Schiff-base–bearing new bis(thiosemicarbazone) derivatives were prepared from terephthalaldehyde and various thiosemicarbazides. FT–IR, 1H NMR, 13C NMR, and UV–Vis spectroscopic methods and elemental analysis were used to elucidate the identification of the synthesized molecules. The in vitro antioxidant activity of the synthesized compounds was analysed with the 1,1-diphenyl-2-picryl hydrazyl free-radical–trapping process. The synthesized compounds exhibited lower antioxidant activity than the standard ascorbic acid. IC50 values of the synthesized molecules measured from 3.81 ± 0.01 to 29.05 ± 0.11 μM. Among the synthesized compounds, compound 3 had the best antioxidant activity. Moreover, this study explained the structure–activity relationship of the synthesized molecules with different substituents in radical trapping reactions.

New bis(isatins-thio/carbohydrazones) based on Schiff bases were prepared from terephthalaldehyde biscarbohydrazone and 5-substituted isatins in the presence of a drop of sulfuric acid under reflux in ethanol. Terephthalaldehyde bis(thio/carbohydrazone) was synthesized by the reaction of (thio)/carbohydrazide and terephthalaldehyde in the presence of a few drops of acetic acid under reflux in ethanol. The structures of these synthesized compounds were determined using IR, 1H NMR, and 13C NMR spectroscopy and elemental analysis. The in vitro antioxidant activity of all the compounds was determined by the 1,1-diphenyl-2-picryl hydrazyl (DPPH.) free radical scavenging method. Compound 2 showed the best antioxidant activity.