1-Methylpiperazine → 5-(4-Methylpiperazin-1-yl)-2-nitroaniline

HRID 2068987Notes

Reaction equation

HRID 2068987 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]([N+:9]([O-:11])=[O:10])=[C:6]([CH:8]=1)[NH2:7].[CH3:12][N:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1>C(O)C>[CH3:12][N:13]1[CH2:18][CH2:17][N:16]([C:2]2[CH:3]=[CH:4][C:5]([N+:9]([O-:11])=[O:10])=[C:6]([CH:8]=2)[NH2:7])[CH2:15][CH2:14]1

Participants

4

Reactant 2

HCID 531671-MethylpiperazineHCID 742185-Chloro-2-nitroaniline

Product 1

HCID 27600345-(4-Methylpiperazin-1-yl)-2-nitroanilineYield 99%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
-5 °C

Procedure

5-Chloro-2-nitroaniline (401 g, 2.32 mol) was added to a 4-neck 12 L round bottom flask fitted with an overhead stirrer, condenser, gas inlet, addition funnel, and thermometer probe. The flask was then purged with N2. 1-Methylpiperazine (977 g, 1.08 L, 9.75 mol) and 100% ethanol (650 mL) were added to the reaction flask with stirring. The flask was again purged with N2, and the reaction was maintained under N2. The flask was heated in a heating mantle to an internal temperature of 97° C. (+/−5° C.) and maintained at that temperature until the reaction was complete (typically about 40 hours) as determined by HPLC. After the reaction was complete, heating was discontinued and the reaction was cooled to an internal temperature of about 80° C. with stirring, and water (3.15 L) was added to the mixture via an addition funnel over the period of 1 hour while the internal temperature was maintained at 82° C. (+/−3° C.). After water addition was complete, heating was discontinued and the reaction mixture was allowed to cool over a period of no less than 4 hours to an internal temperature of 20-25° C. The reaction mixture was then stirred for an additional hour at an internal temperature of 20-30° C. The resulting mixture was then filtered, and the flask and filter cake were washed with water (1×1 L), 50% ethanol (1×1 L), and 95% ethanol (1×1 L). The golden yellow solid product was placed in a drying pan and dried to a constant weight of 546 g (99% yield) under vacuum at about 50° C. in a vacuum oven.

Workup

  1. customfitted with an overhead stirrer, condenser, gas inlet, addition funnel
  2. customThe flask was then purged with N2
  3. customThe flask was again purged with N2
  4. temperaturethe reaction was maintained under N2
  5. temperaturemaintained at that temperature until the reaction
  6. customtypically about 40 hours
  7. temperatureheating
  8. temperaturethe reaction was cooled to an internal temperature of about 80° C.
  9. stirringwith stirring
  10. additionwater (3.15 L) was added to the mixture via an addition funnel over the period of 1 hour while the internal temperature
  11. temperaturewas maintained at 82° C. (+/−3° C.)
  12. additionAfter water addition
  13. temperatureheating
  14. temperatureto cool over a period of no less than 4 hours to an internal temperature of 20-25° C
  15. stirringThe reaction mixture was then stirred for an additional hour at an internal temperature of 20-30° C
  16. filtrationThe resulting mixture was then filtered
  17. filtrationthe flask and filter cake
  18. washwere washed with water (1×1 L), 50% ethanol (1×1 L), and 95% ethanol (1×1 L)
  19. customdried to a constant weight of 546 g (99% yield) under vacuum at about 50° C. in a vacuum oven

Sources & evidence

ORD record
ord-f9d6044eb4404aae8e3f789d1c37a8f5
Source dataset
uspto-grants-2012_10
Patent number
US08299081B2

Reaction notes

Loading…