Synthesis of Pyrimidine Fused Quinolines by Ligand-Free Copper-Catalyzed Domino Reactions

Abstract

Herein, we report two novel methods for the synthesis of pyrimidine fused quinolines using a one-pot C-C and C-N bond forming strategy from the reaction of 6-aminouracils with 2-bromobenzaldehydes or 2-bromobenzyl bromide derivatives in the presence of 10 mol % CuCl₂ without using any ligand. The reaction of 2-bromobenzaldehyde or its derivatives with 6-aminouracils in the presence of K₂CO₃ as base and a catalytic amount of CuCl₂ in DMF medium under microwave heating conditions provides corresponding pyrimidine fused quinoline derivatives in good yields within 30 min. Alternatively, pyrimidine fused quinoline derivatives have been synthesized from the reaction of 2-bromobenzyl bromides with 6-aminouracil derivatives in the presence of molecular oxygen, CuCl₂ (10 mol %), and K₂CO₃ as base in DMF under reflux conditions. Structures of all the products were unambiguously confirmed by spectroscopic techniques and by recording single crystal XRD of 3a.