Novel method for controlling chemical reactions discovered

Substituted aromatic compounds are among the most important building blocks for organic compounds such as medicines, pesticides and many materials. The function of the molecules is determined by the spatial linkage of the various building blocks, the „substitution pattern“. A research team from the Department of Organic Chemistry at Kiel University (CAU) has now presented a method in the scientific journal Chem to produce compounds with a substitution pattern that is otherwise difficult to access more efficiently than before. In order to achieve the necessary activation of carbon-hydrogen bonds, they developed a special palladium catalyst. For the first time, it can selectively control a previously impossible position within molecules.

Long-standing research gap closed

With their new method, the scientists have closed a long-standing research gap. In principle, substituted aromatic compounds have three positions to which a catalyst can dock in order to trigger a reaction, known as ortho,meta and para . Depending on the position, different chemical products with fundamentally different properties“ are created in the end, says Manuel van Gemmeren, Professor of Organic Chemistry at the CAU. For the ortho-  and para positions, ways were already known to specifically target catalysts there. Manuel van Gemmeren and his team are now able to selectively target the meta position directly for the first time. This enables them to produce so-called meta-substituted benzylammonium compounds, which are very interesting due to their versatility in organic chemistry.

Normally, these compounds only occur in small quantities mixed with other products.

Until now, they had to be separated from each other in a complicated process. Alternatively, complex synthesis processes were necessary to produce them specifically. Both cases led to unnecessary waste products," explains van Gemmeren. With the new method, meta-substituted benzylammonium compounds can now be produced much more efficiently.

The research team used a principle that has not yet been described in the specialist literature: the palladium catalyst they developed can interact with charges in the molecule. This drastically changes the composition of the resulting products in favour of the previously difficult-to-produce substitution pattern. Calculations by colleagues at the Institut Català d’Investigació Química (ICIQ), Spain, showed that charge interactions are actually responsible for this.

Also interesting for pharmaceutical or agricultural companies

These findings from basic research may also be of interest to pharmaceutical or agricultural companies that are building up huge libraries of structurally related molecules and investigating their biological activity.

Wherever the greatest possible diversity of compounds is systematically investigated, our method can be a helpful tool for closing knowledge gaps,

says van Gemmeren.

The development of the new method is the result of many years of preliminary work that began at the Westfälische Wilhelms-Universität Münster. Here, van Gemmeren established his own research group on the activation of carbon-hydrogen bonds via the Emmy Noether Programme of the German Research Foundation (DFG) before coming to Kiel University in 2022. In Kiel, he will also realise his ERC Starting Grant project „DULICAT“, from which the concept idea for the new method emerged. He has received funding of 1.8 million euros from the European Research Council (ERC) for this project.

An announcement by Kiel University from 24 January 2023