Journal of Flow Chemistry最新文献

Experimental investigations into acoustic cavitation and ultrasound-assited emulsification process between highly viscous liquids were systematically conducted in a laboratory-built ultrasonic microreactor. Under ultrasound irradiation, four cavitation modes were observed simultaneously in soybean oil, including volume, shape, transient collapse and cavitation clouds. Influenced by the intense oscillation of cavitation bubbles, emulsification between viscous liquids was initiated through a dispersion and migration mode. The effects of varying parameters, such as input power, residence time, channel size, HLB value, surfactant concentration and volume ratio between aqueous and oil phase, on the size and polydispersity of prepared emulsion were investigated using water-soybean oil two-phase system as a model. The emulsion size was reduced to 75.60 nm through optimization of experimental parameters. Based on these findings, the ultrasonic microreactor was successfully employed in the preparation of Vitamin E-enriched nano-emulsions. A fine emulsion with low average size (47.69 nm) and good storage stability (60 days) was prepared within 2 min, further indicating the potential application of ultrasonic microreactor in the beverage and pharmaceutical industries.

The separation of silybin A (SilA) and B (SilB) diastereomers in optically pure compounds is challenging due to their very similar physical and chemical properties. However, such separation is crucial for evaluating the biological activity of the diasteroisomers SilA and SilB, which show very different performance in pharmacological applications like treating prostate cancer, liver diseases, and Alzheimer’s disease. The most common isolation method is based on high-performance liquid chromatography, but it is slow and has a yield in pure SilB of hundreds of milligrams per day. An alternative chemo-enzymatic separation method, utilizing an immobilized lipase CALB catalyst to stereoselectively acetylate silybin B (1b), offers advantages in terms of higher productivity, selectivity, and scalability, particularly when applied in flow reactors. This study delves into the kinetics of Sil acetylation catalyzed by Novozym 435 in a continuous flow milli-reactor, investigated at various temperatures, volumetric flow rates, and Sil initial concentrations. It is noteworthy that, at the current state of the art, there is a lack of kinetic studies on this reaction, emphasizing the novelty and significance of this work. The kinetic and fluid dynamic parameters were estimated using a non-linear regression analysis of experimental data. The examined reaction showed a null apparent activation energy, explaining the temperature insensitivity of the final acetylated silybin B (1b) concentration. Furthermore, the decrease in steady-state concentrations of the acetylated products with increasing volumetric flow rates indicated that the reaction was occurring in a kinetic regime. Interestingly, a maximum starting Sil concentration was identified, above which there was no favorable impact on conversion.

In the continuous struggle for improvements in laboratory processes, flow synthesis has been widely used for being safer, more reproducible, as for improving yields and scalability. Therefore, flow ozonolysis has become a turning point as flow reactors provides a much safer work environment and reactions can now be produced at industrial scales. In this review we would discuss several reactors used in flow ozonolysis and its importance for the safety of the ozonolysis process.

Organic azides are widely used in organic synthesis. Continuous flow processing can be used to bypass their isolation, and can therefore be useful in mitigating the hazards associated with these potentially toxic and explosive reagents. Nonaflyl azide has been reported as an effective, bench-stable, and relatively safe diazo transfer reagent that can be useful in the preparation of azides from amines and so avoid the use of alkyl halides. Here we demonstrate the synthesis and purification of nonaflyl azide in continuous flow with isolation of the neat, pure reagent by membrane filtration. The neat reagent was used in the preparation of organic azides from primary amines, and then applied to the synthesis of triazoles. A variety of triazoles, including the antiseizure drug Rufinamide, were prepared from primary amines and alkynes via the CuAAC click reaction in a semi-batch parallel array without isolation of alkyl azide intermediates. A telescoped two-stage continuous flow process was also designed and demonstrated to form triazoles via the same CuAAC reaction, which avoids the handling of the intermediate reactive azides.

Droplet-based microfluidics exhibit numerous benefits leading to relevant innovations and many applications in various fields. The precise handling of droplets in capillaries, including droplet formation, manipulation, and separation, is essential for successful operation. Only a few reports are known concerning the separation of segmented flows, particularly the continuous separation of droplets, which is of high interest regarding the control of biochemical and chemical reactions or other applications where the contact time of the involved phases is crucial. Here, the separation must be flexible and adjusted to different flow parameters, such as the surface tension, the volumetric flow rates, and their ratios. This contribution presents two novel open-source approaches based on additive manufacturing and mechanical deforming for continuous liquid–liquid separation under various flow conditions. The Laplace pressure is the driving force for the separation, which is adjusted to the flow conditions by adapting the distance of pinning points provided by the design of the devices. Details of the device design and experimental setup are shown along with limitations to promote further development and to increase availability for researchers. With the right parameters, sophisticated separations can be realized by inexpensive laboratory equipment and simple control of them. It was found that the distance between the pinning points needs to enlarged for increasing volumetric flow rates and reduced for higher viscosities of the continuous phase respectively higher amounts of the dispersed phase. The open source approach of this article expands the exploration space in addition to commercially available phase separators only available to a selected group of people.

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In this paper, we demonstrate the use of machine learning to optimize the continuous flow process of a crucial intermediate in the production of Nemonoxacin. Our focus is to achieve the good yield and enantioselectivity in the construction of chiral methyl group utilize the initial 29 experimental datasets and consider six important variables. Employing Single-Objective Bayesian optimization (SOBO), we achieved an impressive predicted yield of up to 89.7%, which is consistent with the experimental results, with a yield of 89.5%. Additionally, A Multi-Objective Bayesian Optimization (MOBO) algorithm, namely qNEHVI, to strike a balance between yield and enantioselectivity in the continuous flow system is applied. The algorithm’s prediction, with a yield of 81.8% and enantioselectivity of 97.85%, was experimentally validated, yielding 83.8% and 97.2%, respectively. This study effectively demonstrates that Bayesian optimization is a powerful tool for optimizing the continuous process in the production of active pharmaceutical ingredients (APIs).