Defect-rich MOF-303 as a dual acid-base heterogeneous catalyst for the one- pot Biginelli synthesis of dihydropyrimidinones

Defect-rich MOF-303 as a dual acid-base heterogeneous catalyst for the one- pot Biginelli synthesis of dihydropyrimidinones | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Defect-rich MOF-303 as a dual acid-base heterogeneous catalyst for the one- pot Biginelli synthesis of dihydropyrimidinones Nuhaa Shaheed, Ahmad Shaabani This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6248371/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 24 Oct, 2025 Read the published version in Scientific Reports → Version 1 posted 10 You are reading this latest preprint version Abstract Bifunctional MOF-303 (Al) exhibits promising catalytic activity for the Biginelli reaction. However, its intrinsic microporosity may hinder reactant and product diffusion and reducing efficiency. Introducing defects is crucial for enhancing its catalytic performance. In this work, defect-rich MOF-303 was prepared by grinding the hydrothermally synthesized MOF-303 into a fine powder. The resulting material was thoroughly characterized and exhibited excellent catalytic performance in the solvent-free synthesis of diverse dihydropyrimidinones under moderate reaction conditions, achieving yields between 94% and over 99%. Moreover, the catalyst was successfully recycled over five cycles with minimal activity loss. The structures of the obtained products were confirmed by IR, ¹H NMR, and melting point analysis. The simple preparation method using commercially inexpensive reagents, high catalytic performance under mild conditions, and recyclability of defect-rich MOF-303 highlight its potential as an efficient and sustainable catalyst for the Biginelli reaction. Physical sciences/Chemistry Physical sciences/Materials science Defect-rich MOF-303 Biginelli reaction Dihydropyrimidinone Solvent-free Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 1. Introduction The synthesis of dihydropyrimidinone scaffolds (DHPMs) via the Biginelli reaction has attracted significant attention due to the diverse pharmacological and therapeutic properties of these heterocyclic products [ 1 – 3 ], as well as the simplicity and eco-friendliness of the one-pot multicomponent Biginelli protocol [ 4 – 6 ]. This reaction involves the condensation of an aromatic aldehyde, urea, and a β-ketoester under strongly acidic conditions [ 7 – 9 ]. Since its discovery by Pietro Biginelli in 1893, extensive research has been dedicated to unraveling its mechanistic pathways and developing efficient catalytic systems [ 10 – 12 ]. Traditional studies have established that the acidic catalysts facilitate the reaction by activating carbonyl groups, increasing their electrophilicity, and thereby accelerating the condensation process [ 13 ]. However, recent findings suggest that the coexistence of acid and base catalytic sites can enhance the reaction through a dual-mode activation. In this mechanism, acid sites activate carbonyl groups of aldehyde compounds, while basic moieties strengthen the nucleophilicity of urea and the enol form of ethyl acetoacetate, ultimately driving the reaction forward [ 14 ]. In this context, metal-organic frameworks (MOFs) have emerged as promising candidates for designing bifunctional acid-base catalysts for the Biginelli reaction. Composed of metal nodes interconnected by organic linkers, MOFs provide a highly tunable platform for integrating both acidic and basic sites at optimal distances, ensuring synergistic catalysis without mutual deactivation. Several bifunctional MOFs have been reported to exhibit high catalytic activity in DHPM synthesis, attributed to their dual-mode activation via acid-base synergistic effects [ 15 – 18 ]. However, some of those previously reported bifunctional MOFs suffer from low porosity, resulting in moderate catalytic performance [ 19 ]. Additionally, the most efficient bifunctional MOF-based catalysts often require complex ligand synthesis, which limits their large-scale applicability [ 20 , 21 ]. In this regard, MOF-303 (Al), constructed from electron-rich N- containing pyrazole ligands and aluminum nodes, presents an intriguing framework with both Lewis acid and Brønsted base sites, making it highly effective for dual-activation catalysis. More importantly, it can be synthesized on a large scale using high-yield environmentally friendly techniques. However, its predominantly microporous structure may restrict reactant and product diffusion, potentially limiting catalytic efficiency. To overcome this limitation, introducing defects into the MOF-303 framework is essential for enhancing mass transfer and improving overall catalytic performance [ 22 – 24 ]. This study explores the catalytic potential of defect-rich MOF-303 as a highly efficient, recyclable, and sustainable heterogeneous catalyst for the Biginelli reaction. To achieve this, MOF-303 was fabricated using a hydrothermal synthesis method, followed by a simple grinding process to obtain a fine powder of defect-rich MOF-303, thereby enhancing its porosity and catalytic site accessibility. To the best of our knowledge, the catalytic potential of defect-rich MOF-303(Al) as a heterogeneous catalyst for the Biginelli reaction has not yet been investigated. 2. Experimental section 2.1. Chemicals Aluminum chloride hexahydrate (AlCl 3 .6H 2 O, 97%), 1H-pyrazole-3,5-dicarboxylic acid monohydrate (H 2 PZDC.H 2 O, 98%), and sodium hydroxide (NaOH, 98%), benzaldehyde, p -methylbenzaldehyde, p -methoxybenzaldehyde, methyl acetoacetate, urea, choline chloride (ChCl), N,-N -dimethylformamide (DMF), dichloromethane (DCM), methanol (MeOH), ethanol (EtOH), toluene, acetonitrile (ACN), tetrahydrofuran (THF), ethyl acetate (EtOAc), and deuterated dimethyl sulfoxide (DMSO-d 6 ) were bought from Sigma Aldrich/Merck Co. All chemical materials and solvents were utilized without further purification. 2.2. Characterization and instrumentation Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectra were recorded on a Bruker ALPHA Platinum ATR-FTIR spectrometer. The X-ray powder diffraction (PXRD) patterns were recorded on an STOE diffractometer with Cu-Kα radiation (λ = 1.5418 Å). Field emission scanning electron microscopy (FE-SEM) was carried out using an Inspect F-50, in which all samples were sputtered with gold before inspection. The energy-dispersive X-ray spectroscopy (EDS) analysis was conducted via Edax Ametek (Octane Super-A). Thermogravimetric analysis (TGA) was carried out using STA-1500 instrument at a heating rate of 10 ◦C min -1 in the air. The Brunauer- Emmett-Teller (BET) equation was employed to compute the surface area from the obtained adsorption data at P/P0 in the range of 0.05–0.2. The total pore volume was estimated from the nitrogen adsorption data obtained at P/P 0 = 0.95. For thin-layer chromatography (TLC), silica gel plates (HSGF 254) were used, and compounds were visualized by irradiation with UV light. Organic solvents were removed under reduced pressure by a rotary evaporator. 1 H NMR analyses were performed at room temperature on a Bruker 300 MHz apparatus using deuterated dimethyl sulfoxide (DMSO-d 6 ) as the solvent and tetramethylsilane (TMS) as the internal standard. The melting points were determined in open capillaries with a Stuart Melting Point Apparatus and are uncorrected. 2.3. Synthesis of defect-rich MOF-303 (Al) Defect-rich MOF-303 was prepared by grinding the hydrothermally synthesized MOF-303, following a method reported by Yaghi’s group [ 25 ]. Briefly, H 2 PZDC.H 2 O (1.74 g, 10 mmol) and NaOH (0.6 g, 15 mmol) were dissolved in 90 mL deionized water using sonication and placed in a 250 mL VWR bottle (Solution A). A separate solution of AlCl 3 .6H 2 O (2.41 g, 10 mmol) in 10 mL of deionized water (Solution B) was added dropwise to Solution A under vigorous stirring, causing the reaction mixture to turn milky white midway through the addition. The jar was then tightly sealed and placed in a preheated oven at 120°C for 24 hours. After completion of the reaction, the mixture was allowed to cool naturally to room temperature. The resulting white precipitate was collected by centrifugation and washed with deionized water three times per day for three consecutive days to remove residual aluminum chloride and sodium chloride. Subsequently, the water-washed MOF-303 was further washed with anhydrous ethanol in the same way to eliminate unreacted linker molecules from the pores. Finally, the purified MOF-303 powder was dried in air overnight and activated in a vacuum oven at 80°C for 12 hours. The obtained MOF-303 was then ground for two minutes until a fine powder was achieved before further characterization and investigation. 2.4. Synthesis of urea-based DES The urea-based deep eutectic solvent (DES) was prepared using a previously reported method [ 26 ]. Briefly, ChCl and urea were mixed in a 1:2 molar ratios and stirred at 80°C for 2 hours. The obtained colorless mixture was then cooled to room temperature, forming a homogeneous, viscous liquid under ambient conditions for further application. 2.5. General procedure for the synthesis of DHPMs via the Biginelli condensation reaction The synthesis of DHPM derivatives was performed at the optimized reaction conditions, where a mixture of benzaldehyde (1.0 mmol), methyl acetoacetate (1.0 mmol), urea (1.5 mmol), and defect-rich MOF-303 catalyst (0.05 mmol) was gently stirred at 80°C in a preheated oil bath for 4 hours. Five minutes after the reaction began, the mixture solidified, indicating the formation of the DHPM product. To monitor the reaction progress, small aliquots were taken at regular intervals. These portions were extracted with n -hexane and analyzed by TLC (using a 1:3 ethyl acetate: n-hexane mixture as the mobile phase). Upon completion of the reaction, the mixture was cooled to room temperature. Ethyl acetate (15 mL) was then added, and the insoluble catalyst was recovered by filtration through Celite under suction. The organic layer was washed twice with brine (15 mL) and dried over anhydrous Na 2 SO 4 . After evaporation of the solvent, the crude product was recrystallized from methanol (MeOH) to afford pure 3,4-dihydropyridine-2 (1H)-one (DHPM). All products were characterized by IR and 1 H NMR spectroscopy and by comparison with the melting points of reported compounds. For the recycling experiment, the recovered heterogeneous catalyst was washed with deionized water and EtOH respectively several times (3 × 3 mL), activated in a vacuum oven at 80 ◦C for 12 h, and reused for successive runs. 3. Results and discussion 3.1. Catalyst synthesis and characterization MOF-303 was first hydrothermally synthesized using aluminum ions and pyrazole dicarboxylate linkers (H₃PDC), following literature procedures [ 25 ]. The as-synthesized MOF-303 was then smoothly ground to obtain a fine powder of defect-rich MOF-303. This grinding process weakens the Al–O coordination bonds, leading to missing-linker and missing-cluster defects, which enhance porosity and increase the concentration of catalytic sites, as shown in Scheme 1 . FTIR spectra were obtained to investigate the chemical bonding, confirm the presence of the pyrazole unit, and identify the functional groups in the as-synthesized material. As shown in Fig. 1 , the characteristic peaks of defect-rich MOF-303 closely match those reported in the literature. The broad stretching bands observed in the range of 2850–3629 cm -1 can be attributed to -N -H and O-H bonds, which result from surface-adsorbed water.[ 27 , 28 ] A small band at 1743 cm -1 indicates the presence of free protonated carboxylic acid groups in the organic linker. This confirms the formation of defects resulting from the disruption of Al–O coordination bonds during the grinding process [ 29 , 30 ]. The sharp peaks at 1589 and 1385 cm -1 correspond to the asymmetric and symmetric stretching vibrations of coordinated carboxylate (-COO-Al) groups, confirming the interaction between the H 2 PZDC ligands and Al 3+ ions, thus validating the successful formation of the MOF-303 framework [ 22 , 31 ]. Additionally, absorption bands observed at 1525, 1475, and 1003 cm -1 correspond to the stretching vibrations of -C = N-, -C-C-, and -N-NH bonds, respectively [ 32 ]. Figure 2 shows that the characteristic XRD patterns of the defect-rich MOF-303 powder closely align with the simulated pattern (CCDC 2078717) and previously reported data, confirming the material's structural integrity. The distinct peaks at specific 2θ values indicate the high crystallinity of defect-rich MOF-303 [ 33 ]. Additionally, slight peak broadening observed in the PXRD pattern suggests the presence of structural defects. This broadening can be attributed to the disruption of Al–O coordination bonds induced by grinding, as supported by the presence of free protonated carboxylic acid groups in the FTIR spectrum (Fig. 1 ). The thermal behavior of defect-rich MOF-303 was investigated using TGA at a heating rate of 10 C min -1 in the air, and the corresponding thermogram was depicted in Fig. 3 . The TGA profile reveals two distinct weight loss steps. The first weight loss (35 wt%) occurring below 150°C corresponds to the evaporation of surface-adsorbed water and ethanol molecules trapped in the MOF-303 pores. Notably, this weight loss is higher than that reported for pristine MOF-303 (20%) [ 34 ], which suggests the presence of free uncoordinated carboxylic acid groups and/or unsaturated Al sites that can adsorb additional water. This observation further supports the defect formation indicated by FTIR and PXRD analyses. The second significant weight loss of ~ 55 wt% above 400 ◦C demonstrates the degradation of organic components and structure collapsing. According to the TGA profile, defect-rich MOF-303 (Al) is thermally stable above 400 ◦C, which is agreeable to the reported in the literature [ 33 ]. To investigate the porosity and surface characteristics of defect-rich MOF-303, BET analysis was performed using nitrogen adsorption at 77 K, with the sample degassed under vacuum at 150°C for 4 hours. The results, shown in Fig. 4 and Table 1 , agree with previously reported data [ 25 ]. Figure 4 a presents the nitrogen adsorption isotherm, which exhibits typical type-I behavior, indicative of microporous materials according to the IUPAC classification. However, at higher relative pressures (P/P₀ ≈ 0.89), the adsorption begins to increase, a trend often observed in type II isotherms. This suggests the presence of additional external surface area, likely attributed to larger crystals or agglomerates [ 32 ]. Moreover, the desorption isotherm does not coincide with the adsorption curve, revealing a hysteresis loop of type H3. This loop is characteristic of mesopores formed by interparticle contacts, allowing for additional nitrogen adsorption and capillary condensation [ 28 ]. As shown in Table 1 , the specific surface area and pore volume of defect-rich MOF-303 were found to be 1283.2 m 2 /g and 1.0448 cm 3 /g, respectively, indicating a highly porous structure. The pore size distribution, calculated using the Barrett-Joyner-Halenda (BJH) method, reveals an average mesopore size of 3.257 nm, with a significant proportion of micropores, along with a smaller fraction of macropores in the range of 50 to 60 nm, as illustrated in Fig. 4 b. This broad pore size distribution suggests the presence of irregular voids and larger mesopores created by defects. These results align well with the findings from FTIR, PXRD, and TGA (Figs. 1 – 3 ), further confirming the successful introduction of defects within the MOF-303 framework. Table 1 Textural properties of defect-rich MOF-303. BET surface area m 2 /g mean pore diameter (nm) Total pore volume (cm 3 /g) Defect-rich MOF-303 1283.2 3.257 1.0448 The morphology and elemental distribution of defect-rich MOF-303 were investigated using FE-SEM and EDS analysis. As shown in Fig. 5 a, defect-rich MOF-303 exhibits cubic-shaped, well-intergrown crystals that form larger crystals or agglomerates. This morphology contributes to the increase in the N 2 adsorption curve at higher relative pressures, as discussed earlier. EDS analysis (Fig. 5 b), combined with elemental mapping (Figs. 5 c– 5 f), reveals that aluminum, carbon, oxygen, and nitrogen, are homogeneously distributed throughout the MOF-303 crystals. The elemental percentages observed in the EDS analysis are in good agreement with the calculated values [ 25 ]. 3.2. Catalytic application With its high surface area, hierarchical porous structure, excellent thermochemical stability, and the coexistence of N -functionalized channels along with a high density of exposed Al 3+ sites as hard Lewis acids, defect-rich MOF-303 meets the essential criteria for a bifunctional heterogeneous catalyst in the multicomponent Biginelli reaction. To assess its catalytic performance, a series of control experiments were carried out using benzaldehyde, methyl acetoacetate, and urea in a 1:1:1.5 molar ratio as the model reaction. The molar ratio with urea in excess was based on many previous studies, which illustrated that a slight excess of urea enhances the reaction by stabilizing the iminium ion through hydrogen bonding and proton transfer, contributing to an improved reaction outcome [ 13 ]. Initially, the model reaction was carried out under solvent-free conditions using 7 mg of catalyst to optimize the reaction temperature and time, and the results are shown in Table 2 . The progress of the reaction was easily monitored by observing the solidification of the reaction mixture and was further verified by thin-layer chromatography (TLC). No by-products were detected via TLC. Clearly, performing the reaction at room temperature resulted in a negligible yield, even after a prolonged reaction time (Table 2 , entry 1). The percentage of isolated yield gradually increased with the reaction temperature at shorter reaction times, reaching the highest yield at 80°C (Table 1 , entries 2–5), after which the yield showed no significant improvement (Table 2 , entries 6 and 7). Therefore, 80°C was chosen as the optimum reaction temperature for further investigation. The catalyst load is an important factor in this procedure. The influence of different catalyst dosages (7 mg, 10 mg, 20 mg, and 30 mg) at the optimum reaction temperature revealed that the maximum product yield (> 99%) was achieved with 10 mg of catalyst (Table 2 , entry 8). Increasing the catalyst amount beyond this point resulted in a decrease in yield (Table 2 , entries 9 and 10). Therefore, 10 mg of catalyst was selected as the optimal amount for further studies. Table 2 Effect of reaction temperature and catalyst load on the model Biginelli reaction catalyzed by MOF-303. Entry Catalyst load (mg) Temperature (°C) Time (h) Yield (%) 1 7 rt 12 10 2 7 50 10 46 3 7 60 8 59 4 7 70 4 90 5 7 80 2.5 94 6 7 90 2 87 7 7 100 2 85 8 10 80 2.5 > 99 9 20 80 2.5 89 10 30 80 2.5 83 The effect of various solvents, including protic, aprotic, non-polar solvents, and urea-based deep eutectic solvent (DES), was investigated while maintaining the optimal reaction parameters: temperature (80°C, or reflux for solvents with boiling points below 80°C), reaction time (2.5 hours), and catalyst amount (10 mg). It is important to note that no additional urea was required when using the urea-based DES, as urea is already a component of the DES mixture. The results shown in Table 3 revealed that solvent-free conditions and DES resulted in the highest yields (Table 3 , entries 1 and 11). Methanol and ethanol also provided good yields (Table 3 , entries 2 and 3), while the remaining solvents (entries 4–10) yielded negligible results. Consequently, solvent-free conditions were selected as the optimal reaction medium, as they minimize environmental impact and enhance sustainability. Table 3 Solvent effect on the model Biginelli reaction catalyzed by MOF-303. Entry Solvent Temperature (°C) Time (h) Yield % 1 - 80 2.5 > 99 2 MeOH reflux 2.5 94 3 EtOH reflux 2.5 91 4 H 2 O 80 2.5 56 5 DMF 80 2.5 18 6 CH 2 Cl 2 reflux 2.5 40 7 ACN 80 2.5 23 8 THF reflux 2.5 15 9 n -hexane reflux 2.5 20 10 Toluene 80 2.5 32 11 DES 80 2.5 > 99.9 With the optimized reaction conditions in hand, the scope of the Biginelli reaction was investigated using a variety of heterocyclic and aromatic aldehydes, including those with both electron-rich and electron-deficient substituents, as illustrated in Table 4 . Notably, all substrates reacted efficiently and afforded high yields of the corresponding products. The structures of the final products were confirmed after recrystallization using IR and 1 H NMR (see Supporting Information) and by comparing their melting points with those reported in the literature (Table 4 ). Table 4. Scope of aldehyde substrates in the synthesis of DHPM derivatives via the Biginelli reaction. To investigate the durability and recyclability of defect-rich MOF-303, the model Biginelli reaction was performed under optimized conditions across multiple cycles. After each cycle, the solid catalyst was separated from the reaction mixture, thoroughly washed with deionized water and ethanol, and dried in vacuum before reuse. Notably, only a slight decrease in product yield was observed after five cycles (Fig. 6 ), demonstrating the catalyst's stability and reusability. The proposed mechanism of the Biginelli reaction over defect-rich MOF-303 is illustrated in Scheme 2 . By leveraging its dual acid-base catalytic sites, defect-rich MOF-303 promotes the reaction through a dual-mode activation. The process begins with the activation of benzaldehyde via Lewis acid-base interactions between an accessible Al 3+ site in the metal node and the oxygen atom of the carbonyl group. Simultaneously, the electron-rich N -containing pyrazole ligands act as Lewis bases, deprotonating urea to enhance its nucleophilicity. The activated urea then attacks the polarized carbonyl group of benzaldehyde, forming a hemiaminal intermediate that rapidly dehydrates to generate the imine intermediate. Subsequently, the imine undergoes Michael addition with the enol tautomer of the β-ketoester, followed by intramolecular cyclization and final dehydration, yielding the DHPM product. To evaluate the catalytic potential of defect-rich MOF-303 for the Biginelli reaction, its performance was compared with previously reported bifunctional acid-base MOF catalysts. This comparative study, based on the isolated yield and reaction conditions, is summarized in Table 5 . The results demonstrate that defect-rich MOF-303 exhibits catalytic activity comparable to that of previously reported bifunctional MOFs. However, unlike these catalysts which rely on complex ligands and expensive reagents, MOF-303 is synthesized from readily available cost-effective precursors using a straightforward and environmentally friendly process. These advantages make MOF-303 as a more practical and sustainable alternative for heterogeneous catalysis in the Biginelli reaction. Table 5 Comparison of defect-rich MOF-303 with previously reported dual acid-base MOF catalysts for the Biginelli reaction. Entry Catalyst Time Conditions Yield% Ref 1 CSMCRI-15 (1.5 mol%) 3 h Neat, 60°C 94 [ 15 ] 2 ZIF-8 (1.5 NaOH) (10% wt.) 3h EtOH, 90°C 95 [ 39 ] 3 ADES-1 (0.02 mmol) 10 min Neat, 80°C 94 [ 18 ] 4 Cu-MOF (10 wt%) 2 h Neat, 60°C 86 [ 20 ] 5 Anionic Zn (II)-MOF (10 wt%) 2 h Neat, 60°C 93 [ 16 ] 6 IRMOF-3 (4 mol%) 5 h Neat, 60°C 93 [ 17 ] 7 Cd-MOF (0.03 mmol) 20 min Neat, 70°C 99 [ 19 ] 8 Defect-rich MOF-303 (10 mg) 2.5 h Neat, 80°C > 99 This work 4. Conclusion In summary, defect-rich MOF-303 was prepared by grinding hydrothermally synthesized MOF-303 and thoroughly characterized. Comprehensive characterization confirmed defect formation through FTIR, PXRD, TGA, N 2 adsorption-desorption isotherms, and pore size distribution analysis. FTIR spectra revealed free protonated carboxylic acid groups, indicating disruption of Al–O coordination bonds. PXRD analysis showed slight peak broadening, suggesting structural defects, while TGA exhibited greater weight loss in defect-rich MOF-303 compared to pristine MOF-303, further supporting defect formation. The nitrogen adsorption isotherm displayed a type II trend at a high relative pressure (P/P 0 ~ 0.89), indicative of defect-induced mesoporosity. Meanwhile, pore size distribution analysis confirmed a broad range of irregular voids and larger mesopores, highlighting the hierarchical porous structure. The obtained defect-rich MOF-303 exhibited outstanding catalytic efficiency in the Biginelli reaction under mild reaction conditions (solvent-free, 10 mg catalyst, 80 C, 2.5 h). A dual-activation mode mechanism was proposed to explain its dual acid-base nature. Furthermore, recyclability tests demonstrated the catalyst’s stability over five cycles. Notably, the present catalyst achieved catalytic performance comparable to previously reported dual acid-base MOFs while offering superior economic benefits. These findings highlight defect-rich MOF-303 as a promising, cost-effective, and sustainable bifunctional catalyst for the Biginelli reaction, paving the way for future applications in green and heterogeneous catalysis. Declarations Declaration of competing interest There are no conflicts of interest to declare. Supplementary materials 1 H NMR and FTIR spectra of DHPM derivatives. Author Contribution Nuhaa Shaheed: Writing – review & editing, Writing – original draft, Visualization, Validation, Software, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. Ahmad Shaabani: Writing – review & editing, Supervision, Project administration. All authors reviewed the manuscript. Acknowledgments We gratefully acknowledge the financial support provided by Shahid Beheshti University in Tehran, Iran. 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Zheng, H.L. Nguyen, N. Hanikel, K.K.-Y. Li, Z. Zhou, T. Ma, O.M. Yaghi, High-yield, green and scalable methods for producing MOF-303 for water harvesting from desert air, Nature Protocols 18(1) (2023) 136-156. N. Noorani, A. Mehrdad, Improving the Separation of CO 2 /N 2 Using Impregnation of a Deep Eutectic Solvent on a Porous MOF, ACS Omega 9(8) (2024) 9516-9525. Q. Shen, S. Cong, J. Zhu, Y. Zhang, R. He, S. Yi, Y. Zhang, Novel pyrazole-based MOF synergistic polymer of intrinsic microporosity membranes for high-efficient CO 2 capture, J. Membr. Sci. 664 (2022) 121107. N. Shaheed, S. Javanshir, M. Esmkhani, M.G. Dekamin, M.R. Naimi-Jamal, Synthesis of nanocellulose aerogels and Cu-BTC/nanocellulose aerogel composites for adsorption of organic dyes and heavy metal ions, Scientific Reports 11(1) (2021) 18553. F. Vermoortele, R. Ameloot, L. Alaerts, R. Matthessen, B. Carlier, E.V.R. Fernandez, J. Gascon, F. Kapteijn, D.E. De Vos, Tuning the catalytic performance of metal–organic frameworks in fine chemistry by active site engineering, J. Mater. Chem. 22(20) (2012) 10313-10321. J.W. Yoon, Y.-K. Seo, Y.K. Hwang, J.-S. Chang, H. Leclerc, S. Wuttke, P. Bazin, A. Vimont, M. Daturi, E. Bloch, P.L. Llewellyn, C. Serre, P. Horcajada, J.-M. Grenèche, A.E. Rodrigues, G. Férey, Controlled Reducibility of a Metal–Organic Framework with Coordinatively Unsaturated Sites for Preferential Gas Sorption, Angew. Chem. Int. Ed. 49(34) (2010) 5949-5952. H. Kim, S. Jee, J. Park, M. Jung, R. Muhammad, K. Choi, H. Oh, High D 2 /H 2 selectivity performance in MOF-303 under ambient pressure for potential industrial applications, Sep. Purif. Technol. 325 (2023) 124660. S. Głowniak, B. Szczęśniak, J. Choma, M. Jaroniec, Mechanochemical Synthesis of MOF-303 and Its CO 2 Adsorption at Ambient Conditions, Molecules 29(11) (2024) 2698. Y.-H. Lin, H.-H. Lin, Y.-S. Lee, W.-Y. Yu, S.-C. Luo, D.-Y. Kang, MOF-303 with Lowered Water Evaporation Enthalpy for Solar Steam Generation, ACS Applied Materials & Interfaces 16(37) (2024) 49640-49650. A. Ma, H. Cong, H. Deng, Multivariate MOF for optimizing atmospheric water harvesting, Green Energy & Environment 7(4) (2022) 575-577. R. Kong, S.-B. Han, J.-Y. Wei, X.-C. Peng, Z.-B. Xie, S.-S. Gong, Q. Sun, Highly efficient synthesis of substituted 3, 4-dihydropyrimidin-2-(1 H)-ones (DHPMs) catalyzed by Hf (OTf) 4: Mechanistic insights into reaction pathways under metal Lewis acid catalysis and solvent-free conditions, Molecules 24(2) (2019) 364. M. Litvić, I. Večenaj, Z.M. Ladišić, M. Lovrić, V. Vinković, M. Filipan-Litvić, First application of hexaaquaaluminium(III) tetrafluoroborate as a mild, recyclable, non-hygroscopic acid catalyst in organic synthesis: a simple and efficient protocol for the multigram scale synthesis of 3,4-dihydropyrimidinones by Biginelli reaction, Tetrahedron 66(19) (2010) 3463-3471. R. Fu, Y. Yang, W. Lai, Y. Ma, Z. Chen, J. Zhou, W. Chai, Q. Wang, R. Yuan, Efficient and Green Microwave-Assisted Multicomponent Biginelli Reaction for the Synthesis of Dihydropyrimidinones Catalyzed by Heteropolyanion-Based Ionic Liquids Under Solvent-Free Conditions, Synth. Commun. 45(4) (2015) 467-477. V. Singh, K. Rajput, P. Verma, S. Singh, V. Srivastava, A green approach for the synthesis of 2-oxo-1, 2, 3, 4-tetrahydropyrimidines through oxidative functionalization of methyl arenes/benzyl derivatives via in situ generated urea, Res. Chem. Intermed. 49(7) (2023) 2969-2987. M. Sayed, A. Soliman, H.N. Abdelhamid, Metal-organic framework (ZIF-8) for Knoevenagel condensation and multi-components Biginelli Reaction, J. Solid State Chem. 332 (2024) 124534. Schemes Schemes 1 and 2 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files scheme1.jpg Scheme 1. Schematic illustration of preparative method of defect-rich MOF-303. scheme2.jpg Scheme 2. Proposed mechanism of catalytic synthesis of dihydropyrimidinone using defect-rich MOF-303. Cite Share Download PDF Status: Published Journal Publication published 24 Oct, 2025 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 12 Jun, 2025 Reviews received at journal 14 Apr, 2025 Reviewers agreed at journal 04 Apr, 2025 Reviews received at journal 31 Mar, 2025 Reviewers agreed at journal 21 Mar, 2025 Reviewers invited by journal 21 Mar, 2025 Editor assigned by journal 21 Mar, 2025 Editor invited by journal 21 Mar, 2025 Submission checks completed at journal 19 Mar, 2025 First submitted to journal 17 Mar, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6248371","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":433844751,"identity":"13e9214c-79a0-47a7-92e2-0d2a4280bace","order_by":0,"name":"Nuhaa Shaheed","email":"","orcid":"","institution":"Shahid Beheshti University","correspondingAuthor":false,"prefix":"","firstName":"Nuhaa","middleName":"","lastName":"Shaheed","suffix":""},{"id":433844752,"identity":"28548634-67c5-47cc-82cc-52181db7c856","order_by":1,"name":"Ahmad Shaabani","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3klEQVRIiWNgGAWjYHACNiA+wMDAzHyAGSLA2ECsFrYEUrUw8BgwE+Uq/gb2Zw9+1NyRN2fn+fy5sI1Bnr+Bue0DPi0SB3jMDXuOPTPc2cy7TXpmG4PhjAOMzTPwWnP/DZsED9thxg2Hebcx87YxMG5gYGzGq0P+APszyT//DttvOMzz+DNQiz1BLQYHGMykedsOJwK1MAAZDIkEtRge4DGTlu17lrzhMJuZ9IxzEskzDhPQIgdy2Jtvd2w3nD/8+HNBmY1tf3v7Y7xa0IEEME5J0jAKRsEoGAWjABsAAP73RehF79EYAAAAAElFTkSuQmCC","orcid":"","institution":"Shahid Beheshti University","correspondingAuthor":true,"prefix":"","firstName":"Ahmad","middleName":"","lastName":"Shaabani","suffix":""}],"badges":[],"createdAt":"2025-03-18 01:38:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6248371/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6248371/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-025-21172-6","type":"published","date":"2025-10-24T16:16:32+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":79548956,"identity":"8416f7fe-eaa7-469a-8998-eb295ba9af83","added_by":"auto","created_at":"2025-03-31 06:25:39","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":41803,"visible":true,"origin":"","legend":"\u003cp\u003eATR-FTIR spectra of defect-rich MOF-303.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6248371/v1/fc48bebf5f5c35f737796634.jpg"},{"id":79548310,"identity":"ed068e5d-f929-4ba1-a5e2-1cb6ded5c69f","added_by":"auto","created_at":"2025-03-31 06:17:37","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":23596,"visible":true,"origin":"","legend":"\u003cp\u003ePXRD pattern of defect-rich MOF-303.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6248371/v1/f9bb05abf472da72aa3304d4.jpg"},{"id":79548329,"identity":"7cb850d9-391b-418d-8213-2fd2dc8b3ad0","added_by":"auto","created_at":"2025-03-31 06:17:38","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":34046,"visible":true,"origin":"","legend":"\u003cp\u003eTGA thermogram of defect-rich MOF-303.\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6248371/v1/9ecb137588f7b2091eddfbd7.jpg"},{"id":79548371,"identity":"7d528895-3558-43e9-9d42-dfe9967e0a7d","added_by":"auto","created_at":"2025-03-31 06:17:40","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":45111,"visible":true,"origin":"","legend":"\u003cp\u003e(a) N\u003csub\u003e2\u003c/sub\u003e adsorption-desorption isotherm and (b) the pore size distribution of defect-rich MOF-303.\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6248371/v1/c3badd989019f0dfc5f73d83.jpg"},{"id":79548312,"identity":"88b11b08-903c-4ebf-a317-6c0f32ddc8f4","added_by":"auto","created_at":"2025-03-31 06:17:37","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":96239,"visible":true,"origin":"","legend":"\u003cp\u003e(a) FE-SEM images, (b) EDS spectrum, and (c-f) single-element mapping images of defect-rich MOF-303.\u003c/p\u003e","description":"","filename":"5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6248371/v1/301a1b3f5441a59198b74b19.jpg"},{"id":79548978,"identity":"e9bf23e7-21ca-494c-b2b4-9ae9173bdfd8","added_by":"auto","created_at":"2025-03-31 06:25:40","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":34538,"visible":true,"origin":"","legend":"\u003cp\u003eRecyclability of defect-rich MOF-303 in the Biginelli reaction.\u003c/p\u003e","description":"","filename":"6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6248371/v1/4a550d39b62da109ff9b76e5.jpg"},{"id":94490379,"identity":"1a079545-7b79-4091-9c16-dc7593235150","added_by":"auto","created_at":"2025-10-27 17:09:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1136117,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6248371/v1/d8afad3b-708a-46a5-98a8-5ea4d3307da9.pdf"},{"id":79548940,"identity":"1995b607-33bb-4c04-a18e-5cb7dacc0975","added_by":"auto","created_at":"2025-03-31 06:25:37","extension":"jpg","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":28084,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eScheme 1\u003c/strong\u003e. Schematic illustration of preparative method of defect-rich MOF-303.\u003c/p\u003e","description":"","filename":"scheme1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6248371/v1/3baa65facc4306d659b09a8d.jpg"},{"id":79548313,"identity":"3a2e3dfe-3643-4885-a2b4-2d2223d00387","added_by":"auto","created_at":"2025-03-31 06:17:37","extension":"jpg","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":65105,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eScheme 2.\u003c/strong\u003e Proposed mechanism of catalytic synthesis of dihydropyrimidinone using defect-rich MOF-303.\u003c/p\u003e","description":"","filename":"scheme2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6248371/v1/93a5e87bcced288dede67166.jpg"}],"financialInterests":"No competing interests reported.","formattedTitle":"Defect-rich MOF-303 as a dual acid-base heterogeneous catalyst for the one- pot Biginelli synthesis of dihydropyrimidinones","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eThe synthesis of dihydropyrimidinone scaffolds (DHPMs) \u003cem\u003evia\u003c/em\u003e the Biginelli reaction has attracted significant attention due to the diverse pharmacological and therapeutic properties of these heterocyclic products [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], as well as the simplicity and eco-friendliness of the one-pot multicomponent Biginelli protocol [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. This reaction involves the condensation of an aromatic aldehyde, urea, and a β-ketoester under strongly acidic conditions [\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Since its discovery by Pietro Biginelli in 1893, extensive research has been dedicated to unraveling its mechanistic pathways and developing efficient catalytic systems [\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Traditional studies have established that the acidic catalysts facilitate the reaction by activating carbonyl groups, increasing their electrophilicity, and thereby accelerating the condensation process [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. However, recent findings suggest that the coexistence of acid and base catalytic sites can enhance the reaction through a dual-mode activation. In this mechanism, acid sites activate carbonyl groups of aldehyde compounds, while basic moieties strengthen the nucleophilicity of urea and the enol form of ethyl acetoacetate, ultimately driving the reaction forward [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. In this context, metal-organic frameworks (MOFs) have emerged as promising candidates for designing bifunctional acid-base catalysts for the Biginelli reaction. Composed of metal nodes interconnected by organic linkers, MOFs provide a highly tunable platform for integrating both acidic and basic sites at optimal distances, ensuring synergistic catalysis without mutual deactivation. Several bifunctional MOFs have been reported to exhibit high catalytic activity in DHPM synthesis, attributed to their dual-mode activation via acid-base synergistic effects [\u003cspan additionalcitationids=\"CR16 CR17\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. However, some of those previously reported bifunctional MOFs suffer from low porosity, resulting in moderate catalytic performance [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Additionally, the most efficient bifunctional MOF-based catalysts often require complex ligand synthesis, which limits their large-scale applicability [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. In this regard, MOF-303 (Al), constructed from electron-rich \u003cem\u003eN-\u003c/em\u003econtaining pyrazole ligands and aluminum nodes, presents an intriguing framework with both Lewis acid and Br\u0026oslash;nsted base sites, making it highly effective for dual-activation catalysis. More importantly, it can be synthesized on a large scale using high-yield environmentally friendly techniques. However, its predominantly microporous structure may restrict reactant and product diffusion, potentially limiting catalytic efficiency. To overcome this limitation, introducing defects into the MOF-303 framework is essential for enhancing mass transfer and improving overall catalytic performance [\u003cspan additionalcitationids=\"CR23\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis study explores the catalytic potential of defect-rich MOF-303 as a highly efficient, recyclable, and sustainable heterogeneous catalyst for the Biginelli reaction. To achieve this, MOF-303 was fabricated using a hydrothermal synthesis method, followed by a simple grinding process to obtain a fine powder of defect-rich MOF-303, thereby enhancing its porosity and catalytic site accessibility. To the best of our knowledge, the catalytic potential of defect-rich MOF-303(Al) as a heterogeneous catalyst for the Biginelli reaction has not yet been investigated.\u003c/p\u003e"},{"header":"2. Experimental section","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Chemicals\u003c/h2\u003e \u003cp\u003eAluminum chloride hexahydrate (AlCl\u003csub\u003e3\u003c/sub\u003e.6H\u003csub\u003e2\u003c/sub\u003eO, 97%), 1H-pyrazole-3,5-dicarboxylic acid monohydrate (H\u003csub\u003e2\u003c/sub\u003ePZDC.H\u003csub\u003e2\u003c/sub\u003eO, 98%), and sodium hydroxide (NaOH, 98%), benzaldehyde, \u003cem\u003ep\u003c/em\u003e-methylbenzaldehyde, \u003cem\u003ep\u003c/em\u003e-methoxybenzaldehyde, methyl acetoacetate, urea, choline chloride (ChCl), \u003cem\u003eN,-N\u003c/em\u003e-dimethylformamide (DMF), dichloromethane (DCM), methanol (MeOH), ethanol (EtOH), toluene, acetonitrile (ACN), tetrahydrofuran (THF), ethyl acetate (EtOAc), and deuterated dimethyl sulfoxide (DMSO-d\u003csub\u003e6\u003c/sub\u003e) were bought from Sigma Aldrich/Merck Co. All chemical materials and solvents were utilized without further purification.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2. Characterization and instrumentation\u003c/h2\u003e \u003cp\u003eAttenuated total reflectance Fourier transform infrared (ATR-FTIR) spectra were recorded on a Bruker ALPHA Platinum ATR-FTIR spectrometer. The X-ray powder diffraction (PXRD) patterns were recorded on an STOE diffractometer with Cu-Kα radiation (λ\u0026thinsp;=\u0026thinsp;1.5418 \u0026Aring;). Field emission scanning electron microscopy (FE-SEM) was carried out using an Inspect F-50, in which all samples were sputtered with gold before inspection. The energy-dispersive X-ray spectroscopy (EDS) analysis was conducted via Edax Ametek (Octane Super-A). Thermogravimetric analysis (TGA) was carried out using STA-1500 instrument at a heating rate of 10 ◦C min\u003csup\u003e-1\u003c/sup\u003e in the air. The Brunauer- Emmett-Teller (BET) equation was employed to compute the surface area from the obtained adsorption data at P/P0 in the range of 0.05\u0026ndash;0.2. The total pore volume was estimated from the nitrogen adsorption data obtained at P/P\u003csub\u003e0\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;0.95. For thin-layer chromatography (TLC), silica gel plates (HSGF 254) were used, and compounds were visualized by irradiation with UV light. Organic solvents were removed under reduced pressure by a rotary evaporator. \u003csup\u003e1\u003c/sup\u003eH NMR analyses were performed at room temperature on a Bruker 300 MHz apparatus using deuterated dimethyl sulfoxide (DMSO-d\u003csub\u003e6\u003c/sub\u003e) as the solvent and tetramethylsilane (TMS) as the internal standard. The melting points were determined in open capillaries with a Stuart Melting Point Apparatus and are uncorrected.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3. Synthesis of defect-rich MOF-303 (Al)\u003c/h2\u003e \u003cp\u003eDefect-rich MOF-303 was prepared by grinding the hydrothermally synthesized MOF-303, following a method reported by Yaghi\u0026rsquo;s group [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Briefly, H\u003csub\u003e2\u003c/sub\u003ePZDC.H\u003csub\u003e2\u003c/sub\u003eO (1.74 g, 10 mmol) and NaOH (0.6 g, 15 mmol) were dissolved in 90 mL deionized water using sonication and placed in a 250 mL VWR bottle (Solution A). A separate solution of AlCl\u003csub\u003e3\u003c/sub\u003e.6H\u003csub\u003e2\u003c/sub\u003eO (2.41 g, 10 mmol) in 10 mL of deionized water (Solution B) was added dropwise to Solution A under vigorous stirring, causing the reaction mixture to turn milky white midway through the addition. The jar was then tightly sealed and placed in a preheated oven at 120\u0026deg;C for 24 hours. After completion of the reaction, the mixture was allowed to cool naturally to room temperature. The resulting white precipitate was collected by centrifugation and washed with deionized water three times per day for three consecutive days to remove residual aluminum chloride and sodium chloride. Subsequently, the water-washed MOF-303 was further washed with anhydrous ethanol in the same way to eliminate unreacted linker molecules from the pores. Finally, the purified MOF-303 powder was dried in air overnight and activated in a vacuum oven at 80\u0026deg;C for 12 hours. The obtained MOF-303 was then ground for two minutes until a fine powder was achieved before further characterization and investigation.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4. Synthesis of urea-based DES\u003c/h2\u003e \u003cp\u003eThe urea-based deep eutectic solvent (DES) was prepared using a previously reported method [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Briefly, ChCl and urea were mixed in a 1:2 molar ratios and stirred at 80\u0026deg;C for 2 hours. The obtained colorless mixture was then cooled to room temperature, forming a homogeneous, viscous liquid under ambient conditions for further application.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5. General procedure for the synthesis of DHPMs via the Biginelli condensation reaction\u003c/h2\u003e \u003cp\u003eThe synthesis of DHPM derivatives was performed at the optimized reaction conditions, where a mixture of benzaldehyde (1.0 mmol), methyl acetoacetate (1.0 mmol), urea (1.5 mmol), and defect-rich MOF-303 catalyst (0.05 mmol) was gently stirred at 80\u0026deg;C in a preheated oil bath for 4 hours. Five minutes after the reaction began, the mixture solidified, indicating the formation of the DHPM product. To monitor the reaction progress, small aliquots were taken at regular intervals. These portions were extracted with \u003cem\u003en\u003c/em\u003e-hexane and analyzed by TLC (using a 1:3 ethyl acetate: n-hexane mixture as the mobile phase). Upon completion of the reaction, the mixture was cooled to room temperature. Ethyl acetate (15 mL) was then added, and the insoluble catalyst was recovered by filtration through Celite under suction. The organic layer was washed twice with brine (15 mL) and dried over anhydrous Na\u003csub\u003e2\u003c/sub\u003eSO\u003csub\u003e4\u003c/sub\u003e. After evaporation of the solvent, the crude product was recrystallized from methanol (MeOH) to afford pure 3,4-dihydropyridine-2 (1H)-one (DHPM). All products were characterized by IR and \u003csup\u003e1\u003c/sup\u003eH NMR spectroscopy and by comparison with the melting points of reported compounds. For the recycling experiment, the recovered heterogeneous catalyst was washed with deionized water and EtOH respectively several times (3 \u0026times; 3 mL), activated in a vacuum oven at 80 ◦C for 12 h, and reused for successive runs.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results and discussion","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.1. Catalyst synthesis and characterization\u003c/h2\u003e \u003cp\u003eMOF-303 was first hydrothermally synthesized using aluminum ions and pyrazole dicarboxylate linkers (H₃PDC), following literature procedures [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. The as-synthesized MOF-303 was then smoothly ground to obtain a fine powder of defect-rich MOF-303. This grinding process weakens the Al\u0026ndash;O coordination bonds, leading to missing-linker and missing-cluster defects, which enhance porosity and increase the concentration of catalytic sites, as shown in Scheme \u003cspan refid=\"Sch1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFTIR spectra were obtained to investigate the chemical bonding, confirm the presence of the pyrazole unit, and identify the functional groups in the as-synthesized material. As shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, the characteristic peaks of defect-rich MOF-303 closely match those reported in the literature. The broad stretching bands observed in the range of 2850\u0026ndash;3629 cm\u003csup\u003e-1\u003c/sup\u003e can be attributed to \u003cem\u003e-N\u003c/em\u003e-H and O-H bonds, which result from surface-adsorbed water.[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] A small band at 1743 cm\u003csup\u003e-1\u003c/sup\u003e indicates the presence of free protonated carboxylic acid groups in the organic linker. This confirms the formation of defects resulting from the disruption of Al\u0026ndash;O coordination bonds during the grinding process [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. The sharp peaks at 1589 and 1385 cm\u003csup\u003e-1\u003c/sup\u003e correspond to the asymmetric and symmetric stretching vibrations of coordinated carboxylate (-COO-Al) groups, confirming the interaction between the H\u003csub\u003e2\u003c/sub\u003ePZDC ligands and Al\u003csup\u003e3+\u003c/sup\u003e ions, thus validating the successful formation of the MOF-303 framework [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Additionally, absorption bands observed at 1525, 1475, and 1003 cm\u003csup\u003e-1\u003c/sup\u003e correspond to the stretching vibrations of -C\u0026thinsp;=\u0026thinsp;N-, -C-C-, and -N-NH bonds, respectively [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows that the characteristic XRD patterns of the defect-rich MOF-303 powder closely align with the simulated pattern (CCDC 2078717) and previously reported data, confirming the material's structural integrity. The distinct peaks at specific 2θ values indicate the high crystallinity of defect-rich MOF-303 [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Additionally, slight peak broadening observed in the PXRD pattern suggests the presence of structural defects. This broadening can be attributed to the disruption of Al\u0026ndash;O coordination bonds induced by grinding, as supported by the presence of free protonated carboxylic acid groups in the FTIR spectrum (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe thermal behavior of defect-rich MOF-303 was investigated using TGA at a heating rate of 10 C min\u003csup\u003e-1\u003c/sup\u003e in the air, and the corresponding thermogram was depicted in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. The TGA profile reveals two distinct weight loss steps. The first weight loss (35 wt%) occurring below 150\u0026deg;C corresponds to the evaporation of surface-adsorbed water and ethanol molecules trapped in the MOF-303 pores. Notably, this weight loss is higher than that reported for pristine MOF-303 (20%) [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e], which suggests the presence of free uncoordinated carboxylic acid groups and/or unsaturated Al sites that can adsorb additional water. This observation further supports the defect formation indicated by FTIR and PXRD analyses. The second significant weight loss of ~\u0026thinsp;55 wt% above 400 ◦C demonstrates the degradation of organic components and structure collapsing. According to the TGA profile, defect-rich MOF-303 (Al) is thermally stable above 400 ◦C, which is agreeable to the reported in the literature [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eTo investigate the porosity and surface characteristics of defect-rich MOF-303, BET analysis was performed using nitrogen adsorption at 77 K, with the sample degassed under vacuum at 150\u0026deg;C for 4 hours. The results, shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, agree with previously reported data [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Figure\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ea presents the nitrogen adsorption isotherm, which exhibits typical type-I behavior, indicative of microporous materials according to the IUPAC classification. However, at higher relative pressures (P/P₀ \u0026asymp; 0.89), the adsorption begins to increase, a trend often observed in type II isotherms. This suggests the presence of additional external surface area, likely attributed to larger crystals or agglomerates [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Moreover, the desorption isotherm does not coincide with the adsorption curve, revealing a hysteresis loop of type H3. This loop is characteristic of mesopores formed by interparticle contacts, allowing for additional nitrogen adsorption and capillary condensation [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. As shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, the specific surface area and pore volume of defect-rich MOF-303 were found to be 1283.2 m\u003csup\u003e2\u003c/sup\u003e/g and 1.0448 cm\u003csup\u003e3\u003c/sup\u003e/g, respectively, indicating a highly porous structure. The pore size distribution, calculated using the Barrett-Joyner-Halenda (BJH) method, reveals an average mesopore size of 3.257 nm, with a significant proportion of micropores, along with a smaller fraction of macropores in the range of 50 to 60 nm, as illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eb. This broad pore size distribution suggests the presence of irregular voids and larger mesopores created by defects. These results align well with the findings from FTIR, PXRD, and TGA (Figs.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e), further confirming the successful introduction of defects within the MOF-303 framework.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eTextural properties of defect-rich MOF-303.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBET surface area m\u003csup\u003e2\u003c/sup\u003e/g\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003emean pore diameter (nm)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTotal pore volume (cm\u003csup\u003e3\u003c/sup\u003e/g)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDefect-rich MOF-303\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1283.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.257\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0448\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe morphology and elemental distribution of defect-rich MOF-303 were investigated using FE-SEM and EDS analysis. As shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ea, defect-rich MOF-303 exhibits cubic-shaped, well-intergrown crystals that form larger crystals or agglomerates. This morphology contributes to the increase in the N\u003csub\u003e2\u003c/sub\u003e adsorption curve at higher relative pressures, as discussed earlier. EDS analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eb), combined with elemental mapping (Figs.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ec\u0026ndash;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ef), reveals that aluminum, carbon, oxygen, and nitrogen, are homogeneously distributed throughout the MOF-303 crystals. The elemental percentages observed in the EDS analysis are in good agreement with the calculated values [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.2. Catalytic application\u003c/h2\u003e \u003cp\u003eWith its high surface area, hierarchical porous structure, excellent thermochemical stability, and the coexistence of \u003cem\u003eN\u003c/em\u003e-functionalized channels along with a high density of exposed Al\u003csup\u003e3+\u003c/sup\u003e sites as hard Lewis acids, defect-rich MOF-303 meets the essential criteria for a bifunctional heterogeneous catalyst in the multicomponent Biginelli reaction. To assess its catalytic performance, a series of control experiments were carried out using benzaldehyde, methyl acetoacetate, and urea in a 1:1:1.5 molar ratio as the model reaction. The molar ratio with urea in excess was based on many previous studies, which illustrated that a slight excess of urea enhances the reaction by stabilizing the iminium ion through hydrogen bonding and proton transfer, contributing to an improved reaction outcome [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Initially, the model reaction was carried out under solvent-free conditions using 7 mg of catalyst to optimize the reaction temperature and time, and the results are shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The progress of the reaction was easily monitored by observing the solidification of the reaction mixture and was further verified by thin-layer chromatography (TLC). No by-products were detected via TLC. Clearly, performing the reaction at room temperature resulted in a negligible yield, even after a prolonged reaction time (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, entry 1). The percentage of isolated yield gradually increased with the reaction temperature at shorter reaction times, reaching the highest yield at 80\u0026deg;C (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, entries 2\u0026ndash;5), after which the yield showed no significant improvement (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, entries 6 and 7). Therefore, 80\u0026deg;C was chosen as the optimum reaction temperature for further investigation. The catalyst load is an important factor in this procedure. The influence of different catalyst dosages (7 mg, 10 mg, 20 mg, and 30 mg) at the optimum reaction temperature revealed that the maximum product yield (\u0026gt;\u0026thinsp;99%) was achieved with 10 mg of catalyst (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, entry 8). Increasing the catalyst amount beyond this point resulted in a decrease in yield (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, entries 9 and 10). Therefore, 10 mg of catalyst was selected as the optimal amount for further studies.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eEffect of reaction temperature and catalyst load on the model Biginelli reaction catalyzed by MOF-303.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEntry\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCatalyst load (mg)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTemperature (\u0026deg;C)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTime (h)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eYield (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ert\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e59\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e94\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e87\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e85\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e10\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e80\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e2.5\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026gt;\u0026thinsp;99\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e89\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e83\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe effect of various solvents, including protic, aprotic, non-polar solvents, and urea-based deep eutectic solvent (DES), was investigated while maintaining the optimal reaction parameters: temperature (80\u0026deg;C, or reflux for solvents with boiling points below 80\u0026deg;C), reaction time (2.5 hours), and catalyst amount (10 mg). It is important to note that no additional urea was required when using the urea-based DES, as urea is already a component of the DES mixture. The results shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e revealed that solvent-free conditions and DES resulted in the highest yields (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, entries 1 and 11). Methanol and ethanol also provided good yields (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, entries 2 and 3), while the remaining solvents (entries 4\u0026ndash;10) yielded negligible results. Consequently, solvent-free conditions were selected as the optimal reaction medium, as they minimize environmental impact and enhance sustainability.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSolvent effect on the model Biginelli reaction catalyzed by MOF-303.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEntry\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSolvent\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTemperature (\u0026deg;C)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTime (h)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eYield %\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMeOH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ereflux\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e94\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEtOH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ereflux\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e91\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eH\u003csub\u003e2\u003c/sub\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e56\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDMF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCH\u003csub\u003e2\u003c/sub\u003eCl\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ereflux\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eACN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTHF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ereflux\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003en\u003c/em\u003e-hexane\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ereflux\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eToluene\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDES\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;99.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eWith the optimized reaction conditions in hand, the scope of the Biginelli reaction was investigated using a variety of heterocyclic and aromatic aldehydes, including those with both electron-rich and electron-deficient substituents, as illustrated in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. Notably, all substrates reacted efficiently and afforded high yields of the corresponding products. The structures of the final products were confirmed after recrystallization using IR and \u003csup\u003e1\u003c/sup\u003eH NMR (see Supporting Information) and by comparing their melting points with those reported in the literature (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cimg 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\" width=\"553\" height=\"174\"\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4.\u003c/strong\u003e Scope of aldehyde substrates in the synthesis of DHPM derivatives via the Biginelli reaction.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cimg 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\" width=\"410\" height=\"486\"\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e \u003cp\u003eTo investigate the durability and recyclability of defect-rich MOF-303, the model Biginelli reaction was performed under optimized conditions across multiple cycles. After each cycle, the solid catalyst was separated from the reaction mixture, thoroughly washed with deionized water and ethanol, and dried in vacuum before reuse. Notably, only a slight decrease in product yield was observed after five cycles (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e), demonstrating the catalyst's stability and reusability.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe proposed mechanism of the Biginelli reaction over defect-rich MOF-303 is illustrated in Scheme \u003cspan refid=\"Sch2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. By leveraging its dual acid-base catalytic sites, defect-rich MOF-303 promotes the reaction through a dual-mode activation. The process begins with the activation of benzaldehyde via Lewis acid-base interactions between an accessible Al\u003csup\u003e3+\u003c/sup\u003e site in the metal node and the oxygen atom of the carbonyl group. Simultaneously, the electron-rich \u003cem\u003eN\u003c/em\u003e-containing pyrazole ligands act as Lewis bases, deprotonating urea to enhance its nucleophilicity. The activated urea then attacks the polarized carbonyl group of benzaldehyde, forming a hemiaminal intermediate that rapidly dehydrates to generate the imine intermediate. Subsequently, the imine undergoes Michael addition with the enol tautomer of the β-ketoester, followed by intramolecular cyclization and final dehydration, yielding the DHPM product.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eTo evaluate the catalytic potential of defect-rich MOF-303 for the Biginelli reaction, its performance was compared with previously reported bifunctional acid-base MOF catalysts. This comparative study, based on the isolated yield and reaction conditions, is summarized in Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e. The results demonstrate that defect-rich MOF-303 exhibits catalytic activity comparable to that of previously reported bifunctional MOFs. However, unlike these catalysts which rely on complex ligands and expensive reagents, MOF-303 is synthesized from readily available cost-effective precursors using a straightforward and environmentally friendly process. These advantages make MOF-303 as a more practical and sustainable alternative for heterogeneous catalysis in the Biginelli reaction.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of defect-rich MOF-303 with previously reported dual acid-base MOF catalysts for the Biginelli reaction.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEntry\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCatalyst\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTime\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eConditions\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eYield%\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCSMCRI-15 (1.5 mol%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNeat, 60\u0026deg;C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eZIF-8 (1.5 NaOH) (10% wt.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eEtOH, 90\u0026deg;C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eADES-1 (0.02 mmol)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNeat, 80\u0026deg;C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCu-MOF (10 wt%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNeat, 60\u0026deg;C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAnionic Zn (II)-MOF (10 wt%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNeat, 60\u0026deg;C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIRMOF-3 (4 mol%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNeat, 60\u0026deg;C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCd-MOF (0.03 mmol)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNeat, 70\u0026deg;C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDefect-rich MOF-303 (10 mg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.5 h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNeat, 80\u0026deg;C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eThis work\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4. Conclusion","content":"\u003cp\u003eIn summary, defect-rich MOF-303 was prepared by grinding hydrothermally synthesized MOF-303 and thoroughly characterized. Comprehensive characterization confirmed defect formation through FTIR, PXRD, TGA, N\u003csub\u003e2\u003c/sub\u003e adsorption-desorption isotherms, and pore size distribution analysis. FTIR spectra revealed free protonated carboxylic acid groups, indicating disruption of Al\u0026ndash;O coordination bonds. PXRD analysis showed slight peak broadening, suggesting structural defects, while TGA exhibited greater weight loss in defect-rich MOF-303 compared to pristine MOF-303, further supporting defect formation. The nitrogen adsorption isotherm displayed a type II trend at a high relative pressure (P/P\u003csub\u003e0\u003c/sub\u003e\u0026thinsp;~\u0026thinsp;0.89), indicative of defect-induced mesoporosity. Meanwhile, pore size distribution analysis confirmed a broad range of irregular voids and larger mesopores, highlighting the hierarchical porous structure. The obtained defect-rich MOF-303 exhibited outstanding catalytic efficiency in the Biginelli reaction under mild reaction conditions (solvent-free, 10 mg catalyst, 80 C, 2.5 h). A dual-activation mode mechanism was proposed to explain its dual acid-base nature. Furthermore, recyclability tests demonstrated the catalyst\u0026rsquo;s stability over five cycles. Notably, the present catalyst achieved catalytic performance comparable to previously reported dual acid-base MOFs while offering superior economic benefits. These findings highlight defect-rich MOF-303 as a promising, cost-effective, and sustainable bifunctional catalyst for the Biginelli reaction, paving the way for future applications in green and heterogeneous catalysis.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eDeclaration of competing interest\u003c/h2\u003e \u003cp\u003eThere are no conflicts of interest to declare.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eSupplementary materials\u003c/h2\u003e \u003cp\u003e \u003csup\u003e1\u003c/sup\u003eH NMR and FTIR spectra of DHPM derivatives.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eNuhaa Shaheed: Writing \u0026ndash; review \u0026amp; editing, Writing \u0026ndash; original draft, Visualization, Validation, Software, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. Ahmad Shaabani: Writing \u0026ndash; review \u0026amp; editing, Supervision, Project administration. All authors reviewed the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgments\u003c/h2\u003e \u003cp\u003eWe gratefully acknowledge the financial support provided by Shahid Beheshti University in Tehran, Iran.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eAll data generated or analyzed during this study are included in this manuscript and its supplementary information file\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eO.A. Elbanna, M.S. Adly, A.M.A. Hagr, A.I. Ahmed, A.A. Ibrahim, Eco-friendly and efficient sulfamic acid functionalized MIL-53 (Al) nanocomposite for removal of hazardous pollutants from wastewater and catalytic synthesis of 3,4-dihydropyrimidinone pharmacological moiety, J. Mol. Struct. 1312 (2024) 138463.\u003c/li\u003e\n\u003cli\u003eL.G. do Nascimento, I.M. Dias, G.B. Meireles de Souza, I. Dancini-Pontes, N.R.C. Fernandes, P.S. de Souza, G. Roberto de Oliveira, C.G. 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Solid State Chem. 332 (2024) 124534.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Schemes","content":"\u003cp\u003eSchemes 1 and 2 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Defect-rich MOF-303, Biginelli reaction, Dihydropyrimidinone, Solvent-free","lastPublishedDoi":"10.21203/rs.3.rs-6248371/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6248371/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBifunctional MOF-303 (Al) exhibits promising catalytic activity for the Biginelli reaction. However, its intrinsic microporosity may hinder reactant and product diffusion and reducing efficiency. Introducing defects is crucial for enhancing its catalytic performance. In this work, defect-rich MOF-303 was prepared by grinding the hydrothermally synthesized MOF-303 into a fine powder. The resulting material was thoroughly characterized and exhibited excellent catalytic performance in the solvent-free synthesis of diverse dihydropyrimidinones under moderate reaction conditions, achieving yields between 94% and over 99%. Moreover, the catalyst was successfully recycled over five cycles with minimal activity loss. The structures of the obtained products were confirmed by IR, \u0026sup1;H NMR, and melting point analysis. The simple preparation method using commercially inexpensive reagents, high catalytic performance under mild conditions, and recyclability of defect-rich MOF-303 highlight its potential as an efficient and sustainable catalyst for the Biginelli reaction.\u003c/p\u003e","manuscriptTitle":"Defect-rich MOF-303 as a dual acid-base heterogeneous catalyst for the one- pot Biginelli synthesis of dihydropyrimidinones","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-31 06:17:31","doi":"10.21203/rs.3.rs-6248371/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-06-12T05:56:45+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-14T18:42:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"6907891789266857403164469474714526487","date":"2025-04-04T07:18:22+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-03-31T04:18:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"330313308000430062424017892817977599246","date":"2025-03-21T09:33:18+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-03-21T07:13:35+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-03-21T07:10:14+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-03-21T06:56:44+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-03-19T14:02:51+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-03-18T01:35:26+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"dc9a69a5-99ba-427f-89fe-62dc989e9f75","owner":[],"postedDate":"March 31st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":46196594,"name":"Physical sciences/Chemistry"},{"id":46196595,"name":"Physical sciences/Materials science"}],"tags":[],"updatedAt":"2025-10-27T16:32:43+00:00","versionOfRecord":{"articleIdentity":"rs-6248371","link":"https://doi.org/10.1038/s41598-025-21172-6","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-10-24 16:16:32","publishedOnDateReadable":"October 24th, 2025"},"versionCreatedAt":"2025-03-31 06:17:31","video":"","vorDoi":"10.1038/s41598-025-21172-6","vorDoiUrl":"https://doi.org/10.1038/s41598-025-21172-6","workflowStages":[]},"version":"v1","identity":"rs-6248371","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6248371","identity":"rs-6248371","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}