Miscellaneous Imidazole Ring Construction

Imidazole synthesis utilizing 2-aminopyridines as amine source 

The use of microwave has recently been used to provide 5-amino-imidazoles from 2-aminopyridines. At a higher temperature and longer reaction times, dehydration occurs to form the imidazo-pyridinium salts. Reaction with hydrazine adds to the pyrimidinium salt, which then undergoes rearrangement to open the ring. The unstabilized diene undergoes hydrolysis to provide the 2-amino-4,5-di-substituted 1/f-imidazole. Chemically, PPA can be used to form the pyrimidinium salt also.  

Interestingly, when lower temperature and energy microwave is used, loss of water does not occur, and die imidazolin-pyridinium salt forms. When this intermediate is subjected to the hydrolysis conditions, a Dimroth-type rearrangement is proposed to occur which leads to the alkyl substituent that was at die 1-position of the imidazole ring to now be on the 2-amino-substituent as shown. 

Cyclization of an imino-Heck type reaction has been reported. Cyclization of a protected amidine gave reasonable yield of the l,3 5-tri-substituted imidazole in good yield. Pd is proposed to insert into the 0-N bond of the activated ester, cyclize, eliminate, and rearomatize.  

A Stetter-type multi-component reaction (MCR) was described earlier for the preparation of the precursor for imidazoles. Another MCR has been applied to the formation of imidazoles from simple building blocks.  

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