Solvent free synthesis of Chalcones from Aldehydes and Ketones using Heterogeneous Niobic Acid catalyst

Abstract

Chalcone, an important organic molecule featuring an α, β-unsaturated carbonyl framework, holds significant relevance in both organic synthesis and medicinal chemistry. It acts as a key intermediate in the production of polymers, fine chemicals, agrochemicals, and a range of pharmaceutical compounds due to its notable biological activities, including anti-inflammatory, anticancer, and antimicrobial properties. The synthesis of chalcones from aldehydes and ketones has traditionally relied on methods such as Claisen–Schmidt condensation, Meyer–Schuster rearrangement, Suzuki coupling, and Fries rearrangement. However, these approaches often demand elevated temperatures, prolonged reaction times, and substantial amounts of reagents or additives. While homogeneous acid catalysts like HCl, BF₃•Et₂O, and p-toluene sulfonic acid have been used in chalcone synthesis, they commonly yield low product output and pose challenges in catalyst separation and reuse. On the other hand, heterogeneous catalysts such as MgO, Fe₃O₄@MOF, supported BF₃, B₂O₃, LiNO₃ on natural phosphate, calcined hydrotalcites, and alkali-modified zeolites have also been explored. However, these systems often suffer from moderate yields, complex preparation procedures, harsh operating conditions, and environmental drawbacks.Moreover, in many cases, the Lewis acid sites of these catalysts become deactivated due to interaction with water generated during the reaction, leading to a decline in their catalytic performance. To overcome these obstacles, the development of a water-tolerant and efficient catalytic system is essential. Niobic acid (Nb₂O₅•nH₂O), a solid acid catalyst known for its water stability, offers a promising solution. Studies suggest that the Lewis acidic Nb⁵⁺ centers in niobic acid activate ketones by coordinating with their carbonyl groups, facilitating enol formation. Simultaneously, its Brønsted acid sites (–OH groups) enhance the electrophilicity of aldehydes by protonating their carbonyl oxygen. This dual activation by Lewis and Brønsted acid sites enables efficient carbon–carbon bond formation followed by dehydration, producing α, β-unsaturated chalcones under mild and eco-friendly conditions.Furthermore, the catalyst retains its activity over successive cycles, exhibiting minimal loss in performance upon reuse. This method supports a wide range of substrates, delivering high yields (up to 98%) with various aldehydes (e.g., 4-methylbenzaldehyde, 4-chlorobenzaldehyde) and ketones (e.g., 4-bromoacetophenone, tetralone). Therefore, this study aims to investigate the use of niobic acid (Nb₂O₅•nH₂O) as a sustainable, efficient, and recyclable catalyst for the synthesis of chalcones. Keywords: Chalcone, Nb2O5.nH2O, Lewis and Brønsted acid sites, water-tolerant