4- Aminoimidazole

When cyanamide replaces the cyanate, thiocyanate or isothiocyanate in the general method a useful route to 2-aminoimidazoles is opened up [29-31]. The intermediate guanidine whieh is formed in these reactions can often be isolated, and so the process could also be classified as a 1,5 bond formation (see Section 2.2). 

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No minor tautomers were detected for 2-aminoimidazoles fused with benzo and naphtho rings 54-56 [76AHC(S1), p. 430 84CHEC-I(5)345 96CHEC-II(3)77]. 

Iminoimidazolin-4-ones 227b are the only tautomers detected for 4-hydroxy-2-aminoimidazoles (R = H, Ph R = H) (91KGS62). Similar tautomeric forms are also characteristic of l-methyJ-2-imino-5-benzylideneim-idazole-4-one 228 (91KGS62) and 3-amino-l,2,4-triazol-5-ones 229 (R = R = H, COMe) (Scheme 78) [76AHC(S1), p. 482]. 

Only equivocal chemical evidence appears to be available for the unsubstituted aminoimidazoles. The failure of 2-aminoimidazole to undergo diazotization was originally interpreted to indicate that it existed in the imino form more recently, the 4-amino analog has been reported to behave as a normal aromatic amine. The infrared spectra of substituted aminoimidazoles of type 192 193 were con-... 

Unexpectedly, reaction of 73 with 2-aminoimidazole in MeCN in the presence of K2C03 afforded the hydrogen-bonded dimeric product 68, in which the betaine molecule is strongly associated to the corresponding pyridotriazi-nium iodide (Equation 2) <1996T11349>. 

A microwave-assisted, one-pot, two-step protocol was developed for the construction of polysubstituted 2-aminoimidazoles 101 via the sequential formation of imidazo[l,2-a]pyrimidinium salts from readily available 2-aminopyrimidines 99 and a-bromocarbonyl compounds 100, followed by opening of the pyrimidine ring with hydrazine <06OL5781>. A... 

Aminoimidazole (16) has also been identified as a metabolite from marine sponges (74MI1) and has been implicated as an in vivo progenitor of a class of marine pigments (92TL4385). 

Methods of preparation for this ring system have been reviewed in CHEC(1984) and CHEC-II(1996) <1984CHEC(5)607, 1996CHEC-II(8)345>, and elsewhere . The most usual approaches to this ring system are from the reaction of 2-aminopyrimidines with cr-halocarbonyl compounds, or 2-aminoimidazoles with /3-dicarbonyl compounds. 

The reaction of 2-aminoimidazole and EMME in boiling acetic acid for 3-6 hr yielded ethyl imidazo[l,2-a]pyrimidine-6-carboxylate (1113, R = R = H) (59JOC779). 

The direct nitration of imidazole with acidic reagents is difficult due to facile nitrogen protonation (pA aH 7). Nitration of imidazoles proceeds in the 4- and 5-positions with the amidine 2-position being quite inert. Imidazole can be directly nitrated to 4,5-dinitroimidazole but no further. 2,4,5-Trinitroimidazole (TNI) can be prepared from the successive nitration of 2-nitroimidazole the latter synthesized from the diazotization of 2-aminoimidazole in the presence of excess sodium nitrite and a copper salt. The nitrative cleavage of polyiodoimidazoles also provides a route to polynitroimidazoles. " ... 

Reaction of dehydro-L-ascorbic acid with guanidine derivatives gave the 2-aminoimidazole acyclo-C-nucleoside analog 1213, as shown in Scheme 241 (92T6385). 

Guanidines with a-halo ketones form 2-aminoimidazoles. a-Hydroxy ketones also react with amidines to form imidazoles, and a variety of substituents can be introduced into the imidazole nucleus (CHEC 4.08). 

Support-bound 1,2-diamines can be readily converted into imidazolidinones by treatment with carbonyl diimidazole [128,129]. The required diamines have been prepared on cross-linked polystyrene by reduction of peptides bound to MBHA resin with borane. Similarly, bicyclic imidazolines have been prepared from triamines and thiocarbonyl diimidazole (Entry 10, Table 14.3). Dehydration of polystyrene-bound monoacyl ethylene-1,2-diamines yields 4,5-dihydroimidazoles (cyclic amidines, Entry 5, Table 13.18). Several groups have reported the synthesis of 2-aminoimidazol-4-ones from resin-bound amino acid derivatives (e.g., Entry 6, Table 15.11). Most of these compounds are, however, unstable, and slowly decompose if dissolved in DMSO (Jesper Lau, private communication). 

The presence or absence of the dioxolane protecting group in dienes dictates whether they participate in normal or inverse-electron-demand Diels-Alder reactions.257 The intramolecular inverse-electron-demand Diels-Alder cycloaddition of 1,2,4-triazines tethered with imidazoles produce tetrahydro-l,5-naphthyridines following the loss of N2 and CH3CN.258 The inverse-electron-demand Diels-Alder reaction of 4,6-dinitrobenzofuroxan (137) with ethyl vinyl ether yields two diastereoisomeric dihydrooxazine /V-oxide adducts (138) and (139) together with a bis(dihydrooxazine A -oxide) product (140) in die presence of excess ethyl vinyl ether (Scheme 52).259 The inverse-electron-demand Diels-Alder reaction of 2,4,6-tris(ethoxycarbonyl)-l,3,5-triazine with 5-aminopyrazoles provides a one-step synthesis of pyrazolo[3,4-djpyrimidines.260 The intermolecular inverse-electron-demand Diels-Alder reactions of trialkyl l,2,4-triazine-4,5,6-tricarboxylates with protected 2-aminoimidazole produced li/-imidazo[4,5-c]pyridines and die rearranged 3//-pyrido[3,2-[Pg.460]

An Australian sponge Axinella sp. has afforded the novel axinellamines A-D (1310-1313), which exhibit activity against Helicobacter pylori (1301). The similar massadine (1314) from the Japanese sponge Stylissa aff. massa inhibits geranylger-anyltransferase type I and the fungus Candida albicans (1302). Like many of these 2-aminoimidazole alkaloids, 1310-1314 were isolated as acid salts trifluoroacetic acid salts in these cases. 

Mourabit AA, Potier P (2001) Sponge s Molecular Diversity Through the Ambivalent Reactivity of 2-Aminoimidazole A Universal Chemical Pathway to the Oroidin-Based Pyrrole-Imidazole Alkaloids and Their Palau amine Congeners. Eur J Org Chem 237... 

The common character of cyclocondensations involving a,(3-unsaturated carbonyls and their synthetic equivalents with aminoazoles was described in several publications. The reaction of chalcones 152 and the corresponding Mannich bases 153 with 2-aminobenzimidazole 154 yields 1,4-dihydro-benzo[4,5]imidazo[l,2-<2]pyrimidines 158 [159], with 5-aminopyrazoles 155 yields 4,7-dihydropyrazolo[l,5- ]pyrimidines 159 [160, 161], with 5-aminotetra-zole 156 yields 4,7-dihydrotetrazolo[l,5-<2]pyrimidines 160 [162] and with 2-aminoimidazoles 157 yields 5,8-dihydroimidazo[l,2- ]pyrimidines 161 [163] (Scheme 3.47). 

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