Researchers solve an organic chemistry problem — ScienceDaily

Scientists have developed a strategy that could boost the development of drugs containing pyridine and organic functional materials.

In chemicals used in agriculture, as well as pharmaceuticals and a variety of materials, pyridines are often found as so-called functional units that decisively determine the chemical properties of substances. Pyridines belong to the group of ring-shaped carbon-hydrogen (CH) compounds (“heterocycles”) and contain one nitrogen atom (N). For chemists, direct functionalization of the carbon-hydrogen bonds (CH bonds) of pyridines is a straightforward approach to the design and modification of complex molecules, even in the final step of the synthesis sequence.

The latter means that the active ingredients can be chemically modified without having to rebuild them. The functionalization of pyridine at a certain position relative to the nitrogen atom – in the difficult to access “meta-position” – is extremely challenging and rare. A team of researchers led by Prof. Armido Studer of the Institute of Organic Chemistry of the University of M√ľnster has developed a new strategy to bring various functional groups to the meta position of pyridines. Their study has now been published in the journal Science.

Chemists use a temporary dearomatization of pyridine: its electronic properties are reversed, producing a stable intermediate product — a dienamine. By means of radical and polar chemistry, researchers are able, with a high degree of selectivity, to bring large numbers of fluorinated alkanes, as well as a number of “electron-poor substituents” (electrophiles), to the meta position. These transformations also include medically and agrochemically relevant features such as astrifluoromethyl and halogen groups. “The important thing,” says Dr. Hui Cao, a postdoc in the Studer working group, “is that functionalized dienamine intermediates are easily re-flavored into meta-functionalized pyridines under acidic conditions.”

His colleague Dr. Qiang Cheng adds: ‘The high degree of efficiency, broad range of applications and meta-selectivity of our approach allow us to functionalize twelve different types of drugs.’ Furthermore, the team developed processes in which drugs can be transformed directly into trifluoromethyl derivatives and replaced with chlorine, in so-called one-pot reactions, which require little effort and take place in a single reaction vessel. For this purpose, chemists use cheap and commercially available reagents. “Our study provides an answer to the unsolved problem of pyridine functionalization at the meta position,” says Armido Studer. “We believe this publication will significantly boost the development of pyridine-containing medicines and organic functional materials.”

Source of the story:

Materials provided by University of Munster. Note: Content can be edited for style and length.

Leave a Reply

Your email address will not be published. Required fields are marked *