By Brandon Jolly
Our dependence on the chemical industry for our everyday products, ranging from plastics to pharmaceuticals, will not fade away anytime soon, if at all. Thus, it is imperative that the chemical manufacturing industry adapt methods of sustainable processes that minimize waste while maintaining, or even improving productivity. Two particular methods of chemical synthesis that have gained significant attention within the last few decades are continuous flow synthesis and electrochemistry. In this blog post, we aim to introduce these two subjects and discuss their benefits to chemical synthesis in the context of sustainability. Specifically, this post is a supplement to a video about flow electrochemistry posted on our twitter page.
Continuous Flow Processing
To begin to understand the benefits of implementing continuous flow in chemical synthesis, let’s use an everyday task as an analogy. Imagine you want to cook two eggs. A small pan would suffice to cook them in reasonable time. Now imagine you need to cook four, or even up to eight eggs. You’ll need a bigger pan to ensure the eggs cook quickly and evenly. Now let’s say you need to make one hundred eggs. How big of a pan would you need? If you don’t have a big pan, how long would it take to cook all one hundred eggs in a reasonably large sized pan or how much extra heat (cost and energy consumption) would be needed? In addition to practical, time, and energy related concerns, it would be difficult to get all one hundred eggs to be cooked evenly.
What if there was some way you could efficiently cook two eggs at a time on a small pan, and then remove the cooked ones and add in more uncooked ones? You could simply cook two, take them out, then add two more manually. However, imagine a scenario in which you could remove the cooked ones and add in uncooked ones in a continuous, and controlled manner. This hypothetical scenario would allow you to efficiently and evenly cook without taking a ridiculous amount of time and excess energy, making it more sustainable (though we hope you enjoy). This is more or less what continuous flow allows chemists to do.
We can directly translate this idea to a model chemical reaction. Take for example a simple chemical reaction, conversion of compound A plus B produces C at some specific temperature (T) above room temperature (r.t.), shown in Figure 1. Typically conducted in beakers or flasks, the transfer of heat in such a chemical reaction is inefficient as it’s scaled up, as discussed in the cooking example. In addition, one issue that did not arise in the prior example is the efficiency by which species A and B are mixed, which is also required for the reaction to occur and may also be a limiting factor when scaling up. This is precisely where continuous flow is employed. Instead of using a larger beaker or flask, and ramping up temperature or waiting an excessive amount of time, we can simply use a minimal sized reactor (usually narrow tubing, labeled as reactor coil) and continuously pump any desired volume through it, shown in Figure 1. In doing so, continuous flow presents itself as a method to maintain (or often improve)1, 2 efficiency in chemical reactions when translating research lab scale reactions to the industrial scale. The benefits of continuous flow span beyond what is discussed here, and it is expected that it will be continuously flowed (pun intended) into academic and industrial settings.
Electron transfer at the molecular level is often a fundamental step in chemical reactions (labeled as redox reactions). Chemists have usually carried out these reactions by adding an equivalent or excess amount of oxidants (molecules that remove electrons) and reductants (molecules that donate electrons), collectively termed “redox reagents”. This poses adverse environmental effects as the redox reagents are not incorporated into the final product, and simply serve to add or remove electrons. One way to avoid this undesired waste is to use electrochemistry, which uses conductive materials (electrodes) and electricity to carry out redox reactions. This is more sustainable than adding redox reagents as ideally the electrodes can be removed from the reaction, cleaned, and used again. Further, as solar electricity continues to be developed and improved, there’s a potential for the electricity applied to these electrodes to come from renewable means. Thus, electrochemistry presents itself as a green alternative in chemical synthesis. For more on electrochemistry as a green synthetic method, check out one of our prior blog posts.
In addition to sustainability, electrochemistry (redox reactions in general) has been used as a way to switch reactions on and off, as reactivity is often related to the precise amount of electrons a molecule has.3 This allows precise control over when particular reactions occur.
Combining Continuous Flow and Electrochemistry: Relation to Integrated Catalysis
The synergism between continuous flow and electrochemistry has been recently explored for the efficient and sustainable production of primarily pharmaceuticals,4 as well as other fine chemicals.1 However, as the name of our center suggests, we are interested in integrating catalytic systems for the production of plastics and chemicals. In this subsection, we’ll briefly introduce how continuous flow and electrochemistry align with our interest in integrated catalysis.
Put simply, integrated catalysis refers to the idea of getting two or more catalyzed chemical reactions to work in tandem to transform a particular chemical to a desired product through multiple reactions, all in one reaction vessel (see webinar by Prof. Paula Diaconescu). Traditionally, if multiple chemical reactions are required to transform some starting compound to a desired product, each reaction is carried out one by one, with some separation/purification work in between each step. Thus, the potential benefits of doing so are to reduce the time needed and waste generated in traditional chemical synthesis, as each step requires particular solvents and additives, which may not always be recovered.
Though integrating catalytic systems poses challenges at the chemical level related to compatibility of solvents and additives, it also presents a technical, more engineering challenge. Continuous flow can assist with combining catalytic systems in somewhat of an assembly line fashion, shown schematically in Figure 2. Catalysts may be attached to sections of surfaces through various methods (see webinar by Prof. Alex Miller on surface attachment strategies), which may be incorporated into a flow reactor in which flow provides a mode of transport between catalytic sites (see webinar by Prof. Chong Liu on microscopic mass transport in integrated catalysis). Further, as discussed earlier, electrochemistry can be used as a sort of on/off switch for each step. Combined with the assembly line that continuous flow enables, having an on/off switch ensures minimal interference between steps. Thus, our center has worked on designing and appropriate flow reactor that can carry out electrochemical reactions. Since efficient mass transfer is a key characteristic of continuous flow that maintains or improves productivity of chemical reactions, we are interested in first probing mass transport in our custom built flow reactor using electrochemistry, which is highlighted on our twitter page.
1. Akwi, F. M.; Watts, P., Continuous flow chemistry: where are we now? Recent applications, challenges and limitations. Chem. Commun. 2018, 54, 13894-13928.
2. Bannock, J. H.; Krishnadasan, S. H.; Heeney, M.; de Mello, J. C., A gentle introduction to the noble art of flow chemistry. Mater. Horiz. 2014, 1, 373-378.
3. Wei, J.; Diaconescu, P. L., Redox-Switchable Ring-Opening Polymerization with Ferrocene Derivatives. Acc. Chem. Res. 2019, 52, 415-424.
4. Baumann, M.; Moody, T. S.; Smyth, M.; Wharry, S., A Perspective on Continuous Flow Chemistry in the Pharmaceutical Industry. Org. Process Res. Dev. 2020, 24, 1802-1813.