The oxidation reaction of two common and widespread phytocannabinoids, namely cannabigerol 1 and cannabidiol 2 with a panel of four single electron transfer reagents has been revised and further investigated. A certain degree of selectivity of the process described herein has been recorded. The fate of the reaction largely depends on the solvent used and the type of reagent. Thus, when cerium ammonium nitrate was employed, the mononitro derivatives 3 and 4 of both 1 and 2 were obtained when the process was carried out in CH 3 CN, while cannabigeroquinone 5 and cannabidiolquinone 6 were the only products when Et 2 O was used as the solvent. Mn(OAc) 3 yielded cannabigeroquinone 5 from cannabigerol 1 , while provided an inseparable mixture of products in the case of cannabigerol 2 as the substrate. Oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone resulted in the selective formation of cannabichromenequinone 7 from cannabigerol 1 , while cannabidiol 2 yielded an inseparable mixture of products also in this case. Finally, the reaction with 2,2,6,6-(tetramethylpiperidin-1-yl)oxyl free radical provided selectively the two quinones 5 and 6 from cannabigerol 1 and cannabidiol 2 , respectively. Yields of the above mentioned adducts ranged from 70 % to 90 %. Notably, while quinone forms and cyclized adducts like compounds 5–7 have been already described in the literature, nitro functionalization of phytocannabinoids as in 2-(2 E )-3,7-dimethylocta-2,6-dienyl-4-nitro-5-pentylbenzene-1,3-diol 3 and 2-(1 R,6 R)-3-methyl-6-(prop-1-en-2-yl)cyclohex-2-en-1-yl-4-nitro-5-pentylbenzene-1,3-diol 4 is disclosed herein for the first time. • SET oxidation of CBG and CBD yields distinct quinonoid derivatives. • CAN and TEMPO provide mild, selective, and high-yield oxidations. • Solvent polarity crucially influences quinone formation and selectivity. • CBG oxidations are well-defined; CBD often forms complex mixtures. • Redox insights enable biomimetic and sustainable cannabinoid functionalization.
Collevecchio et al. (Fri,) studied this question.