A synthetic route to unsymmetrical 1,8-naphthyridine spacer based ligands is presented. Reaction of a 7-ethyldipyridyl-1,8-naphthyridine-2-carboxaldehyde intermediate with 2-aminophenol or 4,6-di-tert-butyl 2-aminophenol led to the formation of ligands, HL1 and HL2, respectively. Both combined two distinct binding sites: a dipyridyl and an iminophenol site linked through a 1,8-naphthyridine spacer. Treatment of HL1 with copper(II) triflate in the presence of triethylamine/H2O in acetonitrile afforded a tetranuclear complex (1tox·2CH3CN). X-ray analysis revealed that the structure is constituted by the association of two identical dinuclear units in which the imine is oxidized to an amide group during the complexation. The coordination capabilities of the corresponding free amide ligands H2L1ox and H2L2ox, prepared by an independent route, were explored using copper(II) triflate in the presence of triethylamine/H2O. With the amide ligand, H2L1ox, a similar tetranuclear copper complex (1tox·2DMF) compared to the one isolated after complexation with the imine ligand HL1 was formed, as evidenced by X-ray diffraction studies. In contrast, H2L2ox, where the amido phenol arm exhibits two additional tert-butyl groups, has allowed the formation of a trinuclear copper complex (2triox·H2O).