1-Bromo-3-chloropropane → 1-(3-Chlorophenyl)-4-(3-chloropropyl)piperazine hydrochloride

HRID 1075395Notes

Reaction equation

HRID 1075395 reaction equation
[OH-].[Na+].Cl.[Cl:4][C:5]1[CH:6]=[C:7]([N:11]2[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)[CH:8]=[CH:9][CH:10]=1.Br[CH2:18][CH2:19][CH2:20][Cl:21]>CC(C)=O>[ClH:4].[Cl:21][CH2:20][CH2:19][CH2:18][N:14]1[CH2:15][CH2:16][N:11]([C:7]2[CH:8]=[CH:9][CH:10]=[C:5]([Cl:4])[CH:6]=2)[CH2:12][CH2:13]1

Participants

5

Reactant 3

HCID 80061-Bromo-3-chloropropaneHCID 14798Sodium HydroxideHCID 256811-(3-Chlorophenyl)piperazine monohydrochloride

Product 1

HCID 130351201-(3-Chlorophenyl)-4-(3-chloropropyl)piperazine hydrochlorideYield 111%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A 25% NaOH solution (320 ml, 2.0 mol) is added dropwise to a stirred solution of 1-(3-chlorophenyl)-piperazine hydrochloride (196.5 g, 1.0 mol) and 1-bromo-3-chloropropane (99.0 ml, 1.0 mol) in acetone (200 ml) while maintaining temperature of 0°-10° C. After the addition is completed, the mixture is allowed to warm to room temperature and is stirred for 18 hours. The upper organic phase is then separated and concentrated under reduced pressure. The residual oil is taken up in 250 ml acetone and filtered. The filtrate is concentrated under reduced pressure and the oily residue is dissolved in 1 l of 15% boiling HCl solution. A viscous oil is separated from the cooled mixture and poured into 1 l of ice-H2O with vigorous stirring, forming white precipitates. Recrystallization of the solid from boiling water gave 171.8 g (55.6% yield) of 1-(3-Chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride; m.p 199.5-200.5° C. 1H nmr (d-DMSO) δ 11.55 (bs, 1H, HCl), 7.29 (t, 1H, J=8.1 Hz, phenyl H), 7.08 (t, 1H, J=2.0 Hz, phenyl H), 6.99 (dd, 1H, J=2.1, 8.3 Hz, phenyl H), 6.89 (dd, 1H, J=1.5, 7.7 Hz, phenyl H), 3.90 (d, 2H, J=12.8 Hz, CH2), 3.80 (t, 2H. J=6.4 Hz, CH2), 3.58 (d, 2H, J=11.4 Hz, CH2), 3.09-3.41 (overlapping 8H, CH2), 2.30 (m, 2H, CH2); 13C nmr (d-DMSO) δ 150.8, 134.0, 130.7, 119.2, 115.3, 114.2, 53.3, 50.5, 44.8, 42.5, 26.2.

Workup

  1. temperaturewhile maintaining temperature of 0°-10° C
  2. additionAfter the addition
  3. customThe upper organic phase is then separated
  4. concentrationconcentrated under reduced pressure
  5. filtrationfiltered
  6. concentrationThe filtrate is concentrated under reduced pressure
  7. dissolutionthe oily residue is dissolved in 1 l of 15%
  8. customA viscous oil is separated from the cooled mixture
  9. additionpoured into 1 l of ice-H2O with vigorous stirring
  10. customforming white precipitates
  11. customRecrystallization of the solid

Sources & evidence

ORD record
ord-3b6d948e44cd41498c5c42891abf82f7
Source dataset
uspto-grants-1999_05
Patent number
US05900485

Reaction notes

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