4-Nitropyrazolin-5-ones as Readily Available Fungicides of theNovel Structural Type for Crop Protection: Atom-Efficient ScalableSynthesis and Key Structural Features Responsible for Activity

The development of new types of fungicides for agriculture and medicine is highly desirable due to the uprising fungalresistance against commonly used compounds. Herein, 4-substituted-4-nitropyrazolin-5-ones (nitropyrazolones) were proposed ashighly active fungicides of the novel structural type. Thefirst scalable and practical method for the nitropyrazolone synthesis wasproposed, which is atom-efficient, is applicable for the multigram scale synthesis, and allows for production of a wide variety ofnitropyrazolones with high yields and purity. The synthesized compounds demonstrated high fungicidal activity against the broadspectrum of phytopathogenic fungi (Venturia inaequalis,Rhizoctonia solani,Fusarium oxysporum,Fusarium moniliforme,Bipolarissorokiniana, andSclerotinia sclerotiorum). Their mycelium growth inhibiting activity was comparable or superior to that of kresoxim-methyl.In vitroactivity againstStaphyloccocus aureus,Candida albicans, andAspergillus nigerrevealed that nitropyrazolones arepromising candidates against human pathogens. The key factors for the manifestation of high fungicidal activity were established tobe an aromatic substituent on the N1 atom and small substituents, such as methyl, at the C3 and C4 positions of the pyrazolone ring.

Automated summary

This study presents a novel structural type of highly active fungicides, nitropyrazolones, and proposes a scalable method for their synthesis. The synthesized compounds demonstrate high fungicidal activity against various phytopathogenic fungi and human pathogens.