Synthesis of (all-rac)-α-tocopherol in supercritical carbon dioxide: Tuning of the product selectivity in batch and continuous-flow reactors

Article abstract of DOI:10.1002/adsc.200404312

α-Tocopherol was synthesized using a condensation reaction of 2,3,6-trimethylhydroquinone with isophytol in supercritical CO₂ using batch and continuous-flow reactors. In the batch reaction catalyzed by a fluorinated molecular catalyst bearing strong Bronsted acidity, C ₆F₅CHTf₂ (Tf=SO₂CF₃), an increase in the CO₂ pressure causes a marked increase in the product selectivity for α-tocopherol, albeit with a slight decrease in the product yield. The solubility measurements by extraction experiments and the supercritical fluid NMR (scNMR) indicate that the homogeneous and non-polar reaction phase in scCO₂ is crucial to obtain α-tocopherol with high selectivity. A continuous flow scCO₂ process for the condensation reaction can be performed with a strong acid resin, Amberlyst 15, as a solid acid catalyst to give the desired product with high selectivity.