Hydrochloric Acid → 4H-Pyran-4-one, 5-hydroxy-2-methyl-

HRID 1928670Notes

Reaction equation

HRID 1928670 reaction equation
[CH:1]1[C:6](=[O:7])[C:5]([OH:8])=[CH:4][O:3][C:2]=1[CH2:9]Cl.Cl>[Zn].O>[OH:8][C:5]1[C:6](=[O:7])[CH:1]=[C:2]([CH3:9])[O:3][CH:4]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 82051Chlorokojic acid

Product 1

HCID 695214H-Pyran-4-one, 5-hydroxy-2-methyl-Yield 65.4%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

Chloro-kojic Acid (20.0 g; 125 mmol)—an inhibitor of tyrosinase with an EC50 of 6.8 μM—was added in portions to HPLC grade water (60 mL) and heated with an oil bath to ˜50° C. Zinc dust (16.2 grams) was carefully added in portions (5 min). An addition funnel was then attached. The reaction temperature was then increased to ˜70° C. and concentrated HCl (37 mL) was added drop-wise over 60 min; the reaction was vigorously stirred for an additional 3 hours. Next, excess zinc was removed via hot Büchner filtration. Standard extraction and purification methods afforded allomaltol (10.3 g; 81.7 mmol; 65% yield); see Liu, Z. D. et al, Bioorg. Med. Chem. 2001, 9, 563-573. Allomaltol was found to be a more potent inhibitor of tyrosinase than kojic acid with an EC50 of 3.4 μM. 1H NMR (DMSO-d5) δ 9.3-8.3 (br s, 1H; 5-OH); 7.97 (s, 1H; 6-H); 6.23 (s, 1H; 3-H); 2.24 (s, 3H; 2-CH3).

Workup

  1. customAn addition funnel was then attached
  2. temperatureThe reaction temperature was then increased to ˜70° C.
  3. customNext, excess zinc was removed via hot Büchner filtration
  4. extractionStandard extraction and purification methods

Sources & evidence

ORD record
ord-b869cca052cd4ccfa0517f104f1e70ed
Source dataset
uspto-grants-2012_05
Patent number
US08183398B2

Reaction notes

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