Synthesis of Diflunisal via Suzuki Cross-Coupling: A Comprehensive Laboratory Experiment Integrating Chemical Tools

This article presents an advanced organic chemistry laboratory experiment for undergraduate students that integrates various subdisciplines. The experiment focuses on the synthesis of diflunisal, a nonsteroidal anti-inflammatory drug, through a palladium-catalyzed Suzuki cross-coupling reaction. The activity emphasizes reaction mechanisms, atom economy, and the environmental impact of synthetic processes. Students gain hands-on experience with transition-metal catalysis and compound characterization, with a particular focus on NMR (Nuclear Magnetic Resonance) techniques. The level of difficulty can be adjusted by the instructor to match the students’ expertise. Additionally, databases can be used to investigate synthetic pathways and optimize reaction conditions, fostering essential research skills. Moreover, the biaryl nature of diflunisal allows the introduction of the concept of axial chirality and atropisomerism. By integrating experimental work, NMR analysis, database-driven activities and theoretical conformational analysis, this project provides students with a comprehensive understanding of interdisciplinary chemistry. It develops their practical and analytical skills, preparing them to address complex scientific challenges independently. Students consolidate their understanding of concepts by working in teams to present their experimental results in a scientific poster session. This final activity, conducted in a conference-like setting, promotes teamwork, scientific communication, peer interaction, and critical thinking.