N-Aminoimidazoles

The scope of direct amination reactions is not too great in comparison with all other methods for synthesizing simple N-aminoimidazoles. Probably the first specific example of N-amination of imidazoles was the synthesis of l-tosylamino-2,4,5-triphenylimidazole on treatment of the lophine anion with tosylazide [Eq. (9)] (72BCJ306). However, the yield of 35 was small because of the side formation of 2,4,6-triphenyl-l,3,5-triazine and diphenyl acetylene. 

N-Aminoimidazolium salts 36 were obtained in good yield on short-term heating of 1-R-imidazoles and MSH in methylene chloride (74CPB482 74JHC781). All other methods of obtaining of N-aminoimidazoles are based on cyclization and recyclization reactions. Thus, at the end of the last century Fischer et al synthesized l-amino-3-phenylimidazoline-2-thione (37) in 45% yield by cyclization of 2-(2,2-diethoxyethyl)-4-phenyl-thiosemicarbazide in acid (1894CB2203). 

Syntheses of condensed N-aminoimidazoles can also occur by building new rings onto A -aminoimidazole as shown by Eq. (24) (79MI1 90KGS1689) and Eq. (25) (88KGS1070). 

Aminoimidazole (64) has been reported to react with various bifunctional reagents to give bicyclic systems (Scheme 6). In some cases the initial N-addition-elimination product has been isolated (e.g., 68 and 69). 

Dioxane solutions of 4(5)-aminoimidazole (64) have been treated with several reagents [92JCS(P1)2789], Imidazo[l,5-a]-l,3,5-triazines (65 R = Ph, Me SMe) were obtained by reaction with methyl N-cyanobenzimidate (57 R = Ph), ethyl N-cyanoacetimidate (58 R = Me), and dimethyl yV-cyanodithioiminocarbonate (59 R = SMe). The uncy-clized product (68 R = H) (73%), obtained by condensation with ethyl N-cyanoformimidate (58 R = H), underwent facile cyclization to give the imidazo[l,5-a]-l,3,5-triazine (65 R = H). Likewise, the condensation adduct (69 R = H) (78%) was obtained using ethoxy methyleneurethane (60 R = H) and this underwent base-catalyzed cyclization to give the imidazo[ 1,5-a]-1,3,5-triazinone (67). Imidazo[l, 5-a]pyrimidines (66 R = H, Me) were obtained from the condensation of 4(5)-aminoimidazole... 

The modes of reaction of several 5-aminoimidazoles (96) with the reagents (135-142) are summarized in Table V. The variation of product structure with reagent is clearly discemable. The preference for C- or N-addition has been interpreted in terms of a frontier orbital analysis of the reactants [92JCS(P1)2779, 92JCS(P1)2789] (see Section VI,C). The... 

Using the INDO approximation on fully optimized geometries, the lone pair orbital energy (eN) (of 3-N) in 4-aminoimidazole (179 R = R2 = H) was calculated to be 0.4482 au and the protonation energy (AEp) of the same molecule was calculated to be 374.9 kcal mol-1 (83H1717). 

Diethyl N-hetarylaminomethylenemalonates were prepared in good yields in the reactions of diethyl N.N-dimethylaminomethylenemalonate and 5-aminoimidazole, 5-aminoisothiazole or 2-aminothiophene hydrochlorides in DMF or acetic acid at 20-80°C for 1-5 hr [77JAP(K)116460],... 

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 the 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-d]pyrimidines.260 The intermolecular inverse-electron-demand Diels-Alder reactions of trialkyl l,2,4-triazine-4,5,6-tricarboxylates with protected 2-aminoimidazole produced l//-imidazo[4,5-c]pyridincs and the rearranged 3 / /- py r i d 0 [ 3,2 - d] py r i m i d i n - 4 -... 

PFACRI N -[(5 -phosphoribosyl)formimino]-5-aminoimidazole-4-carboxamide ribonucleotide isomerase ImGPS imidazole 3-glycerol phosphate synthase OMPDC orotidine 5 -phosphate decarboxylase R5PE ribulose 5-phosphate epimerase HUMPS hex-3-ulose monophosphate... 

Dacarbazine is a synthetic compound that functions as an alkylating agent following metabolic activation by liver microsomal enzymes by oxidative N-demethylation to the monomethyl derivative. This metabolite spontaneously decomposes to 5-aminoimidazole-4-carboxamide, which is excreted in the urine, and diazomethane. The diazomethane generates a methyl carbonium ion that is believed to be the likely cytotoxic species. Dacarbazine is administered parenterally and is not schedule-dependent. It produces marked nausea, vomiting, and myelosuppression. Its major applications are in melanoma, Hodgkin s disease, and soft tissue sarcomas. 

Independent of the actual mechanism, functional divergence between two proteins with a common ancestor is exemplified in the /la-barrel structures of N-(phosphor-ibosyl-formimino)-aminoimidazole-carboxamide ribonucleotide isomerase (HisA) and imidazole glycerol phosphate synthase (HisF) of the histidine biosynthetic pathway [16]. The hypothesis of a common origin of the two enzymes was formulated based on sequence comparison [17] and has recently found support by the identification of extensive structural similarities [18],... 

Abbreviations ADCA, adipyl-cephalosporic acid epPCR, error-prone PCR IGPS, indole-3-glycerol phosphate synthase MO, monooxygenase MS, mutator strain PRAI, phosphoribosylanthranilate iso-merase ProFARI, N -[5-phosphoribosyl)formimino]-5-aminoimidazole-4-carboxylamide ribonucleotide isomerase SDM, site-directed mutagenesis, StEP, staggered extension process... 

Ethyl jV - cy ano met hylaceti midate (or formiraidate) reacts with primary amines to form 1-substituted 5-aminoimidazoles.75 76 Similarly, reaction between ethyl N - (carbamoylcyano methyl )for mi -midate (and other imidates) and hydrazine, phenylhydrazine, or 2-methylsemicarbazide yields l-aminoimidazole-4-carboxyamides... 

Restricted rotation (atropisomerism) about N-N single bonds in 1-aminoimidazole derivatives... 

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