Base-Catalyzed Diversity-Orientated Synthesis of Tetra-/Dihydrothiophenecarboxamides and Preliminary Evaluation as Antifungal Agents

Here, we report a facile and mild method for the diverse synthesis of tetra-/dihydrothiophenecarboxamide derivatives ( 3–6 ) via base-initiated [3 + 2] cycloaddition reactions of 1-carbonyl cyclopropanecarboxamides ( 1 ) with isothiocyanates ( 2 ) using EtOH as the solvent, in which a new catalytic mechanism is proposed. In the reaction, EtOH acts as an effective solvent as well as a crucial nucleophilic agent. Further, preliminary antifungal activity tests show that compounds 3b, 3c, 3n, 3w, 4n, and 5e have moderate activities against R. solani ranging from 34.0 to 62.5 % inhibition, while compounds 4o and 6a exhibit lower potency toward F. graminearum with inhibition rates of 20.0% and 25.5% at a concentration of 100 μg/mL.