Síntese mecanoquímica de 3-aciltionaminonas e sua aplicação na mecanossíntese de isoxazóis e pirazóis

Abstract

The 3-acylthioenaminones are characterized by an N-C=C-C=S a-acylated conjugate system which makes this species an interesting starting material for obtaining various derivatives, such as nitrogen heterocycles. These include azoles, especially pyrazoles and isoxazoles, molecules widely used in medicine and agriculture due to their bioactive properties and low cost. Thus, the study of the synthesis and reactivity of 3-acylthioenaminones using sustainable methodologies, such as mechanochemistry, arises as a necessity, since the number of works described in the literature with this focus is still scarce. Thus, we investigated the synthesis of 3-acylthioenaminones from acyclic enaminones and isothiocyanates through mechanochemistry in order to obtain a library of compounds, which later were used against bidentate nucleophiles to investigate their reactivity and obtain azoles. We established an unprecedented methodology for the solvent-free synthesis of 3-acylthioenaminones using mechanochemistry, 18 molecules were obtained with yields from 23% to 96% and the majority of the compounds were in the form of E/Z isomeric mixtures. Furthermore, investigating the reactivity of this species against dinucleophiles under different reaction conditions, it was possible to synthesize 8 pyrazole nuclei, 4 isoxazoles, 3 hydrazones and 1 hybrid of pyrazoles-thiadiazoles with yields from 12% to 78%. A total of 35 molecules were obtained, 26 are new in the literature, these were characterized by melting point, gas chromatography, infrared spectroscopy, 1H and 13C Nuclear Magnetic Resonance (NMR). Thus, mechanochemistry proved to be an efficient technique for obtaining 3-acylthioenaminones and their derivatives.