Application of Deep Eutectic Solvents in the Synthesis of Substituted 2-Mercaptoquinazolin-4(3H)-Ones: A Comparison of Selected Green Chemistry Methods

Abstract

In this study, deep eutectic solvents (DESs) were used as green and eco-friendly media for the synthesis of substituted 2-mercaptoquinazolin-4(3H)-ones from different anthranilic acids and aliphatic or aromatic isothiocyanates. A model reaction on anthranilic acid and phenyl isothiocyanate was performed in 20 choline chloride-based DESs at 80 °C to find the best solvent. Based on the product yield, choline chloride:urea (1:2) DES was found to be the most effective, while DESs acted both as solvents and catalysts. Desired compounds were prepared with moderate to good yields using stirring, microwave-assisted, and ultrasound-assisted synthesis. Significantly, higher yields were obtained with mixing and ultrasonication (16–76%), while microwave-induced synthesis showed lower effectiveness (13–49%). The specific contribution of this research is the use of DESs in combination with the above-mentioned green techniques for the synthesis of a wide range of derivatives. The structures of the synthesized compounds were confirmed by 1H and 13C NMR spectroscopy.

N-, O- and S-Heterocycles Synthesis in Deep Eutectic Solvents

“…A dual role of the DES, as both the green medium and catalyst, through the formation of hydrogen bonds with the reactants and reaction intermediates, was hypothesized [47]. In 2022, the same authors, starting from aliphatic or aromatic isoth variously substituted anthranilic acids (63), were also able to synthe mercaptoquinazolin-4(3H)-one derivatives of 64, Scheme 21 [49]. Twenty based eutectic mixtures were screened, showing the combination ChCl/ur as the most effective to perform the reaction.…”

“…In 2022, the same authors, starting from aliphatic or aromatic isothiocyanates and variously substituted anthranilic acids (63), were also able to synthetize in DES 2-mercaptoquinazolin-4(3H)-one derivatives of 64, Scheme 21 [49]. Twenty different ChCl-based eutectic mixtures were screened, showing the combination ChCl/urea 1:2 mol/mol as the most effective to perform the reaction.…”

“…In the reaction performed at 80 • C for 1 h, the use of stirring or ultrasounds led to higher yields of the heterocycles 64 (17-76%), while microwave-induced synthesis showed lower results (64 yields: 10-49%), Scheme 21. Moreover, the recyclability of the DES was examined showing that the reusability of the eutectic mixture was good for four recycles, without any appreciable reduction in the product yield [49].…”

“…x FOR PEER REVIEW mixture was good for four recycles, without any appreciable reduction in the p yield [49]. The same eutectic mixture ChCl/urea has been applied both as a reaction medium and as a promoter for the synthesis of benzo-fused seven-membered N-heterocyclic systems such as tricyclic 1,4-benzodiazepines 68 and 1,4-benzoxazepines 69 (Scheme 22) [50].…”

Green synthesis of 2‐thioxo‐4‐quinazolinones from 2‐aminobenzamide and isothiocyanates

“…38 Mario et al used choline chloride-based deep eutectic solvents (DES) to synthesize 2-thioxo-4-quinazolinones from various anthranilic acids and aliphatic or aromatic isothiocyanates. 39 Here, we report novel organic solvent-free and additive-free green synthetic methods of straightforward access to 2-thioxo-4-quinazolinones from 2-aminobenzamide and isothiocyanates.…”