Continuous Synthesis Research Articles

Heterogeneous Fe-N-C Catalyst for Aerobic Dehydrogenation of Hydrazones to Diazo Compounds Used for Carbene Transfer.

Organic diazo compounds are versatile reagents in chemical synthesis and would benefit from improved synthetic accessibility, especially for larger scale applications. Here, we report a mild method for the synthesis of diazo compounds from hydrazones using a heterogeneous Fe-N-C catalyst, which has Fe ions dispersed within a graphitic nitrogen-doped carbon support. The reactions proceed readily at room temperature using O2 (1 atm) as the oxidant. Aryl diazoesters, ketones, and amides are accessible, in addition to less stable diaryl diazo compounds. Initial-rate data show that the Fe-N-C catalyst achieves faster rates than a heterogeneous Pt/C catalyst. The oxidative dehydrogenation of hydrazones may be performed in tandem with Rh-catalyzed enantioselective C-H insertion and cyclopropanation of alkenes, without requiring isolation of the diazo intermediate. This sequence is showcased by using a flow reactor for continuous synthesis of diazo compounds.

REVIEW ON THE SYNTHESIS OF ALPHA-LIPOIC ACID AND ITS THERAPEUTIC POTENTIAL IN EXPERIMENTAL MODEL OF DEMENTIA

LA or (±)-α-Lipoic acid (6,8-thioctic acid, 5-(1,2-dithiolan-3-yl)pentanoic acid) (LA) is a heterocyclic thia fattyacid consisting of pentanoic acid and a 1,2-dithiolan-3-yl group at the 5-position. LA is an amphiphilic pharmacophorewith excellent antioxidant, anti-inflammatory and neuroprotective effects attested by numerous studies for its potentialutility in both the treatment and diverse forms of prophylaxis of neurodegenerative disorders, especially Alzheimer’sdisease. This article aims to assess the differences in neuroprotective effect after short-term (11 days) and longterm(51 days) LA administration in an experimental rat model of scopolamine-induced dementia by correlatingbiochemical data on acetylcholinesterase activity with behavioural data. Behaviourally appraised changes in learningand memory appear to correlate with biochemical changes in AChE activity. The neuroprotective effect of LA, asascertained by its beneficial effects on learning and memory in a scopolamine animal model, appears to be associatedwith cholinergic mechanisms (a decrease in AChE activity), and to be larger after short-term administration ratherthan long-term administration. These results further underscore the candidacy of LA as a viable drug candidatesuitable for continued investigation and derivate synthesis endeavours.

Continuous synthesis of calcium hydrogen phosphate dihydrate (DCPD) in an annular rotating flow loop reactor

The synthesis of calcium hydrogen phosphate dihydrate (DCPD) involves a gas–liquid-solid three-phase slurry system that poses challenges for precise control using traditional batch reactors to produce crystals with controlled morphologies and particle sizes. In this study, an annular rotating flow loop reactor (ARLR) was developed to continuously synthesize DCPD. The unique internal loop and annular rotating flow field of the reactor delivered exceptional plug-flow characteristics, ensuring that the obtained DCPD exhibited a controlled morphology and particle size. The morphology of DCPD was adjusted to be bowknot-shaped (BS) agglomerate crystals, reaching a length of 120 μm and a D50 size of 70 μm. The ARLR can achieve long-term stable operation with high-solid holdup slurries, outputting up to 125 g/h by maintaining precise and controllable flow and mixing conditions. Notably, ARLR marked a significant advancement in processing high-solid-holdup slurries, offering the adaptability to adjust the geometric design for various slurry systems and forecasting promising prospects.

Continuous Scalable Synthesis and Concentration Variation of Organozinc Compounds

Continuous Scalable Synthesis and Concentration Variation of Organozinc Compounds

QCM Biosensors for pathogen detection in water and food: review of published literature

Introduction:This article is the result of the review “QCM Biosensors for the Detection of Pathogens in Water and Food: A Review,’ conducted during the years 2023 and 2024 at the Universidad Distrital Francisco José de Caldas”Problem: The fast evolution of pathogen detection through biosensors requires a continuous synthesis of literatu-re to provide an integral comprehension of the state of the art to new researchers. Objective:Perform bibliography research about QCM Biosensors used for pathogen detection in food and water covering a period from 2018 to 2023.Methodology: The research includes three phases: An explanation of the principles of QCM biosensors, their use in water and food pathogen detection, and their use in industry, with an emphasis on water quality.Result:QCM biosensors are solid, measure mass changes at the micro and nanometric scales, and are widely used in the food industry due to their accuracy and ease of use.Conclusion: The review highlights the effectiveness of QCM biosensors when detecting different food contami-nants and pathogens. It underlines the practical research necessity and importance of updating review papers to orientate future investigations in this specific area.Originality:The originality of this review lies on its detailed approach to QCM biosensor use in food pathogen detection.Limitations:The constant evolution of the field of pathogen detection in addition to the diversity of QCM biosen-sors and the wide range of pathogens studied may make it difficult to generalize certain findings.

Gas–Liquid Microchemical Oxidation for Continuous Synthesis Processes: A Short Review

AbstractGas–liquid oxidation processes, despite their wide application in the chemical industry, still pose considerable safety concerns. Microchemical technology has received high recognition for its intrinsic safety performance and process-intensification capability in hazardous reactions. This Short Review offers a comprehensive summary on how microchemical technology can be employed to achieve gas–liquid oxidation processes for continuous synthesis of chemicals in a safe, efficient, and controlled manner. Herein, we discuss the key aspects of gas–liquid dispersion and hydrodynamics, as well as mass transfer characteristics on microscale, and present representative gas–liquid oxidation cases in microflow reactors. Finally, the current challenges in industrial applications and potential academic research directions are presented.1 Introduction2 Microbubble Generation Technology for Gas–Liquid Oxidation Reactions3 Hydrodynamic and Mass-Transfer Characteristics of Gas–Liquid Oxidation Microreactors4 Gas–Liquid Oxidation Reactions in Microreactors5 Conclusion and Outlook

Impurity Profiling for a Scalable Continuous Synthesis and Crystallization of Carbamazepine Drug Substance

Impurity Profiling for a Scalable Continuous Synthesis and Crystallization of Carbamazepine Drug Substance

Continuous and Scalable Laser Synthesis of Atom Clusters with Tunable Surface Oxidation for Electrocatalytic Water Splitting

Continuous and Scalable Laser Synthesis of Atom Clusters with Tunable Surface Oxidation for Electrocatalytic Water Splitting

Continuous flow synthesis of hierarchical low silica X zeolite

Zeolites, renowned for their versatile applications in catalysis, adsorption, and ion exchange, have long been synthesized using conventional batch processes. However, the inherent limitations of these methods, such as resource-intensive conditions and inconsistent product quality, underscore the need for a sustainable and efficient approach. In this study, a continuous flow synthesis process was established for the synthesis of industrially important low silica X (LSX) zeolite using a tubular reactor. The synthesis gel was subjected to aging for 5 days at room temperature to facilitate nucleation and crystal growth combined with the fast-heating rate in a tubular reactor at 363 K & 1.1 atm., which in turn produces LSX after 40 min. The synthesized product was confirmed by the XRD, FE-SEM, EDS, XRF, TEM, and N2 adsorption-desorption; the data was compared with the LSX sample synthesized by batch process. The result implies that LSX prepared by continuous flow has a pure phase of LSX with the hierarchical structure, which provides better adsorption capacity of CO2 at 298 K up to 20 bar. Due to continuous flow synthesis, the crystallization time was reduced and faster kinetics which may be helpful for scale-up the process for LSX synthesis.

Ultrafast and efficient continuous flow organic synthesis with a modified extruder-grinder system

The study introduces a groundbreaking continuous system that combines an extruder and grinder to enable catalyst-free and solvent-free reactions under mild conditions. This temperature-controlled system facilitates the synthesis of highly functionalized chromenes, which have valuable applications in generating combinatorial libraries and complex target molecules. The newly developed mill extruder machine offers several advantages for industrial production on a large scale. It effectively reduces waste, saves energy, and enhances time efficiency. This system represents a significant advancement in the field, providing a new strategy for one-pot synthesis of various types of highly functionalized spirooxindoles and chromenes. Remarkably, these reactions can be accomplished within a short timeframe of 2–10 min, yielding impressive results of 75–98%. The results demonstrate superior performance compared to traditional reaction methods, making it an appealing tool and hotspot area of research in green chemistry.

Microfluidic flow synthesis of Al2O3 nanofluids for efficient phase-change boiling heat transfer enhancement of electronic devices

Integrating microchannel flow boiling heat transfer with nanofluids is an effective method for cooling electronic devices. However, traditional methods have significant limitations in achieving facile synthesis of nanofluids with desirable properties. In this study, we propose a straightforward synthesis strategy using microfluidic reactors, which enables continuous and high-throughout synthesis of Al2O3 nanofluids with high purity and long-term stability. These nanofluids were found to enhance boiling heat transfer performance by delaying bubbles coalescence, increasing surface nucleation sites, improving the nucleation rate, and enhancing wettability by observation of the bubble behavior. Specifically, the critical heat flux (CHF) and corresponding heat transfer coefficient (HTC) are increased by a maximum of 32 % and 26 %, respectively, with negligible change in pressure drop. Moreover, the heat transfer performance deteriorates with increasing concentration of alumina nanofluids. These findings not only provide guidance of microchannel flow boiling with nanofluids, but also present valuable insights for the application of nanofluids in two-phase cooling systems for electronic devices.

Continuous and controllable synthesis of MnO2 adsorbents for H2S removal at low temperature

H2S is an extremely noxious impurity generated from nature and chemical industrial processes. High performing H2S adsorbents are required for chemical industry and environmental engineering. Herein, α-, γ-, and δ-MnO2 adsorbents with high sulfur capacity were synthesized through a continuous-flow approach with a microreactor system, achieving much higher efficiency than hydrothermal methods. The relationship between crystal structure and synthesis conditions such as residence time, reaction temperature, concentration of K+ in solution and reactant ratio is discussed. According to the H2S breakthrough tests at 150 °C, continuously prepared α-, γ-, and δ-MnO2 exhibited sulfur capacities of 669.5, 193.8 and 607.6 mg S/g sorbent, respectively, which was at a high level among the reported adsorbents. Such enhanced performance is related to the large surface area and mesopore volume, high reducibility, and a large number of oxygen species with high reactivity and mobility. Manganese sulfide and elemental sulfur were formed after desulfurization, which indicated the reaction consisted of two steps: redox and sulfidation of the sorbents. This study provides an innovative design strategy for the construction of nanomaterials with high H2S adsorption performances.

Continuous Flow Electrochemical Synthesis of Olivine-Structured NaFePO4 Cathode Material for Sodium-Ion Batteries from Recycle LiFePO4.

To mitigate the environmental impact of the improper disposal of spent LiFePO4 batteries and reduce resource waste, the development of LiFePO4 recycling technologies is of paramount importance. Meanwhile, olivine-structured NaFePO4 in sodium-ion batteries has received great attention, due to its high theoretical specific capacity of 154 mAh g-1 and excellent stability. However, olivine NaFePO4 only can be synthesized from olivine LiFePO4. Accordingly, in this proposal, developing the continuous flow electrochemical solid-liquid reactor-based metal ion insertion technology is to utilize the olivine FePO4, recycled from LiFePO4, and to synthesize NaFePO4. Additionally, by employing I- as the reducing agent, NaFePO4 is successfully synthesized with a discharge-specific capacity of 134 mAh g-1 at 0.1C and a remarkable capacity retention rate of 86.5% after 100 cycles at 0.2C. And the reasons for sodium deficiency in the synthesized NFP are elucidated through first-principles calculations. Furthermore, the kinetics of the solid-solution reaction 2 (Na2/3+βPO4→ Na1-αFePO4) mechanism improve with cycling and are sensitive to temperature. Utilizing a minimal amount of reducing agent in the electrochemical reactor, NaFePO4 synthesis is successfully achieved. This innovative approach offers a new, cost-effective, and environmentally friendly strategy for preparing NaFePO4 from recycling LiFePO4.

Flow synthesis of silver nanoparticles using water in supercritical CO2 emulsion

Rapid and continuous synthesis of metal nanoparticles using green solvent system is still a serious challenge for both fundamental and practical research. In this work, we report a new flow process using water in supercritical CO2 (w/scCO2) emulsion and applied it to the synthesis of silver nanoparticles (AgNPs). To investigate the performance of our system, AgNPs were synthesized by batch, flow and w/scCO2 emulsion flow system at 40 ºC while using AgNO3, NaBH(OAc)3, trisodium citrate and Aerosol-OT as precursor, reducer, stabilizer and emulsifier. As a result, we demonstrated that water droplets in w/scCO2 emulsion significantly contribute to a rise in the size controllability and productivity (product yield). Additionally, w/scCO2 emulsion flow process allowed the control of mean size from 4.0 to 36.6 nm and yield from 25% to 65% by changing the CO2 pressure and Aerosol-OT concentration. Furthermore, synthesized AgNPs successfully gave citrate-modified surface with high zeta potential of –54 mV and the transparent water dispersion with unimodal size distribution, showing promising potential to allow various practical applications.

Biocatalytic Synthesis of l‐Pipecolic Acid by a Lysine Cyclodeaminase: Batch and Flow Reactors

Abstractl‐Pipecolic Acid (l‐PA) is a valuable building block for the synthesis of pharmaceuticals such as anesthetics and immunosuppressants. Thus, more efficient and greener strategies are desired for its production. Herein, we have applied a previously engineered variant of the Lysine Cyclodeaminase from Streptomyces pristinaespiralis (e‐SpLCD) for the bioconversion of l‐Lysine into l‐PA. The reaction can be performed by the free e‐SpLCD reaching full conversion to 50 mM l‐PA. From a biotechnological perspective, the process scale‐up has been trialed in a SpinChem® reactor, albeit with lower conversion yields. To further enhance the biocatalyst stability, we present a detailed study of the e‐SpLCD immobilization on microparticles. This enabled the integration of the immobilized biocatalyst into a packed‐bed reactor for the continuous flow synthesis of l‐PA. The full conversion was achieved in 90 min, maintaining also high operational stability. Remarkably, the addition of exogenous cofactor was not needed for the flow reaction, although the long‐term operational stability was improved by the addition of NAD+.

Recent advances in nano-related natural antioxidants, their extraction methods and applications in the food industry

Natural antioxidants, such as phenolic compounds, carotenoids, vitamins, and microelements, are predominant in fruits, vegetables, herbs, and spices. The accretion interest of consumers in utilizing natural ingredients in food products, have accelerated the appeal for functional “natural” operations. Therefore, understanding how natural antioxidants especially nano-antioxidants, and their delivery systems when used in antioxidant polymers for food packaging are extracted from natural sources, would help prevent oxidation reactions. Given the increasing role of natural antioxidants in the daily lives of today’s communities, a continuous synthesis of relevant literature is pertinent. To supplement existing information, recent advances in nano-related natural antioxidants, their extraction methods and applications in the food industry are discussed in this current work. Insightfully positioning antioxidants within the nano-delivery systems, this current work reveals the potential nanotechnology provides in enhancing the absorption of antioxidants in human metabolic systems.

Synthetic Vesicles for Sustainable Energy Recycling and Delivery of Building Blocks for Lipid Biosynthesis†.

ATP is a universal energy currency that is essential for life. l-Arginine degradation via deamination is an elegant way to generate ATP in synthetic cells, which is currently limited by a slow l-arginine/l-ornithine exchange. We are now implementing a new antiporter with better kinetics to obtain faster ATP recycling. We use l-arginine-dependent ATP formation for the continuous synthesis and export of glycerol 3-phosphate by including glycerol kinase and the glycerol 3-phosphate/Pi antiporter. Exported glycerol 3-phosphate serves as a precursor for the biosynthesis of phospholipids in a second set of vesicles, which forms the basis for the expansion of the cell membrane. We have therefore developed an out-of-equilibrium metabolic network for ATP recycling, which has been coupled to lipid synthesis. This feeder-utilizer system serves as a proof-of-principle for the systematic buildup of synthetic cells, but the vesicles can also be used to study the individual reaction networks in confinement.

Photocatalytic Regeneration of Reactive Cofactors with InP Quantum Dots for the Continuous Chemical Synthesis

Photocatalytic Regeneration of Reactive Cofactors with InP Quantum Dots for the Continuous Chemical Synthesis

Front Cover: Continuous Synthesis of a Macrocyclic Sulfite of Polyethylene Glycol by Cascaded Continuous Stirred Tank Reactors (CSTRs) (Chem. Eur. J. 25/2024)

Front Cover: Continuous Synthesis of a Macrocyclic Sulfite of Polyethylene Glycol by Cascaded Continuous Stirred Tank Reactors (CSTRs) (Chem. Eur. J. 25/2024)

Continuous Synthesis of a Macrocyclic Sulfite of Polyethylene Glycol by Cascaded Continuous Stirred Tank Reactors (CSTRs).

Invited for the cover of this issue is the group of Long Pan and co-workers at Asymchem Life Sciences (Tianjin) Co. Ltd. The image depicts a novel continuous process for the synthesis of a macrocyclic poly(ethylene glycol) (PEG) sulfite, the precursor to PEG macrocyclic sulfate, a useful building block in PEG chemistry. Read the full text of the article at 10.1002/chem.202304319.