Accelerating your process optimization: sampling from reactions in-progress means better decisions in less time

Significance of the Topic

The detailed monitoring of reaction kinetics under process conditions is essential for fine chemical and pharmaceutical development. In-situ sampling at elevated pressures and temperatures delivers richer datasets, reduces material consumption and accelerates decision making in reaction optimization.

Objectives and Study Overview

This study demonstrates the use of an automated Optimization Sampling Reactor (OSR) to track hydrogenation of trans-cinnamic acid under pressurized conditions. Objectives include validating precise micro-sampling up to 400 psi, comparing catalyst supports and generating consistent kinetic profiles across eight parallel reactors.

Methodology

The core workflow involves:

• Preparing eight 40 mL stirred reactors loaded with substrate and catalyst.
• Purging and pressurizing each vessel via a controlled atmosphere sampling port.
• Collecting multiple 100 µL time-point samples at 0, 24, 48, 72 and 96 min without halting stirring.
• Diluting samples and quantifying conversion by HPLC.

Instrumentation

• Optimization Sampling Reactor (OSR) module with eight overhead-stirred reactors and O-ring-sealed antechamber for pressure equilibration.
• Lab Execution and Analysis (LEA) software for centralized data capture.
• High-performance liquid chromatography (HPLC) for quantitative analysis.
• Junior automated deck for sample transfer, dilution and plate handling.

Results and Discussion

Sampling precision was maintained below 4% RSD over volumes of 100–1000 µL at pressures up to 400 psi. The hydrogenation of trans-cinnamic acid with 5% Pd/C achieved complete conversion within 96 min, with <5% standard deviation across reactors. Lower-activity 5% Rh on alumina required 50 mg catalyst per run; matrix-supported Rh was twice as active as Degussa type but both supports delivered <1% CV in formation profiles over eight replicates.

Benefits and Practical Applications

• Eliminates the need for multiple quenched reactions by enabling repeated in-process sampling.
• Reduces material and time requirements in kinetic and impurity profiling.
• Supports semi-batch operation, mimicking plant-scale additions and withdrawals without process interruption.
• Centralizes experimental data under a single ID for long-term traceability.

Future Trends and Applications

Integration of real-time gas uptake measurement and advanced analytics will enrich kinetic modelling. Expanding OSR workflows to photochemical, electrochemical and multi-phase systems can further broaden its utility in process research. Coupling automated sampling with machine learning could drive predictive optimization across diverse reaction classes.

Conclusion

The OSR platform enables reliable in-situ sampling and reagent dosing under challenging conditions, delivering high-density kinetic data with minimal resource use. This approach streamlines reaction screening and optimization, enhancing scale-up success for pressurized chemistries.

Reference

• Unchained Labs. Accelerating your process optimization: sampling from reactions in-progress means better decisions in less time. Application Note, Rev C, 2018.