Expanding 1,2,4-triketone Toolbox for use as Aluorinated Building Blocks in the Synthesis of Pyrazoles, Pyridazinones and β-diketohydrazones

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. © 2021 Elsevier B.V.This work carried out in the framework of the basic theme of the Russian Academy of Sciences (state registration № AAAA-A19-119011790132-7). Single-crystal X-ray diffraction analysis for 3g, 3f and 10a was performed using the equipment of the JRC PMR IGIC RAS. Single-crystal X-ray diffraction analysis for 5d, 7a, 9a and physicochemical studies were carried out using the equipments of the Center for Joint Use "Spectroscopy and Analysis of Organic Compounds" at the Postovsky Institute of Organic Synthesis UB RAS