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Journal articles on the topic 'Continuous flow reactor synthesis'

Author: Grafiati

Published: 5 June 2025

Last updated: 24 June 2025

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1

Lindeque, Rowan, and John Woodley. "Reactor Selection for Effective Continuous Biocatalytic Production of Pharmaceuticals." Catalysts 9, no. 3 (2019): 262. http://dx.doi.org/10.3390/catal9030262.

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Enzyme catalyzed reactions are rapidly becoming an invaluable tool for the synthesis of many active pharmaceutical ingredients. These reactions are commonly performed in batch, but continuous biocatalysis is gaining interest in industry because it would allow seamless integration of chemical and enzymatic reaction steps. However, because this is an emerging field, little attention has been paid towards the suitability of different reactor types for continuous biocatalytic reactions. Two types of continuous flow reactor are possible: continuous stirred tank and continuous plug-flow. These reactor types differ in a number of ways, but in this contribution, we focus on residence time distribution and how enzyme kinetics are affected by the unique mass balance of each reactor. For the first time, we present a tool to facilitate reactor selection for continuous biocatalytic production of pharmaceuticals. From this analysis, it was found that plug-flow reactors should generally be the system of choice. However, there are particular cases where they may need to be coupled with a continuous stirred tank reactor or replaced entirely by a series of continuous stirred tank reactors, which can approximate plug-flow behavior. This systematic approach should accelerate the implementation of biocatalysis for continuous pharmaceutical production.

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2

Dragone, Vincenza, Victor Sans, Mali H. Rosnes, Philip J. Kitson, and Leroy Cronin. "3D-printed devices for continuous-flow organic chemistry." Beilstein Journal of Organic Chemistry 9 (May 16, 2013): 951–59. http://dx.doi.org/10.3762/bjoc.9.109.

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We present a study in which the versatility of 3D-printing is combined with the processing advantages of flow chemistry for the synthesis of organic compounds. Robust and inexpensive 3D-printed reactionware devices are easily connected using standard fittings resulting in complex, custom-made flow systems, including multiple reactors in a series with in-line, real-time analysis using an ATR-IR flow cell. As a proof of concept, we utilized two types of organic reactions, imine syntheses and imine reductions, to show how different reactor configurations and substrates give different products.

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3

Hollenbach, Rebecca, Delphine Muller, André Delavault, and Christoph Syldatk. "Continuous Flow Glycolipid Synthesis Using a Packed Bed Reactor." Catalysts 12, no. 5 (2022): 551. http://dx.doi.org/10.3390/catal12050551.

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Glycolipids are a class of biodegradable biosurfactants that are non-toxic and based on renewables, making them a sustainable alternative to petrochemical surfactants. Enzymatic synthesis allows a tailor-made production of these versatile compounds using sugar and fatty acid building blocks with rationalized structures for targeted applications. Therefore, glycolipids can be comprehensively designed to outcompete conventional surfactants regarding their physicochemical properties. However, enzymatic glycolipid processes are struggling with both sugars and fatty acid solubilities in reaction media. Thus, continuous flow processes represent a powerful tool in designing efficient syntheses of sugar esters. In this study, a continuous enzymatic glycolipid production catalyzed by Novozyme 435® is presented as an unprecedented concept. A biphasic aqueous–organic system was investigated, allowing for the simultaneous solubilization of sugars and fatty acids. Owing to phase separation, the remaining non-acylated glucose was easily separated from the product stream and was refed to the reactor forming a closed-loop system. Productivity in the continuous process was higher compared to a batch one, with space–time yields of up to 1228 ± 65 µmol/L/h. A temperature of 70 °C resulted in the highest glucose-6-O-decanoate concentration in the Packed Bed Reactor (PBR). Consequently, the design of a continuous biocatalytic production is a step towards a more competitive glycolipid synthesis in the aim for industrialization.

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4

Bálint, Erika, Ádám Tajti, Katalin Ladányi-Pára, Nóra Tóth, Béla Mátravölgyi та György Keglevich. "Continuous flow synthesis of α-aryl-α-aminophosphonates". Pure and Applied Chemistry 91, № 1 (2019): 67–76. http://dx.doi.org/10.1515/pac-2018-0923.

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AbstractThe synthesis of α-aryl-α-aminophosphonates was performed by the three-component Kabachnik-Fields reaction of primary amines, benzaldehyde derivatives and dialkyl phosphites in a continuous flow microwave reactor. The target compounds could be obtained in high (~90%) yields without any catalyst in simple alcohols as the solvent. The flow process elaborated required shorter reaction times and lower excess of the reagent, as compared to the “traditional” batch reactions, and allowed the synthesis of the α-aminophosphonates on a somewhat larger scale.

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5

Silva, Renan Rodrigues de Oliveira, and Mauri Sergio Alves Palma. "Flow synthesis of n-substituted 5-benzylidinethiazolidine-2,4-dione." STUDIES IN ENGINEERING AND EXACT SCIENCES 3, no. 2 (2022): 385–402. http://dx.doi.org/10.54021/sesv3n2-006.

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Process intensification based on micro reactor technology allows safe manner and a new pathway to run organic synthesis due to its intrinsic characteristics, and can reduce time-to-market of new drugs. The main objective of this work was to study the batch and flow reaction of five n-substituted 5-benzylidenethiazolidine-2,4-dione heterocyclic intermediates present in the synthesis of glitazone class drugs, in capillary micro reactor. Batch process was conducted with ethanol as solvent at the boiling point and pyrrolidine as promoting base of the reaction. Higher yields were obtained in shorter reaction times in temperatures above solvent boiling point. Also, we evaluated that 3.8 micro reactors in parallel would be necessary to reach the same mean molar flow rate of a 60 mL batch reactor. Kinetic and thermodynamic study indicated that the reaction followed the second-order model and allowed estimating its main thermodynamic parameters. The continuous flow micro reactor proved to be an efficient alternative to the batch process in scaling up the production of Active Pharmaceutical Ingredient intermediates (APIs).

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6

Okafor, Obinna, Andreas Weilhard, Jesum A. Fernandes, Erno Karjalainen, Ruth Goodridge, and Victor Sans. "Advanced reactor engineering with 3D printing for the continuous-flow synthesis of silver nanoparticles." Reaction Chemistry & Engineering 2, no. 2 (2017): 129–36. http://dx.doi.org/10.1039/c6re00210b.

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3D printing has been employed to manufacture advanced reactor geometries based on miniaturised continuous-flow oscillatory baffled reactors (mCOBRs) and they have been applied for the fouling free continuous-flow synthesis of silver nanoparticles with optimal size control.

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7

Suwanpitak, Kittipat, Pornsak Sriamornsak, Inderbir Singh, Tanikan Sangnim, and Kampanart Huanbutta. "Three-Dimensional-Printed Vortex Tube Reactor for Continuous Flow Synthesis of Polyglycolic Acid Nanoparticles with High Productivity." Nanomaterials 13, no. 19 (2023): 2679. http://dx.doi.org/10.3390/nano13192679.

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Polyglycolic acid (PGA) nanoparticles show promise in biomedical applications due to their exceptional biocompatibility and biodegradability. These nanoparticles can be readily modified, facilitating targeted drug delivery and promoting specific interactions with diseased tissues or cells, including imaging agents and theranostic approaches. Their potential to advance precision medicine and personalized treatments is evident. However, conventional methods such as emulsification solvent evaporation via batch synthesis or tubular reactors via flow chemistry have limitations in terms of nanoparticle properties, productivity, and scalability. To overcome these limitations, this study focuses on the design and development of a 3D-printed vortex tube reactor for the continuous synthesis of PGA nanoparticles using flow chemistry. Computer-aided design (CAD) and the design of experiments (DoE) optimize the reactor design, and computational fluid dynamics simulations (CFD) evaluate the mixing index (MI) and Reynolds (Re) expression. The optimized reactor design was fabricated using fused deposition modeling (FDM) with polypropylene (PP) as the polymer. Dispersion experiments validate the optimization process and investigate the impact of input flow parameters. PGA nanoparticles were synthesized and characterized for size and polydispersity index (PDI). The results demonstrate the feasibility of using a 3D-printed vortex tube reactor for the continuous synthesis of PGA nanoparticles through flow chemistry and highlight the importance of reactor design in nanoparticle production. The CFD results of the optimized reactor design showed homogeneous mixing across a wide range of flow rates with increasing Reynolds expression. The residence time distribution (RTD) results confirmed that increasing the flow rate in the 3D-printed vortex tube reactor system reduced the dispersion variance in the tracer. Both experiments demonstrated improved mixing efficiency and productivity compared to traditional tubular reactors. The study also revealed that the total flow rate had a significant impact on the size and polydispersity index of the formulated PGA nanoparticle, with the optimal total flow rate at 104.46 mL/min, leading to smaller nanoparticles and a lower polydispersity index. Additionally, increasing the aqueous-to-organic volumetric ratio had a significant effect on the reduced particle size of the PGA nanoparticles. Overall, this study provides insights into the use of 3D-printed vortex tube reactors for the continuous synthesis of PGA nanoparticles and underscores the importance of reactor design and flow parameters in PGA nanoparticle formulation.

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8

Baxendale, Ian R., Christian Hornung, Steven V. Ley, Juan de Mata Muñoz Molina, and Anders Wikström. "Flow Microwave Technology and Microreactors in Synthesis." Australian Journal of Chemistry 66, no. 2 (2013): 131. http://dx.doi.org/10.1071/ch12365.

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A bespoke microwave reactor with a glass containment cell has been developed for performing continuous flow reactions under microwave heating. The prototype unit has been evaluated using a series of standard organic chemical transformations enabling scale-up of these chemical processes. As part of the development, a carbon-doped PTFE reactor insert was utilized to allow the heating of poorly absorbing reaction media, increasing the range of solvents and scope of reactions that can be performed in the device.

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9

Lange, Paul P., Lukas J. Gooßen, Philip Podmore, Toby Underwood, and Nunzio Sciammetta. "Decarboxylative biaryl synthesis in a continuous flow reactor." Chemical Communications 47, no. 12 (2011): 3628. http://dx.doi.org/10.1039/c0cc05708h.

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10

Andreev, D. V., L. L. Makarshin, A. G. Gribovskii, et al. "Triethanolamine synthesis in a continuous flow microchannel reactor." Chemical Engineering Journal 259 (January 2015): 252–56. http://dx.doi.org/10.1016/j.cej.2014.07.118.

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11

Waterford, Matthew, Simon Saubern, and Christian H. Hornung. "Evaluation of a Continuous-Flow Photo-Bromination Using N-Bromosuccinimide for Use in Chemical Manufacture." Australian Journal of Chemistry 74, no. 8 (2021): 569. http://dx.doi.org/10.1071/ch20372.

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A continuous-flow photo-bromination reaction on benzyl and phenyl groups was conducted using N-bromosuccinimide as the bromine source inside a preparatory-scale glass plate reactor. This flow reactor system was capable of independently controlling light intensity, wavelength, and reaction temperature, hence exerting an exceptional level of control over the reaction. A short optimisation study for the synthesis of 2-bromomethyl-4-trifluoromethoxyphenylboronic acid pinacol ester resulted in best conditions of 20°C and 10min residence time using an LED (light-emitting diode) array at 405nm and acetonitrile as the solvent. The present study evaluates the potential for this easy-to-handle bromination system to be scaled up for chemical manufacture inside a continuous-flow glass plate reactor. The combination with an in-line continuous flow liquid–liquid extraction and separation system, using a membrane separator, demonstrates the potential for continuous flow reaction with purification in an integrated multi-stage operation with minimal manual handling in between.

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12

Jamison, Timothy F., Timothy M. Monos, Jonathan N. Jaworski, and John C. Stephens. "Continuous-Flow Synthesis of Tramadol from Cyclohexanone." Synlett 31, no. 19 (2020): 1888–93. http://dx.doi.org/10.1055/s-0039-1690884.

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A multioperation, continuous-flow platform for the synthesis of tramadol, ranging from gram to decagram quantities, is described. The platform is segmented into two halves allowing for a single operator to modulate between preparation of the intermediate by Mannich addition or complete the fully concatenated synthesis. All purification operations are incorporated in-line for the Mannich reaction. ‘Flash’ reactivity between meta-methoxyphenyl magnesium bromide and the Mannich product was controlled with a static helical mixer and tested with a combination of flow and batch-based and factorial evaluations. These efforts culminated in a rapid production rate of tramadol (13.7 g°h–1) sustained over 56 reactor volumes. A comparison of process metrics including E-Factor, production rate, and space-time yield are used to contextualize the developed platform with respect to established engineering and synthetic methods for making tramadol.

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13

Bagley, Mark C., Vincenzo Fusillo, Robert L. Jenkins, M. Caterina Lubinu, and Christopher Mason. "One-step synthesis of pyridines and dihydropyridines in a continuous flow microwave reactor." Beilstein Journal of Organic Chemistry 9 (September 30, 2013): 1957–68. http://dx.doi.org/10.3762/bjoc.9.232.

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The Bohlmann–Rahtz pyridine synthesis and the Hantzsch dihydropyridine synthesis can be carried out in a microwave flow reactor or using a conductive heating flow platform for the continuous processing of material. In the Bohlmann–Rahtz reaction, the use of a Brønsted acid catalyst allows Michael addition and cyclodehydration to be carried out in a single step without isolation of intermediates to give the corresponding trisubstituted pyridine as a single regioisomer in good yield. Furthermore, 3-substituted propargyl aldehydes undergo Hantzsch dihydropyridine synthesis in preference to Bohlmann–Rahtz reaction in a very high yielding process that is readily transferred to continuous flow processing.

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14

Thomson, Christopher G., Ai-Lan Lee, and Filipe Vilela. "Heterogeneous photocatalysis in flow chemical reactors." Beilstein Journal of Organic Chemistry 16 (June 26, 2020): 1495–549. http://dx.doi.org/10.3762/bjoc.16.125.

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The synergy between photocatalysis and continuous flow chemical reactors has shifted the paradigms of photochemistry, opening new avenues of research with safer and scalable processes that can be readily implemented in academia and industry. Current state-of-the-art photocatalysts are homogeneous transition metal complexes that have favourable photophysical properties, wide electrochemical redox potentials, and photostability. However, these photocatalysts present serious drawbacks, such as toxicity, limited availability, and the overall cost of rare transition metal elements. This reduces their long-term viability, especially at an industrial scale. Heterogeneous photocatalysts (HPCats) are an attractive alternative, as the requirement for the separation and purification is largely removed, but typically at the cost of efficiency. Flow chemical reactors can, to a large extent, mitigate the loss in efficiency through reactor designs that enhance mass transport and irradiation. Herein, we review some important developments of heterogeneous photocatalytic materials and their application in flow reactors for sustainable organic synthesis. Further, the application of continuous flow heterogeneous photocatalysis in environmental remediation is briefly discussed to present some interesting reactor designs that could be implemented to enhance organic synthesis.

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15

Shukla, C. A., A. A. Kulkarni, and V. V. Ranade. "Selectivity engineering of the diazotization reaction in a continuous flow reactor." Reaction Chemistry & Engineering 1, no. 4 (2016): 387–96. http://dx.doi.org/10.1039/c5re00056d.

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In situ generated diazonium salts are useful intermediates for the synthesis of fine chemicals and active pharmaceutical ingredients. This paper presents a methodology for selectivity engineering of the diazotization reaction in continuous reactors.

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16

Liu, Zhendong, Kotatsu Okabe, Chokkalingam Anand, et al. "Continuous flow synthesis of ZSM-5 zeolite on the order of seconds." Proceedings of the National Academy of Sciences 113, no. 50 (2016): 14267–71. http://dx.doi.org/10.1073/pnas.1615872113.

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The hydrothermal synthesis of zeolites carried out in batch reactors takes a time so long (typically, on the order of days) that the crystallization of zeolites has long been believed to be very slow in nature. We herein present a synthetic process for ZSM-5, an industrially important zeolite, on the order of seconds in a continuous flow reactor using pressurized hot water as a heating medium. Direct mixing of a well-tuned precursor (90 °C) with the pressurized water preheated to extremely high temperature (370 °C) in the millimeter-sized continuous flow reactor resulted in immediate heating to high temperatures (240–300 °C); consequently, the crystallization of ZSM-5 in a seed-free system proceeded to completion within tens of or even several seconds. These results indicate that the crystallization of zeolites can complete in a period on the order of seconds. The subtle design combining a continuous flow reactor with pressurized hot water can greatly facilitate the mass production of zeolites in the future.

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17

Hornung, Christian H., Miguel Á. Álvarez-Diéguez, Thomas M. Kohl, and John Tsanaktsidis. "Diels–Alder reactions of myrcene using intensified continuous-flow reactors." Beilstein Journal of Organic Chemistry 13 (January 19, 2017): 120–26. http://dx.doi.org/10.3762/bjoc.13.15.

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This work describes the Diels–Alder reaction of the naturally occurring substituted butadiene, myrcene, with a range of different naturally occurring and synthetic dienophiles. The synthesis of the Diels–Alder adduct from myrcene and acrylic acid, containing surfactant properties, was scaled-up in a plate-type continuous-flow reactor with a volume of 105 mL to a throughput of 2.79 kg of the final product per day. This continuous-flow approach provides a facile alternative scale-up route to conventional batch processing, and it helps to intensify the synthesis protocol by applying higher reaction temperatures and shorter reaction times.

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18

Szabó, Balázs, Kiara Szakter, Angelika Thurner, Ferenc Faigl, János Éles, and István Greiner. "A Novel, Domino Synthesis of Tricyclic Benzimidazole Derivatives Using Continuous Flow." Periodica Polytechnica Chemical Engineering 64, no. 1 (2019): 1–8. http://dx.doi.org/10.3311/ppch.14275.

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A novel method for synthesis of tricyclic benzimidazole derivatives by using continuous flow reactor is reported. Disadvantages of the well-known batch methods have been avoided utilizing the flow chemistry technology. Beside the one pot reductive cyclization using H-Cube Pro®, the dehydration step was also optimized producing the desired lactam compounds. Then the acylation was optimized under microwave conditions and that reaction was also integrated into the flow system using an Asia heater module. This acylation dramatically reduced the reaction time under continuous-flow conditions, with a residence time of 30 min.

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19

Dunne, Peter W., Alexis S. Munn, Chris L. Starkey, Tom A. Huddle, and Ed H. Lester. "Continuous-flow hydrothermal synthesis for the production of inorganic nanomaterials." Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences 373, no. 2057 (2015): 20150015. http://dx.doi.org/10.1098/rsta.2015.0015.

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As nanotechnology becomes increasingly important and ubiquitous, new and scalable synthetic approaches are needed to meet the growing demand for industrially viable routes to nanomaterial production. Continuous-flow hydrothermal synthesis or supercritical water hydrothermal synthesis (scWHS) is emerging as a versatile solution to this problem. The process was initially developed to take advantage of the tunable chemical and physical properties of superheated water to produce metal oxide nanoparticles by rapid nucleation and precipitation. The development of new mixing regimes and reactor designs has been facilitated by the modelling of reactor systems. These new reactor designs further exploit the properties of supercritical water to promote faster and more uniform mixing of reagent streams. The synthetic approach has been expanded beyond the metal oxide systems for which it was conceived, and now encompasses metal sulfides, metal phosphates, metal nanoparticles and metal–organic frameworks. In many of these cases, some degree of size and shape control can be achieved through careful consideration of both chemistry and reactor design. This review briefly considers the development of scWHS reactor technology, before highlighting some of our recent work in expanding the scope of this synthetic method to include a wide range of materials.

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20

Brocken, Laurens, Paul D. Price, Jane Whittaker, and Ian R. Baxendale. "Continuous flow synthesis of poly(acrylic acid) via free radical polymerisation." Reaction Chemistry & Engineering 2, no. 5 (2017): 662–68. http://dx.doi.org/10.1039/c7re00063d.

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The free radical polymerisation of aqueous solutions of acrylic acid (1) has been studied using a continuous flow reactor to quickly screen reaction parameters such as temperature, residence time, monomer- and initiator concentration.

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21

Holmes, Nicholas, Geoffrey R. Akien, Robert J. D. Savage, et al. "Online quantitative mass spectrometry for the rapid adaptive optimisation of automated flow reactors." Reaction Chemistry & Engineering 1, no. 1 (2016): 96–100. http://dx.doi.org/10.1039/c5re00083a.

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22

Nakamura, Hiroyuki, Masato Uehara, and Hideaki Maeda. "Nanocrystals Synthesis by Microreactors." Advances in Science and Technology 45 (October 2006): 652–59. http://dx.doi.org/10.4028/www.scientific.net/ast.45.652.

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A microreactor is a continuous flow reactor, which can control reaction conditions precisely. We applied the microreactors to CdSe based nanocrystals synthesis and tuning particle size, optical properties. Furthermore, homogeneous coating of ZnS and its coating amount tuning was possible for optical properties improvement.

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23

Du, Li-Hua, Miao Xue, Meng-Jie Yang та ін. "Ring-Opening of Epoxides with Amines for Synthesis of β-Amino Alcohols in a Continuous-Flow Biocatalysis System". Catalysts 10, № 12 (2020): 1419. http://dx.doi.org/10.3390/catal10121419.

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An efficient method for the preparation of β-amino alcohols catalyzed by lipase TL IM from Thermomyces lanuginosus in a continuous-flow reactor was developed. The eco-friendly biocatalyst combined with continuous-flow reaction technology displayed high efficiency in the synthesis of β-amino alcohols. The benign reaction conditions (35 °C) and short residence time (20 min), together with the use of low cost and readily available starting materials, make this synthetic approach a promising alternative to current β-amino alcohol synthesis.

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24

Tukacs, József M., Richard V. Jones, Ferenc Darvas, Gábor Dibó, Gábor Lezsák та László T. Mika. "Synthesis of γ-valerolactone using a continuous-flow reactor". RSC Advances 3, № 37 (2013): 16283. http://dx.doi.org/10.1039/c3ra43032d.

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25

Reich, Jannis A., Miriam Aßmann, Kristin Hölting, Paul Bubenheim, Jürgen Kuballa, and Andreas Liese. "Shift of the reaction equilibrium at high pressure in the continuous synthesis of neuraminic acid." Beilstein Journal of Organic Chemistry 18 (May 20, 2022): 567–79. http://dx.doi.org/10.3762/bjoc.18.59.

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The importance of a compound that helps fight against influenza is, in times of a pandemic, self-evident. In order to produce these compounds in vast quantities, many researchers consider continuous flow reactors in chemical industry as next stepping stone for large scale production. For these reasons, the synthesis of N-acetylneuraminic acid (Neu5Ac) in a continuous fixed-bed reactor by an immobilized epimerase and aldolase was investigated in detail. The immobilized enzymes showed high stability, with half-life times > 173 days under storage conditions (6 °C in buffer) and reusability over 50 recycling steps, and were characterized regarding the reaction kinetics (initial rate) and scalability (different lab scales) in a batch reactor. The reaction kinetics were studied in a continuous flow reactor. A high-pressure circular reactor (up to 130 MPa) was applied for the investigation of changes in the position of the reaction equilibrium. By this, equilibrium conversion, selectivity, and yield were increased from 57.9% to 63.9%, 81.9% to 84.7%, and 47.5% to 54.1%, respectively. This indicates a reduction in molar volume from N-acetyl-ᴅ-glucosamine (GlcNAc) and pyruvate (Pyr) to Neu5Ac. In particular, the circular reactor showed great potential to study reactions at high pressure while allowing for easy sampling. Additionally, an increase in affinity of pyruvate towards both tested enzymes was observed when high pressure was applied, as evidenced by a decrease of KI for the epimerase and KM for the aldolase from 108 to 42 mM and 91 to 37 mM, respectively.

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Nitelet, Antoine, Vanessa Kairouz, Hélène Lebel, André Charette, and Gwilherm Evano. "Continuous Flow Chlorination of Alkenyl Iodides Promoted by Copper Tubing." Synthesis 51, no. 01 (2018): 251–57. http://dx.doi.org/10.1055/s-0037-1610398.

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A simple continuous flow synthesis of alkenyl chlorides from the corresponding readily available alkenyl iodides in copper reactor tubing is described. A variety of alkenyl chlorides were obtained in good to excellent yields with full retention of the double bond geometry. The reaction time was reduced by a factor of 24–48 compared to the batch process.

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Nathanael, Konstantia, Nina M. Kovalchuk, and Mark J. H. Simmons. "Comparison of Microfluidic Synthesis of Silver Nanoparticles in Flow and Drop Reactors at Low Dean Numbers." Micromachines 16, no. 1 (2025): 75. https://doi.org/10.3390/mi16010075.

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

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Liu, Yawen, and Evgeny V. Rebrov. "Direct Amide Synthesis over Composite Magnetic Catalysts in a Continuous Flow Reactor." Catalysts 11, no. 2 (2021): 146. http://dx.doi.org/10.3390/catal11020146.

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Composite magnetic catalysts containing different amounts of sulfated titania (33–50 wt %) have been prepared by means of high energy ball-milling between TiO2 and NiFe2O4. The catalysts have been characterized with N2 adsorption/desorption isotherms, XRD, temperature programmed oxidation (TPO) and vibrating sample magnetometer (VSM). The catalytic activity was measured in the reaction of aniline and 4-phenylbutyric acid in the continuous mode under conventional and inductive heating. The effect of catalyst loading in the reactor on reaction and deactivation has been studied, indicating the catalyst containing 50 wt % titania gave the highest reaction rate and least deactivation. The operation in a flow reactor under inductive heating increased the amide yield by 25% as compared to conventional heating. The initial reaction rate decreased by 30% after a period of 15 h on stream. The catalyst activity was fully restored after a treatment with an air flow at 400 °C.

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Hölting, Kristin, Miriam Aßmann, Paul Bubenheim, Andreas Liese, and Jürgen Kuballa. "Modelling Approach for the Continuous Biocatalytic Synthesis of N-Acetylneuraminic Acid in Packed Bed Reactors." Processes 12, no. 10 (2024): 2191. http://dx.doi.org/10.3390/pr12102191.

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Continuous flow technologies have become increasingly important for biocatalytic processes. In this study, we present the application and modelling of covalently immobilised N-acetylglucosamine 2-epimerase and N-acetylneuraminic acid lyase in packed bed reactors for the synthesis of N-acetylneuraminic acid. The immobilised enzymes were stable under continuous flow process conditions with half-life times of >28 d (epimerase immobilised on hexamethylamino methacrylate HA403/M) or 58 d (lyase immobilised on dimenthylamino methacrylate ECR8309M), suitable for continuous flow applications. Kinetic studies revealed Michaelis–Menten kinetic behaviour for both enzymes. The kinetic parameters and the inhibitions were analysed under continuous flow conditions and were integrated into a process model using Python. The model was validated by varying flow rates, the mass of immobilised enzymes and the reactor dimensions and shows a low error compared to the measured data. An error accuracy of 6% (epimerase) or 9% (lyase) was achieved. The product concentrations of the enzyme cascade at the end of the packed bed reactor can be predicted with an accuracy of 9% for the calculation of a large column (84.5 mL) or of 24% if several small columns (2.5 mL, 0.8 mL) are connected in series. The developed model has proved to be valid and will be used to optimise the process with respect to substrate concentrations, reactor dimensions and flow rate.

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Wimmer, Eric, Daniel Cortés-Borda, Solène Brochard, Elvina Barré, Charlotte Truchet, and François-Xavier Felpin. "An autonomous self-optimizing flow machine for the synthesis of pyridine–oxazoline (PyOX) ligands." Reaction Chemistry & Engineering 4, no. 9 (2019): 1608–15. http://dx.doi.org/10.1039/c9re00096h.

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31

Siraev, Ramil, Pavel Ilyushin, and Dmitry Bratsun. "Mixing control in a continuous-flow microreactor using electro-osmotic flow." Mathematical Modelling of Natural Phenomena 16 (2021): 49. http://dx.doi.org/10.1051/mmnp/2021043.

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In recent years, pharmaceutical production has been stimulating the gradual miniaturization of continuous-flow chemical reactors. This process eventually resulted in the emergence of a new generation of microreactors. The advantages of these new reactor types are the flexible production that allows us to quickly reconfigure the scheme, small reactant quantities used for the synthesis, the control of the main reaction parameters with high accuracy. Nevertheless, a decrease in the thickness of the channels where the species contact and react forces us to search for new non-mechanical mechanisms for mixing. This problem is relevant for the slow reaction occurring in a slot where diffusion alone cannot provide mixing at reasonable distances from the entrance. It is also true for the fast reaction that takes place in a frontal manner. In this work, we consider the efficiency of mixing the reactants induced by electro-osmotic flow in a Hele-Shaw configuration with non-uniform zeta potential distribution. As a test reaction, we take the neutralization reaction with simple albeit non-linear kinetics. The reaction occurs between two miscible solutions, which are initially separated in space and come into contact in a continuous-flow microreactor. The reaction proceeds frontally, which prevents the efficient mixing of the reactants due to diffusion. Using direct numerical simulations of 2D and 3D flows, we demonstrate that the zeta potential applied to boundaries can effectively control the mixing rate of fluids by lengthening the front of the reaction. This approach makes it possible to increase the yield of the reaction product.

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32

Blacker, A. John, and Katherine E. Jolley. "Continuous formation of N-chloro-N,N-dialkylamine solutions in well-mixed meso-scale flow reactors." Beilstein Journal of Organic Chemistry 11 (December 2, 2015): 2408–17. http://dx.doi.org/10.3762/bjoc.11.262.

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The continuous flow synthesis of a range of organic solutions of N,N-dialkyl-N-chloramines is described using either a bespoke meso-scale tubular reactor with static mixers or a continuous stirred tank reactor. Both reactors promote the efficient mixing of a biphasic solution of N,N-dialkylamine in organic solvent, and aqueous sodium hypochlorite to achieve near quantitative conversions, in 72–100% in situ yields, and useful productivities of around 0.05 mol/h with residence times from 3 to 20 minutes. Initial calorimetric studies have been carried out to inform on reaction exotherms, rates and safe operation. Amines which partition mainly in the organic phase require longer reaction times, provided by the CSTR, to compensate for low mass transfer rates in the biphasic system. The green metrics of the reaction have been assessed and compared to existing procedures and have shown the continuous process is improved over previous procedures. The organic solutions of N,N-dialkyl-N-chloramines produced continuously will enable their use in tandem flow reactions with a range of nucleophilic substrates.

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33

Mandai, Kyoko, Tetsuya Yamamoto, Hiroki Mandai, and Aiichiro Nagaki. "Rapid gas–liquid reaction in flow. Continuous synthesis and production of cyclohexene oxide." Beilstein Journal of Organic Chemistry 18 (June 13, 2022): 660–68. http://dx.doi.org/10.3762/bjoc.18.67.

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The enhanced reaction rate in the epoxidation of cyclohexene with air as an oxidant was discovered without any added catalyst utilizing a continuous flow reactor constructed with readily available stainless steel parts and devices. This continuous-flow process demonstrates a significant improvement in reaction time for highly selective epoxide production over the batch process due to the efficient mass transfer between the liquid phase and air. The flow process discovered was operated continuously with good operational stability, evaluated by a constant high yield of cyclohexene oxide, to obtain the desired product with high productivity.

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34

Lackner, Florian, Katharina Hiebler, Bianca Grabner, and Heidrun Gruber-Woelfler. "Optimization of a Catalytic Chemoenzymatic Tandem Reaction for the Synthesis of Natural Stilbenes in Continuous Flow." Catalysts 10, no. 12 (2020): 1404. http://dx.doi.org/10.3390/catal10121404.

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In view of the development of efficient processes for the synthesis of high-value compounds, the combination of bio- and chemocatalysis is highly promising. In addition, implementation of immobilized catalysts into continuous setups allows a straightforward separation of the target compound from the reaction mixture and ensures uniform product quality. In this work, we report the optimization of a chemoenzymatic tandem reaction in continuous flow and its extended application for the synthesis of pharmacologically active resveratrol and pterostilbene. The tandem reaction involves enzymatic decarboxylation of coumaric acid employing encapsulated phenolic acid decarboxylase from B. subtilis and a Heck coupling of the obtained vinylphenol with an aryl iodide using heterogeneous Pd-Ce-Sn oxides implemented in a packed bed reactor. By optimization of the reaction conditions for the limiting cross-coupling step, the yield of (E)-4-hydroxystilbene using the fully continuous setup could be more than doubled compared to previous work. Furthermore, the improved chemoenzymatic cascade could also be applied to the synthesis of resveratrol and pterostilbene in a continuous fashion. Leaching of the metal catalyst at high temperatures limited the process in many perspectives. Therefore, the feasibility of a reactor setup with reversed flow was experimentally evaluated and approved.

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35

Briggs, Michael E., Anna G. Slater, Neil Lunt, et al. "Dynamic flow synthesis of porous organic cages." Chemical Communications 51, no. 98 (2015): 17390–93. http://dx.doi.org/10.1039/c5cc07447a.

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Two imine-based porous organic cages were successfully synthesised in continuous flow. The same flow reactor was then used to scramble the constituents of these two cages in differing ratios to form cage mixtures.

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36

Khabiyev, Alibek, Savas Dilibal, Assel Mussulmanbekova, Magzhan Kanapiya, and Daniyar Kerimkulov. "Additively Manufactured Continuous Processing Reactor System for Producing Liquid-Based Pharmaceutical Substances." Applied Sciences 14, no. 16 (2024): 6853. http://dx.doi.org/10.3390/app14166853.

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In this study, an AM-based continuous processing reactor system was designed, manufactured, and assembled on a laboratory scale for the generation of pharmaceutical substances with an improved process control. The developed AM-based (additively manufactured) continuous pharmaceutical reactor system for the synthesis of metronidazole derivatives aimed to optimize both the physical and the chemical processes with time savings. Using AM, we were able to build reactor subcomponents with complex designs and precise dimensions, which facilitated the precise control of the reaction parameters and reduced the amount of chemicals required compared to macroscale reactors. The assembly of the whole reactor system consisted of main reactor bodies, mixers, valves, heat exchangers, electrical motors, and a microcontroller system. The assembled reactor system revealed a continuous flow of reagents and ensured uniform mixing and reaction conditions, thereby increasing the process efficiency and product quality. Five metronidazole derivatives were synthesized via two continuous processes, involving metronidazole reduction and its subsequent reactions with terephthalic aldehyde and anthracen-9(10H)-one to form Schiff bases. The optimal conditions were determined as follows: compound A (72% yield, 120 min, 55 °C), compounds B and C (63% and 68% yield, respectively, 8 h, 65 °C), and compounds D and E (74% and 85% yield, respectively, 8 h, 45 °C).

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37

Kermagoret, Anthony, Benjamin Wenn, Antoine Debuigne, Christine Jérôme, Thomas Junkers, and Christophe Detrembleur. "Improved photo-induced cobalt-mediated radical polymerization in continuous flow photoreactors." Polymer Chemistry 6, no. 20 (2015): 3847–57. http://dx.doi.org/10.1039/c5py00299k.

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38

Herath, Ananda, and Nicholas D. P. Cosford. "Continuous-flow synthesis of highly functionalized imidazo-oxadiazoles facilitated by microfluidic extraction." Beilstein Journal of Organic Chemistry 13 (February 7, 2017): 239–46. http://dx.doi.org/10.3762/bjoc.13.26.

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A versatile continuous-flow synthesis of highly functionalized 1,2,4-oxadiazoles starting from carboxylic acids is reported. This process was applied to the multistep synthesis of imidazo[1,2-a]pyridin-2-yl-1,2,4-oxadiazoles, using a three reactor, multistep continuous-flow system without isolation of intermediates. This continuous-flow method was successfully combined with a single-step liquid–liquid microextraction unit to remove high boiling point polar solvents and impurities and provides the target compounds in high purity with excellent overall yields.

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Margi, Nikhil H., and Ganapati D. Yadav. "Design and Development of Novel Continuous Flow Stirred Multiphase Reactor: Liquid–Liquid–Liquid Phase Transfer Catalysed Synthesis of Guaiacol Glycidyl Ether." Processes 8, no. 10 (2020): 1271. http://dx.doi.org/10.3390/pr8101271.

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Phase transfer catalysed (PTC) reactions are used in several pharmaceutical and fine chemical industrial processes. We have developed a novel stirred tank reactor (Yadav reactor) to conduct batch and continuous liquid–liquid–liquid (L-L-L) PTC reactions. The reactor had a provision of using three independent stirrers for each phase, thereby having complete control over the rate of mass transfer across the two interfaces. In the continuous mode of operation, the top and bottom phases were continuously fed into the reactor while the middle phase was used as a batch. All three stirrers were used independently, thereby having independent control of mass transfer resistances. The reactor in a batch mode showed higher conversion and selectivity compared to a conventional batch reactor. L-L-L PTC reaction in the continuous mode was successfully performed without loss of the middle catalyst phase and with steady conversion and selectivity. The reaction of guaiacol with epichlorohydrin was conducted as a model reaction, with a 76% conversion of epichlorohydrin, 85% selectivity of guaiacol glycidyl ether, and the middle catalyst phase was stable throughout the process.

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40

Bondioli, Federica, Anna Bonamartini Corradi, Anna Maria Ferrari, and Cristina Leonelli. "Synthesis of Zirconia Nanoparticles in a Continuous-Flow Microwave Reactor." Journal of the American Ceramic Society 91, no. 11 (2008): 3746–48. http://dx.doi.org/10.1111/j.1551-2916.2008.02666.x.

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41

Corradi, Anna Bonamartini, Federica Bondioli, Anna Maria Ferrari, Bonaventura Focher, and Cristina Leonelli. "Synthesis of silica nanoparticles in a continuous-flow microwave reactor." Powder Technology 167, no. 1 (2006): 45–48. http://dx.doi.org/10.1016/j.powtec.2006.05.009.

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42

Liu, Lingtao, Geng Sun, Chen Wang, et al. "Aqueous phase Fischer–Tropsch synthesis in a continuous flow reactor." Catalysis Today 183, no. 1 (2012): 136–42. http://dx.doi.org/10.1016/j.cattod.2011.09.040.

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43

Lange, Paul P., Lukas J. Goossen, Philip Podmore, Toby Underwood, and Nunzio Sciammetta. "ChemInform Abstract: Decarboxylative Biaryl Synthesis in a Continuous Flow Reactor." ChemInform 42, no. 29 (2011): no. http://dx.doi.org/10.1002/chin.201129079.

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44

Watts, Paul, and Charlotte Wiles. "Micro reactors, flow reactors and continuous flow synthesis." Journal of Chemical Research 36, no. 4 (2012): 181–93. http://dx.doi.org/10.3184/174751912x13311365798808.

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45

Wong, Wai Kuan, Swee Kun Yap, Yi Chen Lim, Saif A. Khan, Frédéric Pelletier, and Elena Cristina Corbos. "Robust, non-fouling liters-per-day flow synthesis of ultra-small catalytically active metal nanoparticles in a single-channel reactor." Reaction Chemistry & Engineering 2, no. 5 (2017): 636–41. http://dx.doi.org/10.1039/c7re00072c.

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46

Shen, Bo, and Timothy F. Jamison. "Continuous Flow Photochemistry for the Rapid and Selective Synthesis of 2’-Deoxy and 2’,3’-Dideoxynucleosides." Australian Journal of Chemistry 66, no. 2 (2013): 157. http://dx.doi.org/10.1071/ch12426.

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A new photochemical flow reactor has been developed for the photo-induced electron-transfer deoxygenation reaction to produce 2′-deoxy and 2′,3′-dideoxynucleosides. The continuous flow format significantly improved both the efficiency and selectivity of the reaction, with the streamlined multi-step sequence directly furnishing the highly desired unprotected deoxynucleosides.

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47

Li, Mi, Xiao Wu, Dongxue Han, et al. "A High-Efficiency Single-Mode Traveling Wave Reactor for Continuous Flow Processing." Processes 10, no. 7 (2022): 1261. http://dx.doi.org/10.3390/pr10071261.

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This paper proposes a high-efficiency single-mode traveling wave reactor based on a rectangular waveguide and its design method for continuous flow processing. The reactor has a large-capacity reaction chamber (1000 mm × 742.8 mm × 120 mm) that can provide high-energy-efficiency and approximately uniform microwave heating. The microwave heating uniformity is improved by maintaining single-mode microwave transmission and eliminating higher-order modes in such a multi-mode reaction chamber. The high energy efficiency of microwave heating is achieved by adopting impedance matching techniques. The incident microwave in the reactor can remain in a traveling wave state, and the power reflection can be minimized. Several numerical simulations based on multi-physics modeling are conducted to investigate the heating uniformity, the energy efficiency and the flexibility under different operation conditions. The results show the microwave energy efficiency can be higher than 99%, and meanwhile, the coefficient of temperature variation can be lower than 0.4. Furthermore, when the reactor is operated under different flow velocities and with different heating materials, both the energy efficiency and the heating uniformity can also meet the above requirements. The proposed reactor can be used in the applications such as oil processing, wastewater tackling, chemical synthesis, beverage sterilization and other microwave-assisted continuous flow processes that require high heating uniformity, high energy efficiency and good adaptability.

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48

Seyler, Helga, Stefan Haid, Tae-Hyuk Kwon, et al. "Continuous Flow Synthesis of Organic Electronic Materials – Case Studies in Methodology Translation and Scale-up." Australian Journal of Chemistry 66, no. 2 (2013): 151. http://dx.doi.org/10.1071/ch12406.

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The continuous flow synthesis of functional thiophene derivatives was examined. Methodology for the lithiation of thiophene building blocks was developed using a commercial bench-top flow reactor. In addition, the advantages of flow processing were demonstrated in the synthesis of a high performance organic dye in gram scale.

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49

Fortunato, Milene A. G., Chi-Phong Ly, Filipa Siopa, and Carlos A. M. Afonso. "Process Intensification for the Synthesis of 6-Allyl-6-azabicyclo[3.1.0]hex-3-en-2-ol from 1-Allylpyridinium Salt Using a Continuous UV-Light Photoflow Approach." Methods and Protocols 2, no. 3 (2019): 67. http://dx.doi.org/10.3390/mps2030067.

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A new home-made UV photochemical reactor (95 cm of irradiation zone) consisting of a 12 parallel quartz tubes flow reactor, PQT6 (95 cm under irradiation and an internal diameter of 0.6 cm) was assembled to perform photochemical transformations in continuous-flow. PQT6 was evaluated for the photoreaction of 1-allylpyridinium bromide (1a) to 6-allyl-6-azabicyclo[3.1.0]hex-3-en-2-ol (2a), in a continuous process. This technology provides reduced reaction times, continuous production of 2a, and a productivity of 129 mg h−1, corresponding to 1.94 g of isolated 2a after 15 h of irradiation.

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Yu, Jianming, Lijie Yang, Jing Jiang, et al. "Scalable Production of High-Quality Silver Nanowires via Continuous-Flow Droplet Synthesis." Nanomaterials 12, no. 6 (2022): 1018. http://dx.doi.org/10.3390/nano12061018.

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Silver nanowires (Ag NWs) have shown great potential in next-generation flexible displays, due to their superior electronic, optical, and mechanical properties. However, as with most nanomaterials, a limited production capacity and poor reproduction quality, based on the batch reaction, largely hinder their application. Here, we applied continuous-flow synthesis for the scalable and high-quality production of Ag NWs, and built a pilot-scale line for kilogram-level per day production. In addition, we found that trace quantities of water could generate sufficient vapor as a spacer under high temperature to efficiently prevent the back-flow or mixed-flow of the reaction solution. With an optimized synthetic formula, a mass production of pure Ag NWs of 36.5 g/h was achieved by a multiple-channel, continuous-flow reactor.

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