Traditionally, organic chemistry students have been instructed to analyze reactions using standard offline analytical methods, such as High-Performance Liquid Chromatography (HPLC), Nuclear Magnetic Resonance (NMR) Spectroscopy, and Gas Chromatography (GC).
During Part I of his two part The Role of Process Analytical Technology (PAT) in Green Chemistry and Green Engineering online seminar series, Dominique Hebrault discussed scale-up challenges faced today by chemists and engineers. Too often, offline sampling methods – mostly chromatographic methods such as High Performance Liquid Chromatography (HPLC) or Gas Chromatography (GC) – are used to monitor processes which fail to resolve common issues like reaction monitoring, poor mass balance, delayed initiation/reaction stalled, and loss of yield/by-products. From a reaction engineering standpoint, obtaining heat mass balance information and preliminary kinetic data can be difficult using traditional offline methods during process scale-up. Forming the final solid can be challenging using traditional offline methods, including filtration/drying a bottleneck, excessive washing, polymorph inconsistency, and batch to batch variability can be difficult.