Lithium-Acetate-Mediated Biginelli One-Pot Multicomponent Synthesis under Solvent-Free Conditions and Cytotoxic Activity against the Human Lung Cancer Cell Line A549 and Breast Cancer Cell Line MCF7

Harshita Sachdeva,Diksha Dwivedi

doi:10.1100/2012/109432

Harshita Sachdeva, Diksha Dwivedi

Open Access

https://doi.org/10.1100/2012/109432

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Abstract

Various Biginelli compounds (dihydropyrimidinones) have been synthesized efficiently and in high yields under mild, solvent-free, and eco-friendly conditions in a one-pot reaction of 1,3-dicarbonyl compounds, aldehydes, and urea/thiourea/acetyl thiourea using lithium-acetate as a novel catalyst without the addition of any proton source. Comparative catalytic efficiency of lithium-acetate and polyphosphoric acid to catalyze Biginelli condensation is also studied under neat conditions. The reaction is carried out in the absence of any solvent and represents an improvement of the classical Biginelli protocol and an advantage in comparison with FeCl3 ·6H2O, NiCl2 ·6H2O and CoCl2 ·6H2O that were used with HCl as a cocatalyst. Compared to classical Biginelli reaction conditions, the present method has advantages of good yields, short reaction times, and experimental simplicity. The obtained products have been identified by spectral (1H NMR and IR) data and their melting points. The prepared compounds are evaluated for anticancer activity against two human cancer cell lines (lung cancer cell line A549 and breast cancer cell line MCF7).

Highlights

Multicomponent reactions (MCRs) have emerged as an efficient and powerful tool in modern synthetic organic chemistry because the synthesis of complex organic molecules from simple and readily available substrates can be achieved in a very fast and efficient manner without the isolation of any intermediate [1, 2]
Perusal of literature revealed that the Biginelli reaction, which was discovered more than a century ago, is one of the most important MCRs for the synthesis of dihydropyrimidinones based on acid-catalyzed three component condensation of β-dicarbonyl compound, an aldehyde, and urea or thiourea [3, 4]
During our quest to develop novel catalysts for multicomponent reactions, we have found that lithiumacetate is effective promoter of Biginelli reaction

Summary

Introduction

Multicomponent reactions (MCRs) have emerged as an efficient and powerful tool in modern synthetic organic chemistry because the synthesis of complex organic molecules from simple and readily available substrates can be achieved in a very fast and efficient manner without the isolation of any intermediate [1, 2]. The pioneering work of Toda et al [5] has shown that many exothermic reactions can be accomplished in high yield by just grinding solids together using mortar and pestle, a technique known as “grindstone chemistry,” which is one of the “green chemistry techniques.”. In addition to being energy efficient, grindstone chemistry results in high reactivity and less waste products. Such reactions are simple to handle, reduce pollution, comparatively cheaper to operate, and may be regarded as more economical and ecologically favorable procedure in chemistry [7]. Solid-state reactions occur more efficiently and more selectively than does the solution reaction, since molecules in the crystals are arranged tightly and regularly [8]

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