Nitrobenzene → 5,7-Dihydroxy-8-acetyl-4-propyl-coumarin

HRID 840325Notes

Reaction equation

HRID 840325 reaction equation
[OH:1][C:2]1[CH:11]=[C:10]([OH:12])[CH:9]=[C:8]2[C:3]=1[C:4]([CH2:14][CH2:15][CH3:16])=[CH:5][C:6](=[O:13])[O:7]2.[N+](C1C=CC=CC=1)([O-])=O.[C:26](OC(=O)C)(=[O:28])[CH3:27]>ClCCCl>[OH:1][C:2]1[CH:11]=[C:10]([OH:12])[C:9]([C:26](=[O:28])[CH3:27])=[C:8]2[C:3]=1[C:4]([CH2:14][CH2:15][CH3:16])=[CH:5][C:6](=[O:13])[O:7]2

Participants

5

Reactant 3

HCID 7416NitrobenzeneHCID 7918Acetic AnhydrideHCID 53912605,7-Dihydroxy-4-propylcoumarin

Product 1

HCID 129682825,7-Dihydroxy-8-acetyl-4-propyl-coumarinYield 12.2%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent2×

Conditions

Temperature
75 °C

Procedure

To a mixture of 5,7-dihydroxy-4-propyl-coumarin (2.06 g 9.36 mmol) and anhydrous AICI3 (2.53 g, 18.7 mmol) was added 1,2-dichloroethane (120 mL). The resulting suspension was heated to 75° C. with vigorous stirring. After 30 minutes of stirring, a brown slurry was obtained, then nitrobenzene was introduced into the mixture resulting in an orange colored solution. A solution of anhydrous AICI3 (2.53 g, 18.7 mmol) and acetic anhydride (0.88 mL, 9.36 mmol) in 1,2-dichloroethane (40 mL) was added dropwise over a period of 1-2 hours. After addition, the mixture was allowed to stir at 75° C. for another two hours and subsequently cooled to room temperature. The resulting mixture was poured into ice and 1N HC1. The precipitated product was filtered and then taken into ethyl acetate and the aqueous solution was extracted thoroughly with ethyl acetate (3×100 mL). The combined ethyl acetate extracts were dried over Na2SO4 and the solvent was removed under reduced pressure. The resulting solid was purified by column chromatography (1:1 hexane/ethyl acetate) yielding 5,7-dihydroxy-8-acetyl-4-propyl-coumarin (0.30 g, 12%): mp. 221-224° C.; 1H NMR (DMSO-d6) δ0.94 (t, 3H), 1.58 (sextet, 2H), 2.66 (s, 3H) 2.87 (t, 2H), 6.01 (s, 1H), 6.29 (s, 1H).

Workup

  1. customa brown slurry was obtained
  2. customresulting in an orange colored solution
  3. additionAfter addition
  4. stirringto stir at 75° C. for another two hours
  5. temperaturesubsequently cooled to room temperature
  6. additionThe resulting mixture was poured into ice and 1N HC1
  7. filtrationThe precipitated product was filtered
  8. extractionthe aqueous solution was extracted thoroughly with ethyl acetate (3×100 mL)
  9. dry with materialThe combined ethyl acetate extracts were dried over Na2SO4
  10. customthe solvent was removed under reduced pressure
  11. customThe resulting solid was purified by column chromatography (1:1 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-aae16d5c4e284a29b58981606ae41638
Source dataset
uspto-grants-2002_04
Patent number
US06365626B1

Reaction notes

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