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

• Published in: Journal of fluorine chemistry 2022-01, Vol.253, p.109932, Article 109932
• Main Authors: Edilova, Yulia O., Kudyakova, Yulia S., Kiskin, Mikhail A., Burgart, Yanina V., Saloutin, Victor I., Bazhin, Denis N.
• Format: Article
• Language: English
• Subjects: Acetonitrile; Ethanol; Fluorination; Furan-3(2H)-one; Hydrazines; Lithium; Pyrazole; Pyrazoles; Pyridazinone; Solvents; Β-diketohydrazone; Β-diketonate
• ISSN: 0022-1139; 1873-3328
• DOI: 10.1016/j.jfluchem.2021.109932

•Pyrazoles, pyridazinones or 1,3-diketohydrazones were prepared via 1,2,4-triketone transformation with hydrazines.•The impact of solvent on the condensation reaction is revealed.•The nature of perfluoroalkyl group determinated the regioisomeric pyrazole formation. Fluorinated lithium β-diketonates bearing a methyl acetal group behave in the condensation reactions with hydrazines as trielectrophilic building blocks for the preparation of pyrazoles, pyridazinones and β-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-RF-pyrazoles were obtained from the acid-catalyzed cyclocondensation of lithium β-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 β-diketohydrazones formation via initial acetal fragment interaction with N,N-dinucleophile. [Display omitted]