Synthesis of 2-Substituted Imidazoles and Benzimidazoles and of 3-Substituted Pyrazoles by Lithiation of N- (Dialkylamino)Methyl Heterocycles

Abstract

The lithiation of N-(dialkylamino)methyl (aminal) derivatives of imidazole, benzimidazole, and pyrazole (themselves readily available from the parent heterocycles, formaldehyde, and a secondary amine) occurs smoothly at the 2-, 2-, and 5-positions, respectively, upon treatment with n-butyllithium in ether or tetrahydrofuran. Reaction with electrophiles, and subsequent facile acid-catalyzed hydrolysis of the protecting group, provides 2-substituted imidazoles, 2-substituted benzimidazoles, and 3(5)-substituted pyrazoles in good overall yields. © 1988, American Chemical Society. All rights reserved.