Synthesis and herbicidal activities of acylalanine-containing 3-(pyridin-2-yl)benzothiazol-2-ones

3-(Pyridin-2-yl)benzothiazol-2-one derivatives are a novel class of protoporphyrinogen oxidase (PPO) inhibitors. Although they demonstrate extraordinary herbicidal activity against broadleaf weeds, their efficacy against grass weeds remains limited. To develop broad-spectrum herbicide candidates, a series of 3-(pyridin-2-yl)benzothiazol-2-one derivatives bearing acylalanine moiety were designed in this study.

Using a hybridization-substructure-combination strategy, the active groups of acylalanine fungicides were incorporated into the 3-(pyridin-2-yl)benzothiazol-2-one scaffold. Starting from benzothiazol-2-one, 20 title compounds were synthesized via aromatic nucleophilic substitution, nitration, reduction, N-alkylation and acylation successively. The herbicidal activities of these compounds against Echinochloa crus-galli and Portulaca oleracea were preliminarily evaluated by Petri dish assays. Additionally, the post-emergence herbicidal activity of the most potent compounds, I-09 and I-13, was further assessed against multiple weed species in greenhouse pot experiments. Compound I-09 demonstrated 100% post-emergence herbicidal efficacy against broadleaf weeds (Solanum nigrum; Capsella bursa-pastoris; Descurainia sophia; Veronica polita) at an application rate of 75 g a.i./ha. Structure-activity relationship (SAR) analysis revealed that the herbicidal activity was determined by the synergistic effects of substituents on the pyridine ring and side chains attached to the aniline moiety. The 3-fluoro-5-trifluoromethyl-pyridine group was identified as the optimal substitution pattern at the 3-position of benzothiazol-2-one, and the simultaneous introduction of ethyl acetyl and propionyl groups was found to be essential for maintaining activity.

A new class of acylalanine-containing 3-(pyridin-2-yl)benzothiazol-2-one derivatives was discovered as promising candidates for herbicides. We hope these findings will provide valuable information for the development of herbicides. © 2025 Society of Chemical Industry.