Title: Green, Renewable, and Continuous Manufacturing of the Active Pharmaceutical Ingredient Paracetamol.
Committee Members: Andreas Bommarius, Carsten Sievers, Marta Hatzell, Stefan France, Matthew Realff, and Christopher Luettgen
Location: April 10, 2025, 8 am to 10 am in ES&T 2229.
Paracetamol, the active ingredient of Tylenol®, is one of the largest scale active pharmaceutical ingredients (API) in the world. Current methods to produce paracetamol use non-renewable petrochemical feedstocks, are unselective, have poor Green Chemistry metrics, and include potentially hazardous reaction conditions. New processes to paracetamol should be renewable, Green, selective, and safe. Lignin derived phenol and its derivatives are a promising source of the aromatic unit structures needed to synthesize many APIs. To that end, we explore chemical routes to synthesize paracetamol from three phenol derivatives: hydroquinone, p-benzoquinone, and 4-nitrophenol. We show that routes from 4-nitrophenol have the greatest potential for industrial viability and scale-up through a detailed analysis of the Green Chemistry metrics of routes starting from each feedstock. In addition, we develop novel reactor systems to synthesize paracetamol from 4-nitrophenol with significant improvements in the reaction yield as well as the process mass intensity compared to existing literature.