Affiliation:
1. Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, Prov.le Lecce-Monteroni, 73100 Lecce, Italy
2. Dipartimento di Chimica, Università degli Studi di Bari “Aldo Moro”, Consorzio C.I.N.M.P.I.S., Via E. Orabona 4, 70125 Bari, Italy
Abstract
A new 2-amino imidazole derivative, 5-(4-chlorophenyl)-N,1-di-o-tolyl-1H-imidazole-2-amine (3), has been synthesized using a green approach. The reaction was conducted in a ChCl (cholinium chloride)/urea eutectic mixture, which is a nature-inspired and environmentally friendly reaction medium. The proposed reaction mechanism involves the preliminary regioselective alkylation of the Nsp2 of guanidine (2), followed by an intramolecular condensation between the carbonyl moiety and the secondary N′sp3. Finally, a tautomerization/aromatization step furnished the final product (3). Notably, 2-amino imidazole (3) could be isolated in high yield (91%), just by filtration from the DES/water mixture and subsequent crystallization; the remaining ChCl/urea could be recycled, after water removal, for four consecutive reactions without any significant drop in the (3) yield. The product has been fully characterized by 1H, 13C, 2D 1H-13C HSQC, and 2D 1H-13C HMBC NMR; FT-IR spectroscopy; and EI-MS spectrometry.
Subject
Organic Chemistry,Physical and Theoretical Chemistry,Biochemistry
Reference25 articles.
1. Tamm, M., Randoll, S., Herdtweck, E., Kleigrewe, N., Kehr, G., Erker, G., and Rieger, B. (2006). Imidazolin-2-Iminato Titanium Complexes: Synthesis, Structure and Use in Ethylene Polymerization Catalysis. Dalton Trans., 459–467.
2. Titanium Complexes with Imidazolin-2-Iminato Ligands;Tamm;Chem. Commun.,2004
3. Guanidine Organocatalysis;Selig;Synthesis,2013
4. 2-Aminoimidazoles in Medicinal Chemistry;Kikelj;Mini-Rev. Med. Chem.,2013
5. Emedastine: A Potent, High Affinity Histamine H1-Receptor-Selective Antagonist for Ocular Use: Receptor Binding and Second Messenger Studies;Sharif;J. Ocul. Pharmacol. Ther.,2009