Mild Nitration of Pyrazolin-5-ones by a Combination of Fe(NO3 )3 and NaNO2 : Discovery of a New Readily Available Class of Fungicides, 4-Nitropyrazolin-5-ones.

4-Nitropyrazolin-5-ones have been synthesized by the nitration of pyrazolin-5-ones at room temperature by employing the Fe(NO3 )3 /NaNO2 system. The method demonstrated selectivity towards the 4-position of pyrazolin-5-ones even in the presence of NPh and allyl substituents, which are sensitive to nitration. It was shown that other systems containing FeIII and nitrites, namely Fe(NO3 )3 /tBuONO, Fe(ClO4 )3 /NaNO2 , and Fe(ClO4 )3 /tBuONO, were also effective. Presumably, FeIII oxidizes the nitrite (NaNO2 or tBuONO) to form the NO2 free radical, which serves as the nitrating agent for pyrazolin-5-ones. The synthesized 4-nitropyrazolin-5-ones were discovered to be a new class of fungicides. Their in vitro activities against phytopathogenic fungi were found comparable or even superior to those of commercial fungicides (fluconazole, clotrimazole, triadimefon, and kresoxim-methyl). These results represent a promising starting point for the development of a new type of plant protection agents that can be easily synthesized from widely available reagents.