Nitrogen heterocycles are one of the most valuable scaffolds in organic chemistry for the production of various drugs. Heterocyclic structures are also of interest in the development of new functional materials and agrochemicals. Among nitrogen heterocycles, 1,2,5-oxadiazoles (furazans) and their N-oxides (furoxans) occupy a special place due to their great potential for application in various fields: they exhibit various pharmacological activities and are also of interest as parts of organic solar cells. Despite such prospects for the use of 1,2,5-oxadiazoles, methods of their chemoselective functionalization are practically not presented in the literature.
Researchers from laboratory № 19 of the Zelinsky Institute succeeded in developing a direct one-pot approach to the functionalization of readily available aminofurazans and aminofuroxans through a cascade of diazotization / reduction / condensation reactions. As a result, a wide range of N-(1,2,5-oxadiazolyl) hydrazones was obtained in high yields under mild conditions. The unusual hydrolytic stability of the synthesized compounds, along with their isosterism with respect to promising drug candidates for the treatment of various parasitic diseases, such as leishmaniasis, schistosomiasis, and Chagas disease, makes possible their potential use in medicinal chemistry.
Dmitry M. Bystrov, Ivan V. Ananyev, Leonid L. Fershtat, and Nina N. Makhova Direct Synthesis of N-(1,2,5-Oxadiazolyl)hydrazones through a Diazotization/Reduction/Condensation Cascade J. Org. Chem. 2020, 85, 23, 15466–15475. DOI: 10.1021/acs.joc.0c02243.