Ethyl Acetoacetate → Coumarin

HRID 1358098Notes

Reaction equation

HRID 1358098 reaction equation
C[C:2]1(C)[CH2:11][CH2:10][C:9](C)(C)[C:8]2C=[C:6]([OH:14])[CH:5]=[CH:4][C:3]1=2.C(OCC)(=O)CC(C)=[O:19]>OS(O)(=O)=O.C([O-])(O)=O.[Na+]>[O:19]1[C:8]2[C:3](=[CH:2][CH:11]=[CH:10][CH:9]=2)[CH:4]=[CH:5][C:6]1=[O:14]

Participants

5

Reactant 2

HCID 8868Ethyl AcetoacetateHCID 2687865,5,8,8-Tetramethyl-5,6,7,8-tetrahydronaphthalen-2-ol

Product 1

HCID 323Coumarin

Reagents, catalysts & solvents 2

HCID 1118Sulfuric AcidSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
100 °C

Procedure

1,2,3,4-Tetrahydro-1,1,4,4,6-pentamethylbenzo[5,6-g]coumarin (Structure 4 of Schemes 1 and 2, where R1, R4, R6=H, R2 and R3 together form a tetramethyl saturated six-membered carbocyclic ring, R5=methyl). To a flame-dried 50-mL r.b. flask containing 5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphth-2-ol (2.03 g, 9.94 mmol) in 4 mL 75% H2SO4 was added ethyl acetoacetate (Structure 3 of Scheme 1, where R5=methyl, R6=H, R′=ethyl) (3.19 mL, 25.0 mmol, 2.52 equiv), and the mixture was heated to 100° C. for 3 h. Upon cooling to room temperature, the mixture was poured over ice (50 g), diluted with saturated NaHCO3 (50 mL), and stirred for 30 min. The mixture was then extracted with EtOAc (3×50 mL) and the organic layer was washed with brine (50 mL), dried (Na2SO4), and concentrated under reduced pressure. The crude product mixture was purified by flash column chromatography (silica gel, hexanes/EtOAc, 4:1) to remove residual ethyl acetoacetate, providing the desired coumarin as a white solid (Rf0.62, hexanes/EtOAc, 2:1). Recrystallization from hexanes/EtOAc afforded 2.12 g (79%) of 1,2,3,4-tetrahydro-1,1,4,4,6-pentamethylbenzo[5,6-g]coumarin as white prisms (mp 126-128° C.). 1H NMR (400 MHz, CDCl3) 7.51 (s, 1H), 7.25 (s, 1H), 6.20 (d, 1H, J=0.8 Hz), 2.43 (d, 3H, J=0.9 Hz), 1.72 (s, 4H), 1.33 and 1.31 (2s, 2×3H). 13C NMR (100 MHz, CDCl3) 161.2, 152.2, 151.4, 150.4, 141.5, 122.2, 117.9, 114.3, 107.1, 34.92, 34.84, 34.58, 34.20, 32.22, 31.83, 18.49. IR (thin film) 2923 (m), 1716 (s), 1612 (m). Anal. Calcd for C18H22O: C, 79.96; H, 8.20. Found: C, 80.06; H, 8.06.

Workup

  1. temperatureUpon cooling to room temperature
  2. extractionThe mixture was then extracted with EtOAc (3×50 mL)
  3. washthe organic layer was washed with brine (50 mL)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product mixture was purified by flash column chromatography (silica gel, hexanes/EtOAc, 4:1)
  7. customto remove residual ethyl acetoacetate

Sources & evidence

ORD record
ord-99a2631017b74e4cbd36b86ed2a093cb
Source dataset
uspto-grants-2003_07
Patent number
US06593493B1

Reaction notes

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