Continuous Flow System Research Articles

Continuous Flow Alkylation of Morpholine and Aniline catalyzed by Mesoporous Al‐SBA‐15

A continuous flow alkylation process is disclosed to synthesize N‐methylated derivatives of aniline and morpholine, compounds vital to the pharmaceutical, agrochemical, and polymer industries, using a mesoporous Al‐SBA‐15 catalyst. Conversions reached up to 99% with almost complete selectivity for monoalkylated products under optimized temperature, pressure, and flow conditions. Compared to traditional batch methods, the continuous flow system enabled precise control of reaction parameters, significantly enhancing efficiency, reducing solvent use, and minimizing by‐product formation. The results demonstrate the process's feasibility for industrial applications, emphasizing its potential for more sustainable, cost‐effective large‐scale production and the role of continuous flow systems in developing safer, scalable, and environmentally friendly chemical processes.

Enhanced FeIV═O Generation via Peroxymonosulfate Activation by an Edge-Site Engineered Single-Atom Iron Catalyst.

As an oxidant, the ferryl-oxo complex (FeIV═O) offers excellent reactivity and selectivity for degrading recalcitrant organic contaminants. However, enhancing FeIV═O generation on heterogeneous surfaces remains challenging because the underlying formation mechanism is poorly understood. This study introduces edge defects onto a single-atom Fe catalyst (FeNC-edge) to promote FeIV═O generation via peroxymonosulfate (PMS) activation. In the presence of PMS, the FeNC-edge catalyst at a low dose (20 mg L-1, equivalent to 0.14 mg L-1 Fe) exhibits unprecedented activity for organic contaminant degradation. Electrochemical analysis, in situ Raman spectroscopy, and FeIV═O probe experiments confirm that FeIV═O generation is enhanced on the surface of FeNC-edge. Density functional theory calculations reveal that the introduced edge sites concentrate electron density on active Fe atoms, facilitating charge transfer from Fe to PMS. Notably, FeNC-edge immobilized on a polymeric membrane functioned as a continuous-flow oxidation system with efficient catalyst recycling and minimal Fe leaching.

Kinetics with UVC Irradiation Using a Continuous-Flow System: Mathematical Fitting Compared to Microbiological Analysis

Fresh produce contamination poses a significant public health risk. Traditional disinfection methods using chemical solutions, while effective, raise environmental and health concerns. This study explores UVC irradiation, a promising non-chemical alternative proven to be effective against a broad spectrum of microorganisms. We investigated the optimal UVC dosage for reducing microorganisms on fresh vegetables washed in water. Our findings suggest that dosages of approximately 2 mJ/cm2 in water and 9 mJ/cm2 in vegetables achieve reductions of up to 99%. Additionally, we established a nominal radiation application rate of 2.38 mW/cm2/s, reflecting the treatment intensity. Understanding the fundamental mechanisms of UVC irradiation and its interactions with microorganisms is crucial. Elucidating these mechanisms can significantly improve optimization efforts and seamlessly integrate UVC irradiation into food safety protocols. Implementing this strategy offers immense potential to elevate food safety standards in the industry while minimizing environmental impact. This approach aligns perfectly with sustainability objectives by providing a chemical-free solution for food disinfection.

Continuous-Flow Ritter Reaction for Sustainable Amide Synthesis Using a Recyclable m-Phenolsulfonic Acid-Formaldehyde Resin Catalyst.

Herein, a rapid and efficient continuous-flow synthesis of amides is described. The Ritter reaction, catalyzed by a reusable solid acid catalyst composed of m-phenolsulfonic acid-formaldehyde resin (PAFR II), was used to convert nitriles and alcohols to amides in up to 90% yield. The continuous-flow system facilitates short reaction times and maintains activity for several weeks. This method is scalable, environmentally sustainable, and enables catalyst recycling.

Comparison of Microfluidic Synthesis of Silver Nanoparticles in Flow and Drop Reactors at Low Dean Numbers.

This study evaluates the performance of continuous flow and drop-based microfluidic devices for the synthesis of silver nanoparticles (AgNPs) under identical hydrodynamic and chemical conditions. Flows at low values of Dean number (De < 1) were investigated, where the contribution of the vortices forming inside the drop to the additional mixing inside the reactor should be most noticeable. In the drop-based microfluidic device, discrete aqueous drops serving as reactors were generated by flow focusing using silicone oil as the continuous phase. Aqueous solutions of reagents were supplied through two different channels merging just before the drops were formed. In the continuous flow device, the reagents merged at a Tee junction, and the reaction was carried out in the outlet tube. Although continuous flow systems may face challenges such as particle concentration reduction due to deposition on the channel wall or fouling, they are often more practical for research due to their operational simplicity, primarily through the elimination of the need to separate the aqueous nanoparticle dispersion from the oil phase. The results demonstrate that both microfluidic approaches produced AgNPs of similar sizes when the hydrodynamic conditions defined by the values of De and the residence time within the reactor were similar.

Tire Wear Particles Exposure Enhances Denitrification in Soil by Enriching Labile DOM and Shaping the Microbial Community.

Tire wear particles (TWP) are emerging contaminants in the soil environment due to their widespread occurrence and potential threat to soil health. However, their impacts on soil biogeochemical processes remain unclear. Here, we investigated the effects of TWP at various doses and their leachate on soil respiration and denitrification using a robotized continuous-flow incubation system in upland soil. Fourier transform ion cyclotron resonance mass spectrometry and high-throughput sequencing were employed to elucidate the mechanisms underpinning the TWP effects. We show that TWP increased soil CO2, N2, and N2O emissions, which were attributed to the changes in content and composition of soil dissolved organic matter (DOM) induced by TWP and their leachate. Specifically, the labile DOM components (H/C ≥ 1.5 and transformation >10), which were crucial in shaping the denitrifying community, were significantly enriched by TWP exposure. Furthermore, the abundances of denitrification genes (nirK/S and nosZ-I) and the specific denitrifying genera Pseudomonas were increased following TWP exposure. Our findings provide new insights into impacts of TWP on carbon and nitrogen cycling in soil, highlighting that TWP exposure may exacerbate greenhouse gas emissions and fertilizer N loss, posing adverse effects on soil fertility in peri-urban areas and climate change mitigation.

Coimmobilized Dual Enzymes in a Continuous Flow Reactor for the Efficient Synthesis of Optically Pure γ/δ-Lactones.

Enzyme catalysis is a promising method for producing chiral chemicals with high stereoselectivity under mild conditions. However, the traditional batch reaction suffers from low enzyme stability, low cofactor recycling, and poor enzyme reusability. Here, we present a continuous-flow method using coimmobilized dual enzymes for the synthesis of chiral γ-/δ-lactones, which are widely used in fragrances and flavors. Typically, a carbonyl reductase mutant SmCRM5 from Serratia marcescens, was coimmobilized by covalent binding with BmGDH, a glucose dehydrogenase capable of recovering and recycling the cofactor NADPH. After immobilization, SmCRM5 and BmGDH exhibited a 8.9-/8.7-fold increase in catalytic efficiency (kcat/Km) and a 57-/15-fold increase in half-life at 30 °C, respectively. We demonstrated that coimmobilized dual enzymes used in a continuous flow reactor showed a higher reaction rate and a higher space-time yield (1586 g·L-1 d-1) than free enzymes and immobilized enzymes in a batch reaction for the production of (R)-δ-decalactone. This continuous flow reactor can run continuously for more than 650 h with 99% ee and 80% conversion, and the total volume exceeds 1500 reactor volumes. The robustness of this continuous-flow immobilized enzyme system provides a green and efficient method for the synthesis of high value-added chiral chemicals.

Hydrogen Production from Formic Acid Using KIT-6 Supported Non-NobleMetal-Based Catalysts.

The aim of this study is to investigate the activity of KIT-6 supported nickel (Ni) and cobalt (Co) catalysts, and the effect of Co incorporation to the Ni@KIT-6 catalyst in the formic acid (FA) dehydrogenation. Ni and Co are inexpensive and readily available non-noble transition metals that are considered ideal for dehydrogenation reactions due to their high activity against C-C and C-H bond breaking. In this study, KIT-6 supported catalysts were tested for hydrogen production from FA in a conventionally heated packed-bed continuous-flow system. N2 adsorption-desorption isotherms of the samples were found to be consistent with Type-IV according to the International Union of Pure and Applied Chemistry (IUPAC) classification. The introduction of metal loading resulted in the preservation of the mesoporous structure of the support material. X-ray diffraction (XRD) patterns of the catalysts exhibited the characteristic amorphous silica structure. Diffuse Reflectance Infrared Fourier Transform Spectroscopy (DRIFT) analysis, Lewis acidity of Co-based catalysts was found to be higher than the Ni-based catalysts. The complete formic acid conversion was observed at 200-350 °C. The highest H2 selectivity was obtained with the 3Ni@KIT-6 catalyst. The Co-based catalysts exhibited relatively lower catalytic activity, which was linked to increased coke formation within these catalysts.

Safe and Sustainable Industrial-Scale Production of Anhydrous Diazomethane via a Fully DCS/SIS-Controlled Continuous Flow System: Synthesis of α-Haloketones

Safe and Sustainable Industrial-Scale Production of Anhydrous Diazomethane via a Fully DCS/SIS-Controlled Continuous Flow System: Synthesis of α-Haloketones

Dynamic kinetic studies of lysozyme removal as protein waste using weak ion exchange nanofiber membranes in flow systems: Linear and nonlinear model analysis

BackgroundThis study explores lysozyme removal using a weak ion exchange nanofiber membrane in a continuous flow system. Understanding removal kinetics is critical for designing, optimizing, and scaling industrial processes. Kinetic models play a crucial role in predicting removal behaviors, including the pseudo-first-order, pseudo-second-order, Elovich, Avrami, and intra-particle diffusion models. Each model provides different insights based on its assumptions, making them suitable for analyzing various removal systems and mechanisms. MethodsThe study investigated the effects of four parameters—removal pH, initial lysozyme concentration, loading flow rate, and the number of membranes stacking layers—on dynamic kinetic binding behavior. Both linear and non-linear kinetic models were employed to analyze experimental results, focusing on removal rates and mechanisms. Significant FindingsAnalysis revealed key insights into removal kinetics. The change in removal pH significantly affected the binding rate and capacity. Higher initial concentrations increased binding rates, while changes in loading flow rate influenced removal rate and capacity. Increasing the number of membrane stacking layers enhanced the removal capacity and increased the pressure drop. These findings underscore the importance of optimizing parameters for efficient removal in biotechnology and wastewater treatment.

Pulsed Electric Field Pretreatment Enhances the Enzyme Hydrolysis of Baker's Yeast.

Baker's yeast is a key starting material for producing extracts with diverse compositions and applications. This study investigates the effect of pulsed electric field (PEF) pretreatment, which induces irreversible electropermeabilization, on the enzymatic hydrolysis of yeast. Cell suspensions were exposed to monopolar rectangular pulses in a continuous flow system followed by 4 h of incubation with Alcalase at concentrations of 0.2% and 0.5%. PEF pretreatment significantly improved enzymatic hydrolysis, with maximum intracellular content recovery under electrical conditions resulting in outlet temperatures of 56-58 °C. The released protein reached 163.7 ± 13 mg per gram of dry cell weight (DCW). SDS-PAGE analysis showed that the extracts predominantly contained peptides with molecular masses below 4.7 kDa. The phenolic content was comparable to that of cell lysates obtained after mechanical disruption. The free α-amino nitrogen content and total antioxidant activity reached 218.2 ± 26 mg/gDCW and 53.4 ± 4.6 mg TE/gDCW, respectively, representing 3.2-fold and 2.65-fold increases compared to cell lysates. The hydrolysates from PEF-pretreated cells demonstrated a positive effect on the proliferation of the human keratinocyte cell line HaCat. The obtained data lead to the conclusion that PEF pretreatment is a promising approach to enhance the production of yeast hydrolysates with various applications.

Visible-Light-Induced Divergent Oxygenation of Methylbenzene Utilizing Aryl Halides.

The selective oxidation of methylbenzene to value-added products is of indisputable importance in organic synthesis. Although photocatalytic oxidation reactions of toluene have achieved great success for the preparation of its oxidative products, such as carboxylic acids, benzaldehyde, and benzoate, there remains a lack of a unified photocatalytic system for the selective preparation of these oxidation products. Herein, we report a metal- and additive-free photocatalytic protocol enabled by aryl halides using O2 as a green oxidant for the selective synthesis of the above-mentioned three oxidation products by adjusting the reaction solvent. This strategy features many advantages, including environmentally friendly and mild reaction conditions, broad substrate applicability and functional group tolerance, and potential practical application for the synthesis of aromatic carboxylic drugs and polymer materials and degradation of polystyrene waste. The continuous-flow system was utilized for the oxidation of toluene, which resulted in a reduced reaction time and increased production efficiency. Detailed mechanistic investigation revealed that the hydrogen atom transfer process was facilitated by the bromine radical from aryl halides for further oxidation, and an electron donor-acceptor complex of methylbenzene and aryl halides may exist.

Oxidation of benzyl alcohol derivatives into carboxylic acids with a new Acetobacter malorum strain: boosting the productivity in a continuous flow system

The one-shot green oxidation of different benzyl alcohol derivatives into the corresponding carboxylic acids was achieved by using Acetobacter malorum DSM 112354, a newly isolated strain. Oxidation of benzyl alcohol was initially optimized considering productivity after 8 h as response parameter. Under optimized conditions, a set of para-substituted benzyl alcohols was tested, showing the great versatility of Acetobacter malorum DSM 112354 which was able to oxidize all the substrates albeit with different rates and conversions. The effect of the substituent position was subsequently studied using 2-(hydroxymethyl)phenol, 3-(hydroxymethyl)phenol, and 4-(hydroxymethyl)phenol as starting materials, showing that all the substrates were efficiently transformed (74-98% molar conversion in 2-24 h). Finally, the oxidation of 1,4-phenylenedimethanol gave 4-(hydroxymethyl)benzoic acid proceeded with excellent regioselectivity, since <3% of terephthalic acid was observed. This regioselective reaction was optimized using Ba-alginate immobilized cells of Acetobacter malorum DSM 112354 in a continuous multiphasic flow reactor. The process continuously run for 24 h allowed the obtainment of 0.65 g of HMBA using a 14.4 mL reactor. This intensification was associated with upgraded biocatalyst productivity (37.1 mmolP/gcells dry weight) and space-time yield (45.1 mgP/mL d).

Electrocatalytic Hydrogenation of Nitrogen-Containing Compounds Using a Proton-Exchange Membrane Reactor

Proton-exchange membrane (PEM) reactors, including a membrane electrode assembly (MEA) consisting of a proton exchange membrane and an electro-catalyst supported on carbon, has attracted attention as an useful device for electrocatalytic hydrogenation [1,2]. With this reactor, a continuous flow system can be constructed without the need for a supporting electrolyte, making hydrogenation reactions very ubiquitous. Although there have been several reports on the reductive transformations using PEM reactors, its application for nitrogen-containing organic compounds is still limited.We herein report the reduction of nitrogen-containing compounds having a cyano or nitro group by using a PEM reactor. We will also report on the reduction of quinoline and other nitrogen-containing aromatic compounds.[1] Takano, K.; Tateno, H.; Matsumura, Y.; Fukazawa, A.; Kashiwagi, T.; Nakabayashi, K.; Nagasawa, K.; Mitsushima, S.; Atobe, M. Bull. Chem. Soc. Jpn. 2016, 89, 1178–1183.[2] Mitsudo, K.; Inoue, H.; Niki, Y.; Sato, E.; Suga, S. Beilstein J. Org. Chem. 2022, 18, 1055–1061.

Electrochemical Nitrate Reduction to Ammonia on AuCu Single‐Atom Alloy Aerogels under Wide Potential Window

AbstractElectrocatalytic nitrate reduction to ammonia (NO3RR) is very attractive for nitrate removal and ammonia production in industrial processes. However, the nitrate reduction reaction is characterized by intense hydrogen competition at strong reduction potentials, which greatly limits the Faraday efficiency at strong reduction potentials. Herein, we reported an AuxCu single‐atom alloy aerogels (AuxCu SAAs) with three‐dimensional network structure with significant nitrate reduction performance of Faraday efficiency (FE) higher than 90 % over a wide potential range (0 ~ −1 V RHE). The FE of the catalyst was close to 100 % at a high reduction potential of −0.8 VRHE, accompanying with NH3 yield reaching 6.21 mmol h&lt;M−&gt;1 cm&lt;M−&gt;2. More importantly, the catalyst maintained a long‐term operation over 400 h at 400 mA cm&lt;M−&gt;2 for the NO3RR using a continuous flow system in a H‐cell. Experimental and theoretical analysis demonstrate that the catalyst can lower the energy barrier for the hydrogenation reaction of *NO2, leading to a rapid consumption of the generated *H, facilitate the hydrogenation process of NO3RR, and inhibit the competitive HER at high overpotentials, which efficiently promotes the nitrate reduction reaction, especially in industrial applications.

Electrochemical Nitrate Reduction to Ammonia on AuCu Single-Atom Alloy Aerogels under Wide Potential Window.

Electrocatalytic nitrate reduction to ammonia (NO3RR) is very attractive for nitrate removal and ammonia production in industrial processes. However, the nitrate reduction reaction is characterized by intense hydrogen competition at strong reduction potentials, which greatly limits the Faraday efficiency at strong reduction potentials. Herein, we reported an AuxCu single-atom alloy aerogels (AuxCu SAAs) with three-dimensional network structure with significant nitrate reduction performance of Faraday efficiency (FE) higher than 90 % over a wide potential range (0 ~ -1 V RHE). The FE of the catalyst was close to 100 % at a high reduction potential of -0.8 VRHE, accompanying with NH3 yield reaching 6.21 mmol h<M->1 cm<M->2. More importantly, the catalyst maintained a long-term operation over 400 h at 400 mA cm<M->2 for the NO3RR using a continuous flow system in a H-cell. Experimental and theoretical analysis demonstrate that the catalyst can lower the energy barrier for the hydrogenation reaction of *NO2, leading to a rapid consumption of the generated *H, facilitate the hydrogenation process of NO3RR, and inhibit the competitive HER at high overpotentials, which efficiently promotes the nitrate reduction reaction, especially in industrial applications.

Green synthesis of infrared controlled AgNP/graphite/polyvinylidene fluoride composite membranes for removal of organic pollutants

The effectiveness of light-sensitive particle-added composites as alternative materials in the treatment of waste water was investigated. Infrared responsive polyvinylidene membranes were prepared with anchoring the graphite supported silver particles reduced by quince seed extract. X-ray diffractometer, scanning electron microscope and Fourier transform infrared spectroscopy analysis were used to characterize physicochemical and structural properties of composites. Photoluminescence, surface area and contact angle measurements were carried out. The filtration performances of the membranes were tested under infrared light in a continuous flow system. Methyl orange and bovine serum albumin solutions were used as model pollutants. The silver-graphite additive acted as light absorber and energy converter. Owing to the photothermal effect, the water flux, rejection and roughness of the AgNP-G-P membrane improved significantly, and those were recorded as 74.7 L.m−2.h−1.bar−1, 54.6 % and, 75.0, respectively (32.5, 22 and 74.1 %, respectively, for PVDF). The composites almost retained their initial performance after repeated use and did not cause solution leaching. In this study photothermal particles, which are frequently used in medical applications, were successfully adapted to the filtration system. It has the ability to add a specific and new dimension to the protection of the environment by purifying wastewater.

A Chemoenzymatic Cascade for the Formal Enantioselective Hydroxylation and Amination of Benzylic C-H Bonds.

We report the synthesis and characterization of an artificial peroxygenase (CoN4SA-POase) with CoN4 active sites by supporting single-atom cobalt on polymeric carbon nitrogen, which exhibits high activity, selectivity, stability, and reusability in the oxidation of aromatic alkanes to ketones. Density functional theory calculations reveal a different catalytic mechanism for the artificial peroxygenase from that of natural peroxygenases. In addition, continuous-flow systems are employed to combine CoN4SA-POase with enantiocomplementary ketoreductases as well as an amine dehydrogenase, enabling the enantioselective synthesis of chiral alcohols and amines from hydrocarbons with significantly improved productivity. This work, emulating nature and beyond nature, provides a promising design concept for heme enzyme-based transformations.

Photosensitizer-Free Benzo[1,4]oxazin-2-one Synthesis by Continuous-Flow Photochemistry.

We report a photosynthetic method for producing 2H-benzo[b][1,4]oxazin-2-ones from aryl azides and α-ketoacids. This method is highly sustainable, requiring only visible light irradiation of the substrates and no external additives. Furthermore, we implemented a continuous-flow system to achieve efficient light irradiation and rapid mixing, significantly improving reaction efficiency and reducing reaction time compared to the batch process. The flow system enabled gram-scale synthesis. We also demonstrated the utility of the products, by employing the benzo[1,4]oxazin-2-one moiety as a directing group for C-H activation on the 3-aryl substituent. This green approach highlights the potential for developing environmentally friendly synthetic processes.

Design and implementation of a sample environment for in situ moisture-dependent neutron dark-field imaging experiments

We present the design and construction of a custom neutron-transparent sample environment for in situ moisture-dependent neutron dark-field imaging (NDFI) experiments for the imaging facilities at the Paul Scherrer Institute (PSI), Villigen, Switzerland. This simple setup, combined with a moisture generator, features a continuous flow system to ensure a constant homogeneous flow of humid air to manipulate the sample’s moisture conditions at room temperature. To facilitate neutron dark-field imaging measurements, the chamber has a slim design to maximize the sample-detector distance scanning range. The chamber can maintain static or dynamic relative humidity conditions, allowing for humidity cycles. Beyond moisture-dependent studies, the system’s versatility allows its utilization in any type of gas stream-dependent study. This technical note details the engineering considerations, construction process, and validation of this sample environment.