Hydrochloric Acid → 6-Methyl-4-phenyl-2-chromanol

HRID 563871Notes

Reaction equation

HRID 563871 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>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

6

Reactant 4

HCID 313Hydrochloric AcidHCID 2879P-CresolHCID 4837PiperazineHCID 637511Cinnamaldehyde

Product 1

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

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

p-Cresol (150 g, 1.387 mol) was stirred with piperazine (72 g, 0.832 mol, 0.6 eq) in toluene (1.5 L, 10 ml/g) and then heated at reflux under Dean & Stark conditions for at least 30 minutes to remove water giving a clear pale yellow solution. Trans-Cinnamaldehyde (262 ml, 275 g, 2.081 mol, 1.5 eq) was then added over 2 hours whilst maintaining the reaction mixture at reflux under Dean & Stark conditions. Once the addition was complete, heating of the reaction mixture was continued at reflux under Dean & Stark conditions for a further 4 hours. The black solution was allowed to cool to 80° C. and then slowly quenched over 45 minutes with a solution of 0.67M HCl(aq) (750 ml, 0.601 mol, 1.3 eq). The two-phase solution was then stirred vigorously for at least 12 hours at a temperature of 75-80° C. The stirring was then stopped and the mixture allowed to cool to room temperature and the phases separated. The toluene solution was then washed with 1M HCl(aq) (750 ml, 5 ml/g), then water (3×750 ml, 5 ml/g). The 3,4-dihydro-6-methyl-4-phenyl-2H-benzopyran-2-ol was not isolated but instead the toluene solution was used directly in the reductive amination step (Example 2).

Workup

  1. temperatureheated
  2. temperatureat reflux under Dean & Stark conditions for at least 30 minutes
  3. customto remove water giving a clear pale yellow solution
  4. temperaturewhilst maintaining the reaction mixture
  5. temperatureat reflux under Dean & Stark conditions
  6. additionOnce the addition
  7. temperatureheating of the reaction mixture
  8. temperatureat reflux under Dean & Stark conditions for a further 4 hours
  9. temperatureto cool to room temperature
  10. customthe phases separated
  11. washThe toluene solution was then washed with 1M HCl(aq) (750 ml, 5 ml/g)

Sources & evidence

ORD record
ord-b304c532515741d6b0ab70c9968094f6
Source dataset
uspto-grants-2011_11
Patent number
US08067594B2

Reaction notes

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