A simple method opens access to new fluorine-containing heterocycles

Researchers at the Ural Federal University (UrFU, Russia) have developed a simple, and a quite effective method for producing fluorine-containing heterocycles. This approach is based on available reagents to produce substances for applications in medicinal chemistry and agrochemistry. A description of the method and the new compounds obtained with it was published in the journal Molecules.

"One of the most well-known qualitative reactions in school chemistry is the bromination of the multiple bonds in alkenes. This transformation always proceeds smoothly and leads to discoloration of the bromine solution,” said Dmitrii Obydennov, associate professor at the Department of Organic Chemistry and High-Molecular Compounds at UrFU. “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 bromination processes and the possibility of formation of a large number of byproducts, we managed to carry out the transformation with high selectivity and good conversion."

Studies have shown that the new method can be used to produce a number of new fluorinated 4-pyrones. These pyrones were chemically very active molecules and selectively entered into a variety of reactions, scientists explain. 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 is one of the best for obtaining fluorine-containing pyrones. There are three reasons. First, it is a one-pot reaction. Second, it includes a simple way to isolate the target product. Third, it is quite general. This allows the nature of the aromatic substituent to be varied as well as the length of the fluorine-containing chain and the number of fluorine atoms in it.

"Together with our colleagues, we decided to study the reaction in detail in order to extend it to a wide range of compounds,” said Dmitrii Obydennov. “We investigated the influence of the nature of the solvent on the bromination. It turned out that carrying out the reaction in dichloromethane or benzene was the best condition. By changing the number of bromine equivalents, we managed to achieve the introduction of two or three bromine atoms. At the second stage of work, we investigated the cyclization of bromine-bearing molecules by intramolecular substitution of bromine to obtain heterocyclic compounds, 4-pyrones. To simplify the process as much as possible and increase its efficiency, we decided to synthesize the target pyrones in one-pot mode, that is, without isolating brominated intermediate products.”

Note

About 30% of all pharmaceuticals 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 and to increase the reactivity, as compared to non-fluorinated analogs. Due to low selectivity, introducing fluorine atoms into a molecule by direct fluorination is a complicated and problematic process. 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.