5- Amino-4-unsubstituted imidazoles reaction with

Diazo coupling in N-unsubstituted imidazoles occurs with equal case at either C-2 or C-4(5) (or both) in reactions which have been shown to involve reaction of the imidazole anion with the diazonium ion [10]. lire intensely coloured azo dyes which are formed have long been used for identification of imidazoles, especially in qualitative chromatography [7]. The azo groups can be reduced to amino or hydrazine groups, providing a useful alternative approach, especially to 2-aminoimidazoles (see Section 8.3),... 

Diazo coupling is expected to occur only with highly reactive systems, and experiment bears this out. Diazonium ions couple with the anions of N-unsubstituted imidazoles at the 2-position (e.g. 125 yields 126) and with indazoles (127) in the 3-position. In general, other azoles react only when they contain an amino, hydroxyl, or potential hydroxyl group, e.g. the 4-hydroxypyrazole (128), the triazolinone (129) and the thiazolidinedione (130) (all these reactions occur on the corresponding anions). 

A novel approach to adenine and hypoxanthine derivatives involves a high-temperature intramolecular cyclization of 4(5)-substituted-amino-5(4)-unsubstituted-imidazole intermediates. For example, reaction of 1,2-dimethylimidazol-5-amine with (ethoxymethylene)urethane gives the Af -ethoxycarbonyl-jV -(imidazol-5-yl)formimidamide which under thermal cyclization is rapidly transformed into 8,9-dimethylhypoxanthine (3). 

The electrolysis of asymmetric ketones 43 led to the formation of isomers and stereoisomers. Kinetic measurements for the formation of ketimine 43 in saturated ammoniacal methanol indicated that at least 12 h of the reaction time were required to reach the equilibrium in which approximately 40% of 42 was converted into the ketimine 43. However, the electrolysis was completed within 2.5 h and the products 44 were isolated in 50-76% yields. It seems that the sluggish equilibrium gives a significant concentration of ketimine 43 which is oxidized by the 1 generated at the anode, and the equilibrium is shifted towards formation of the product 44. 2,5-Dihydro-IH-imidazols of type 44, which were unsubstituted on nitrogen, are rare compounds. They can be hydrolyzed with hydrochloric acid to afford the corresponding a-amino ketones as versatile synthetic intermediates for a wide variety of heterocyclic compounds, that are otherwise difficult to prepare. 

Another pharmaceutically important fused-imidazole ring system is the popular sleeping aid medication zolpidem. Bromination of 4-methylacetophenone and condensation with methylated 2-amino pyridine provides the fused-imidazole in good overall yield. Note that the ring nitrogen on the aminopyridine reaction reacts with the bromide carbon. Mannich-type alkylation at the unsubstituted 5-position provides the dimethylaminomethyl substituent in good yield. Further elaboration yields zolpidem. ... 

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