4-cyanoimidazoles

The addition of nucleophiles to double and triple bond systems is often a convenient way of effecting an intramolecular ring closure. Addition to cyano groups has received considerable attention, as in addition to ring formation it provides a convenient method for the introduction of an amino group. Reaction of methyl Af-cyanodithiocarbimidate with Af-methylaminoacetonitrile resulted in displacement of methanethiol and formation of (314). Sodium ethoxide treatment in DMF converted (314) into a 4-amino-5-cyanoimidazole... 

Hydrolysis of the trifluoromethyl group of 2 tnfluoiomethylimidazoles is promoted by the formation of the anion, which readily eliminates fluoride. The resultant ditluorodiazafulvene then easily adds water The remaining steps in the hydrolysis ate predictable When aqueous ammonia is used, 2-cyanoimidazoles result [40] (equation 4])... 

We include here a short discussion of diazocyclopentadiene (4.21), its 2,3,4,5-tetra-cyano derivative (4.22), and the analogous heterocyclic compound 2-diazo-4,5-di-cyanoimidazole (4.23). Their synthesis and properties are discussed in Sections 2.6 and 12.2, where it is mentioned that they show in some respects the behavior of diazonium ions, i.e., of the mesomeric structure 4.21b (also analogously for 4.22 and 4.23). 

Another cyclization of 3 -adenylic acid (3 -AMP) to 2, 3 -cyclic adenylic acid (2, 3 -cAMP) took place by condensation with carbiminodiimidazole (or iV-cyanoimidazole) in aqueous or anhydrous medium. It is supposed that the reaction of 3 -AMP probably proceeds via a phosphoric imidazolide [9]... 

Photochemical reactions of HCN tetramers in such eutectic solutions to give 4-amino-3-cyanoimidazole (Orgel, 2004)... 

The photocyclization of cis-diaminomaleonitrile (372) to 4-amino-5-cyanoimidazole (373) has been shown to proceed via the trans isomer 374.308 4-Amino-3-cyanopyrazole does not seem to be an intermediate in this transformation.309 Analogous cyclizations have been reported in the imidazole 373 which undergoes further photoreaction to yield the bicycle 375, and in o-aminobenzonitrile which is converted into indazole.310 This photocyclization has been extended to include enaminonitriles 376 spectroscopic evidence for the intermediacy of iminoketenimes 377 in this311 and other similar transformations312 have been reported. 

Photolysis of DAMN over a relatively long period of time produces 4-amino-5-cyanoimidazole (8) (Scheme 2). Unlike the photoreaction producing 7, which may be an intermediate to 8, this conversion is irreversible (74JA6707). 

Amino-5-cyanoimidazole can also be obtained nonphotochemically. The monocarboxamide from hydrolysis of 13 (R = H) (see Section IIl.B) undergoes Hoffmann rearrangement on treatment with chlorine and sodium hydroxide to give 8 (Scheme 2) (76JAP(K)51-1466, 1467, 1468). 

Name 8-[ l-(2-Chlorophenyl)-4-cyanoimidazol-5-ylamino]-4-methoxy-2//-chromen-7-carboxylic acid... 

Reaction of 5-azido-4-cyanoimidazole with active methylene compounds R1COCH2R2 (R =Me, R2 = COMe R1 Me, R2 = COPh R1 Me, R2 = C02Et) or malononitrile in the presence of base led to either imidazo[5,l-z/]-[l,2,3,5]tetrazepines or imidazolyltriazoles, depending on the reaction conditions <1995JHC457>. 

Substituted imidazole 1-oxides 263 upon treatment with dimethyl or diethyl sulfate furnish l-alkoxy-3-subtituted imidazolium salts 283 that were converted to the tetrafluoroborate 283 (A- = BF4 ) or hexafluorophos-phates 283 (A = PF6-) by treatment with sodium tetrafluoroborate or hexa-fluorophosphate (2007ZN(A)295). The tetrafluoroborates 283 (A = BF4 ) reacted with cyanide ion to give 2-cyanoimidazoles 285 (1975JCS(P1)275). The reaction probably follows a mechanism similar to that suggested to be operative in the pyrazole series encompassing O-alkylation succeeded by nucleophilic addition and elimination of methanol (Scheme 85). 

Reaction of 4,5-disubstituted imidazole 1-oxide with trimethylsilyl cyanide (TMSCN) leads to 2-cyanoimidazole. If devoid of substituents at C4 and C5, the cyano (CN) group also enters these positions (1996JOC6971). The reactivity of the 2-, 4-, and 5-position is comparable and 245 reacts with TMSCN affording the isomeric cyanoimidazoles 296-298 in a ratio that depends on the nature of the 3-substituent, solvent polarity, and reaction temperature. These parameters could be optimized to give each of the three cyano compounds as the major product. Mechanisms (iii) and (iv) (Section 1.5.1.3 and 1.5.1.4) account for the formation of 296-298 (Scheme 88). 

Several novel IOji bicyclic imidazoles (63 or 65), obtained from polysubstituted imidazoles, were reported during this period. The first synthesis of an imidazo[4 ,5 4,5]thieno[3,2-d]pyri-midine commences with l-benzyl-2-(methylthio)-4-bromo-5-cyanoimidazole (62) [95TL12807]. Sequential metallation, sulfurization, S-alkyiation, and Thorpe cyclization of 62 afforded the thienoimidazole intermediate 63. Precursor 62 was obtained from 1 -benzyl-2,4,5-tribromoimida-zole in a series of metallation-electrophile trapping protocols. Nitroimidazo[l,5-a]imidazoles (65) were readily obtained from l-(acylmethyl)-2-methyl-4-nitro-5-bromoimidazoles (64) by sequential amination and cyclization [94KGS490]. 

Pyrolysis of the triazolo[4,5-rf]pyrimidine 42 did not give the expected cyanoimidazole 216, but the only identifiable products were HCN and ammonia due to the fragmentation of the pyrimidine ring (70T3965). 

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