Introduction
Solvent evaporation is a major challenge during reaction profiling, as it can lead to concentration variability and compromised experimental results. In conventional systems, solvents are lost due to repeated septum piercing during sampling.
The ReactALL™ system, featuring SmartCap™ technology, provides an innovative solution by preventing solvent evaporation through a reflux mechanism, even during active sampling.
This application note summarizes an experimental evaluation of solvent retention using the ReactALL system, conducted by Hawkins et al. [1]
Experimental
Two solvent loss assessments were conducted:
- Assessment Without Sampling: Tetrahydrofuran (THF) was added to pre-weighed glass reactor vials, sealed with SmartCap, and heated to 68°C under reflux for 20 hours with stirring. Solvent loss was determined by measuring the reactor’s mass before and after the experiment.
- Assessment With Sampling: Multiple organic solvents, including MTBE, THF, ethylacetate, 2-MeTHF, acetonitrile, 1,2-dichloroethane, trifluorotoluene and toluene, were heated to their boiling points under reflux conditions. Using the automated sampling feature, 16 samples were withdrawn, and solvent loss was calculated based on the mass of the aliquots and the final reactor mass after sampling.
The total solvent loss was calculated by correcting the mass lost for the aliquots removed during sampling, as described by the following equations:
Where:
Results
In the first assessment without sampling, no solvent loss was detected after 20 hours under reflux, indicating that the ReactALL system effectively retained solvent during static conditions. In the second assessment with repeated sampling, solvent loss was minimal across all tested solvents except MTBE, which exhibited a higher loss of 13%. Other solvents, such as THF, ethyl acetate, and toluene, demonstrated solvent losses of 6.6%, 4%, and 2.1%, respectively, indicating that the SmartCap technology significantly reduced evaporation even during active sampling. An inverse correlation was observed between the solvent’s boiling point and the amount of solvent loss for most of the solvents.
Conclusion
The ReactALL™ system demonstrated minimal solvent loss, with no loss under static reflux conditions and 9% loss during repeat sampling, except for MTBE. Its SmartCap and reflux design effectively maintain solvent integrity, ensuring precise concentration control for accurate and reproducible experimental results. This makes the system ideal for complex reaction profiling where solvent retention is critical.
References
[1] Hawkins, J. M., Pfisterer, D. M., Algera, R. F., & Monfette, S. (2024). The ReactALL Platform: Experimental Data and Case Studies. Organic Process Research & Development. https://doi.org/10.1021/acs.oprd.4c00210
Data and figures are adapted with permission from Org. Process Res. Dev. 2024, 28, 9, 3637–3644. Copyright © 2024 American Chemical Society.
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Read the full application note "Solvent selection with SmartCap technology"