Mechanochemistry in Senior Undergraduate Laboratory: NHC Complexes, Catalysis, and Sonogashira Cross-Coupling

Incorporating sustainable chemical practices into advanced synthesis and catalysis courses in university chemistry programs is essential for bridging gaps in traditional synthesis and for raising sustainability awareness among students. This work highlights the role of mechanochemistry in organic-inorganic synthesis and catalysis, emphasizing the green chemistry principles and metrics through a module with three laboratory sessions. The module is supported by a series of questions to reinforce laboratory activities and chemistry principles, including mechanochemistry, N-heterocyclic carbene (NHC) organometallic complexes, and Sonogashira coupling with different metal catalysts. Students synthesized a Cu-NHC complex through a solvent-free, eco-friendly mechanochemical method using automated ball milling in the first laboratory session. In the subsequent sessions, the Cu-NHC complex was employed as both a metal-transfer reagent to prepare Au-NHC and a catalyst for Sonogashira cross-coupling. Students compared Pd- and Pd-free Cu-catalyzed Sonogashira couplings, examining the role of the catalyst and its impact on the reaction mechanism and yield. The products were isolated and purified through simple methods, including precipitation, washing, and chromatography, followed by characterization by NMR spectroscopy, mass spectrometry, and melting point analysis. All procedures were performed under air and were feasible for students to complete within a typical laboratory time frame.