Flow Chemistry: Volume 2 Flow Chemistry – Applications [2. rev. and exten. edition] 9783110693690, 9783110693614

Citation preview

Ferenc Darvas, György Dormán, Volker Hessel, Steven V. Ley (Eds.) Flow Chemistry

Also of Interest Flow Chemistry. Fundamentals Ferenc Darvas, György Dormán, Volker Hessel, Steven V. Ley (Eds.),  ISBN ----, e-ISBN (PDF) ----, e-ISBN (EPUB) ---- Fundamentals and Applications: also available as a set Set-ISBN ---- Chemical Reaction Engineering. A Computer-Aided Approach Tapio Salmi, Johan Wärnå, José Rafael Hernández Carucci, César A. de Araújo Filho,  ISBN ----, e-ISBN (PDF) ----, e-ISBN (EPUB) ---- Dissipativity in Control Engineering. Applications in Finite- and Infinite-Dimensional Systems Alexander Schaum,  ISBN ----, e-ISBN (PDF) ----, e-ISBN (EPUB) ---- Product-Driven Process Design. From Molecule to Enterprise Edwin Zondervan, Christhian Almeida-Rivera, Kyle Vincent Camarda,  ISBN ----, e-ISBN (PDF) ----, e-ISBN (EPUB) ---- Engineering Catalysis Dmitry Yu. Murzin,  ISBN ----, e-ISBN (PDF) ----, e-ISBN (EPUB) ----

Flow Chemistry

Volume 2: Applications Edited by Ferenc Darvas, György Dormán, Volker Hessel, Steven V. Ley

Editors Dr. Ferenc Darvas InnoStudio Inc. Graphisoft Park Záhony u.7 Budapest 1031 Hungary [email protected] Prof. György Dormán ThalesNano Nanotechnology Inc. Graphisoft Park Zahony u. 7 Budapest 1031 Hungary [email protected]

Prof. Volker Hessel EC&MS Research University of Adelaide Engineering North Building Adelaide, SA 5005 Australia [email protected]

Prof. Steven V. Ley Department of Chemistry University of Cambridge Lensfield Road Cambridge CB2 1EW United Kingdom [email protected]

ISBN 978-3-11-069361-4 e-ISBN (PDF) 978-3-11-069369-0 e-ISBN (EPUB) 978-3-11-069376-8 Library of Congress Control Number: 2021940758 Bibliographic information published by the Deutsche Nationalbibliothek The Deutsche Nationalbibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data are available on the Internet at http://dnb.dnb.de. © 2021 Walter de Gruyter GmbH, Berlin/Boston Cover image: Royalty Free Stock Illustration, ID: 1701258115; designer: jijomathaidesigners, Idukki, India Typesetting: Integra Software Services Pvt. Ltd. Printing and binding: CPI books GmbH, Leck www.degruyter.com

Preface In the last decade, the field of flow chemistry has advanced tremendously and a plethora of applications have been reported in different fields at an unparalleled speed. The characteristics of flow reactors are their exceptionally fast heat and mass transfer. Using so-called microreactors, virtually instantaneous mixing can be achieved for all but the fastest reactions. Similarly, the accumulation of heat, formation of hot spots, and dangers of thermal runaways can be prevented. As a result of the small reactor volumes, the overall safety of the process is significantly improved, even when harsh reaction conditions are used. Thus, this technology offers a unique way to perform ultrafast, exothermic reactions, and allows the execution of reactions which proceed via highly unstable or even explosive intermediates. In addition, efficient telescoping of reaction sequences can be beneficial in terms of minimizing the number of unit operations and avoiding intermediate isolations, which are of particular interest to the pharmaceutical industry where complex multistep sequences often need to be performed. In contrast to what existed only a few years ago, the flow chemistry literature is now full of publications from not only academic groups but also from scientists working in the industry reporting the results of their many different research activities in this field. Despite the fact that there appears to be ample literature in the flow chemistry space ‒ including several extensive monographs, books, and highly cited review articles ‒ there is a lack of suitable textbooks that can be used for teaching purposes and that can explain the fundamentals to newcomers to the field. A complaint often heard from companies is that there are not enough scientists with the unique training and skillsets of a flow chemist, that is, a person having been educated at the interface of synthetic chemistry and chemical engineering, with additional expertise – for example – in analytical chemistry and data-rich experimentation/machine learning. The first edition of the present Graduate Textbook on Flow Chemistry published in 2014 was, therefore, a highly welcome and urgently needed addition to the steadily growing flow chemistry literature! Now, several years on, the second edition of this textbook is released. The original format has been kept the same, namely, a separation into two independent volumes, one dealing with fundamentals, and a second volume, more relating to the many diverse applications that can be realized with this enabling technique. Both volumes not only discuss basic theory but also leave ample room for discussing practical considerations. The individual 22 chapters have been authored by experts in their respective fields, wisely chosen by the editors of this textbook, now ‒ in addition to the original editorial team (Ferenc Darvas, Volker Hessel and György Dormán) ‒ also including Steven Ley.

https://doi.org/10.1515/9783110693690-202

VI

Preface

It is my hope and genuine expectation that the second edition of this Graduate Textbook on Flow Chemistry will become the standard reference work in the field, both at the university level and at other research institutions, where scientists have to get familiar with this rapidly developing field. October, 2021

C. Oliver Kappe Professor University of Graz, Austria

Acknowledgments Since the publication of the first edition of the Graduate Textbook on Flow Chemistry in 2014, the field has advanced tremendously. Thus, the original editors, Ferenc Darvas, György Dormán, and Volker Hessel, joined by Steven V. Ley, have decided to write a new edition, which, besides providing a broad introduction to the subject, also covers the current state of continuous-flow chemistry and also discusses practical considerations and emerging fields. The editors would like to express their sincere gratitude to the many people who have helped to bring this book to fruition. First and foremost, the editors express their heartfelt appreciation to all authors and coauthors for their outstanding contribution, cooperation, enthusiasm, spirit, and constructive comments throughout the planning and writing of the new chapters. A very special thanks are due to all the instrument suppliers for their contribution to the “Technology overview/Overview of the devices” chapter (AM Technology, Corning, Little Things Factory, Microinnova, Syrris, ThalesNano, Uniqsis, Vapourtec, and Zaiput). The editors’ thanks are extended to Szilvia Gilmore (Flow Chemistry Society) for her tireless efforts for coordinating and monitoring the whole project and to Réka Darvas for the great cover design, for the second time. The editors are immensely grateful to the editorial team at De Gruyter Publishing House, especially to Nadja Schedensack, our ever-patient Project Manager, Kristin Berber-Nerlinger, for all the preliminary organization and preparation work, and Karin Sora, Vice President STEM, for the wonderful support and guidance. Finally, the editors want to thank C. Oliver Kappe for the visionary introduction to the textbook.

https://doi.org/10.1515/9783110693690-203

Contents Preface

V

Acknowledgments About the editors Contributing authors

VII XI XIII

Gabriele Laudadio and Timothy Noël 1 Photochemical transformations in continuous-flow reactors

1

Martin Linden, Maximilian M. Hielscher, Balázs Endrődi, Csaba Janáky and Siegfried R. Waldvogel 2 Electrochemical processes in flow 31 D. V. Ravi Kumar, Suneha Patil and Amol A. Kulkarni 3 Continuous flow methods for synthesis of functional materials Tanja Junkers 4 Polymer synthesis in continuous flow

69

99

Genovéva Filipcsei, Zsolt Ötvös, Réka Angi, Balázs Buchholcz, Ádám Bódis and Ferenc Darvas 5 Flow chemistry for nanotechnology 135 Francesco Ferlin, Nam Nghiep Tran, Aikaterini Anastasopoulou, Marc Escribà Gelonch, Daniela Lanari, Federica Valentini, Volker Hessel and Luigi Vaccaro 6 From green chemistry principles to sustainable flow chemistry 159 Antonio M. Rodríguez, Iván Torres-Moya, Angel Díaz-Ortiz, Antonio de la Hoz and Jesús Alcázar 7 Flow chemistry in fine chemical production 193 Kai Wang, Jian Deng, Chencan Du and Guangsheng Luo 8 Scale-up of flow chemistry system 229

X

Contents

Sara Miralles-Comins, Elena Alvarez, Pedro Lozano and Victor Sans 9 Exothermic advanced manufacturing techniques in reactor engineering: 3D printing applications in flow chemistry 259 Francesca Paradisi and László Poppe 10 Continuous-flow biocatalysis with enzymes and cells

277

Steven V. Ley, Oliver S. May, Oliver M. Griffiths and Karin Sowa 11 Outlook, future directions, and emerging applications 313 Answers to the study questions Index

359

347

About the editors Dr. Ferenc Darvas acquired his degrees in Budapest, Hungary (medical chemistry MS, computer sciences BS, PhD in experimental biology). He has been teaching in Hungary, Spain, Austria, and the USA. Dr. Darvas has been involved in introducing microfluidics/flow chemistry methodologies for synthetizing drug candidates since the late 1990s, which led him to found ThalesNano, the inventor of H-Cube®, and the recipient of the R&D100 Award (Technical Oscar), twice. Dr. Darvas was awarded Senator Honoris Causa by the University of Szeged, Hungary (2019), and as Fellow of the American Chemical Society (2016). Dr. Darvas is also the founder and active president of the Flow Chemistry Society, Switzerland, founder and editorial board member of the Journal of Flow Chemistry, founder of the Space Chemistry Consortium, organizer of the Space Chemistry Symposium series at ACS, and initiator of the world’s first anti-Covid drug discovery experiments on ISS.

Prof. György Dormán obtained his PhD in organic chemistry from the Technical University of Budapest, Hungary, in 1986. Between 1982–1988 and 1996–1999, he worked at Sanofi – Chinoin in Budapest in various research positions. In 1988–1989, he spent a postdoctoral year in the UK (University of Salford). Between 1992 and 1996, he was a visiting scientist at the State University of New York, Stony Brook. Between 1999 and 2008, he served ComGenex/AMRI as chief scientific officer. In 2008, he joined ThalesNano and worked as a director of Scientific Innovation until 2015. Since 2016, he is a consultant of InnoStudio Inc. In 2011, he became honorary professor at the University of Szeged. He is an author of 116 scientific papers and book chapters. He is a member of the editorial board of Molecular Diversity and Mini-Reviews in Medicinal Chemistry and member of the advisory board of Journal of Flow Chemistry.

Prof. Volker Hessel studied chemistry at Mainz University and received his PhD in 1993. Further career steps were as follows: 1994, Institut für Mikrotechnik Mainz/D as vice director R&D and director R&D; 2005, Eindhoven University of Technology/NL as professor; 2019, at the University of Warwick/UK as parttime professor. In 2018, he was appointed as deputy dean (research) and professor at the University of Adelaide, Australia. He is research director of Adelaide’s Andy Thomas Centre of Space Resources. Prof. Hessel’s research is on microfluidic and plasma processes and their application to health, chemistry, agrifood, and space. He has published 502 peer-reviewed papers (h-index: 61, Scopus) and was authority in the Parliament Enquete Commission “Future of Chemical Industry.” He received the AIChE Award “Excellence in Process Development Research” and the IUPAC-ThalesNano Prize in Flow Chemistry, as well as the ERC Advanced/Proof of Concept/Synergy and FET OPEN Grants.

https://doi.org/10.1515/9783110693690-205

XII

About the editors

Prof. Steven V. Ley obtained his PhD from Loughborough University, UK, and completed postdoctoral studies at the Ohio State University, USA, and Imperial College London, UK. He was appointed to the staff of Imperial College, London, becoming professor in 1983 and head of department in 1989. He was elected to the Royal Society, London, in 1990, moved to Cambridge University to the 1702 Chair of Chemistry in 1992, and was president of the Royal Society of Chemistry 2000–02. Steve’s research interests include many aspects of organic chemistry, including synthesis, products, methodology, biotransformations, enabling technologies, and, in particular, natural extensive work on flow chemistry. He has been the recipient of numerous international awards, including the IUPAC-ThalesNano Prize in Flow Chemistry and, recently, the prestigious ACS Arthur C. Cope Award.

Contributing authors Jesús Alcázar Discovery Chemistry Janssen Pharmaceutical Companies of J&J Janssen-Cilag, S.A. 45007 Toledo, Spain [email protected] Chapter 7

Ferenc Darvas InnoStudio Inc. Graphisoft Park Záhony u.7 1031 Budapest, Hungary [email protected] Chapter 5

Elena Alvarez Dept Bioquimica, Biologia Molecular e Inmunologia Facultad de Quimica Universidad de Murcia Campus Reg Excelencia Int Mare Nostrum E-30100 Murcia, Spain Chapter 9

Jian Deng Department of Chemical Engineering State Key Laboratory of Chemical Engineering Tsinghua University Beijing 100084, China [email protected] Chapter 8

Aikaterini Anastasopoulou Department of Chemical and Biomolecular Engineering University of Delaware Newark, DE 19716, USA [email protected] Chapter 6 Ádám Bódis InnoStudio Inc. Graphisoft Park Záhony u.7 1031 Budapest, Hungary [email protected] Chapter 5 Balázs Buchholcz InnoStudio Inc. Graphisoft Park Záhony u.7 1031 Budapest, Hungary [email protected] Chapter 5

https://doi.org/10.1515/9783110693690-206

Angel Díaz-Ortiz Facultad de Ciencias y Tecnologías Químicas Universidad de Castilla-La Mancha 13071 Ciudad Real, Spain [email protected] Chapter 7 Chencan Du Department of Chemical Engineering State Key Laboratory of Chemical Engineering Tsinghua University Beijing 100084, China [email protected] Chapter 8 Balázs Endrődi Department of Physical Chemistry and Materials Science University of Szeged Szeged Hungary [email protected] Chapter 2

XIV

Contributing authors

Francesco Ferlin Laboratory of Green S.O.C. Dipartimento di Chimica, Biologia e Biotecnologie Università degli Studi di Perugia Perugia, Italy [email protected] Chapter 6 Genovéve Filipcsei Tavanta Therapeutics Hungary Inc. Madarász Viktor u. 47 1138 Budapest, Hungary [email protected] Chapter 5 Marc Escribà Gelonch Laboratoire de Génie des Procédées Catalytiques Centre National de la Recherche Scientifique (CNRS) CPE-Lyon, France [email protected] Chapter 6 Oliver M. Griffiths Yusuf Hamied Department of Chemistry University of Cambridge Cambridge, CB2 1EW, UK [email protected] Chapter 11 Volker Hessel School of Chemical Engineering and Advanced Materials University of Adelaide Adelaide, Australia and School of Engineering University of Warwick Coventry CV4 7AL, UK [email protected] Chapter 6

Maximilian Hielscher Department of Chemistry Johannes Gutenberg University Mainz Germany [email protected] Chapter 2 Antonio de la Hoz Facultad de Ciencias y Tecnologías Químicas Universidad de Castilla-La Mancha 13071 Ciudad Real, Spain [email protected] Chapter 7 Csaba Janáky Department of Physical Chemistry and Materials Science University of Szeged Szeged Hungary [email protected] Chapter 2 Tanja Junkers Polymer Reaction Design Group School of Chemistry Monash University Clayton, VIC 3800, Australia [email protected] Chapter 4 Amol A. Kulkarni Chem. Eng. Proc. Dev. Division CSIR-National Chemical Laboratory Pashan, Pune, India [email protected] Chapter 3 Daniela Lanari Laboratory of Green S.O.C. Dipartimento di Chimica, Biologia e Biotecnologie Università degli Studi di Perugia Perugia, Italy [email protected] Chapter 6

Contributing authors

Gabriele Laudadio Flow Chemistry Van’t Hoff Institute for Molecular Sciences University of Amsterdam Amsterdam, The Netherlands [email protected] Chapter 1

Sara Miralles-Comins Institute of Advanced Materials (INAM) Universitat Jaume I Avda. Sos Baynat s/n 12071 Castellon, Spain [email protected] Chapter 9

Steven V. Ley Yusuf Hamied Department of Chemistry University of Cambridge Cambridge CB2 1EW, UK [email protected] Chapter 11

Timothy Noël Flow Chemistry Van’t Hoff Institute for Molecular Sciences University of Amsterdam Amsterdam, The Netherlands [email protected] Chapter 1

Martin Linden Department of Chemistry Johannes Gutenberg University Mainz Mainz, Germany [email protected] Chapter 2

Zsolt Ötvös Tavanta Therapeutics Hungary Inc. Madarász Viktor u. 47 1138 Budapest, Hungary [email protected] Chapter 5

Guangsheng Luo Department of Chemical Engineering State Key Laboratory of Chemical Engineering Tsinghua University Beijing 100084, China [email protected] Chapter 8 Pedro Lozano Dept Bioquimica, Biologia Molecular e Inmunologia Facultad de Quimica Universidad de Murcia Campus Reg Excelencia Int Mare Nostrum E-30100 Murcia, Spain Chapter 9 Oliver S. May Yusuf Hamied Department of Chemistry University of Cambridge Cambridge CB2 1EW, UK [email protected] Chapter 11

XV

Francesca Paradisi Department of Chemistry and Biochemistry University of Bern Bern, Switzerland [email protected] Chapter 10 Suneha Patil Chem. Eng. Proc. Dev. Division CSIR-National Chemical Laboratory Pashan, Pune, India [email protected] Chapter 3 László Poppe Department for Organic Chemistry and Technology Budapest University of Technology and Economics Budapest, Hungary [email protected] Chapter 10

XVI

Contributing authors

Darbha Venkata Ravi Kumar AMRITA Vishwa Vidyapeetham Chennai Campus Thiruvallur, Chennai Tamil Nadu, India [email protected] Chapter 3 Antonio M. Rodríguez Instituto Regional de Investigación Científica Aplicada (IRICA) Universidad de Castilla-La Mancha 13071 Ciudad Real, Spain [email protected] Chapter 7 Victor Sans Institute of Advanced Materials (INAM) Universitat Jaume I Avda. Sos Baynat s/n 12071 Castellon, Spain [email protected] Chapter 9 Karin Sowa Faculty of Chemistry and Pharmacy Institute for Organic Chemistry University of Münster Münster, Germany [email protected] Chapter 11 Iván Torres-Moya Facultad de Ciencias y Tecnologías Químicas Universidad de Castilla-La Mancha 13071 Ciudad Real, Spain [email protected] Chapter 7

Nam Nghiep Tran School of Chemical Engineering and Advanced Materials University of Adelaide Adelaide, Australia and Department of Chemical Engineering Can Tho University Can Tho, Vietnam [email protected] Chapter 6 Luigi Vaccaro Laboratory of Green S.O.C. Dipartimento di Chimica, Biologia e Biotecnologie Università degli Studi di Perugia Perugia, Italy [email protected] Chapter 6 Federica Valentini Laboratory of Green S.O.C. Dipartimento di Chimica, Biologia e Biotecnologie Università degli Studi di Perugia Perugia, Italy [email protected] Chapter 6 Siegfried R. Waldvogel Department of Chemistry Johannes Gutenberg University Mainz Mainz, Germany [email protected] Chapter 2 Kai Wang Department of Chemical Engineering State Key Laboratory of Chemical Engineering Tsinghua University Beijing 100084, China [email protected] Chapter 8

Gabriele Laudadio and Timothy Noël

1 Photochemical transformations in continuous-flow reactors 1.1 Introduction The use of photons to overcome kinetic and thermodynamic barriers has provided diverse opportunities to access novel and unique synthetic pathways to organic chemists for the construction of organic molecules [1]. In the past decade, photocatalysis has become a vibrant research field with many researchers from both academia and industry implementing this mode of molecule activation into their scientific programs [2]. Despite the rapid progress in terms of synthetic chemistry, some technological issues were encountered. Most of these issues have been associated with the Bouguer–Lambert– Beer law (vide infra), which dictates that photons will be absorbed as they travel through the reaction medium. This means that the light intensity will rapidly diminish with increasing reactor diameters. Hence, photochemistry is perceived as inherently not scalable. However, this statement can be regarded as false when using continuousflow reactors with small internal dimensions, for example, micro- or millireactor technology [3]. In such reactors, reactants can be continuously introduced into the narrow channels (i.e.,