Improving the Selectivity toward Three‐Component Biginelli versus Hantzsch Reactions by Controlling the Catalyst Hydrophobic/Hydrophilic Surface Balance

Abstract

The catalytic activities and selectivities of two kinds of mesoporous solid acids SBA‐15‐PrSO3H 1, SBA‐15‐Ph‐PrSO3H 2, and a periodic mesoporous organosilica (PMO) based solid acid Et‐PMO‐Me‐PrSO3H 3 that comprise different physicochemical surface properties were compared in an environmentally benign one‐pot, three‐component Biginelli reaction of aldehydes, β‐ketoesters and urea or thiourea under solvent‐free conditions. Among these mesoporous solid acid catalysts, 3, which has a hydrophobic/hydrophobic balance in the nanospaces (mesochannels) in which the active sites are located, is found to be a significantly more selective catalytic system in the Biginelli reaction; it produces the corresponding 3,4‐dihydropyrimidin‐2‐one\thione (DHPM) 5 derivatives in good to excellent yields and excellent selectivities. Notably, in the case of conducting the three‐component coupling reaction of benzaldehyde, metylacetoacetate and urea in the presence of 1 result in the generation of a mixture of Hantzsch dihydropyridine 4 (≈37 %) and Biginelli dihydropyrimidinone 5 (≈49 %), whereas the same reaction with 2 (catalyst loading of 1 mol % as well) furnishes the corresponding aldolic product methyl‐2‐benzylidene‐3‐oxobutanoate 6 as the major product (≈80 %) with concomitant formation of small amounts of 5 (<10 %) under essentially the same reaction conditions that are employed with catalyst 3. Water adsorption–desorption analysis of the catalysts is employed to possibly relate the observed selectivity to the difference in physicochemical properties of the materials.

Novel Ordered Mesoporous Carbon Based Sulfonic Acid as an Efficient Catalyst in the Selective Dehydration of Fructose into 5-HMF: the Role of Solvent and Surface Chemistry

“…Furthermore, the high concentration of silanol groups in these silica-based materials may serve as handles for not only the covalent immobilization of active sites, they can provide a means of incorporating additional organic functionality on the catalyst surface, thus enabling to control (adjust) the surface hydrophobicity and in turn enhancing their performance (activity, selectivity, and durability) in varied acid-catalyzed chemical transformations. [50][51][52][53][54][55] Along this line, we 53 and others 49 have discovered that anchoring of sulfonic acid functions on PMO possessing an appropriate density of additional organic functional groups results in versatile solid acids that provided the possibility of achieving high degree of selectivities in the 5 biphasic (aqueous:organic) dehydration of fructose into 5-HMF or biodiesel synthesis through the adjusting the surface hydrophobic-hydrophilic balanced of the catalysts. Although these systems were shown to offer improved catalytic performance in the described reactions, due to the inorganic and thus inherent hydrophilicity of silica framework in these materials their catalytic activity would tend to potentially decline by gradual adsorption of water through the processes (for example dehydration of hexose) in which water participates as product and/or reaction medium.…”

Recent Advances in Homogeneous and Heterogeneous Catalyst in Biginelli Reaction from 2015‐19: A Concise Review

“…The hydrophobic/hydrophilic feature of catalyst played a significant role over selectivity over Biginelli reaction. The catalysts represented in the Figure have the remarkable selectivity towards the product formation . In the model reaction of 13 (1 mmol), 1 (1 mmol) and 3 (1.2 mmol) under solvent ‐free condition at 90 °C for 1.5 h of reaction time was carried out.…”

Similarity and Competition between Biginelli and Hantzsch Reactions: an Opportunity for Modern Medicinal Chemistry

“…There are several examples in the literature which demonstrate that the increase of reaction temperatures to over 100°C is responsible for both the release of the water absorbed on the solid surface, thus activating the catalytic hydrolysis of urea, and the switch to the Hantzsch reaction (entries 3-5, Table 2). Moreover, the morphology of the solid catalyst, as well as its acidity, play a role in the competition, [98][99][100] in particular for a solid support with a higher surface area and lower acidity. Indeed, low acidity means low catalytic efficiency toward both MCRs.…”