3-Phenylprop-2-Enal → 3,4-Dihydro-2-hydroxy-4-phenyl-2H-1-benzopyran-6-ethanol

HRID 563874Notes

Reaction equation

[OH:1][C:2]1[CH:10]=[CH:9][C:5]([CH2:6][CH2:7][OH:8])=[CH:4][CH:3]=1.N1CCNCC1.[CH:17](=[O:26])[CH:18]=[CH:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.Cl>C1(C)C=CC=CC=1>[OH:8][CH2:7][CH2:6][C:5]1[CH:4]=[C:3]2[C:2](=[CH:10][CH:9]=1)[O:1][CH:17]([OH:26])[CH2:18][CH:19]2[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 4-hydroxyphenethyl alcohol (Tyrosol) (5.0 g, 36 mmol, 1 equiv), piperazine (1.87 g, 22 mmol, 0.6 equiv) and toluene (50 ml) at reflux under N2 and Dean & Stark conditions was added cinnamaldehyde (6.4 ml, 51 mmol, 1.4 equiv) and the reaction mixture maintained at heat for 17 h. The reaction was cooled to 80° C. and quenched with aqueous HCl (0.7 molar, 1.3 equiv) then stirred at heat for 18 h. The biphasic mixture was allowed to cool to ambient temperature, separated, the organic phase washed with aqueous HCl and water and the organic phase concentrated to a black residue under reduced pressure. Flash chromatography eluting with 20% EtOAc/Heptane afforded the title compound as the main constituent of an approximately 80% pure yellow oil, Rf=0.37 (50% EtOAc/Heptane) and structure confirmed by 1H NMR and LC-MS (M+1=271).

Workup

temperaturethe reaction mixture maintained
temperatureat heat for 17 h
temperatureat heat for 18 h
temperatureto cool to ambient temperature
customseparated
washthe organic phase washed with aqueous HCl and water
concentrationthe organic phase concentrated to a black residue under reduced pressure
washFlash chromatography eluting with 20% EtOAc/Heptane

Sources & evidence

ORD record: ord-cf44e8f3a6c442b18da8f8016a0957d7
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08067594B2

Reaction notes

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