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Russian scientists have proposed a method for the synthesis of a new, stable and non–explosive source of hydrogenated acid - 4-(dimethylamino)pyridinium azide. This compound can be obtained in multigram quantities and used for the synthesis of physiologically active substances used in the treatment of a variety of diseases: from cancer and AIDS to insomnia.

Specialists of the N.D. Zelinsky Institute of Organic Chemistry (IOH) of the Russian Academy of Sciences, the Dm Rogachev National Medical Research Center for Pediatric Hematology, Oncology and Immunology (NMIC DGOI) of the Ministry of Health of the Russian Federation, Lomonosov Moscow State University and Kazan Federal University worked on the project.

In recent decades, organic compounds such as alkylazides have aroused increasing interest among scientists because of the possibility of their use in organic synthesis, in biology and medicine, as well as as energy-intensive compounds. In medicine, alkylazides are used to carry out "click reactions", in which module molecules, as a constructor, are assembled into an ensemble by a simple interaction resembling pressing a key on a computer with a finger ("click"). In particular, it is used to modify potential drugs or biological objects (peptides, nucleosides) with fluorescent labels. This makes it possible to study the distribution of the medicinal substance in the body, the places of inflammation or localization of tumors, etc. In addition, they are used to obtain well-known and develop new medicines.

"To obtain alkylazides, either metal azides or hydrogenated acid are usually required. But the use of nitric acid in its pure form is limited by its volatility, high toxicity and instability. At the same time, the use of metal azides is limited by their low solubility in standard solvents used in organic synthesis. 4-(dimethylamino)pyridinium azide can be considered as a stable form of hydrogenated acid, since it contains it in its composition, but its disadvantages are uncharacteristic for it. Unlike the classical reagents used to introduce the azide function into the molecule, the reagent developed by us is stable, non-explosive, small-hygroscopic (i.e. it almost does not absorb water vapor from the air), soluble both in water and in various organic solvents, that is, safe and convenient when used in practice. The synthesis of our reagent is easily scaled, which makes it possible to obtain it in quantities of tens of grams or more in one load," said Ivan Andreev, project manager for the RNF grant (project 21-73-10212), senior researcher at the Chemical Synthesis Laboratory of the NMIC DGOI.

"For example, the reaction of the disclosure of donor-acceptor cyclopropanes by an azide ion with the formation of alkylazides is a key stage in the synthesis of a variety of polycyclic N-heterocycles, including natural compounds, their analogues and physiologically active molecules. At the same time, such a transformation in the "classical version" – with the participation of metal azides – takes place under harsh conditions at high temperatures for a long time and is accompanied by various side processes, which leads to a decrease in the yields of the target products. The use of 4-(dimethylamino)pyridinium azide in a proton ionic liquid made it possible to obtain target alkylazides with good yields under milder conditions, as well as to avoid the use of toxic solvents used in existing processes," added Igor Trushkov, Head of the Laboratory of Directed Functionalization of Organic Molecular Systems of the IOH RAS.

In the future, scientists plan to expand the scope of application of the developed reagent to obtain other classes of practically useful organic compounds.

The article was published in the journal Advanced Synthesis & Catalysis
The information is taken from the portal "Scientific Russia" (https://scientificrussia.ru /)

The figure shows a green crocodile (4—(dimethylamino)pyridinium azide, the color of the crocodile is a reference to the environmental friendliness of processes using it) in a proton ionic liquid (Protic Ionic Liquid = PIL), breaking the bond in the molecule, as a graphic image of the synthetic application of the developed reagent © Ivan A. Andreev et al./ Advanced Synthesis & Catalyst, 2022

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