Benzyl Alcohol → Benzenamine, N-(2-methylpropyl)-2-nitro-5-(phenylmethoxy)-

HRID 1430416Notes

Reaction equation

HRID 1430416 reaction equation
[CH2:1]([NH2:5])[CH:2]([CH3:4])[CH3:3].F[C:7]1[CH:12]=[C:11](F)[CH:10]=[CH:9][C:8]=1[N+:14]([O-:16])=[O:15].[CH2:17]([OH:24])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(=O)([O-])[O-].[K+].[K+]>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.O.C1(C)C=CC=CC=1>[CH2:17]([O:24][C:11]1[CH:12]=[CH:7][C:8]([N+:14]([O-:16])=[O:15])=[C:9]([CH:10]=1)[NH:5][CH2:1][CH:2]([CH3:4])[CH3:3])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

8

Reactant 4

HCID 244Benzyl AlcoholHCID 6558IsobutylamineHCID 11430Potassium CarbonateHCID 679672,4-Difluoronitrobenzene

Product 1

HCID 67954014Benzenamine, N-(2-methylpropyl)-2-nitro-5-(phenylmethoxy)-Yield 81%

Reagents, catalysts & solvents 3

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 962WaterSolvent3×HCID 1140TolueneSolvent2×

Conditions

Temperature
37.5 °C

Procedure

Isobutylamine (25 mL, 121 mmol) was added dropwise to a toluene solution (40 mL) of 2,4-difluoronitrobenzene (8.0 g, 50.3 mmol) under ice cooling, and the mixture was stirred at 35-40° C. for 2 hours. Water was added to the reaction solution, and toluene extraction was performed, followed by washing with water. The resulting organic layer was concentrated under reduced pressure until reduced to about half (the concentrated solution including a crude product of 5-fluoro-N-isobutyl-2-nitroaniline). Benzyl alcohol (10.4 mL, 100 mmol), tetrabutyl ammonium hydrogen sulfate (1.71 g, 5.0 mmol), potassium carbonate (10.42 g, 75.4 mmol), and water (0.8 mL) were added to the resulting solution, and the mixture was heated under reflux for 3 hours. After the reaction solution was cooled, water (84 mL) was added thereto, followed by toluene extraction. After the resulting organic layer was washed with water, the solvent was distilled off, and cyclopentyl ether was added to the resulting residue. The mixture was stirred for 1 hour. Precipitated crystals were collected by filtration, and the resulting crystals were dried at 50° C., thereby obtaining 12.2 g of a yellow, powdery target compound (yield: 81%).

Workup

  1. washby washing with water
  2. concentrationThe resulting organic layer was concentrated under reduced pressure
  3. temperaturethe mixture was heated
  4. temperatureunder reflux for 3 hours
  5. temperatureAfter the reaction solution was cooled
  6. extractionfollowed by toluene extraction
  7. washAfter the resulting organic layer was washed with water
  8. distillationthe solvent was distilled off
  9. additioncyclopentyl ether was added to the resulting residue
  10. stirringThe mixture was stirred for 1 hour
  11. customPrecipitated crystals
  12. filtrationwere collected by filtration
  13. customthe resulting crystals were dried at 50° C.

Sources & evidence

ORD record
ord-b16c9a8fabfe44a6b0aab28f59186bc3
Source dataset
uspto-grants-2015_01
Patent number
US08940889B2

Reaction notes

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