Investigação do uso de micro-ondas/solventes eutéticos profundos na síntese de espiro 1,3,4-tiadiazolinas derivadas da isatina

• Ano de defesa: 2021
• Autor(a) principal: Castro, Aleff Cruz de
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal da Paraíba; Brasil; Química; Programa de Pós-Graduação em Química; UFPB
• Palavras-chave em Português: Espiro-oxindóis; Irradiação por micro-ondas; Reação one-pot; Reação multicomponente; ChCl/ácido oxálico; Spirooxindoles; Microwave irradiation; One-pot reaction; Multicomponent reaction; ChCl/oxalic acid; CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA
• Link de acesso: https://repositorio.ufpb.br/jspui/handle/123456789/23539

Compounds with an oxindolic nucleus have consolidated importance in the literature due to their therapeutic potential, as well as 1,3,4-thiadiazolin compounds, which are also explored in several pharmacological applications. In the field of green chemistry, the alternative methodology proposed here aims to minimize the use of conventional and toxic solvents, as well as the amount of the acetylating agent used in the synthesis of 1,3,4-thiadiazoline nucleus. Due to effective thermal management, microwave-assisted reactions are widely applied to obtain spirocompounds, as well as the use of eutetic solvents that also allow the exploration of one-pot multicomponent reactions. The combination of these two factors minimizes the number of steps involved in the process and, consequently, its cost. The work considers two groups of isatin derivatives, the first of which is constituted by twelve monomeric spirocyclic compounds based on isatin/thiadiazoline, whose obtainment is already reported through a two-step synthesis. Thus, the use of five deep eutetic solvents (DES) based on different organic acids, as solvent/catalyst in obtaining spiro compounds was explored. The optimization of the reaction conditions indicated the use of DES choline chloride/oxalic acid under microwave irradiation at 100 ºC as suitable conditions for the synthesis. The results obtained for the monomers, characterized by conventional physical methods (IR, 1H and 13C NMR), demonstrated the applicability of the protocol to all compounds, reaching yields of up to 79%. Spiros derived from N-methylisatin, 5,7-dichloroisatin and N-allyl 5,7-dichloroisatin showed the best yields. Several compounds in this series maintained their yields practically unchanged, enabling the use of one-pot synthesis as an alternative faster, cleaner, and more economical. All the synthesized spirocycles showed signals in 1H and 13C NMR consistent with the proposed structures. The second group studied consists of six (unpublished) spirocyclic dimers that were initially synthesized from a two-step reaction (obtaining thiosemicarbazones and conversion to spiro thiadiazolines) to establish a comparison parameter with the results obtained via the one-pot reaction. Bis-isatins with different spacers and substituents on the aromatic ring (obtained with a yield of 73%–97%) were used to obtain the dimeric thiosemicarbazones via microwave irradiation at reaction times of 30-40 min, with yields 65%– 82%. After its isolation, further cyclization by acetylation with acetic anhydride to generate the desired spirocompounds under microwave irradiation for 30 min, resulted in 30%–57% yields. The use of the one-pot methodology for these dimeric compounds, based on the optimal conditions, showed less effective compared to the monomers, so that only two compounds showed yields close to those obtained by the two-step route. Mono and dichlorinated dimers showed significantly lower yields (8%-13%), indicating the need to explore specific reaction conditions based on the use of DES and microwaves that maximize the obtainment of these compounds.