Sulfuric Acid → 4-Ethyl-7-hydroxycoumarin

HRID 897061Notes

Reaction equation

HRID 897061 reaction equation
[C:1]1([CH:8]=[CH:7][CH:6]=[C:4]([OH:5])[CH:3]=1)[OH:2].[C:9]([CH2:13][C:14](OCC)=[O:15])(=O)[CH2:10][CH3:11].FC(F)(F)C(O)=O.S(=O)(=O)(O)O>>[CH2:10]([C:9]1[C:8]2[C:1](=[CH:3][C:4]([OH:5])=[CH:6][CH:7]=2)[O:2][C:14](=[O:15])[CH:13]=1)[CH3:11]

Participants

5

Reactant 4

HCID 1118Sulfuric AcidHCID 5054ResorcinolHCID 6422Trifluoroacetic acidHCID 78656Ethyl 3-oxovalerate

Product 1

HCID 53958914-Ethyl-7-hydroxycoumarinYield 42.4%

Procedure

Resorcinol (1.21 g, 11.0 mmol) was dissolved in hot ethyl propionylacetate (1.52 g, 10.0 mmol). To this stirred mixture at ice-water temperature was added dropwise a mixture of trifluoroacetic acid (1.70 mL, 22.0 mmol) and concentrated sulphuric acid (2.2 mL, 22.0 mmol) at such a rate that the reaction temperature was kept below 10° C. (about 30 min). The reaction mixture was then allowed to warm to room temperature and thereupon stirred for an additional 3 h before being quenched cautiously with ice-water. After stirring the suspension that formed for 1 h, the bright yellow precipitate was collected by suction filtration, washed exhaustively with water and then re-dissolved into acetone. The resulting solution was heated with activated charcoal, filtered and evaporated to give a light orange residue which was dried azeotropically with isopropyl alcohol. The crude product that obtained was purified by recrystallisation from acetone/hexane (2:3) to give 3 as creamy crystals (806 mg, 4.24 mmol, 42%); mp 175-178° C. [Lit. [68] 177° C. (ethanol)]; δ (400 MHz, DMSO-d6) 1.22 (3H, t, J=7.3 Hz, CH3), 2.77 (2H, q, J=7.3 Hz, CH2), 6.09 (1H, s, C3-H), 6.71 (1H, d, JC6-H, C8-H=2.4 Hz, C8-H), 6.80 (1H, dd, JC8-H, C6-H=2.4 Hz and JC3-H, C6-H=8.4 Hz, C6-H), 7.64 (1H, d, JC6-H, C5-H=8.8 Hz, C5-H) and 10.53 (1H, s, exchanged with D2O, OH); MS (FAB+) m/z (rel. intensity) 190.8[100, (M+H)+]; MS (FAB−) m/z (rel. intensity) 342.8[60, (M−H+NBA)−], 188.8[100, (M−H)−]. Found: C, 69.4; H, 5.35; C11H10O3 requires C, 69.43; H, 5.30%.

Workup

  1. customwas kept below 10° C.
  2. custom(about 30 min)
  3. custombefore being quenched cautiously with ice-water
  4. stirringAfter stirring the suspension
  5. customthat formed for 1 h
  6. filtrationthe bright yellow precipitate was collected by suction filtration
  7. washwashed exhaustively with water
  8. dissolutionre-dissolved into acetone
  9. temperatureThe resulting solution was heated with activated charcoal
  10. filtrationfiltered
  11. customevaporated
  12. customto give a light orange residue which
  13. dry with materialwas dried azeotropically with isopropyl alcohol
  14. customThe crude product that obtained
  15. customwas purified by recrystallisation from acetone/hexane (2:3)

Sources & evidence

ORD record
ord-e187fe43fb4446f491d5c9f0b6adf262
Source dataset
uspto-grants-2005_07
Patent number
US06921776B1

Reaction notes

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