Nitric Acid → 7-Bromo-6-nitro-2-piperazinylquinoline

HRID 1492118Notes

Reaction equation

HRID 1492118 reaction equation
[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8](Cl)=[N:9]2)=[CH:4][CH:3]=1.[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[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([N:13]3[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)=[N:9]2)=[CH:4][C:3]=1[N+:21]([O-:23])=[O:22]

Participants

8

Reactant 3

HCID 944Nitric AcidHCID 821911-PiperazinecarboxaldehydeHCID 142210347-Bromo-2-chloroquinoline

Product 1

HCID 99743107-Bromo-6-nitro-2-piperazinylquinoline

Reagents, catalysts & solvents 4

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

Conditions

Temperature
125 °C

Procedure

A stirred mixture of 19 (70 mg, 0.29 mmol) and 1-Piperazinecarboxaldehyde (4 ml) was heated at 125° C. for 30 min. under argon. The mixture was then cooled and diluted with saturated aqueous 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 CH2Cl2 (3×), and the combined organic layers were dried (MgSO4). Concentration yielded the quipazine analogue 3 (47 mg, 48% from 19). 1H NMR d (ppm): 1.60 s (NH), 3.00 dd (CH2), 3.80 dd (CH2), 7.04 d (CH arom), 7.87 d (CH arom), 7.95 s (CH arom), 8.24 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 CH2Cl2 (3×)
  16. dry with materialthe combined organic layers were dried (MgSO4)
  17. concentrationConcentration

Sources & evidence

ORD record
ord-d97b878d95334f0289a2366f4b8d82dd
Source dataset
uspto-grants-1994_12
Patent number
US05372813

Reaction notes

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