Synthesis of Eugenol-Fluorinated Triazole Derivatives and Evaluation of Their Fungicidal Activity

Eugenol (C10H12O2, 4-allyl-2-methoxyphenol) is a phenolic natural product that has several biological activities and possibilities of applications. It is herein described the synthesis of eugenol-fluorinated triazole derivatives and evaluation of their fungicidal activity. The reaction of eugenol with epichlorohydrin resulted in the preparation of (+/-)-2-((4-allyl-2-methoxyphenoxy) methyl)oxirane (1) in 88% yield. The azidolysis of 1 with sodium azide gave the azido-alcohol (+/-)-1-(4-allyl-2-methoxyphenoxy)-3-azidopropan-2-ol (2) in 94% yield. The CuAAc reaction between compound 2 and different terminal alkynes afforded a series of eleven derivatives (3a-3k) within 48-80% yield. All the synthesized compounds were characterized by infrared (IR) and nuclear magnetic resonance (H-1 and C-13) spectroscopies and high-resolution mass spectrometry. The in vitro inhibitory activity of the compounds on the mycelial growth of a strain of Colletotrichutn sp., that causes anthracnose disease on papaya fruits, was evaluated. The best result was observed for compound 1-(4-allyl-2-methoxyphenoxy) 3 (4 (2 fluoropheny1)-1H-1,2,3-triazol-1-yl)propan-2-ol (3d) that showed a mean growth-inhibition zone of 5.10 mm in a well-diffusion assay, and may serve as a template for additional structural modifications, aiming for more potent fungicidal activity.