorideHCID 130351201-(3-Chlorophenyl)-4-(3-chloropropyl)piperazine hydrochloride

Product 1

HCID 1014441-(3-Chlorophenyl)-4-(3-chloropropyl)-piperazine

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent

Procedure

A 50% sodium hydroxide solution (430.6 g., 5.333 mole) is added dropwise to a stirred solution of 1-(3-chlorophenyl)piperazine hydrochloride (502.0 g., 2.153 mole) and 1-bromo-3-chloropropane (339.0 g., 2.153 mole) in 435 ml. water and 535 ml. acetone while maintaining temperature of 0°-10° C. Stirring is continued for a 16 hr. period at room temperature and the upper organic phase then separated and concentrated under reduced pressure. The remaining residual oil is taken up in 500 ml. acetone, filtered and the filtrate concentrated under reduced pressure to an oily residue which is dissolved in boiling dilute hydrochloric acid (1.67 liter water plus 280 ml. concentrated HCl, 3.36 mole). The oil which initially separates from the cooled acid solution, solidifies on standing and is collected, rinsed with cold water and air dried. Crystallization of this material from water employing activated charcoal affords 438.4 g. (66%) of 1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride, m.p. 196.5°-198.5° C. The hydrochloride salt is converted to the free base with aqueous 10% sodium hydroxide and recovered by extracting with ether (dried over magnesium sulfate). Concentration of the etheral extract affords 1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine free base as an oily residue.

Workup

  1. customperiod at room temperature and the upper organic phase then separated
  2. concentrationconcentrated under reduced pressure
  3. filtrationacetone, filtered
  4. concentrationthe filtrate concentrated under reduced pressure to an oily residue which
  5. dissolutionis dissolved
  6. customis collected
  7. washrinsed with cold water and air
  8. customdried
  9. customCrystallization of this material from water employing activated charcoal
  10. customaffords 438.4 g
  11. customrecovered
  12. extractionby extracting with ether (dried over magnesium sulfate)
  13. extractionConcentration of the etheral extract

Sources & evidence

ORD record
ord-b1017521c029497fa7959ceaee32b117
Source dataset
uspto-grants-1983_05
Patent number
US04386091

Reaction notes

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