Catalytic Static Mixers Enable the Continuous Hydrogenation of Cannabidiol and Tetrahydrocannabinol

Abstract

In this work, we investigated the catalytic hydrogenation of cannabidiol (CBD), delta-8-tetrahydrocannabinol (∆8-THC) and delta-9-tetrahydrocannabinol (∆9-THC) by using catalytic static mixer (CSM) technology within a shell-and-tube reactor. Hydrogenation of these compounds is typically reported in batch at milligram quantities and affords a mixture of products. We were interested in developing a robust preparative-scale synthesis of 8,9-dihydrocannabidiol (H2CBD) and tetrahydrocannabidiol (H4CBD) from CBD, and hexahydrocannabinol (HHC) from ∆8-THC and ∆9-THC. We examined the influence of different noble metal¬-based CSMs (Pt/alumina, Pd/alumina, Pd-electroplated and Ru/alumina) and different operating conditions on the reaction performance. Pd/alumina CSMs were found to be unsuitable due to the formation of impurities, which partly arose due to double bond isomerization. Pd-electroplated CSMs displayed very low activity. Ru/alumina CSMs were observed to undergo rapid catalyst deactivation. Pt/alumina CSMs displayed high activity and good selectivity, even though signs of deactivation were still present at temperatures higher than 80 °C. We linked this deactivation to a combined influence of internal mass transfer limitation and accumulation of adsorbed molecules on the metal surface. After a careful fine-tuning of the operating conditions over Pt/alumina CSMs, we could obtain H2CBD, H4CBD and HHC in high yield from the corresponding cannabinoid derivative. Kinetic modeling and parameter fitting were successfully performed for the hydrogenation of CBD, which incorporated catalyst deactivation. Catalytic static mixer (CSM) technology is therefore demonstrated an industrially viable solution for the hydrogenation of cannabinoid derivatives.