Imidazoles from nitroallylic acetates and α-bromonitroalkenes with amidines: synthesis and trypanocidal activity studies

Abstract

Cascade reactions of amidines with nitroallylic acetates and α-bromonitroalkenes provide potentially bioactive imidazoles in good to excellent yields in most cases. While 2,4-disubstituted imidazol-5-yl acetates are formed in the first case, 2,4-disubstituted imidazoles, bearing no substituent at position 5, are the products in the second case. These two series of imidazoles, viz. 2,4,5-trisubstituted and 2,4-disubstituted, were screened for their activity against the protozoan parasite Trypanosoma cruzi which is responsible for Chagas disease. As many as three compounds were as active as the standard benznidazole and two others were 2-3-fold more active highlighting the potential of substituted imidazoles, easily accessible from nitroalkenes, as possible anti-parasitic agents.

Regio- and stereoselective synthesis of functionalized and fused heterocycles from Morita–Baylis–Hillman adducts of dicyclopentadienone

“…To our surprise, our previously established conditions for the [3 + 3] annulation of amidines 9 with MBH acetates of nitroalkenes (DABCO, CH 3 CN, rt) and bromonitroalkenes (CS 2 CO 3 , CH 3 CN, rt), 22 did not work well for the reaction of 9a with MBH acetate 3a. Therefore, we envisaged to perform the reaction of amidine 9a using the corresponding MBH bromide 3b.…”

Ruthenium(II)‐Catalyzed C−H/N−H Alkyne Annulation of Nonsymmetric Imidazoles: Mechanistic Insights by Computation and Photophysical Properties

“…Aware of the importance of imidazoles, our research group has developed, in cooperation with the Namboothiri group, new methods for the synthesis of trypanocidal imidazoles via cascade reaction of nitroallylic acetates with amidines [3] and by the reaction of nitroallylic acetates and α-bromonitroalkenes with amidines. [4] Among our efforts towards the synthesis of new azoles with potential biological activities, the use of βlapachone, a simple and efficient building block, also allowed us to access active imidazoles against susceptible and resistant strains of Mycobacterium tuberculosis, the tubercle bacillus that causes tuberculosis. [8] In this context, in the last few years, we have also focused on the development of new azole molecules from natural quinones, such as β-lapachone, aiming to explore their fluorescent aspects to obtain molecular probes.…”

Ultrasound‐Promoted Mild, and Efficient Protocol for Three‐Component Synthesis of 2,4,5‐Trisubstituted Imidazoles Using Urea and PPh3 as the Sources of Nitrogen and Organocatalyst

“…In recent decades, 2,4,5-trisubstituted imidazoles have received particular attention owing to their remarkable biological activities, for example, trifenagel (platelet aggregation inhibitor), [24] fenflumizole (non-steroidal anti-inflammatory agent), [25] compounds 1, 2 and TPBI as potent antibacterial, [26][27][28] 3PBI as potent antifungal, [27] and 3 as a trypanocidal agent [29] (Figure 2).…”