A Greener Synthesis of the Nonsteroidal Anti-inflammatory Drug Celecoxib

A laboratory experiment was developed to introduce green chemistry concepts through the synthesis of the nonsteroidal, anti-inflammatory drug, celecoxib. There are a range of issues based on the traditional synthesis of celecoxib including the use of a toxic solvent such as toluene, which is becoming severely restricted in its use, and other issues such as high energy consumption due to long reaction times together with wasteful extractions. A greener synthesis has been developed by making use of 2,2,5,5-tetramethyloxolane (TMO), a hindered ether, as a solvent that can be potentially biobased together with reducing reaction times and optimizing extraction procedures. These changes reduced waste by over 100 kg per kilogram of product. When implemented with students, they synthesized celecoxib, and the adaptations to the traditional process were discussed and evaluated using green chemistry metrics in conjunction with the DOZN tool together with the underlying reaction mechanisms.