Impact of Reactant Dissolution in the Kinetics of a Catalytic Hydrogenation for the Production of Argatroban
Filippo Nanto, Dario Ciato, Mariano Stivanello, Paolo Canu
TL;DR
This study examines how reactant dissolution affects the hydrogenation process for making Argatroban, showing how temperature, stirring, and catalyst loading influence reaction efficiency and accuracy of measurements.
Contribution
The paper introduces a refined first-principles model that incorporates catalyst effects on dissolution and improves prediction accuracy.
Findings
Increasing temperature from 40 to 80 °C reduced batch time by 58% but increased impurities.
Catalyst loading significantly affects reagent dissolution rate and batch time.
A refined model incorporating dissolution mass transfer improved prediction accuracy of reaction kinetics.
Abstract
An experimental study was performed for a fed-batch catalytic hydrogenation for the production of Argatroban. The penultimate expensive and scarcely available intermediate is characterized by a slow dissolution rate that evolves in parallel with the reaction process. The study investigated the coupling between the reaction and dissolution kinetics. In these circumstances, the standard Area Percentage method in HPLC was found to be misleading, requiring calibration and then absolute peak area measurements to correctly identify the dissolution rate and thus the actual chemical kinetics. Experiments quantified the role of the temperature, stirring rate, and catalyst loading. Shifting from 40 to 80 °C reduced the batch time by 58%, although higher temperatures promoted the formation of undesired impurities. Stirring rate controlled the initial reaction phases when reagent dissolution is…
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Taxonomy
TopicsInnovative Microfluidic and Catalytic Techniques Innovation · Crystallization and Solubility Studies · Thermal and Kinetic Analysis