Three-component reaction of β-keto esters, aromatic aldehydes and urea/thiourea promoted by caffeine, a green and natural, biodegradable catalyst for eco-safe Biginelli synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones derivatives under solvent-free conditions

Abstract

Caffeine was found to be a natural and green and biodegradable catalyst for the one-pot, three-component condensation Biginelli reaction of ?-keto esters, aromatic aldehydes and urea/thiourea to afford the corresponding 3,4-dihydropyrimidin-2(1H)-ones/thiones derivatives under solvent-free conditions. The remarkable features of this green procedure are high yields, short reaction times, simplicity of operation and work-up procedures, the availability and easy handling of this solid catalyst, avoidance of hazardous or toxic catalysts and organic solvents and economic availability of the catalyst.

<p>In silico Design and Synthesis of Tetrahydropyrimidinones and Tetrahydropyrimidinethiones as Potential Thymidylate Kinase Inhibitors Exerting Anti-TB Activity Against <em>Mycobacterium tuberculosis</em></p>

“…All six test compounds 1a-d and 2a-b were assessed using the agar incorporation method, which was performed three [44,45] Notes: a Yields calculated after being purified using the recrystallization method; ethanol was used as a solvent. b cLogP of the title compounds was calculated using ChemDraw Professional 16.…”

Caffeine as a naturally green and biodegradable catalyst promoted convenient and expedient synthetic route for the synthesis of polysubstituted dihydro-2-oxypyrroles

“…The design of multi-component reactions (MCRs) [22][23][24][25][26][27][28][29][30][31][32] has received great attention from research groups in medicinal chemistry, drug discovery and materials science due to their significant advantages over conventional linear-type synthesis, including simple procedures, environmental friendliness, atom economy, and the ability to generate architecturally complex molecules in one synthetic step. Finally, due to the above considerations and in continuation of our work on the development of useful and green synthetic methodology for the preparation of biologically active heterocyclic compounds using of caffeine as catalyst [33], we report herein, synthesis of polysubstituted dihydro-2-oxypyrroles via one-pot, four condensation domino reaction between aromatic/ aliphatic amines (1 and 3), dialkyl acetylenedicarboxylate 2 and formaldehyde 4 in the presence of caffeine as a cost effective, green, biodegradable and readily catalyst under mild conditions (Scheme 1).…”

Glutamic acid as green and bio-based α-amino acid catalyst promoted one-pot access to polyfunctionalized dihydro-2-oxypyrroles

“…18 Some of these methods have limitations such as long reaction times, low yields and the use of strongly acidic conditions, high temperature, difficult work-up, toxic and expensive catalysts. Due to our interest in the use of green catalysts 19 in multi-component reactions [20][21][22][23] and in continuation of our earlier efforts in employing green methodologies using L-glutamic acid (Fig. 2) as as catalyst, 24 herein, we report a convenient and green one-pot protocol for the facile and mild synthesis of polyfunctionalized dihydro-2-oxypyrroles.…”