ADDITION AND ELIMINATION OF HCL TO TETRAHYDROCANNABINOL ISOMERS - A METHOD FOR THE PREPARATION OF STEREOSPECIFICALLY H-2-LABELED CANNABINOIDS

Addition of HCl gas to (-)Delta(8)-, (-)Delta(9)-, or (-)Delta(9,11)-T HC solutions at -60 degrees C results in the formation of 9 alpha- and 9 beta-chlorohexahydrocannabinol (Cl-HHC). The addition appears to in volve initial protonation of the double bond in the form of a bridged hydrogen cation followed by attack of the chloride anion at the most s ubstituted 9-position. For both steps in the addition reaction the ste reochemistry is dependent on the double bond position in the THC isome r. Elimination of HCl from each of the two addition products using pot assium-tert-amylate leads exclusively to Delta(9)-THC in the case of 9 beta-Cl-HHC and to Delta(9,11)-THC in the case of 9 alpha-Cl-HHC. The individual addition products can be separated and used to obtain regi o-and stereochemically H-2-isotopically labeled tetrahydrocannabinols which can be used in biophysical and biochemical studies.