Solvent-Free Biginelli Reactions Catalyzed by Hierarchical Zeolite Utilizing a Ball Mill Technique: A Green Sustainable Process

Ameen Shahid, Nesreen Ahmed, Tamer Saleh, Shaeel Al-Thabaiti, Sulaiman Basahel, Wilhelm Schwieger, Mohamed Mokhtar
2017 Catalysts  
A sustainable, green one-pot process for the synthesis of dihydropyrimidinones (DHPMs) derivatives by a three-component reaction of β-ketoester derivatives, aldehyde and urea or thiourea over the alkali-treated H-ZSM-5 zeolite under ball-milling was developed. Isolation of the product with ethyl acetate shadowed by vanishing of solvent was applied. The hierachical zeolite catalyst (MFI27_6) showed high yield (86%-96%) of DHPMs in a very short time (10-30 min). The recyclability of the catalyst
more » ... ty of the catalyst for the subsequent reactions was examined in four subsequent runs. The catalyst was shown to be robust without a detectable reduction in catalytic activity, and high yields of products showed the efficient protocol of the Biginelli reactions. Catalysts 2017, 7, 84 2 of 18 and 100% selectivity with minimal waste amounts. This method essential to be cost-effective, safe, resource-efficient, energy-efficient and ecologically benign. In this respect, the atom economy [1] and the E-factor [2] must be taken into account. On the other hand, the modern drug discovery processes require the use of a multicomponent as a key source of molecular diversity. Moreover, the one-pot synthesis provides minimal by-products, low cost, shorter time and lower energy in comparison to the classical stepwise synthetic route. The Biginelli reaction is considered to be one of the most studied multicomponent reactions. The reaction products of the reaction are dihydropyrimidinones (DHPMs), which are energetic therapeutic synthons that show a varied range of biological actions such as antiseptic, anti-inflammatory, antiviral, anti-tumor [3] [4] [5] . A huge number of dihydropyrimidinones derivatives have biological value, e.g., antagonists, antihypertensive agents, significant calcium channel blockers, and neuropeptide antagonists [6] [7] [8] [9] [10] [11] . The research into structural modification of DHPMs 1 has led to the discovery of pharmacologically active compounds, as represented in the DHPMs scaffold (Figure 1 ). Catalysts 2017, 7, 84 2 of 18 selectivity with minimal waste amounts. This method essential to be cost-effective, safe, resourceefficient, energy-efficient and ecologically benign. In this respect, the atom economy [1] and the Efactor [2] must be taken into account. On the other hand, the modern drug discovery processes require the use of a multicomponent as a key source of molecular diversity. Moreover, the one-pot synthesis provides minimal byproducts, low cost, shorter time and lower energy in comparison to the classical stepwise synthetic route. The Biginelli reaction is considered to be one of the most studied multicomponent reactions. The reaction products of the reaction are dihydropyrimidinones (DHPMs), which are energetic therapeutic synthons that show a varied range of biological actions such as antiseptic, antiinflammatory, antiviral, anti-tumor [3-5]. A huge number of dihydropyrimidinones derivatives have biological value, e.g., antagonists, antihypertensive agents, significant calcium channel blockers, and neuropeptide antagonists [6] [7] [8] [9] [10] [11] . The research into structural modification of DHPMs 1 has led to the discovery of pharmacologically active compounds, as represented in the DHPMs scaffold ( Figure 1) . Additionally, the diaryl sulfone purpose remained an effective antimicrobial agent [12] . Dapsone [13] and Promine [14] (Figure 2 ) are specimens of some famous drugs, that comprise diaryl sulfone function, and are widely available in the market. Notably, the blend of a diaryl sulfone ring with several forms of heterocyclic equivalents exhibited significant biological actions [15] [16] [17] [18] [19]. Therefore, the insertion of a diaryl sulfone moiety to the DHPMs could provide novel derivatives of expected biological and pharmacological activities.
doi:10.3390/catal7030084 fatcat:p2siwn6ksrbldkqax2qzhzn5ry