Design, Synthesis, and Antifungal Activity of Novel 2-Ar-1,2,3-Triazole Derivatives

Triazoles are crucial molecular frameworks in the development of fungicidal compounds. Although there has been extensive research on triazole derivatives for fungicide discovery, the investigation of 2-Ar-substituted-1,2,3-triazoles remains in progress. This study reports the synthesis and evaluation of the fungicidal activity of 27 distinct 2-Ar-substituted-1,2,3-triazole derivatives. These derivatives were synthesized from anilines through a three-step process, with the key step being the Cu(II)-catalyzed annulation reaction of readily accessible alkyl 3-aminoacrylates with aryldiazonium salts. All derivatives were novel, and their structures were characterized using ¹H NMR, ¹³C NMR, and high-resolution mass spectrometry. Their antifungal activity was tested against five phytopathogenic fungi. Twelve of the target compounds exhibited better performance than the positive control hymexazol in the fungal test. Notably, compound 6d demonstrated the most potent inhibition against Botryosphaeria dothidea with an EC₅₀ value of 0.90 mg/L. The structure-activity relationships are also discussed in this paper. Preliminary studies on the antifungal mechanism of compound 6d revealed that it inhibits ergosterol synthesis and alters the morphology and ultrastructure of the B. dothidea mycelium. These results suggest that the designed 2-Ar-substituted-1,2,3-triazole-containing hydrazone derivatives warrant further investigation as potential lead compounds for novel antifungal agents.