Amino-4- cyanoformimidoyl imidazole

Solid barium hydroxide dihydrate (8.0 g) is added to a suspension of the amidine (24) (3.0 g, 22.2 mmol) in 95% aqueous ethanol (270 ml), and the mixture is stirred vigorously ( 50min), till TLC shows that all of the (24) has been consumed the solution turns deep yellow. Ether (300 ml) is added, and carbon dioxide is bubbled through the solution (10 min). The precipitated barium carbonate and unchanged barium hydroxide are filtered off and the solid is washed with ether. The combined filtrate and washings are rotary evaporated below 30°C to give the product as a pale green solid (2.17 g, 72%), m.p. 300°C (dec.). 

1-Aryl group Yield (%) 1-Aryl group Yield (%) 

To a stirred solution of the formamidine (1.00 g) in either dry ethyl acetate, ethanol, or a 1 1 mixture of ethyl acetate and isopropanol is added DBU (10 drops, 50 nl), and the reaction is monitored by TLC (Camlab polygram G254 silica gel 9 1 chloroform-ethanol). The solid dissolves, and after l-3h the product precipitates as an off-white to pale yellow product, which is filtered off, washed with diethyl ether or light petroleum, and dried under vacuum to give the title compounds in 53-96% yields. 

An aqueous solution of 1 M potassium hydroxide (1 ml) is added to a suspension of the formamidine (1 mmol) in ethanol (1 ml). The mixture is stirred at room temperature ( 1 h). The precipitated product is filtered, washed with water, a few drops of ethanol and, finally, with diethyl ether before drying under vacuum. (See Table 2.2.3.) 

Similarly, 1-aralkyl analogues can be made by base-induced cyclization of iV-aralkyl formamidincs related to (24) (e.g. 5-amino-l-benzyl-4-cyanoimidazole (77%)) [33], 

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When 5-amino-4-(cyanoformimidoyl)imidazoles 68 are reacted with tosyl isocyanate, 70 are formed (Scheme 10 Table 8) <1996JHC855>. After a 7- o-4)g-cyclization of intermediates 69a-d, a Dimroth rearrangement takes place to give the thermodynamic products 70a-d. 

The fully-unsaturated 1,3-benzodiazepine 310 is formed by a photoreaction of the 1-substituted isoquinoline 7V-imide 309 (Scheme 169) <1980CPB2602>. The same principle has been applied to prepare thieno-, furo-, and pyrrolo-fused 1,3-diazepines <1980CC454, 1981CPB1539>. The imidazolo-fused l,3-benzodiazepin-2-ones 313 can be prepared by the reaction of 5-amino-4-(cyanoformimidoyl)imidazoles 311 with tosyl isocyanate. The mechanism of this reaction includes a 1-exo-dig cyclization of intermediates 312 followed by a Dimroth rearrangement to give the thermodynamic products 313 (Scheme 170) <1996JHC855, CHEC-III(13.05.9.2.2)174>. 

Trifluoromethylpurines have been prepared mainly through formation of the pyrimidine ring starting from highly functionalised imidazoles. 5-Amino-4-(cyanoformimidoyl)imidazole 29 reacted rapidly with neat trifluoroacetic anhydride to give the 6-cyano-2-trifluoromethylpurine 30 (20 °C, 10 min, 52 %) [55] (Scheme 13). However, hydrolysis to the 6-carboxamidopurine 31 was observed when the reaction was carried out over several days [55,56]. This latter transformation has been applied to prepare 9-(3-hydroxy-propyl)-2-trifluoromethyl-9H-purine-6-carboxamide [57]. 

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