Synthesis and Cytotoxicity of bis(pyrazol-1-yl)-Alkane Derivatives with Polymethylene Linkers and Related Mono- and Dipyrazolium Salts

Reactions of α,ω-dibromoalkanes with pyrazole and 3,5-dimethylpyrazole in superbasic medium of dimethyl sulfoxide – potassium hydroxide were used for the synthesis of bidentate ligands: bis(pyrazol-1-yl)alkanes and bis(3,5-dimethylpyrazol-1-yl)alkanes linked by alkyl chains containing between four and twelve methylene groups. Oxidative iodination of the obtained compounds with I2–HIO₃–H₂SO₄ system in acetic acid provided diiodo derivatives: bis(4-iodopyrazol-1-yl)alkanes and bis(4-iodo-3,5-dimethylpyrazol-1-yl)alkanes. The obtained diiodo derivatives of pyrazole were further converted to mono- and dipyrazolium salts by alkylation of nitrogen atom at position 2 of the pyrazole rings with iodomethane, as well as with methyl triflate. These products are of interest as precursors to mesoionic N-heterocyclic carbene complexes. The cytotoxicity of the obtained compounds was studied against THP-1 monocytic leukemia cells.