Journal of Flow Chemistry最新文献

We describe the integration of a minimally modified household air fryer into flow chemistry experiments as a safe and cost-effective platform for conducting esterification reactions at the undergraduate and high school levels. By leveraging the continuous processing principles of flow chemistry alongside the controlled heating capabilities of an air fryer, students can efficiently synthesize esters from readily available carboxylic acids and alcohols in the absence of other solvents and with minimal workup (phase separation from an aqueous solution, washings) in good isolated yields (typically well over 50%) and high purity (> 95%, as shown by ¹H NMR spectra of the crude isolated products). This affordable low-tech setup offers a practical and engaging demonstration of organic synthesis and flow chemistry, making it well-suited for instructional use in both secondary and post-secondary educational settings.

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The preparation of pyridine N-oxides plays a critical role in functionalization of pyridines, which enhances the physical, chemical and biological properties of pyridine derivatives. And, the corresponding N-oxides are usually generated easily from the oxidation of pyridines by peracids. However, the peracids are extremely explosive even though they are used via preparation in situ. In this context, we developed a highly safe, economical and practical strategy to produce pyridine N-oxides using the cheap and environmentally friend H₂O₂ as terminal oxidation in continuous flow system. The solid-supported polyacrylic acid was used as catalyst which improved the reaction stability and operational safety and was reusable. In addition, the mixing efficiency was also enhanced by the solid-supported catalyst and made the scale-up synthesis achievable. Specifically, the output of this continuous flow synthesis could be increased to 67.93 kg/d and 24.8 t/a using a thicker tube reactor which was 200 m long, 1 cm thick and filled with solid-supported acid catalyst to give 10 L volume.

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Boron-containing compounds are essential building blocks in organic synthesis. A significant advancement in the preparation of alkyl boranes relied on the use of B₂Cat₂ with competent radical precursors under chemical, photochemical, and electrochemical conditions. However, these molecules are unstable and require one-pot formation of corresponding pinacol boranes to be isolated. In this work, we present a continuous flow electrochemical decarboxylative borylation approach telescoped with the exchange from unstable catechol boranes intermediates to isolable pinacol boranes. The study encompassed the optimization of a single-pass protocol employing an electrochemical microreactor, followed by the telescoped pinacol addition. No supporting electrolyte was necessary to successfully execute the process. The continuous-flow approach was validated across 11 examples comprising primary, secondary, and tertiary alkyl carboxylic acids.

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A Continuous Flow Photochemistry (CFP) - based protocol has been developed for the synthesis of a complex isomeric API impurity, Sulindac E-Isomer (2), which is a USP reference standard. The reported flow photochemical E/Z isomerization reaction is more efficient than metal catalyzed multistep batch process (residence time of 3 min in flow vs overall reaction time of 20 h in batch process; 44% product formation in photocatalytic flow process vs 13.82% in batch isomerization step) and proceeds with a clean reaction profile without any byproduct formation. The improved product formation is attributed to the triplet energy transfer from the photocatalyst and supported by density functional theory (DFT) calculations. The robustness of this approach was demonstrated on a multigram scale providing the potential for future application in the synthesis of isomeric API impurities and enabling USP reference standard development and availability towards ensuring quality and safety of medicines.

The development of efficient and sustainable methodologies for the synthesis of fluoroalkyl chalcogen compounds has gained significant attention in recent years. In this study, we focus on the photoredox-catalyzed continuous-flow synthesis of perfluorinated chalcogenide compounds via the perfluoroalkylation of diaryl, dialkyl, dibenzyl, and diphenacyl diselenides with perfluoroalkyl iodides. The flow setup allowed superior irradiation efficiency, better mass and heat transfer, and reduced over-irradiation, leading to enhanced reaction performance compared to traditional batch methods. The methodology proved to be versatile across a wide range of substrates, including various organodiselenide compounds and perfluoroalkyl iodides (R_F-I), demonstrating the influence of steric and electronic effects on reactivity. This research highlights the potential of continuous-flow technology for efficient, scalable photoredox catalysis, providing a versatile platform for the synthesis of perfluorinated compounds showcasing the effect of flow chemistry on reaction optimization and process intensification. Evidence for an electron transfer reaction involving TMEDA: R_F-I complex is provided by cyclic voltammetry.

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Perfluoroalkyl-chalcogen (Se-R_F) groups enhance lipophilicity and bioavailability in organofluorine compounds. This study advances continuous-flow synthesis for selective Se-R_F bond formation, improving yield and scalability. We explore photoredox catalysis with benzyl, alkyl, and phenacyl diselenides, elucidating mechanisms of selective perfluoroalkyl radical (R_F•) generation for efficient organodiselenide functionalization.

In recent years, electron donor–acceptor (EDA) complexes have emerged as sustainable, cost-effective, and inherently safer alternatives to traditional transition metal-based photocatalysts in photochemical processes. Formed via the association of neutral electron-rich and electron-deficient species, EDAs offer an environmentally benign route to radical generation across a broad spectrum of reactions. Concurrently, flow chemistry has gained prominence as a burgeoning area of scientific inquiry, enhancing reaction control, safety, mixing efficiency, and, critically, light penetration. In this mini review, we highlight recent works that have explored the use of EDA photochemistry with flow methodologies, while assessing both the promising practical advantages and current limitations in bringing these two fields together.

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Flow chemistry provides a new method for medicinal chemistry education owing to its continuous operation, improved reaction efficiency, and safety. In the improved experiment, dioxane was used as a solvent to dissolve salicylic acid and acetic anhydride; this helped reduce the corrosion of the equipment by the reaction solution, prevent injuries, and ensure good fluidity. Simultaneously, a feeding system under nitrogen protection was designed and applied to avoid the hydrolysis of acetic anhydride and deterioration of salicylic acid. The entire experiment included dissolution pre-experiments, energy-saving and consumption reduction experiment. Paracetamol was synthesized using a technique that had also been applied in undergraduate teaching experiments. Compared to previously reported aspirin synthesis experiments, this method enhances the safety of the experiment and diversity of cultivation abilities. This experiment not only improves the teaching effect but also provides an example of the application of flow chemistry and medicinal chemistry in teaching.

This work introduces a sustainable and efficient continuous-flow process for the degradation of persistent dyes, employing a continuous stirred tank reactor (CSTR) integrated with a recycled iron rod (rIR) that simultaneously serves as a mechanical agitator and a catalyst source. The system relies on Fe(II)-mediated activation of periodate (PI) to drive oxidative degradation of persistent textile dyes without the need for external iron dosing. Process performance was systematically evaluated under varying conditions, including PI flow rate (40–300 µL/s), submerged rod length (1–8 cm), rotation speed (0–500 rpm), dye concentration (5–40 mg/L), pH (3–6), and dye flow rate (1.20-1.83) mL/s. High conversion efficiency (up to 100%) was achieved under moderate PI flow, extended rIR immersion, increased rotation speed, acidic conditions, and low inlet dye concentrations (5–10 mg/L). pH values superior than 3 significantly hindered Fe(II) release and diminished degradation efficiency. Water matrix effects revealed minimal interference in mineral water but marked inhibition in river and seawater due to competing action. Comparison with external Fe(II)/PI systems showed that rIR releases Fe(II) in the range of 10–40 µM, depending on oxidant availability and hydrodynamic conditions. The system likely operates through a non-radical mechanism involving high-valent Fe(IV) = O intermediates. Overall, the rIR/PI process presents a low-cost and environmentally friendly strategy for continuous dye removal from lightly polluted water sources.

Scalable synthesis of the nanoparticulate iridium-based electrocatalysts (Ir-IrO_x) for the oxygen evolution reaction (OER) in acidic media is demonstrated using single phase microwave- (MW-) assisted milli-fluidic continuous flow synthesis (MF-CFS) technique. The flow reactions were initiated in the MW cavity reactor, where Ir⁴⁺ was reduced by NaBH₄ to form Ir-IrO_x nanoparticles (NPs) of particle size ranging from 2.0 to 3.5 nm. Effects of (i) the Ir precursor concentration, (ii) the pre-mixing time interval between precursor/reducing agent mixing and injection of the mixture in the MW cavity (t_pre−mix) and (iii) the residence time in the MW cavity (t_r) were investigated to optimize the reaction conversion efficiency (𝜂_c) and the electrochemical performance of the synthesized electrocatalysts. The value of 𝜂_c was impressively increased from 52% to ~ 98% by changing the value of t_r from 2.4 min to 4.7 min while keeping all other parameters constant. The Ir-IrO_x electrocatalysts synthesized under optimal synthesis conditions demonstrate an excellent OER mass activity of 351 A g⁻¹ compared to that of 305 A g⁻¹ for the commercial IrO₂. During a potentiodynamic accelerated stress test (AST), the synthesized electrocatalysts show an electrochemical stability comparable to or higher than that of the commercial IrO₂. The Ir-IrO_x sample having the optimal OER performance exhibited an OER activity retention of 40% compared to 31% for the commercial IrO₂. Longer t_r and additional MW exposure of the reaction bath was found to decrease the oxidation number of the Ir-IrO_x surface efficiently, enhancing both the OER activity and durability of the synthesized Ir-IrO_x sample.