Sulfuric Acid → Ibuprofen, (+-)-

HRID 2163604Notes

Reaction equation

HRID 2163604 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 1N sodium hydroxide solution and hexane. The hexane layer was extracted with about 10 ml. of 1N 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 1N 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-257af4ea6d284c709feed2083243b229
Source dataset
uspto-grants-1979_01
Patent number
US04135051

Reaction notes

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