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Herein, we describe the development of a continuous flow approach to chiral spiropenicillanates with remarkable bioactive properties from 6‐alkylidenepenicillanates through phosphine‐catalyzed [3+2] annulation of allenoates or 1,3‐dipolar cycloaddition with diphenyldiazomethane. Model reactions were carried out using simple alkenes, such as methyl vinyl ketone and N‐substituted maleimides, leading to the corresponding products in excellent yields (up to 96 %). The [3+2] annulation reaction was subsequently extended to the reactivity of 6‐alkylidenepenicillanates, a more complex 2π‐component with an exocyclic carbon‐carbon double bond, allowing the synthesis of spirocyclic compounds. The 1,3‐dipolar cycloaddition reactions between 6‐alkylidenepenicillanates and diphenyldiazomethane under continuous flow conditions gave the corresponding spiro‐1‐pyrazolinepenicillanates in high yields (up to 81 %). Thermal ring contraction, via N2 extrusion, of spiro‐1‐pyrazolinepenicillanates under continuous flow conditions led to spirocyclopropanepenicillanates in quantitative yields. The continuous flow proved to be an efficient methodology for the synthesis of spiropenicillanates and represents a more sustainable approach for the larger‐scale synthesis of spiropenicillanates with relevant biological activity. [ABSTRACT FROM AUTHOR]

Water remediation with biomass derivatives has attracted attention for its sustainable impact on the earth. Chemical procedures for new adsorbent and active biomaterials must be implemented to remove organic pollutants more efficiently. Herein, we obtained a sustainable, environmentally, and low‐cost biochar from bamboo Dendrocalamus giganteus (BBC, B400) by thermal treatment at 400 °C without physical and chemical pre‐ and post‐treatments. By electron paramagnetic resonance (EPR), we determined the quantification and ageing of persistent free radicals (PFRs, 1016–1019 spins/g) present in BBC over time. We demonstrated the removal efficiency (R %) of B400 against methylene blue (MB) aqueous solutions without and with different concentrations of H2O2 using a novel B400‐packed column‐flow system. Results demonstrated that the MB removal efficiency via physical adsorption and chemical degradation strongly depended on the concentration of carbon‐centred PFRs and their stability over time. Collectively, a reduced concentration of PFRs and their full passivation by proper treatments led to a remarkable loss of MB removal efficiency, thus evidencing that a PFR‐mediated radical degradation mechanism was predominant in the MB removal process. Experiments with t‐butanol alcohol (TBA) on aged B400 as a radical scavenger of the hydroxyl radical (⋅OH) have evidenced the critical role of PFRs in generating reactive oxygens species (ROSs) in solution, which catalysed the oxidative degradation of MB. Kinetics studies carried out on removal efficiency data vs time by all experiments established that the MB removal profiles of fresh B400 were best described by a pseudo‐second order (PSO) kinetic model, thus suggesting that chemical mechanisms such as electron transfer reactions and PFRs‐mediated degradation were the main contributors to MB removal. On the contrary, MB removal profiles of aged B400 with reduced or insignificant content of PFRs best fitted kinetic models, which describe physical absorption and diffusional nor radical processes, which led to a lower removal efficiency. These findings will be helpful for potential pilot and large‐scale experiments to remove a wide range of contaminants in water. [ABSTRACT FROM AUTHOR]

The document "Green Chemistry" published by the Royal Society of Chemistry features cutting-edge research on sustainable practices and innovations in the field of chemistry. The contents include critical reviews, tutorial reviews, communications, and papers covering a wide range of topics such as biochar systems, catalysts for biomass conversion, energy conversion, and storage, as well as biodegradable polymers and synthesis methods. The journal aims to connect communities, inspire new ideas, and promote environmentally friendly solutions in chemistry. [Extracted from the article]

This is a review on the feasibility of monolithic porous supports in biocatalysis carried out in a continuous flow system. It discusses factors affecting the efficiency and stability of enzyme immobilisation, kinetic parameters of enzyme processes carried out inside a monolith, biocatalysis in single and two-phase systems, and cascade reactions including cofactor regeneration. It also covers materials engineering (monolith types) and issues related to the flow of reactants through the monolith (chemical engineering). Emphasis is placed on the fact that the application of (bio)catalysis improves selectivity and atom economy, thus lowering the E factor. However, biocatalysts need to be employed in a reactor, which can aid further improvement towards green chemistry goals. The application of enzymes in flow chemistry has been shown to lead to higher space time yields (STYs) compared to batch reactions. In particular, with monolithic reactors a drastic decrease in volume and thus solvent can be achieved. By immobilising very high densities of enzymes directly on the monolith, reaction times dwindle, improving STYs. The small reaction volumes enable excellent heat transfer, helping to save energy. The underlying principles of monolithic flow reactors and their application in mono- and bi-phasic biocatalytic systems will be examined. [ABSTRACT FROM AUTHOR]

The "Chemical Society Reviews" journal, published by The Royal Society of Chemistry, features a variety of research articles on topics such as metal oxide catalysis, nanoplasmonic biosensors, and stretchable optoelectronic materials. The journal covers a range of subjects related to chemistry, including environmental sustainability, bioelectronic interfaces, and energy conversion. Researchers interested in cutting-edge developments in the field of chemistry may find valuable insights in this publication. [Extracted from the article]

Utilizing electrons directly offers significant potential for advancing organic synthesis by facilitating novel reactivity and enhancing selectivity under mild conditions. As a result, an increasing number of organic chemists are exploring electrosynthesis. However, the efficacy of electrochemical transformations depends critically on the design of the electrochemical cell. Batch cells often suffer from limitations such as large inter-electrode distances and poor mass transfer, making flow cells a promising alternative. Implementing flow cells, however, requires a foundational understanding of microreactor technology. In this review, we briefly outline the applications of flow electrosynthesis before providing a comprehensive examination of existing flow reactor technologies. Our goal is to equip organic chemists with the insights needed to tailor their electrochemical flow cells to meet specific reactivity requirements effectively. We also highlight the application of reactor designs in scaling up electrochemical processes and integrating high-throughput experimentation and automation. These advancements not only enhance the potential of flow electrosynthesis for the synthetic community but also hold promise for both academia and industry. [ABSTRACT FROM AUTHOR]

R‐22 gas (ClCF2H) is utilized in continuous flow for the installation of CF2H and CF2D groups on heteroatoms. A judiciously designed flow system suppresses the intrinsic SN2 reaction between heteroatom anions and ClCF2H, allowing for selective carbene‐based fragment coupling to yield X‐CF2D products with deuterium incorporation levels up to 96%. A broad scope of X–CF2H and X–CF2D products (X=S, O, N) is obtained with a short residence time of 5 minutes and scalability is demonstrated. [ABSTRACT FROM AUTHOR]

Synthetic organic electrochemistry is recognized as one of the most sustainable forms of redox chemistry that can enable a wide variety of useful transformations. In this study, readily prepared pyrolytic carbon electrodes are explored in several powerful rAP transformations as well as C−C and C−N bond forming reactions. Pyrolytic carbon provides an alternative to classic amorphous carbon‐based materials that are either expensive or ill‐suited to large‐scale flow reactions. [ABSTRACT FROM AUTHOR]

Heterogeneous visible light photocatalysis is a compelling approach to address sustainability in synthetic photochemistry. However, the use of solid‐state photocatalysts remains very unpopular in organic synthesis because of their limited accessibility and the black‐box effect associated to the lack of rational between their molecular structure and their photochemical properties. Herein, we disclose the synthesis, characterization, photocatalytic properties and synthetic applications of a simple and readily available solid‐state conjugated organic polymer, poly‐(para‐phenylene ethynylene) 1, which exhibits a strong oxidative power upon irradiation with visible light (E(1*/1⋅−)=+1.67 V vs SCE). Comparisons with structural analogues highlighted the superior photocatalytic activity of this linear semiconductor, on account of its fully conjugated architecture. The associated excited‐state reactivity enabled the transformation of various amines into imines in batch and continuous flow reactors together with straightforward photocatalyst recycling. Mechanistic investigations revealed concomitant photoredox and energy transfer pathways, that led to the formation of the desired products. Ultimately, the inline generation of imines was exploited in telescoped three‐component Ugi reactions (3CR) in batch and flow toward biologically relevant α‐acylaminoamides. [ABSTRACT FROM AUTHOR]

The selective monoaddition of polymerizable vinyl monomers like styrenes and methacrylates in a living manner has been achieved for the flash‐flow preparation of molecules in a defined sequence with high selectivity. We demonstrated the sequence‐defined synthesis of multifunctional molecules using an initiator, functionalized styrenes, diarylethylenes, various methacrylates, and an electrophilic trapping reagent at the living terminus (six‐component sequential connection at maximum) without any intermediate purification steps. The anionic living terminus of the vinyl monomers in the flow system described herein is active for polymerization, such that the styrene or methacrylate sequence can be expanded to afford highly dispersed oligomers without affecting other single units, which means that the unequivocal sequences were successfully inserted into the internal or terminal positions. The methodology described herein provides an adaptable method for the construction of new molecular spaces based on unimolecular sequence control and pinpoint functionalization. [ABSTRACT FROM AUTHOR]

The control over the movement of electrons during chemical reactions with oriented external electric fields (OEEFs) has been predicted to offer a general approach to catalysis. Recently, we suggested that many problems to realize electric‐field catalysis in practice under scalable bulk conditions could possibly be solved on multiwalled carbon nanotubes in electromicrofluidic reactors. Here, we selected monoterpene cyclizations to assess the scope of our system in organic synthesis. We report that electric‐field catalysis can function by stabilizing both anionic and cationic transition states, depending on the orientation of the applied field. Moreover, electric‐field catalysis can promote reactions which are barely accessible by general Brønsted and Lewis acids and field‐free anion‐π and cation‐π interactions, and drive chemoselectivity toward intrinsically disfavored products without the need for pyrene interfacers attached to the substrate to prolong binding to the carbon nanotubes. Finally, interfacing with chiral organocatalysts is explored and evidence against contributions from redox chemistry is provided. [ABSTRACT FROM AUTHOR]

Etherification and amination of aryl halide scaffolds are commonly used reactions in parallel medicinal chemistry to rapidly scan structure–activity relationships with abundant building blocks. Electrochemical methods for aryl etherification and amination demonstrate broad functional group tolerance and extended nucleophile scope compared to traditional methods. Nevertheless, there is a need for robust and scale‐transferable workflows for electrochemical compound library synthesis. Herein we describe a platform for automated electrochemical synthesis of C−X arylation (X=NH, OH) in flow to access compound libraries. A comprehensive Design of Experiment (DoE) study identifies an optimal protocol which generates high yields across>30 aryl halide scaffolds, diverse amines (including electron‐deficient sulfonamides, sulfoximines, amides, and anilines) and alcohols (including serine residues within peptides). Reaction sequences are automated on commercially available equipment to generate libraries of anilines and aryl ethers. The unprecedented application of potentiostatic alternating polarity in flow is essential to avoid accumulating electrode passivation. Moreover, it enables reactions to be performed in air, without supporting electrolyte and with high reproducibility over consecutive runs. Our method represents a powerful means to rapidly generate nucleophile independent C−X arylation compound libraries using flow electrochemistry. [ABSTRACT FROM AUTHOR]

Microfluidic‐assisted synthesis of nanoparticles has generated significant interest for its precise control and high throughput capabilities. Among various nanomaterials, gold nanoparticles (AuNPs) have shown remarkable potential in numerous applications, such as disease detection, photothermotherapy, drug delivery, and even defense applications. Recent synthesis strategy of peptide‐mediated method has sparked greater interest by offering unique chiroptical properties and their applications in biomedical applications. In this study, the use of droplet microfluidics is explored for the synthesis of peptide‐mediated AuNPs, aiming to accelerate automated production via flow chemistry. This method leads to the formation of anisotropic gold particles, with sizes ranging from hundreds of nanometers to the micron scale. The interfacial energy is identified at the water/oil interface as a critical factor influencing this outcome, with L‐glutathione (L‐GSH) playing a significant role in the development of hyper‐branched structures. These results demonstrate the capability of droplet microfluidics in producing anisotropic gold particles at micron scales, presenting new possibilities for the advancement of nanoparticle synthesis techniques. [ABSTRACT FROM AUTHOR]

Pralidoxime salts are important medical countermeasures towards different organophosphorus compounds, either nerve agents or pesticides, as they act as acetylcholinesterase reactivators, avoiding health issues and even death that can result from intoxication with such chemicals. In this work, we present an expeditious study focuses on the optimization of a two‐step continuous‐flow synthesis of 2‐PAM. Initial attempts to replace the solvent composition in the oxime formation reaction with acetonitrile resulted in lower yields, highlighting the significance of a polar protic solvent. Subsequent optimization under continuous‐flow conditions revealed the successful execution of oxime formation at room temperature with a residence time of 20 minutes, achieving an impressive 96 % conversion, surpassing literature‐reported conditions. The methylation step required a high residence time of 60 minutes at 120 °C for a substantial conversion of 78 %. The two‐step continuous‐flow process demonstrated robustness, yielding 75 %, with space‐time yields of 0.32 g/h and 0.18 g/h. Further concentration adjustments increased space‐time yields to 3.2 g/h and 2.2 g/h. Despite solvent incompatibility, a strategic alteration of the reaction sequence allowed for a successful cascade process, integrating the methylation step in acetonitrile and the oxime formation in water. The continuous‐flow system, incorporating a heat exchanger, exhibited stability, maintaining full conversion and a space‐time yield of 0.3 g/h over extended periods. This systematic optimization not only enhances the efficiency of 2‐PAM synthesis but also provides insights into a scalable and practical continuous‐flow cascade process. [ABSTRACT FROM AUTHOR]

Chemical reactions and transformations in non‐traditional vessels have gained significant interest in recent years. Flow chemistry, with its advantages in mixing, mass transfer, scalability, and automation, is a driving force behind this paradigm shift. In particular, the Vortex Fluidic Device (VFD) has emerged as a versatile tool across various applications, from organic synthesis to materials science. In this study, the role of the VFD in performing the Biginelli reaction, a multicomponent reaction widely used in pharmaceutical and polymer science, for a post‐polymerization modification is explored. By conducting the Biginelli reaction in the VFD, rapid product formation with low catalyst loading and without the need for high temperatures is achieved. However, the critical need to understand and know solution viscosity, especially within the context of modifying macromolecules is highlighted. [ABSTRACT FROM AUTHOR]

This critical review provides an overview of the sustainability outcomes associated with flow chemistry, as a new concept in process chemistry, and its related technology and engineering field, microreaction technology. This study is broad in scope and covers cost and life cycle assessment methodologies applied to flow chemistry. The present review differs from past studies by providing a mechanistic viewpoint, i.e., starting by listing key levers (e.g. mass transfer), and then unravelling their impact on costs and life cycle, using reported flow chemistry studies as examples to underline the sustainability capability. This way, this review transitions from informing on how flow chemistry and microreactors can improve fundamental principles in chemical engineering and chemistry to their translation to improved sustainability. Gaps and opportunities in the reporting of microreactor/flow chemistry are identified. To put the reported achievements into perspective, a life cycle assessment (LCA) study is conducted that reports on the effects of the key levers, as identified in this study, for a flow chemistry reaction at the pilot scale, conducted at an industrial site (technology readiness level 4). This way, this study provides a quantitative forecast of what principally can be achieved when maximising the key levers, in terms of the individual LCA impact categories and their total average outcome. [ABSTRACT FROM AUTHOR]

The development of novel strained spiro heterocycles (SSHs) as bioisosteres for aromatic or non‐strained aliphatic rings is highly sought after for improving drug design. Their high molecular rigidity and predictable vectorization can enhance drug‐likeness, target selectivity and clinical success. Towards this goal, 1‐oxa‐2,6‐diazaspiro[3.3]heptane (ODASE) is reported as a novel potential SSH‐bioisostere. We demonstrate through theoretical studies the potential of this strained spiro heterocycle to act as a bioisostere for piperazine. We have developed its synthesis from the highly strained azabicyclo[1.1.0]butyl intermediate through a robust and mild flow technology‐assisted two‐step protocol. Its tolerance and stability towards medicinally relevant N‐functionalisation protocols are studied, as well as its mild reduction to the C3‐aminoalkylazetidinol motif found in the anti‐cancer drug cobimetinib. [ABSTRACT FROM AUTHOR]

Hypoxia occurs in different pathological settings as a consequence of poor vascularization, and it results in reduced efficacy of some current nosocomial treatments i. e. chemotherapy and photodynamic therapy. In order to overcome these boundaries, aromatic endoperoxides (EPOs) have been studied and proposed as oxygen‐releasing agents (ORAs) due to their ability to reversibly bind molecular oxygen (O2), liberating it upon suitable triggering. DFT calculation of the dissociation energy (Ediss) of the intramolecular O−O bridge and structural crystallographic data of synthesized and studied EPOs drove the design of an array of 9,10‐disubstituted anthracenes among which three candidates were carefully selected. Once optimized the synthesis of the aromatic substrates, for the first time the corresponding EPOs have been produced under continuous flow irradiation in the presence of a sub‐stoichiometric amount of a photosensitizer in organic solvents. The release of O2 could be obtained straightforwardly at 37.5 °C by thermolysis. In accordance with the calculated Ediss=3.2 kcal mol−1 and an experimental t1/2=40 minutes, 3,3′‐(anthracene‐9,10‐diyl)bis(prop‐2‐yn‐1‐ol) resulted as the best candidate for the sustained release of O2 under physiologically relevant conditions. Its exploitation as ORA to relieve hypoxia will be evaluated and described in due course. [ABSTRACT FROM AUTHOR]

This review deals with C1 carbenoid chemistry, with a focus on lithium carbenoid species generated in flash flow systems. Strict control of the temperature, residence time, and mixing efficiency has led to various transformation reactions involving epoxidation, cyclopropanation, and homologation, among others. The use of other metal species, including trifluoromethylpotassium (CF3 K) and magnesium/ zinc carbenoids, in flow systems is also introduced. 1 Introduction 1.1 Lithium Carbenoids in C1 Chemistry 1.2 Flow Chemistry for C1 Lithium Carbenoids 2 Flow Reactions Involving Carbenoid Species 2.1 Deprotonative Generation of Lithium Carbenoid Species 2.2 Generation of Lithium Carbenoid Species via Halogen–Lithium Exchange 2.3 Generation of Lithium Carbenoid Species via Reductive Lithiation 2.4 Generation of Lithium Carbenoid Species via Alkyllithiation 2.5 Generation of Trifluoromethylpotassium Species in Flow 2.6 Generation of Other Metal Carbenoid Species 3 Conclusion [ABSTRACT FROM AUTHOR]

Benzo[1,3,2]dithiazole‐1,1,3‐trioxides are bench‐stable and easy‐to‐use reagents. In photoredox catalysis, they generate methyl and perdeuteromethyl radicals which can add to a variety of radical acceptors, including olefins, acrylamides, quinoxalinones, isocyanides, enol silanes, and N‐Ts acrylamide. As byproduct, a salt is formed which can be regenerated to the original methylating agent. Flow chemistry provides an option for reaction scale‐up further underscoring the synthetic usefulness of these methylation reagents. Mechanistic investigations suggest a single‐electron transfer (SET) pathway induced by photoredox catalysis. [ABSTRACT FROM AUTHOR]

Referring to selected examples of reproducible green syntheses using hybrid sol‐gel catalysts of the SiliaCat series from different doctoral theses and research works published between 2015 and early 2024, this study briefly illustrates how said catalysts have been applied in a number of green synthetic methods of significant industrial relevance. This shows evidence that the nanochemistry "bottom‐up" sol‐gel approach based on catalytic species entrapped in organically modified silicas as effective and versatile heterogeneous catalysts developed between the late 1990s and 2010 has succeeded. Subsequent developments will show how the use of said materials in automated syntheses, supplying data to machine learning algorithms actually leads to faster and cheaper optimization of the reaction conditions. Said progress ultimately will further accelerate industrial uptake of heterogeneous catalysis under flow in the fine chemical industry whose reluctance to change processes was due to the need to replace financially amortized (and expensive) production plants. [ABSTRACT FROM AUTHOR]

Graphene oxide (GO) is broadly investigated in the electrochemical field. However, for industrial applications, it still suffer from high pollution, low efficiency, poor production quality, and safety concerns associated with traditional synthesis methods. Herein, guided by theoretical analyses, a new oxygen‐atom‐transfer (OAT) mechanism for periodate oxidizing graphite is revealed, exhibiting controllable reaction activity, strong orbital interaction, and abundant electron transfer. Moreover, a flow chemistry strategy with high mass/heat transfer rates is designed to enhance interlayer diffusion and reaction dynamics between oxidants and graphite, ensuring the efficient synthesis of GO within several minutes. As a result, both low oxygen‐content GO with large size, and high oxygen‐content GO with adequate active sites can be precisely and safely synthesized. Benefitting from the controllability of oxygen content and lateral size, the as‐prepared GO sheets can be facilely assembled into fiber/film electrodes that present high mechanical flexibility, large electrical conductivity, and outstanding electrochemical performance. [ABSTRACT FROM AUTHOR]

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. Highlights: Silybin B was more selectively acetylated compared to silybin A. Reaction rate was insensitive to temperature due to exothermic adsorption. Kinetics and adsorption parameters were obtained by non-linear regression analysis. Good prediction achieved with axial dispersion model and Eley-Rideal mechanism. Flow chemistry boosts silibinin enzymatic resolution over traditional methods. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Microreactor technologies have emerged as versatile platforms with the potential to revolutionize chemistry and materials research, offering sustainable solutions to global challenges in environmental and health domains. This survey paper provides an in-depth review of recent advancements in microreactor technologies, focusing on their role in facilitating accelerated discoveries in chemistry and materials. Specifically, we examine the convergence of microfluidics with machine intelligence and automation, enabling the exploitation of the cyber-physical environment as a highly integrated experimentation platform for rapid scientific discovery and process development. We investigate the applicability and limitations of microreactor-enabled discovery accelerators in various chemistry and materials contexts. Despite their tremendous potential, the integration of machine intelligence and automation into microreactor-based experiments presents challenges in establishing fully integrated, automated, and intelligent systems. These challenges can hinder the broader adoption of microreactor technologies within the research community. To address this, we review emerging technologies that can help lower barriers and facilitate the implementation of microreactor-enabled discovery accelerators. Lastly, we provide our perspective on future research directions for democratizing microreactor technologies, with the aim of accelerating scientific discoveries and promoting widespread adoption of these transformative platforms. [ABSTRACT FROM AUTHOR]

Aqueous synthesis of covellite CuS nanoparticles holds significant importance in the field of nanomaterials and environmental sustainability. Using water as a solvent and reactant in the synthesis process aligns with green chemistry principles. It enhances nanoparticle production's scalability and safety. CuS nanoparticles have gained attention for their diverse applications in catalysis, energy storage, and environmental remediation. Aqueous synthesis reduces the environmental footprint associated with hazardous organic solvents, making it an eco‐friendly approach. We report on synthesis routes toward covellite CuS nanocrystals (NCs), emphasizing easy and fast synthesis techniques. Additionally, we develop a flow synthesis of small near infrared active CuS NCs in a custom‐made flow reactor. Combining the advantages of aqueous synthesis and flow chemistry yields a robust and sustainable method for producing covellite CuS NCs readily dispersible in water medium, paving the way for their widespread application in diverse fields. [ABSTRACT FROM AUTHOR]

The batch processes of APIs/pharmaceutical synthesis are prone to suffer significant limitations, including longer process time, shortage of skilled manpower, laborious post-synthetic work-up, etc. To address the inherent limitations of batch processes, a novel approach was undertaken, resulting in the establishment and development of a visible light-assisted modular photo-flow reactor with a seamlessly integrated post-synthetic work-up procedure enabling the efficient synthesis of dihydropyranones from furfuryl alcohols. The reaction uses sun light as green energy source, and the novel photo-flow reactor platform developed with an integrated system enabling a downstream process in a time and labor-efficient manner which facilitates the Achmatowicz rearrangement, resulting in a fast (10 min) formation of the dihydropyranone products.

Amino acids are vital motifs in the domain of biochemistry, serving as the foundational unit for peptides and proteins, while also holding a crucial function in many biological processes. Due to their bifunctional character, they have been also used for combinatorial chemistry purposes, such as the preparation of DNA-encoded chemical libraries. We developed a practical synthesis for α-heteroaryl-α-amino acids starting from an array of small heteroaromatic halides. The reaction sequence utilizes a photochemically enhanced Negishi cross-coupling as a key step, followed by oximation and reduction. The prepared amino esters were validated for on-DNA reactivity via a reverse amidation–hydrolysis–reverse amidation protocol.

A flow photochemical reaction system for a π-Lewis acidic metal-catalyzed cyclization/radical addition sequence was developed, which utilizes in situ-generated 2-benzopyrylium intermediates as the photoredox catalyst and electrophilic substrates. The key 2-benzopyrylium intermediates were generated in the flow reaction system through the intramolecular cyclization of ortho-carbonyl alkynylbenzene derivatives by the π-Lewis acidic metal catalyst AgNTf2 and the subsequent proto-demetalation with trifluoroacetic acid. The 2-benzopyrylium intermediates underwent further photoreactions with benzyltrimethylsilane derivatives as the donor molecule in the flow photoreactor to provide 1H-isochromene derivatives in higher yields in most cases than the batch reaction system.

Kittipat Suwanpitak,1 Kampanart Huanbutta,2 Nopphon Weeranoppanant,3 Pornsak Sriamornsak,4,5 Chonlada Panpipat,1 Tanikan Sangnim1 1Faculty of Pharmaceutical Sciences, Burapha University, Chonburi, 20131, Thailand; 2Department of Manufacturing Pharmacy, College of Pharmacy, Rangsit University, Pathum Thani, 12000, Thailand; 3Department of Chemical Engineering, Faculty of Engineering, Burapha University, Chonburi, 20131, Thailand; 4Department of Industrial Pharmacy, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, 73000, Thailand; 5Academy of Science, the Royal Society of Thailand, Bangkok, 10300, ThailandCorrespondence: Tanikan Sangnim, Faculty of Pharmaceutical Sciences, Burapha University, 169, Seansook, Muang, Chonburi, 20131, Thailand, Email tanikan@go.buu.ac.thIntroduction: Lipid-based nanoparticles (LNPs) is increasingly recognized for their potential in drug delivery, offering protection to hydrophobic drugs from degradation. Industrial synthesis of LNPs, exemplified by Pfizer-BioNTech and Moderna mRNA vaccines, utilizes flow chemistry or microfluidics, showcasing its scalability. This study explores the utilization of a novel design reactor, the vortex tube reactor, within flow chemistry for LNPs synthesis, aiming to optimize its conditions and compare them with batch synthesis.Methods: LNPs were synthesized using the vortex tube reactor, incorporating bovine serum albumin (BSA) as a model drug in the aqueous phase, alongside 1.2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and cholesterol in the organic phase. Design of experiments (DoE), specifically Box-Behnken design, was employed to optimize parameters, including X1: the flow rate ratio (10– 100 mL/min), X2: the aqueous-to-organic volumetric ratio (1:1– 10:1), and X3: the number of reactor units (1– 5 units). Responses evaluated encompassed physical properties and productivity. Optimized conditions were determined by minimizing particle size (Y1), polydispersity index (Y2), and zeta potential (Y3), while maximizing entrapment efficiency (Y4), drug loading (Y5), and productivity (Y5).Results: Results indicated that optimal conditions were achieved at X1 of 100 mL/min, X2 of 5.278, and X3 of 1 unit. LNPs synthesized under these conditions exhibited favorable physical properties and productivity, with uniformity maintained across batches. The vortex tube reactor demonstrated superiority over batch synthesis, yielding smaller particles (166.23 ± 0.98 nm), more uniform nanoparticles (PDI 0.17 ± 0.01), and higher entrapment (67.75 ± 1.55%) and loading capacities (36.39 ± 0.83%), indicative of enhanced productivity (313.4 ± 12.88 mg/min).Conclusion: This study elucidates the potential of flow chemistry, particularly utilizing the vortex tube reactor, for large-scale LNPs formulation, offering insights into parameter relationships and advancing nanoparticle synthesis for drug delivery applications. Keywords: flow chemistry, lipid-based nanoparticles, nanoparticles synthesis, biological product

Recent years have witnessed significant advancements in methodologies and techniques for the synthesis of energetic materials, which are expected to shape future manufacturing and applications. Techniques including continuous flow chemistry, electrochemical synthesis, microwave-assisted synthesis, and biosynthesis have been extensively employed in the pharmaceutical and fine chemical industries and, gratifyingly, have found broader applications. This review comprehensively introduces recent advancements in the utilization of these emerging techniques, aiming to provide a catalyst for the development of novel green methods and techniques for synthesizing energetic materials.

@AntonioPulcine1, @KenYamazaki5, @EvelineTiekink, @TrevorAHamlin, @tnoel82, @HimsUva, @VU Science, @NoelGroupUvA.The homologous series of gaseous C1‐4 alkanes represents one of the most abundant sources of short alkyl fragments. However, their application in synthetic organic chemistry is exceedingly rare due to the challenging C−H bond cleavage, which typically demands high temperatures and pressures, thereby limiting their utility in the construction of complex organic molecules. In particular, the formation of C(sp2)−C(sp3) bonds is crucial for constructing biologically active molecules, including pharmaceuticals and agrochemicals. In this study, we present the previously elusive coupling between gaseous alkanes and (hetero)aryl bromides, achieved through a combination of Hydrogen Atom Transfer (HAT) photocatalysis and nickel‐catalyzed cross coupling at room temperature. Utilizing flow technology allowed us to conduct this novel coupling reaction with reduced reaction times and in a scalable fashion, rendering it practical for widespread adoption in both academia and industry. Density Functional Theory (DFT) calculations unveiled that the oxidative addition constitutes the rate‐determining step, with the activation energy barrier increasing with smaller alkyl radicals. Furthermore, radical isomerization observed in propane and butane analogues could be attributed to the electronic properties of the bromoarene coupling partner, highlighting the crucial role of oxidative addition in the observed selectivity of this transformation. [ABSTRACT FROM AUTHOR]

Photocatalytic synthesis of value‐added chemicals has gained increasing attention in recent years owing to its versatility in driving many important reactions under ambient conditions. Selective hydrogenation, oxidation, coupling, and halogenation with a high conversion of the reactants have been realized using designed photocatalysts in batch reactors with small volumes at a laboratory scale; however, scaling‐up remains a critical challenge due to inefficient utilization of incident light and active sites of the photocatalysts, resulting in poor catalytic performance that hinders its practical applications. Flow systems are considered one of the solutions for practical applications of light‐driven reactions and have experienced great success in photolytic and homogeneous photocatalysis, yet their applications in heterogeneous photocatalysis are still under development. In this perspective, we have summarized recent progress in photolytic and photocatalytic synthetic chemistry performed in flow systems from the view of reactor design with a special focus on heterogeneous photocatalysis. The advantages and limitations of different flow systems, as well as some practical considerations of design strategies are discussed. [ABSTRACT FROM AUTHOR]

Metal–organic frameworks (MOFs) and their composites have garnered significant attention in recent years due to their exceptional properties and diverse applications across various fields. The conventional batch synthesis methods for MOFs and their composites often suffer from challenges such as long reaction times, poor reproducibility, and limited scalability. Continuous flow synthesis has emerged as a promising alternative for overcoming these limitations. In this short review, we discuss the recent advancements, challenges, and future perspectives of continuous flow synthesis in the context of MOFs and their composites. The review delves into a brief overview of the fundamental principles of flow synthesis, highlighting its advantages over batch methods. Key benefits, including precise control over reaction parameters, improved scalability and efficiency, rapid optimization capabilities, enhanced reaction kinetics and mass transfer, and increased safety and environmental sustainability, are addressed. Additionally, the versatility and flexibility of flow synthesis techniques are discussed. The article then explores various flow synthesis methods applicable to MOF and MOF composite production. The techniques covered include continuous flow solvothermal synthesis, mechanochemical synthesis, microwave and ultrasound-assisted flow synthesis, microfluidic droplet synthesis, and aerosol synthesis. Notably, the combination of flow chemistry and aerosol synthesis with real-time characterization is also addressed. Furthermore, the impact of flow synthesis on the properties and performance of MOFs is explored. Finally, the review discusses current challenges and future perspectives in the field of continuous flow MOF synthesis, paving the way for further development and broader application of this promising technique. [ABSTRACT FROM AUTHOR]

Oxidation flow reactors (OFRs) have been extensively utilized to examine the formation of secondary organic aerosol (SOA). However, the UV lamps typically employed to initiate the photochemistry in OFRs can result in an elevated reactor temperature when their implications are not thoroughly evaluated. In this study, we conducted a comprehensive investigation into the temperature distribution within an Aerodyne potential aerosol mass OFR (PAM-OFR) and then examined the subsequent effects on flow and chemistry due to lamp heating. A lamp-induced temperature increase was observed, which was a function of lamp-driving voltage, number of lamps, lamp types, OFR residence time, and positions within the PAM-OFR. Under typical PAM-OFR operational conditions (e.g., < 5 d of equivalent atmospheric OH exposure under low- NOx conditions), the temperature increase typically ranged from 1–5 °C. Under extreme (but less frequently encountered) conditions, the heating could reach up to 15 °C. The influences of the increased temperature over ambient conditions on the flow distribution, gas, and condensed-phase chemistry within PAM-OFR were evaluated. Our findings indicate that the increase in temperature altered the flow field, resulting in a diminished tail on the residence time distribution and corresponding oxidant exposure due to faster recirculation. According to simulation results from a radical chemistry box model, the variation in absolute oxidant concentration within PAM-OFR due to temperature increase was minimal (< 5 %). The temperature influences on seed organic aerosol (OA) and newly formed secondary OA were also investigated, suggesting that an increase in temperature can impact the yield, size, and oxidation levels of representative biogenic and anthropogenic SOA types. Recommendations for temperature-dependent SOA yield corrections and PAM-OFR operating protocols that mitigate lamp-induced temperature enhancement and fluctuations are presented. We recommend blowing air around the reactor's exterior with fans during PAM-OFR experiments to minimize the temperature increase within PAM-OFR. Temperature increases are substantially lower for OFRs utilizing less powerful lamps compared to the Aerodyne version. [ABSTRACT FROM AUTHOR]

Brazil has one of the greatest biodiversities on the planet, where various crops play a strategic role in the country's economy. Among the highly appreciated biomasses is babassu, whose oil extraction generates residual babassu mesocarp (BM), which still needs new strategies for valorization. This work aimed to use BM as a support for the immobilization of Thermomyces lanuginosus lipase (TLL) in an 8.83 mL packed‐bed reactor, followed by its application as a biocatalyst for the synthesis of hexyl laurate in an integrated process. Initially, the percolation of a solution containing 5 mg of TLL at 25 °C and flows ranging from 1.767 to 0.074 mL min−1 was investigated, where at the lowest flow rate tested (residence time of 2 h), it was possible to obtain an immobilized derivative with hydrolytic activity of 504.7 U g−1 and 31.7 % of recovered activity. Subsequent studies of treatment with n‐hexane, as well as the effect of temperature on the immobilization process, were able to improve the activities of the final biocatalyst BM‐TLLF, achieving a final hydrolysis activity of 7023 U g−1 and esterification activity of 430 U ⋅ g−1 against 142 U g−1 and 113.5 U g−1 respectively presented by the commercial TLIM biocatalyst. Desorption studies showed that the TL IM has 18 mg of protein per gram of support, compared to 4.92 mg presented by BM‐TLL. Both biocatalysts were applied to synthesize hexyl laurate, achieving 98 % conversion at 40 °C within 2 h. Notably, BM‐TLLF displayed exceptional recyclability, maintaining catalytic efficiency over 12 cycles. This reflects a productivity of 180 mg of product ⋅ h−1 U−1 of the enzyme, surpassing 46 mg h−1 U−1 obtained for TLIM. These results demonstrate the efficacy of continuous flow technology in creating a competitive and integrated process offering an exciting alternative for the valorization of residual lignocellulosic biomass. [ABSTRACT FROM AUTHOR]

The document is a contents list for the journal "Green Chemistry," published by The Royal Society of Chemistry. It highlights the articles and research papers included in the issue, covering topics such as sustainable water treatment, lignocellulose pretreatment, and biomass valorization. The journal aims to promote cutting-edge research for a greener and more sustainable future. [Extracted from the article]

Continuous manufacturing of platform chemicals from lignocellulose is highly desirable for a fossil fuel independent future. We demonstrate highly selective production of para-xylene (pX) from ethylene and 2,5-dimethylfuran (DMF) in a packed bed microreactor using phosphorous-decorated zeolite beta (P-BEA), with pX selectivity up to 97% at 80% DMF conversion. We map the effect of reactor temperature, space velocity, concentration, gas-to-liquid ratio, and process pressure. Time-on-stream (TOS) and in situ regeneration studies show minimal productivity degradation over ∼5 h TOS and full productivity restoration upon regeneration for multiple cycles. Most non-selective Brønsted acidity occurs at low TOS and is attributed to the remaining trace Al bridge site. External mass transfer limitations are implicated at low space velocities. We combine the TOS data with NMR, XRD, and Raman to develop structure–performance insights into the catalyst behavior. A comparison with mesoporous P-supported materials illustrates that P-BEA is an excellent catalyst for size selectivity and long-term stability. [ABSTRACT FROM AUTHOR]

The reduction of aromatic compounds constitutes a fundamental and ongoing area of investigation. The selective reduction of polycyclic aromatic compounds to give either fully or partially reduced products remains a challenge, especially in applications to complex molecules at scale. Herein, we present a selective electrochemical hydrogenation of polycyclic arenes conducted under mild conditions. A noteworthy achievement of this approach is the ability to finely control both the complete and partial reduction of specific aromatic rings within polycyclic arenes by judiciously varying the reaction solvents. Mechanistic investigations elucidate the pivotal role played by in situ proton generation and interface regulation in governing reaction selectivity. The reductive electrochemical conditions show a very high level of functional‐group tolerance. Furthermore, this methodology represents an easily scalable reduction (demonstrated by the reduction of 1 kg scale starting material) using electrochemical flow chemistry to give key intermediates for the synthesis of specific drugs. [ABSTRACT FROM AUTHOR]

In the context of advanced nanomaterials research, nanogels (NGs) have recently gained broad attention for their versatility and promising biomedical applications. To date, a significant number of NGs have been developed to meet the growing demands in various fields of biomedical research. Summarizing preparation methods, physicochemical and biological properties, and recent applications of NGs may be useful to help explore new directions for their development. This article presents a comprehensive overview of the latest NG synthesis methodologies, highlighting advances in formulation with different types of hydrophilic or amphiphilic polymers. It also underlines recent biomedical applications of NGs in drug delivery and imaging, with a short section dedicated to biosafety considerations of these innovative nanomaterials. In conclusion, this article summarizes recent innovations in NG synthesis and their numerous applications, highlighting their considerable potential in the biomedical field. [ABSTRACT FROM AUTHOR]

Alkaline zinc‐ferricyanide flow batteries are efficiency and economical as energy storage solutions. However, they suffer from low energy density and short calendar life. The strongly alkaline conditions (3 mol L−1 OH−) reduce the solubility of ferri/ferro‐cyanide (normally only 0.4 mol L−1 at 25 °C) and induce the formation of zinc dendrites at the anode. Here, we report a new zinc‐ferricyanide flow battery based on a mild alkalescent (pH 12) electrolyte. Using a chelating agent to rearrange ferri/ferro‐cyanide ion‐solvent interactions and improve salt dissociation, we increased the solubility of ferri/ferro‐cyanide to 1.7 mol L−1 and prevented zinc dendrites. Our battery has an energy density of ~74 Wh L−1catholyte at 60 °C and remains stable for 1800 cycles (1800 hours) at 0 °C and for >1400 cycles (2300 hours) at 25 °C. An alkalescent zinc‐ferricyanide cell stack built using this alkalescent electrolyte stably delivers 608 W of power for ~40 days. [ABSTRACT FROM AUTHOR]

This article explores the potential of using volatile organic compounds (VOCs) in environmentally friendly industrial processes. It discusses the challenges associated with working with VOCs and presents a study on their reaction with organolithium species in a flow microreactor system. The study demonstrates successful molecular transformations with high yields and purity, suggesting that this approach could lead to the development of novel, environmentally friendly industrial processes. Additionally, the article discusses the development of a flow microreactor system for selective formylation of organolithium species, which significantly improves yield compared to a batch reaction system and allows for safe and precise handling of VOCs. This approach has the potential to contribute to the sustainable development of organic synthesis using VOCs. [Extracted from the article]

This paper presents the work performed to transition a lab-scale synthesis (1 g) to a large-scale (400 g) synthesis of the 3-5-diamino-1H-Pyrazole Disperazol, a new pharmaceutical for treatment of antibiotic-resistant Pseudomonas aeruginosa biofilm infections. The potentially hazardous diazotisation step in the lab-scale synthesis was transformed to a safe and easy-to-handle flow chemistry step. Additionally, the paper presents an OSHA-recommended safety assessment of active compound E, as performed by Fauske and Associates, LLC, Burr Ridge, IL, USA. [ABSTRACT FROM AUTHOR]

A series of supported N‐heterocyclic carbene silver complexes (NHC‐Ag(I)) were prepared and characterized as catalysts for the borono‐Minisci reaction. After characterization, the synthesized catalysts were evaluated in batch mode to determine the reaction performance and kinetics. Interestingly, cyclic voltammetric analysis showed that the structure of both the complex and the ligand significantly influences the Ag(I)/Ag(II) redox potential and, in turn, the catalytic efficiency. Among the tested catalysts, the Si‐supported NHC‐Ag(I) 6 afforded the desired products in good to excellent yields in only 15 min, providing a complementary tactic to standard homogeneous approaches. [ABSTRACT FROM AUTHOR]

Small carbo‐ and heterocyclic ring systems have experienced a significant increase in importance in recent years due to their relevance in modern pharmaceuticals, as building blocks for designer materials or as synthetic intermediates. This necessitated the development of new synthetic methods for the preparation of these strained ring systems focusing on effectiveness and scalability. The high ring strain of these entities as well as the use of high‐energy reagents and intermediates has often challenged their synthesis. Continuous flow approaches have thus emerged as highly effective means to safely and reliably access these strained scaffolds. In this short review, key developments in this field are summarised showcasing the power of continuous flow approaches for accessing 3‐ and 4‐membered ring systems via thermal, photo‐ and electrochemical processes. [ABSTRACT FROM AUTHOR]

The design of new and more sustainable synthetic protocols to access new materials or valuable compounds will have a high impact on the broader chemistry community. In this sense, continuous‐flow photochemistry has emerged as a powerful technique which has been employed successfully in various areas such as biopharma, organic chemistry, as well as materials science. However, it is important to note that chemical processes must not only advance towards new or improved chemical transformations, but also implement new technologies that enable new process opportunities. For this reason, the design of novel photoreactors is key to advancing photochemical strategies. In this sense, the use of equipment and techniques embracing processes intensification is important in developing more sustainable protocols. Among the most recent applications, spinning continuous flow reactors, such as rotor reactors or vortex reactors, have shown promising performance as new synthetic tools. Nevertheless, there is currently no review in the literature that effectively summarizes and showcases the most recent applications of such type of photoreactors. Herein, we highlight fundamental aspects and applications of two categories of spinning reactors, the Spinning Disc Reactors (SDRs) and Thin Film Vortex reactors, critiquing the scope and limitations of these advanced processing technologies. Further, we take a view on the future of spinning reactors in flow as a synthetic toolbox to explore new photochemical transformations. [ABSTRACT FROM AUTHOR]

Development of the efficient and practical method for the synthesis of deuterated compounds which occupies the broadest area among stable isotopes is one of the most essential issues toward the industrial advance and building a sustainable society. This review describes recent advances in deuteration reactions, where the continuous flow chemistry plays pivotal roles for the successful installation of deuterium atom into diverse organic frameworks, opening new fields of isotope‐based synthetic chemistry. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Generally, chemical engineering students get well acquainted with the batch synthesis of various active pharmaceutical ingredients, however, only tiny focus is provided to undergraduates on the topic of flow chemistry. In this paper, we report that students participating in the chemical engineering BSc course at the Budapest University of Technology and Economics were encouraged to perform the flow synthesis of paracetamol, a common pain painkiller. Two different synthetic routes for the continuous production of paracetamol were investigated and compared the batch and flow methods. Thus, these experiments allowed the students to discover flow chemistry for themselves under supervision: how to set up a flow system, how to carry out a reaction continuously, and to experience the advantages of flow chemistry over batch synthesis. In addition, students also got familiar with in-line Fourier transform infrared spectroscopy, as one of the reactions was monitored in real-time. [ABSTRACT FROM AUTHOR]

This paper presents a comprehensive study focusing on the detection and characterization of droplets with volumes in the nanoliter range. Leveraging the precise control of minute liquid volumes, we introduced a novel spectroscopic on-chip microsensor equipped with integrated microfluidic channels for droplet generation, characterization, and sensing simultaneously. The microsensor, designed with interdigitated ring-shaped electrodes (IRSE) and seamlessly integrated with microfluidic channels, offers enhanced capacitance and impedance signal amplitudes, reproducibility, and reliability in droplet analysis. We were able to make analyses of droplet length in the range of 1.0–6.0 mm, velocity of 0.66–2.51 mm/s, and volume of 1.07 nL–113.46 nL. Experimental results demonstrated that the microsensor's performance is great in terms of droplet size, velocity, and length, with a significant signal amplitude of capacitance and impedance and real-time detection capabilities, thereby highlighting its potential for facilitating microcapsule reactions and enabling on-site real-time detection for chemical and biosensor analyses on-chip. This droplet-based microfluidics platform has great potential to be directly employed to promote advances in biomedical research, pharmaceuticals, drug discovery, food engineering, flow chemistry, and cosmetics. [ABSTRACT FROM AUTHOR]