| Abstract [eng] |
In pursuit of new ways to synthesize and advance the bioapplications of oxygen heterocycles, new synthetic methodologies for the synthesis of 2H-chromenes, utilizing cannabinol molecule as the backbone and oxepanes were elaborated. The synthetic studies accomplished in this work include new procedures to access cannabinol propargyl ether derivatives and cannabinol 2H-chromenes synthesis. Furthermore, in addition to new ways to synthesize oxepane derivatives, investigation of the effect of solvent and base nature for the formation of these heterocyclic compounds were evaluated. Cannabinol propargyl ether derivatives were synthesized using cannabinol as the starting material, which in the presence of a weak base, can be alkylated with a variety of propargyl bromides. Propargyl bromide analogs can be synthesized from different propargyl alcohols by Appel reaction treating them with molecular bromine, triphenylphosphine in DCM solution producing desired products in high yields. The latter can be cyclized using catalytic amounts of indium(III) chloride or copper(I) bromide in toluene or 1,4-dioxane producing target 2H-chromenes in acceptable yields. (E)-1-(2-cinnamyloxy)phenyl)ethanone derivatives were synthesized by alkylation reaction using appropriate 2-hydroxyacetophenones, cinnamyl bromide, and potassium carbonate in DMF solution. All desired products were separated from the reaction mixture in high yields. The corresponding 3,4-dihydrobenzo[b]oxepin-5(2H)-ones were synthesized using cyclization reactions with different solvent and base pairs: DMSO/LiHMDS, DMSO/NaH, DMSO/KHMDS, THF/LiHMDS, DMA/NaH. However, DMSO and NaH were the only solvent/base pair with which all 3,4-dihydrobenzo[b]oxepin-5(2H)-one derivatives were observed in a reaction mixture. The findings disclosed provided the guidelines for further optimization of these newly discovered cyclization methods. |
