Journal of Flow Chemistry最新文献

{"title":"Control of mixing in a continuous-flow microreactor with an integrated bubble","authors":"Dmitry Bratsun,&nbsp;Aleksey Mizev,&nbsp;Ramil Siraev,&nbsp;Elena Krasnyakova","doi":"10.1007/s41981-025-00343-6","DOIUrl":"10.1007/s41981-025-00343-6","url":null,"abstract":"<p>Continuous-flow microreactors are increasingly used to replace batch reactors in fine organic synthesis. The interest of pharmaceutical production and similar industries in greater flexibility in reconfiguring synthesis systems motivates the design of increasingly miniature devices, in which mechanical mixing is difficult to apply, while the diffusion mechanism is inefficient. In this paper, using the example of a T-shaped continuous-flow microreactor, we propose to supplement the reaction chamber with a unit that rapidly mixes flowing solutions due to the concentration-capillary mechanism. Two syringe pumps supply a less dense isobutyric acid (<span>(mathrm {C_{3}H_{7}COOH})</span>) aqueous solution to the upper inlet and denser sodium hydroxide (<span>(textrm{NaOH})</span>) aqueous solution to the lower inlet, establishing a stably stratified two-layer system at the reaction chamber entrance. The contact between the solutions triggers a neutralization reaction. At a distance from the entrance, an additional inlet helps to form a gas bubble within the chamber. We show experimentally and numerically that the integration of an air bubble in a channel leads to the excitation of a self-oscillatory process near the air-liquid surface. The convective mixing process occurs in a pulsed mode, which includes a phase of rapid homogenization of the medium and subsequent restoration of heterogeneity by the base flow. We have determined the flow stability map on the plane of solution flow rates. We demonstrate that one can control the activation of convection, which enhances the mixing process, by manipulating the flow rates.</p>","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":"15 1","pages":"59 - 66"},"PeriodicalIF":2.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Continuous-flow synthesis of prenyl chloride on-demand through surface-mediated hydrochlorination","authors":"Hang Zhao,&nbsp;Xiao Xiao,&nbsp;Runqi Hao,&nbsp;Dan Chen,&nbsp;Jiawei Ke,&nbsp;Minjie Liu,&nbsp;Li Wan,&nbsp;Fener Chen","doi":"10.1007/s41981-025-00344-5","DOIUrl":"10.1007/s41981-025-00344-5","url":null,"abstract":"<div><p>1-Chloro-3-methyl-2-butene is an important synthetic precursor or alkylating agent in the preparation of various bioactive chemicals and essential nutrients for human beings. A flow surface-mediated HCl in situ generation and subsequent hydrochlorination of isoprene were realized in the PTFE tubing reactor and the packed-bed reactor separately. Up to 86% isolated yield of 1-chloro-3-methyl-2-butene was achieved in the packed-bed reactor by performing the flow hydrochlorination at -15 °C within a 15 min residence time in the presence of 0.5 equiv. SOCl₂. The in-line recycling and regenerating of solid proton donor Al₂O₃ were accomplished via simple washing with DCM and MeOH in sequence, the activity of Al₂O₃ filled in the packed-bed reactor maintain consistent on the isolated yield of 1-chloro-3-methyl-2-butene after ten times consecutive reutilization. The flow platform consisting of two parallel packed-bed reactors were assembled for the continuous synthesis of desired 1-chloro-3-methyl-2-butene without interruption through delicate coordinating opening direction of a series of three-way valves. Long-term stability and reliability were demonstrated by continuous running the designed cyclic rotation system for 10 h, the targeted hydrochlorination product was furnished in 91–93% yield.</p><h3>Graphical abstract</h3><p>Continuous-flow synthesis of prenyl chloride was enabled by cross-sequential utilization strategy using two parallel packed-bed reactors and precise alternating a series of three-way valves opening direction.</p>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":"15 1","pages":"39 - 46"},"PeriodicalIF":2.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143570977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Best practice approach for temperature measurement in flow chemistry based on CFD simulation","authors":"Vanessa Nuredin,&nbsp;Lisa Schulz,&nbsp;Norbert Kockmann,&nbsp;Thorsten Röder","doi":"10.1007/s41981-024-00341-0","DOIUrl":"10.1007/s41981-024-00341-0","url":null,"abstract":"<div><p>The exact measurement of the temperature in laboratory continuous flow processes is of high importance for many investigations e.g. of heat transfer or reaction kinetics. In particular, miniaturization poses high challenges on temperature measurement due to increased heat transfer. Despite the high relevance of this topic, there are only few publications dealing with accurate inline temperature measurement in flow chemistry and no studies examining the influence of the installation of the temperature sensor on the actual measured temperature. This work deals with inline temperature measurement using a conventional Pt100 sensor with 1.6 mm outer diameter and 20 mm measuring length in a T-piece in a continuous flow reactor on the micro-scale. The issue of heat loss in the T-piece is illustrated in a computational fluid dynamics CFD simulation. The T-piece temperature and the corresponding temperature measured by the Pt100 sensor in an insulated and not insulated T-piece are simulated and compared with experimental data. Moreover, different insert positions and orientations of the Pt100 sensor are simulated and discussed. The extensive CFD simulations demonstrate that using the side-on position of the Pt100 within an insulated T-piece leads to the most precise temperature measurements. Furthermore, the study shows that tilting of the Pt100 inside the T-piece has almost no influence on the temperature measurement as long as the measuring section of the Pt100 is fully inserted. Based on these results, a best practice approach for inline temperature measurement in micro-scale continuous flow reactors is presented for minimal measurement error.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":"15 1","pages":"47 - 58"},"PeriodicalIF":2.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s41981-024-00341-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative economic analysis of batch vs. continuous manufacturing in catalytic heterogeneous processes: impact of catalyst activity maintenance and materials costs on total costs of manufacturing in the production of fine chemicals and pharmaceuticals","authors":"F. Mendoza Suarez,&nbsp;B. Tatarchuk","doi":"10.1007/s41981-024-00342-z","DOIUrl":"10.1007/s41981-024-00342-z","url":null,"abstract":"<div><p>To evaluate the feasibility of transforming batch manufacturing processes in the fine chemicals and pharmaceutical industries to continuous synthesis, Capex, Opex and the total cost of manufacturing are estimated for production facilities for the hydrogenation of a nitro compound to its final amino counterpart. Two cases are evaluated: First, a high annual production dedicated plant, designed on the basis of processing 100,000 kg of the principal raw material per year, where raw materials cost, catalyst cost, and catalyst activity maintenance are varied over a broad range for typical industrial cases. Second, a “short campaign” model for a small volume production trial setup designed for the manufacture of only 100 kg of the final product, as a way to evaluate relevant industrial scenarios of scale-up and process development. A comparison is made between slurry batch, catalyst basket batch reactor and fixed bed continuous reactor manufacturing facilities. The hydrogenation of 2,4-dinitrotoluene was chosen as a probe reaction for the development of the manufacturing processes, with costs of the key raw material varying between $5 and $100 per kilogram, costs of catalyst varying between $100 and $1,500 per kilogram, and catalyst activity maintenances varying between 1,000 and 2,000,000 total turnovers before a change in catalyst load is necessary. For low catalyst activity maintenance, the total manufacturing costs for the fixed bed reactor process were always found to be higher than those of the two other alternatives. As catalyst activity maintenance increases, the manufacturing costs for the continuous alternative rapidly fall, reaching savings between 37 and 75% compared to the base batch reactor case, depending on the combination of costs of the key raw material and catalyst used.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":"15 1","pages":"21 - 38"},"PeriodicalIF":2.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s41981-024-00342-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143570989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extraction and mass transfer of glyoxylic acid in a capillary microchannel","authors":"Junnan Wang,&nbsp;Yating Li,&nbsp;Ting Wang,&nbsp;Tianyang Feng,&nbsp;Chunying Zhu,&nbsp;Youguang Ma,&nbsp;Taotao Fu","doi":"10.1007/s41981-024-00340-1","DOIUrl":"10.1007/s41981-024-00340-1","url":null,"abstract":"<div><p>A solvent extraction system for extracting glyoxylic acid from aqueous solutions by using trioctylamine in n-octanol in a microchannel is developed, operating in the slug flow regime. The extraction system is composed of two preheating capillary loops, a T-junction micromixer, and a capillary microchannel. The influences of the volume ratio of the organic phase to the aqueous phase (O/A ratio), temperature, concentration of trioctylamine, total flow rate, and residence time on extraction and mass transfer are systematically investigated. A relationship between the total volumetric mass transfer coefficient and the capillary number, Reynolds number, capillary diameter and length is proposed. This study holds significant implications for the efficient extraction of glyoxylic acid in microchannels.</p></div>","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":"15 1","pages":"11 - 20"},"PeriodicalIF":2.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143570966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact in continuous flow heated mechanochemical technology: An improved solketal synthesis","authors":"Rémi Nguyen,&nbsp;Samy Haloumi,&nbsp;Irene Malpartida,&nbsp;Christophe Len","doi":"10.1007/s41981-024-00339-8","DOIUrl":"10.1007/s41981-024-00339-8","url":null,"abstract":"<div><p>Impact in Continuous flow Heated Mechanochemistry (ICHEM) was used for the production of solketal at 60 °C using glycerol and acetone in the presence of homogeneous FeCl₃.6H₂O (1 mol%). In our optimized conditions, the target compound was obtained in 96% yield (conversion of 97% and selectivity of 99%) with a productivity of 276 g day^–1 with a 80 mL continuous flow reactor. This new technology combines beads mechanochemistry and continuous flow and offers: (i) a better mixing of the two unsoluble parts (glycerol and acetone) by reducing the viscosity of the feed stream and (ii) an alternative of the single-screw and double-screw extruders which are unefficient with a liquid reaction media.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":"15 1","pages":"1 - 9"},"PeriodicalIF":2.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143570967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A modular flow process intensification towards lipid peptoids nano assembly formation","authors":"Thaissa P. F. Rosalba,&nbsp;Guilherme J. P. Gonçalves,&nbsp;Carlos Eduardo M. Salvador,&nbsp;Alexandre Fonseca,&nbsp;Carlos Kleber Z. Andrade","doi":"10.1007/s41981-024-00338-9","DOIUrl":"10.1007/s41981-024-00338-9","url":null,"abstract":"<div><p>Nanotechnology has emerged as a groundbreaking field with profound implications for drug delivery systems, offering precise targeting, controlled release, and enhanced therapeutic efficacy. Continuous flow process is a compelling approach in the production of nanoparticles, providing numerous advantages over traditional batch methods. By maintaining uniform conditions and precise control over reaction parameters, continuous flow systems enable enhanced reproducibility, scalability, and efficiency in nanoparticle synthesis. In this context, microfluidic hydrodynamic focusing (MHF) is a promising method for continuous flow lipid nanoparticle synthesis. Herein, we report a study for the development of a single-step continuous flow process to generate nanoparticles using a PLA chip device inspired by microfluidic techniques. A lipid peptoid synthesized via Ugi reaction was chosen from an ongoing study to evaluate the most appropriate conditions for the continuous flow process. It was possible to produce nanoparticles with small size and the optimized parameters generated nanoparticles with sizes ≤ 200 nm, making them good candidates for drug delivery system.</p><h3>Graphical abstracts</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":"14 4","pages":"677 - 689"},"PeriodicalIF":2.0,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Towards an approach to small-scale aryllithium flash flow chemistry using low-cost, low volume reactors","authors":"James A. K. Cochrane,&nbsp;Aaron J. Rigby,&nbsp;Raminder S. Mulla","doi":"10.1007/s41981-024-00335-y","DOIUrl":"10.1007/s41981-024-00335-y","url":null,"abstract":"<p>Two low-cost reactors for aryllithium generation and trapping with an electrophile in flow have been developed for use with small quantities of limiting reagent (600 <span>(upmu )</span>mol) using reductions in flow rates as the approach to miniaturisation. To this end, a number of inexpensive, commercially available mixing elements were characterised via model lithium-halogen exchange reactions to determine their performance at low (&lt; 5 mL min^-1) flow rates. From these studies, a glass chip mixer, and 250 <span>(upmu )</span>m tee-pieces were identified for use at low flow rates and therefore incorporated into the aforementioned reactors. These reactors were demonstrated to be suitable for the successful lithiation and trapping of a selection of ArX substrates. <b>Impact of flow: </b>Organolithium chemistry greatly benefits from translation to flow. Increased heat transfer means that reactions may be run at higher temperatures than in batch, with drastically reduced reaction times. Moreover, the precise control of stoichiometry via flow rates, coupled with the improved mixing in flow leads to improved functional group tolerance and selectivity.</p>","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":"14 4","pages":"667 - 675"},"PeriodicalIF":2.0,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Seeded-growth synthesis of 20–60 nm monodisperse citrate-capped gold nanoparticles in a millifluidic reactor","authors":"Mabel Cornwell,&nbsp;Spyridon Damilos,&nbsp;Ivan P. Parkin,&nbsp;Asterios Gavriilidis","doi":"10.1007/s41981-024-00334-z","DOIUrl":"10.1007/s41981-024-00334-z","url":null,"abstract":"<div><p>Gold nanoparticles have diverse applications, requiring advancements in their synthesis that facilitate scale up, size control and reproducibility. Using a seeded-growth method in a 20 mL two-phase flow reactor (ID 2.4 mm) at 35 °C, highly monodisperse gold nanoparticles of any chosen size from 20 to 60 nm were produced. Heptane was utilised as the segmenting fluid to transport the aqueous reagent-containing droplets through a coiled PTFE reactor preventing their interaction with the reactor walls and thus reactor fouling. Gold seeds ~ 12 nm were produced via a passivated Turkevich synthesis by reduction of high pH Au(III) solution using citric acid as reducing agent. For the seeded-growth in flow, the reagents utilised were the seed solution (diluted accordingly), a stabilising Tris base solution, tetrachloroauric(III) acid trihydrate and hydrogen peroxide as reducing agent. Seeded-growth synthesis was also performed using as seeds commercial 10 nm gold nanoparticles, with excellent Coefficient of Variation (CoV) and Optical Density (OD) of the grown particles (CoV &lt; 8% and OD ≥ 1) demonstrating that they are monodisperse and have high concentration. The synthesis was able to produce 18 mL/h of grown nanoparticles solution at 2.2–2.8 mg Au/h without any divergence in the quality of the produced particles for over eight hours.</p></div>","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":"14 4","pages":"655 - 666"},"PeriodicalIF":2.0,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s41981-024-00334-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formation of double emulsion droplets in flow-focusing microchips: a numerical parametric study","authors":"Chengyi Hu,&nbsp;Fan Jiang,&nbsp;Ju Yan","doi":"10.1007/s41981-024-00337-w","DOIUrl":"10.1007/s41981-024-00337-w","url":null,"abstract":"<div><p>A microfluidic chip is introduced for generating double emulsion droplets, consisting of a coaxial focusing center structure combined with a flow-focusing structure. The volume of fluid method (VOF) was adopted to numerically simulate and validate the formation of double emulsion droplets in the device. The impact of microfluidics on the dimensions and molding position of double emulsion droplets was examined under varying flow parameters and physical properties. Results demonstrate that the impact of the alteration in the flow rate of the middle phase is pivotal in the droplet generation process in comparison to the outer phase. An increase in the flow rate of the middle phase results in a notable enlargement of the double emulsion droplets. An increase in viscosity affects the forming regime, causing a transition in the droplet regime. Furthermore, interfacial tension exerts a notable impact on the positioning of droplet formation. The microfluidic device outlined in this paper effectively generates double emulsion droplets characterized by high monodispersity and excellent stability, which serves as a new reference for the practical generation of double emulsion droplets.</p></div>","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":"14 4","pages":"641 - 653"},"PeriodicalIF":2.0,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}