39021-62-0Relevant articles and documents
Imidazole alkaloids. IV. Synthesis of (±) isoanatine and (±)-anatine
Tchissambou,Benechie,Khuong-Huu
, p. 1801 - 1802 (1978)
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4,5-Disubstituted N-Methylimidazoles as Versatile Building Blocks for Defined Side-Chain Introduction
Przybyla, Daniel,Nubbemeyer, Udo
supporting information, p. 695 - 703 (2017/02/05)
Fungerin is a 1,4,5-trisubstituted imidazole natural product characterised by a broad spectrum of antifungal activities. We planned to develop flexible strategies to access to such compounds. Imidazoles bearing suitable anchor groups at C-4 and C-5 allow the introduction of various substituted side-chains, generating libraries of fungerin derivatives for biological tests. Starting from commercially available reactants, two N-methyl 4,5-substituted imidazole core units were synthesised. Derivatives of type 1 contained two orthogonally protected C-1 anchors. Selective side-chain introduction was achieved through a sequence of Grignard coupling at C-5 to replace a tosylate and a Horner olefination through an aldehyde attached to C-4. Two target fungerin derivatives were synthesised. Since the organometallic substitution of the C-5-CH2-positioned leaving group proved to suffer from limitations concerning potential competing side-reactions, a type 2 imidazole core was built up. These structures had a halogen centre at C-4 and a hydroxyethyl anchor at C-5. Now, selective side-chain introduction allowed us to use Julia olefination to form the allyl side-chain at C-5 and Heck reactions to introduce the C-4 acryl substituents. Eight derivatives, including fungerin, were synthesised by this latter strategy, without producing any regioisomers. The second approach had the advantage that various side-chains could be coupled at C-4 and C-5 in two final steps. Thus, this strategy represents a versatile way to build up libraries of fungerin derivatives for biological testing.
Development of a regioselective N-methylation of (benz)imidazoles providing the more sterically hindered isomer
Van Den Berge, Emilie,Robiette, Raphael
, p. 12220 - 12223 (2014/01/06)
An efficient and highly regioselective N-methylation of (NH)-(benz)imidazoles furnishing the sterically more hindered, less stable, and usually minor regioisomer has been developed. The methodology involves very mild reaction conditions and tolerates a wide range of functional groups.
Regiochemistry of N-substitution of some 4(5)-substituted imidazoles under solvent-free conditions
Oresmaa, Larisa,Taberman, Helena,Haukka, Matti,Vainiotalo, Pirjo,Aulaskari, Paula
, p. 1445 - 1451 (2008/09/18)
(Chemical Equation Presented) Imidazole-4(5)-carboxaldehyde and 4(5)-cyanoimidazole were N-benzylated and N-methylated using benzyl chloride and methyl iodide on zinc oxide (ZnO), alumina, and KF/alumina under basic conditions without solvent. Triethylamine (Et3N) or potassium carbonate was added as base in the reactions on ZnO and alumina. Imidazole-4(5)-carboxaldehyde was also benzylated on silica and carbon nanotubes. The effect of bases and solids on the product distribution of 1,4- and 1,5-substituted compounds was investigated. In some cases, the product ratios were different for imidazole-4(5)-carboxaldehyde and 4(5)-cyanoimidazole. In the reactions on KF/alumina the 1,4-product was favored for both compounds. The combination of Et3N and ZnO favored the 1,5-product, however for the nitrile effect was not so pronounced. When N-benzylation and methylation of the aldehyde were performed in the presence of catalytic amount of zinc chloride with Et3N as base, the product distributions were the same as in the reactions on ZnO. Nitrile gave different product ratios on ZnO and in the presence of ZnCl2. In addition, a mixture of N-benzylimidazole and 1,3-dibenzylimidazolium was produced when imidazole was benzylated on KF/alumina. Only the latter product was afforded when two equivalents of benzyl chloride were used.
