3-Phenylprop-2-Enal → 6-Methyl-4-phenyl-2-chromanol

HRID 563872Notes

Reaction equation

HRID 563872 reaction equation
[CH:1]1[C:6]([OH:7])=[CH:5][CH:4]=[C:3]([CH3:8])[CH:2]=1.N1CCNCC1.[CH:15](=[O:24])[CH:16]=[CH:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.Cl>O.C1(C)C=CC=CC=1>[CH3:8][C:3]1[CH:2]=[CH:1][C:6]2[O:7][CH:15]([OH:24])[CH2:16][CH:17]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:5]=2[CH:4]=1

Participants

7

Reactant 4

HCID 3073-Phenylprop-2-EnalHCID 313Hydrochloric AcidHCID 2879P-Cresol2×HCID 4837Piperazine

Product 1

HCID 112301966-Methyl-4-phenyl-2-chromanol

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of p-cresol (25 g, 0.231 mol, 1 equiv), piperazine (11.94 g, 0.139 mol, 0.6 equiv) and toluene (250 ml, 10 ml/g) at reflux under Dean & Stark conditions was added cinnamaldehyde (45.83 g, 44 ml, 0.347 mol, 1.5 equiv) over a 2 hour period and reaction mixture monitored by HPLC for the presence of p-cresol. Upon completion (2 to 3 hours), the mixture was cooled to 80° C. and a solution of c.HCl (25 ml, 0.301 mol, 1.3 equiv) in water (100 ml, 5 ml/g) was slowly added and heated at 80-90° C. for at least 5 hours. The resulting solution was allowed to cool to room temperature and the phases separated. The toluene solution was washed with 1M HCl (125 ml, 5 ml/g), then water (3×125 ml). The resulting organic layer was taken into the reductive amination step (Step B) as a crude mixture.

Workup

  1. customperiod and reaction mixture
  2. temperatureheated at 80-90° C. for at least 5 hours
  3. temperatureto cool to room temperature
  4. customthe phases separated
  5. washThe toluene solution was washed with 1M HCl (125 ml, 5 ml/g)

Sources & evidence

ORD record
ord-7839e90e8f58457fb2a1041d13c82065
Source dataset
uspto-grants-2011_11
Patent number
US08067594B2

Reaction notes

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