Synthesis and Antioxidant Activity Evaluation of Novel 1,3,5-Triazine Derivatives Bearing a 4-(4-Aminophenyl)morpholin-3-one Moiety

Abstract

A series of novel 1,3,5-triazine 4-(4-aminophenyl)morpholin-3-one derivatives were synthesized in two stages. First, the nitrogen-ring 1,3,5-triazine was reacted with 4-(4-aminophenyl)morpholin-3-one to obtain 4-{4-[(4,6-dichloro-1,3,5-triazin-2-yl)amino]phenyl}morpholin-3-one via C²–N coupling under mild basic conditions at a low temperature (K₂CO₃, 0°C). The subsequent C–O couplings of the product at the C⁴ and C⁶ positions with various phenols were performed under reflux in the presence of K₂CO₃ to yield the target 4-(4-{[4,6-bis(substituted phenoxy)-1,3,5-triazin-2-yl]amino}phenyl)morpholin-3-ones. All the synthesized compounds were characterized by IR and ¹H and ¹³C NMR spectroscopy and mass spectrometry. The products were tested for antioxidant activity by the DPPH assay using ascorbic acid as reference drug (IC₅₀ = 350.01 ± 3.07 µM). It was found that the derivatives with electron-donor substituents in the phenoxy group (3-Me, 4-Me, and 4-Et) exhibited a notable antioxidant effect (IC₅₀ ≈ 210 µM), with the highest potency of them demonstrated by the 4-ethyl derivative (IC₅₀ = 190.55 ± 0.94 µM).