The imidazole scaffold can often be found in a wide variety of bioactive compounds, it serves as the fundamental core of numerous natural products, including histidine, purine, histamine and DNA-base structures[1]. Imidazole derivatives have garnered significant attention in medicinal chemistry due to their diverse biological activities, such as antifungal properties. Clinically, imidazole-based compounds, particularly Miconazole, Econazole, Ketoconazole and Clotrimazole, are widely used to treat yeast and fungal infections[2].
Fig. 1. Synthesis of imidazole-2-thioles containing carbazolyl moiety
In this work, we investigated reactions of 3-amino-9-ethylcarbazole with α-haloketones. The reaction of 3-amino-9-ethylcarbazole with α-haloketones in methanol at room temperature in the presence of sodium bicarbonate resulted in formation of mixture of mono- and bis-addition products. The yields of the formed compounds 2a,b and 3a,b depended on the duration of the reaction. Subsequently, 1-(4-chlorophenyl)-2-((9-ethyl-9H-carbazol-3-yl)amino)ethan-1-one 3a and 2-((9-ethyl-9H-carbazol-3yl)amino)-1-phenylethan-2-one 3b have been cyclized to imidazolethiols 4a,b during the reaction with potassium thiocyanate in glacial acetic acid. Obtained compound 4b have been alkylated with various haloalkanes resulting in formation of compounds -7.
The structures of compounds -4a,b and -7 have been confirmed by elemental analysis, \(^{1}\)H and \(^{13}\)C NMR spectral data.
[1] Benas Balandis, Povilas Kavaliauskas, Birutė Grybaitė, Vidmantas Petraitis, Rūta Petraitienė, Ethan Naing, Andrew Garcia, Ramunė Grigalevičiūtė, Vytautas Mickevičius // Microorganisms, 2023, 11,935, doi:10.3390, 1-14.
[2] D. Serdaliyeva, T. Nurgozhin, E. Satbayeva, M. Khayitova, A. Seitaliyeva, and L. Ananyeva, "Journal of Clinical Medicine of Kazakhstan," J. Clin. Med. Kazakhstan, vol. 19, no. 3, pp. 11–15, 2022, doi:10.23950/jcmk/12117.
