Applying Flow Chemistry: Methods, Materials, and Multistep SynthesisClick to copy article linkArticle link copied!
Abstract
The synthesis of complex molecules requires control over both chemical reactivity and reaction conditions. While reactivity drives the majority of chemical discovery, advances in reaction condition control have accelerated method development/discovery. Recent tools include automated synthesizers and flow reactors. In this Synopsis, we describe how flow reactors have enabled chemical advances in our groups in the areas of single-stage reactions, materials synthesis, and multistep reactions. In each section, we detail the lessons learned and propose future directions.
Cited By
This article is cited by 430 publications.
- Jack J. Bennett, Paul V. Murphy. Flow Chemistry for Synthesis of 2-(C-Glycosyl)acetates from Pyranoses via Tandem Wittig and Michael Reactions. Organic Process Research & Development 2024, 28
(5)
, 1848-1859. https://doi.org/10.1021/acs.oprd.3c00414
- Or Galant, Charles E. Diesendruck, Sabrina Spatari. Environmental Impact Differences of Single-Chain Nanoparticle Production by Batch and Flow Chemistry. Organic Process Research & Development 2024, 28
(5)
, 1607-1617. https://doi.org/10.1021/acs.oprd.3c00244
- Michael Laue, Maximilian Schneider, Markus Gebauer, Winfried Böhlmann, Roger Gläser, Christoph Schneider. General, Modular Access toward Immobilized Chiral Phosphoric Acid Catalysts and Their Application in Flow Chemistry. ACS Catalysis 2024, 14
(8)
, 5550-5559. https://doi.org/10.1021/acscatal.4c00985
- Moseen A. Shaikh, Akash S. Ubale, Boopathy Gnanaprakasam. Amberlyst-A26-Mediated Corey–Chaykovsky Cyclopropanation of 9-Alkylidene-9H-fluorene under Continuous Process. The Journal of Organic Chemistry 2024, 89
(4)
, 2283-2293. https://doi.org/10.1021/acs.joc.3c02260
- Junu Kim, Yusuke Hayashi, Sara Badr, Kazuya Okamoto, Toshikazu Hakogi, Haruo Furukawa, Satoshi Yoshikawa, Hayao Nakanishi, Hirokazu Sugiyama. Hybrid Modeling of an Active Pharmaceutical Ingredient Flow Synthesis in a Ring-Opening Reaction of an Epoxide with a Grignard Reagent. Industrial & Engineering Chemistry Research 2023, 62
(43)
, 17824-17834. https://doi.org/10.1021/acs.iecr.3c02137
- Jacek Zakrzewski, Polina Yaseneva, Connor J. Taylor, Matthew J. Gaunt, Alexei A. Lapkin. Scalable Palladium-Catalyzed C(sp3)–H Carbonylation of Alkylamines in Batch and Continuous Flow. Organic Process Research & Development 2023, 27
(4)
, 649-658. https://doi.org/10.1021/acs.oprd.2c00378
- Arianna Brandolese, David H. Lamparelli, Miquel A. Pericàs, Arjan W. Kleij. Synthesis of Biorenewable Terpene Monomers Using Enzymatic Epoxidation under Heterogeneous Batch and Continuous Flow Conditions. ACS Sustainable Chemistry & Engineering 2023, 11
(12)
, 4885-4893. https://doi.org/10.1021/acssuschemeng.3c00370
- Andrea Laybourn, Karen Robertson, Anna G. Slater. Quid Pro Flow. Journal of the American Chemical Society 2023, 145
(8)
, 4355-4365. https://doi.org/10.1021/jacs.2c13670
- Yong-Ju Kwon, Sang-gi Lee, Won-Suk Kim. Continuous Flow Synthesis of N-Sulfonyl-1,2,3-triazoles for Tandem Relay Cu/Rh Dual Catalysis. The Journal of Organic Chemistry 2023, 88
(2)
, 1200-1214. https://doi.org/10.1021/acs.joc.2c02808
- Alessandra Zizzari, Ermelinda Bloise, Elisabetta Perrone, Diego Romano Perinelli, Marc Schmutz, Valentina Arima, Giuseppe Mele, Luigi Carbone. Environmentally Friendly Method of Assembly of Cardanol and Cholesterol into Nanostructures Using a Continuous Flow Microfluidic Device. ACS Sustainable Chemistry & Engineering 2022, 10
(26)
, 8484-8494. https://doi.org/10.1021/acssuschemeng.2c01554
- Anish Das, Chris Weise, Matthias Polack, Raphael D. Urban, Benjamin Krafft, Sadat Hasan, Hannes Westphal, Rico Warias, Simon Schmidt, Tanja Gulder, Detlev Belder. On-the-Fly Mass Spectrometry in Digital Microfluidics Enabled by a Microspray Hole: Toward Multidimensional Reaction Monitoring in Automated Synthesis Platforms. Journal of the American Chemical Society 2022, 144
(23)
, 10353-10360. https://doi.org/10.1021/jacs.2c01651
- Wanqing Chen, Meysam Sharifzadeh Mirshekarloo, Sally El Meragawi, Geosmin Turpin, Rowan Pilkington, Anastasios Polyzos, Mainak Majumder. Controlled Nanopore Formation in Graphene/Graphene Oxide Nanosheets: Implication for Water Transport. ACS Applied Nano Materials 2022, 5
(3)
, 3811-3823. https://doi.org/10.1021/acsanm.1c04445
- Makoto Ono, Yuji Sumii, Yamato Fujihira, Takumi Kagawa, Hideyuki Mimura, Norio Shibata. Pentafluoroethylation of Carbonyl Compounds Using HFC-125 in a Flow Microreactor System. The Journal of Organic Chemistry 2021, 86
(20)
, 14044-14053. https://doi.org/10.1021/acs.joc.1c00728
- Daniel C. Crowley, Thomas A. Brouder, Aoife M. Kearney, Denis Lynch, Alan Ford, Stuart G. Collins, Anita R. Maguire. Exploiting Continuous Processing for Challenging Diazo Transfer and Telescoped Copper-Catalyzed Asymmetric Transformations. The Journal of Organic Chemistry 2021, 86
(20)
, 13955-13982. https://doi.org/10.1021/acs.joc.1c01310
- Vankudoth Ramesh, Maram Gangadhar, Jagadeesh Babu Nanubolu, Praveen Reddy Adiyala. Visible-Light-Induced Deaminative Alkylation/Cyclization of Alkyl Amines with N-Methacryloyl-2-phenylbenzoimidazoles in Continuous-Flow Organo-Photocatalysis. The Journal of Organic Chemistry 2021, 86
(18)
, 12908-12921. https://doi.org/10.1021/acs.joc.1c01555
- Conrad Kuhwald, Andreas Kirschning. Matteson Reaction under Flow Conditions: Iterative Homologations of Terpenes. Organic Letters 2021, 23
(11)
, 4300-4304. https://doi.org/10.1021/acs.orglett.1c01222
- Martin Mayer, Knut R. Asmis. Online Monitoring of Isomeric Reaction Intermediates. The Journal of Physical Chemistry A 2021, 125
(14)
, 2801-2815. https://doi.org/10.1021/acs.jpca.0c11371
- Huaming Sheng, Emily B. Corcoran, Zachary E. X. Dance, Joseph P. Smith, Zhihao Lin, Victoria Ordsmith, Simon Hamilton, Ping Zhuang. Quantitative Perspective on Online Flow Reaction Profiling Using a Miniature Mass Spectrometer. Organic Process Research & Development 2020, 24
(11)
, 2611-2618. https://doi.org/10.1021/acs.oprd.0c00294
- Nathan Collins, David Stout, Jin-Ping Lim, Jeremiah P. Malerich, Jason D. White, Peter B. Madrid, Mario Latendresse, David Krieger, Judy Szeto, Vi-Anh Vu, Kristina Rucker, Michael Deleo, Yonael Gorfu, Markus Krummenacker, Leslie A. Hokama, Peter Karp, Sahana Mallya. Fully Automated Chemical Synthesis: Toward the Universal Synthesizer. Organic Process Research & Development 2020, 24
(10)
, 2064-2077. https://doi.org/10.1021/acs.oprd.0c00143
- Charlotte S. Teschers, Ryan Gilmour. Flow Photocleavage for Automated Glycan Assembly (AGA). Organic Process Research & Development 2020, 24
(10)
, 2234-2239. https://doi.org/10.1021/acs.oprd.0c00286
- Antonella Carangio, Lee J. Edwards, Eneritz Fernandez-Puertas, Jerome F. Hayes, Maciej M. Kucharski, Graham W. Rutherford, Katherine M. P. Wheelhouse, Glynn D. Williams. Evaluation of Sponge Metal Catalysts in a Trickle Bed Reactor for the Continuous Hydrogenation of an Aliphatic Nitro Intermediate. Organic Process Research & Development 2020, 24
(10)
, 1909-1915. https://doi.org/10.1021/acs.oprd.9b00447
- Manish Walia, Christiana N. Teijaro, Alex Gardner, Thi Tran, Jinfeng Kang, Senzhi Zhao, Sarah E. O’Connor, Vincent Courdavault, Rodrigo B. Andrade. Synthesis of (−)-Melodinine K: A Case Study of Efficiency in Natural Product Synthesis. Journal of Natural Products 2020, 83
(8)
, 2425-2433. https://doi.org/10.1021/acs.jnatprod.0c00310
- Antimo Gioiello, Alessandro Piccinno, Anna Maria Lozza, Bruno Cerra. The Medicinal Chemistry in the Era of Machines and Automation: Recent Advances in Continuous Flow Technology. Journal of Medicinal Chemistry 2020, 63
(13)
, 6624-6647. https://doi.org/10.1021/acs.jmedchem.9b01956
- Benjamin Heinz, Dimitrije Djukanovic, Maximilian A. Ganiek, Benjamin Martin, Berthold Schenkel, Paul Knochel. Selective Acylation of Aryl- and Heteroarylmagnesium Reagents with Esters in Continuous Flow. Organic Letters 2020, 22
(2)
, 493-496. https://doi.org/10.1021/acs.orglett.9b04254
- Lucas
A. Morrill, Robert B. Susick, Jason V. Chari, Neil K. Garg. Total Synthesis as a Vehicle for Collaboration. Journal of the American Chemical Society 2019, 141
(32)
, 12423-12443. https://doi.org/10.1021/jacs.9b05588
- Andrew R. Bogdan, Amanda W. Dombrowski. Emerging Trends in Flow Chemistry and Applications to the Pharmaceutical Industry. Journal of Medicinal Chemistry 2019, 62
(14)
, 6422-6468. https://doi.org/10.1021/acs.jmedchem.8b01760
- Xin-peng Ma, Jin-sha Chen, Xiao-hua Du. A Continuous Flow Process for the Synthesis of Hymexazol. Organic Process Research & Development 2019, 23
(6)
, 1152-1158. https://doi.org/10.1021/acs.oprd.9b00047
- Nirmala Mohanta, Moreshwar B. Chaudhari, Naveen Kumar Digrawal, Boopathy Gnanaprakasam. Rapid and Multigram Synthesis of Vinylogous Esters under Continuous Flow: An Access to Transetherification and Reverse Reaction of Vinylogous Esters. Organic Process Research & Development 2019, 23
(5)
, 1034-1045. https://doi.org/10.1021/acs.oprd.9b00067
- Yuta Endo, Mai Furusawa, Toshiya Shimazaki, Yusuke Takahashi, Yuichi Nakahara, Aiichiro Nagaki. Molecular Weight Distribution of Polymers Produced by Anionic Polymerization Enables Mixability Evaluation. Organic Process Research & Development 2019, 23
(4)
, 635-640. https://doi.org/10.1021/acs.oprd.8b00403
- Maik Pahl, Martin Mayer, Maximilian Schneider, Detlev Belder, Knut R. Asmis. Joining Microfluidics with Infrared Photodissociation: Online Monitoring of Isomeric Flow-Reaction Intermediates. Analytical Chemistry 2019, 91
(5)
, 3199-3203. https://doi.org/10.1021/acs.analchem.8b05532
- Parthasarathy Gandeepan, Thomas Müller, Daniel Zell, Gianpiero Cera, Svenja Warratz, Lutz Ackermann. 3d Transition Metals for C–H Activation. Chemical Reviews 2019, 119
(4)
, 2192-2452. https://doi.org/10.1021/acs.chemrev.8b00507
- Aaron
A. Bedermann, T. Andrew McTeague, Timothy F. Jamison. Automated On-Demand Titration of Organometallic Reagents in Continuous Flow. Organic Process Research & Development 2019, 23
(2)
, 278-282. https://doi.org/10.1021/acs.oprd.8b00434
- Aline A. N. de Souza, Nathalia S. Silva, Andressa V. Müller, André S. Polo, Timothy J. Brocksom, Kleber T. de Oliveira. Porphyrins as Photoredox Catalysts in Csp2–H Arylations: Batch and Continuous Flow Approaches. The Journal of Organic Chemistry 2018, 83
(24)
, 15077-15086. https://doi.org/10.1021/acs.joc.8b02355
- Jorge García-Lacuna, Gema Domínguez, Jaime Blanco-Urgoiti, Javier Pérez-Castells. Cobalt Octacarbonyl-Catalyzed Scalable Alkyne Cyclotrimerization and Crossed [2 + 2 + 2]-Cycloaddition Reaction in a Plug Flow Reactor. Organic Letters 2018, 20
(17)
, 5219-5223. https://doi.org/10.1021/acs.orglett.8b02168
- Juliana
M. de Souza, Timothy J. Brocksom, D.Tyler McQuade, Kleber T. de Oliveira. Continuous Endoperoxidation of Conjugated Dienes and Subsequent Rearrangements Leading to C–H Oxidized Synthons. The Journal of Organic Chemistry 2018, 83
(15)
, 7574-7585. https://doi.org/10.1021/acs.joc.8b01307
- Renan Galaverna, Rafael L. Ribessi, Jarbas J. R. Rohwedder, Julio C. Pastre. Coupling Continuous Flow Microreactors to MicroNIR Spectroscopy: Ultracompact Device for Facile In-Line Reaction Monitoring. Organic Process Research & Development 2018, 22
(7)
, 780-788. https://doi.org/10.1021/acs.oprd.8b00060
- Laurel
M. Heckman, Zhi He, Timothy F. Jamison. Synthesis of Highly Substituted 2-Arylindoles via Copper-Catalyzed Coupling of Isocyanides and Arylboronic Acids. Organic Letters 2018, 20
(11)
, 3263-3267. https://doi.org/10.1021/acs.orglett.8b01132
- Cuiju Zhu, João C.
A. Oliveira, Zhigao Shen, Huawen Huang, Lutz Ackermann. Manganese(II/III/I)-Catalyzed C–H Arylations in Continuous Flow. ACS Catalysis 2018, 8
(5)
, 4402-4407. https://doi.org/10.1021/acscatal.8b00166
- Roger A. Sheldon and John M. Woodley . Role of Biocatalysis in Sustainable Chemistry. Chemical Reviews 2018, 118
(2)
, 801-838. https://doi.org/10.1021/acs.chemrev.7b00203
- Shiguang Pan, Shuo Yan, Takao Osako, and Yasuhiro Uozumi . Batch and Continuous-Flow Huisgen 1,3-Dipolar Cycloadditions with an Amphiphilic Resin-Supported Triazine-Based Polyethyleneamine Dendrimer Copper Catalyst. ACS Sustainable Chemistry & Engineering 2017, 5
(11)
, 10722-10734. https://doi.org/10.1021/acssuschemeng.7b02646
- H. Samuel Ewan, Kiran Iyer, Seok-Hee Hyun, Michael Wleklinski, R. Graham Cooks, and David H. Thompson . Multistep Flow Synthesis of Diazepam Guided by Droplet-Accelerated Reaction Screening with Mechanistic Insights from Rapid Mass Spectrometry Analysis. Organic Process Research & Development 2017, 21
(10)
, 1566-1570. https://doi.org/10.1021/acs.oprd.7b00218
- Matthew B. Plutschack, Bartholomäus Pieber, Kerry Gilmore, and Peter H. Seeberger . The Hitchhiker’s Guide to Flow Chemistry. Chemical Reviews 2017, 117
(18)
, 11796-11893. https://doi.org/10.1021/acs.chemrev.7b00183
- Irina V. Rassokhina, Tatyana A. Tikhonova, Sergey G. Kobylskoy, Igor Yu. Babkin, Valerii Z. Shirinian, Vladimir Gevorgyan, Igor V. Zavarzin, and Yulia A. Volkova . Synthesis of Imidazo[2,1-b]thiazoles via Copper-Catalyzed A3-Coupling in Batch and Continuous Flow. The Journal of Organic Chemistry 2017, 82
(18)
, 9682-9692. https://doi.org/10.1021/acs.joc.7b01762
- Michael R. Chapman, Maria H. T. Kwan, Georgina King, Katherine E. Jolley, Mariam Hussain, Shahed Hussain, Ibrahim E. Salama, Carlos González Niño, Lisa A. Thompson, Mary E. Bayana, Adam D. Clayton, Bao N. Nguyen, Nicholas J. Turner, Nikil Kapur, and A. John Blacker . Simple and Versatile Laboratory Scale CSTR for Multiphasic Continuous-Flow Chemistry and Long Residence Times. Organic Process Research & Development 2017, 21
(9)
, 1294-1301. https://doi.org/10.1021/acs.oprd.7b00173
- Clément Audubert and Hélène Lebel . Mild Esterification of Carboxylic Acids via Continuous Flow Diazotization of Amines. Organic Letters 2017, 19
(16)
, 4407-4410. https://doi.org/10.1021/acs.orglett.7b02231
- Caili Huang, Mengmeng Cui, Zhiwei Sun, Feng Liu, Brett A. Helms, and Thomas P. Russell . Self-Regulated Nanoparticle Assembly at Liquid/Liquid Interfaces: A Route to Adaptive Structuring of Liquids. Langmuir 2017, 33
(32)
, 7994-8001. https://doi.org/10.1021/acs.langmuir.7b01685
- Ahmed Adeyemi, Joakim Bergman, Jonas Brånalt, Jonas Sävmarker, and Mats Larhed . Continuous Flow Synthesis under High-Temperature/High-Pressure Conditions Using a Resistively Heated Flow Reactor. Organic Process Research & Development 2017, 21
(7)
, 947-955. https://doi.org/10.1021/acs.oprd.7b00063
- Naruki Konishi, Tatsuya Shirahata, Masaki Yokoyama, Tatsuya Katsumi, Yoshikazu Ito, Nozomu Hirata, Takashi Nishino, Kazuishi Makino, Noriko Sato, Takayuki Nagai, Hiroaki Kiyohara, Haruki Yamada, Eisuke Kaji, and Yoshinori Kobayashi . Synthesis of Bisdesmosidic Oleanolic Acid Saponins via a Glycosylation-Deprotection Sequence under Continuous Microfluidic/Batch Conditions. The Journal of Organic Chemistry 2017, 82
(13)
, 6703-6719. https://doi.org/10.1021/acs.joc.7b00841
- Sandra Schulze, Maik Pahl, Ferdinand Stolz, Johannes Appun, Bernd Abel, Christoph Schneider, and Detlev Belder . Liquid Beam Desorption Mass Spectrometry for the Investigation of Continuous Flow Reactions in Microfluidic Chips. Analytical Chemistry 2017, 89
(11)
, 6175-6181. https://doi.org/10.1021/acs.analchem.7b01026
- Upendra K. Sharma, Hannes P. L. Gemoets, Felix Schröder, Timothy Noël, and Erik V. Van der Eycken . Merger of Visible-Light Photoredox Catalysis and C–H Activation for the Room-Temperature C-2 Acylation of Indoles in Batch and Flow. ACS Catalysis 2017, 7
(6)
, 3818-3823. https://doi.org/10.1021/acscatal.7b00840
- Gabriel Glotz, Donald J. Knoechel, Philip Podmore, Heidrun Gruber-Woelfler, and C. Oliver Kappe . Reaction Calorimetry in Microreactor Environments—Measuring Heat of Reaction by Isothermal Heat Flux Calorimetry. Organic Process Research & Development 2017, 21
(5)
, 763-770. https://doi.org/10.1021/acs.oprd.7b00092
- Péter Bana, Ágnes Lakó, Nóra Zsuzsa Kiss, Zoltán Béni, Áron Szigetvári, János Kóti, György István Túrós, János Éles, and István Greiner . Synthesis of Urea Derivatives in Two Sequential Continuous-Flow Reactors. Organic Process Research & Development 2017, 21
(4)
, 611-622. https://doi.org/10.1021/acs.oprd.7b00019
- Jian Cao, Gang Xu, Pengyu Li, Minli Tao, and Wenqin Zhang . Polyacrylonitrile Fiber Supported N-Heterocyclic Carbene Ag(I) As Efficient Catalysts for Three-Component Coupling and Intramolecular 1,3-Dipolar Cycloaddition Reactions under Flow Conditions. ACS Sustainable Chemistry & Engineering 2017, 5
(4)
, 3438-3447. https://doi.org/10.1021/acssuschemeng.7b00103
- Rasmus K. Jensen, Nikolaj Thykier, Martin V. Enevoldsen, and Anders T. Lindhardt . A High Mobility Reactor Unit for R&D Continuous Flow Transfer Hydrogenations. Organic Process Research & Development 2017, 21
(3)
, 370-376. https://doi.org/10.1021/acs.oprd.6b00441
- Joseph D’Attoma, Titi Camara, Pierre Louis Brun, Yves Robin, Stéphane Bostyn, Frédéric Buron, and Sylvain Routier . Efficient Transposition of the Sandmeyer Reaction from Batch to Continuous Process. Organic Process Research & Development 2017, 21
(1)
, 44-51. https://doi.org/10.1021/acs.oprd.6b00318
- Sergey A. Dergunov, Alibek T. Khabiyev, Sergey N. Shmakov, Mariya D. Kim, Nasim Ehterami, Mary Clare Weiss, Vladimir B. Birman, and Eugene Pinkhassik . Encapsulation of Homogeneous Catalysts in Porous Polymer Nanocapsules Produces Fast-Acting Selective Nanoreactors. ACS Nano 2016, 10
(12)
, 11397-11406. https://doi.org/10.1021/acsnano.6b06735
- Matthieu Teci, Michael Tilley, Michael A. McGuire, and Michael G. Organ . Handling Hazards Using Continuous Flow Chemistry: Synthesis of N1-Aryl-[1,2,3]-triazoles from Anilines via Telescoped Three-Step Diazotization, Azidodediazotization, and [3 + 2] Dipolar Cycloaddition Processes. Organic Process Research & Development 2016, 20
(11)
, 1967-1973. https://doi.org/10.1021/acs.oprd.6b00292
- Daniel Cortés-Borda, Ksenia V. Kutonova, Corentin Jamet, Marina E. Trusova, Françoise Zammattio, Charlotte Truchet, Mireia Rodriguez-Zubiri, and François-Xavier Felpin . Optimizing the Heck–Matsuda Reaction in Flow with a Constraint-Adapted Direct Search Algorithm. Organic Process Research & Development 2016, 20
(11)
, 1979-1987. https://doi.org/10.1021/acs.oprd.6b00310
- Takahide Fukuyama, Yuki Fujita, Muhammad Abid Rashid, and Ilhyong Ryu . Flow Update for a Cossy Photocyclization. Organic Letters 2016, 18
(20)
, 5444-5446. https://doi.org/10.1021/acs.orglett.6b02727
- Momoe Nakano, Yasuhiro Nishiyama, Hiroki Tanimoto, Tsumoru Morimoto, and Kiyomi Kakiuchi . Remarkable Improvement of Organic Photoreaction Efficiency in the Flow Microreactor by the Slug Flow Condition Using Water. Organic Process Research & Development 2016, 20
(9)
, 1626-1632. https://doi.org/10.1021/acs.oprd.6b00181
- Mao Chen, Mingjiang Zhong, and Jeremiah A. Johnson . Light-Controlled Radical Polymerization: Mechanisms, Methods, and Applications. Chemical Reviews 2016, 116
(17)
, 10167-10211. https://doi.org/10.1021/acs.chemrev.5b00671
- Jianguo Du, Minli Tao, and Wenqin Zhang . Fiber-Supported Acid–Base Bifunctional Catalysts for Efficient Nucleophilic Addition in Water. ACS Sustainable Chemistry & Engineering 2016, 4
(8)
, 4296-4304. https://doi.org/10.1021/acssuschemeng.6b00785
- Aiichiro Nagaki, Yuichi Nakahara, Mai Furusawa, Tomoya Sawaki, Tetsuya Yamamoto, Hideaki Toukairin, Shinsuke Tadokoro, Toshiya Shimazaki, Toshihide Ito, Masakazu Otake, Hidenori Arai, Naoya Toda, Keita Ohtsuka, Yusuke Takahashi, Yuya Moriwaki, Yuta Tsuchihashi, Katsuyuki Hirose, and Jun-ichi Yoshida . Feasibility Study on Continuous Flow Controlled/Living Anionic Polymerization Processes. Organic Process Research & Development 2016, 20
(7)
, 1377-1382. https://doi.org/10.1021/acs.oprd.6b00158
- Matthias Klaper, Werner Fudickar, and Torsten Linker . Role of Distance in Singlet Oxygen Applications: A Model System. Journal of the American Chemical Society 2016, 138
(22)
, 7024-7029. https://doi.org/10.1021/jacs.6b01555
- Andrew R. Bogdan, Manwika Charaschanya, Amanda W. Dombrowski, Ying Wang, and Stevan W. Djuric . High-Temperature Boc Deprotection in Flow and Its Application in Multistep Reaction Sequences. Organic Letters 2016, 18
(8)
, 1732-1735. https://doi.org/10.1021/acs.orglett.6b00378
- Aiichiro Nagaki, Katsuyuki Hirose, Osamu Tonomura, Satoshi Taniguchi, Toshiki Taga, Shinji Hasebe, Norio Ishizuka, and Jun-ichi Yoshida . Design of a Numbering-up System of Monolithic Microreactors and Its Application to Synthesis of a Key Intermediate of Valsartan. Organic Process Research & Development 2016, 20
(3)
, 687-691. https://doi.org/10.1021/acs.oprd.5b00414
- Karin M. Krone, Rico Warias, Cornelia Ritter, Aitao Li, Carlos G. Acevedo-Rocha, Manfred T. Reetz, and Detlev Belder . Analysis of Enantioselective Biotransformations Using a Few Hundred Cells on an Integrated Microfluidic Chip. Journal of the American Chemical Society 2016, 138
(7)
, 2102-2105. https://doi.org/10.1021/jacs.5b12443
- Eleonora Ballerini, Raimondo Maggi, Ferdinando Pizzo, Oriana Piermatti, Dmitri Gelman, and Luigi Vaccaro . An Efficient and Waste-Minimized One-Pot Procedure for the Preparation of N-Boc-γ-amino Alcohols Starting from α,β-Unsaturated Ketones in Flow. Organic Process Research & Development 2016, 20
(2)
, 474-479. https://doi.org/10.1021/acs.oprd.5b00163
- Thomas Westermann and Leslaw Mleczko . Heat Management in Microreactors for Fast Exothermic Organic Syntheses—First Design Principles. Organic Process Research & Development 2016, 20
(2)
, 487-494. https://doi.org/10.1021/acs.oprd.5b00205
- Carl J. Mallia and Ian R. Baxendale . The Use of Gases in Flow Synthesis. Organic Process Research & Development 2016, 20
(2)
, 327-360. https://doi.org/10.1021/acs.oprd.5b00222
- Paolo Filipponi, Antimo Gioiello, and Ian R. Baxendale . Controlled Flow Precipitation as a Valuable Tool for Synthesis. Organic Process Research & Development 2016, 20
(2)
, 371-375. https://doi.org/10.1021/acs.oprd.5b00331
- Michael Tilley, Guanlong Li, Paul Savel, Debasis Mallik, and Michael G. Organ . Intelligent Continuous Collection Device for High-Pressure Flow Synthesis: Design and Implementation. Organic Process Research & Development 2016, 20
(2)
, 517-524. https://doi.org/10.1021/acs.oprd.5b00363
- Bartholomäus Pieber, D. Phillip Cox, and C. Oliver Kappe . Selective Olefin Reduction in Thebaine Using Hydrazine Hydrate and O2 under Intensified Continuous Flow Conditions. Organic Process Research & Development 2016, 20
(2)
, 376-385. https://doi.org/10.1021/acs.oprd.5b00370
- Rosaria Ciriminna, Riccardo Delisi, Yi-Jun Xu, and Mario Pagliaro . Toward the Waste-Free Synthesis of Fine Chemicals with Visible Light. Organic Process Research & Development 2016, 20
(2)
, 403-408. https://doi.org/10.1021/acs.oprd.5b00424
- Neil Hawbaker, Eric Wittgrove, Bianca Christensen, Neal Sach, and Donna G. Blackmond . Dispersion in Compartmentalized Flow Systems: Influence of Flow Patterns on Reactivity. Organic Process Research & Development 2016, 20
(2)
, 465-473. https://doi.org/10.1021/op500360w
- Ádám Georgiádes, Sándor B. Ötvös, and Ferenc Fülöp . Exploring New Parameter Spaces for the Oxidative Homocoupling of Aniline Derivatives: Sustainable Synthesis of Azobenzenes in a Flow System. ACS Sustainable Chemistry & Engineering 2015, 3
(12)
, 3388-3397. https://doi.org/10.1021/acssuschemeng.5b01096
- Paula F. Carneiro, Bernhard Gutmann, Rodrigo O. M. A. de Souza, and C. Oliver Kappe . Process Intensified Flow Synthesis of 1H-4-Substituted Imidazoles: Toward the Continuous Production of Daclatasvir. ACS Sustainable Chemistry & Engineering 2015, 3
(12)
, 3445-3453. https://doi.org/10.1021/acssuschemeng.5b01191
- Marcus Baumann and Ian R. Baxendale . Batch and Flow Synthesis of Pyrrolo[1,2-a]-quinolines via an Allene-Based Reaction Cascade. The Journal of Organic Chemistry 2015, 80
(21)
, 10806-10816. https://doi.org/10.1021/acs.joc.5b01982
- Gang Wang, Cansheng Yuan, Boyi Fu, Luye He, Elsa Reichmanis, Hongzhi Wang, Qinghong Zhang, and Yaogang Li . Flow Effects on the Controlled Growth of Nanostructured Networks at Microcapillary Walls for Applications in Continuous Flow Reactions. ACS Applied Materials & Interfaces 2015, 7
(38)
, 21580-21588. https://doi.org/10.1021/acsami.5b06851
- Alejandro Carnero, Yogesh S. Sanghvi, Vicente Gotor, Susana Fernández, and Miguel Ferrero . Process Development of Biocatalytic Regioselective 5′-O-Levulinylation of 2′-Deoxynucleosides. Organic Process Research & Development 2015, 19
(7)
, 701-709. https://doi.org/10.1021/acs.oprd.5b00152
- Shing-Hing Lau, Alicia Galván, Rohan R. Merchant, Claudio Battilocchio, José A. Souto, Malcolm B. Berry, and Steven V. Ley . Machines vs Malaria: A Flow-Based Preparation of the Drug Candidate OZ439. Organic Letters 2015, 17
(13)
, 3218-3221. https://doi.org/10.1021/acs.orglett.5b01307
- Carlos Eduardo M. Salvador, Bartholomäus Pieber, Philipp M. Neu, Ana Torvisco, Carlos Kleber Z. Andrade, and C. Oliver Kappe . A Sequential Ugi Multicomponent/Cu-Catalyzed Azide–Alkyne Cycloaddition Approach for the Continuous Flow Generation of Cyclic Peptoids. The Journal of Organic Chemistry 2015, 80
(9)
, 4590-4602. https://doi.org/10.1021/acs.joc.5b00445
- ThingSoon Jong and Mark Bradley . Flow-Mediated Synthesis of Boc, Fmoc, and Ddiv Monoprotected Diamines. Organic Letters 2015, 17
(3)
, 422-425. https://doi.org/10.1021/ol503343b
- Kerry Gilmore, Stella Vukelić, D. Tyler McQuade, Beate Koksch, and Peter H. Seeberger . Continuous Reductions and Reductive Aminations Using Solid NaBH4. Organic Process Research & Development 2014, 18
(12)
, 1771-1776. https://doi.org/10.1021/op500310s
- Toshiki Nokami, Kuninobu Matsumoto, Taka-aki Itoh, Yukinobu Fukaya, and Toshiyuki Itoh . Synthesis of Ionic Liquids Equipped with 2-Methoxyethoxymethyl/Methoxymethyl Groups Using a Simple Microreactor System. Organic Process Research & Development 2014, 18
(11)
, 1367-1371. https://doi.org/10.1021/op500131u
- Chenjie Zhu, Chenglun Tang, Zhi Cao, Wei He, Yong Chen, Xiaochun Chen, Kai Guo, and Hanjie Ying . Fully Automated Continuous Meso-flow Synthesis of 5′-Nucleotides and Deoxynucleotides. Organic Process Research & Development 2014, 18
(11)
, 1575-1581. https://doi.org/10.1021/op5002066
- Takahide Fukuyama, Takenori Totoki, and Ilhyong Ryu . Flow Update for the Carbonylation of 1-Silyl-Substituted Organolithiums under CO Pressure. Organic Letters 2014, 16
(21)
, 5632-5635. https://doi.org/10.1021/ol5026958
- Aiichiro Nagaki, Daisuke Ichinari, and Jun-ichi Yoshida . Three-Component Coupling Based on Flash Chemistry. Carbolithiation of Benzyne with Functionalized Aryllithiums Followed by Reactions with Electrophiles. Journal of the American Chemical Society 2014, 136
(35)
, 12245-12248. https://doi.org/10.1021/ja5071762
- Kazuki Hashimoto, Naoya Kumagai, and Masakatsu Shibasaki . Self-Assembled Asymmetric Catalyst Engaged in a Continuous-Flow Platform: An Anti-Selective Catalytic Asymmetric Nitroaldol Reaction. Organic Letters 2014, 16
(13)
, 3496-3499. https://doi.org/10.1021/ol501432h
- Mousa Asadi, Shannon Bonke, Anastasios Polyzos, and David W. Lupton . Fukuyama Reduction and Integrated Thioesterification/Fukuyama Reduction of Thioesters and Acyl Chlorides Using Continuous Flow. ACS Catalysis 2014, 4
(6)
, 2070-2074. https://doi.org/10.1021/cs5004917
- Joël Turconi, Frédéric Griolet, Ronan Guevel, Gilles Oddon, Roberto Villa, Andrea Geatti, Massimo Hvala, Kai Rossen, Rudolf Göller, and Andreas Burgard . Semisynthetic Artemisinin, the Chemical Path to Industrial Production. Organic Process Research & Development 2014, 18
(3)
, 417-422. https://doi.org/10.1021/op4003196
- Semih Sevim, Alessandro Sorrenti, Octavio Graniel, David Muñoz-Rojas, Salvador Pané, Josep Puigmartí-Luis. Role and impact of glass in chemistry, flow chemistry, and microfluidic technologies. 2025, 259-276. https://doi.org/10.1016/B978-0-323-85488-7.00003-9
- Farzad Bastan, Mohammad Kazemeini. Enhanced production of Pirfenidone through a microfluidic system: A novel and thorough chemical kinetics investigation. Chemical Engineering and Processing - Process Intensification 2024, 204 , 109928. https://doi.org/10.1016/j.cep.2024.109928
- Sebastian Gillhuber, Joshua O. Holloway, Kai Mundsinger, Jochen A. Kammerer, Jeffrey R. Harmer, Hendrik Frisch, Christopher Barner-Kowollik, Peter W. Roesky. Visible light photoflow synthesis of a Cu(
ii
) single-chain polymer nanoparticle catalyst. Chemical Science 2024, 15
(37)
, 15280-15290. https://doi.org/10.1039/D4SC03079F
- Adrianna Pach, Aleksandra Szot, Krzysztof Fitzner, Magdalena Luty-Błocho. Opportunities and Challenges in the Synthesis of Noble Metal Nanoparticles via the Chemical Route in Microreactor Systems. Micromachines 2024, 15
(9)
, 1119. https://doi.org/10.3390/mi15091119
- Seungjun Lee, Gyung-Tak Kim, Jueun Kim, Taehoon Kang, Taeshik Earmme, Ye-Jin Hwang. Precision control of molecular weight ratios in fully conjugated block copolymers using flow synthesis. Polymer Chemistry 2024, 15
(12)
, 1166-1172. https://doi.org/10.1039/D3PY01333B
- Firdaus Parveen, Henry J. Morris, Harvey West, Anna G. Slater. Continuous flow synthesis of meso-substituted porphyrins with inline UV–Vis analysis. Journal of Flow Chemistry 2024, 14
(1)
, 23-31. https://doi.org/10.1007/s41981-023-00305-w
- Timo Schuett, Patrick Endres, Tobias Standau, Stefan Zechel, Rodrigo Q. Albuquerque, Christian Brütting, Holger Ruckdäschel, Ulrich S. Schubert. Application of Digital Methods in Polymer Science and Engineering. Advanced Functional Materials 2024, 34
(8)
https://doi.org/10.1002/adfm.202309844
- Yangyang Xu, Fang Zhao, Xuhong Guo. Continuous microflow visible-light photocatalytic N-formylation of piperidine and its kinetic study. Chinese Chemical Letters 2024, 35
(1)
, 108642. https://doi.org/10.1016/j.cclet.2023.108642
- Kangbo Feng, Jiong Chen, Shuangxi Gu, Haifeng Wang, Fen'er Chen. New Progress of Fully Continuous Flow Reaction Technologies in Pharmaceutical Synthesis (2019~2022). Chinese Journal of Organic Chemistry 2024, 44
(2)
, 378. https://doi.org/10.6023/cjoc202307005
Article Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.
Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.
The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated.