Synthesis of 4(5)-Acyl-, 1-Substituted 5-Acyl, and 1-Substituted 4-Acyl-1H-imidazoles from 4-Aminoisoxazoles

Article abstract of DOI:10.1021/jo00389a015

4-Aminoisoxazoles can be acylated with a wide variety of activated carboxylic acids.Hydrogenation of the resulting amides gives α-(acylamino)enaminones, which cyclize to 4(5)-acylimidazoles upon treatment with base.This method allows for the synthesis of acylimidazoles with a wide range of substituents at C-2.Utilization of N-substituted 4-aminoisoxazoles in the same sequence of reactions yields 1-substituted 5-acylimidazoles, a substitution pattern not otherwise easily prepared.Treatment of α-(acylamino)enaminones, derived from N-unsubstituted isoxazoles, with primary amines leads to incorporation of the amine at the β-position with concomitant expulsion of ammonia.This sequence efficiently yields 1-substituted and 1,2-disubstituted 4-acylimidazoles but does not give satisfactory yields of 5-substituted 4-acylimidazoles due to steric inhibition of the amine exchange.