General Papers
ARKIVOC 2015 (v) 219-229
Cyclic amidines as precursors for imidazoles Marc Y. Stevens,*a Ewa Rozycka-Sokolowska, b Gabriella Andersson,a Luke R. Odell,a Bernard Marciniak,b and John A. Joulec a
Division of Organic Pharmaceutical Chemistry, Department of Medicinal Chemistry, BMC, Box 574, Uppsala University, S-75123, Uppsala, Sweden b Institute of Chemistry, Environmental Protection and Biotechnology, Jan Długosz University, 42-200 Częstochowa, Poland c The School of Chemistry, The University of Manchester, Manchester M13 9PL, UK E-mail:
[email protected] DOI: http://dx.doi.org/10.3998/ark.5550190.p009.134 Abstract The regioselective nucleophilic reactivity of cyclic amidines is considered in the context of their reactions with 2-haloketones to generate imidazoles. Since the tautomer with an endocyclic imine is favoured, reaction with the 2-haloketone electrophile proceeds via initial alkylation at the ring nitrogen. This was confirmed by repeating a suitable literature reaction and submitting the isolated product to single-crystal X-ray analysis. Keywords: Imidazole synthesis, cyclic amidine, regioselectivity, single-crystal analysis
Introduction The best-known method for the ring synthesis of imidazoles1–4 involves the interaction of an amidine 2 and a 2-halo-ketone 1, with elimination of hydrogen halide and water, giving a 2,4(5)disubstituted imidazole 3 (Scheme 1).5 Usually, amidines are handled as their resonance-stabilised amidinium salts, 4, being easily converted into the free amidine with mild base. 2-Hydroxy-aldehydes (sugars) also react in like fashion with formamidine acetate, to produce 4(5)-substituted imidazoles.6,7
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