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

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence