Journal of Flow Chemistry最新文献

Pharmaceutical industry is challenged by the rising development costs, strict regulatory and environmental requirements all while racing to deliver complex molecules to market. The need to be the first-in-class brings about shorter lifetime to the launched products in favor of better functioning followers. In addition, a shift from large volume blockbusters towards small volume production of complex molecules presents a unique opportunity to challenge the status quo in pharmaceutical manufacturing. Traditional batch manufacturing, while foundational, presents hurdles in scaling and efficiency, particularly for demanding reactions. Continuous manufacturing has emerged as a promising alternative, delivering better control and uniformity of operating conditions, mirroring the efficiencies found in small-scale batch reactors. However, continuous manufacturing is not universally applicable. As a solution, a combination of the two into hybrid manufacturing processes, appears to fill this gap effectively. While the concept of hybrid manufacturing is not new, the current perspective adds an additional angle to the integration of both technologies. Authors propose to sustain the continuity of the operation for batch mode processes by decreasing the reactor size and increasing the level of automation. Furthermore, modular fabrication of smaller-footprint technological platforms is expected to synergize other advancements in the field, such as digitalization, automation, and standardization. As a result, a leap towards the implementation of advanced manufacturing to drive sustainability in pharmaceutical industry is more tangible than ever.

Emulsification processes are often found in the process industry and their evaluation is crucial for product quality and safety. Numerous methods exist to analyze critical quality attributes (CQA) such as the droplet sizes and droplet size distribution (DSD) of an emulsification process. During the emulsification process, the optical process accessibility may be limited due to high disperse phase content of liquid-liquid systems. To overcome this challenge, a modular, optical measurement flow cell is presented to widen the application window of optical methods in emulsification processes. In this contribution, the channel geometry is subject of optimization to modify the flow characteristics and produce high optical quality. In terms of rapid prototyping, an iterative optimization procedure via SLA-3D printing was used to increase operability. The results demonstrated that the flow cell resulting from the optimization procedure provides a broad observation window for droplet detection.

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To understand and predict the effect of mixing in a mixer or reactor, characterization is essential. The Villermaux-Dushman system of competitive parallel reactions is one of the most frequently used methods to obtain details on the micromixing behavior in mixers and reactors. For quantitative information, a model can convert experimental data into a universal micromixing time, which can be used to compare set-ups and reaction conditions. Different modeling approaches have been developed over time and complicate the comparison of results with newfound micromixing times. In this work, these different modeling approaches are elaborated upon to show the significant differences that can arise between these models. Special attention goes out to a model for continuous-flow mixers, which operates differently and has different characteristics compared to mixing in conventional batch reactors. The volume fractions of the two phases being mixed are generally closer to one another in flow mixers, requiring adaptations in the experimental and modeling approach. Several models were tested, after which the interaction by exchange with the mean (IEM) model was selected. Using this model, micromixing times were determined for a variety of continuous-flow mixers under different operating conditions.

Continuous flow chemistry has become the method of choice for the synthesis of toxic and explosive intermediates such as diazo reagents because they can be generated on demand and readily used, eliminating the need to handle hazardous materials. This inherent increase in safety makes it more feasible to use these reagents in day-to-day synthesis. Herein, we describe a continuous flow, metal-free, easy-to-use method for the preparation of semi-stabilized and unstabilized diazo reagents. The scope of the described continuous flow oxidation of hydrazones using a packed bed column with iodosylbenzene includes 13 semi-stabilized and 13 unstabilized diazo reagents in solution in dichloromethane while producing only 1 equivalent of water and iodobenzene as by-products. These otherwise difficult to access compounds are further reacted either in situ or at the reactor outlet to yield esters and ethers in good to excellent yields (47–96%).

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Due to the miniaturization of equipment for flow chemistry and microprocess engineering, low-cost sensors and analytical devices are becoming increasingly important for automated inline process control and monitoring. The combination of 3D printing technology and open-source lab automation facilitates the creation of a microfluidic toolbox containing tailored actuators and sensors for flow chemistry, enabling a flexible and adaptable design and efficient processing and control based on the measured data. This contribution presents a set of 3D-printed microfluidic sensor flow cells for inline measurement of temperature, electrical conductivity (EC), and pH value, while compensating for the temperature dependence of EC and pH. The tailored sensor flow cells were tested using model reactions in a single-phase capillary flow system. They have an accuracy comparable to reference sensors in batch measurements. The sensor data can be used to monitor the reaction progress (conversion), determine the kinetic data (activation energy, pre-exponential factors) of saponification reactions, and identify titration characteristics (equivalence and isoelectric points) of neutralization reactions. Hence, the 3D-printed microfluidic sensor flow cells offer an attractive alternative to commercial analytical flow devices for open-source and low-cost lab automation.

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Microbubble reactors play an important role in the development of gas-liquid reaction process enhancement. However, the urgent demand for high efficiency and low energy consumption in gas-liquid reaction processes, as well as the trend towards large-scale production, have put forward higher requirements for the design and optimization of microbubble reactors. In this study, a self-priming microbubble reactor was designed and its structure parameters were optimized by (computational fluid dynamics) CFD simulations. Based on the grid division method combining structured and unstructured grids, the most suitable mesh number is selected, and the simulation calculation time is saved on the premise of ensuring the accuracy. The effects of five structural parameters on the gas content and energy loss was discussed and the optimal structural parameters of the microbubble reactor were determined as follows: the diffusion section length is 75 mm, the contraction angle is 22°, the diffusion angle is 10.5°, the inlet diameter of the gas phase is 6 mm, the inlet diameter of the liquid phase flowing into the gas chamber is 3 mm, the diffusion section inlet diameter is 5 mm. Under the condition of the same inlet flow rate, the outlet gas content of the optimized gas-liquid reactor is increased by 42.9% compared with the initial structure. In the wastewater treatment experiment, the microbubble reactor reduced the chemical oxygen demand of wastewater by 61% within three hours. This study provides significant references for the design of the self-priming microbubble reactor.

In the realm of flow chemistry, Do-It-Yourself (DIY) flow setups represent a versatile and cost-effective alternative to expensive commercially available reactors. Not only they are budget friendly, but also unlock a world of possibilities for researchers to explore and create customized setups tailored to their specific needs. This minireview serves as a short compendium of DIY flow systems to assist flow researchers in the challenging task of finding a suitable setup for their experiments and facilitate the transition from batch to flow chemistry. Our goal is to demonstrate that flow chemistry can be affordable, easy-to-build, and reproducible at the same time. Therefore, herein we review and describe selected illustrative examples of easily assembled/constructed DIY flow setups, with a particular emphasis on how to select the most suitable one based on the specific chemistry of interest, ranging from simple homogeneous monophasic reactions to more complex systems for photo-, electrochemistry, and so on. In addition, we briefly comment on the significance of DIY approach on education, particularly its integration into the standard undergraduate curriculum as a key educational tool for young chemists. Ultimately, we hope this mini review will help and encourage the reader to go with the flow and get started with the fine art of flow chemistry.

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Hundred-gram scale of highly selective catalytic hydrogenation of folic acid has been developed, which is adopted continuous-flow technology with Raney Ni as a catalyst. Through optimization of the reaction condition, a high conversion rate of folic acid (> 99%) and a high selectivity (99%) of tetrahydrofolate have been achieved. Additionally, a high-purity calcium-6S-5-methyltetrahydrofolate (6S-5-MTHF.Ca) has been synthesized from tetrahydrofolate obtained by continuous hydrogenation through chiral resolution, methylation, salting and recrystallization (purity: 99.5%, de: 97.6%). Compared to known methods, this method provides a feasible procedure using simple, inexpensive, and readily available reagents, making it a step-economical and cost-effective alternative strategy for production of tetrahydrofolate and its active derivatives.

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