Deep eutectic solvent co-catalyzed synthesis and antimicrobial activity of Morita-Baylis-Hillman adducts from isatin derivatives

• Published in: Journal of molecular structure Vol. 1273; p. 134323
• Main Authors: de-Andrade, Sandro-Dutra, Andrade, Isadora-Maria-Gouveia, Castro, Aleff, Montenegro, Yohana-Maria-Rodrigues, das-Neves-Moreira, Dayse, Maia, Rachel-Azevedo, Martins, Felipe-Terra, Vaz, Boniek-Gontijo, Franco-dos-Santos, Gabriel, Lima, Edeltrudes-de-Oliveira, Oliveira, Nayana-da-Rocha, Farias, Brenda-Kercya-da-Silva, Lima-Junior, Claudio-Gabriel
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 05-02-2023
• Subjects: 3-Substituted-3-hydroxy-2-oxindoles; C-C bond; Green solvents; MBHA; MBHA; 3-Substituted-3-hydroxy-2-oxindoles; Green solvents; C-C bond
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2022.134323

•Deep eutectic solvent-based protocol for cleaner synthesis of compounds with pharmacological potential.•Short reaction times at room temperature with a less amount of catalyst compared to literature reports for MBHR under conventional solvents.•Possibility of reusing DES used as solvent/co-catalyst without compromising reaction yields•Isolation and characterization of the MBHR/transesterification co-product 3h by IR, NMR, and X-ray crystallography.•Compound 3a showed antimicrobial activity against almost all strains of bacteria and fungi tested, showing growth inhibition at a concentration of 32 μg/mL.
A series of fourteen Morita-Baylis-Hillman adducts has been synthesized from isatin derivatives using deep eutectic solvents containing choline chloride (ChCl). Research results showed that the solvent based on ChCl/ethylene glycol (1:2) is a very effective alternative for the synthesis of adducts derived from acrylonitrile, resulting in compounds with excellent yields and short reaction times, after optimization of the catalyst (DABCO). Regarding the synthesis of adducts derived from methyl acrylate, the system ChCl/Urea (1:2) was the most effective, since it suppresses the formation of transesterification co-products between the adducts and the solvent. The use of these systems reduced the amount of catalyst required compared to literature data, acting as co-catalyst. The structure of a transesterification by-product was established by X-ray crystallography. The synthesized compounds were screened for antimicrobial activities. At a concentration of 32 μg/mL, the N-methylisatin/acrylonitrile adduct inhibited the growth of most microorganism species used in biological assays, showing bactericidal and fungicidal nature.
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