Selective Construction For Polyfluoroarylated Pyrazole Ethers

Fluorine has peculiar characteristics such as high electronegativity and small covalent radius render fluorocarbons unique. The introduction of fluorine atom or fluorine-containing functional groups into an organic molecule imparts unique physicochemical properties, including high metabolic stability, solubility, and lipophilicity, as well as the ability to hydrogen band. Consequently, the organofluroine compounds are versatile in the fields of pharmaceutical and agrochemical chemistry.Pyrazolone frameworks were a class of important subunits, and compounds bearing such moiety frequently exhibited wide applications in pharmaceutical and agrochemical. Pyrazolone, as an ambident nucleophile, were mainly focused on the Michael addition reactions by employing pyrazolone as a carbon nucleophile. However, fewer examples have been documented for organic transformations by using pyrazolone as an oxygen nucleophile.In this thesis, we developed a base initiated intermolecular SNAr reaction between pyrazolones and polyfluoroarenes via the selective C-F bond cleavage. Different parameters were tested to screen the appropriate reaction conditions such us solvent, temperature and additives. Under the optimized condition, 19 products were synthesized in moderate to high yields(44-88%). Additionally, our method was also applied to isoxazol substrates with polyfluoroarenes. This thesis provided a new alternative way for the preparation of polyfluoroarylated ethers, which was simple, mild and low toxicity compared with the transition metal catalyzed reactions. Furthermore, it is expected that this approach might be used for assembling valuable pharmaceutical and bioactive molecules in the future.