1- Alkyl-2-methylimidazoles, acylation

The preparation of 2-alkyl- and 2-acyl-l-methylimidazole-4-carboxylates from (Z)-y8-dimethylamino-o -isocyanoacrylate (21) with an alkyl or acyl halide bears similarities to the foregoing DAMN procedures (Scheme 2.1.8) 152, 53]. ITie isocyanoacrylates can be made quite readily by reaction of DMF diethylacetal with the carbanion generated when the isocyanide (22) is metallated f53J. 

Other similar methods which involve cyclization of iV-substituted diaminoalkenes or -alkanes include the preparation of 2-alkyl- and 2-acyl-l-methylimidazole-4-carboxylates from methyl (Z)-j -dimethylamino-a-isocyanoacrylate (191) in reaction with an alkyl or acyl halide <82LA2093>, the preparation of perfluorinated 3-imidazolines (192) <83S169>, the high yield synthesis of 2-imidazolines by decay of phosphaza compounds (193) in a version of the intramolecular Staudinger reaction <85T793>, and the formation of 1,3-diaroylimidazolidines (34-71%) when bis-alkylidene-or -arylidene-ethylenediamines react with acid chlorides in polar solvents (Scheme 129)... 

Chiral 2-(3-oxoalkyl)pyrroles and 3-(3-oxoalkyl)indoles can also be accessed by reaction in the presence of 10 mol% of chiral bis(oxazoline)/metal complexes in CH2C12 in very high yields and with ee values over 90% <2005JA4154>. Alkylation of pyrrole and of substituted indoles with, -unsaturated acyl phosphonates <2003JA10780> or 2-acyl N-methylimidazoles catalyzed by a chiral bis(oxazolinyl)pyridine (pybox)/scandium(III) triflate complex also exhibits good enantioselectivity over a broad range of substrates <2005JA8942>. 

The Friedel-Crafts alkylation of the parent pyrrole and of substituted indoles with a,P-unsaturated acyl phospho-nates 468 <2003JA10780> and 2-acyl iV-methylimidazoles 469 catalyzed by the chiral bis(oxazolinyl)pyridine (pybox)/scandium(lIl) triflate complex 467 exhibits good enantioselectivities over a broad range of substrates (Scheme 97, Equation 113) <2005JA8942>. The desired alkylation products 470-472 were formed in good yields and enantioselectivities. 

Imidazoles have been N-acylated by isocyanates (at elevated tempera-tures) " (Scheme 21), acid halides, and alkyl chlorocarbonates, but 2-methylimidazole would not react with formamide and phosphoryl chloride. Trifluoromethylsulfonation forms the imidazolide which is a convenient reagent for the introduction of the triflate group. ° With highly basic I-substituted imidazoles, acetyl halides form the 1-acetyl-... 

Since N-acylation is a reversible process, it has allowed the regiospecific alkylation of imidazoles to give the sterically less-favored derivative, i.e., the 1,5-disubstituted derivative (e.g., 109 Scheme 22). ° The sequence followed is (1) acylation (2) alkylation (often with oxonium reagents) and (3) deacylation with alcohol, water, or base. The N-acylation of 2-substituted imidazoles using ethyl chloroformate, triethylamine, and acetonitrile gives JV-alkoxycarbonylimidazoles ° which can lose carbon dioxide to give the JV-alkyl derivatives. The reaction is of limited use in the synthesis of asymmetrically substituted imidazoles since, whereas 2-ethyl-4-methylimidazole gave >95% of l-carbethoxy-2-ethyl-4-methylimidazole, the subsequent decarboxylation afforded a 3 1 mixture of 1,2-diethyl-4-methyl and l,2-diethyl-5-methyl compounds. 

Direct tri-0-alkylation of calix[4]arenes has been reported to lead to the syn/syn isomer using bases such as BaO, BaO/Ba(OH)2 or CaH2 in DMF " . The tribenzoate of the p-unsubstituted calix[4]arene, one of the first examples of selectively derivatized calix[4]arenes, was obtained as the anti-syn isomer (benzoyl chloride/pyridine) , while the tribenzoate of 2a obtained in toluene with iV-methylimidazole as base (70% yield) was described as the syn-syn isomer, assuming a partial cone conformation with an inverted phenol ring . Both tris(3,5-dinitrobenzoates) of 2a were obtained by acylation with 3,5-dinitrobenzoyl chloride/l-methylimidazole. While 95% of the syn-syn isomer was formed in acetonitrile, 70% of the anti-syn isomer was obtained in chloroform . 

Esterification reactions readily occur in ionic liquids. A simple example is the reaction of acetic, decanoic and octadecanoic acid with alcohols such as methanol, 1-butanol or 1-octanol. Here, Tang et al. used the ionic liquid [H-MIM][BF4] (this is a simple mixture of 1-methylimidazole and tetrafluoroboric acid) as a solvent and catalyst for the reaction [189]. Singer and coworkers have shown that benzoyl chloride reacts with ethers to give alkyl benzoates [190] in chloroaluminate(iii) ionic liquids. This reaction results in the acylative cleavage of ethers, and a number of reactions with cyclic and acyclic ethers were investigated in the ionic liquid [EMIMjl-AICI3 (X = 0.67). Two examples are shown in Scheme 5.2-79. 

Lithio-l-methylimidazole reacts with alkyl or aryl nitriles to give 2-acyl-1-methylimidazoles (acid anhydrides, acid chlorides and amides give poor, nonreproducible yields of the ketones). These then yield 1-methylimidazolethylenes via a Wittig reaction. Vinylimidazoles are reported to be potentially useful as monomers in the s)uithesis of heterocyclic pol)miers (eq 6). ... 

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