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

Importance of topic

In process development and fine chemical research, detailed kinetic profiles and impurity monitoring are essential for selecting optimal reaction conditions. Automated in-situ sampling from pressurized reactors eliminates the need for multiple replicate reactions and accelerates decision making. By accessing time-resolved data directly from ongoing reactions, researchers can make informed choices on yield improvement, purity control and scale-up strategies in less time.

Objectives and study overview

This application note illustrates how the Optimization Sampling Reactor (OSR) from Unchained Labs enables precise sampling and reagent addition under pressure. The study focuses on validating OSR performance through hydrogenation of trans-cinnamic acid using different catalysts and reaction parameters. Key aims include demonstrating sampling accuracy at varying pressures, comparing catalyst supports and generating reproducible kinetic data across eight parallel reactors.

Used methodology and instrumentation

Reactions were performed in an OSR module consisting of eight 40 mL stirred reactors, each independently controlled for temperature (–20 °C to 150 °C) and pressure (ambient to 400 psi). Samples and reagents are transferred via a sealed antechamber that equilibrates pressure before needle injection or withdrawal. Stirring paddles with hollow shafts allow continuous mixing during sampling, while halting agitation enables catalyst settling if required. All experimental parameters and analytical results were captured in the Lab Execution and Analysis (LEA) software. Reaction progress was monitored by HPLC after dilution in THF/MeCN.

Main results and discussion

• Sampling precision was evaluated at volumes of 100–1000 µL and pressures up to 400 psi, yielding relative standard deviations below 4% and accuracy within 95–105%.
• Hydrogenation with 5% Pd/C at 50 psi H₂ and 40 °C achieved smooth conversion profiles, with reproducibility across all eight reactors.
• To reduce weighing variability, 5% Rh on alumina was tested on two supports: matrix-type and Degussa. Matrix support gave higher reaction rates, while Degussa provided slower, more controlled conversions—ideal for extended kinetic studies.
• All catalyst comparisons showed coefficient of variation below 1% across time points, illustrating high inter-reactor consistency.

Benefits and practical applications

The OSR enables multi-point sampling and reagent dosing in a single run, drastically reducing material use and operator time. Its controlled atmosphere port technology supports semi-batch operation mimicking industrial conditions. Centralized data management via LEA ensures traceability and facilitates collaboration. This approach streamlines reaction screening, catalysis optimization and scale-up decision making in pharmaceutical and fine chemical laboratories.

Future trends and potential uses

• Integration with online spectroscopic probes and mass spectrometry for real-time analytics.
• Application of machine learning to kinetic datasets for predictive reaction modeling.
• Expansion to multiphase and gas-liquid reactions, including continuous flow adaptations.
• Automated scale-down of complex catalytic networks and multi-step sequences.

Conclusion

The OSR platform delivers precise, reproducible sampling under high pressure and temperature, enabling rapid kinetic studies without multiple reaction set-ups. Its robust design and automated data capture accelerate process optimization, support reliable catalyst comparisons and enhance scale-up success rates.

Reference

No formal literature references were provided in the original text.