Design, Synthesis, and Herbicidal Activities of N-(5-(3,5-Methoxyphenyl)-(thiazole-2-yl))phenoxyacetamide Derivatives

Thiazole and phenoxyacetic acid are key moieties in many natural and synthetic biologically active agents. A series of <i>N</i>-(5-(3,5-methoxyphenyl)-(thiazole-2-yl))phenoxyacetamide derivatives <b>6an-6bd</b> were designed and synthesized, and their structures were confirmed by NMR and HRMS. Most of derivatives exhibited superior inhibition of <i>Echinochloa crusgalli</i> (E.c.) and <i>Lactuca sativa</i> (L.s.) seed germination by the Petri dish bioassay. Indeed, herbicidal bioassays indicated that <b>6an</b> (2-(2,4-dichlorophenoxy)-<i>N</i>-(5-(3,5-dimethoxyphenyl)-1,3,4-thiadiazol-2-yl)acetamide) had the best inhibition against L.s. (IC₅₀ = 42.7 g/ha, 375 g/ha at field experiments). <b>6an</b> also had no harmful effect on <i>Zea mays</i> at 2- to 4-fold field usage. Moreover, transcriptomics and metabolomics analysis showed that <b>6an</b> significantly influenced cell metabolism, including galactose metabolism and ascorbate and aldarate metabolism. These discoveries highlight that <b>6an</b> shows promise to be developed as a potential herbicide.