New Approaches to 2-Aminoimidazoles and Their Derivatives

The class of 2-aminoimidazoles has gained broader interest over the last two decades due to their structural diversity and the biological activities of several members. However, the lack of practical methods for the synthesis of 1-substituted and 1-unsubstituted 2-aminoimidazoles encumbers the facile preparation of libraries of natural product analogues. This work focuses on the study of new approaches for the synthesis of diversely substituted 2-aminoimidazoles and their derivatives. In chapter II, we describe a new approach to 4(5)-mono- and 4,5-disubstituted 2-amino-1H-imidazoles via microwave-assisted Pd-catalyzed arylation of 2-substituted imidazo[1,2-a]pyrimidines and subsequent cleavage of the pyrimidine ring with hydrazine. Microwave-assisted procedures have been proven to be excellently suited for the synthesis of 2,3-substituted imidazo[1,2-a]pyrimidines and 4(5)-mono- and 4,5-disubstituted 2-amino-1H-imidazoles. Chapter III deals with the synthesis of polysubstituted 2-aminoimidazoles from substituted 2-aminopyrimidines and α-bromocarbonyl compounds via intermediary imidazo[1,2-a]pyrimidinium salts. A stepwise synthesis of 1,5-disubstituted 2-aminoimidazoles was performed under conventional conditions together with the isolation and characterization of the intermediates. The rapid formation of deeply coloured azadiene intermediates upon reaction of 2-(p-nitrophenyl)imidazo[1,2-a]pyrimidinium perchlorate with amines was used for the visual detection of resin bound amino acids in solid-phase synthesis. A microwave-assisted one-pot two step protocol was developed to synthesize 1,4-, 1,5- and 1,4,5-substituted 2-aminoimidazoles in high yields. This protocol was successfully applied for a total synthesis of well known marine sponge alkaloids of the isonaamine family. Moreover, the microwave-assisted cleavage of intermediate 2,3-dihydro-2-hydroxyimidazo[1,2-a]pyrimidinium bromides by hydrazine provided a new synthetic approach to 4,5-disubstituted 2-alkylamino-1H-imidazoles. In chapter IV, we describe a new approach for the synthesis of protected 1,4,5-substituted 2-aminoimidazoles from substituted propargylamines via highly efficient one-pot Ag+-mediated guanylation and subsequent Ag+-catalyzed intramolecular cyclization. This method provides an access to 2-amino-4-benzylimidazoles, which are related to many marine sponge alkaloids.Summary Samenvatting Chapter 1. Introduction and Goals Goals Chapter 2. Microwave-Assisted Synthesis of Substituted 2-Amino-1H-imidazoles from Substituted Imidazo[1,2-a]pyrimidines Chapter 3. Synthesis of Substituted 2-Aminoimidazoles from 2-Aminopyrimidines and α-Bromocarbonyl Compounds via Imidazo[1,2-a]pyrimidinium Salts Chapter 4. Synthesis of Polysubstituted 2-Aminoimidazoles from N-Propargylguanidines General Conclusions Experimental part References List of publicationsnrpages: 220status: publishe