Benzene → (-)-Dihydroquinine

HRID 839514Notes

Reaction equation

HRID 839514 reaction equation
C1C=CC=CC=1.[CH3:7][CH2:8][CH:9]1[CH:14]2[CH2:15][CH:16]([C@@H:17]([OH:30])[C:18]3[CH:19]=[CH:20][N:21]=[C:22]4[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][C:23]=34)[N:11]([CH2:12][CH2:13]2)[CH2:10]1>CO>[CH3:7][CH2:8][C@@H:9]1[C@@H:14]2[CH2:15][C@@H:16]([C@H:17]([OH:30])[C:18]3[CH:19]=[CH:20][N:21]=[C:22]4[C:23]=3[CH:24]=[C:25]([O:28][CH3:29])[CH:26]=[CH:27]4)[N:11]([CH2:12][CH2:13]2)[CH2:10]1

Participants

4

Reactant 2

HCID 241BenzeneHCID 6432105Dihydroquinidine

Product 1

HCID 121515(-)-Dihydroquinine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution containing 1.25 g. of dihydroquinidinone in 50 ml. of benzene containing 0.5 ml. of methanol was maintained at 20° for 21/2 days under nitrogen. The solution was evaporated to complete dryness under vacuum, and the residue was redissolved in benzene and again evaporated to dryness. The resulting oily residue was dissolved in 50 ml. of dry benzene, and 3 ml. of a 25% solution of di-isobutyl aluminum hydride in toluene were added dropwise with stirring under an atomsphere of dry nitrogen. The reaction was quenched after about 30 minutes by adding 10 ml. of water-methanol (1:1), and the mixture was stirred vigorously for 30 minutes. The benzene layer was decanted. The aqueous aluminum suspension was washed several times with benzene and the combined benzene phases were dried over anhydrous magnesium sulfate and evaporated to dryness. The crude product (1.25 g. of colorless foam) was a practically pure mixture of dihydroquinidine and dhydroquinine (about 1:1) as determined by thin layer chromatography; and a specific rotation [α]D24,5 + 62.2° (c 1.64, ethanol). Crystallization from ethanol yielded 490 mg. of pure dihydroquinidine having a melting point of 167°-169°. Chromatographic separation from mother liquors gave 550 mp of dihydroquinine, m.p. 168°-170°, [α]D29 -137.5°.

Workup

  1. additionA solution containing 1.25 g
  2. customThe solution was evaporated to complete dryness under vacuum
  3. dissolutionthe residue was redissolved in benzene
  4. customagain evaporated to dryness
  5. dissolutionThe resulting oily residue was dissolved in 50 ml
  6. additionof a 25% solution of di-isobutyl aluminum hydride in toluene were added dropwise
  7. customThe reaction was quenched after about 30 minutes
  8. additionby adding 10 ml
  9. stirringof water-methanol (1:1), and the mixture was stirred vigorously for 30 minutes
  10. customThe benzene layer was decanted
  11. washThe aqueous aluminum suspension was washed several times with benzene
  12. dry with materialthe combined benzene phases were dried over anhydrous magnesium sulfate
  13. customevaporated to dryness
  14. additiona practically pure mixture of dihydroquinidine
  15. customa specific rotation [α]D24,5 + 62.2° (c 1.64, ethanol)
  16. customCrystallization from ethanol
  17. customyielded 490 mg
  18. customChromatographic separation from mother liquors

Sources & evidence

ORD record
ord-a5ab0b8f13ae41d7be3f829f3edd43e3
Source dataset
uspto-grants-1978_06
Patent number
US04096146

Reaction notes

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