Cyanoimidazole-5-carboxamide

A mixture of DAMN (4g), formic acid (4 ml) and xylene (150ml) is stirred at room temperature (30 min), and then refluxed (6 h). The resulting dark solids (which adhere to the walls of the flask) are collected, washed with diethyl ether, and extracted repeatedly with hot water. Concentration of the aqueous extracts gives the above product (3.9 g, 77%), m.p. 273 C. From the residue some iimdazolc-4,5-dicarboxamidc (0.12g, 2.2%) is obtained. 

Whereas diiminosuccinonitrile is converted by trifluoracetic anhydride into 27/-imidazoles, these sometimes rearrange at fairly low temperatures ( 80°C) to l,2-dialkyl-4,5-dicyanoimidazoles [17, 29, 30.  

2-ethoxy-l-hydroxy-3-imidazoline 3-oxides (7) (R = OEt) are formed in 60-65% yields [47, 48], Further heating in ethanol or merely increasing the reaction time gives 2-ethoxy-l-hydroxyimidazoles (e.g. (8) (R = OEt, R = Me, = Ph, 80%)). The isomer (8) (R = OEt, R = Ph, R = Me) can again be made by the acetylation-aromatization sequence above [47]. 

Reaction of phosgene with the anti isomer of 1-amino-1-phenyl-2-propanone oxime gives l-hydroxy-5-methyl-4-phcny -3-iraidazolin-2-one in 25% yield [49]. A review of A -oxide formation has appeared recently [50], and discussions of other approaches to the compounds are found in Section 4.1 and Chapter 5. 

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Oxidation of the Schiff bases (22) of diaminomaleonitrile monoamide gives 4-cyanoimidazole-5-carboxamides with a variety of 2-substituents. When diaminomaleonitrile reacts with formamidine, the condensation product (23) can form imidazoles in two ways. Direct loss of ammonia gives 4,5-dicyanoimidazole, but isomerization, followed by cycliz-ation in which HCN is eliminated, gives 4-amino-5-cyanoimidazole. With further formamidine this latter product is converted into adenine (Scheme 11) (79JOC4532). 

Oxidation of the Schiff bases (19) made from the monoamide of DAMN (derived from DAMN by hydration of one of the nitrile functions) gives 4-cyanoimidazole-5-carboxamides (20) in good yields ( 70% or more) (Scheme 2.1.7). Such oxidations can be readily accomplished using hydrogen peroxide with a catalytic amount of sodium molybdate fSl]. 

Oxidation of Schiff bases of the monoamide 8 derived from diamino-maleonitrile gives 4-cyanoimidazole-5-carboxamides (Eq. 4). A new synthesis of 2-formyl-4-methyl-l-phenylimidazole 3-oxide (10) involves the fluoride-ion-promoted cyclization of the trimethylsilyl ether of JV-dichloro-acetyl-A-phenylaminopropanone oxime (9). ... 

An often used method to produce cyano compounds from carboxaldoxtmes and carboxamides is to dehydrate them with phosphorus pentoxide, which is a very low-priced reagent. In this way, l-benzyl-4-bromo-5-cyanoimidazole 21 was prepared in 28% yield from 20, although, surprisingly, the product was accompanied... 

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