Sulfuric Acid → Ibuprofen, (+-)-

HRID 903112Notes

Reaction equation

HRID 903112 reaction equation
C[O:2][C:3]([CH:5]([C:7]1[CH:16]=[CH:15][C:10]([CH2:11][CH:12]([CH3:14])[CH3:13])=[CH:9][CH:8]=1)[CH3:6])=[O:4].[OH-].[Na+].C(C1C=CC(C(=O)CC)=CC=1)C(C)C.S(=O)(=O)(O)O>CCCCCC.CO>[OH:4][C:3]([CH:5]([C:7]1[CH:8]=[CH:9][C:10]([CH2:11][CH:12]([CH3:13])[CH3:14])=[CH:15][CH:16]=1)[CH3:6])=[O:2]

Participants

7

Reactant 4

HCID 1118Sulfuric AcidHCID 14798Sodium Hydroxide2×HCID 1088341-(4-(2-Methylpropyl)phenyl)-1-propanoneHCID 109101Ibuprofen methyl ester

Product 1

HCID 3672Ibuprofen, (+-)-

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8058HexaneSolvent2×

Procedure

A 5.11 g. portion of the crude ibuprofen methyl ester prepared as described above was dissolved in 20 ml. of hexane and 12 ml. of methanol and cooled to 0° to 5° C. Then 6.0 g. (75 mmole) of a 50% sodium hydroxide solution was added and the resulting mixture was heated under reflux for 2 hours. On cooling, the mixture was transferred to a separatory funnel with about 50 ml. of 1 N sodium hydroxide solution and hexane. The hexane layer was extracted with about 10 ml. of 1 N aqueous sodium hydroxide and the combined aqueous layer was extracted with 50 ml. of fresh hexane. The neutral fraction isolated from the combined hexane extracts consisted primarily of p-isobutylpropiophenone. The aqueous layer was acidified with 50% aqueous sulfuric acid and extracted 3 times with 50 ml. portions of hexane. The combined hexane extracts were washed 3 times with 50 ml. portions of water and dried over sodium sulfate. Removal of solvent by vacuum evaporation gave crude ibuprofen as a pale yellow solid, weighing 4.20 g., having a purity of 96.7% by Glc analysis, again the impurities being about 1.4% p-isobutylbenzoic acid and 1.1% of the meta isomer of ibuprofen. The crude yield was 80.8% of theory. Recrystallization of the crude ibuprofen from hexane (2 ml./g.) gave 3.44 g. (70.3% chemical yield) ibuprofen.

Workup

  1. dissolutionabove was dissolved in 20 ml
  2. temperaturethe resulting mixture was heated
  3. temperatureunder reflux for 2 hours
  4. temperatureOn cooling
  5. customthe mixture was transferred to a separatory funnel with about 50 ml
  6. extractionThe hexane layer was extracted with about 10 ml
  7. extractionof 1 N aqueous sodium hydroxide and the combined aqueous layer was extracted with 50 ml
  8. customThe neutral fraction isolated from the combined hexane
  9. extractionextracted 3 times with 50 ml
  10. washThe combined hexane extracts were washed 3 times with 50 ml
  11. dry with materialportions of water and dried over sodium sulfate
  12. customRemoval of solvent
  13. customby vacuum evaporation

Sources & evidence

ORD record
ord-569fbe985b7f43fdab1ebdb90e4d972a
Source dataset
uspto-grants-1980_10
Patent number
US04226790

Reaction notes

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