Nitric Acid → 3-Bromo-6-nitro-2-piperazin-1-yl-quinoline

HRID 1492112Notes

Reaction equation

HRID 1492112 reaction equation
[Br:1][C:2]1[C:3](Cl)=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2.[N:13]1(C=O)[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1.[N+:21]([O-])([OH:23])=[O:22]>C([O-])(O)=O.[Na+].C1COCC1.OS(O)(=O)=O.[OH-].[Na+]>[Br:1][C:2]1[C:3]([N:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([N+:21]([O-:23])=[O:22])=[CH:7][CH:6]=2

Participants

8

Reactant 3

HCID 944Nitric AcidHCID 821911-PiperazinecarboxaldehydeHCID 112187363-BROMO-2-CHLOROQUINOLINE

Product 1

HCID 102464403-Bromo-6-nitro-2-piperazin-1-yl-quinoline

Reagents, catalysts & solvents 4

HCID 1118Sulfuric AcidSolvent2×HCID 8028TetrahydrofuranSolventHCID 14798Sodium HydroxideSolvent2×HCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
120 °C

Procedure

A stirred mixture of 7 (200 mg, 0.83 mmol) and 1-Piperazinecarboxaldehyde (4 ml) was heated at 120° C. for 15 min. under argon. The mixture was then cooled and diluted with 0.5M NaHCO3. The aqueous phase was extracted with ether (3×) and the combined extractions were dried (MgSO4). Concentration yielded a residue which was immediately dissolved in THF (10 ml) and 4M H2SO4 (5 ml). The solution was then brought to reflux and stirred for 1 h. The solution was cooled and poured into 1M NaOH. The resulting suspension was then extracted twice with ether and the ether extracts were dried (MgSO4). Evaporation of the solvent afforded a material which was immediately dissolved in H2SO4 (5 ml). To this solution was added dropwise HNO3 (0.1 ml) at -10° C. The mixture was stirred 15 min. at -10° -0° C., poured onto ice, and diluted with 1M NaOH until basic. The mixture was then extracted with CH2C2 (3×), and the combined organic layers were dried (MgSO4). Concentration yielded the quipazine analogue 1 (189 mg, 68% based on 7). 1H NMR d (ppm): 1.9 br (NH), 3.1 dd (CH2), 3.5 dd (CH2), 7.8 d (CH arom), 8.3 s (CH arom), 8.3 d (CH arom), 8.5 s (CH arom).

Workup

  1. temperatureThe mixture was then cooled
  2. extractionThe aqueous phase was extracted with ether (3×)
  3. extractionthe combined extractions
  4. dry with materialwere dried (MgSO4)
  5. concentrationConcentration
  6. customyielded a residue which
  7. temperatureto reflux
  8. temperatureThe solution was cooled
  9. extractionThe resulting suspension was then extracted twice with ether
  10. dry with materialthe ether extracts were dried (MgSO4)
  11. customEvaporation of the solvent
  12. customafforded a material which
  13. stirringThe mixture was stirred 15 min. at -10° -0° C.
  14. additionpoured onto ice
  15. extractionThe mixture was then extracted with CH2C2 (3×)
  16. dry with materialthe combined organic layers were dried (MgSO4)
  17. concentrationConcentration

Sources & evidence

ORD record
ord-f64aab4469a44541b02a0990ce68300d
Source dataset
uspto-grants-1994_12
Patent number
US05372813

Reaction notes

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