Filling the gap: Chemistry of 3,5-bis(trifluoromethyl)-1H-pyrazoles

Pyrazoles represent important building blocks for the preparation of bioactive compounds and a large variety of materials, due to their rich coordination chemistry. Unusual and interesting properties may be imparted to molecules embodying highly fluorinated pyrazoles, but to date only few examples of polyfluorinated pyrazoles have been described. In this work we report an improved preparation of 3,5-bis(trifluoromethyl)-1H-pyrazole, the subsequent transformation into hitherto unknown 4-functionalized (F, Cl, Br, I, NO2, NH2) derivatives and the evaluation of selected chemical and physical properties of these compounds.

Graphical abstractAn optimized synthesis of 3,5-bis(trifluoromethyl)-1H-pyrazole was developed and a series of 4-substituted derivatives were prepared and characterizedFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Optimized preparation of 3,5-bis(trifluoromethyl)-1H-pyrazole. ► Halogenated derivatives of 3,5-bis(trifluoromethyl)-1H-pyrazole. ► Nitro and amino derivatives of 3,5-bis(trifluoromethyl)-1H-pyrazole. ► Electrophilic substitution of EWG-substituted pyrazoles. ► 3,5-Bis(trifluoromethyl)pyrazole as a potential privileged scaffold in drug discovery.