A series of rhodanine derivatives was synthesized in the Knoevenagel condensation of rhodanine and different aldehydes using choline chloride:urea (1:2) deep eutectic solvent. This environmentally friendly and catalyst free approach was very effective in the condensation of rhodanine with commercially available aldehydes, as well as the ones synthesized in our laboratory. All rhodanine derivatives were subjected to 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) scavenging activity investigation and quantitative structure-activity relationship (QSAR) studies were performed to elucidate their structure-activity relationship. The best multiple linear QSAR model demonstrate a stability in the internal validation and Y-randomization (R2 = 0.81; F = 24.225; Q2loo = 0.72; R2Yscr = 0.148). Sphericity of the molecule, ratio of symmetric atoms enhanced atomic mass along the principle axes in regard to total number of atoms in molecule, and 3D distribution of the atoms higher electronegativity (O, N, and S) in molecules are important characteristic for antioxidant ability of rhodanine derivatives. Molecular docking studies were carried out in order to explain in silico antioxidant studies, a specific protein tyrosine kinase (2HCK). The binding interactions of the most active compound have shown strong hydrogen bonding and van der Waals interactions with the target protein.

Deep eutectic solvents, as green and environmentally friendly media, were utilized in the synthesis of novel coumarinyl Schiff bases. Novel derivatives were synthesized from 2-((4-methyl-2-oxo-2H-chromen-7-yl)oxy)acetohydrazide and corresponding aldehyde in choline chloride:malonic acid (1:1) based deep eutectic solvent. In these reactions, deep eutectic solvent acted as a solvent and catalyst as well. Novel Schiff bases were synthesized in high yields (65–75%) with no need for further purification, and their structures were confirmed by mass spectra, 1H and 13C NMR. Furthermore, their antioxidant activity was determined and compared to antioxidant activity of previously synthesized derivatives, thus investigating their structure–activity relationship utilizing quantitative structure-activity relationship QSAR studies. Calculation of molecular descriptors has been performed by DRAGON software. The best QSAR model (Rtr = 0.636; Rext = 0.709) obtained with three descriptors (MATS3m, Mor22u, Hy) implies that the pairs of atoms higher mass at the path length 3, three-dimensional arrangement of atoms at scattering parameter s = 21 Å−1, and higher number of hydrophilic groups (-OH, -NH) enhanced antioxidant activity. Electrostatic potential surface of the most active compounds showed possible regions for donation of electrons to 1,1-diphenyl-2-picryhydrazyl (DPPH) radicals.

A study of 1,2,4‐triazole synthesis from 2‐((4‐methyl‐2‐oxo‐2H‐chromen‐7‐yl)oxy)acetohydrazide (1) or 2‐(7‐hydroxy‐2‐oxo‐2H‐chromen‐4‐yl)acetohydrazide (2) and various isothiocyanates, in deep eutectic solvents, was performed. In order to find the best conditions for 1,2,4‐triazole formation, a model reaction on 1 and phenylisothiocyanate was performed in 14 different choline chloride based deep eutectic solvents, at two different temperatures (40 °C and 80 °C). Pure 1,2,4‐triazoles were obtained in choline chloride/urea (1:2) and choline chloride/N‐methyl urea (1:3) deep eutectic solvents at 80 °C. Pure thiosemicarbazides were obtained in choline chloride/ethane‐1,2‐diol (1:2), choline chloride/malic acid (1:1), choline chloride/malonic acid (1:1), choline chloride/butane‐1,4‐diol (1:3) and choline chloride/glycerole (1:2) at 40 °C. The ratio of 1,2,4‐triazoles and thiosemicarbazides in reaction mixtures was determined by HPLC and 1H NMR. After the best conditions for 1,2,4‐triazole synthesis were found, some coumarinyl 1,2,4‐triazoles were synthesized from two different coumarinyl hydrazides (1 and 2) and various alkyl and aryl isothiocyanates in one step reaction.

In this study, two fast and efficient protocols for green synthesis of 3-substituted quinazolinones were perfomed. A synthesis of 2-methyl-3-substituted quinazolinones was performed in natural deep eutectic solvents, while 3-aryl quinazolinones were obtained by using microwave assisted synthesis. Benzoxazinone, which was used as an intermediate in the synthesis of 2-methyl-3-substituted quinazolinones, was prepared conventionally from anthranilic acid and acetic anhydride. In order to find the most appropriate synthetic path, twenty natural deep eutectic solvents were applied as a solvent in these syntheses. Choline chloride:urea (1 : 2) was found to be the most efficient solvent and was further used in the synthesis of 2-methyl quinazolinone derivatives (2–12). 3-Aryl quinazolinones (13–17), on the other hand, were synthesized in one-pot microwave-assisted reaction of anthranilic acid, different amines and trimethyl orthoformate. All compounds were synthesized in good to excellent yields, characterized by LC-MS/MS spectrometry and 1H- and 13C-NMR spectroscopy.

This mini-review encapsulates the latest findings (past 10 years) in the field of the deep eutectic solvents (DESs) application in the alkylation/arylation of different heterocyclic compounds. These solvents have been developed to fulfill the green chemistry concept demands and have been proven excellent for the application in various fields. This review describes their application in different types of alkylation, C-, N-, O- and S-alkylation. P-alkylation has not yet been published within this scope. Not only have the authors in this study proven that DESs could be successfully applied for this specific type of reaction, but they have also offered an excellent insight into the mechanisms of their action.