Facile Synthesis of Optically Active Imidazole Derivatives.docVIP

Molecules 2007, 12, 1183-1190 molecules ISSN 1420-3049 ? 2007 by MDPI /molecules Full Paper Facile Synthesis of Optically Active Imidazole Derivatives Ales Marek, Jiri Kulhanek, Miroslav Ludwig and Filip Bures* Department of Organic Chemistry, Faculty of Chemical Technology, University of Pardubice, nam. Cs. legii 565, Pardubice, 53210, Czech Republic * Author to whom correspondence should be addressed; E-mail: filip.bures@upce.cz Received: 11 May 2007; in revised form: 22 May 2007 / Accepted: 23 May 2007 / Published: 30 May 2007 Abstract: Five optically active imidazole derivatives have been synthesized via a facile 4-step reaction sequence starting from commercially available and inexpensive N-Cbz amino acids. While microwave assisted condensation was unsuccessful, the condensation of the corresponding α-bromoketones with formamidine acetate in liquid ammonia was revealed to be a useful method for the synthesis of such imidazole derivatives. The derivatives thus prepared are structurally-related to histamine. Keywords: Imidazole, condensation, optically active ligand Introduction From time immemorial, organic chemists have been attempting to synthesize, isolate and characterize heterocyclic molecules for their unique chemical and physical properties. Despite the fact that many convenient synthetic methods have been utilized for preparing the basic heterocycles [1], a facile synthesis of optically active analogues still remains a challenge. Among the many possible targets enantiopure five-membered heterocyclic derivatives such as imidazole are of particularly interest. For instance, naturally occurring 4-substituted imidazoles such as histidine or histamine and their significance as an essential amino acid or its decarboxylation product, are well known. Imidazole chemistry currently attracts considerable attention, where the imidazole derivatives are widely applied as N-ligands coordin