Scientists have developed a strategy that could give impetus to the development of pyridine-containing drugs and organic functional materials.
In chemicals used in agriculture, as well as in pharmaceuticals and various materials, pyridines are often found as so-called functional units that determine the chemical properties of substances. Pyridines belong to the group of ring-shaped carbon-hydrogen (CH) compounds (“heterocycles”) and contain a nitrogen (N) atom. For chemists, the direct functionalization of the carbon-hydrogen bonds (CH-bonds) of pyridines is a simple approach to the design and modification of complex molecules, including at the final stage of the synthesis sequence.
The latter means that the active ingredients can be chemically modified without having to create them from scratch. Functionalization of pyridine in a certain position in relation to the nitrogen atom – in the hard-to-reach “meta-position” – is extremely difficult and rare. A group of researchers led by Professor Armida Studer from the Institute of Organic Chemistry at the University of Münster has developed a new strategy to obtain different functional groups in the meta-position of pyridines. Their research is now published in a journal Science.
Chemists use temporary dearomatization of pyridine: its electronic properties change, forming a stable intermediate product – dianamine. With the help of radical and polar chemistry, the researchers managed to transfer a large number of fluorinated alkanes, as well as a number of “electron-poor substituents” (electrophiles) to the metaposition with a high degree of selectivity. These transformations also include medically and agrochemically important functionalities such as atrifluoromethyl and halogen groups. “Importantly,” says Dr. Hui Cao, a postdoc in Studer’s working group, “the functionalized dianamine intermediates are readily aromatized to meta-functionalized pyridines under acidic conditions.”
His colleague, Dr. Qiang Cheng, adds, “The high degree of efficacy, wide range of applications, and metaselectivity of our approach enable the functionalization of twelve different types of drugs.” In addition, the team developed processes in which drugs can be converted directly to trifluoromethyl and chloro-substituted derivatives – in so-called one-pot reactions that require little effort and take place in a single reaction vessel. For this, chemists use inexpensive, commercially available reagents. “Our study provides an answer to the unsolved problem of pyridine functionalization in the meta position,” says Armida Studer. “We believe that this publication will provide a significant boost to the development of pyridine-containing drugs and organic functional materials.”