Ryan Hughes, Product Marketing Executive, Syrris
Move over, microwave chemistry – flow chemistry is taking over
Microwave chemistry is dead.
OK, OK, not quite dead. Microwave chemistry has its place in small scale batch chemistry and reaction optimization, but the fanfare that microwave chemistry created over 20 years ago has largely died off – and for good reason.
Why did microwave chemistry take off over two decades ago?
On the face of it, microwave chemistry is a promising avenue for chemists to take. At small scale, microwave chemistry offers the ability to rapidly superheat and pressurize reactions usually up to 20 bar, and it’s easy to get started with – everyone has access to a kitchen microwave!
Heating effect of microwave chemistry
Using microwaves to heat a reaction vessel negates the need for an oil/water bath or vessel jacket, and microwaves can heat uniformly throughout the vessel volume (providing it is sufficiently thin). This avoids the issue resulting from conventional heating where the core of the reaction vessel takes longer to achieve the target temperature, reducing temperature gradients. Microwave chemistry also provides instant heating and the ability to instantly remove the heat source at the press of a button.
Microwave heating can have certain benefits over traditional heating methods (e.g. oil baths), including;
- reaction rate acceleration
- milder reaction conditions
- higher chemical yield
- lower energy usage
- different reaction selectivities
- Selective heating
While early microwave chemistry papers postulated the possibility of heating specific molecules in a reaction, it was quickly accepted that the repartitioning of thermal energy from targeted molecules to the rest of the reaction would be so rapid as to negate any effects. However, solid phase reactions display much higher heat transfer resistances, opening up the appealing possibility of selective heating “hot spots” through microwave chemistry.
Belief in “non-thermal microwave effects”
There are two proposed microwave effects; “specific microwave effects” and “non-thermal microwave effects”.
“Specific microwave effects” are those that cannot be easily emulated through traditional heating methods; for example, the elimination of vessel wall effects, or selective heating of specific reaction components.
“Non-thermal microwave effects” have been proposed to explain unusual observations in microwave chemistry and are not supposed to require the transfer of microwave energy into thermal energy.
Since the first publication in 1986 reported the use of microwaves to “accelerate” chemical reactions, various publications have since discussed the presence of “non-thermal microwave effects” and “whether the observed effects can in all instances be rationalized by purely thermal/kinetic phenomena (thermal microwave effects) arising from the rapid heating and high bulk reaction temperatures attained with microwave dielectric heating, or whether some effects are connected to so-called specific or non-thermal microwave effects”.
While the existence of non-thermal microwave effects is controversial, the reference to them in various publications helped boost the prominence of microwave chemistry.
Why have continuous flow chemistry systems made microwave chemistry largely redundant?
The rapid rise in continuous flow chemistry publications has coincided with a decline in microwave chemistry papers, and it isn’t a coincidence.
The graph above shows a sudden drop in the number of publications referencing “microwave synthesis” in 2015
Ability to scale-up
One of the major drawbacks of microwave chemistry is the difficulty in scale-up. Microwaves can realistically only be used in reactors of up to a few liters, meaning beyond this scale researchers will have to find another way of heating the vessel, and therefore possibly change the entire setup or reaction. Efforts have been made to produce continuous flow microwave systems, but these are expensive and offer no benefits over normal flow chemistry heating modules.
Continuous flow chemistry systems can be likened to bathroom faucets; turn it on and the flow could fill up a tiny cup, but leave the flow running and you could fill a bath. It’s this ease of scale-up that makes continuous flow chemistry such an attractive synthetic technique to chemists who need to consider scale-up of their reactions.
Rapid heating – and cooling
Efficient heat transfer and the ability to provide virtually instantaneous heat helped microwave chemistry gain its popularity, but continuous flow chemistry systems easily do this too. What makes continuous flow chemistry systems stand apart from microwave chemistry is also the ability to rapidly cool reactions as well.
Sorry to tell you, but the “microwave effect” doesn’t exist…
Oliver Kappe is a big name in continuous flow chemistry, but a lot of his original focus was on microwave chemistry. In 2013, Kappe and team published a paper strongly refuting the existence of non-thermal microwave effects.
“From our perspective, after more than a decade of intense research in this area, we must now conclude that nonthermal microwave effects simply do not exist. Undoubtedly, there will be many more claims to the existence of these effects in organic chemistry (and in other fields) in the future. Unless those claims are independently verified, we would caution the scientific community against taking the existence of those effects for granted.”
Conclusion: Microwave chemistry isn’t dead, but continuous flow chemistry beats it in most cases
It isn’t fair to say microwave chemistry is completely dead – it’s still an excellent and easily accessible technique for experimental batch chemistry at
There’s a reason why labs that focused on microwave chemistry in the past have switched to continuous flow chemistry techniques. Rapid heating/cooling and high-pressure reactions are easily achieved in
An example of converting batch microwave chemistries to continuous flow chemistry
Researchers at the Institute of Applied Synthetic Chemistry (Vienna, Austria) and the Department of Chemistry at Durham University (Durham, UK) have successfully translated the batch microwave process of synthesizing methyl glycosides via Fischer glycosylation into a continuous flow chemistry procedure.
Fischer glycosylation – developed in the early 1890s as the earliest glycosylation protocol – still remains one of the most valuable preparative methods for simple glycosides. In 2005, Bornaghi et al. reported on the microwave-acceleration of Fischer glycosylation to overcome the long reaction times required under the classical conventionally heated processes. While this decreased reaction times, it introduced a scale-up limit; the translation of this batch technique to continuous flow has removed the scale-up limit without compromising on the reaction time improvements it gained. Read the open access paper here.
What do you think about the future of microwave chemistry?
We’d love to know what you think on the subject, so let us know in the comments below!
Find out more about continuous flow chemistry today
Discover how continuous flow chemistry systems work in our “What is flow chemistry and how does it work?” blog post, and then discover the 9 main reasons chemists are switching to continuous flow in this blog post.
Already know why chemists are switching to continuous flow chemistry? Then discover the award-winning Syrris Asia Flow Chemistry System today!
- Kappe, C. O. (2004), Controlled Microwave Heating in Modern Organic Synthesis. Angewandte Chemie International Edition, 43: 6250-6284. doi:10.1002/anie.200400655 (Open Access)
- Kappe, C. O., Pieber, B.
andDallinger, D. (2013), Microwave Effects in Organic Synthesis: Myth or Reality?. Angew. Chem. Int. Ed., 52: 1088-1094. doi:10.1002/anie.201204103
- Aronow, J., Stanetty, C., Baxendale, I.R. et al. Monatsh Chem (2019) 150: 11. https://doi.org/10.1007/s00706-018-2306-8
About Ryan Hughes
As Product Marketing Executive, Ryan is responsible for the inbound and outbound global marketing of the Syrris brand. Acting as the link between the Products, Sales, and Marketing teams, Ryan collaborates with various team members to help raise brand and product awareness and to help educate our audience on various topics, including flow chemistry, batch chemistry, reaction calorimetry, and process scale-up. Read Ryan’s bio here.
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