On the mechanochemical synthesis of C-scorpionates with an oxime moiety and their application in the copper-catalyzed azide–alkyne cycloaddition (CuAAC) reaction

Abstract

The development of sustainable processes requires the integration of the principles of green chemistry. In this work, we develop the solvent-free synthesis of bis- and tris-(pyrazol-1-yl)methanes from pyrazole and halooximes via 1,4-addition to conjugated α-halogenated nitrosoalkenes generated in situ under ball milling. The pro-ligands were complexed with copper, using a solvent-free procedure with equimolar quantities of reactants, to give catalysts copper(II) C-scorpionates with the oxime substituent at the C-center. The new catalysts were used to efficiently catalyze azide–alkyne cycloaddition reactions under solvent-free mechanochemical conditions. Through the overall process, we combine atom economy, the use of safer solvents and auxiliaries, design for energy efficiency and reduction of derivatives and catalysis (the 1st, 5th, 6th, 8th, and 9th principles of Green Chemistry). The sustainability metrics show that mechanochemistry provides a greener and more sustainable approach for the preparation of the catalysts and for the copper-catalyzed azide–alkyne cycloaddition (CuAAC) reactions. The development of novel C-scorpionates and their metal complexes, and their subsequent application in CuAAC reactions under mechanochemical conditions, presents an exciting avenue for the future of sustainable click chemistry.