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

Abstract

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.