Investigação do Solvente Eutético Cloreto de Colina/Etilenoglicol na preparação de adutos de Morita-Baylis-Hillman derivados da acrilonitrila

Abstract

Morita-Baylis-Hillman reaction (MBHR) is an important C-C bonding reaction, with great potential associated with obtaining polyfunctionalized molecules. It is an organocatalyzed reaction, with high atomic economy and mild reaction conditions to produce adducts used as versatile blocks for compounds with biological potential. However, MBHR still has a number of limitations, mainly the long reaction time and low yield due to the reactivity of the activated alkene and the electrophile. The use of new catalysts and co-catalysts/solvents, such as Ionic Liquids (IL) and recently Deep Eutectic Solvents (DES), have been investigated as an alternative to overcome these adversities. In this context, the present work describes the synthesis of Morita-Baylis-Hillman adducts from acrylonitrile and isatin derivatives, using the Choline chloride/Ethylene glycol [ChCl/EG] mixture as a deep eutectic solvent in MBHR conducted at room temperature. Seventeen isatin derivatives were investigated as electrophiles and acrylonitrile as a Michael acceptor, in reactions catalyzed by 1,4-diazabicyclo [2.2.2] octane (DABCO) (15 mol%). It was found that the presence of DES promoted a significant decrease in reaction times, which ranged from 25 to 57 minutes, with good to excellent yields (77 - 99%) compared to literature data for the same compounds obtained via synthesis with conventional solvents. The role of DES as a co-catalyst was based on the most recent proposed mechanisms for MBHR involving polar protic solvents. All synthesized adducts were evaluated for bactericidal and fungicidal. The N-methylated adduct (1e) showed a strong inhibition of microbial growth, with a minimum inhibitory concentration of 32 μg/mL against 84% of the species of bacteria and fungi studied.