Investigação do uso de solventes eutéticos profundos como co-catalisador na reação de Morita-Baylis-Hillman envolvendo derivados de isatina e ésteres acrílicos

Abstract

The search for greener synthetic protocols has been a challenge for Chemistry in recent decades. This work describes the use of Deep Eutectic Solvents (DES) as

a substitute for volatile organic solvents and as a co-catalyst in the Morita-Baylis- Hillman Reaction (MBHR). We investigated some DES consisting of choline

chloride (ChCl), glycerol (G), ethylene glycol (EG) and urea (U), applied in MBHR using as electrophiles, isatin, 5-chloroisatin, 5,7-dichloroisatin, 5- fluoroisatin, 5- nitro-isatin, 5-methyl-isatin and their respective N-alkylated derivatives. As Michael acceptors, acrylonitrile, methyl acrylate and 2-hydroxyethyl acrylate were used, and the experiments were conducted at room temperature, leading to obtaining twelve Morita-Baylis-Hillman adducts with yields that varied between 40 - 98%, in reactions lasting from 50 minutes to 30 hours, according to the type of DES and Michael acceptors used. The unpublished adducts derived from 2- hydroxyethyl acrylate (11 and 11a) were obtained during the investigations and completely characterized and elucidated by Infrared (IR) spectroscopic techniques, 1H and 13C Nuclear Magnetic Resonance and High Resolution Mass Spectrometry. We also sought to establish protocols reducing the amount of DABCO to catalytic proportions (15 mol%), in addition to a probable replacement

with Hexamethylenetetramine (HMTA), which is less expensive and non- hygroscopic. In this case, even comparing their behavior by altering DES and

Michael's acceptor, it was observed that the use of HMTA was not satisfactory in relation to DABCO. Throughout the investigation, we identified that the DES consisting of ChCl:EG (1:2) promoted a transesterification reaction with methyl acrylate, which made its use unfeasible as a solvent for reactions involving this Michael acceptor. New protocols were proposed for the synthesis of the adduct derived from 2-hydroxyethyl acrylate (11) using DESs constituted by ChCl:EG (1:2) and ChCl:U (1:2). The substitution of DES ChCl:EG (1:2) for ChCl:U (1:2) and the use of 50 mol% of DABCO proved to be a very promising methodology, reducing the reaction times (5 – 30h) in relation to other protocols established in the literature and satisfactory yields (45 - 95%). An investigation into the prototype reaction between N-methylisatin and methyl acrylate was carried out by Electrospray Mass Spectrometry (ESI(+)-MS), allowing to identify some reaction intermediates that are proposed in this work. The DES consisting of ChCl:U (1:2) was reused two more times, but the increased viscosity of the reaction medium proved to be a limiting factor to be overcome.