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

Tatjana Gazivoda Kraljević,Mario Komar,Igor Jerković,Maja Molnar

doi:10.3390/molecules27020558

Tatjana Gazivoda Kraljević, Mario Komar + Show 2 more

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https://doi.org/10.3390/molecules27020558

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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.

Highlights

Quinazolinones, as oxygen- and nitrogen-containing fused heterocyclic compounds, Quinazolinones, as oxygenand nitrogen-containing heterocyclic compounds, are an important scaffold in pharmaceutical and medicinalfused chemistry showing significant are an important scaffold in pharmaceutical and medicinal chemistry showing significant biological activities
Considerable we describe aattention synthesis reducing the adverse effects on the environment
As our previous results [33] indicated that products could be synthesized in ChCl:urea (1:2) deep eutectic solvents (DESs), we investigated the influence of reaction temperature (40 ◦ C, 60 ◦ C, and 80 ◦ C) and time

Summary

Introduction

Quinazolinones, as oxygen- and nitrogen-containing fused heterocyclic compounds, Quinazolinones, as oxygenand nitrogen-containing heterocyclic compounds, are an important scaffold in pharmaceutical and medicinalfused chemistry showing significant are an important scaffold in pharmaceutical and medicinal chemistry showing significant biological activities. They exist in the form of two isomers. The keto functionality may be biological activities The keto functionality may be present on the second, fourth, or both carbon atoms of the quinazoline nucleus (Figure 1). Present on the second, fourth, or both carbon atoms of the quinazoline nucleus (Figure 1) [1]. Present on the second, fourth, or both carbon atoms of the quinazoline nucleus (Figure 1) [1]. [1].

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