A New Synthetic Method for the 2-Substitution of N-Unsubstituted Benzimidazoles: Formaldehyde as a Versatile Protecting Agent for Heterocyclic NH

Article abstract of DOI:10.1021/jo00273a032

N-Unsubstituted benzimidazoles 1 are readily converted in a one-pot sequence into 2-substituted derivatives 2 with good overall yields.N-Protection with formaldehyde and lithiation with lithium N,N-diisopropylamide (LDA), n-butyllithium, or tert-butyllithium gives the dilithiohemiaminals 6, which readily react with a range of electrophiles at the 2-carbon.The 2-substituted 1-(lithioxymethyl)benzimidazoles 7 undergo smooth acid-catalyzed dehydroxymethylation under mild conditions to give N-unsubstituted 2-substituted benzimidazoles 2.