Benzyl Alcohol → 5-benzyloxy-N-methyl-2-nitroaniline

HRID 1430404Notes

Reaction equation

HRID 1430404 reaction equation
[CH3:1][NH2:2].F[C:4]1[CH:9]=[C:8](F)[CH:7]=[CH:6][C:5]=1[N+:11]([O-:13])=[O:12].[CH2:14]([OH:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=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>[CH2:14]([O:21][C:8]1[CH:7]=[CH:6][C:5]([N+:11]([O-:13])=[O:12])=[C:4]([CH:9]=1)[NH:2][CH3:1])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

8

Reactant 4

HCID 244Benzyl AlcoholHCID 6329MethylamineHCID 11430Potassium CarbonateHCID 679672,4-Difluoronitrobenzene

Product 1

HCID 679540515-benzyloxy-N-methyl-2-nitroanilineYield 95%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
37.5 °C

Procedure

An aqueous solution of 40% methyl amine (82 mL, 0.94 mol) was added dropwise to a toluene solution (500 mL) of 2,4-difluoronitrobenzene (50.0 g, 0.31 mol) under ice cooling, and the mixture was stirred for 2 hours at 35 to 40° C. 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. Benzyl alcohol (65 mL, 0.63 mol), tetrabutyl ammonium hydrogen sulfate (10.7 g, 31.5 mmol), potassium carbonate (65.2 g, 0.47 mol) and water (5 mL) were added to the resulting solution, and the resulting mixture was heated under reflux for 4 hours. After the reaction solution was cooled, water (250 mL) was added thereto, and the mixture was stirred at 70° C. for 1 hour. The mixture was stirred under ice cooling for 30 minutes, and then precipitated crystals were collected by filtration. After the resulting crystals were washed with water, methanol (500 mL) was added. The mixture was heated under reflux for 30 minutes, and then stirred at 10° C. or less for 1 hour. Precipitated crystals were collected by filtration, and then washed with methanol (100 mL). The resulting crystals were dried at 50° C., thereby obtaining 76.9 g of an orange, powdery 5-benzyloxy-N-methyl-2-nitroaniline (yield: 95%).

Workup

  1. washby washing with water
  2. concentrationThe resulting organic layer was concentrated under reduced pressure
  3. temperaturethe resulting mixture was heated
  4. temperatureunder reflux for 4 hours
  5. temperatureAfter the reaction solution was cooled
  6. stirringthe mixture was stirred at 70° C. for 1 hour
  7. stirringThe mixture was stirred under ice cooling for 30 minutes
  8. customprecipitated crystals
  9. filtrationwere collected by filtration
  10. washAfter the resulting crystals were washed with water, methanol (500 mL)
  11. additionwas added
  12. temperatureThe mixture was heated
  13. temperatureunder reflux for 30 minutes
  14. stirringstirred at 10° C. or less for 1 hour
  15. customPrecipitated crystals
  16. filtrationwere collected by filtration
  17. washwashed with methanol (100 mL)
  18. customThe resulting crystals were dried at 50° C.

Sources & evidence

ORD record
ord-3a0c7f17d4364b32aef27ccd77bc1e58
Source dataset
uspto-grants-2015_01
Patent number
US08940889B2

Reaction notes

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