New 4-fluoroalkyl substituted N-phenylpyrazoles: Synthesis promoted by DAST and multinuclear NMR analysis

• DAST in fluorination reactions of 4-(formyl) and 4-(hydroxymethyl) 3-aryl-1H-1-phenylpyrazoles.
• Mono- and difluoromethyl groups insertion at C4 position of phenylpyrazoles.
• New 3-aryl-4-(di)fluoromethyl-1H-1-phenylpyrazoles are synthesized.
• Fluorinated compounds 1H, 13C and 19F spin-spin coupling NMR spectra assignments are presented and discussed.
• New 19F NMR assignments for the fluoromethyl groups at C4 position of phenylpyrazoles.

This paper reports a synthetic and NMR spectroscopic studies of two new series of 4-fluorinated 1,3,5-substituted 1H-pyrazoles. Firstly, an efficient synthesis of new series of 3-aryl-4-(di)fluoromethyl-1H-1-phenylpyrazoles, where [aryl = Ph, 4-NO2C6H4, 4-CH3OC6H4] is described, from fluorination reactions of 4-(formyl)- and 4-(hydroxymethyl)-1H-1-phenylpyrazoles in dichloromethane as solvent at room temperature, employing diethylaminosulfur trifluoride (DAST) as fluorinating agent in 41 to 73% yield. The 4-formyl-pyrazoles are obtained in 54–58% yield by Vilsmeier–Haack reaction using a mixture of POCl3/DMF with arylhydrazones, which were derived from the respective aryl methyl ketones and phenylhydrazine. The 4-hydroxymethyl-pyrazole precursors were easily obtained from the reduction of 4-formyl-pyrazoles by sodium borohydride (NaBH4) in 52–87% yield. Subsequently, the present work also discusses the 1H, 13C and 19F NMR spectroscopic data.

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