Less waste thanks to mechanochemistry

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"Chemistry is when it smokes and stinks" is an old saying. But green chemistry shows that things can be done differently.

Green chemistry has been firmly established in research at TU Wien for more than a decade. With the inter-university Master’s in Green Chemistry, it is now also gaining visibility in teaching. Michael Schnürch heads the Organic and Biological Chemistry research area at TU Wien and is himself researching green alternatives to conventional processes. The aim of green chemistry is to reduce negative effects on human health, but also on the environment.

The twelve principles of green chemistry

To achieve this, green chemistry is based on twelve principles: (1) waste prevention, (2) nuclear economy, (3) less harmful synthesis, (4) development of safer chemicals, (5) safer solvents and excipients, (6) efficient energy use, (7) use of renewable resources, (8) minimization of derivatives, (9) catalysis, (10) biodegradability, (11) real-time analysis to reduce pollutant emissions and (12) inherently safer chemistry to prevent accidents.

A recently successfully applied method therefore uses mechanical aids to synthesize materials. "Mechanochemistry works without solvents, or requires only very small quantities of them. All that is needed are the reactants and a mechanism that grinds the individual components together and brings them into close contact," explains Michael Schnürch. Ball mills are used here, as they are actually known from the field of process engineering. The fact that reactants can already react with each other during mechanical mixing was something I first discovered by chance as a doctoral student when I was grinding two substances together," recalls Schnürch.

Waste reduction through mechanochemistry

Mechanochemistry thus opens up completely new and at the same time sustainable possibilities, because in conventional processes a large proportion of the resources used, such as solvents and contaminated water (together often over 80 %), are disposed of after synthesis. As mechanochemistry manages without or with significantly fewer of these two components, a correspondingly large amount of waste can be avoided. Schnürch sees the pharmaceutical industry in particular as a potential and important user of green methods. "Large quantities of waste are generated in the production of medicines in particular, as drugs often have a complex structure and are produced in several steps."

At the same time, Michael Schnürch knows that not every reaction in a ball mill is successful. "Sometimes it simply needs solvents or additional energy," says the chemist. The more reactants are involved in a reaction, the more difficult it is to use mechanochemical methods. In the recent past, other synthesis methods that are considered sustainable have therefore also been used, such as organic electrochemistry or photochemical processes. Visible light also plays an important role here. Both can even be combined with mechanochemistry, for example by using transparent ball mills and allowing light to penetrate. But the use of ball mills made of certain materials - such as copper - can also have an influence on the chemical reaction. The possibilities for finding new methods here are virtually inexhaustible.

Almost one hundred percent yield

Schnürch and his team have now been able to show that their mechanochemical method for allylation is far superior to traditional chemistry in solution and can deliver almost five times more yield of the desired product. Not only does this avoid a lot of waste (principle 1), it also fulfills four other principles of green chemistry (principles 3, 5, 6 and 9). In addition, the method presented by Michael Schnürch and Johanna Templ can also be used to modify chemical compounds at a later stage in the synthesis process, which is particularly important in the development of active pharmaceutical ingredients. This was demonstrated by the modification of a number of drugs, such as the antidepressant paroxetine or the compound betahistine, which is used to treat dizziness.

Original publication

Templ, J., & Schnürch, M. (2023). Allylation of C-, N-, and O-Nucleophiles via a Mechanochemically-Driven Tsuji-Trost Reaction Suitable for Late-Stage Modification of Bioactive Molecules. Angewandte Chemie International Edition, https://doi.org/10.1002/anie­.202314637 .