Dr. Jean-Christophe M. Monbaliu, University of Liège, Belgium, created the Center for Integrated Technology and Organic Synthesis, where he is currently developing new methods for organic synthesis using micro- and mesofluidic reactors. Here he talks to Dr. Vera Koester for ChemViews Magazine about combining fundamental and applied aspects of chemical manufacturing, flow chemistry, and his motivation.
How did your interest in chemistry develop?
I have always been very passionate about all branches of chemistry. Understanding, or at least trying to rationalize, why and how molecules react is very fulfilling. As a Ph.D. student, I explored fundamental aspects of synthetic organic chemistry, combining computational chemistry, mechanism rationalization and synthetic methodology. I became rapidly attracted to applied organic chemistry, and my first post-doc marked a pivotal point in my career in this regard. Since then, I am integrating various aspects of chemical engineering and reactor technology in my research projects.
Can you please briefly explain the focus of your work and why it is of current interest?
My work revolves around synthetic organic chemistry, but is multidisciplinary in essence. My lab is currently working on three mainstream axes: (a) the development of new processes for active pharmaceuticals, (b) the valorization of biomass and platform molecules, and (c) peptide chemistry.
These projects rely on the intimate combination of fundamental and applied aspects of chemical manufacturing, which probably makes them very unique. For instance, some mechanistic aspects are looked at through computational chemistry to identify and suppress side-reactions, hence, improving process efficiency. For instance, computing competitive reaction mechanisms often provides insights on critical process parameters such as reaction temperature or possible additives to increase selectivity. It can contribute to design safer and more sustainable processes.
On the other hand, groundbreaking reactor technologies are also integrated in our projects to enable the handling of hazardous/transient species, and to implement unconventional conditions. In particular, we develop processes using quick and controlled exposure of chemicals to high temperature or alternative activation techniques to speed up reactions, hence, reducing the time frame for chemical processes from several hours to a few minutes, sometimes even less. We also exploit all the assets of flow reactor technologies to design safer processes using highly reactive species (i.e. unstable, rapidly decaying or explosive). One of our objectives is to contribute to the design of compact and highly efficient chemical processes.
Can you explain in more detail for somebody not familiar with flow chemistry what it exactly is and what it is used for?
Flow chemistry is a general term used to describe the performance of a chemical reaction in micro- or mesofluidic reactors (MFRs) in a continuous manner. Unlike traditional macroscopic laboratory equipment, MFRs are characterized by internal channels with well-defined dimensions and architectures (typical diameters ranging from 250 to 800 µm), in which the chemicals are continuously injected and reacted. Such small dimensions account for most of the assets of MFRs in terms of high heat exchange efficiency and fast mixing, with tremendous benefits for processing chemicals. They provide a much more controlled environment for chemical reactions and, despite their small dimensions, their inherent continuous nature enables industrial-scale applications with often superior outputs compared to classical equipment.
As an organic chemist, I was often very frustrated with the inherent limitations of traditional lab batch equipment and strategies. Micro/mesofluidic reactors and continuous flow chemistry drastically expand the horizon of what is achievable in the lab for transforming chemicals, and offer many new options. Flow chemistry also challenges the conventions, and sets a new paradigm for chemical transformations.
Where do you see the field developing over the next 10/15 years?
I often hear criticism from colleagues and coworkers: “Only small molecules can be synthesized in flow” or “Chemistry students have to learn chemistry (i.e., in a conventional way) before playing around with technology”. Well, look at what happened with computers – 15 years ago, only a few enthusiasts would have dreamed of what computers are now capable of achieving. In my opinion, the same stands for flow chemistry – the complexity of what is achievable keeps increasing. Visionary academic institutions, including the University of Liège, have already understood that, and invest in implementing flow chemistry both in early chemistry curricula and in research labs. Flow chemistry is a game changer, not only for research labs, but also for production strategies.
What motivates you in your work?
Challenges. You never get bored with continuous flow chemistry: There are always new challenges to deal with, not only on the molecular level, but also with the technology and its practical implementation in the lab. It forces you to reinvent chemistry. I also enjoy the multidisciplinary aspects of my research.
You have been in the US and in Belgium. Does the relatively small Belgian chemical community have advantages?
It is indeed a small but vibrant and active community. Obviously, we don’t have the same resources and funding as in the US, but we are not that far behind. Being located in the heart of Europe is also a great asset. There are many opportunities to interact with industry and smaller research centers; it is a very fertile place for researchers.
What would you like to be doing ten years from now?
Hopefully, I will still have some time to spend in the lab – that is where I can fully unleash my creativity as a chemist. There are so many reactions that I would love to revisit. A more precise forecast would be difficult – some outstanding encounters have already changed my perspectives. A sure thing is that I will keep multidisciplinary as a credo.
What do you do in your spare time?
I wish I had more – I cherish the time with my wife and son. I also keep being a researcher: I explore new culinary horizons, read a lot, and enjoy spending time outdoors.
Thank you very much for this interview.
Jean-Christophe M. Monbaliu, born in Brussels, Belgium, studied chemistry at the Université catholique de Louvain, Belgium, where he received his Ph.D. in Organic Chemistry. In 2008, he started a postdoc at the Faculty of Bioscience Engineering of the Ghent University, Belgium, where he was later appointed as a postdoctoral associate of the Research Foundation-Flanders. In 2010, he was awarded a Belgian American Educational Foundation fellowship that triggered his relocation to the USA. He joined the Center for Heterocyclic Compounds at the University of Florida, Gainesville, USA. In 2012, he was appointed at the Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
In 2013, he came back to Belgium and settled at the University of Liège. Monbaliu created the Center for Integrated Technology and Organic Synthesis there, where he is currently developing new methods for organic synthesis using micro- and mesofluidic reactors.
Selected Publications
- R. Gérardy, M. Winter, A. Vizza and J.-C. M. Monbaliu, Assessing inter- and intramolecular continuous-flow strategies towards methylphenidate (Ritalin) hydrochlorid, React. Chem. Eng. 2017, ASAP. DOI:10.1039/C6RE00184J
- J.-C. M. Monbaliu, T. Stelzer, E. Revalor, N. Weeranoppanant, K. F. Jensen, A. S. Myerson, Compact and integrated approach for advanced end-to-end production, purification, and aqueous formulation of lidocaine hydrochlorid, Org. Process Res. Dev. 2016, 20, 1347–1353. DOI: 10.1021/acs.oprd.6b00165
- A. Adamo, R. L. Beingessner, M. Behnam, J. Chen, T. F. Jamison, K. F. Jensen, J.-C. M. Monbaliu, A. S. Myerson, E. Revalor, D. R. Snead, T. Stelzer, N. Weeranoppanant, S. Y. Wong, P. Zhang, On-demand continuous flow production of pharmaceuticals in a compact, reconfigurable system, Science 2016, 352, 61–67. DOI: 10.1126/science.aaf1337
- L. Raibaut, M. Cargoët, N. Ollivier, Y.-M. Chang, H. Drobecq, E. Boll, R. Desmet, J.-C. M. Monbaliu, Oleg Melnyk, Accelerating chemoselective peptide bond formation using bis(2-selenylethyl)amido peptide selenoester surrogates, Chem. Sci. 2016, 7, 2657–2665. DOI: 10.1039/C5SC03459K
- L. Di Marco, M. Hans, L. Delaude, J.-C. M. Monbaliu, Continuous-flow N-heterocyclic carbenes generation and organocatalysi, Chem. Eur. J. 2016, 22, 4508–4514. DOI: 10.1002/chem.201505135
- N. Lamborelle, J. Simon, A. Luxen, J.-C. M. Monbaliu, Continuous-flow thermolysis for the preparation of vinylglycine derivative, Org. Biomol. Chem. 2015, 13, 11602–11606. DOI: 10.1039/C5OB02036K
