Synthesis of Unsymmetrical Alkynes via the Alkylation of Sodium Acetylides. An Introduction to Synthetic Design for Organic Chemistry Students

This article describes an inquiry-based experiment for the undergraduate organic chemistry laboratory. The use of acetylides as nucleophiles is a common theme used in most organic textbooks as an introduction to retrosynthetic analysis. We have developed a problem-based application of this methodology for the first-semester organic laboratory. In this experiment, students are assigned to work in teams to design a microscale synthesis of an unsymmetrical alkyne using commercially available terminal alkynes and alkyl halides. Team members work collaboratively to perform the synthesis and characterize the resulting products using TLC, IR, and 1H NMR spectroscopy. Depending on the chosen reactants, students observe both substitution and elimination products, or in some cases, no reaction at all. Therefore, data interpretation is an important component of this experiment. Students must determine the composition of their product mixtures by comparison to starting materials. The structures of expected and unexpected products must be elucidated and justified mechanistically. Our students perform this experiment prior to the investigation of elimination reactions in the lecture, which adds a discovery element. This experiment can be performed in two three-hour lab periods; however, advance preparation is required for the synthetic design of an assigned target.