5- Aminoimidazoles, reactivity

The recently reported rearrangement (1581) of 2-allylamino-4-carboxamido-5-aminothiazoIes to 4-aminoimidazole-5-carboxamide in presence of sodium bicarbonate probably involves the electrophilic reactivity of C-2, which allows the ring opening. 

Nucleophilic processes that introduce chlorine include displacement of diazonium functions, but these are not well known in the imidazoles because of the instability of many simple aminoimidazoles. In one instance the lack of success may have been a function of the high stability of 5-ethoxycarbonyl-4-diazoimidazole. Other 1-substituted 4-diazonium salts showed expected reactivity, and 1-substituted 5-aminoimidazoles formed sufficiently reactive diazonium salts to give good yields of the 5-chloro compounds [80JCS(P1)2310]. Most of the thrust in this reaction strategy has focused on the preparation of fluoroimidazoles (see B,2,d). 

Mourabit AA, Potier P (2001) Sponge s Molecular Diversity Through the Ambivalent Reactivity of 2-Aminoimidazole A Universal Chemical Pathway to the Oroidin-Based Pyrrole-Imidazole Alkaloids and Their Palau amine Congeners. Eur J Org Chem 237... 

Mourabit AA, Potier P. Sponge s molecular diversity through the ambivalent reactivity of 2-aminoimidazole a universal chemical pathway to the oroidin-based pyrrole-imidazole alkaloids and their palau amine congeners. Fur. J. Org. Chem. 2001 2 237-243. 

Except for trifluoroacetamide, which gave an excellent yield of 2-trifluoro-methylpurin-6-one (see 19) when refluxed for 2 hr with 4-aminoimidazole-5-carboxamide,231 the higher amides lack the reactivity of formamide. 

The ability of the 2-aminoimidazole 36/37 to tautomerize allows it to incorporate both electrophilic and nucleophilic sites into the molecule simultaneously (Fig. 13.4). This concept is further emphasized when considering the vinylogous compound 38/39 (26), which is thought to make up the basic building block of the PIAs (oroidin). This ambiphiUc reactivity allows for the vast number of speculative cyclization and dimerization pathways. 

---