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

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).