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Theoretical and experimental investigation of the polyeletrophilic β-enamino diketone: straightforward and highly regioselective synthesis of 1,4,5-trisubstituted pyrazoles and pyrazolo[3,4-d]pyridazinones
- da Silva, Michael J. V., Silva, Raí G. M., Melo, Ulisses Z., Gonçalves, Davana S., Back, Davi F., Moura, Sidnei, Pontes, Rodrigo M., Basso, Ernani A., Gauze, Gisele F., Rosa, Fernanda A.
- RSC advances 2015 v.6 no.1 pp. 290-302
- Lewis acids, aniline, electrospray ionization mass spectrometry, hydrazines, monitoring, nuclear magnetic resonance spectroscopy, pyrazoles, regioselectivity
- Obtaining a new precursor enamino diketone with five electrophilic centers is reported, along with theoretical and experimental studies of its reactivity against mono- or dinucleophiles. The Fukui function showed that the β-carbon is the most electrophilic center, followed by the carbonyl ketone and the carbonyl ester, respectively. The reaction of enamino diketone with aniline and hydrazines allowed for the synthesis of a new enamino diketone and 1,4-disubstituted pyrazoles-5-carboxylates, respectively. The regiochemistry and mechanism of syntheses of 1,4-disubstituted pyrazoles-5-carboxylates were determined from reaction monitoring by ESI-MS, NMR analysis and crystallographic data, and fully agreed with the theoretical results. The versatility and efficiency of the enamino diketone was demonstrated by the reaction with hydrazines furnishing multi-functionalized pyrazoles and pyrazolo[3,4-d]pyridazinone derivatives with high regioselectivity.