Synthesis and Fungicidal Evaluation of Pyridylpyrazole Derivatives Bearing a Benzoxazinone Scaffold via a Metal-Free Approach

To develop novel, green, and highly effective fungicides, a series of benzoxazinone-functionalized pyridylpyrazole derivatives (8a–8z) were designed and synthesized via a metal-catalyst-free route using a pyraziflumid intermediate. The synthetic procedure included diazotization, cyclization, hydrolysis, and methanesulfonyl chloride-mediated dehydrative cyclization. The optimal conditions (3.0 equiv pyridine in water, BF4− as the counterion, 25 °C, 3 h) afforded a maximum yield of 63.7%. Bioassays showed that 8p exhibited 92.0% inhibition against maize rust (Puccinia polysora) and 8q exhibited 90.5% inhibition against cucumber anthracnose (Colletotrichum orbiculare) at 50 mg/L. Substituents on the aromatic and pyridyl moieties jointly regulated fungicidal activity, with distinct pathogen-dependent selectivity. Docking results revealed that 8j bound to succinate dehydrogenase (SDHI) with a binding energy of −11.8 kcal/mol, and the polar interaction between its carbonyl group and Lys163 was key to enhancing binding affinity. This study provides a scientific basis for the green synthesis and rational design of pyridylpyrazole-based fungicides.