Expanding 1,2,4-triketone toolbox for use as fluorinated building blocks in the synthesis of pyrazoles, pyridazinones and β-diketohydrazones

Fluorinated lithium beta-diketonates bearing a methyl acetal group behave in the condensation reactions with hydrazines as trielectrophilic building blocks for the preparation of pyrazoles, pyridazinones and beta-diketohydrazones. For the first time, solvent-induced regioisomeric and heterocyclic ring size-controlled formation was observed for 1,2,4-triketone analogues. Fluoroalkylated acetyl NH-pyrazoles or substituted 5-R-F-pyrazoles were obtained from the acid-catalyzed cyclocondensation of lithium beta-diketonates with (aryl)hydrazines in ethanol. In methanol solvent acetyl-containing 3-CF3-pyrazoles were isolated because of inverse nucleophilic attack of arylhydrazines. The use of aprotic acetonitrile in the condensation resulted in regioselective trifluorinated pyridazinones and fluorinated beta-diketohydrazones formation via initial acetal fragment interaction with N,N-dinucleophile.

Automated summary

In this study, fluorinated lithium beta-diketonates reacted with hydrazines to form pyrazoles, pyridazinones, and beta-diketohydrazones, and solvent-induced regioisomeric and heterocyclic ring size-controlled formation was observed. Acid-catalyzed cyclocondensation in ethanol yielded fluoroalkylated acetyl NH-pyrazoles or substituted 5-R-F-pyrazoles, while acetyl-containing 3-CF3-pyrazoles were isolated in methanol solvent due to inverse nucleophilic attack of arylhydrazines.