Imidazole N-alkylation

Imidazole, 4-alkyl-synthesis, 5, 482 Imidazole, 5-alkyl-synthesis, 5, 481 Imidazole, N-alkyl-metallation, 5, 415-416 reactions, 5, 449-450 synthesis, 5, 387 Imidazole, 1 -alkyl-5-amino-synthesis, 5, 462... 

Michael Addition of Imidazole N-alkyl-imidazoles were also S5mthesized over amino-grafted MCM-41 and NbMCM-41 catalysts by Michael addition between imidazole and ethyl acrylate, at 333K, under sonic... 

Imidazole, 4-acetyl-5-methyl-2-phenyl-synthesis, 5, 475 Imidazole, 1-acyl-reactions, 5, 452 rearrangement, 5, 379 Imidazole, 2-acyl-synthesis, 5, 392, 402, 408 Imidazole, 4-acyl-synthesis, 5, 468 Imidazole, C-acyl-UV spectra, 5, 356 Imidazole, N-acyl-hydrolysis rate constant, 5, 350 reactions, 5, 451-453 synthesis, 5, 54, 390-393 Imidazole, alkenyl-oxidation, 5, 437 polymerization, 5, 437 Imidazole, 1-alkoxycarbonyl-decarboxylation, 5, 453 Imidazole, 2-alkoxy-l-methyl-reactions, 5, 102 thermal rearrangement, 5, 443 Imidazole, 4-alkoxymethyl-synthesis, 5, 480 Imidazole, alkyl-oxidation, 5, 430 synthesis, 5, 484 UV spectra, 5, 355 Imidazole, 1-alkyl-alkylation, 5, 73 bromination, 5, 398, 399 HNMR, 5, 353 synthesis, 5, 383 thermal rearrangement, 5, 363 Imidazole, 2-alkyl-reactions, 5, 88 synthesis, 5, 469... 

Die Reduktion kann bis zum 3-Oxo(Thiono)-5,6-diphenyl-hexahydro-l,2,4-triazin weitergeftihrt werden, dabei wird jedoch beim 3-Oxo-tetrahydro-Derivat in Acetonitril bei pH — 1 (-1,0 V) unter Ringverengung das 2-Hydroxy-4,5-diphenyl-imidazol (50% d.Th. F 318°) gebildet. Zur Reduktion der N-Alkyl-l,2,4-triazinone s, S. 613. 

Herrmann has prepared several unsymmetrical salts 7 from 1-alkyl-imidazoles (Scheme 6). The chirality was introduced, after N-alkylation of the imidazole by chloro acetonitrile, by addition of enantiomerically pure aminoalcohols onto the nitrile to form an oxazolidine ring [14],... 

Because esters 745 a, b of imidazole-acetic acid are unstable when stored for long periods, owing to intramolecular catalysis by the imidazole moiety, the esters should be converted into their salts or free acids and stored as such. Only tert-butyl imidazole-(4,5)acetates derived from tert-butyl 4-chloroacetoacetate seem to be stable [232, 233]. N-alkyl-substituted amidines give rise to a mixture of alkyl N-alkylimidazole-4- and 5-acetates [232, 233]. 

The reaction of 1-amino-1-deoxyketoses, and their N-alkyl and N-aryl derivatives, with alkyl or aryl isothiocyanates (Huber et al, 1960) was studied in more detail, and new 4-(alditol-l-yl)-l-alkyl(aryl)-3-alkyl(aryl)-l,3-dihydro-2H-imidazole-2-thiones were obtained. These compounds were used as starting materials for the synthesis of OL-histidines, DL-histidine-2-thiol, and other imidazole derivatives of biological interest. 

In a similar vein, alkylation of 4-(5)-nitro-imidazole with N-(2-chloroethyl)morpholine affords a mixture of N-alkylated imidazoles (61 and 62). The compound containing the adjacent ring substituents (61) is the antitrichomonal agent nimorazole.15... 

Whereas pyrrole was reported not to give N/H insertion by ketocarbenoids, such a reaction mode does occur with imidazole Copper-catalyzed decomposition of ethyl diazoacetate at 80 °C in the presence of imidazole gives ethyl imidazol- 1-ylacetate exclusively (93 %) small amounts of a C-alkylated imidazole were obtained additionally under purely thermal conditions 244). N/H insertion also takes place at benzimidazole 245 a). The reaction is thought to begin with formation of an N3-ylide, followed by N1 - C proton transfer leading to the formal N/H insertion product. Diazomalonic raters behave analogously however, they suffer complete or partial dealkoxycarbonylation under the reaction conditions 244) (Scheme 34). N-alkylation of imidazole and benzimidazole by the carbenoids derived from co-diazoacetophenone and 2-(diazoacetyl)naphthalene has also been reported 245 b>. 

A related example involves the N-alkylation of azaheterocycles such as imidazole (Scheme 4.8). These reactions are typically performed using 1.5 equivalents of the alkyl halide and a catalytic amount of tetrabutylammonium bromide (TBAB). The reactants are adsorbed either on a mixture of potassium carbonate and potassium hydroxide or on potassium carbonate alone and then irradiated with microwaves (domestic oven) for 0.5 to 1 min. With benzyl chloride, a yield of 89% was achieved after 40 s [18]. 

Scheme 4.8 N-Alkylation of imidazole with alkyl halides under phase-transfer-catalysis conditions.

The Tsuji-Trost reaction is the Pd(0)-catalyzed allylation of a nucleophile [48-51]. The NH group in imidazole can take part as a nucleophile in the Tsuji-Trost reaction, whose applications are found in both nucleoside and carbohydrate chemistry. Starting from cyclopentadiene and paraformaldehyde, cyclopentenyl allylic acetate 64 was prepared in diastereomerically-enriched form via a Prins reaction [52], Treating 64 with imidazole under Pd(0) catalysis provided the N-alkylated imidazole 65. 

Electrophiles can add to N-3, the azomethine =N-of 1,3-azoles as they can to the pyridine nitrogen. N-Alkylation is complicated in the case of imidazole... 

Imidazo[4,5-/ ]pyridines are exclusively hydroxylated in the imidazole ring however, no yield was reported (Equation 3) . N-Alkylation, N-deprotection, palladium-catalyzed cross-coupling, and thionation of imidazo[4,5-/ ]pyridines were reviewed in <1996CHEC-II(7)283>. 

Heterocycles containing an NH group, such as pyrroles, indoles, imidazoles, triazoles, etc., can be linked to insoluble supports as N-alkyl, N-aryl, or N-acyl derivatives (Table 3.29). The optimal choice depends mainly on the NH acidity of the heterocycle in question. Increasing acidity will facilitate the acidolytic cleavage of N-benzyl groups and the nucleophilic cleavage of /V-acyl groups from these heterocycles. 

Substituted imidazole 1-oxides 228 can be prepared by N-oxidation of imidazoles 248, by N-alkylation of 1-hydroxyimidazoles 249, or by cycliza-tion using suitable starting materials derived from a 1,2-dicarbonyl compound, an aldehyde, an amine, and hydroxyamine. The substituents at the three first starting materials are transferred to the product and make control over the substituents in the imidazole 1-oxide 228 possible depending on the protocol used by the synthesis. The synthesis of 3-hydroxyimidazole 1-oxides is presented in Section 3.1.6. 

In addition to phosphines and pyridines, N-alkylated imidazoles are also known to act as a nucleophilic catalysts in acylation reactions [1], In the approach by Miller et al. short oligopeptides incorporating N-alkylhistidine derivatives were used as enantioselective acylation catalysts [27]. The design of, e.g., the tripeptide... 

Benhida, R. Gharbaoui, T. Lechevallier, A. Beugelmans, R. Derives N-alkyles du 4-nitro-imidazole. Synthese par chimie radicalaire (SrnI) et amenagements fonctionnels. Bull. Soe. Chim. Fr. 1994, 333, 200-209. 

The close proximity of functional groups in 1,2-disubstituted benzenes can sometimes bring about an unexpected reactivity. Attempts to N-alkylate ortho-nitroani-lines under strongly basic reaction conditions, for instance, lead to the formation of N-alkoxybenzimidazoles (Scheme 6.10). The main force driving this reaction is the formation of an imidazole ring, a heteroarene with high resonance energy and thermal stability. 

---