Toluene → alpha-Tocopherol

HRID 1734316Notes

Reaction equation

HRID 1734316 reaction equation
[CH3:1][C:2]1[C:3]([OH:11])=[C:4]([CH3:10])[C:5]([CH3:9])=[C:6]([CH:8]=1)O.[CH3:12][CH:13]([CH2:15][CH2:16][CH2:17][CH:18]([CH2:20][CH2:21][CH2:22][CH:23]([CH2:25][CH2:26][CH2:27][C:28]([OH:32])([CH:30]=[CH2:31])[CH3:29])[CH3:24])[CH3:19])[CH3:14].C1(C)C=CC=CC=1>C(OCC)(=O)C.FC(F)(F)S([O-])(=O)=O.[Sc+3].FC(F)(F)S([O-])(=O)=O.FC(F)(F)S([O-])(=O)=O>[CH3:10][C:4]1[C:3]([OH:11])=[C:2]([CH3:1])[C:8]2[CH2:31][CH2:30][C@:28]([CH2:27][CH2:26][CH2:25][C@@H:23]([CH2:22][CH2:21][CH2:20][C@@H:18]([CH2:17][CH2:16][CH2:15][CH:13]([CH3:12])[CH3:14])[CH3:19])[CH3:24])([CH3:29])[O:32][C:6]=2[C:5]=1[CH3:9]

Participants

6

Reactant 3

HCID 1140TolueneHCID 10453Isophytol2×HCID 12785Trimethylhydroquinone2×

Product 1

HCID 14985alpha-TocopherolYield 99.2%

Reagents, catalysts & solvents 2

HCID 2734571Scandium(III) triflateCatalystHCID 8857Ethyl AcetateSolvent2×

Procedure

Suspended in 20 ml of ethyl acetate were 10.0 g (65.8 mmol) of trimethylhydroquinone (TMH) and 0.32 g (0.658 mmol) of scandium trifluoromethanesulfonate, followed by heating under reflux for 10 minutes under an argon gas stream. After a solution of 20.3 g (68.4 mmol) of isophytol in 20 ml of ethyl acetate was added dropwise over 30 minutes under heating and reflux, TMH and isophytol were reacted for 3 hours. The reaction mixture was cooled, to which 100 ml of toluene were added. The resulting mixture was washed twice with 200-ml portions of water and then concentrated under reduced pressure. The residue was added with 100 ml of toluene and 100 ml of 2-butanone. The organic layer was washed twice with 200-ml portions of a 1N aqueous solution of sodium hydroxide and then with 200 ml of a saturated aqueous solution of sodium chloride. The organic layer was then dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column (eluent: n-hexane-diethyl ether system), whereby 28.1 g of the title compound were obtained in the form of a brown oil. (Yield: 99%, GLC purity: 95%)

Workup

  1. temperatureby heating
  2. temperatureunder reflux for 10 minutes under an argon gas stream
  3. temperatureunder heating
  4. temperaturereflux
  5. additionwere added
  6. washThe resulting mixture was washed twice with 200-ml portions of water
  7. concentrationconcentrated under reduced pressure
  8. additionThe residue was added with 100 ml of toluene and 100 ml of 2-butanone
  9. washThe organic layer was washed twice with 200-ml portions of a 1N aqueous solution of sodium hydroxide
  10. dry with materialThe organic layer was then dried over magnesium sulfate
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by chromatography on a silica gel column (eluent: n-hexane-diethyl ether system)

Sources & evidence

ORD record
ord-f86dfee1228541589c00c86111ce0fcc
Source dataset
uspto-grants-1996_07
Patent number
US05532387

Reaction notes

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