Journal of Flow Chemistry最新文献

{"title":"Continuous heterogeneous synthesis of hexafluoroacetone and its machine learning-assisted optimization","authors":"Tingting Qi,&nbsp;Guihua Luo,&nbsp;Haotian Xue,&nbsp;Feng Su,&nbsp;Jianli Chen,&nbsp;Weike Su,&nbsp;Ke-Jun Wu,&nbsp;An Su","doi":"10.1007/s41981-023-00273-1","DOIUrl":"10.1007/s41981-023-00273-1","url":null,"abstract":"<div><p>Conventional batch synthesis of hexafluoroacetone (HFA), an important pharmaceutical intermediate, suffers from complex catalyst preparation, harsh reaction conditions (up to 200 °C), and low selectivity. In this study, we developed a continuous flow system that employs a micro packed-bed reactor (MPBR) filled with Lewis acid catalysts. After an initial screening of reaction conditions and catalysts in the batch reactor, a Bayesian Optimization model and the multi-objective optimization algorithm qNEHVI were used to find a compromise between conversion and energy efficiency for the reaction in the continuous flow system. After 14 rounds of experiments, BO found the best results with conversion of 98.6%, selectivity of 99.9%, and an energy cost of 0.121 kWh per kg of product at 25.1 °C, atmospheric pressure, and a GHSV of 931.5 h^− 1 reaction conditions. The study demonstrates that BO can be used as an efficient tool for multi-objective optimization of heterogeneous catalysis in continuous flow.</p><h3>Graphical abstract</h3>\u0000 <figure><div><div><div><picture><img></picture></div></div></div></figure>\u0000 </div>","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":"13 3","pages":"337 - 346"},"PeriodicalIF":2.7,"publicationDate":"2023-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s41981-023-00273-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4545528","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":"Continuous catalytic aerobic oxidation of o‑chlorotoluene to o-chlorobenzoic acid under slug flow conditions","authors":"Jiming Liu,&nbsp;Linchang Liu,&nbsp;Wei Zhang,&nbsp;Peng Li,&nbsp;Xin Li,&nbsp;Zhiqun Yu,&nbsp;Weike Su","doi":"10.1007/s41981-023-00272-2","DOIUrl":"10.1007/s41981-023-00272-2","url":null,"abstract":"<div><h2>\u0000Abstract</h2><div><p>\u0000A continuous-flow process was developed for the aerobic oxidation of <i>o</i>-chlorotoluene (OCT) to <i>o</i>-chlorobenzoic acid (OCBA) with pure oxygen. Acetic acid as cosolvent and CoBr₂/MnBr₂ as catalyst, with a small amount of acetaldehyde as the radical initiator to make the reaction rapidly stimulates. Through the regulation of gas–liquid mixing, slug flow obtains similar mass transfer coefficient of annular flow and the reactor volume was further reduced. The reaction parameters were easily controlled by take the advantages of continuous-flow reactor. Under the optimal reaction conditions, the isolated yield of OCBA reached up to 94%. Compared with the traditional batch process, shorter residence time, higher product yield and operation safety are achieved by adapting simple continuous-flow system.\u0000</p></div></div>","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":"13 3","pages":"325 - 335"},"PeriodicalIF":2.7,"publicationDate":"2023-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4393525","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":"Accurate determination of the kinetics of toluene nitration in a liquid–liquid microflow system","authors":"Jing Song,&nbsp;Yongjin Cui,&nbsp;Yujun Wang,&nbsp;Kai Wang,&nbsp;Jian Deng,&nbsp;Guangsheng Luo","doi":"10.1007/s41981-023-00271-3","DOIUrl":"10.1007/s41981-023-00271-3","url":null,"abstract":"<div><p>The nitration of toluene with mixed acid is one of the most representative nitration reactions. Accurate kinetic study is essential for controlling the reaction and designing reactors. Due to the characteristics of fast rate, high exothermicity and heterogeneity in toluene nitration, the effects of mass and heat transfer may result in inaccurate determination of kinetics. In this work, the adiabatic temperature rises of the reaction system were studied to provide precise ranges of experimental conditions for accurately controlling the reaction rate and heat release rate in a liquid–liquid microflow system. The adiabatic temperature rise was successfully controlled to below 0.3 °C. The effects of mass and heat transfer on the reaction rate were completely eliminated, so that the kinetic study was carried out under the control of intrinsic kinetics only. The activation energy for toluene nitration was determined to be 28.00 kJ/mol. The activation energies for the formation of <i>o</i>-nitrotoluene and <i>p</i>-nitrotoluene were obtained for the first time, which were 25.71 and 31.91 kJ/mol, respectively. The obtained kinetic models can predict the reaction performance of toluene nitration very well.\u0000</p></div>","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":"13 3","pages":"311 - 323"},"PeriodicalIF":2.7,"publicationDate":"2023-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4875728","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 Friedel–Crafts acetylation of phenols and electron-rich arenes and heteroarenes","authors":"Kévin Saint-Jacques,&nbsp;André B. Charette","doi":"10.1007/s41981-023-00270-4","DOIUrl":"10.1007/s41981-023-00270-4","url":null,"abstract":"<div><p>An expedient and efficient synthesis of acetyl phloroglucinol from phloroglucinol under continuous flow is reported. This compound is an important building block to access numerous flavonoids. The reported acetylation reaction of phloroglucinol is more efficient than under batch conditions (residence time of 1 min in flow vs 10–15 h in batch; ≥ 98% yield in flow vs 65–86% yield in batch), and proceeds without any formation of the diacetylated product. The desired product was produced with a throughput of ≥ 98 g/h using a simple set-up. The conditions that highlight the use of ethyl acetate, a biomass-derived solvent and acetic anhydride or acetyl chloride were tested in the Friedel–Crafts acetylation of other electron-rich phenols and heterocycles.\u0000</p></div>","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":"13 2","pages":"193 - 199"},"PeriodicalIF":2.7,"publicationDate":"2023-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4396068","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":"Correction to: FOMSy: 3D-printed flexible open-source microfluidic system and flow synthesis of PET-tracer","authors":"Florian Menzel,&nbsp;Jonathan Cotton,&nbsp;Thomas Klein,&nbsp;Andreas Maurer,&nbsp;Thomas Ziegler,&nbsp;Jochen M. Neumaier","doi":"10.1007/s41981-023-00269-x","DOIUrl":"10.1007/s41981-023-00269-x","url":null,"abstract":"","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":"13 3","pages":"359 - 359"},"PeriodicalIF":2.7,"publicationDate":"2023-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s41981-023-00269-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4739672","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":"Micro-Batch flow reactor for the photoproduction of H2O2 from water/real seawater","authors":"Aswin Gopakumar,&nbsp;Tong Zhang,&nbsp;Shoubhik Das","doi":"10.1007/s41981-023-00257-1","DOIUrl":"10.1007/s41981-023-00257-1","url":null,"abstract":"<div><p>Photocatalytic generation of H₂O₂ with heterogeneous catalysts has attracted much attentions and impressive strategies have been used to increase the photocatalytic efficiency. However, applications of these strategies to large scale are still underdeveloped. For this reason, development of flow photocatalytic strategy is highly necessary. Considering this, we have developed a serial micro-batch flow reactor for the generation of H₂O₂ which could easily scale up the reaction to1L scale with high reproducibility with the modified g-C₃N₄. With this flow reactor, the generated concentration of H₂O₂ has been reached to 6.89 mM and 5.89 mM in pure water and seawater, respectively.</p><h3>Graphical Abstract</h3>\u0000 <figure><div><div><div><picture><source><img></source></picture></div></div></div></figure>\u0000 </div>","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":"13 2","pages":"185 - 192"},"PeriodicalIF":2.7,"publicationDate":"2023-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4743063","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":"Advances in continuous polymer analysis in flow with application towards biopolymers","authors":"Samuel B. H. Patterson,&nbsp;Raymond Wong,&nbsp;Graeme Barker,&nbsp;Filipe Vilela","doi":"10.1007/s41981-023-00268-y","DOIUrl":"10.1007/s41981-023-00268-y","url":null,"abstract":"<div><p>Biopolymers, polymers derived from renewable biomass sources, have gained increasing attention in recent years due to their potential to replace traditional petroleum-based polymers in a range of applications. Among the many advantages of biopolymers can be included their biocompatibility, excellent mechanical properties, and availability from renewable feedstock. However, the development of biopolymers has been limited by a lack of understanding of their properties and processing behaviours. Continuous analysis techniques have the potential to hasten progress in this area by providing real-time insights into the properties and processing of biopolymers. Significant research in polymer chemistry has focused on petroleum-derived polymers and has thus provided a wealth of synthetic and analytical methodologies which may be applied to the biopolymer field. Of particular note is the application of flow technology in polymer science and its implications for accelerating progress towards more sustainable and environmentally friendly alternatives to traditional petroleum-based polymers. In this mini review we have outlined several of the most prominent use cases for biopolymers along with the current state-of-the art in continuous analysis of polymers in flow, including defining and differentiating atline, inline, online and offline analysis. We have found several examples for continuous flow analysis which have direct application to the biopolymer field, and we demonstrate an atline continuous polymer analysis method using size exclusion chromatography.</p><h3>Graphical abstract</h3>\u0000 <figure><div><div><div><picture><source><img></source></picture></div></div></div></figure>\u0000 </div>","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":"13 2","pages":"103 - 119"},"PeriodicalIF":2.7,"publicationDate":"2023-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s41981-023-00268-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5160218","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":"FOMSy: 3D-printed flexible open-source microfluidic system and flow synthesis of PET-tracer","authors":"Florian Menzel,&nbsp;Jonathan Cotton,&nbsp;Thomas Klein,&nbsp;Andreas Maurer,&nbsp;Thomas Ziegler,&nbsp;Jochen M. Neumaier","doi":"10.1007/s41981-023-00267-z","DOIUrl":"10.1007/s41981-023-00267-z","url":null,"abstract":"<div><p>In this work, we introduce a low-cost open-source flow system that includes a dual syringe pump with implemented pressure sensor and back pressure regulator. The entire system can be built for around 500 €. Commercially available flow systems can be very expensive with equipment starting at, but often greatly exceeding, 10,000 €. This high price of entry makes such technology prohibitively expensive for many research groups. Such systems stand to benefit the emerging academic pharmaceutical field by providing the experience and availability of reliable and affordable solutions. To implement accessible flow chemistry at research facilities, the systems must be made affordable. In addition, space in research laboratories is usually limited and commercially available flow systems can be very bulky. Having a compact and individually adjustable system is thus beneficial, with 3D printing technology offering the solution. Our compact 3D-printed system meets the needs of many applications in flow chemistry research as well as educational requirements for universities. As a proof of concept, we conceptualized, developed, and tested a custom flow system that can be used to synthesize [¹⁸F]2-fluoro-2-desoxy-d-glucose ([¹⁸F]FDG), the most commonly used PET-tracer. This system was designed to perform the typical functions and operations required in radiotracer production i.e. radiofluorination, dilution, SPE-trapping, deprotection, and SPE-elution. With this proof-of-concept in hand, the system can be easily customized to produce other radiopharmaceuticals.</p><h3>Graphical Abstract</h3>\u0000 <figure><div><div><div><picture><source><img></source></picture></div></div></div></figure>\u0000 </div>","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":"13 3","pages":"247 - 256"},"PeriodicalIF":2.7,"publicationDate":"2023-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s41981-023-00267-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4869100","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":"Rapid plugged flow synthesis of nucleoside analogues via Suzuki-Miyaura coupling and heck Alkenylation of 5-Iodo-2’-deoxyuridine (or cytidine)","authors":"Sujeet Gaware,&nbsp;Santosh Kori,&nbsp;Jose Luis Serrano,&nbsp;Rambabu Dandela,&nbsp;Stephen Hilton,&nbsp;Yogesh S. Sanghvi,&nbsp;Anant R. Kapdi","doi":"10.1007/s41981-023-00265-1","DOIUrl":"10.1007/s41981-023-00265-1","url":null,"abstract":"<div><p>Nucleosides modification via conventional cross-coupling has been performed using different catalytic systems and found to take place via long reaction times. However, since the pandemic, nucleoside-based antivirals and vaccines have received widespread attention and the requirement for rapid modification and synthesis of these moieties has become a major objective for researchers. To address this challenge, we describe the development of a rapid flow-based cross-coupling synthesis protocol for a variety of C5-pyrimidine substituted nucleosides. The protocol allows for facile access to multiple nucleoside analogues in very good yields in a few minutes compared to conventional batch chemistry. To highlight the utility of our approach, the synthesis of an anti-HSV drug, BVDU was also achieved in an efficient manner using our new protocol.</p><h3>Graphical abstract</h3>\u0000 <figure><div><div><div><picture><source><img></source></picture></div></div></div></figure>\u0000 </div>","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":"13 3","pages":"293 - 310"},"PeriodicalIF":2.7,"publicationDate":"2023-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s41981-023-00265-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4656267","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":"Leveraging first-principles and empirical models for disturbance detection in continuous pharmaceutical syntheses","authors":"Cameron Armstrong,&nbsp;Yuma Miyai,&nbsp;Anna Formosa,&nbsp;Pratiik Kaushik,&nbsp;Luke Rogers,&nbsp;Thomas D. Roper","doi":"10.1007/s41981-023-00266-0","DOIUrl":"10.1007/s41981-023-00266-0","url":null,"abstract":"<p>A strategy for combining theoretical and empirical model predictions to enhance process monitoring and disturbance detection in continuous pharmaceutical manufacturing is investigated using the first two steps of ciprofloxacin. The first-principles component is a dynamic model that reads in process parameter data and returns a concentration prediction for each species in the system using well-established equations and numerical discretization. The input data for the dynamic model comes from low-cost and reliable sensors that are already commonly deployed in manufacturing scenarios, such as flowmeters and thermocouples, making the approach amenable to potential uniform deployment across numerous manufacturing sites. The empirical component is infrared spectra collected from an inline flow cell that feeds to a partial least squares regression model for product concentration. Process parameter disturbances were introduced while continuously collecting the outlet stream infrared spectra, reagent flowrates, reactor temperature, and running the theoretical and empirical prediction models. Post-processing included the application of changepoint analysis, which is a statistical method of determining changes in the mean of a given time-series dataset. Both types of disturbances were captured as changepoints in the theoretical and empirical model predictions and could be obtained more rapidly by analyzing the residuals between the two predictions. This indicates that the deployment of theoretical models along with empirical is a robust approach for rapidly detecting deviations in the process health, reducing the time that potentially out of specification material is sent downstream. Additionally, by comparing trends in the models with the process parameter data, root-cause analysis can be rapidly carried out for a given disturbance. This places emphasis on holistic process monitoring by incorporating characterization knowledge and understanding into the process along with applying all available data sources to ensure product quality.</p>","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":"13 3","pages":"275 - 291"},"PeriodicalIF":2.7,"publicationDate":"2023-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s41981-023-00266-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4655436","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}