Pyridines are frequently found in pharmaceuticals and a number of materials, as well as compounds used in agriculture, as functional units said to be crucial in determining the chemical properties of substances.
Pyridines are ring-shaped carbon-hydrogen (CH) compounds known as heterocycles containing a nitrogen (N) atom.
For chemists, directly replacing the carbon-hydrogen bonds (CH bonds) of pyridines provides an easy way to create and modify complex compounds, even at the final step of the synthesis process. In the latter case, it is possible to chemically modify the active ingredients rather than recreate them.
It is extremely difficult and rare to functionalize pyridine in a specific position relative to the nitrogen atom, that is, the elusive "meta position".
Dr. A new method for inserting various functional groups into the meta-position of pyridines has been developed by a research team at the Institute of Organic Chemistry at the University of Münster under the direction of Armido Studer. The publication “Science” has now published this work.
Scientists temporarily aromatize pyridine by reversing its electrical properties, resulting in a stable intermediate called dienamine. Using radical and polar chemistry, researchers are able to selectively put many fluorinated alkanes as well as a number of "electron-poor substituents" (electrophiles) into the meta position.
Functions such as trifluoromethyl and halogen groups important in medicine and agricultural chemistry are also converted during these processes. A postdoctoral fellow in the Studer study group, Dr. According to Hui Cao, the most important factor is that under acidic conditions, functionalized dienamine intermediates easily meta-functionalize to pyridines.
His colleague Dr. Qiang Cheng continues: “The high degree of efficiency, wide range of applications, and meta-selectivity of our approach enables the functionalization of twelve different types of pharmaceuticals.” In addition, the group created procedures that allow instant conversion of pharmaceuticals to trifluoromethyl and chlorine substituted derivatives. These procedures are known as "one-pot reactions", which require very little effort and take place in a single reaction vessel. Chemists use affordable, easily accessible chemicals for this purpose. According to Armido Studer, "Our work offers a solution to the open question of functionalization of pyridine at the meta position." “We believe this publication will significantly advance the development of organic functional materials and pyridine-containing drugs.”