Acetone → 6-Hydroxy-2,2-dimethylchroman-4-one

HRID 1818051Notes

Reaction equation

HRID 1818051 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[C:9](=[O:11])[CH3:10].[CH3:12][C:13]([CH3:15])=O.N1CCCCC1>N1C=CC=CC=1>[OH:8][C:5]1[CH:4]=[C:3]2[C:2](=[CH:7][CH:6]=1)[O:1][C:13]([CH3:15])([CH3:12])[CH2:10][C:9]2=[O:11]

Participants

5

Reactant 3

HCID 180Acetone2×HCID 8082Piperidine2×HCID 102792-Acetylhydroquinone

Product 1

HCID 35198596-Hydroxy-2,2-dimethylchroman-4-oneYield 76%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent2×

Procedure

To a 250 mL, 2-necked round bottom flask equipped with a magnetic stir bar and a water-jacketed condenser capped with a balloon was added 2′,5′-dihydroxyacetophenone (2, 8.00 g, 52.6 mmol), reagent grade acetone (19.45 mL, 263 mmol), piperidine (5.2 mL, 52.6 mmol) and freshly distilled pyridine (50 mL). The mixture was heated to a vigorous reflux with stirring under a nitrogen atmosphere for 2 d. The solvent was evaporated and the concentrate was dried under high vacuum. Reagent grade acetone (19.45 mL, 263 mmol), piperidine (5.2 mL, 52.6 mmol) and freshly distilled pyridine (50 mL) were added, and vigorous reflux with stirring under a nitrogen atmosphere was continued for 2d more. The solvent was evaporated, ethyl acetate (30 mL) and 30% aqueous CuSO4 (30 mL) were added to the concentrate. The organic phase was washed with brine (1×30 mL), dried over MgSO4, filtered, concentrated and dried under high vacuum. The dry crude product was passed through a silica gel column using 2:1 hexanes/ethyl acetate as eluent (Rf=0.3). The product gives off a purple color on an analytical silica gel plate illuminated with a short wave UV lamp. The fractions containing the pure product were transferred to a pre-weighed flask, the solvent was evaporated and the concentrate was dried under high vacuum. The reaction furnished 7.65 g of 3 (76%) as a brown solid. 1H NMR (300 MHZ, CDCl3): δ 7.32 (m, 1H), 7.04 (m, 1H), 6.82 (m, 1H), 5.48 (bs, 1H), 2.68 (s, 2H), 1.42 (s, 6H). 13C NMR (75.5 MHZ, CDCl3): δ 193.8, 154.4, 149.9, 125.2, 120.0, 119.6, 110.7, 79.0, 48.7, 26.5; HRMS (EI+): calculated for C11H12O3 [M+] m/z 192.0786, found 192.0788.

Workup

  1. customTo a 250 mL, 2-necked round bottom flask equipped with a magnetic stir bar and a water-jacketed condenser
  2. customcapped with a balloon
  3. temperatureThe mixture was heated to
  4. temperaturea vigorous reflux
  5. customThe solvent was evaporated
  6. customthe concentrate was dried under high vacuum
  7. temperaturevigorous reflux
  8. stirringwith stirring under a nitrogen atmosphere
  9. customThe solvent was evaporated
  10. additionethyl acetate (30 mL) and 30% aqueous CuSO4 (30 mL) were added to the concentrate
  11. washThe organic phase was washed with brine (1×30 mL)
  12. dry with materialdried over MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customdried under high vacuum
  16. customThe dry crude product
  17. customThe product gives off a purple color on an analytical silica gel plate
  18. customilluminated with a short wave UV lamp
  19. additionThe fractions containing the pure product
  20. customwere transferred to a pre-weighed flask
  21. customthe solvent was evaporated
  22. customthe concentrate was dried under high vacuum

Sources & evidence

ORD record
ord-bc9bf3286c33466fbcecf28cc9c19f66
Source dataset
uspto-grants-2009_10
Patent number
US07598403B2

Reaction notes

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