Multicomponent synthesis of spiro 1,3,4‐thiadiazolines with anticancer activity by using deep eutectic solvent under microwave irradiation

This work describes a simple and efficient alternative method for obtaining 1,3,4‐thiadialzolinic spirocompounds, combining the use of deep eutectic solvents (DES) with microwave irradiation in a one‐pot process. A series of DES based on different acids was explored as a solvent in a three‐component reaction including isatin derivatives (monomeric and dimeric), thiosemicarbazide, and acetic anhydride. Choline chloride and oxalic acid (1:1) showed better results concerning the other solvents evaluated, reaching yields of up to 79% when applied to the other compounds of the proposed series. For most of the monomeric compounds, the yields were very close to or higher than those reported in the literature for two‐step synthesis. These results demonstrate the possibility of using one‐pot synthesis as a faster, cleaner, and more efficient alternative method for obtaining thiadiazolines with expressive cytotoxic activity. Monomeric and dimeric spiro‐thiadiazolines were synthesized through a multicomponent reaction using DES as a solvent/catalyst system, showing promising results in relation to literature reports for two‐step reactions.