Palladium nanoparticles for the synthesis of phenanthridinones and benzo[c]chromenes via C–H activation reaction†
Abstract
In the present work, derivatives of phenanthridine-6(5H)-ones and benzo[c]chromenes were efficiently prepared through an intramolecular C–H bond functionalization reaction catalyzed by photochemically synthesized Pd-PVP nanoparticles. The heterocycles were obtained via intramolecular arylation of the corresponding N-methyl-N-aryl-2-halobenzamide or aryl-(2-halo)benzyl ethers using K2CO3 as base in a mixture of H2O : DMA as solvent without additives or ligands. High yields of the heterocyclic compounds were achieved (up to 95%) using a moderately low catalyst loading (1–5 mol%) under an air atmosphere at 100 °C. The reaction exhibited very good tolerance to diverse functional groups (OMe, Me, tBu, Ph, OCF3, CF3, F, Cl, –CN, Naph), and both bromine and iodine substrates showed great reactivity. Finally, the in vitro antiproliferative activity of phenanthridine-6(5H)-ones and benzo[c]chromenes was evaluated against six human solid tumor cell lines. The more active compounds exhibit activity in the low micromolar range. 1-Isopropyl-4-methyl-6H-benzo[c]chromene was identified as the best compound with promising values of activity (GI50 range 3.9–8.6 μM). Thus, the benzochromene core was highlighted as a novel organic building block to prepare potential antitumor agents.