Isatin → 1,2,3,4-Tetrahydroacridine

HRID 1974257Notes

Reaction equation

HRID 1974257 reaction equation
[NH:1]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:4](=O)[C:2]1=O.[OH-].[K+].[C:14]1(=O)[CH2:19][CH2:18]C[CH2:16][CH2:15]1>C(O)C>[CH2:7]1[C:6]2[C:11](=[N:1][C:16]3[C:2]([CH:4]=2)=[CH:18][CH:19]=[CH:14][CH:15]=3)[CH2:10][CH2:9][CH2:8]1

Participants

5

Reactant 3

HCID 7054IsatinHCID 7967CyclohexanoneHCID 14797Potassium Hydroxide

Product 1

HCID 1553151,2,3,4-Tetrahydroacridine

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
310 °C

Procedure

A solution of isatin (40 g. 0.272 mol) in 30% aqueous potassium hydroxide (160 ml., 1.5 mol.) was added to a solution of cyclohexanone (69.7 g. 0.712 mol.) in ethanol (300 ml.) and the mixture heated at reflux with stirring for 10 hours. The ethanol was removed in vacuo and the residue dissolved in water (400 ml.) and extracted with ether (3 × 50 ml.). The aqueous phase was acidified with acetic acid and the resultant solid was washed with water, dried and heated at 310° C in a Wood's metal bath for 35 minutes. The cooled melt was diluted with 2N HCl (200 ml.) and extracted with chloroform (2 × 200 ml.) and the extracts discarded. The aqueous phase was adjusted to pH 9.0 with sodium carbonate and extracted with ethyl acetate (4 × 100 ml.) The combined extracts were washed with brine, dried and the solvent removed and the residual oily solid recrystallised from (bp 40°-60°) petrolum ether to give 1,2,3,4-tetrahydroacridine as colourless needles (38 g.). A sample (1 g.) was dissolved in anhydrous ether and treated with ethereal hydrogen chloride. The resultant solid was removed and recrystallised from isopropanol to give 1,2,3,4-tetrahydroacridine hydrochloride quarter hydrate as colourless needles m.p. 232° C. (Found C,70.2; H,6.5; N,5.9, C13H13N.HCl. 1/4H2O requires: C,69.7; H, 6.5; N, 6.2%).

Workup

  1. temperaturethe mixture heated
  2. temperatureat reflux
  3. customThe ethanol was removed in vacuo
  4. dissolutionthe residue dissolved in water (400 ml.)
  5. extractionextracted with ether (3 × 50 ml.)
  6. washthe resultant solid was washed with water
  7. customdried
  8. additionThe cooled melt was diluted with 2N HCl (200 ml.)
  9. extractionextracted with chloroform (2 × 200 ml.)
  10. extractionextracted with ethyl acetate (4 × 100 ml.) The combined extracts
  11. washwere washed with brine
  12. customdried
  13. customthe solvent removed
  14. customthe residual oily solid recrystallised from (bp 40°-60°) petrolum ether

Sources & evidence

ORD record
ord-3c9be0c6a0c84205880a9965d7b47975
Source dataset
uspto-grants-1976_12
Patent number
US04000278

Reaction notes

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