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

• Published in: Journal of heterocyclic chemistry Vol. 60; no. 3; pp. 392 - 405
• Main Authors: Castro, Aleff, Andrade, Isadora Maria Gouveia, Coelho, Maísa Cavalcanti, Costa, Daniel Pereira, Moreira, Dayse das Neves, Maia, Rachel Azevedo, Lima, Gesiane da Silva, Santos, Gabriel Franco, Vaz, Boniek Gontijo, Militão, Gardênia Carmen Gadelha, Silva, Paulo Bruno Norberto, Vasconcellos, Mário Luiz Araujo de Almeida, Lima‐Junior, Claudio Gabriel
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Inc 01-03-2023; Wiley Subscription Services, Inc
• Subjects: Anticancer properties; Choline; Irradiation; Oxalic acid; Solvents; Synthesis
• ISSN: 0022-152X; 1943-5193
• DOI: 10.1002/jhet.4591

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.