Hexamethylenetetramine → 1,5-Naphthyridine-3-carbaldehyde

HRID 385598Notes

Reaction equation

HRID 385598 reaction equation
[CH3:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[N:9][CH:8]=[CH:7][CH:6]=2.BrN1C(=[O:18])CCC1=O.N(C(C)(C)C#N)=NC(C)(C)C#N.C1N2CN3CN(C2)CN1C3.[OH-].[Na+]>C1C=CC=CC=1.O.C(Cl)(Cl)Cl.C(O)(=O)C>[N:4]1[C:5]2[C:10](=[N:9][CH:8]=[CH:7][CH:6]=2)[CH:11]=[C:2]([CH:1]=[O:18])[CH:3]=1

Participants

10

Reactant 5

HCID 4101HexamethylenetetramineHCID 6547AzobisisobutyronitrileHCID 14798Sodium HydroxideHCID 67184N-bromobutanimide2×HCID 5888843-methyl-1,5-naphthyridine

Product 1

HCID 497616061,5-Naphthyridine-3-carbaldehydeYield 8.8%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 241BenzeneSolventHCID 962WaterSolventHCID 6212ChloroformSolvent

Procedure

To a solution of 0.26 g of 3-methyl-1,5-naphthyridine in 4 mL of benzene, 0.35 g of N-bromosuccinimide and 29 mg of azobisisobutyronitrile were added, and the mixture was heated under reflux while stirring for 2 hours 15 minutes. Thereto was further added 0.13 g of N-bromosuccinimide, and the mixture was heated under reflux while stirring for 30 minutes. After cooling to room temperature, a solution of 0.50 g of hexamethylenetetramine in 1.5 mL of water was dropped to the reaction mixture under cooling with ice, thereto was added 1.5 mL of acetic acid, and the mixture was heated under reflux while stirring for 1 hour 20 minutes. After cooling to room temperature, chloroform and a 20% aqueous sodium hydroxide solution were added to the reaction mixture and the mixture was adjusted to pH 8.5. The organic layer was separated, and the aqueous layer was extracted with chloroform. The organic layer and the extract were combined, the resultant solution was washed with water and a saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resultant residue was purified by flash silica gel column chromatography using an eluent of hexane:ethyl acetate=1:1 to obtain 25 mg of 1,5-naphthyridine-3-carbaldehyde as a slightly yellow solid.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux
  3. temperaturethe mixture was heated
  4. temperatureunder reflux
  5. stirringwhile stirring for 30 minutes
  6. temperatureunder cooling with ice
  7. temperaturethe mixture was heated
  8. temperatureunder reflux
  9. stirringwhile stirring for 1 hour 20 minutes
  10. temperatureAfter cooling to room temperature
  11. customThe organic layer was separated
  12. extractionthe aqueous layer was extracted with chloroform
  13. washthe resultant solution was washed with water
  14. dry with materiala saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate
  15. distillationThe solvent was distilled off under reduced pressure
  16. customthe resultant residue was purified by flash silica gel column chromatography

Sources & evidence

ORD record
ord-af2049c7e3dd436d96659a326adb68d9
Source dataset
uspto-grants-2013_02
Patent number
US08367831B2

Reaction notes

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