1‐Alkyl‐3‐methylimidazole‐2‐thiones were prepared from amino esters in one pot and converted to inherently halide‐free 1‐alkyl‐3‐methylimidazolium benzoates by oxidation with benzoyl peroxide followed by a novel anion exchange. Also reported are the outcomes of exchanges with other anions, acidifications of the imidazolium benzoates to other salts, and extension of the method to the syntheses of 1,3‐diphenylimidazolium and 3‐methyl‐ and ‐butylthiazolium salts.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

A DBU-mediated aldol condensation-dehydration sequence has been used to prepare a series of synthetically important substituted 2-and 3-azachalcones. Michael products that typically accompany this sequence with inorganic bases were not observed in this protocol of high practical value.Keywords: aldol reaction; azachalcones; chemoselectivity; organic catalysis; pyridinecarboxaldehydes Azachalcones are valuable intermediates for Diels-Alder and Michael reactions as well as many other conversions.[1] Although there are many ways to prepare azachalcones (Scheme 1), [2 -4] none appear universally applicable to synthesize a wide variety of azachalcones using a common synthetic protocol. All current approaches suffer from subsequent Michael addition to the desired azachalcone to varying degrees. In one case, the precipitate isolated from the condensation of 2 and acetophenone was actually an oily mixture of the Michael adduct 13 or 14 and the desired azachalcone (9 or 10).[2] In condensations of 1 and several substituted benzaldehydes, cyclic products (e.g., 15) were reportedly isolated regardless of the stoichiometry used.[5] These compounds form in high yields under conditions identical to those suggested for the synthesis of the azachalcones, and their structures were confirmed using X-ray crystallography. Aryl-substituted oligopyridines (17) are isolated in 40% yield via the Krçhnke methodology by using Michael adduct 16, generated under conditions identical to those used to prepare the azachalcones.[6] A reliable preparation of azachalcones therefore necessitates the prevention of the Michael pathway.A recent study by Wachter-Jursczak and co-workers proposed that the Michael pathway is favored by coordination of the metal ion to the azachalcone through an interaction with the nitrogen.[7] The cation withdraws electron density from the conjugated system, making the enone a better Michael acceptor (Scheme 2). Only the Michael adducts (e.g., 13 and 14) were isolated from condensations using 2 and 2-quinolinecarboxaldehyde. The study showed that the reaction of 2-quinolinecarboxaldehyde could be stopped at the dehydration product by applying stoichiometric amounts of pyridine to bind the metal ion. The same approach, however, did not prevent Michael addition in reactions involving 2.In order to circumvent all of the problems noted above, we considered application of an organic base to eliminate the metal ion from the reaction mixture. We chose 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as the base because it is readily available, highly basic, and of low nucleophilicity.[8] In our continuing interest with organocatalysis and specifically the use of thioureas to catalyze Diels-Alder reactions, we sought a series of substituted azachalcones that would elucidate the binding mechanism of thiourea catalysts.[9] Since these catalysts are believed to activate dienophiles through hydrogen bonding, azachalcones present the potential for activation by bidentate chelation.For comparison with literature data, we first pre...

Glycine was acylated with isothiocyanates and condensed to 3-alkyl 2-thiohydantoins, which were reduced with a mixture of sodium borohydride and lithium chloride and dehydrated to 1-alkyl imidazole-2-thiones. These were oxidatively desulfurized to imidazoles with benzoyl peroxide. No chromatography was required for model compounds. The methods developed were used to elaborate tyrosine to 1,4-di(p-methoxybenzyl)imidazole, a common intermediate in the syntheses of three imidazoles from the sponge Leucetta.