A one-pot route to -acyl ureas: a formal four-component hydrolytic reaction involving aminonitrones and isocyanide dibromides

• Published in: New journal of chemistry 2020-01, Vol.44 (4), p.1253-1262
• Main Authors: Il'in, Mikhail V, Lesnikova, Liana A, Bolotin, Dmitrii S, Novikov, Alexander S, Suslonov, Vitalii V, Kukushkin, Vadim Yu
• Format: Article
• ISSN: 1144-0546; 1369-9261
• DOI: 10.1039/c9nj05445f

One-pot interplay between aminonitrones, isocyanides, dibromine, and water proceeds to give N -acyl ureas. This formally four-component reaction occurs via the initial generation of electrophilically activated 1,2,4-oxadiazolium salts, which then hydrolyze to grant N -acyl ureas. XRD structural and theoretical DFT studies indicated that the quasi-cyclic conformation of the N -acyl ureas is caused by moderate strength (6.2-7.8 kcal mol −1 ) intramolecular resonance-assisted hydrogen bonding, while their solid-state dimerization is determined by the collective action of intermolecular N-H O (4.1-7.5 kcal mol −1 ) and C-H O (1.6-4.7 kcal mol −1 ) hydrogen bonding. The results of the kinetic study accompanied by DFT calculations show that the generated 2-substituted 1,2,4-oxadiazolium salts are, as expected, significantly more reactive toward nucleophilic addition than the corresponding 1,2,4-oxadiazoles. A one-pot route to N -acyl ureas proceeds via generation of electrophilically activated 2-substituted 1,2,4-oxadiazolium salts. The conformation of the N -acyl ureas is stabilized via moderate strength (6.2-7.8 kcal mol −1 ) resonance-assisted hydrogen bonds.