Chemists Have Developed a Simple Method for Producing New Fluorine-Containing Heterocycles

10:49, August 11, 2021

It can later be used to produce substances for medical and agrochemical applications

Chemists at Ural Federal University have developed a very simple and quite effective method for producing fluorine-containing heterocycles. This approach makes it possible to produce substances of interest for medical and agrochemical applications using available reagents. A description of the method and the new compounds obtained with it are published in the journal Molecules.

"One of the most well-known qualitative reactions in high school chemistry is the bromination of the multiple bond in alkenes. This transformation always proceeds smoothly and leads to discoloration of the bromine solution. We decided to investigate in this reaction complex molecules containing a double bond and a fragment of fluorinated 1,3-diketone, which can also be easily brominated. Despite the competition of these two processes of interaction with bromine and the possibility of formation of a large number of byproducts, we managed to carry out the transformation with high selectivity and good conversion," explains Dmitry Obydennov, Associate Professor at the Department of Organic Chemistry and High-Molecular Compounds at UrFU.

Studies have shown that the new method can be used to produce a number of new fluorinated 4-pyrons. These pyrons were chemically very active molecules and selectively entered into a variety of reactions, scientists say. Thus, based on these active molecules and the method found can create a wide range of new fluorinated compounds that are the basic heterocyclic structures for medicinal chemistry (substances with antiviral, anticancer, anti-inflammatory activity, etc.) and agrochemistry (herbicides, insecticides, fungicides, etc.).

The method proved to be one of the best for obtaining fluorine-containing pyrons for three reasons: it is single-reactor, includes a simple way to isolate the target product, and is quite general, allowing the nature of the aromatic substituent, the length of the fluorine-containing chain, and the number of fluorine atoms in it to be varied.

"Together with our colleagues, we decided to study the reaction in detail in order to extend it to a wide range of compounds. The influence of the nature of the solvent on the course of bromination was investigated. It turned out that the best conditions were to conduct the reaction in dichlomethane or benzene. By changing the amount of bromine equivalents, we managed to achieve the introduction of two or three bromine atoms. At the second stage of work, we investigated cyclization of bromine-containing molecules by intramolecular substitution of bromine to obtain heterocyclic compounds, 4-pyrone. To simplify the process as much as possible and increase its efficiency, we decided to synthesize the target pyrons in single-reactor mode, that is, without isolating bromine intermediate products," describes the work process Dmitry Obydennov. 

Chemists have been working on the improvement of this method for three years. The research was supported by the Russian Science Foundation (project no. 18-13-00186).

Reference

About 30% of all medicinal compounds contain the fluorine atom. Fluorine is one of the most electronegative elements. It is introduced into the structure of the molecule to improve the physical and biological properties as well as to increase the reactivity, as compared to non-fluorinated analogues. Introducing fluorine atoms into a molecule by direct fluorination is a complicated and problematic process due to low selectivity. Therefore, scientists are working on the search and selection of new active reagents, which will serve as a basis for the construction of fluorine-containing molecules of complex structure.