How the lockdown helped establish the mechanism of the reaction. Scientists of the ZIOC have discovered an unusual multicomponent process

The study of the mechanisms of organic reactions is often a long and difficult work. Particularly complex are the processes that result in the formation of a number of intermediates. The identification of each intermediate can be a separate serious task.

In 2020, researchers of the Academician N.K. Kochetkov Laboratory of Carbohydrates and Biocides of the Zelinsky Institute studied a multicomponent reaction between aldehydes, acetoacetic esters, cyano-containing C-H acids, and ammonium acetate. It was found that refluxing the starting compounds in methanol for two hours led to the stereoselective formation of 1,4,5,6-tetrahydropyridines. Domino condensation processes with the formation of various heterocycles are well known in the literature. It was assumed that the product was formed as a result of a domino process consisting of a sequence of reactions of Knoevenagel condensation, Michael addition, Mannich reaction, cyclization, and dehydration. However, when studying the reaction mass left at room temperature for three months due to the lockdown caused by the epidemic of the COVID-19 virus, it was found that the mixture contains both 1,4,5,6-tetrahydropyridine and its isomeric 3,4, 5,6-tetrahydropyridine. Further research showed that another reaction “is present” in the domino process — the isomerization of tetrahydropyridines. The scientists also established the structure of the sub-products of the process and the times of their formation.

Source:

A.N. Vereshchagin, T.M. Iliyasov, K.A. Karpenko, R.N. Akchurin, M.M. Minyaev. “Tetrahydropyridines Stereoselective Formation. How Lockdown Assisted in Mechanism Features Identification”. Molecules, 2022, Vol. 27, 4367. DOI: 10.3390/molecules27144367.