Microwave-Assisted Green Synthesis

Climate change, resource shortages, and budget cuts for research and development are forcing scientists to rethink traditional methods. While developing new approaches focused on environmental friendliness, chemists introduced the term “green chemistry”^[1] to capture the idea of environmentally friendly design of chemical processes. The term green synthesis is now widely used to indicate chemical reactions that are performed employing environmentally benign and sustainable processes/materials. In order to structure approaches to this sustainable idea, 12 principles have been defined, each one bringing chemists closer to green synthesis. These principles are:^[2]

1. Waste prevention
2. Maximization of atom economy
3. Less hazardous syntheses
4. Design of safer chemicals
5. Usage of safer solvents and auxiliaries
6. Energy efficiency
7. Usage of renewable feedstocks
8. Reduction of chemical derivatives
9. Catalysts
10. Design for degradation
11. Real-time analysis for pollution prevention
12. Safe chemistry for accident prevention

Since modern sealed-vessel microwave systems support many of the above-mentioned principles, they are well-suited for microwave-assisted green synthesis. 

Microwave-assisted synthesis only makes sense under sealed vessel conditions.^[3] Consequently, when sealing the vessels, the waste of water for reflux heating (or actually cooling) is reduced to zero since reflux condensers are of no use. Dedicated microwave reactors cool the reaction mixtures either by compressed air or by fan, which makes them perfectly suited for microwave-assisted green synthesis.

The most important beneficial effect of microwave-assisted synthesis compared to conventionally heated reactions is that the reaction times are shortened and the yields are improved. There are thousands of examples that show this beneficial effect.^[4] Therefore, regarding this special requirement, almost any microwave-assisted reaction is a step towards green synthesis.

Apparently, simple heating to 160 °C lets the reaction work without acid catalyst. At room temperature, however, sulfuric acid is required to give similar results. This is a very effective demonstration of microwave-assisted green chemistry.

Some time ago, the Kappe research group compared the energy consumption of conventional hot plates with microwave reactors.^[12] It showed with different reaction types (Diels-Alder, hydrolysis, Suzuki coupling, and cyclocondensation) that, compared to conventionally heated experiments, microwave-assisted synthesis consumes far less energy. These findings are based on the fact that under microwave conditions, reactions simply proceed faster until full conversion is reached. The results are very impressive and show that microwave-assisted synthesis indeed makes chemistry “greener”.

Besides parallel synthesis, successful catalyst screening was also done in an automated microwave-assisted system. A 24-position autosampler, placed on top of the microwave synthesis reactor Monowave 400, automatically handled 24 reaction mixtures with individual catalysts to find the optimum catalyst for the present reactions.^[16-17]

As mentioned above, there is an approach towards microwave-assisted green chemistry to perform reactions neat – without any solvent.^[6] This reduces the risk of explosions due to the absence of explosive, low-boiling solvents.

Besides this, modern dedicated microwave-synthesis reactors adhere to the highest safety standards. Because they can reach temperatures up to 300 °C and pressures up to 80 bar, the safety standards are very high in order to keep everything under safe control. In line with safety regulations, the instruments are designed in order to minimize the risk for potential hazards to provide maximum safety for chemists and the environment. 

[1] Anastas, P. T., Warner, J. C. (2000). Green Chemistry: Theory and Practice. Oxford University Press
[2] American Chemical Society (2023). https://www.acs.org/greenchemistry/principles/12-principles-of-green-chemistry.html 
[3] Refer to Chapter 3.3.2. of Kremsner, J. M., Stadler, A. (2018). A Chemist’s Guide to Microwave Synthesis, 3rd Edition. Anton Paar Publishing, Graz, https://www.anton-paar.com/us-en/synthesis-guide/
[4] Kappe, C. O., Stadler, A., Dallinger, D. (2012). Microwaves in Organic and Medicinal Chemistry, 2nd Edition. Wiley-VCH, Weinheim
[5] Baumgartner, B. et al. (2016). Macromol. Chem. Phys. 217, 485 
[6] Ganji, P. (2020). Biomass Conv. Bioref. 10, 823
[7] Amaya-García, F. et al. (2021). ChemSusChem 14, 1853
[8] López-Lira, C. et al. (2021). Bioorg. Chem. 111, 104823
[9] Santos, A. F. M. et al. (2022). Liq. Cryst. 49, 1809
[10] Bijalwan, K. et al. (2022). ChemNanoMat 8, e202200044
[11] Glasnov, T. N. et al. (2009). ChemMedChem 4, 1816
[12] Razzaq, T., Kappe, C. O. (2008). ChemSusChem 1, 123
[13] Jacobsen, J. et al. (2019). Dalton Trans. 48, 8433
[14] Dreischarf, A. C.  et al. (2017). Inorg. Chem. 56, 2270
[15] Damm, M., Kappe, C. O. (2012). Mol. Divers. 16, 5
[16] Karmakar et al. (2019). New J. Chem. 43, 9843
[17] Frija, L. M. T. et al. (2020). J. Mol. Struct. 1222, 128831
[18] Hebert, O. et al. (2022). Synthesis 53, 5215
[19] Cantillo, D. et al. (2013). J. Org. Chem. 78, 4530
[20] Tang, H. et al. (2022). Colloid Surface A, 651, 129564