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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. A PAT strategy aims to acquire and transform data into actionable information that speeds reaction understanding and process knowledge to maximize the yield, quality, and sustainability of chemical syntheses.
Depending 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 and orthogonal 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 develop deeper reaction understanding and process knowledge for trending areas of synthetic chemistry.
There are several 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 the implementation of real-time reaction analysis technology.
- Data-Rich Experimentation (DRE): DRE provides process efficiencies and sustainability by utilizing PAT and advanced, dynamic modeling to yield information to enable the 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: Organocatalysis, organometallic catalysis, and biocatalysis are among the most active areas of development in the design of efficient, sustainable syntheses and processes. 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 the development and scale-up of robust crystallization.
- 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. Accomplishing this requires thorough the reaction understanding and process knowledge provided by PAT.
- Polymer Synthesis: In-situ analytical methods track the conversion of monomers to the formation of polymers to determine reaction kinetics and to control the effect of variables on key polymer attributes. Real-time analysis continually monitors polymer melts, extrusions, and films to ensure product quality.