Rapid Amide Coupling in Water for Undergraduate Laboratories

Chemistry in water is an emerging field that fulfills the fifth principle of green chemistry: replacing toxic organic solvents with their benign counterparts. Although some pharmaceutical industries have developed and adopted chemistry in water, its implementation in teaching laboratories is still limited. Therefore, we have designed an experiment dedicated to the undergraduate curriculum covering sustainable, completely organic-solvent-free amide coupling, which is one of the most heavily used reactions in the pharmaceutical industry. The designed experiment aims to acquaint students with the 12 principles of green chemistry, inform them of the shortcomings of the traditional synthetic procedures of amide coupling, make them aware of waste generation from toxic organic solvents, and show them the effectiveness of water as a benign reaction medium. With the training throughout the lab sessions, students were taught micellar catalysis, NMR (nuclear magnetic resonance) spectroscopy, IR (infrared) spectroscopy, separation techniques, and safety data.