Continuous Flow Reactor Research Articles

Stable and Versatile Pd Precursors for the Preparation of Robust Pd Catalysts Under Continuous-Flow.

To achieve global sustainability, the chemical and engineering communities require the development of versatile precursors that can be used to synthesize robust catalysts. To meet this demand, we developed a new Pd precursor for highly efficiently incorporating fine Pd-metal into supports. An atmospherically stable Pd precursor (Pd-80) was prepared by thermally promoting the aerobic oxidation of tetrakis(triphenylphosphine)palladium. The physical properties of Pd-80 were investigated by NMR spectroscopy, SEM, XPS, solvent-relaxation NMR spectroscopy, and dynamic light scattering (DLS) experiments. We also prepared a cordierite-supported Pd catalyst (Pd/cordierite) by stirring Pd-80 and cordierite powder in chloroform at room temperature. Pd/cordierite selectively catalyzed the hydrogenation of various reducible functional groups, including alkynes, azides, nitro groups, olefins, CO2Bn, N-Cbz, O-Bn, aromatic ketones, and styrene oxide, in continuous-flow hydrogenation reactions. The Pd/cordierite-catalyzed continuous-flow hydrogenation of nitrobenzene derivatives afforded the corresponding anilines, with catalytic activities maintained for over 250 h of continuous operation with a turnover number (TON) of 61,090.

Structure-Directed Quaternary Ammonium Hydroxide Resins: High-Performance Heterogeneous Base Catalysts for Continuous-Flow Carbon-Carbon Bond-Forming Reactions.

Quaternary ammonium hydroxide resins are widely recognized for their effectiveness as immobilized bases and are frequently utilized as commodity chemicals for anion-exchange applications. However, despite their accessibility, chemically controlling their properties has proven challenging, hindering research and development efforts toward their use as solid base catalysts. This study investigates the synthetic factors that are crucial for achieving high functional performance in polystyrene resins. Using commercially available resin as a benchmark and the continuous-flow Henry reaction as a model system, we explore and evaluate newly synthesized resin catalysts to maximize their basic catalytic activity.

Evaluating the efficacy of microalgal-bacterial granular sludge system in lake water remediation.

The microalgal-bacterial granular sludge (MBGS) process is attracting attention as a green wastewater treatment technology. However, research on the application of MBGS in lake water remediation is limited. Thus, this experiment investigated the feasibility and the efficacy of the MBGS process for the treatment of natural lake water in a continuous-flow tubular reactor. The averageremoval efficiencies of COD, NH4+-N, NO3--N, NO2--N, TN, PO43--P, TP, and turbidity by MBGS system in the day/night cycles were 50.10/61.39%, 63.52/75.23%, 43.37/73.57%, 90.72/93.48%, 78.30/80.02%, 71.13/74.62%, 65.08/70.57%, 92.32/89.84%, respectively. As the experiment progressed, the total chlorophyll content in MBGS decreased as the granule size increased, while the extracellular polymeric substances content increased, suggesting that thelake water contributed to bacterial growth and favored the stability of MBGS. Moreover, the eukaryotic microorganisms were dominated by Chlorophyta and Rotifera, and prokaryotic microorganisms were dominated by Proteobacteria in MBGS. By promoting the decomposition of various organic compounds in the lake water and inhibiting sludge expansion, these microorganisms helpthe MBGS system tomaintain excellent granular characteristics and performance. Overall, the MBGS system proved to be a feasible option for the remediation of natural lake waters.

Continuous flow synthesis of the antiviral drug tecovirimat and related sp3-rich scaffolds.

Herein we report a 2-step continuous flow synthesis of the antiviral drug tecovirimat, which is used for the treatment of monkeypox and smallpox. This work exploits a high-temperature pericyclic cascade process between cycloheptatriene and maleic anhydride generating a key sp3-rich scaffold, which affords the desired API after further condensation with an acyl hydrazide. Additional investigations of the key intermediate in reactions with different hydrazines revealed the accessibility of different heterocyclic chemotypes, depending on the substitution pattern of the hydrazine used. Ultimately, the streamlined and scalable access to these sp3-rich scaffolds enables improved access to tecovirimat and structurally related entities with high drug-like character.

Multistep and multivectorial assembly line library synthesis in flow

Multistep and multivectorial assembly line library synthesis in flow

Polynomial chaos expansions on principal geodesic Grassmannian submanifolds for surrogate modeling and uncertainty quantification

In this work we introduce a manifold learning-based surrogate modeling framework for uncertainty quantification in high-dimensional stochastic systems. Our first goal is to perform data mining on the available simulation data to identify a set of low-dimensional (latent) descriptors that efficiently parameterize the response of the high-dimensional computational model. To this end, we employ Principal Geodesic Analysis on the Grassmann manifold of the response to identify a set of disjoint principal geodesic submanifolds, of possibly different dimension, that captures the variation in the data. Since operations on the Grassmann require the data to be concentrated, we propose an adaptive algorithm based on Riemannian K-means and the minimization of the sample Fréchet variance on the Grassmann manifold to identify “local” principal geodesic submanifolds that represent different system behavior across the parameter space. Polynomial chaos expansion is then used to construct a mapping between the random input parameters and the projection of the response on these local principal geodesic submanifolds. The method is demonstrated on four test cases, a toy-example that involves points on a hypersphere, a Lotka-Volterra dynamical system, a continuous-flow stirred-tank chemical reactor system, and a two-dimensional Rayleigh-Bénard convection problem.

Assessment of Hazards in the High‐Pressure Continuous Flow Reactor for Dimethyl Ether (DME) Synthesis

AbstractThe objective of this study is to conduct a thorough hazard analysis specifically tailored to identify hazards and suggest precautions associated with the intricate process of dimethyl ether (DME) production. This exothermic nature of DME production introduces the critical concern of thermal runaway. Furthermore, the DME synthesis process demands precise control over both pressure and flow rate. These parameters are important for increasing DME selectivity and CO conversion. Inadequate monitoring of these values may not only prevent the synthesis from proceeding but may also lead to major risks to health and safety. For this reason, proactive measures must be implemented to eliminate or minimize the risks. The significance of such measures cannot be overstated, as they serve to safeguard not only the integrity of the synthesis process but also the surrounding environment and human health. To delve deeper into the hazard evaluation, a comprehensive Hazard and Operability (HAZOP) analysis has been carried out, focusing specifically on the reactor within the DME process. This methodical examination involves a systematic review of potential deviations, identifying the associated hazards, and proposing effective preventive measures. The HAZOP analysis serves as a pivotal tool in ensuring the overall safety and reliability of the DME process.

Continuous Flow Synthesis of Furfuryl Ethers over Pd/C Catalysts via Reductive Etherification of Furfural in Ethanol

Continuous Flow Synthesis of Furfuryl Ethers over Pd/C Catalysts via Reductive Etherification of Furfural in Ethanol

Optimization of diformylfuran production from 5-hydroxymethylfurfural via catalytic oxidation in a packed-bed continuous flow reactor.

DFF's diverse applications in pharmaceuticals, fungicides, and polymer synthesis motivate the development of efficient production methods. This study reports the continuous-flow synthesis of DFF from 5-HMF in a packed-bed reactor. The Box-Behnken design coupled with response surface methodology (RSM) was employed to optimize the reaction parameters (catalyst, solvent, temperature, oxygen flow rate, catalyst amount) for DFF yield. Ru/Al2O3 in toluene proved to be the most effective catalyst-solvent combination. The optimal conditions for DFF production were identified as: 140 °C reaction temperature, 10 ml min-1 oxygen flow rate, and 0.15 g catalyst loading. Under these conditions, a DFF yield of 84.2% was achieved.

Controlling the optoelectronic properties of nitrogen-doped carbon quantum dots using biomass-derived precursors in a continuous flow system

The synthesis of carbon quantum dots (CQDs) from high molecular weight biomass-derived precursors poses a significant challenge due to the complex molecular structures and low conversion efficiency. This work demonstrates a green, rapid, and sustainable continuous hydrothermal flow synthesis (CHFS) approach for nitrogen-doped carbon quantum dots (NCQDs) from various biomass-derived precursors, including high molecular weight polymeric sources like chitosan, lignin, and humic acid. We find that the precursor structure significantly impacts the size of the fabricated NCQDs and their optical properties. Citric acid, a low molecular weight precursor, yields NCQDs with excitation-independent emission, higher quantum yields, and low non-radiative losses, while NCQDs derived from polymeric precursors exhibit excitation-dependent, red-shifted, and lower efficiency emission. Theoretical calculations, performed to understand the configuration and distribution of nitrogen dopants within the NCQD structure, show that pyridinic and graphitic nitrogen atoms exhibit a strong preference to aggregate near the centre of the edge of the NCQD and not in the vertices nor in the graphitic core, thus affecting the HOMO and LUMO, bandgap, and light absorption and emission wavelengths. The life cycle assessment (LCA) analysis highlights the green and scalable advantages of the CHFS process for producing NCQDs compared to batch methods, making it a sustainable and economically viable approach for large-scale NCQD synthesis from high molecular weight biomass-derived precursors. Hence, the combination of experimental data and theoretical calculations provides a comprehensive understanding of the structure-property relationships in these NCQDs.

Three-dimensional gel network structure of agarose interlayer dispersed Pd nanoparticles in copper foam electrode for electrocatalytic degradation of doxycycline hydrochloride

In this study, we successfully prepared palladium/agarose/copper foam (Pd/AG/CF) composite electrodes by utilizing the three-dimensional network structure agarose (AG), a green material derived from biomass, and homogeneously immobilizing palladium (Pd) atoms on a copper foam (CF) substrate through a facile route. The electrode showed excellent performance in the electrocatalytic degradation of doxycycline (DOX), with a high DOX degradation rate of 92.19 % in 60 min. In-depth studies revealed that palladium can form metal-metal interactions with the CF substrates, which enhances the electron transfer on the catalyst surface. In addition, the introduction of agarose effectively prevented the agglomeration of palladium nanoparticles. In addition, the hydroxyl functional groups in the molecular structure of agarose facilitate interactions between water molecules and the electrode interface through the formation of hydrogen bonds, thereby further enhancing the efficiency of the electrocatalytic reaction. In addition to good stability and reusability. Microbial toxicity test results show that the degraded wastewater has minimal impact on the environment. Also, possible degradation pathways of DOX were explored in this study. Finally, a novel continuous flow reactor was designed, featuring a unique design that ensures full contact between wastewater and the composite electrodes, thereby achieving continuous and efficient treatment of antibiotic wastewater.

Controlled two-step synthesis of n-type conjugated ladder polymers using a flow reactor

The coplanar backbone of conjugated ladder polymers (cLPs) enhances electron transfer and π-π interactions, making cLPs promising materials for various applications in organic electronics and optoelectronics. Nevertheless, the limited solubility and intricate synthetic processes for cLPs make it challenging to control their molecular weight and corresponding properties, and pose as significant obstacles to their widespread application. Here, an n-type cLP, PNDI-2BocL, was synthesized using a flow reactor for the first time, with controlled molecular weights. The polymerization reaction conditions to synthesize a precursor polymer, PNDI-2Boc, were first optimized in flow, followed by sequential ladderization in batch through the injection of an acid solution. The reaction time of polymerization was varied from 7.5 to 15 min, yielding soluble PNDI-2BocL with a number-averaged molecular weight (Mn) ranging from 9.8 to 54.0 kg/mol with a deviation of 11 %. Additionally, 15 min of polymerization and ladderization were successfully conducted in a single flow system sequentially for the first time. In the molecular weight-dependent studies, higher optical absorption at longer wavelengths, increased degrees of crystallinity, and higher electron mobilities in organic field-effect transistors (OFETs) were observed for higher molecular weight PNDI-2BocL. Our results highlight the importance of controlling the molecular weights of cLPs and demonstrate that the flow synthesis technique provides a viable solution for synthesizing soluble cLPs in a controlled, reproducible, and rapid manner.

Light Induced Diastereoselective Ketoesterification To Access 6,5-Fused Tetrahydrobenzofuranones in Batch and Continuous Flow Conditions.

Ketoesterification stands as a pivotal technique in organic synthesis, particularly due to its essential role in the construction of numerous natural products and bioactive compounds. In this study, we have successfully accomplished a visible-light-induced cyclization and diastereoselective direct ketoesterification of cyclohexadienones, facilitating access to cis 6,5-fused tetrahydrobenzofuranone derivatives. The utilization of TEMPO radical quenching experiments has provided insights, suggesting an ionic mechanism underlying this methodology. Additionally, the regioselective addition of 2-oxo-2-phenylacetate to the least hindered side in a cis-selective fashion makes this protocol more appealing toward natural product development. Incorporation of a continuous flow reaction into the batch protocol has notably bolstered the efficiency and reaction rate. Furthermore, the demonstration of gram-scale reactions in the flow setup and synthetic utility with NaOH underscore the scalability and practical applicability of this approach.

Development of the telescoped flow Pd-catalyzed aerobic alcohol oxidation/reductive amination sequence in the synthesis of new phosphatidylinositide 3-kinase inhibitor (CPL302415).

Herein, we describe a two-step sequential flow synthesis: Pd-catalyzed aerobic oxidation to an aldehyde 2, which is then converted by reductive amination in H-Cube® PRO into CPL302415 (3). CPL302415 is our new PI3Kδ inhibitor, which is now under evaluation for the treatment of systemic lupus erythematosus. The process was optimized using the DoE approach and generalized to other biologically active derivatives of CPL302415.

Biocatalysis in Non-Conventional Media: Unlocking the Potential for Sustainable Chiral Amine Synthesis.

The application of biocatalysis has become essential in both academic and industrial domains for the asymmetric synthesis of chiral amines, and it serves as an alternative tool to transition-metal catalysis and complements traditional chemical methods. It relies on the swift expansion of available processes, primarily as a result of advanced tools for enzyme discovery, combined with high-throughput laboratory evolution techniques for optimizing biocatalysts. This concept paper explores the utilization of non-conventional media such as ether-type solvents, deep eutectic solvents, and micellar catalysis to enhance biocatalytic reactions for chiral amine synthesis. Each section focuses on the unique properties of these media, including their ability to stabilize enzymes, alter substrate solubility, and modulate enzyme selectivity. The paper aims to provide insights into how these innovative media can overcome traditional limitations, offering new avenues for sustainable and efficient chiral amine production through biocatalytic processes.

Optimize the ratio of immobilized gel materials to improve gel performance and oxygen mass transfer rate: Achieve rapid start-up and efficient and stable operation of partial nitration

A gel filler with diatomaceous earth, activated carbon, and CaCO3 compounded with polyvinyl alcohol was prepared and optimized. Rapid start-up and efficient and stable operation of partial nitrification (PN) was achieved by immobilization of conventional activated sludge. The results showed that the proper material proportion synergistically improved the performance and oxygen mass transfer rate of the gel. The continuous flow reactor was operated for 10d to successfully start PN, and the maximum ammonia oxidation rate of this filler was 58.30 mg·(L·h)−1 during the stable operation, and the nitrite accumulation rate was maintained above 90 %. However, due to the greater mass transfer resistance of unoptimized fillers, more dissolved oxygen waste and nitrogen loss were caused, resulting in delayed expression of biological activity. Based on the kinetic characterization of ammonia-oxidizing bacteria (AOB) within the filler and high-throughput sequencing, it was demonstrated that the rapid start-up and efficient and stable operation of the PN system was due to the highly oxygenophilic and community-dominant position of AOB within this filler. This study provides new options and insights at the level of immobilization technology for the realization and efficient and stable operation of PN.

Selective Hydrogenation Reaction: Utilizing a Microreactor for Continuous Flow Synthesis of Nickel Nanoparticles

Introduction: In this investigation, we employed a continuous flow reactor to synthesize nickel (Ni) nanoparticles exhibiting uniform size distribution and excellent stability. Our focus centered on exploring the impact of reactant dilution and flow rate on the synthesis process. Result: It was observed that the optimization of these parameters played a pivotal role in obtaining small-sized Ni nanoparticles. Specifically, we achieved successful synthesis using a solution of 0.00025 M NiCl2·6H2O and 0.002 M NaBH4, with a flow rate of 25 mL/h. The resulting Ni nanoparticles were effectively coated with the CTAB surfactant, as confirmed through thorough analysis using TEM and PSD techniques. Additionally, the interaction between the surfactant and nanoparticles was verified via FTIR analysis. We subjected them to high-pressure alkene hydrogenation to assess the catalytic activity of the synthesized Ni nanoparticles. Method: Encouragingly, the Ni nanoparticles exhibited excellent performance, producing hydrogenated products with high yields. Moreover, we capitalized on Ni nanoparticles' catalytic effect for synthesizing two natural compounds, brittonin A and dehydrobrittonin A. Remarkably, both compounds were successfully isolated in quantifiable yields. This synthesis protocol boasted several advantages, including low catalyst loading, omission of additives, broad substrate scope, straightforward product separation, and the ability to recover the catalyst up to eight times. In summary, this study effectively showcased the potential of continuous flow reactor technology in synthesizing stable and uniformly distributed nanoparticles. Conclusion: Additionally, it highlighted the effectiveness of Ni nanoparticles as catalysts in various chemical reactions. The findings from this study hold significant implications for developing more efficient and sustainable chemical synthesis protocols.

Mechanism-specific chemical energy accommodation with finite-rate surface chemistry in non-equilibrium flow

During atmospheric reentry, the vehicle surface is exposed to highly non-equilibrium flow. The vehicle surface can experience heterogeneous recombination of reactive atoms, which contributes to its aerothermodynamic heating. This process is followed by chemical energy accommodation (CEA), where the released energy is either transferred to the surface or the internal energy modes of the recombined molecule. Heterogeneous recombination can be categorized into Eley–Rideal (ER) and Langmuir–Hinshelwood mechanisms, which differ in their methods of molecule formation and degrees of CEA. The complete CEA assumption may not consider the dependency of CEA on the mechanisms of heterogeneous recombination. This study aims to consider the mechanism-specific CEA for a more accurate prediction of surface heat flux. The authors implement mechanism-specific CEA within the direct simulation Monte Carlo framework using the finite-rate surface chemistry model, resolving elementary surface reactions and assigning a CEA coefficient, β, to each mechanism. The model is verified through comparisons with analytical solutions of surface coverage and validated against benchmark references. A parametric investigation of rarefied hypersonic flow over a two-dimensional cylinder is conducted under different freestream Mach and Knudsen numbers. Results show a reduction in total heat flux of up to 14.44% using mechanism-specific CEA compared to the complete CEA assumption. The reduction is attributed to the relative contribution of the ER mechanism, which can be a function of atomic partial pressure at the boundary layer.

Visible light driven ZnFe2O4 for the degradation of oxytetracycline in the presence of HSO5− at semi-pilot scale and additional H2 production

This study investigated the synthesis of visible light driven ZnFe2O4 for photocatalytic degradation of oxytetracycline (OTC) in a continuous flow reactor and production of hydrogen (H2). OTC is widely used as a medication and found to create severe health and environmental issues. The use of advanced characterization techniques proved successful formation of ZnFe2O4 which was found to be reusable, stable, highly crystalline, and nano-sized. The prepared ZnFe2O4 caused 60% removal of OTC and removal efficiency of the latter was promoted to 85% by adding HSO5– with ZnFe2O4 at 240 min employing reactor flow rate of 0.1 L/min and concentrations of ZnFe2O4, OTC, and HSO5– as 1.0 g/L, 20 mg/L, and 100 mg/L, respectively. The addition of HSO5– was found to give hydroxyl radical (•OH) and sulfate radical (SO4•−) and the latter caused degradation of OTC into degradation products. The removal of OTC was promoted by factors facilitating the rate of formation of •OH and SO4•−. The ZnFe2O4 proved effective in photocatalytic H2 production and showed H2 production rate of 23.4 μmol h−1 g−1. The results suggest that ZnFe2O4 could be used as an economically viable technology for emerging pollutants degradation and green energy production.

Atmospheric pressure atomic layer deposition for in-channel surface modification of PDMS microfluidic chips

Polydimethylsiloxane (PDMS) is one of the materials of choice for the fabrication of microfluidic chips. However, its broad application is constrained by its incompatibility with common organic solvents and the absence of surface anchoring groups for surface functionalization. Current solutions involving bulk-, ex-situ surface-, and in-situ liquid phase modifications are limited and practically demanding. In this work, we present a simple, novel strategy to deposit a metal oxide nano-layer on the inside of bonded PDMS microfluidic channels using atmospheric pressure atomic layer deposition (AP-ALD). Using three important classes of microfluidic experiments, i.e., (i) the production of micron-sized particles, (ii) the cultivation of biological cells, and (iii) the photocatalytic degradation in continuous flow chemistry, we demonstrate that the metal oxide nano-layer offers a higher resistance against organic solvent swelling, higher hydrophilicity, and a higher degree of further functionalization of the wall. We demonstrate the versatility of the approach by not only depositing SiOx nano-layers, but also TiOx nano-layers, which in the case of the flow chemistry experiment were further functionalized with gold nanoparticles through the use of AP-ALD. This study demonstrates AP-ALD as a tool to broaden the applicability of PDMS devices.