Continuous Flow Reactor Research Articles

Scaling study of miniaturised continuous stirred tank reactors via residence time distribution analysis and application in the production of iron oxide nanoparticles

Magnetically agitated miniaturised continuous stirred tank reactors (mCSTRs) are an attractive platform for the intensification of chemical reactions involving solids by combining active stirring and intensified heat and mass transfer due to their small dimensions. This work investigated the operation of mCSTRs at flowrates up to 60 ml/min (space time of 3 s per tank) as a means of increasing the throughput of fast reactions. Investigation of the residence time distribution under varying operational (flowrate, stirrer rotational speed) and reactor geometrical (stirred volume, stir bar size) parameters, showed deviation from the ideal CSTR behaviour at increasing flowrates, which could be mitigated by keeping the stir bar length close to the tank diameter, increasing stirrer rotational speed, and using larger tank sizes. Assembling mCSTRs into cascades did not amplify non-ideal behaviour and allowed narrowing the residence time distribution at high throughput. Various configurations of mCSTR cascades were evaluated for the synthesis of iron oxide nanoparticles (IONPs) via iron chloride co-precipitation with NaOH, demonstrating the importance of residence time distribution (RTD) control when increasing the throughput of nanoparticle production. Using a 5 × 3 ml mCSTR cascade for the core formation followed by a 5 × 3 ml mCSTR cascade for deagglomeration/stabilisation, the IONP flow synthesis was scaled successfully, producing high quality nanoparticles (7.3 ± 2 nm) at 60.5 ml/min (l/h scale).

Highly Active and Stable P2O5 Catalysts Supported on Mesoporous Silica Promoted with Ce for the O‐Methylation of Catechol

AbstractP2O5 has been widely used as an acid‐base catalyst for the O‐methylation of catechol to guaiacol due to its suitable acid strength; however, its stability, which is a significant concern for industrial applications, has not seen significant breakthroughs. Herein, we developed a facile impregnation strategy to synthesize Ce promote P2O5 supported on mesoporous silica (CeP/SBA). The CeP/SBA‐500 carbonized at 500 °C exhibited the highest catalytic activity with a catechol conversion of 71.5 %. The high activity stems from the addition of Ce, forming CePO4, which exhibits improved surface acidity compared to P2O5. Importantly, chemisorption and in situ infrared studies revealed that CePO4 shows stronger adsorption of catechol, which then rapidly converts to guaiacol. The CeP/SBA‐500 exhibits excellent stability with no activity decrease after 10 h of continuous flow reaction, attributed to the absence of a decrease in CePO4 surface acidity.

A do-it-yourself benchtop device for highly scalable flow synthesis of protein-based nanoparticles

Synthesis of nanoparticles is typically carried out in batch procedures, which offer limited control of parameters, and a narrow range of possible batch volumes. In contrast, flow synthesis systems, usually having a microfluidic chip as a crucial part, are devoid of these drawbacks. However, large scale devices – millifluidic systems – may offer several advantages over microfluidic systems, such as easier and cheaper production, enhanced throughput, and reduced channel clogging. Here we report a millifluidic system for the generation of protein nanoparticles, using the flow format of the original swift thermal formation technology (STF), which can process batch volume ranging from 100 µl to any practically significant amount. Capabilities of the system are demonstrated with model synthesis of Epirubicin-encapsulated BSA nanoparticles. A better degree of scalability of the synthesis over batch procedure is shown: with a 10-fold working volume increase, hydrodynamic diameter and loading capacity changed by only 10 % and 1 % respectively, compared to 60 % and 30 % for the batch synthesis. Additionally, we provide all engineering drawings, electrical circuits, programming code and nuances of assembly and operation, so that our findings can be easily reproduced. The ease of construction of the device and the superior characteristics of the resulting nanoparticles compared to the batch method indicate application potential in both the biomedical research and industrial spheres.

Factorial experimental design for removal of Indigo Carmine and Brilliant Yellow dyes from solutions by coagulation

Textile and food industries produce huge amounts of wastewaters containing dye residues. When these wastewaters are discharged to receiving surface waters like as lakes and rivers, aesthetically unpleasant situations form. Therefore, these wastewaters should be treated. Wastewater treatment is sometimes an expensive operation and cheap methods should be developed. The removal of Indigo Carmine (I.C., Acid dye) and Brilliant Yellow (B.Y., Azo dye) from synthetically prepared solutions was studied by coagulation using iron chloride salt in a batch reactor at room temperature. As an experimental approach, two leveled factorial design with three factors was applied as a function of pH (4-12), iron chloride amount (0.1-0.4 g/500 mL) and dye concentration (100-200 mg/L). Low pHs supported to removal of these two dyes. The results showed that 100% I.C. dye removal and 90.5% B.Y. dye removal were achieved. The all parameters were statistically insignificant for both the dyes. Indigo Carmine and Brilliant Yellow dyes were removed from solutions successfully. The applied treatment method was evaluated as promising due to low sludge production, low cost, low coagulation duration and high performance. A time span of 5 minutes was found as enough for removals of both of the dyes. After treatment of I.C. and B.Y. dyes by coagulation, the coagulated dyes were determined as unreusable due to iron complex by these dyes. Flocculation was found to be ineffective. A continuous flow reactor was successfully adopted for these dyes.

Light Enables Partial Nitrification and Algal-Bacterial Consortium in Rotating Biological Contactors: Performance and Microbial Community

Partial nitrification–anaerobic ammonia oxidation represents an innovative nitrogen removal technique, distinguished by its shortened nitrogen removal pathway and reduced energy demands. Currently, partial nitrification is mostly studied in sequential batch reactors, and some of the methods to realize partial nitrification in continuous flow reactors have problems such as complicated operation and management, and can be easily destabilized. This study introduces a novel system utilizing light to establish an algal-bacterial consortium within a partial nitrification framework, where oxygen is supplied by algae and a novel rotating biological contactor (RBC). This approach aims to simplify the control strategy and decrease the energy required for aeration. The results demonstrated that light at an intensity of 200 μmol/(m2·s) effectively inhibited nitrite-oxidizing bacteria (NOB), swiftly stabilizing partial nitrification. In the absence of light, free ammonia (FA) and free nitric acid (FNA) inhibited NOB, with ammonium removal efficiency (ARE) and nitrite accumulation ratio (NAR) at 68.35% and 34.00%, respectively. By day 88, under light exposure, effluent NO2−-N concentrations surged, with ARE and NAR at 64.21% and 69.45%, respectively. By day 98, NAR peaked at 80.28%. The specific oxygen uptake rate (SOUR) of ammonia-oxidizing bacteria (AOB) and NOB outside the disc was 3.24 mg O2/(g MLSS·h) and 0.75 mg O2/(g MLSS·h), respectively. Extracellular polymeric substance (EPS) content initially decreased, then increased, ultimately exceeding pre-light exposure levels. Microbial abundance significantly declined due to light exposure, with Nitrosomonas related-AOB decreasing by 91.88% from 1.6% to 0.13%, and Nitrospira related-NOB decreasing by 99.23% from 5.19% to 0.04%, respectively. The results indicated that both AOB and NOB were inhibited by light, especially NOB. It is a feasible strategy to achieve partial nitrification and algal-bacterial consortia by using light in a rotating biological contactor.

Electrochemically Induced CO2 Capture Enabled by Aqueous Quinone Flow Chemistry

Electrochemically Induced CO₂ Capture Enabled by Aqueous Quinone Flow Chemistry

Production of high-carbon-number naphthenes for bio-aviation fuels from bio-crude prepared by fast pyrolysis of lignocellulose

Lignocellulose has been suggested as a cost-effective, environmentally sustainable substitute for paraffins, aromatics, and naphthenes in aviation fuel. However, bio-crude derived from the fast pyrolysis of lignocellulose poses challenges because of its high acidity and viscosity arising from oxygenates and water; in addition, the low-carbon-number hydrocarbons obtained from lignocellulose-derived sugars and phenols are unsuitable for aviation fuels. In this investigation, high-carbon-number hydrocarbon fuels are generated from bio-crude through condensation reactions between phenols and saturated cyclic alcohols, achieving a heavy fraction similar to that of aviation fuels. The one-pass, four-step continuous-flow reaction of bio-crude is conducted using a catalysis reactor equipped with carbon-supported palladium, titania-supported nickel–iron, hydrogen-form zeolite Y, and tungstate–zirconia-supported ruthenium. In contrast with conventional two-step hydrodeoxygenation methods yielding 1.1% dimeric cycloalkanes, the suggested multi-step reaction produced 4.5 to 4.7% yields of heavier naphthenes containing twelve or more carbon atoms.

Leaching char with acidic aqueous phase from biomass pyrolysis: Valorization of the leachate via catalytic hydrothermal gasification

Aqueous phase of bio-oil (APB) is a general stream of waste produced from biomass pyrolysis and fractional condensation of pyrolytic volatiles and has very limited applications. We have demonstrated a sequence of leaching of alkali and alkaline earth metallic species (AAEMs) from char and catalytic hydrothermal gasification (CHTG) for valorizing char and APB, respectively. The majority of AAEMs can be removed from the char by leaching with APB and the removal rates were almost equivalent to those leached with HCl (1.0 M). CHTG of an aqueous solution of the spent APB with a total organic carbon of 14,450 ppm was performed in a continuous flow reactor, employing an activated carbon-supported Ru catalyst (Ru loading, 4.6 wt%). The catalyst exhibited a stable activity for carbon conversion of 98.8 % at 350 °C for at least 360 min while gaseous product consisting of H2, CH4, and CO2 was produced with a cold gas efficiency of 101–103 %, on a higher heating value basis. The cold gas efficiency exceeding 100 % is mainly because of the generation of H2 from water through water-gas shift reaction. The CHTG performance of APB was enhanced by char leaching through the uptake of coke-forming precursors of APB onto char and the enrichment of AAEMs in the spent APB. These AAEMs played roles in suppressing coke formation and deposition onto the catalyst and maintaining Ru particle size by providing a less acidic hydrothermal environment.

Enhanced Hydrogen Peroxide Decomposition in a Continuous-Flow Reactor over Immobilized Catalase with PAES-C.

Due to the specificity, high efficiency, and gentleness of enzyme catalysis, the industrial utilization of enzymes has attracted more and more attention. Immobilized enzymes can be recovered/recycled easily compared to their free forms. The primary benefit of immobilization is protection of the enzymes from harsh environmental conditions (e.g., elevated temperatures, extreme pH values, etc.). In this paper, catalase was successfully immobilized in a poly(aryl ether sulfone) carrier (PAES-C) with tunable pore structure as well as carboxylic acid side chains. Moreover, immobilization factors like temperature, time, and free-enzyme dosage were optimized to maximize the value of the carrier and enzyme. Compared with free enzyme, the immobilized-enzyme exhibited higher enzymatic activity (188.75 U g-1, at 30 °C and pH 7) and better thermal stability (at 60 °C). The adsorption capacity of enzyme protein per unit mass carrier was 4.685 mg. Hydrogen peroxide decomposition carried out in a continuous-flow reactor was selected as a model reaction to investigate the performance of immobilized catalase. Immobilized-enzymes showed a higher conversion rate (90% at 8 mL/min, 1 h and 0.2 g) compared to intermittent operation. In addition, PAES-C has been synthesized using dichlorodiphenyl sulfone and the renewable resource bisphenolic acid, which meets the requirements of green chemistry. These results suggest that PAES-C as a carrier for immobilized catalase could improve the catalytic activity and stability of catalase, simplify the separation of enzymes, and exhibit good stability and reusability.

Scalable and Selective Electrochemical Hydrogenation of Polycyclic Arenes.

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.

Elimination of representative antibiotic-resistant bacteria, antibiotic resistance genes and ciprofloxacin from water via photoactivation of periodate using FeS2

The propagation of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) induced by the release of antibiotics poses great threats to ecological safety and human health. In this study, periodate (PI)/FeS2/simulated sunlight (SSL) system was employed to remove representative ARB, ARGs and antibiotics in water. 1 × 107 CFU mL–1 of gentamycin-resistant Escherichia coli was effectively disinfected below limit of detection in PI/FeS2/SSL system under different water matrix and in real water samples. Sulfadiazine-resistant Pseudomonas and Gram-positive Bacillus subtilis could also be efficiently sterilized. Theoretical calculation showed that (110) facet was the most reactive facet on FeS2 to activate PI for the generation of reactive species (·OH, ·O2–, h+ and Fe(IV)=O) to damage cell membrane and intracellular enzyme defense system. Both intracellular and extracellular ARGs could be degraded and the expression levels of multidrug resistance-related genes were downregulated during the disinfection process. Thus, horizontal gene transfer (HGT) of ARB was inhibited. Moreover, PI/FeS2/SSL system could disinfect ARB in a continuous flow reactor and in an enlarged reactor under natural sunlight irradiation. PI/FeS2/SSL system could also effectively degrade the HGT-promoting antibiotic (ciprofloxacin) via hydroxylation and ring cleavage process. Overall, PI/FeS2/SSL exhibited great promise for the elimination of antibiotic resistance from water.

Photocatalytic CO2 reduction to CH4 in continuous flow reactor using Fe2TiO5 enhanced by magnetron sputtering-deposited CuO nanoparticles cocatalyst

Fe2TiO5 is a promising and underexplored material as a semiconductor photocatalyst for CO2 reduction reaction (PCO2RR), aimed at mitigating greenhouse gas emissions. In this study, pure Fe2TiO5 was synthesized via solvothermal method and subsequently calcined across temperatures ranging from 600 to 900 °C. The performance was evaluated within a PCO2RR under simulated sunlight, generating CH4 as a single detectable product. Further enhancement was achieved by depositing CuO nanoparticles below 5 nm onto the Fe2TiO5 surface using magnetron sputtering deposition. The yield of CH4 increased from 0.032 to 0.042 µmol. As far as we know, this marks the inaugural application of Fe2TiO5 as a photocatalyst for CO2 reduction.

Upscaling and Risk Evaluation of the Synthesis of the 3,5-Diamino-1H-Pyrazole, Disperazol.

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.

Nirmatrelvir: From Discovery to Modern and Alternative Synthetic Approaches

The global urgency in response to the COVID-19 pandemic has catalyzed extensive research into discovering efficacious antiviral compounds against SARS-CoV-2. Among these, Nirmatrelvir (PF-07321332) has emerged as a promising candidate, exhibiting potent antiviral activity by targeting the main protease of SARS-CoV-2, and has been marketed in combination with ritonavir as the first oral treatment for COVID-19 with the name of PaxlovidTM. This review outlines the synthetic approaches to Nirmatrelvir, ranging from Pfizer’s original method to newer, more sustainable strategies, such as flow chemistry strategies and multicomponent reactions. Each approach’s novelty and contributions to yield and purification processes are highlighted. Additionally, the synthesis of key fragments comprising Nirmatrelvir and innovative optimization strategies are discussed.

Model-based development of cell voltage control system for modified bio-electro-Fenton process

A modified bio-electro-Fenton (M−BEF) process with a cell voltage control system that improves the efficiency of organic removal and energy savings is demonstrated. The M−BEF process can accomplish bioelectricity generation, H2O2 production, and the Fenton reaction in a continuous-flow reactor. During synthetic wastewater treatment containing biodegradable (glucose) and recalcitrant (biphenyl) organic matter, the effluent chemical oxygen demand (COD) concentration was maintained between 2 and 6 mg L-1. To investigate the impact of different operating schemes on energy usage, model-based design (MBD) modeling and simulations were performed, which showed that COD removal efficiency without an external voltage supply was unstable at < 70 %. The automatic cell voltage control system saved 90 % of the power compared to the continuous cell voltage supply system. Further testing on more environmental samples and pollutants will enable real-time optimization of supplied power and wastewater treatment using the cell voltage control system.

Pt/CB-Catalyzed Chemoselective Hydrogenation Using In Situ-Generated Hydrogen by Microwave-Mediated Dehydrogenation of Methylcyclohexane under Continuous-Flow Conditions

Hydrogen gas (H2) has attracted attention as a next-generation clean energy source. Its efficient and safe preparation and utilization are crucial in both the industry and organic chemistry research. In this study, a Pt/CB (platinum on carbon bead)-catalyzed MW-mediated continuous-flow hydrogenation reaction was developed using methylcyclohexane (MCH) as the reducing agent (hydrogen carrier). Alkynes, alkenes, nitro groups, benzyl esters, and aromatic chlorides were chemoselectively hydrogenated using Pt/CB under MW-assisted continuous-flow conditions. This methodology represents a safe and energy-efficient hydrogenation process, as it eliminates the need for an external hydrogen gas supply or heating jackets as a heating medium. The further application of MW-mediated continuous-flow hydrogenation reactions is a viable option for the efficient generation and utilization of sustainable energy.

Synergistic effect of hydroxyapatite-magnetite nanocomposites in magnetic hyperthermia for bone cancer treatment

Abstract Hydroxyapatite/magnetite (HA-Fe3O4) nanocomposite materials that have the synergistic ability to produce heat when in direct bonding with a bone through HA are regarded competent hyperthermia therapies of bone carcinoma treatment. HA-Fe3O4 nanocomposites with various magnetite concentrations (10, 20, and 30 wt%) were quickly synthesized using a novel continuous microwave-assisted flow synthesis (CMFS) process in a 5 min residence duration at the conditions of pH 11. In this process, initially, phase pure hydroxyapatite and superparamagnetic magnetite nanoparticles followed by a series of HA-Fe3O4 nanocomposites were formed, without a subsequent aging step. The obtained nano-product was physically analyzed using Brunauer-Emmett-Teller (BET) surface area analysis, transmission electron microscopy, and X-ray powder diffraction analysis. X-ray photoelectron spectroscopy was used for the chemical structure analysis of the final nanocomposite product. Zeta potential measurements were carried out to determine colloidal stability associated with the surface charge of the nanocomposites. The magnetic properties were determined using a vibrating sample magnetometer. The results indicated the high magnetization property of the obtained nanoproduct, suitable for hyperthermia application. HA-Fe3O4 nanocomposites have shown remarkable antimicrobial properties against E. coli and S. cerevisiae. Thus, the CMFS system facilitated the rapid production of HA-Fe3O4 nanocomposite particles with fine particle size.

Simultaneous inactivation of Microcystis aeruginosa and degradation of microcystin-LR in water by activation of periodate with sunlight

Harmful algal blooms pose tremendous threats to ecological safety and human health. In this study, simulated solar light (SSL) irradiation was used to activate periodate (PI) for the inactivation of Microcystis aeruginosa and degradation of microcystin-LR (MC-LR). We found that PI-SSL system could effectively inactivate 5 × 106 cells·mL−1 algal cells below the limit of detection within 180 min. ·OH and iodine (IO3· and IO4·) radicals generated in PI-SSL system could rupture cell membranes, releasing intracellular substances including MC-LR into the reaction system. However, the released MC-LR could be degraded into non-toxic small molecules via hydroxylation and ring cleavage processes in PI-SSL system, reducing their environmental risks. High algae inactivation performance of PI-SSL system in solution with a wide pH range (3–9), with the coexisting anions (Cl−, NO3− and SO42−) and the copresence of natural organic matters (humic acid and fulvic acid), real water (lake water and river water), as well as in continuous-flow reactor (14 h) were also achieved. In addition, under natural sunlight irradiation, effective algae inactivation could also be achieved in an enlarged reactor (1 L). Overall, our study showed that PI-SSL system could avoid the inference by the background substances and could be employed as a feasible technique to treat algal bloom water.

The mechanism differences between sulfadiazine degradation and antibiotic resistant bacteria inactivation by iron-based graphitic biochar and peroxydisulfate system

In this study, the activation of peroxydisulfate (PS) by K2FeO4-activation biochar (KFeB) and acid-picking K2FeO4-activation biochar (AKFeB) was investigated to reveal the mechanism differences between iron site and graphitic structure in sulfadiazine (SDZ) degradation and ARB inactivation, respectively. KFeB/PS and AKFeB/PS systems had similar degradation property towards SDZ, but only KFeB/PS system showed excellent bactericidal property. The mechanism study demonstrated that dissolved SDZ was degraded through electron transfer pathway mediated by graphitic structure, while suspended ARB was inactivated through free radicals generated by iron-activated PS, accompanied by excellent removal on antibiotic resistance genes (ARGs). The significant decrease in conjugative transfer frequency indicated the reduced horizontal gene transfer risk of ARGs after treatment with KFeB/PS system. Transcriptome data suggested that membrane protein channel disruption and adenosine triphosphate synthesis inhibition were key reasons for conjugative transfer frequency reduction. Continuous flow reactor of KFeB/PS system can efficiently remove antibiotics and ARB, implying the potential application in practical wastewater purification. In conclusion, this study provides novel insights for classified and collaborative control of antibiotics and ARB by carbon-based catalysts driven persulfate advanced oxidation technology.

Development of a Cryogenic Flow Reactor to Optimize Glycosylation Reactions Based on the Active Donor Intermediate.

The development of a continuous flow reactor for stereospecific glycosylation reactions with deoxy sugars is described. This apparatus that permits optimizing the selectivity of glycosylation reactions based on the stability of the activated intermediate is described. By coupling a flow apparatus with HPLC analysis, we can optimize the yield of TsCl-mediated β-linked deoxy sugar construction in a matter of hours. In all cases, results from continuous flow processing translate into improved results in batch-scale reactions, as demonstrated by competition experiments. This is the result of carrying out optimization to identify the ideal temperature for the reaction of the activated intermediate, as opposed to the initial activation conditions. Such an approach allows for the rapid development of highly selective glycosylation reactions in cases in which classical neighboring group participation is not possible.