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

Abstract BACKGROUND 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. RESULTS 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. CONCLUSION 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.