Journal of Flow Chemistry最新文献

Expedited access to β-lactams via a telescoped three-component Staudinger reaction in flow 通过伸缩三组分斯陶丁格流动反应快速获得 β-内酰胺

IF 2.7 4区化学

Journal of Flow Chemistry Pub Date : 2024-08-23 DOI: 10.1007/s41981-024-00333-0

Federica Minuto, Andrea Basso, Marcus Baumann

{"title":"Expedited access to β-lactams via a telescoped three-component Staudinger reaction in flow","authors":"Federica Minuto, Andrea Basso, Marcus Baumann","doi":"10.1007/s41981-024-00333-0","DOIUrl":"https://doi.org/10.1007/s41981-024-00333-0","url":null,"abstract":"<p>The Staudinger reaction is widely used for the generation of β-lactams <i>via</i> the thermal cycloaddition of imines with ketenes. Traditionally, it cannot be performed as a multicomponent reaction between aldehydes, amines and ketenes, thus limiting its versatility. Recently we reported for the first time a three-component Staudinger reaction in batch, exploiting a photochemical Wolff rearrangement of diazoketones and an in situ generation of the imine. Here we report an expedited continuous flow approach that generates the crucial ketene intermediate prior to its telescoped reaction with an imine component at ambient temperatures. The imine is prepared by an in situ dehydration between amines and aldehydes in a packed bed reactor containing basic alumina as drying agent. The resulting telescoped flow approach features a fast dehydration reaction (t<sub>Res</sub> ca. 3 min) as well as an efficient Wolff rearrangement using LEDs (420 nm) to afford the desired β-lactam products in less than 30 min which compares favorably with reaction times of several days in batch mode. Flow processing thereby affords a safe and streamlined entry to these important targets and allows their effective generation on gram scale. Moreover, this approach exploits several homogeneous and heterogeneous transformations under mild conditions that generate water and nitrogen gas as the only by-products.</p><h3 data-test=\"abstract-sub-heading\">Graphical abstract</h3>","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142178159","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 “One-Column” grignard generation and reaction in continuous flow 高效的 "一柱式 "连续流格氏剂生成和反应

IF 2.7 4区化学

Journal of Flow Chemistry Pub Date : 2024-08-06 DOI: 10.1007/s41981-024-00332-1

Maolin Sun, Hong Li, Hualiang Chen, Rixin Shao, Fanghua Chen, Xiangmin Sang, Weixia Lin, Yueyue Ma, Ruihua Cheng, Jinxing Ye

引用次数: 0

Two deep learning methods in comparison to characterize droplet sizes in emulsification flow processes 比较两种深度学习方法以确定乳化流动过程中的液滴大小

IF 2.7 4区化学

Journal of Flow Chemistry Pub Date : 2024-07-30 DOI: 10.1007/s41981-024-00330-3

Inga Burke, Thajeevan Dhayaparan, Ahmed S. Youssef, Katharina Schmidt, Norbert Kockmann

{"title":"Two deep learning methods in comparison to characterize droplet sizes in emulsification flow processes","authors":"Inga Burke, Thajeevan Dhayaparan, Ahmed S. Youssef, Katharina Schmidt, Norbert Kockmann","doi":"10.1007/s41981-024-00330-3","DOIUrl":"https://doi.org/10.1007/s41981-024-00330-3","url":null,"abstract":"<p>For reliable supervision in multiphase processes, the droplet size represents a critical quality attribute and needs to be monitored. A promising approach is the use of smart image flow sensors since optical measurement is the most commonly used technique for droplet size distribution determination. For this, two different AI-based object detection methods, Mask RCNN and YOLOv4, are compared regarding their accuracy and their applicability to an emulsification flow process. Iterative optimization steps, including data diversification and adaption of training parameters, enable the models to achieve robust detection performance across varying image qualities and compositions. YOLOv4 shows better detection performances and more accurate results which leads to a wider application window than Mask RCNN in determining droplet sizes in emulsification processes. The final droplet detection model YOLOv4 with Hough Circle (HC) for feature extraction determines reliable droplet sizes across diverse datasets of liquid-liquid flow systems (disperse phase content 1–15 vol.-%, droplet size range 5–150 μm). Evaluating the adjustment of Confidence Scores (CS) ensures statistical representation of even smaller droplets. The droplet detection performance of the final YOLOv4 model is compared with a manual image processing method to validate the model in general as well as its accuracy and reliability. Since YOLOv4 in combination with Hough Circle (HC) shows an accurate and robust detection and size determination, it is applicable for online monitoring and characterization of various liquid-liquid flow processes.</p><h3 data-test=\"abstract-sub-heading\">Graphical abstract</h3>","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141862809","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

Enhanced emulsification process between viscous liquids in an ultrasonic capillary microreactor: mechanism analysis and application in nano-emulsion preparation 超声波毛细管微反应器中粘性液体间的强化乳化过程：机理分析及在纳米乳液制备中的应用

IF 2.7 4区化学

Journal of Flow Chemistry Pub Date : 2024-07-22 DOI: 10.1007/s41981-024-00331-2

Sawita Tanwinit, Shuainan Zhao, Chaoqun Yao, Guangwen Chen

{"title":"Enhanced emulsification process between viscous liquids in an ultrasonic capillary microreactor: mechanism analysis and application in nano-emulsion preparation","authors":"Sawita Tanwinit, Shuainan Zhao, Chaoqun Yao, Guangwen Chen","doi":"10.1007/s41981-024-00331-2","DOIUrl":"https://doi.org/10.1007/s41981-024-00331-2","url":null,"abstract":"<p>Experimental investigations into acoustic cavitation and ultrasound-assited emulsification process between highly viscous liquids were systematically conducted in a laboratory-built ultrasonic microreactor. Under ultrasound irradiation, four cavitation modes were observed simultaneously in soybean oil, including volume, shape, transient collapse and cavitation clouds. Influenced by the intense oscillation of cavitation bubbles, emulsification between viscous liquids was initiated through a dispersion and migration mode. The effects of varying parameters, such as input power, residence time, channel size, HLB value, surfactant concentration and volume ratio between aqueous and oil phase, on the size and polydispersity of prepared emulsion were investigated using water-soybean oil two-phase system as a model. The emulsion size was reduced to 75.60 nm through optimization of experimental parameters. Based on these findings, the ultrasonic microreactor was successfully employed in the preparation of Vitamin E-enriched nano-emulsions. A fine emulsion with low average size (47.69 nm) and good storage stability (60 days) was prepared within 2 min, further indicating the potential application of ultrasonic microreactor in the beverage and pharmaceutical industries.</p>","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141741485","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

Novel insights into acetylation kinetics in a continuous Flow milli-reactor for chemo-enzymatic separation of silybin A/B 连续流动毫升反应器中乙酰化动力学的新见解，用于水飞蓟宾 A/B 的化学酶法分离

IF 2.7 4区化学

Journal of Flow Chemistry Pub Date : 2024-07-22 DOI: 10.1007/s41981-024-00329-w

Michele Emanuele Fortunato, Rita Pagano, Valeria Romanucci, Chiara Licenziato, Armando Zarrelli, Martino Di Serio, Giovanni Di Fabio, Vincenzo Russo

{"title":"Novel insights into acetylation kinetics in a continuous Flow milli-reactor for chemo-enzymatic separation of silybin A/B","authors":"Michele Emanuele Fortunato, Rita Pagano, Valeria Romanucci, Chiara Licenziato, Armando Zarrelli, Martino Di Serio, Giovanni Di Fabio, Vincenzo Russo","doi":"10.1007/s41981-024-00329-w","DOIUrl":"https://doi.org/10.1007/s41981-024-00329-w","url":null,"abstract":"<p>The separation of silybin A (<b>SilA</b>) and B (<b>SilB</b>) diastereomers in optically pure compounds is challenging due to their very similar physical and chemical properties. However, such separation is crucial for evaluating the biological activity of the diasteroisomers <b>SilA</b> and <b>SilB</b>, which show very different performance in pharmacological applications like treating prostate cancer, liver diseases, and Alzheimer’s disease. The most common isolation method is based on high-performance liquid chromatography, but it is slow and has a yield in pure <b>SilB</b> of hundreds of milligrams per day. An alternative chemo-enzymatic separation method, utilizing an immobilized lipase CALB catalyst to stereoselectively acetylate silybin B (<b>1b</b>), offers advantages in terms of higher productivity, selectivity, and scalability, particularly when applied in flow reactors. This study delves into the kinetics of <b>Sil</b> acetylation catalyzed by Novozym 435 in a continuous flow milli-reactor, investigated at various temperatures, volumetric flow rates, and Sil initial concentrations. It is noteworthy that, at the current state of the art, there is a lack of kinetic studies on this reaction, emphasizing the novelty and significance of this work. The kinetic and fluid dynamic parameters were estimated using a non-linear regression analysis of experimental data. The examined reaction showed a null apparent activation energy, explaining the temperature insensitivity of the final acetylated silybin B (<b>1b</b>) concentration. Furthermore, the decrease in steady-state concentrations of the acetylated products with increasing volumetric flow rates indicated that the reaction was occurring in a kinetic regime. Interestingly, a maximum starting Sil concentration was identified, above which there was no favorable impact on conversion.</p>","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141741486","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

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 2.7 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 2.7 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":"https://doi.org/10.1007/s41981-024-00327-y","url":null,"abstract":"<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>","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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 2.7 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

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 2.7 4区化学

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

{"title":"Driving sustainability through adoption of hybrid manufacturing in small molecule API production","authors":"","doi":"10.1007/s41981-024-00325-0","DOIUrl":"https://doi.org/10.1007/s41981-024-00325-0","url":null,"abstract":"<h3>Abstract</h3> <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>","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":null,"pages":null},"PeriodicalIF":2.7,"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 2.7 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":"https://doi.org/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><h3 data-test=\"abstract-sub-heading\">Graphical abstract</h3>\u0000","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":null,"pages":null},"PeriodicalIF":2.7,"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