4- -cyanoimidazole, reaction

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... 

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)... 

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). 

A further example of a similar sequence of reactions is provided by the reactions of N-cyaniminodithiocarbonic esters (55) with a-cyanoammonium salts. The initial condensation product (56) cyclizes when heated with sodium ethoxide in DMF, again giving a 4-amino-5-cyanoimidazole. Related is the reaction of (55) with the hydrochloride salt of ethyl methylaminoacetate, which gives imidazoles directly perhaps this might be classified... 

A similar reaction sequence condenses iV-cyanoiminodithiocarbamic esters (7) with a-cyanoammonium salts (e.g. sarcosine nitrile sulfate) (Scheme 2.3.2). The isothiourea product (8) readily cyclizes to give 4-amino-5-cyanoimidazoles when heated with sodium ethoxide in DMF solution. It is possible to convert the dithiocarbamic esters directly into imidazoles if they are heated in DMF solution with sarcosine ethyl ester hydrochloride or methylaminoacetophenone in the presence of triethyamine [3]. These direct cyclizations arc, however, examples of both 1,2 and 1,5 bond formation. (See also Section 3.2). 

Reaction of an imidate with aminomalonodinitrile gives a 1-substituted 5-aminoimidazole-4-nitrile in low to moderate yields (10-60%) (Scheme 4.1.4). The reactions are carried out at room temperature in an acetate buffer, and there are similarities to reactions of DAMN (see Sections 2.1.1, 2.2.1 and 3.1.1) [35], and to the synthesis of 5-amino-4-cyanoimidazole from aminomalonodinitrile and formamidine acetate [41]. The reaction with an ethyl formimidate may initially involve replacement of the ethoxy group by amino followed by ring closure. Yields are reported to be low to moderate, with ethyl A-heteroarylformimidates reacting more readily than the iV-aryl analogues. Indeed, the phenyl derivative will not react at all. 

There are considerable data available on imidazole formation by ring contractions of pyrimidines, pyrazincs and triazines [15, 43, 59-61]. Few of the reactions, however, have synthetic potential except perhaps for the thermolytic conversions of azidopyrimidines and azidopyrazines into 1-cyano-substituled imidazoles, and the reactions of chloropyrimidines and chloropyrazines with potassium amide in liquid ammonia to give 4- and 2-cyanoimidazoles, respectively. Ring contractions of quinoxaline 1-oxides may also have some applications. 

Chloropyrazines undergo ring contraction when treated with potassium amide in liquid ammonia. The reactions resemble those of pyridines and pyrimidines, and may be useful for making 2-cyanoimidazoles despite the formation of product mixtures and low yields. For example, 2-chloropyrazine is converted into a mixture of 2-aminopyrazine (15%), imidazole (14-15%) and 2-cyanoimidazole (30-36%) [82]. In a similar experiment, 2-cyano-4-phenylimidazole (19%) can be obtained 83J. 

The reaction of 2potassium amide in liquid ammonia to give 2-cyanoimidazole, imidazole, and 2-aminopyridine has been investigated (911). It has been found that 2-chloropyrazine containing an excess of in position 1, on treatment with potassium amide in liquid ammonia at — 65° yields 2-aminopyrazine in which the exocyclic nitrogen contains all the excess and an addition-nucleophilic-ring opening-ring closure (ANRORC) mechanism was proposed (822). The mechanism of the conversions into imidazole (823) and... 

A low yield ( 4%) of 4-f-butylamino-5-cyanoimidazole is obtained when 4 moles of HCN in HF reacts with 2,4,4-trimethyIpent-2-ene. The reaction mechanism proposed suggests that the cyclization process can be classified in this section. 

Other researchers have synthesized phenylcyanamides by the reaction of phenylisocyananide dihalides with ammonia,14 or by the reaction of anilines with cyanogen bromide.15 A recently prepared cyanating agent, A -cyanoimidazole, when reacted with aniline yielded phenylcyanamide in high yields under moderate conditions.16 The latter reaction may provide a route to more sensitive cyanamide derivatives. 

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