Heterogeneous Continuous Flow Hydrogenation of Hexafluoroacetone Trihydrate and Its Kinetic Modeling

Abstract

Hexafluoroisopropanol (HFIP) is an important intermediate of sevoflurane, an inhalation anesthetic for pediatric anesthesia, and it is produced industrially mainly by the catalytic hydrogenation reduction of hexafluoroacetone (HFA). In previous studies, the hydrogenation of HFA was usually performed in batch reactors with the disadvantages of harsh reaction conditions and low conversion rates. On the other hand, continuous flow technology is increasingly being used for intrinsically safe hydrogenation processes to avoid safety issues caused by the accumulation of hydrogen gas in high-pressure reactors. In this study, a continuous flow system was developed in a micropackedbed reactor, and the intrinsic kinetics of the reaction were studied. This continuous flow process minimized mass and heat transfer problems and achieved higher productivity in terms of time and space yield than traditional process methods. Under kinetically controlled conditions, the operating conditions were varied with temperature between 363 and 393 K, hydrogen pressure of 10 bar, and catalyst loading between 0.1 and 0.5 g. In the end, we achieved conversion and selectivity of up to 99% and a space−time yield of about 9 times that of the batch reactor. To further investigate the long-term stability of the reaction system, the flow system was successfully operated for 90 h at a liquid flow rate of 0.5 mL/min. In addition, residence time distribution curves at different flow rates were determined, and possible mechanistic pathways of the reaction were explored based on the Langmuir−Hinshelwood method. The reaction was found to be an adsorption−desorption type with a mechanism of competitive adsorption by H 2 dissociation, and the thermodynamic properties associated with the rate constants were estimated.

An Overview of the Synthesis of Hexafluoroisopropanol and Its Key Intermediates

“…63 In 2023, Su's group prepared HFIP by continuous flow hydrogenation of HFA•3H 2 O in a micropacked-bed reactor using Pd/C as the catalyst (►Fig. 4), 64 with operating conditions of temperature between 363 and 393 K, hydrogen pressure of 10 bar, and catalyst loading of 0.1 to 0.5 g. Both the selectivity and conversion were more than 99%, and a space-time yield was approximately nine times that of the batch reactor.…”

Optimization of heterogeneous continuous flow hydrogenation using FTIR inline analysis: a comparative study of multi-objective Bayesian optimization and kinetic modeling

“…Concurrently, kinetic modeling was conducted in alignment with our previously established intrinsic kinetic modeling methodology [18]. It is important to note that nonchemical kinetic phenomena, such as gas-liquid interfacial area, fluid kinetics, solute diffusion, and mass transfer limitations, can significantly impact the accuracy of intrinsic kinetic modeling.…”

“…It is important to note that nonchemical kinetic phenomena, such as gas-liquid interfacial area, fluid kinetics, solute diffusion, and mass transfer limitations, can significantly impact the accuracy of intrinsic kinetic modeling. [18] A comprehensive examination of reaction parameters (e.g., gas-to-liquid flow ratio, mean residence time) was performed to minimize these https://doi.org/10.26434/chemrxiv-2024-m0kf5 ORCID: https://orcid.org/0000-0002-6544-3959 Content not peer-reviewed by ChemRxiv. License: CC BY-NC-ND 4.0 effects, ensuring that the reaction rate data were obtained under conditions of kinetic control (see Supporting Information).…”

“…[14][15][16][17] For instance, Su et al demonstrated the application of kinetic modeling in the heterogeneous flow hydrogenation of hexafluoroacetone trihydrate, revealing an adsorption-desorption mechanism with competitive adsorption of H2 dissociation. [18] Similarly, Yu et al conducted a continuous hydrogenation study of 2-(4-nitrophenyl) butanoic acid and kinetics study in a micropacked-bed reactor, employing kinetic analysis to elucidate the impacts of internal and external diffusion, as well as salt formation. [19] Despite these advances, the application of kinetic modeling in heterogeneous catalysis is often hampered by the complexities associated with non-chemical kinetics phenomena.…”