Synthesis, fungicidal activities and three dimensional quantitative structure-activity relationship of 2-substituted phenyl-5-substituted benzamide-1,3,4-thiadiazole

Thirty-three different 2-substituted phenyl-5-substituted benzamide-1,3,4-thiadiazole E ₁ -E ₃₃ were prepared by reaction of substituted benzoic acid with thiosemicarbazone, phosphorus oxychloride and substituted benzoyl chloride. The structure of the target compounds were confirmed and characterized by proton nuclear magnetic resonance (¹H NMR) and high resolution mass spectroscopy (HRMS). Fungicidal activities of target compounds against Rhizopus nigricans, Penicillium glaucum, Botrytis cinerea, Alternaria brassicae and Aspergillus niger in vitro were studied with the mycelial growth rate method. A preliminary three-dimensional quantitative structure-activity relationship (3D-QSAR) of the target compounds against A. niger was carried out using CoMFA and CoMSIA. The results showed that most of the compounds showed good inhibitory activity, especially at the concentration of 50 µg/mL, the inhibitory rates of compounds E ₁ , E ₂ and E ₂₉ against the tested fungi were more than 80%, which were equivalent to that of the control pesticides, chlorothalonil and carbendazim. The results of the two models are combined to draw the conclusion: the effect of electrostatic field is higher than that of other potential fields. It was advantageous to enhance the fungicidal activity of the compounds when the benzene ring a introduces electron-donating group into 4-position, the 2 and 6-positions of benzene ring a and benzene ring b introduces electron-withdrawing group. The conclusions can provide insight into further design of highly antifungal title compounds.