Glycerol → 4'-(hydroxymethyl)-2,2-dimethyl-3,4-dihydro-2H,5H-spiro[benzo[h]chromene-6,2'-[1,3]dioxolan]-5-one

HRID 1159436Notes

Reaction equation

HRID 1159436 reaction equation
[CH3:1][C:2]1([CH3:18])[CH2:11][CH2:10][C:9]2[C:8](=[O:12])[C:7](=[O:13])[C:6]3[CH:14]=[CH:15][CH:16]=[CH:17][C:5]=3[C:4]=2[O:3]1.[OH:19][CH2:20][CH:21]([CH2:23][OH:24])O.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1C=CC=CC=1>[OH:19][CH2:20][CH:21]1[CH2:23][O:24][C:7]2([C:6]3[CH:14]=[CH:15][CH:16]=[CH:17][C:5]=3[C:4]3[O:3][C:2]([CH3:18])([CH3:1])[CH2:11][CH2:10][C:9]=3[C:8]2=[O:12])[O:13]1

Participants

5

Reactant 3

HCID 753GlycerolHCID 3885Beta-LapachoneHCID 521998p-Toluenesulfonic acid monohydrate

Product 1

HCID 595143894'-(hydroxymethyl)-2,2-dimethyl-3,4-dihydro-2H,5H-spiro[benzo[h]chromene-6,2'-[1,3]dioxolan]-5-oneYield 36%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

To a solution of 2,2-dimethyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione (1.21 g, 5 mmol) in benzene (12 ml) is added glycerol (0.92 g, 10 mmol) and p-toluenesulfonic acid monohydrate (0.28 g, 1.5 mmol). The resulting mixture is refluxed for 6 hours. After removal of the solvent, product is purified by column chromatography on silica gel eluting with 30% ethyl acetate in methylene chloride to provide 0.57 g (36% yield) as a light yellow solid, which is a mixture of diasteromers. M.p. 44-46° C.; 400 MHz 1H NMR (CDCl3) δ: 1.41 (s, 6H), 1.73-1.82 (m, 2H), 2.36-2.42 (m, 1H), 2.48-2.54 (m, 1H), 3.72-3.78 (m, 1H), 4.18 (d, J=2.5 Hz, 1H), 4.20-4.29 (m, 1H), 4.40 (t, J=8.0 Hz, 1H), 4.71-4.74 (m, 1H), 4.85 (d, J=8.8 Hz, 1H), 7.38-7.44 (m, 2H), 7.54-7.56 (m, 1H), 7.75-7.78 (m, 1H); LCMS: Calc. for C18H21O5: 217; Found 217.

Workup

  1. temperatureThe resulting mixture is refluxed for 6 hours
  2. customAfter removal of the solvent, product
  3. customis purified by column chromatography on silica gel eluting with 30% ethyl acetate in methylene chloride
  4. customto provide 0.57 g (36% yield) as a light yellow solid, which
  5. additiona mixture of diasteromers

Sources & evidence

ORD record
ord-ae572e2688db48a5b95a34eb3248c270
Source dataset
uspto-grants-2010_10
Patent number
US07812051B2

Reaction notes

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