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Microwave-Assisted Preparation of 1-Aryl-1H-pyrazole-5-amines
Published on: June 23, 2019
Design and Synthesis of Pyrimidine Amine Containing Isothiazole Coumarins for Fungal Control
Kun Li1,2, Mengyuan Li1,2, Haolin Zhong1,2
1State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, P. R. China.
Abstract:
Developing new fungicides is always crucial to protecting crops. A series of 4-(3,4-dichloroisothiazol-5-yl)-7-(2-((5-(5-pyrimidin-4-yl)amino)ethoxy)-8-methyl) coumarin derivatives were designed and synthesized by Williamson ether condensation and substitution reactions. Structure determinations were clarified by 1H NMR, 13C NMR, and HRMS, and compound 4h crystallized by the fusion method for further structural confirmation. The in vitro bioassay results showed that the target compounds displayed good fungicidal activity against Alternaria solani, Botrytis cinerea, Cercospora arachidicola, Fusarium graminearum, Physalospora piricola, Rhizoctonia solani, and Sclerotinia sclerotiorum. Among them, compounds 4b and 4d showed higher inhibitory activity against R. solani, with EC50 values of 11.3 and 13.7 μg/mL, respectively, and they were more active than the positive control diflumetorim with an EC50 value of 19.8 μg/mL. Molecular docking suggested that compound 4b and diflumetorim may have similar interactions with complex I NADH oxidoreductase. Density functional theory calculation and pesticide-likeness analysis studies gave a rational explanation of their fungicidal activity. These results indicated that compounds 4b and 4d deserved further optimization according to the principle of pesticide-likeness.
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