Addition and elimination of HCl to tetrahydrocannabinol isomers. A method for the preparation of stereospecifically 2H-labeled cannabinoids

Addition of HCl gas to (−)Δ8-, (−)Δ9-, or (−)Δ9,11-THC solutions at −60°C results in the formation of 9α- and 9β-chlorohexahydrocannabinol (Cl-HHC). The addition appears to involve initial protonation of the double bond in the form of a bridged hydrogen cation followed by attack of the chloride anion at the most substituted 9-position. For both steps in the addition reaction the stereochemistry is dependent on the double bond position in the THC isomer. Elimination of HCl from each of the two addition products using potassium-tert-amylate leads exclusively to Δ9-THC in the case of 9β-Cl-HHC and to Δ9,11-THC in the case of 9α-Cl-HHC. The individual addition products can be separated and used to obtain regio- and stereochemically 2H-isotopically labeled tetrahydrocannabinols which can be used in biophysical and biochemical studies.