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Synthesis 2006(1): 133-145  
DOI: 10.1055/s-2005-918490
PAPER
© Georg Thieme Verlag Stuttgart · New York

Titanium(IV) Chloride Promoted Syntheses of New Imidazo[1,2-a]pyridine Derivatives under Microwave Conditions

Lisheng Cai*, Chad Brouwer, Kathryn Sinclair, Jessica Cuevas, Victor W. Pike
PET Radiopharmaceutical Sciences Section, Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Building 10, Room B3C346, 10 Center Drive, Bethesda, MD 20892, USA
Fax: +1(301)4805112; e-Mail: cail@intra.nimh.nih.gov;
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Publication History

Received 6 May 2005
Publication Date:
24 November 2005 (online)

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Abstract

A new method is described for the synthesis of imidazo[1,2-a]pyridine derivatives from the reaction of 2-aminopyridines with α-haloketones. The critical reagent is titanium(IV) chloride, which appears to serve as a strong dehydrating agent to promote formation of putative Schiff base intermediates, which cyclize subsequently to form the products. The reactions were performed rapidly under microwave conditions. Multiple reaction conditions were evaluated, including reaction temperature, solvent and other Lewis acids. Various combinations of substitution patterns in both the α-haloketone and 2-aminopyridine substrates were examined to evaluate the scope of the reaction. The reaction is quite sensitive to substituents in both substrates, especially those with basicity or coordination ability.

Keywords

titanium(IV) chloride - imidazo[1,2-a]pyridine - polycyclic - condensation - Schiff base formation - microwave

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