Imidazole 5-amino-4-cyano

A more direct route involves the treatment of a-amino-cyano-amide with a protected formamidimide. The reaction is reported to take place at ambient temperature and provide good yields of the 1,4,5-tri-substituted and more appropriately functionalized imidazole, which is subsequently transformed into temozolomide. ... 

Imidazole-4-catbonitrile, 5-amino-synthesis, 5, 463 Imidazolecarboxamide, cyano-reactions, 5, 436 Imidazole-4-carboxamide Hofmann reaction, 5, 435 Imidazole-4-carboxamide, 5-amino-in histidine biosynthesis, 1, 90 reactions... 

Four tetramers of hydrogen cyanide have been isolated the well-known diaminomaleonitrile (DAMN), diaminofumaronitrile, 4-amino-5-cyano-imidazole, and an HCN adduct of s-triazine. 

Table 27. Selected examples of correlation between observed and calculated UV transitions (Del Bene and Jaffe). (Other studied compounds include benzene, pyridine, 1,2-diazine, 1,3-diazine, 1,4-diazine, cyclopentadienide ion, pyrazole, imidazole, 2-pyrrole-carboxaldehyde, furfural, benzonitrile, nitrosobenzene, phenol, phenoxide ion, pyridinium ion, 1-hydroxy-pyridinium ion, 2-cyano-pyridine, 3-cyano-pyridine, 4-cyano-pyridine, 2-amino-pyridine, 3-amino-pyridine, 4-amino-pyridine.)...

There have also been a few examples of ring expansions involving azetines. One such instance, which follows a pericyclic mechanism, is the thermolysis of 4-cyano-l-t-octyl-3-t-octylamino-2-t-octyliminoazetine (160), producing the 4-amino-5-cyanoimidazole (Scheme 89). Such azetine species have been implicated as intermediates in the photolysis of enaminonitriles to imidazoles (Section 4.08.1.1.1 Scheme 17). In strongly basic medium the azetidinone (161), which possesses a lactam group, is ring expanded to the 4H-imidazolinone (163), probably via the anionic acylic species (162 Scheme 89) <80AHC(27)241>. 

Treatment of 5-amino-4-cyano-4-methyl-4//-imidazole (642) with formamidine under mild conditions resulted in the formation of (644), with 5-methyl-5//-adenine (643) postulated as a transient intermediate. Rearrangement of (643) as suggested above would produce (644). An independent synthesis of (644) was carried out by treatment of (645) with methyl A-cyanomethanimidate (646) (82JA235, 83JOC3). 

A sugar derivative related to the purine nucleosides, namely methyl 5-(adenin-l-yl)-5-deoxy-2,3-0-isopropylidene-j8-D-ribofurano-side, is formed by the reaction of methyl 5-amino-5-deoxy-2,3-0-iso-propylidene-jS-D-ribofuranoside with l-benzyl-5-cyano-4[(ethoxy-methylene)amino]imidazole, followed by removal of the benzyl group. On fusion, this compound rearranges to methyl 5-deoxy-2,3-0-isopropylidene-5-[(purin-6-yl)amino]-/8-D-ribofuranoside, which can also be obtained from the reaction of methyl 5-amino-5-deoxy-2,3-0-isopropylidene-/8-D-ribofuranoside with 6-chloro-9-(tetrahydropyran-2-yl)purine. In the same manner, methyl 5-amino-5-deoxy-2,3-di-0-p-tolylsulfonyl-/3-D-ribofuranoside reacts with 6-chloro-9-(tetrahydro-pyran-2-yl)purine to give methyl 5-deoxy-5-[9-(tetrahydropyran-2-yl)-purin-6-yl]amino-2,3-di-0-p-tolylsulfonyl-j8-D-ribofuranoside. With liquid ammonia, 5 -0-p-tolylsulfonyladenosine gives 5 -amino-5 -deoxyadenosine. On heating in p-dioxane, ring closure to 3,5 -an-hydroadenosine is observed. ... 

Another important intermediate in the preparation of 1,2-dihydropurines, 6-carbamoyl-and 6-cyanopurine derivatives is 5-amino-l-benzyl-4-[cyano(imino)methyl]imidazole (4). ... 

Acetylacetone (0.6g, 1.08mL, 10.6mmol) was added to a suspension of 5-amino-l-benzyl-4-[cyano(imi-no)methyl]imidazole (4 0.3 g, 1.33 mmol) inCHClj (1 mL), with stirring, at rt. After 19 h a pale-yellow solid was filtered off and recrystallized (CHClj/petroleum ether 40-60 °C) yield 0.2 g (60%) colorless solid mp 210-211 C. 

Strecker reactions are among the most efficient methods of synthesis of a-amino nitriles, useful intermediates in the synthesis of amino acids [73] and nitrogen-containing heterocycles such as thiadiazoles, imidazoles, etc. [74]. Although classical Strecker reactions have some limitations, use of trimethylsilyl cyanide (TMSCN) as a source of cyano anion provides promising and safer routes to these compounds [73b,75]. TMSCN is, however, readily hydrolyzed in the presence of water, and it is necessary to perform the reactions under strictly anhydrous conditions. BusSnCN [76], on the other hand, is stable in water and a potential source of cyano anion, and it has been found that Strecker-type reactions of aldehydes, amines, and BuaSnCN proceed smoothly in the presence of a catalytic amoimt of Sc(OTf)3 in water [77]. No surfactant was needed in this reaction. The reaction was assumed to proceed via imine formation and successive cyanation (it was confirmed that imine formation was much faster than cyanohydrin ether formation under these reaction conditions) again the dehydration process (imine formation) proceeded smoothly in water. 

Oxidative cyclization with DDQ of amino(ribosylamino)maleonitrile in methanol gives a 64% yield of 4-cyano-5-methoxy-2-(D-ribotetrahydroxybutyl)-imidazole, whereas an anomeric mixture of 2-(D-erythrofuranosyl)-4-cyano-5-methoxyimidazole is obtained in 77% total yield by heating the open chain species for 3h at 150°C in a mixture of 2-ethoxyethanol and acetic acid [41]. 

When treated with potassium artiide in liquid ammonia, suitably substituted and activated pyrimidines are converted into imidazoles, a ring eontraction which has been shown by labelling to involve cleavage of the 5,6 bond (Scheme 6.1.6). 5-Amino-4-chloro-2-phenylpyrimidine is converted under the reaction conditions into 4-cyano-2-phenylimidazole in 30-35% yield, rather better than is achieved by Comforth s method (using aminoacetonitrile with... 

Imidazole-2-carboxylates can be made by amidine cyclization (see Section 2.2.1 and Table 2.2.2), by reaction of an aminocarbonyl compound with thioxamate (see Section 4.1 and Scheme 4.1.6), and from 1-cyano-or 1-carbethoxy-substituted 4-amino-2-azabutadienes (see Section 3.2 and Scheme 3.2.3). An improved amidine cyclization treats trichloroacetonitrile with ami noacetaldehyde dimethyl acetal to give the amidine (5), which cyclizes with trifluoroacetic acid at room temperature to give 2-trichloromethylimidazole (Scheme 8.3.2). This is not purified, but converted immediately into ethyl imidazole-2-carboxylate or imidazole-2-carboxylic acid in high yields [10],... 

Cp2TiCl2 has been reduced in the presence of Me3SiCl, zinc powder, and imidazole to give a catalytic system for the reductive radical cyclization of ketonitriles to produce 2-amino-3-cyano-2-cyclopenten-lols in moderate yields with high trans-selectivity.1165... 

Reactions of A(-acyl- or iV-cyano-imidates with primary amines, hydrazines, or hydrazides have been used on occasion. The latter two reagents adapt the process to the synthesis of 1-amino-imidazoles (210) <87HCA187, 93AHC(57)i>. Nucleophilic attack by the amino group displaces the morpholine function in the first step. A related synthesis has provided the best method yet for making... 

---