title: Imidazolium Sulfonates as Environmental-Friendly Catalytic Systems for the Synthesis of Biologically Active 2-Amino-4H-chromenes: Mechanistic Insights.
abstract: Ionic Liquids (ILs) are valuable reaction media extremely useful in industrial sustainable organic synthesis. We describe here the study on the multicomponent reaction (MCR) between salicylaldehyde (2) and ethyl cyanoacetate (3), catalyzed by imidazolium sulfonates, to form chromenes 1, a class of heterocyclic scaffolds exhibiting relevant biological activity. We have clarified the reaction mechanism by combining the experimental results with computational studies. The results reported herein suggest that both the imidazolium core and the sulfonate anions in the selected ILs are involved in the reaction course acting as hydrogen bond donors and acceptors, respectively. Contrarily to the most widely accepted mechanism through initial Knoevenagel condensation, the most favorable reaction pathway consists of an aldolic reaction between reagents followed by heterocyclization, subsequent dehydration, and, finally, the Michael addition of the second molecule of ethyl cyanoacetate (3) to yield the chromenes 1.
authors: Departamento de Química Inorgánica y Química Técnica, Facultad de Ciencias, Universidad Nacional de Educación de Distancia, UNED , Paseo Senda del Rey 9, E-28040-Madrid ( Spain ).
authors: Jacinto
authors: J
authors: Velasco
authors: Departamento de Química Inorgánica y Química Técnica, Facultad de Ciencias, Universidad Nacional de Educación de Distancia, UNED , Paseo Senda del Rey 9, E-28040-Madrid ( Spain ).
authors: Elena
authors: E
authors: Pérez-Mayoral
authors: Departamento de Química Inorgánica y Química Técnica, Facultad de Ciencias, Universidad Nacional de Educación de Distancia, UNED , Paseo Senda del Rey 9, E-28040-Madrid ( Spain ).
authors: Vanesa
authors: V
authors: Calvino-Casilda
authors: Departamento de Química Inorgánica y Química Técnica, Facultad de Ciencias, Universidad Nacional de Educación de Distancia, UNED , Paseo Senda del Rey 9, E-28040-Madrid ( Spain ).
authors: Antonio J
authors: AJ
authors: López-Peinado
authors: Catalytic Spectroscopy Laboratory, Instituto de Catálisis y Petroleoquímica, ICP-CSIC , Marie Curie 2, Cantoblanco, E-28049-Madrid ( Spain ).
authors: Miguel A
authors: MA
authors: Bañares
authors: Instituto de Química Orgánica General, CSIC , c/Juan de la Cierva 3, E-28006-Madrid, ( Spain ).
authors: Elena
authors: E
authors: Soriano
mesh_terms: D000085:Acetates / Q000737:chemistry; D000447:Aldehydes / Q000737:chemistry; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000737:chemistry*; D002384:Catalysis; D060326:Chemistry Techniques, Synthetic; D055772:Green Chemistry Technology; D007093:Imidazoles / Q000737:chemistry*; D052578:Ionic Liquids / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D013451:Sulfonic Acids / Q000737:chemistry*
chemical_list: D000085:Acetates; D000447:Aldehydes; D001578:Benzopyrans; D007093:Imidazoles; D052578:Ionic Liquids; D013451:Sulfonic Acids; C013243:salicylaldehyde; C007659:ethyl cyanoacetate