Exploring the acidic catalytic role of differently structured deep eutectic solvents in the aza-Michael addition of amines to 2-vinylpiridine

• Published in: Monatshefte für Chemie 2020-09, Vol.151 (9), p.1387-1394
• Main Authors: Ballarotto, Marco, Cappellini, Federico, Maestri, Riccardo, Del Giacco, Tiziana, Di Profio, Pietro, Tiecco, Matteo, Germani, Raimondo
• Format: Article
• Language: English
• Subjects: Additives; Amines; Analytical Chemistry; Anticancer properties; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Inorganic Chemistry; Michael reaction; Organic Chemistry; Original Paper; Physical Chemistry; Solvents; Theoretical and Computational Chemistry
• ISSN: 0026-9247; 1434-4475
• DOI: 10.1007/s00706-020-02660-z

The search for innovative and green reaction media is a prominent topic in the recent research in chemistry. Deep Eutectic Solvents (DESs) are currently gaining relevance in this field thanks to their unique properties in terms of their “greenness” as well as in terms of their catalytic properties. In this work we developed an efficient protocol for the conjugate aza-Michael addition of amines to 2-vinylpyridine using 14 differently structured acid DESs as both reaction media and catalysts, so preventing the use of other acid additives. The results are influenced by the acidity of the components of the DESs, showing the best results with weak acids in the DESs components, with isolated yields up to 86%. The aza-Michael reaction is a widely used synthetic route for the C–N bond formation in organic synthesis. In particular, the addition of amines to 2-vinylpyridine is used for the realization of pharmaceutically relevant compounds with anticancer, antiarrhythmic, and analgesic properties. Comparing the results with the ones observed in literature for the same reaction, this procedure revealed to be a convenient and efficient method for this relevant transformation. Graphic abstract