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The application of Process Analytical Technology (PAT) methods is of ever-increasing importance in all areas of academic and industrial synthetic chemistry. Real-time reaction analysis is a major element in an overall PAT strategy, which includes advanced analytics, modeling and digitalization. The overall goal of a PAT strategy is to acquire and transform data into actionable information that speeds reaction understanding and process knowledge to maximize yield, quality and sustainability of chemical syntheses.
Dependent on the specific chemistry, spectroscopic methods including FTIR, Raman, UV/Vis, NIR, NMR and MS can be chosen to enable real-time analysis. State-of-the-art chromatographic methods such as UPLC are also available for online reaction analysis. These technologies provide extensive data streams that can be analyzed with advanced analysis and modeling tools. Frequently, multiple real-time analysis techniques are used in combination to provide data that fully characterize a reaction or process.
Get the “Real-time Reaction Analysis Guide” to learn about key methods to developing deeper reaction understanding and process knowledge for trending areas of synthetic chemistry.
There are a number of current trends and themes in synthetic chemistry that have evolved in which PAT and reaction analysis are important:
- Quality by Design (QbD) Strategy. As an active trend in pharmaceutical and chemical production, QbD requires real-time reaction analysis technology development.
- Data-Rich Experimentation (DRE). DRE provides process efficiencies and sustainability by utilizing PAT and advanced, dynamic modeling to yield information to enable optimization and scale-up of reactions far more rapidly and with fewer experiments.
- Continuous Processing. Pharmaceutical chemistry is rapidly evolving to the use of continuous flow methods, which are well-served by reaction analysis technology to provide uninterrupted, continuous measurements.
- Sustainable Chemistry via Catalysis. In the design of efficient, sustainable syntheses and processes, organocatalysis, organometallic catalysis and biocatalysis are among the most active areas of development. PAT reaction analysis has proven highly valuable in understanding kinetics, mechanisms, catalytic cycles and the effect of reaction parameters in catalyst-based chemistry.
- Particle Engineering. Real-time analysis has proven invaluable in understanding the complexities of crystallization processes, providing data on particle size, size distribution and morphology. PAT tracks the impact of process parameters such as temperature, mixing, addition rate, solute concentration and seeding protocol ensuring development and scale-up of robust crystallizations.
- Biological Processes. Real-time, compositional reaction analysis can provide optimization and active control by measuring the concentration of nutrients, metabolites, biomass, products and by-products as a function of time in biological reactions.
- Sustainable Processes. These processes optimize yield, purity and atom efficiency while simultaneously reducing the use of hazardous materials and energy demands. To accomplish this requires thorough reaction understanding and process knowledge provided by PAT.
- Polymer Synthesis. In-situ analytical methods track the conversion of monomer to the formation of polymers to determine reaction kinetics and to control the effect of variables on key polymer attributes. Real-time analysis is used to continually monitor polymer melts, extrusions and films to ensure product quality.
