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Polyfluoroalkylated antipyrines in Pd-catalyzed transformations
Evgeny V Shchegolkov1, Yanina V Burgart1, Daria A Matsneva1
1Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences S. Kovalevskoi St., 22 Ekaterinburg 620990 Russia saloutin@ios.uran.ru.
Abstract:
In the direct C-H arylation with arylhalogenides in the presence of Pd(OAc)2, trifluoromethyl-containing antipyrine reacts very slowly and incompletely owing to the low nucleophilicity of its C4 center. However, it was effective in modifying polyfluoroalkyl-substituted 4-bromo- and 4-iodo antipyrines by the Suzuki and Sonogashira reactions. It was established that using Pd2(dba)3 as catalyst and XPhos as phosphine ligand was the optimal catalytic system for the synthesis of 4-aryl- and 4-phenylethynyl-3-polyfluoroalkyl-antipyrines. Moreover, iodo-derivatives as the initial reagents were found to be more advantageous compared to bromo-containing analogs. It was found that 4-phenylethynyl-5-CF3-antipyrine has a moderate activity against the influenza virus A/Puerto Rico/8/34 (H1N1) and 4-iodo-5-CF3-antipyrine reveals a weak activity against the vaccine virus (strain Copenhagen) and bovine diarrhea virus (strain VC-1).
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