Design and Evaluation of Pyrazole Herbicides: QSAR-Driven Synthesis for Effective Weed Control and Crop Safety in...

A total of twenty pyrazole derivatives were synthesized using alkoxy or halo acetophenones in reaction with N, N-dimethylformamide dimethylacetal (DMF-DMA). These compounds were characterized through ¹H NMR, ¹³C NMR, and LC-HRMS techniques. Their herbicidal efficacy against barnyard grass (Echinochloa crus-galli) was evaluated via in vitro bioassays. Notably, compound 6a (5-Methoxy-2-(1H-pyrazol-3-yl) phenol) and compound 6s (3-(4-Fluoro-2-hydroxyphenyl) pyrazole) demonstrated inhibition rates of 30.6% to 54.1% and 26.9% to 50.6%, respectively, across concentrations ranging from 62.5 to 1000 µg mL^- 1. In in vivo assessments, compound 6a yielded the highest weed control index (WCI) of 51.32%, followed by compound 6s with a WCI of 50.24%. These findings indicate that compound 6a represents a promising herbicidal agent, effectively managing barnyard grass while exhibiting tolerance toward rice seedlings following both post-emergence and soil application. Toxicity predictions for the synthesized compounds were evaluated for fish (LC₅₀: 0.0001 to 38.1 mg/L), daphnids (LC₅₀: 0.0001 to 27.7 mg/L), and green algae (EC₅₀: 0.0001 to 1.70 mg/L), including chronic toxicity (ChV). Using the ECOSAR model, the assessment found that shorter chain compounds are within acceptable limits. The binding free energy of compound 6a with HPPD was relatively low (-8.3), which was consistent with the findings of bioassay activity studies. As a result, compound 6a could serve as the starting point for the development of novel HPPD inhibitors.