Synthesis and Herbicidal Activity of 2-(2-Oxo-3-pyridyl-benzothiazol-6-yloxy)hexanoic Acids

The discovery of a lead compound is fundamental to herbicide innovation, but the limited availability of valuable lead compounds has hindered their development in recent years. By utilizing the structural diversity-oriented inactive group strategy, 3-(2-pyridyl)-benzothiazol-2-one was identified as a promising lead scaffold for herbicides, starting from benzothiazole which is an inactive moiety commonly found in herbicides such as mefenacet, benazolin, benzthiazuron, and fenthiaprop-ethyl. To investigate the structure-activity relationship (SAR) of these chemicals, a series of 2-(2-oxo-3-pyridyl-benzothiazol-6-yloxy)hexanoic acid derivatives (VI01 ∼ VI28) were synthesized through classical nucleophilic SNAr reaction using halogenated pyridines and 6-methoxybenzothiazole-2-one. The chemical structures of all the title compounds were confirmed by NMR and MS analysis. Petri dish assays indicated that many compounds exhibited potent herbicidal activity against both broad-leaf weeds and grass weeds at 1.0 mg/L. The SAR analysis revealed that the presence of a trifluoromethyl group at the 5-position of pyridine is essential for herbicidal activity. Furthermore, carboxylic esters exhibit higher herbicidal activity compared to carboxylic amides and free acids, and the activity decreased with the extension of the carbon chain. The postemergence herbicidal activity of VI03 against 16 species of weeds was tested by pot experiments in a greenhouse. VI03 demonstrated comparable efficacy in controlling broadleaf weeds and superior efficacy in controlling grass weeds compared to carfentrazone ethyl. The present study has unveiled a novel molecular scaffold exhibiting remarkably potent herbicidal activity. These findings are anticipated to provide valuable insights for the advancement of new herbicides and offer an alternative approach for managing resistant weeds.