Continuous-Flow Synthesis of Δ9-Tetrahydrocannabinol and Δ8-Tetrahydrocannabinol from Cannabidiol

Abstract

A challenging step in the preparation of tetrahydrocannabinol analogs is an acid-catalyzed intramolecular cyclization of the cannabidiol precursor. This step typically affords a mixture of products, which requires extensive purification to obtain any pure products. We report the development of two continuous-flow protocols for the preparation of (−)-trans-Δ9-tetrahydrocannabinol and (−)-trans-Δ8-tetrahydrocannabinol.