Journal of Flow Chemistry最新文献

{"title":"Leveraging flow chemistry for the synthesis of trisubstituted isoxazoles","authors":"Michael Prieschl,&nbsp;Niklas Sulzer,&nbsp;Joerg Sedelmeier,&nbsp;Dainis Kaldre,&nbsp;René Lebl,&nbsp;Kurt Püntener,&nbsp;Stefan Hildbrand,&nbsp;Jason D. Williams,&nbsp;C. Oliver Kappe","doi":"10.1007/s41981-023-00288-8","DOIUrl":"10.1007/s41981-023-00288-8","url":null,"abstract":"<div><p>The synthesis of trisubstituted isoxazoles generally requires multiple individual chemical steps, making them amenable to improvements in efficiency by telescoping as a multistep flow process. Three steps (oximation, chlorination and cycloaddition) were developed in continuous flow mode, aiming to function as an high-yielding and efficient sequence. We demonstrate this sequence using two aldehyde starting materials of interest: one carbocyclic and one heterocyclic. Between these two substrates, significant differences in solubility and reactivity necessitated modifications to the route. Most notably, the chlorination step could be carried out using either an organic N-Cl source (applicable for the carbocyclic aldehyde) or Cl₂ generated on-demand in a flow setup (applicable for the heterocyclic aldehyde). By selecting the most effective method for each substrate, good yields could be achieved over the telescoped sequence.</p></div>","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":"13 4","pages":"405 - 411"},"PeriodicalIF":2.0,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s41981-023-00288-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135342338","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":"Synthesis of BuNENA in a continuous flow microreactor","authors":"Zhi-Yuan Jiang,&nbsp;Jing Hou,&nbsp;Le-Wu Zhan,&nbsp;Bin-Dong Li","doi":"10.1007/s41981-023-00287-9","DOIUrl":"10.1007/s41981-023-00287-9","url":null,"abstract":"<div><p>In order to improve process safety, product purity, and production efficiency in the synthesis of N-n-butyl-N-(2-nitroxy-ethyl)nitramine (BuNENA), a two-stage continuous flow microreactor system was constructed by sequentially connecting the self-designed heart-shaped channel microreactor and the caterpillar microreactor. n-Butylethanolamine was used as the raw material, nitric acid and acetic anhydride were used as the nitrating agents. The results showed that when the flow rate of n-butylethanolamine was 1.00 mL.min^− 1, the temperature of the heart-shaped channel microreactor was 10 ℃, the temperature of the caterpillar microreactor was 35 ℃, the molar ratio of ZnCl₂ to n-butylethanolamine was 2%, the molar ratio of nitric acid to n-butylethanolamine was 2.4, and the molar ratio of ZnCl₂ to n-butylethanolamine was 2.4, the result was best. Under the conditions, the reaction time was shortened to 300 s, the purity of BuNENA was up to 98.1%, and the yield was 87.1%.</p></div>","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":"13 4","pages":"449 - 456"},"PeriodicalIF":2.0,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135474763","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":"Investigating the photochemical reaction of an oxazolone derivative under continuous-flow conditions: from analytical monitoring to implementation in an advanced UVC-LED-driven microreactor","authors":"Gaëlle Lebrun,&nbsp;Marie Schmitt,&nbsp;Michael Oelgemöller,&nbsp;Marc Vedrenne,&nbsp;Jean-François Blanco,&nbsp;Karine Loubière","doi":"10.1007/s41981-023-00284-y","DOIUrl":"10.1007/s41981-023-00284-y","url":null,"abstract":"<div><p>This study examined the photochemical transformation of an oxazolone derivative in a continuous microreactor irradiated by a UVC LED array (273 nm). The aim of this study was to transfer the reaction protocol originally developed under batch conditions to continuous flow and to further evaluate the scope of this application. A custom-built UVC-LED panel was combined with a microchip, and this microflow system allowed to work under perfectly controlled operating conditions. NMR and LC-MS were used to identify and quantify the main products obtained during the reaction. From this, an HPLC method was developed for imine separation, allowing for an easy and fast monitoring of the reaction progress. Subsequently, the influence of the operating conditions (residence time, photon flux density, temperature) on the selectivity and conversion was investigated to identify the most favorable conditions for a specific product. Temperature did not affect conversion but had an impact on the reaction’s selectivity. The developed UVC-LED-driven continuous-flow microreactor was found to be very efficient since a quantum photon balance ratio of 0.7 was enough to convert all the reactant, while at the same time achieving the maximal yield of the target product. Exhaustive irradiation did not change the molar ratio of each compound present in the reaction medium, thus excluding follow-up photoreactions of the products. This work opens promising perspectives for boosting flow photochemistry in the UV-C domain.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":"13 4","pages":"413 - 425"},"PeriodicalIF":2.0,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135480180","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":"The joint effort of enzyme technology and flow chemistry to bring biocatalytic processes to the next level of sustainability, efficiency and productivity","authors":"Silvia Donzella,&nbsp;Martina Letizia Contente","doi":"10.1007/s41981-023-00286-w","DOIUrl":"10.1007/s41981-023-00286-w","url":null,"abstract":"<div><p>The number of biocatalyzed reactions at industrial level is growing rapidly together with our understanding on how we can maximize the enzyme efficiency, stability and productivity. While biocatalysis is nowadays recognized as a greener way to operate in chemistry, its combination with continuous processes has lately come up as a powerful tool to enhance process selectivity, productivity and sustainability. This perspective aims at describing the recent advances of this technology and future developments leading to smart, efficient and greener strategies for process optimization and large-scale production.</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":"14 1","pages":"85 - 96"},"PeriodicalIF":2.0,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s41981-023-00286-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135432354","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":"Recent developments of automated flow chemistry in pharmaceutical compounds synthesis","authors":"Jiashu Wu,&nbsp;Xingxing Yang,&nbsp;Yourong Pan,&nbsp;Tao Zuo,&nbsp;Zuozhou Ning,&nbsp;Chengxi Li,&nbsp;Zhiguo Zhang","doi":"10.1007/s41981-023-00285-x","DOIUrl":"10.1007/s41981-023-00285-x","url":null,"abstract":"<div><p>Recent developments in automated flow chemistry for pharmaceutical compound synthesis have garnered significant attention. Automation in synthesis represents a cutting-edge frontier in the field of chemistry, offering highly efficient, rapid, and reproducible synthetic methods that significantly shorten reaction time and reduce costs. In the realm of pharmaceutical compound synthesis, automated flow chemistry demonstrates unique importance. By utilizing flow chemistry, reactions can be performed under continuous flow conditions, enabling precise reaction control, higher yields, and increased product purity. Additionally, automated flow synthesis overcomes several challenges encountered in traditional batch synthesis, such as decreased generation of chemical waste, optimization of reaction conditions, and enhanced operational safety. This review highlights the recent developments in automated flow synthesis of various pharmaceutical compounds, including large biopharmaceutical molecules, small organic drug molecules, and carbohydrates. It covers automated iterative synthesis and the use of machine learning to enhance synthesis efficiency. Furthermore, it explores the practical application of high-throughput synthesis and screening technologies. Finally, the review offers concise perspectives on potential future developments in the field.</p><h3>Graphical abstract</h3><p>The development of automated flow synthesis kept breaking through new challenges for chemical reactions. Especially with the increasing demand for fast and efficient synthesis of therapeutic compounds, automated systems built a solid foundation for pharmaceutical innovation.</p><p>Solid-phase flow synthesis has been well-developed in the synthesis of large biopharmaceutical molecules; the immobilized support helps replace tedious separation and purification with a simple solvent wash. Additionally, flow-based pathways could provide convenience for automation.</p><p>High-throughput synthesis with in-line analysis offers both high-efficiency production and accurate monitoring. Therefore, this combination could be easily applied to rapid screening processes for building a large library, enhancing the performance of machine learning in reaction, and product prediction.</p><p>Artificial intelligence can be applied to self-optimized synthesis processes. Algorithm-based software could rapidly calculate and optimize insufficient reactions with a learning model built on past reactions posted in the literature. The connected robotic arm can then be automatically set to perform the optimized reaction.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":"13 4","pages":"385 - 404"},"PeriodicalIF":2.0,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135590227","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":"Perspectives on flow biocatalysis: the engine propelling enzymatic reactions","authors":"Ana I. Benítez-Mateos,&nbsp;Francesca Paradisi","doi":"10.1007/s41981-023-00283-z","DOIUrl":"10.1007/s41981-023-00283-z","url":null,"abstract":"<div><p>Flow biocatalysis has emerged as an empowering tool to boost the potential of enzymatic reactions towards more automatized, sustainable, and generally efficient synthetic processes. In the last fifteen years, the increasing number of biocatalytic transformations carried out in continuous flow exemplified the benefits that this technology can bring to incorporate biocatalysis into industrial operations. This perspective aims to capture in a nutshell the available methodologies for flow biocatalysis as well as to discuss the current limitations and the future directions in this field.</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":"14 1","pages":"211 - 218"},"PeriodicalIF":2.0,"publicationDate":"2023-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s41981-023-00283-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135413491","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":"Development of an automated flow chemistry affinity-based purification process for DNA-encoded chemistry","authors":"Robin Dinter,&nbsp;Katharina Götte,&nbsp;Franziska Gronke,&nbsp;Leon Justen,&nbsp;Andreas Brunschweiger,&nbsp;Norbert Kockmann","doi":"10.1007/s41981-023-00282-0","DOIUrl":"10.1007/s41981-023-00282-0","url":null,"abstract":"<div><p>An automated flow chemistry platform for DNA-encoded library (DEL) technologies requires the integration of a purification process for DNA-tagged substrates. It facilitates the development of further DEL reactions, building block rehearsal, and library synthesis. Therefore, a recently developed, manual affinity-based batch purification process for DNA-tagged substrates based on dispersive solid-phase extraction (DSPE) was transferred to automated flow chemistry using tailored 3D-printed microfluidic devices and open-source lab automation equipment. The immobilization and purification steps use Watson–Crick base pairing for a compound-encoding single-stranded DNA, which allows for the thorough removal of impurities and contaminations by washing steps and operationally simple recovery of the purified DNA-encoded compounds. This work optimized the annealing step for flow incubation and DNA purification was accomplished by flow DSPE washing/elution steps. The manually performed batch affinity-based purification process was compared with the microfluidic process by determining qualitative and quantitative DNA recovery parameters. It aimed at comparing batch and flow purification processes with regard to DNA recovery and purity to benefit from the high potential for automation, precise process control, and higher information density of the microfluidic purification process for DNA-tagged substrates. Manual operations were minimized by applying an automation strategy to demonstrate the potential for integrating the microfluidic affinity-based purification process for DNA-tagged substrates into an automated DNA-encoded flow chemistry platform.</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":"13 4","pages":"361 - 373"},"PeriodicalIF":2.0,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s41981-023-00282-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134960496","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":"Droplet generation at T-junctions in parallelized microchannels","authors":"Zhongdong Wang,&nbsp;Xingyu Xiang,&nbsp;Sajawal Raza,&nbsp;Asad Ullah,&nbsp;Chunying Zhu,&nbsp;Tianyang Feng,&nbsp;Youguang Ma,&nbsp;Taotao Fu","doi":"10.1007/s41981-023-00281-1","DOIUrl":"10.1007/s41981-023-00281-1","url":null,"abstract":"<div><p>Microchemical technology is an advanced chemical production technology and the large-scale production for industrial applications is realized by parallelization of microchannels. In this paper, the emulsification process and numbering-up of droplets in asymmetric parallelized microchannels with T-junction are investigated, and the effects of fluid properties and operating conditions on droplet size are analyzed. The droplet generation process is divided into waiting stage, filling stage, necking stage, and pinch-off stage, according to the variation of the characteristic length scale during droplet generation. The flow patterns of droplet swarm in cavities and their influence on fluid distribution are analyzed. The droplet size prediction equation and fluid distribution model in asymmetric parallelized microchannel are constructed. The phenomenon of droplet asynchronous generation due to the coupling of parallelized microchannels during the numbering-up process is analyzed. The effect of asynchronous generation on droplet monodispersity is investigated and the mothod for the prevention of this effect is proposed.</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":"14 1","pages":"313 - 327"},"PeriodicalIF":2.0,"publicationDate":"2023-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48464807","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 7-methoxy-1-tetralone: an important intermediate of (-)-Dezocine","authors":"Liangchuan Lai,&nbsp;Liang Gao,&nbsp;Minjie Liu,&nbsp;Yongxing Guo,&nbsp;Dang Cheng,&nbsp;Meifen Jiang,&nbsp;Fener Chen","doi":"10.1007/s41981-023-00274-0","DOIUrl":"10.1007/s41981-023-00274-0","url":null,"abstract":"<div><p>\u0000Continuous flow technology has been widely adopted in manufacturing active pharmaceutical ingredients (APIs). Herein, we report an expeditious multi-step continuous-flow strategy for an efficient and highly productive flow synthesis of 7-methoxy-1-tetralone, which is an essential intermediate for the opioid analgesic drug (-)-dezocine. Compared with the traditional batch operation, this work presents significant advantages of continuous-flow chemistry with dramatically reduced reaction time, highly improved reaction efficiency, good controls over reaction optimizing conditions, etc. The flow protocol in this work provided the desired product in an overall yield of up to 76.6% with 99% purity, much higher than those from batch process (i.e., 50% yield, 92% purity). Moreover, reaction efficiency is highly improved with a throughput of 0.49 g/h, the total reaction time is markedly reduced from hours in batch to minutes in flow process.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":"13 4","pages":"375 - 383"},"PeriodicalIF":2.0,"publicationDate":"2023-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42373280","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":"Safe and on-demand protocol for the continuous generation of SO2 and Cl2 for subsequent utilization in organic synthesis","authors":"Gulice Yiu Chung Leung,&nbsp;Shannon Thoi Rui Ying,&nbsp;Edwin Chia,&nbsp;Anqi Chen,&nbsp;Gabriel Loh,&nbsp;Balamurugan Ramalingam","doi":"10.1007/s41981-023-00280-2","DOIUrl":"10.1007/s41981-023-00280-2","url":null,"abstract":"<div><p>Hazardous reagents such as sulfur dioxide (SO₂) and chlorine (Cl₂) are powerful and atom-efficient reagents for respectively introducing the ‘SO₂’ moiety and ‘Cl’ atom into organic molecules. However, their use is limited due to a lack of protocols and methods to access them in laboratories readily. This article describes the development of a prototype, method, and process for accessing hazardous gaseous reagents safely on demand continuously for further utilization in organic synthesis. The prototype was validated by producing SO₂ from readily accessible laboratory reagents sodium sulfite (Na₂SO₃) and sulfuric acid (H₂SO₄). The generated SO₂ was successfully utilized for the synthesis of aryl sulfinate salts, which were subsequently converted to sulfonamides and sulfone-containing bicalutamide drugs. The broader applicability of the reactor prototype has also been demonstrated in the generation of chlorine gas from bleach (NaOCl) and hydrochloric acid (HCl), followed by the separation of chlorine gas from an acidic aqueous reaction mixture. The utilization of the separated chlorine gas was demonstrated in the synthesis of silyl chlorides in both batch and continuous manners. The present reactor prototype not only enables safe and convenient access to highly hazardous gaseous reagents for facile organic synthesis in laboratories, but also eliminates the risks in handling, storage, and transportation of hazardous gaseous reagents in cylinders.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":"14 1","pages":"129 - 138"},"PeriodicalIF":2.0,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42193973","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}