Journal of Flow Chemistry最新文献_第2页

Functionalization of unsaturated carbon–carbon bonds by continuous-flow ozonolysis 通过连续流臭氧分解使不饱和碳-碳键官能化

IF 2 4区化学

Journal of Flow Chemistry Pub Date : 2024-07-15 DOI: 10.1007/s41981-024-00328-x

Caio M. Pacheco, Fernanda A. Lima, Mauro R. B. P. Gomez, Lucas B. Barbosa, Raquel A. C. Leão, Rodrigo O. M. A. de Souza

引用次数: 0

Continuous preparation and reaction of nonaflyl azide (NfN3) for the synthesis of organic azides and 1,2,3-triazoles 用于合成有机叠氮化物和 1,2,3-三唑的壬烯呋喃叠氮化物 (NfN3) 的连续制备和反应

IF 2 4区化学

Journal of Flow Chemistry Pub Date : 2024-07-04 DOI: 10.1007/s41981-024-00327-y

Sebastian P. Green, Hannah C. Broderick, Katherine M. P. Wheelhouse, Jason P. Hallett, Philip W. Miller, James A. Bull

{"title":"Continuous preparation and reaction of nonaflyl azide (NfN3) for the synthesis of organic azides and 1,2,3-triazoles","authors":"Sebastian P. Green, Hannah C. Broderick, Katherine M. P. Wheelhouse, Jason P. Hallett, Philip W. Miller, James A. Bull","doi":"10.1007/s41981-024-00327-y","DOIUrl":"10.1007/s41981-024-00327-y","url":null,"abstract":"<div><p>Organic azides are widely used in organic synthesis. Continuous flow processing can be used to bypass their isolation, and can therefore be useful in mitigating the hazards associated with these potentially toxic and explosive reagents. Nonaflyl azide has been reported as an effective, bench-stable, and relatively safe diazo transfer reagent that can be useful in the preparation of azides from amines and so avoid the use of alkyl halides. Here we demonstrate the synthesis and purification of nonaflyl azide in continuous flow with isolation of the neat, pure reagent by membrane filtration. The neat reagent was used in the preparation of organic azides from primary amines, and then applied to the synthesis of triazoles. A variety of triazoles, including the antiseizure drug Rufinamide, were prepared from primary amines and alkynes via the CuAAC click reaction in a semi-batch parallel array without isolation of alkyl azide intermediates. A telescoped two-stage continuous flow process was also designed and demonstrated to form triazoles via the same CuAAC reaction, which avoids the handling of the intermediate reactive azides.</p></div>","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":"14 3","pages":"559 - 568"},"PeriodicalIF":2.0,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s41981-024-00327-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141546631","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}

引用次数: 0

Performance of different microfluidic devices in continuous liquid-liquid separation 不同微流控装置在连续液-液分离中的性能

IF 2 4区化学

Journal of Flow Chemistry Pub Date : 2024-06-13 DOI: 10.1007/s41981-024-00326-z

Bastian Oldach, Ya-Yu Chiang, Leon Ben-Achour, Tai-Jhen Chen, Norbert Kockmann

{"title":"Performance of different microfluidic devices in continuous liquid-liquid separation","authors":"Bastian Oldach, Ya-Yu Chiang, Leon Ben-Achour, Tai-Jhen Chen, Norbert Kockmann","doi":"10.1007/s41981-024-00326-z","DOIUrl":"10.1007/s41981-024-00326-z","url":null,"abstract":"<div><p>Droplet-based microfluidics exhibit numerous benefits leading to relevant innovations and many applications in various fields. The precise handling of droplets in capillaries, including droplet formation, manipulation, and separation, is essential for successful operation. Only a few reports are known concerning the separation of segmented flows, particularly the continuous separation of droplets, which is of high interest regarding the control of biochemical and chemical reactions or other applications where the contact time of the involved phases is crucial. Here, the separation must be flexible and adjusted to different flow parameters, such as the surface tension, the volumetric flow rates, and their ratios. This contribution presents two novel open-source approaches based on additive manufacturing and mechanical deforming for continuous liquid–liquid separation under various flow conditions. The Laplace pressure is the driving force for the separation, which is adjusted to the flow conditions by adapting the distance of pinning points provided by the design of the devices. Details of the device design and experimental setup are shown along with limitations to promote further development and to increase availability for researchers. With the right parameters, sophisticated separations can be realized by inexpensive laboratory equipment and simple control of them. It was found that the distance between the pinning points needs to enlarged for increasing volumetric flow rates and reduced for higher viscosities of the continuous phase respectively higher amounts of the dispersed phase. The open source approach of this article expands the exploration space in addition to commercially available phase separators only available to a selected group of people.</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 3","pages":"547 - 557"},"PeriodicalIF":2.0,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s41981-024-00326-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141350167","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}

引用次数: 0

Continuous flow process optimization aided by machine learning for a pharmaceutical intermediate 利用机器学习优化制药中间体的连续流工艺

IF 2 4区化学

Journal of Flow Chemistry Pub Date : 2024-05-13 DOI: 10.1007/s41981-024-00318-z

Jinlin Zhu, Chenyang Zhao, Li Sheng, Dadong Shen, Gang Fan, Xufeng Wu, Lushan Yu, Kui Du

{"title":"Continuous flow process optimization aided by machine learning for a pharmaceutical intermediate","authors":"Jinlin Zhu, Chenyang Zhao, Li Sheng, Dadong Shen, Gang Fan, Xufeng Wu, Lushan Yu, Kui Du","doi":"10.1007/s41981-024-00318-z","DOIUrl":"10.1007/s41981-024-00318-z","url":null,"abstract":"<div><p>In this paper, we demonstrate the use of machine learning to optimize the continuous flow process of a crucial intermediate in the production of Nemonoxacin. Our focus is to achieve the good yield and enantioselectivity in the construction of chiral methyl group utilize the initial 29 experimental datasets and consider six important variables. Employing Single-Objective Bayesian optimization (SOBO), we achieved an impressive predicted yield of up to 89.7%, which is consistent with the experimental results, with a yield of 89.5%. Additionally, A Multi-Objective Bayesian Optimization (MOBO) algorithm, namely qNEHVI, to strike a balance between yield and enantioselectivity in the continuous flow system is applied. The algorithm’s prediction, with a yield of 81.8% and enantioselectivity of 97.85%, was experimentally validated, yielding 83.8% and 97.2%, respectively. This study effectively demonstrates that Bayesian optimization is a powerful tool for optimizing the continuous process in the production of active pharmaceutical ingredients (APIs).</p></div>","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":"14 3","pages":"539 - 546"},"PeriodicalIF":2.0,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140934607","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}

引用次数: 0

Driving sustainability through adoption of hybrid manufacturing in small molecule API production 在小分子原料药生产中采用混合生产技术，推动可持续发展

IF 2 4区化学

Journal of Flow Chemistry Pub Date : 2024-03-22 DOI: 10.1007/s41981-024-00325-0

Svetlana Borukhova, Robert Sebastian Rönnback

{"title":"Driving sustainability through adoption of hybrid manufacturing in small molecule API production","authors":"Svetlana Borukhova, Robert Sebastian Rönnback","doi":"10.1007/s41981-024-00325-0","DOIUrl":"10.1007/s41981-024-00325-0","url":null,"abstract":"<div><p>Pharmaceutical industry is challenged by the rising development costs, strict regulatory and environmental requirements all while racing to deliver complex molecules to market. The need to be the first-in-class brings about shorter lifetime to the launched products in favor of better functioning followers. In addition, a shift from large volume blockbusters towards small volume production of complex molecules presents a unique opportunity to challenge the status quo in pharmaceutical manufacturing. Traditional batch manufacturing, while foundational, presents hurdles in scaling and efficiency, particularly for demanding reactions. Continuous manufacturing has emerged as a promising alternative, delivering better control and uniformity of operating conditions, mirroring the efficiencies found in small-scale batch reactors. However, continuous manufacturing is not universally applicable. As a solution, a combination of the two into hybrid manufacturing processes, appears to fill this gap effectively. While the concept of hybrid manufacturing is not new, the current perspective adds an additional angle to the integration of both technologies. Authors propose to sustain the continuity of the operation for batch mode processes by decreasing the reactor size and increasing the level of automation. Furthermore, modular fabrication of smaller-footprint technological platforms is expected to synergize other advancements in the field, such as digitalization, automation, and standardization. As a result, a leap towards the implementation of advanced manufacturing to drive sustainability in pharmaceutical industry is more tangible than ever.</p></div>","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":"14 1","pages":"303 - 312"},"PeriodicalIF":2.0,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140202863","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}

引用次数: 0

Efficient pinnick oxidation by a superheated micro-reaction process 通过过热微反应过程实现高效松脂氧化

IF 2 4区化学

Journal of Flow Chemistry Pub Date : 2024-03-20 DOI: 10.1007/s41981-024-00324-1

Jinpei Huang, Yongxiang Li, Yuanzheng Zhou, Yifu Yu, Jingyi Feng, Yongjun Zhang, Yifeng Zhou

{"title":"Efficient pinnick oxidation by a superheated micro-reaction process","authors":"Jinpei Huang, Yongxiang Li, Yuanzheng Zhou, Yifu Yu, Jingyi Feng, Yongjun Zhang, Yifeng Zhou","doi":"10.1007/s41981-024-00324-1","DOIUrl":"10.1007/s41981-024-00324-1","url":null,"abstract":"<p>The Pinnick oxidation, due to its tolerance for sensitive functional groups, is widely used in the process of oxidizing <i>α</i>,<i>β</i>-unsaturated aldehydes to corresponding carboxylic acids. The reaction reagents typically include sodium chlorite, buffer salts, and a scavenger. However, the controllability of Pinnick oxidation in the batch reaction process is poor due to the inherent limitations of the reactor’s performance. This leads to potential safety risks and necessitates the reaction to proceed slowly under conditions of low temperature and low concentration. In this work, we introduced a new continuous micro-reaction process to intensify the Pinnick oxidation. The water-soluble crotonic acid was selected as a typical object of study. Through the study of reaction parameters and the construction of a micro-reaction system, efficient continuous process was achieved under high-temperature and high-pressure conditions for the first time. Compared to the batch process, the reaction benefited from the superheated condition resulting in a significant acceleration of the reaction rate, efficient gas–liquid interphase mass transfer allowing for effective utilization of the generated chlorine dioxide, and the inherent safety of the microreactor enabling an increase in reaction concentration. In addition, the buffer salts used in the Pinnick oxidation has been successfully replaced by hydrochloric acid and applied to the continuous flow. This work shows the tremendous potential of microreactors in utilizing harsh reaction conditions to achieve process intensification.</p>","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":"14 3","pages":"529 - 537"},"PeriodicalIF":2.0,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140203177","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}

引用次数: 0

Rapid prototyping of a modular optical flow cell for image-based droplet size measurements in emulsification processes 用于乳化过程中基于图像的液滴粒度测量的模块化光学流动池的快速原型开发

IF 2 4区化学

Journal of Flow Chemistry Pub Date : 2024-03-19 DOI: 10.1007/s41981-024-00323-2

Inga Burke, Christina Assies, Norbert Kockmann

{"title":"Rapid prototyping of a modular optical flow cell for image-based droplet size measurements in emulsification processes","authors":"Inga Burke, Christina Assies, Norbert Kockmann","doi":"10.1007/s41981-024-00323-2","DOIUrl":"10.1007/s41981-024-00323-2","url":null,"abstract":"<div><p>Emulsification processes are often found in the process industry and their evaluation is crucial for product quality and safety. Numerous methods exist to analyze critical quality attributes (CQA) such as the droplet sizes and droplet size distribution (DSD) of an emulsification process. During the emulsification process, the optical process accessibility may be limited due to high disperse phase content of liquid-liquid systems. To overcome this challenge, a modular, optical measurement flow cell is presented to widen the application window of optical methods in emulsification processes. In this contribution, the channel geometry is subject of optimization to modify the flow characteristics and produce high optical quality. In terms of rapid prototyping, an iterative optimization procedure via SLA-3D printing was used to increase operability. The results demonstrated that the flow cell resulting from the optimization procedure provides a broad observation window for droplet detection.</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 3","pages":"515 - 528"},"PeriodicalIF":2.0,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s41981-024-00323-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140166040","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}

引用次数: 0

Emerging Investigators in Flow Chemistry 2023 2023 年流动化学领域的新兴研究人员

IF 2 4区化学

Journal of Flow Chemistry Pub Date : 2024-03-18 DOI: 10.1007/s41981-024-00322-3

Cecilia Bottecchia, Wu Jie, Luca Capaldo

引用次数: 0

Determination of micromixing times in commercially available continuous-flow mixers: evaluation of the incorporation and interaction by exchange with the mean model 确定市售连续流动混合器的微混合时间：通过与平均模型交换来评估混合和相互作用

IF 2 4区化学

Journal of Flow Chemistry Pub Date : 2024-03-06 DOI: 10.1007/s41981-024-00321-4

Jasper H. A. Schuurmans, Micha Peeters, Matthieu Dorbec, Koen P. L. Kuijpers

{"title":"Determination of micromixing times in commercially available continuous-flow mixers: evaluation of the incorporation and interaction by exchange with the mean model","authors":"Jasper H. A. Schuurmans, Micha Peeters, Matthieu Dorbec, Koen P. L. Kuijpers","doi":"10.1007/s41981-024-00321-4","DOIUrl":"10.1007/s41981-024-00321-4","url":null,"abstract":"<div><p>To understand and predict the effect of mixing in a mixer or reactor, characterization is essential. The Villermaux-Dushman system of competitive parallel reactions is one of the most frequently used methods to obtain details on the micromixing behavior in mixers and reactors. For quantitative information, a model can convert experimental data into a universal micromixing time, which can be used to compare set-ups and reaction conditions. Different modeling approaches have been developed over time and complicate the comparison of results with newfound micromixing times. In this work, these different modeling approaches are elaborated upon to show the significant differences that can arise between these models. Special attention goes out to a model for continuous-flow mixers, which operates differently and has different characteristics compared to mixing in conventional batch reactors. The volume fractions of the two phases being mixed are generally closer to one another in flow mixers, requiring adaptations in the experimental and modeling approach. Several models were tested, after which the interaction by exchange with the mean (IEM) model was selected. Using this model, micromixing times were determined for a variety of continuous-flow mixers under different operating conditions.</p></div>","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":"14 1","pages":"33 - 42"},"PeriodicalIF":2.0,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140046793","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}

引用次数: 0

Access semi-stabilized and unstabilized diazo compounds using iodosylbenzene 利用碘代苯获得半稳定和非稳定重氮化合物

IF 2 4区化学

Journal of Flow Chemistry Pub Date : 2024-02-29 DOI: 10.1007/s41981-024-00320-5

Laurent Vinet, Emmanuelle M. D. Allouche, Vanessa Kairouz, André B. Charette

引用次数: 0