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

Participants

Reaction Conditions

Reaction Steps

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).

Provenance & Evidence