Ethanol → 1,3-Dihydroisobenzofuran

HRID 1659601Notes

Reaction equation

HRID 1659601 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[CH:7]1[CH:8]=[CH:9][C:10]2[C:16](C3C=CC(O)=CC=3)(C3C=CC(O)=CC=3)[O:15][C:13](=O)[C:11]=2[CH:12]=1.C(O)C.O>O1CCCC1.CCOCC>[CH2:13]1[O:15][CH2:16][C:10]2[C:11]1=[CH:12][CH:7]=[CH:8][CH:9]=2

Participants

7

Reactant 4

HCID 702EthanolHCID 962WaterHCID 4764Phenolphthalein2×HCID 21226445Aluminium lithium hydride2×

Product 1

HCID 103271,3-DihydroisobenzofuranYield 156.3%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent3×HCID 8028TetrahydrofuranSolvent2×

Procedure

To a one liter 3-neck flask under nitrogen was added 250 ml of dry tetrahydrofuran followed by 4.61 g of lithium aluminum hydride (95%). Phenolphthalein (20.0 g) dissolved in 250 ml of dry tetrahydrofuran was added dropwise to the well-stirred lithium aluminum hydride suspension at a rate to prevent a violent reaction. Addition was completed in 90 minutes. The reaction mixture was then refluxed for 30 minutes by applying external heat. Silica gel TLC in ether showed some unreacted phenolphthalein was present. Refluxing was continued for 21/2 hours. Silica gel TLC in ether showed no further changes. The heat source was removed, and 60 ml of ethyl acetate was added to the reaction mixture to destroy unreacted lithium aluminum hydride. Then 200 ml of saturated ammonium chloride was added and the pH adjusted to about 4 to 6 with 1N HCl. The organic portion was decanted and the solvent removed under reduced pressure leaving a yellow oil. The oil was dissolved in 350 ml of ether and the ether extracted with a total of 4 liters of 10% sodium carbonate to remove unreacted pheolphthalein. Then the ether was removed leaving a yellow oil which was dissolved in one liter of boiling 20% ethanol: 80% water mixture to give a clear, pink-red solution. Upon cooling, an off-white crystalline product formed, and the solution was allowed to stand in the refrigerator for three days. The solids were filtered, washed with room temperature 20% ethanol to remove a yellow-pink color and collected giving a very pale yellow, crystalline product. Recrystallization from 750 ml of 20% ethanol gave 11.8 g of the corresponding phthalan as a very pale yellow crystalline solid. Silica gel TLC in ether showed only one spot corresponding to the phthalan.

Workup

  1. customa violent reaction
  2. additionAddition
  3. temperatureThe reaction mixture was then refluxed for 30 minutes
  4. temperatureRefluxing
  5. custom2 hours
  6. customThe heat source was removed
  7. addition60 ml of ethyl acetate was added to the reaction mixture
  8. customto destroy unreacted lithium aluminum hydride
  9. additionThen 200 ml of saturated ammonium chloride was added
  10. customThe organic portion was decanted
  11. customthe solvent removed under reduced pressure
  12. customleaving a yellow oil
  13. extractionthe ether extracted with a total of 4 liters of 10% sodium carbonate
  14. customto remove unreacted pheolphthalein
  15. customThen the ether was removed
  16. customleaving a yellow oil which
  17. dissolutionwas dissolved in one liter
  18. temperatureUpon cooling
  19. customan off-white crystalline product formed
  20. waitto stand in the refrigerator for three days
  21. filtrationThe solids were filtered
  22. washwashed with room temperature 20% ethanol
  23. customto remove a yellow-pink color
  24. customcollected
  25. customgiving a very pale yellow, crystalline product
  26. customRecrystallization from 750 ml of 20% ethanol

Sources & evidence

ORD record
ord-55ac234b1f074776a761d82de87f97dc
Source dataset
uspto-grants-1981_12
Patent number
US04304833

Reaction notes

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