Imidazole formation diketone

In the reaction of a-diketones with formamide and formaldehyde at 180°-200°C, no a-hydroxyketones can be detected during the reaction,65 and hence formaldehyde cannot be acting as a reducing agent. It seems then that imidazole formation must be due to generation of ammonia from formamide and subsequent reaction between the diketone, ammonia, and formaldehyde. The advantage of this method over the older Radziszewski synthesis lies in the reduced decomposition of the diketone with consequent reduction in side, reactions which normally produce mixtures of imidazoles. 

An interesting photochemical approach to 4,5-disubstituted N-alkylimidazoles consists of the photolysis of 2,3-dihydro-5,6-disubstituted-pyrazines that can be easily prepared from 1,2-diketones and 1,2-diamino-alkanes. For example, the preparative-scale photolysis, in absolute EtOH with high-pressure Hg lamp (Pyrex filter), of 5,6-dimethyl- or 5,6-diphenyl-2,3-dihydropyrazines 54, yields the corresponding N-methyl-imidazoles 57 in high yields (Scheme 12.16). The reaction mechanism involves the formation of an enediimine intermediate 55, followed by cyclization and re-aromatization [41]. 

With )3-ketoesters, /3-ketoamides and )3-diketones, DAMN is converted into enamines, which can be cyclized purely by heating in an alcoholic solvent. The products are 2-substituted-4,5-dicyanoimidazoles (Scheme 2.1.5) [45], When DAMN reacts with formamidine, the initial condensation product (16)/(17) can form imidazoles either by loss of ammonia (when 4,5-dicyanoinnidazole is formed), or via an isomerization and subsequent cyclization which eliminates HCN to give 4-ainino-5-cyanoimidazole (18). With excess formamidine the latter product is converted into adenine. The intermediate amidines (16)/(17), as transient intermediates, react with aqueous ammonia to form (18), and with acetic acid to give (15) (R = R = H) [48, 50]. The transformation of (17) to (18) is a 1,5 bond formation (Scheme 2.1.6). 

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