Newsletter Issue 02 Mar-Apr 2008

A Simple and Convenient One-Pot Method for the Preparation of Heteroaryl-2-imidazoles from Nitriles

Imidazoles are important in the synthesis of pharmacologically active compounds, but those with a single heterocyclic substituent in the 2-position are not easily prepared. Chemists from AMRI and CGI Pharmaceuticals have retaken an old method an improved it to modern standards. The key intermediates are amidines, which are useful synthetic intermediates for the preparation of different heterocycles. This remarkable synthesis uses as starting materials commercially available nitriles, which are transformed into the corresponding amidines under basic conditions. The amidines are not isolated, but treated with ethyl or methyl aminoacetal. Addition of acid causes the intermediate to cyclize yielding the expected imidazoles in excellent yields. All the procedure can be done one-pot, is easily scaleable and does not need chromatography.

Tetrahedron 64 (4), 645-651, 2008. See: 10.1016/j.tet.2007.11.009

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