Asparagine-EDTA MNPs: A Highly Efficient And Recyclable Magnetic Multifunctional Core-Shell Nanocatalyst For Green Synthesis of Biologically-Active 3,4-Dihydropyrimidin-2(1H)-One Compounds

Asparagine-EDTA MNPs: A Highly Efficient And Recyclable Magnetic Multifunctional Core-Shell Nanocatalyst For Green Synthesis of Biologically-Active 3,4-Dihydropyrimidin-2(1H)-One Compounds | 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 Research Article Asparagine-EDTA MNPs: A Highly Efficient And Recyclable Magnetic Multifunctional Core-Shell Nanocatalyst For Green Synthesis of Biologically-Active 3,4-Dihydropyrimidin-2(1 H )-One Compounds Negin Rostami, Mohammad G Dekamin, Ehsan Valiey, Hamidreza FaniMoghadam This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-971598/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract In this study, the new asparagine grafted on the EDTA-modified Fe 3 O 4 @SiO 2 core-shell (Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine) magnetic nanoparticles were prepared and their structures were properly confirmed using different spectroscopic, microscopic and magnetic methods or techniques such as FT-IR, EDX, XRD, FESEM, TEM, TGA and VSM. The Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine core-shell nanomaterial was examined, as a highly efficient multifunctional and recoverable nanocatalyst, for the synthesis of a wide range of nitrogen-containing heterocycles and biologically-active 3,4-dihydropyrimidin-2(1 H )-one derivatives under solvent-free conditions. It was proved that Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine MNPs, as a catalyst having excellent thermally and magnetic stability, specific morphology and acidic sites, can activate the Biginelli reaction components. Moreover, environmental-friendliness and nontoxic nature properties of the catalyst, cost effectiveness, low catalyst loading, easy separation of the catalyst from products and short time of reaction are some of the remarkable advantages of this green protocol. Nanoscience General Biochemistry Core-Shell magnetic nanoparticles Nano-Ordered catalysts Multi-Component reactions (MCRs) Heterocycles Green and sustainable chemistry Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Introduction Green chemistry has played a key role in the development of human civilization 1–4 . In this regard, magnetic nanoparticles (MNPs) have received considerable interest because of their unique properties 5 . The outstanding properties of MNPs have made them superior and indispensable in many areas of industry and academia including information storage 6 , medicine 7 , drug delivery 8 , magnetic resonance imaging (MRI) 9,10 , biomedical applications 5,11,12 , and environmental remediation 13 as well as heterogeneous catalysis 14–17 . In academia, MNPs represent a promising new technology for performing chemical reactions because they are separated from the reaction medium, comfortably 18,19 . In industry, due to the importance of the cost of chemical processes and the reuse of catalysts, special attention is paid to these nanoparticles 20,21 . MNPs tend to agglomerate under a magnetic field that reduces their surface to volume ratio and consequently decreases catalytic activity 22 . Therefore, MNPs must be stabilized to improve their properties and prevent undesirable agglomeration 23 . In fact, they are coated with a protective layer such as carbon layers 24,25 , organic polymer 26 or silica 27,28 . Moreover, multi-component reactions (MCRs) are the most desirable powerful synthetic route in which three or more reactants come together in a single reaction vessel to form a wide range of acyclic or heterocyclic compounds by the one-pot processes 29,30 . MCRs afford extended molecular complexity and diversity from simple starting materials with high atom economy, which have found application in medicinal and natural products chemistry 31,32 . Indeed, the most significant feature of MCRs is generating almost no by-products or simple molecules such as H 2 O or EtOH 33–37 . Hence, in agreement of the green and sustainable chemistry process, development and the advancement of catalysts to promote MCRs are very important in synthetic and medicinal chemistry 38–40 . Among the various types of nitrogen-containing heterocycles, derivatives of 3,4-dihydropyrimidin-2(1 H )-one, as biologically-active compounds, have found versatile applications such as anti-bacterial, anti-inflammatory, antihypertensive agents, calcium channel blockers, antitumor compounds 41–47 . A simple and general protocol for access to 3,4-dihydropyrimidin-2(1 H )-ones involves a three-component one-pot Biginelli cyclocondensation of ethyl acetoacetate, urea and various aldehydes accelerated by different types of catalytic systems such as polymer-supported catalysts 48 , ionic liquids 49,50 , ionic liquid/silica sulfuric acid 51 , metal−organic framework (MOF) 52,53 , montmorillonite clay 54 , magnetic nanoparticles 55 , Lewis acidic zirconium (IV)-salophen perfluorooctanesulfonate or sulfated polyborate 56,57 , nanocrystalline CdS thin film 46 , graphene oxide 58,59 and mesoporous materials 60,61 as well as environmental friendly energy inputs such as ultrasound 62 or microwave irradiation 63 . Most of the reported methods in this regard have the role of heterogeneous catalysts and high value. However, these have problems such as complicated and tedious separation of products and catalysts, toxic reaction conditions, long reaction times and low yields. Therefore, there is still room to develop more environmentally-benign protocols to promote the Biginelli MCR condensation. In many previous reports, ethylenediaminetetraacetic acid (EDTA) has been used as an ion exchange and chelating agent for various metal ions 64–66 , but this compound has a good ability as an inexpensive and non-toxic cross-linker to make strong bonds with organic materials having nucleophilic centers 67 . On the other hand, asparagine is one of the 20 amino acids found in the cells of the human body and is essential for maintaining balance in the central nervous system 68 . Asparagine can act as a biocompatible precursor and bifunctional organocatalyst due to its high natural abundance and cost-effectiveness with acidic and basic sites 69,70 . In this research, we herein report the synthesis and characterizations of new asparagine grafted on the EDTA-modified Fe 3 O 4 @SiO 2 core-shell magnetic nanoparticles (Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine), as a magnetically recoverable nanocatalyst, to promote the Biginelli reaction efficiently at 60°C under solvent-free conditions (Fig. 1 ). Results And Discussion Characterization of the Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine nanocatalyst (1) The overall procedure for the synthesis of Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine ( 1 ) has been summarized in Fig. 1 . At first, the obtained magnetic nanoparticles were characterized using different physicochemical techniques such as Fourier transform infrared (FT-IR) spectroscopy, energy-dispersive X-ray (EDX) spectroscopy, field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), X-ray diffraction spectroscopy (XRD), vibrating sample magnetometer (VSM), and thermogravimetric analysis (TGA). The FT-IR spectroscopy was employed to determine the functional groups and structure of Fe 3 O 4 (a), Fe 3 O 4 @SiO 2 (b), Fe 3 O 4 @SiO 2 -APTS (c), Fe 3 O 4 @SiO 2 -APTS-EDTA (d) and Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine (e). The results are presented in Fig. 2 . In the spectra of Fe 3 O 4 nanoparticles (Fig. 2 a) the bands displayed at 620 cm −1 and about 3410 cm −1 are attributed to stretching vibration of Fe−O bond and surface hydroxyl groups, respectively. These peaks were observed in all five samples isolated at the different synthetic stages. In the FT-IR spectrum of Fe 3 O 4 @SiO 2 (Fig. 2 b), the absorption bands at 881 and 1036 cm −1 can be ascribed to the presence of Si−O−Si symmetric and Si−O−Si asymmetric stretching modes, reflecting the coating of silica layer on the magnetite nanoparticles 71 . SP 3 C–H stretching vibrations about 2922 cm −1 confirmed the presence of the anchored (3-aminopropyl) triethoxysilane (APTS) group and the band about 1400 cm −1 is assigned to the bending of −NH groups of Fe 3 O 4 @SiO 2 -APTS MNPs (Fig. 2 c) 72 . In the FT-IR spectrum of Fe 3 O 4 @SiO 2 -APTS-EDTA (Fig. 2 d), the peaks at 1635 cm −1 , 1707 cm −1 and 1760 cm −1 corresponding to the C=O vibration of amide, acid and anhydride groups, respectively. In the last step, the peak at 1760 cm −1 , which belongs to the anhydride group has been removed and new peaks at 1651 cm −1 and 1737 cm −1 are attributed to the amide and acid groups in the surface of Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine (Fig. 2 e). These results from the FT-IR spectrum confirm that the silica coating and subsequent steps have been successfully performed on the surface of Fe 3 O 4 . Compositional analysis of the Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine magnetic nanocatalyst ( 1 ) was carried out using energy-dispersive X-ray spectroscopy (EDX). The EDX spectra of the Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine nanomaterial ( 1 ) are depicted in Fig. 3 . In addition, the EDX analysis showed the well-defined peaks related to C, O, N, Si and Fe in the structure of Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine ( 1 ) with the percentages of 40.32, 36.57, 11.69, 6.34 and 5.08, respectively. The morphology and texture of Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine MNPs ( 1 ) were indicated by FESEM analysis and their photographs were presented in Fig. 4 . According to these FESEM photographs, the size and surface shape of nanoparticles are well observed, which proves that the particles are spherical and without agglomeration. The FESEM photographs supported the formation of spherically shaped MNPs, which is in accordance with TEM analysis. The TEM analysis of the Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine ( 1 ) MNPs in two scales is shown in Fig. 5 . The TEM images demonstrated structural order and the morphology suggested that the magnetite nanoparticles have an average diameter size of 41 nm. The XRD pattern of Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine ( 1 ) was shown in Fig. 6 . The reflection peaks were compared with the reference standard patterns related to EDTA (card no. JCPDS, 00-033-1672), Fe 3 O 4 (card no. JCPDS, 01-088-0315) and asparagine (card no. JCPDS, 00-031-1542). The sharp peaks in this pattern are generated by combining several peaks. These new sharp peaks are ascribed to the produced Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine MNPs structures after modification reactions by EDTA and asparagine, respectively. The magnetic properties of MNPs were measured via vibrating sample magnetometery (VSM). The magnetic attributes of Fe 3 O 4 and Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine MNPs ( 1 ) were measured out at room temperature by applied magnetic field -1000 to +1000 Oersted. According to data presented in Fig. 7 , The values of the magnetization saturation (Ms) for Fe 3 O 4 and Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine MNPs ( 1 ) are 73.12 and 20.84 emu/g, respectively. Moreover, the VSM curves of both samples exhibit no hysteresis loops and this property demonstrated that no aggregation occurred in the presence of magnetic fields. A decrease in the magnetic saturation of the Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine was observed after coating with SiO 2 and functionalization with APTS. However, the magnetic saturation of Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine ( 1 ) is sufficient to be recovered by exerting an external magnet. Thermal stability of the Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine nanomaterial ( 1 ) was investigated under the air atmosphere over the temperature range of 50 − 800°C (Fig. 8 ). The Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine MNPs ( 1 ) display three weight loss steps over the temperature range of TGA and the total weight loss of nanocatalyst 1 is around 60%. According to obtained results, in the first step 15% weight loss in the range of 150 − 200°C is due to the evaporation of adsorbed water and organic solvents that remain in the nanocatalyst through its preparation processes. In addition, 22% weight loss in the range of 200 − 400°C corresponds to the loss of EDTA–asparagine moiety. In the last step, the sharp weight loss of 23% at 400-700°C can be assigned to the decomposition of APTS moiety in the MNPs framework. These results also indicate that APTS, EDTA and asparagine has been successfully grafted onto the surface of Fe 3 O 4 @SiO 2 . Above 700°C only Fe 3 O 4 was present. Optimization of conditions in the Biginelli reaction using Fe 3 O 4 @SiO 2 -APTS-EDTA asparagine nanocatalyst (1) In our preliminary experiments, the catalytic activity of as prepared catalyst 1 was evaluated in the formation of dihydropyrimidin-2(1 H )-one derivatives by the Biginelli condensation. For this purpose, reaction conditions were optimized using the equimolar mixtures of urea ( 2 , 1 mmol), 4-chlorobenzaldehyde ( 3a , 1 mmol) and ethyl acetoacetate ( 4a , 1 mmol) as the model reaction ( Eq. 1 ). In a systematic screening, the reaction conditions were investigated precisely by considering of several crucial variables such as catalyst loading, reaction time, solvent and reaction temperature, as given in Table 1 . Initially, in the absence of any catalyst and solvent, the progress of model reaction was slow and the yield of the 9-(4-chlorophenyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydroacridine-1,8(2 H ,5 H )-dione ( 5a ) was trace, even after a long time (Table 1 , entry 1). Then, in the presence of very low amount of Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine ( 1 ) loading, as a nanocatalyst, without any solvent at room temperature, a good yield of the desired product 5a was obtained (Table 1 , entry 2). To achieve an excellent yield, the reaction temperature was increased to 60°C (Table 1 , entry 3). Afterward, the model reaction was performed with lower catalyst 1 loading under solvent-free conditions as well as polar and non-polar solvents. Furthermore, the effect of temperature and different solvents was investigated (Table 1 , entries 4-13). Also, the model reactions in the presence of EDTA and asparagine were separately investigated, but lower yields of the desired product 5a were isolated (Table 1 , entries 14-15). Following the steps of optimizing the reaction conditions, the effect of different solvents and amount of catalyst loadings are summarized in Fig. 9. The model reaction was investigated under solvent-free conditions and different solvents such as EtOH, MeOH, EtOH/H 2 O (1:1), and DMF using Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine nanocatalyst (1) with different loading of the catalyst 1. According to the obtained findings summarized in Table 1 and Fig. 9, the optimum reaction conditions were found to be 10 mg of Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine nanocatalyst (1) loading under solvent-free conditions at 60 °C. After the above experiments, the scope of reaction was expanded by using aromatic aldehydes having electron-withdrawing or electron-donating groups under the optimized conditions ( Eq. 2 ). The results are summarized in Table 2 . As expected, in this novel magnetic heterogeneous catalytic system the reaction rate of aldehydes with electron-donating groups was slower than electron-releasing ones and required more time to complete the reaction. An alternative variation in this reaction was accomplished by utilizing methyl acetoacetate ( 4b ) instead of ethyl acetoacetate ( 4a ) for the synthesis of different Biginelli products. It is worth noting that all the reactions represented very good to excellent yields under solvent-free conditions in short time. The proposed mechanism for the synthesis of 3,4-dihydropyrimidin-2(1H)-one derivatives in the presence of Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine nanocatalyst (1) The proposed mechanism based on the three-component strategy for the synthesis of 3,4-dihydropyrimidin-2(1 H )-one derivatives catalyzed by Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine nanocatalyst ( 1 ) is presented in Fig. 10 . At first, the carbonyl group of aldehyde is activated by Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine ( 1 ) to form intermediate ( I ) through the condensation with urea ( 2 ). Afterward, iminium intermediate ( III ) is produced after leaving the H 2 O in the presence of the magnetic nanocatalyst. Meanwhile, intermediate ( III ) reacts with the enol form of the alkyl acetoacetate ( 4 ) and the corresponding intermediate ( IV ) is generated. Eventually, intramolecular cyclization occurs which is followed by dehydration of intermediate ( V ). At the end of the catalytic cycle, 3,4-dihydropyrimidin-2(1 H )-ones are produced and the catalyst is recycled 60 . Green chemistry metrics In this part of our research, green chemistry metrics for the synthesis of 3,4-dihydropyrimidin-2(1 H )-one by Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine nanocatalyst ( 1 ) were calculated and the results are summarized in Table 3 79,80 . Hence, several parameters of the green approach such as environmental factor (E factor), process mass intensity, reaction mass efficiency, carbon efficiency, and atom economy were evaluated and compared to the ideal values 81 . As presented in Table 3 , all calculated values are close to the ideal values and were reported in supporting information. Reusability of the Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine nanocatalyst (1) One of the critical scales in catalytic processes is reusability and recyclability of the catalyst. For evaluation of this parameter, the model reaction was examined using Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine ( 1 ) for four runs. At the end of the reaction, the catalyst 1 was removed using an external magnet and the recycled catalyst was washed with dry toluene, dried and used in a subsequent model reaction. The obtained results are summarized in Fig. 11 . Considering the results of isolated yields of products, the catalytic activity of Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine nanocatalyst ( 1 ) after four runs is slightly reduced, which demonstrates proper conservancy of the catalytic activity after recycling. Comparative study of Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine nanocatalyst (1) and other catalysts for the Biginelli reaction In order to compare the optimal catalytic activity and reaction conditions of the Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine nanocatalyst ( 1 ) with previously reported catalysts for the three-component Biginelli reaction, we compared reaction conditions and yield of desired product ( 5a ) in Table 4 . As it can be observed from data in Table 4 , all catalytic systems are capable of producing the desired product with satisfactory yields but Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine nanocatalyst ( 1 ) in terms of yield and time factors, the reaction temperature, solvent and amount of catalyst loading demonstrates better performance than the other catalysts. Furthermore, additional advantage of this protocol is its easy separation from the crude products by using an external magnet compared to the most of reported heterogeneous catalytic systems. Experimental Chemicals and Instrumentation Ferric chloride (FeCl 3 .6H 2 O), Ferrous chloride tetrahydrate (FeCl 2 .4H 2 O), (3-aminopropyl) triethoxysilane (APTS, 99%), tetraethyl orthosilicate (TEOS, 99%), ammonia (25 wt%), EDTA (MW = 292.24 g/mol), and asparagine (MW = 132.12 g/mol) were purchased from Merck and used without further purification. Urea, ethyl acetoacetate and aromatic aldehydes were purchased from international chemical companies including Merck and Sigma-Aldrich. The analytical TLC experiments were accomplished using Merck Kieselgel 60 F-254 Al-plates and then visualized by UV light and iodine vapour. Melting points of the products were measured on an Electrothermal 9100 apparatus and uncorrected. The functional groups of the samples were identified by FT-IR spectroscopy on a Perkin Elmer, Frontier FT-MIR spectrometer in the range of 600-4000 cm -1 using KBr discs. The morphology of the nanocatalyst was observed by FESEM TESCAN-MIRA3 and TEM Philips EM 208S. TGA curves of the Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine ( 1 ) were recorded by Bahr company STA 504. X-ray diffraction (XRD) pattern of the catalyst 1 was taken by the Bruker D8 Advance device. The composition of the catalyst was determined by energy-dispersive X-ray (EDX) spectroscopy using a Numerix DXP-X10P instrument. Magnetization measurements were carried out on a BHV-55 vibrating sample magnetometer (VSM). 1 H NMR spectra of the isolated products were recorded at 500 MHz using a Varian-INOVA spectrometer. General procedure for preparation of the magnetic Fe 3 O 4 nanoparticles Preparation of Fe 3 O 4 nanoparticles were according to a reported general method 83 . In this procedure, in a 100 mL round-bottomed flask FeCl 3 .6H 2 O (4.6 g, 0.017 mol) and FeCl 2 .4H 2 O (2.3 g, 0.011 mol) were dissolved in deionized water (60 mL) and stirred for 30 min. Subsequently, aqueous NH 3 (10 mL) was added dropwise into the mixture and heated to 40°C under N 2 atmosphere for 2 h. The black solution was poured from the reaction vessel and Fe 3 O 4 MNPs precipitates were separated from the solution using an external magnet, washed five times with deionized water and EtOH, and dried in the oven at 50°C for 24 h. General procedure for preparation of the silica-coated magnetic nanoparticles (Fe 3 O 4 @SiO 2 ) In accordance to the modified Stöber method, silica-coated Fe 3 O 4 nanoparticles (Fe 3 O 4 @SiO 2 ) were produced by a solvothermal reaction 84 . For this purpose, the Fe 3 O 4 MNPs (1.0 g) were dispersed in 30 mL of distilled water and ultrasonicated for 30 min. Then, a mixture of aqueous NH 3 (2 mL) and EtOH (40 mL) were added dropwise to the magnetite mixture and ultrasonicated for 30 min. Then, a mixture of TEOS (2 mL) and EtOH (40 mL) were added slowly to the suspension solution under continuous stirring for 24 h at 60°C. Eventually, the Fe 3 O 4 @SiO 2 core-shell MNPs were collected using an external magnet, washed with deionized water and EtOH and dried in the oven at 50°C for 5 h. Modification of the Fe 3 O 4 @SiO 2 NPs by (3-aminopropyl) triethoxysilane (Fe 3 O 4 @SiO 2 -APTS) Fe 3 O 4 @SiO 2 core-shell MNPs were modified with (3-aminopropyl) triethoxysilane (APTS) using a typical modified method 85 . Briefly, the Fe 3 O 4 @SiO 2 NPs (1.0 g) were ultrasonicated in 30 mL dried toluene. Subsequently, APTS (2.0 mL) was added to the magnetic mixture and stirred at 105°C for 24 h. After washing with dry toluene, the obtained MNPs separated and dried at 60°C for 12 h in a vacuum oven to prepare the Fe 3 O 4 @SiO 2 -APTS MNPs. Preparation of the EDTA functionalized magnetic nanoparticles (Fe 3 O 4 @SiO 2 -APTS-EDTA) In a round-bottom flask, magnetic Fe 3 O 4 @SiO 2 -APTS NPs (1.0 g) were added to dry toluene (25 mL) and dispersed with ultrasonic for 15 min. Then, EDTA dianhydride (1.0 g) - synthesized according to Repo et al 86 - and acetic anhydride added to the mixture and stirred at 80°C under N 2 atmosphere for 24 h. The magnetic Fe 3 O 4 @SiO 2 -APTS-EDTA NPs were washed five times with EtOH followed by drying at 60°C for 6 h in a vacuum oven. Preparation of the asparagine grafted on the EDTA-modified Fe 3 O 4 @SiO 2 core-shell magnetic nanoparticles (Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine, 1) In the last step, the magnetic Fe 3 O 4 @SiO 2 -APTS-EDTA NPs were dispersed in 25 mL of dry toluene and asparagine (1.0 g) was added to the magnetic mixture and stirred under reflux conditions and N 2 atmosphere for 24 h. Magnetic precipitates were separated using an external magnet and after drying in the oven, brown powder of Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine nanocatalyst ( 1 ) was obtained. General procedure for the synthesis of 3,4-dihydropyrimidin-2(1H)-one (5a-5t) catalyzed by Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine nanomaterial (1) A mixture of urea ( 2 , 1.0 mmol), aromatic aldehyde ( 3 , 1.0 mmol), ethyl or methyl acetoacetate ( 4 , 1.0 mmol), and Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine ( 1 , 10 mg) were added under solvent-free conditions for an appropriate time indicated in Table 2 . After completion of the reaction, as monitored by TLC [eluent: n-hexane: EtOAc: 3:1], the catalyst was separated using an external magnet and the residue was concentrated to result in the crude product. Finally, the crude product was recrystallized from EtOH to obtain the pure product. Conclusion In summary, the novel and thermally stable asparagine grafted on EDTA-modified Fe 3 O 4 @SiO 2 core-shell magnetic nanoparticles (Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine) was prepared for the first time. The Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine heterogeneouse nanocatalyst was used for highly efficient, facile, and green and sustainable synthesis of 3,4-dihydropyrimidin-2(1 H )-one derivatives in a one-pot and three-component protocol through cyclocondensation of alkyl acetoacetate, urea and various aldehydes under solvent-free conditions. Consistency with the ideal values of green chemistry parameters, easy work up procedure, good to excellent yields in shorter reaction times, fast separation and recyclability of the catalyst are the additional advantages for its application in academic and industrial purposes. Declarations Acknowledgements We thank The Research Council of Iran University of Science and Technology (IUST), Tehran, Iran (Grant No 160/19108) for their support. We would also like to acknowledge the support of Iran Nanotechnology Initiative Council (INIC), Iran. References 1 Li, C.-J. & Anastas, P. T. Green Chemistry: present and future. 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Optimization of conditions in the model reaction of urea ( 2 ), 4-chlorobenzaldehyde ( 3a ), ethyl acetoacetate ( 4a ), under different conditions in the presence of Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine nanocatalyst ( 1 ). a Entry Catalyst Solvent Temperature (°C) Time (min) Yield b (%) 5a 1 - Solvent-free r.t 30 Trace 2 Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine Solvent-free r.t 30 85 3 Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine Solvent-free 60 20 95 4 Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine EtOH r.t 20 65 5 Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine EtOH Reflux 20 85 6 Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine MeOH r.t 40 45 7 Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine MeOH Reflux 40 55 8 Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine H 2 O r.t 30 60 9 Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine H 2 O Reflux 30 65 10 Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine EtOH/H 2 O (1:1) r.t 20 63 11 Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine EtOH/H 2 O (1:1) Reflux 20 70 12 Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine DMF r.t 30 55 13 Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine DMF Reflux 30 65 14 EDTA Solvent-free 60 20 75 15 Asparagine Solvent-free 60 20 65 a Reaction conditions: urea ( 2 , 1 mmol), 4-chlorobenzaldehyde ( 3a , 1 mmol), ethyl acetoacetate ( 4a , 1 mmol), Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine ( 1 ) and solvent (3 mL, if not otherwise stated). b Isolated yield. Due to technical limitations, table 2 is only available as a download in the Supplemental Files section. Table 3 Measurement of green chemistry metrics for compound 5a Entry Parameters of the green approach Ideal value Calculated values 1 E factor 0 0.16 2 Atom economy (AE %) 100% 89.1% 3 Carbon efficiency (CE %) 100% 96% 4 Process mass intensity (PMI) 1 1.16 5 Reaction mass efficiency (RME %) 100% 85.5% Table 4. Comparative results of catalysts for the synthesis of 5a Entry Catalyst Catalyst loading Reaction conditions Time (min) Yield (%) 1 Zn(II)-framework 10 wt % Solvent-free/60 °C 120 91 52 2 PANI-FeCl 3 200 mg CH 3 CN/ Reflux 1440 83 82 3 MCM-41-APS-PMDANHSO 3 H 15 mg Solvent-free/80 °C 35 96 60 4 Fe 3 O 4 @SiO 2 -APTMS-Fe(OH) 2 10 mg Neat/ 80 °C 15 95 55 5 zirconium (IV)-salophen perfluorooctanesulfonate 0.05 mmol Solvent-free/ 9 0 °C 30 96 56 6 Fe 3 O 4 @SiO 2 -APTS-EDTA-asparagine 10 mg Solvent-free/60 °C 20 95 This work Additional Declarations No competing interests reported. Supplementary Files Table23292022.pdf ElectronicSupportingInformationForReview3292022.pdf Cite Share Download PDF Status: Posted Version 1 posted 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-971598","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":59735556,"identity":"07b4bcbb-ad5a-4848-889f-695ce3131d77","order_by":0,"name":"Negin Rostami","email":"","orcid":"","institution":"Iran University of Science and Technology","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Negin","middleName":"","lastName":"Rostami","suffix":""},{"id":59735557,"identity":"6e9286d6-5fb3-436c-aaf6-99181c0281fb","order_by":1,"name":"Mohammad G 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1","display":"","copyAsset":false,"role":"figure","size":173954,"visible":true,"origin":"","legend":"Schematic preparation of Fe3O4@SiO2-APTS-EDTA-asparagine (1), as a heterogeneous nanocatalyst, for the synthesis of 3,4-dihydropyrimidin-2(1H)-one 5 derivatives.","description":"","filename":"fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-971598/v1/ca1449a4e9c34ac8be99c829.png"},{"id":15090850,"identity":"6505e5ef-4381-4c00-9c00-9a2bf1e92971","added_by":"auto","created_at":"2021-11-01 14:33:22","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":36725,"visible":true,"origin":"","legend":"FT-IR spectra of the Fe3O4 (a), Fe3O4@SiO2 (b), Fe3O4@SiO2-APTS (c), Fe3O4@SiO2-APTS-EDTA (d) and Fe3O4@SiO2-APTS-EDTA-asparagine (1, e).","description":"","filename":"fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-971598/v1/00ca4f403dd67fac713a9a95.png"},{"id":15090851,"identity":"6982ff90-5b58-45a2-a505-862ef934f910","added_by":"auto","created_at":"2021-11-01 14:33:22","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":107451,"visible":true,"origin":"","legend":"The EDX spectra of the magnetic Fe3O4@SiO2-APTS-EDTA-asparagine nanomaterial (1).","description":"","filename":"fig3.png","url":"https://assets-eu.researchsquare.com/files/rs-971598/v1/345e33c04f25446d8d614ea3.png"},{"id":15090858,"identity":"5b37b941-74ed-4e9d-a78c-d47d5373ef58","added_by":"auto","created_at":"2021-11-01 14:33:22","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1090425,"visible":true,"origin":"","legend":"FESEM images of the magnetic Fe3O4@SiO2-APTS-EDTA-asparagine nanocatalyst (1).","description":"","filename":"fig4.png","url":"https://assets-eu.researchsquare.com/files/rs-971598/v1/c7a0dcc12c5512668e22871d.png"},{"id":15091057,"identity":"205b64ed-cacb-4ab4-8471-8d268be33d26","added_by":"auto","created_at":"2021-11-01 14:36:22","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":688536,"visible":true,"origin":"","legend":"TEM images of the magnetic Fe3O4@SiO2-APTS-EDTA-asparagine nanomaterial (1).","description":"","filename":"fig5.png","url":"https://assets-eu.researchsquare.com/files/rs-971598/v1/27471920f732bbf0893d10f6.png"},{"id":15091320,"identity":"da4ff6cc-251d-4fde-ab23-95bfaf94a1e9","added_by":"auto","created_at":"2021-11-01 14:39:22","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":175671,"visible":true,"origin":"","legend":"XRD patterns of the magnetic Fe3O4@SiO2-APTS-EDTA-asparagine nanocatalyst (1).","description":"","filename":"fig6.png","url":"https://assets-eu.researchsquare.com/files/rs-971598/v1/89bfba6159c693e0ace32399.png"},{"id":15090359,"identity":"8867db42-2d2b-43b3-98fc-6d4e5637dc2c","added_by":"auto","created_at":"2021-11-01 14:30:22","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":8339,"visible":true,"origin":"","legend":"VSM pattern of Fe3O4 (red curve) and magnetic Fe3O4@SiO2-APTS-EDTA-asparagine nanocatalyst (1, green curve).","description":"","filename":"fig7.png","url":"https://assets-eu.researchsquare.com/files/rs-971598/v1/864495edeffb6208f3cf4eba.png"},{"id":15091060,"identity":"e6b59fcb-96b0-4f29-ba34-5fa16e8f9e57","added_by":"auto","created_at":"2021-11-01 14:36:22","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":115366,"visible":true,"origin":"","legend":"TGA curve of the magnetic Fe3O4@SiO2-APTS-EDTA-asparagine nanomaterial (1).","description":"","filename":"fig8.png","url":"https://assets-eu.researchsquare.com/files/rs-971598/v1/c6548dcab924810a20c7f192.png"},{"id":15090856,"identity":"5723c87d-6271-4af2-a8d3-4f47df9e14ef","added_by":"auto","created_at":"2021-11-01 14:33:22","extension":"png","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":31299,"visible":true,"origin":"","legend":"Effect of solvent and the amount of Fe3O4@SiO2-APTS-EDTA-asparagine nanocatalyst (1) on the model reaction.","description":"","filename":"fig9.png","url":"https://assets-eu.researchsquare.com/files/rs-971598/v1/39f2adc26df569d7f372e473.png"},{"id":15091059,"identity":"f4464457-02dd-4a8b-ba71-29d05228ff8e","added_by":"auto","created_at":"2021-11-01 14:36:22","extension":"png","order_by":10,"title":"Figure 10","display":"","copyAsset":false,"role":"figure","size":112532,"visible":true,"origin":"","legend":"The proposed mechanism for the synthesis of 3,4-dihydropyrimidin-2(1H)-one derivatives using ethyl acetoacetate or methyl acetoacetate in the presence of Fe3O4@SiO2-APTS-EDTA-asparagine nanocatalyst (1).","description":"","filename":"fig10.png","url":"https://assets-eu.researchsquare.com/files/rs-971598/v1/4439f08a9dbeff4c586fc078.png"},{"id":15090854,"identity":"750f7ef5-e424-42bf-a5d2-a74af2781bb8","added_by":"auto","created_at":"2021-11-01 14:33:22","extension":"png","order_by":11,"title":"Figure 11","display":"","copyAsset":false,"role":"figure","size":33352,"visible":true,"origin":"","legend":"Reusability of the Fe3O4@SiO2-APTS-EDTA-asparagine nanocatalyst (1) for the synthesis of 5a.","description":"","filename":"fig11.png","url":"https://assets-eu.researchsquare.com/files/rs-971598/v1/5d2d55834eba9bc2232607e9.png"},{"id":19739145,"identity":"10d64079-37e3-45be-924e-58c89d0af191","added_by":"auto","created_at":"2022-03-29 15:03:37","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3131568,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-971598/v1/614779be-0c04-4117-a5e3-9a8166ef85e5.pdf"},{"id":19738968,"identity":"f6bdc909-5a96-4137-b7cc-cae7cf5df97c","added_by":"auto","created_at":"2022-03-29 14:58:11","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":547514,"visible":true,"origin":"","legend":"","description":"","filename":"Table23292022.pdf","url":"https://assets-eu.researchsquare.com/files/rs-971598/v1/2495014b4620e52cb1f033f8.pdf"},{"id":19738972,"identity":"fcb1986e-2a2c-40b7-85dc-1d75346cdb9b","added_by":"auto","created_at":"2022-03-29 14:58:33","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":3615449,"visible":true,"origin":"","legend":"","description":"","filename":"ElectronicSupportingInformationForReview3292022.pdf","url":"https://assets-eu.researchsquare.com/files/rs-971598/v1/c0fb1a699e991b342450da88.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eAsparagine-EDTA MNPs: A Highly Efficient And Recyclable Magnetic Multifunctional Core-Shell Nanocatalyst For Green Synthesis of Biologically-Active 3,4-Dihydropyrimidin-2(1\u003cem\u003eH\u003c/em\u003e)-One Compounds\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eGreen chemistry has played a key role in the development of human civilization\u003csup\u003e1\u0026ndash;4\u003c/sup\u003e. In this regard, magnetic nanoparticles (MNPs) have received considerable interest because of their unique properties\u003csup\u003e5\u003c/sup\u003e. The outstanding properties of MNPs have made them superior and indispensable in many areas of industry and academia including information storage\u003csup\u003e6\u003c/sup\u003e, medicine\u003csup\u003e7\u003c/sup\u003e, drug delivery\u003csup\u003e8\u003c/sup\u003e, magnetic resonance imaging (MRI)\u003csup\u003e9,10\u003c/sup\u003e, biomedical applications\u003csup\u003e5,11,12\u003c/sup\u003e, and environmental remediation\u003csup\u003e13\u003c/sup\u003e as well as heterogeneous catalysis\u003csup\u003e14\u0026ndash;17\u003c/sup\u003e. In academia, MNPs represent a promising new technology for performing chemical reactions because they are separated from the reaction medium, comfortably\u003csup\u003e18,19\u003c/sup\u003e. In industry, due to the importance of the cost of chemical processes and the reuse of catalysts, special attention is paid to these nanoparticles\u003csup\u003e20,21\u003c/sup\u003e. MNPs tend to agglomerate under a magnetic field that reduces their surface to volume ratio and consequently decreases catalytic activity\u003csup\u003e22\u003c/sup\u003e. Therefore, MNPs must be stabilized to improve their properties and prevent undesirable agglomeration\u003csup\u003e23\u003c/sup\u003e. In fact, they are coated with a protective layer such as carbon layers\u003csup\u003e24,25\u003c/sup\u003e, organic polymer\u003csup\u003e26\u003c/sup\u003e or silica\u003csup\u003e27,28\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eMoreover, multi-component reactions (MCRs) are the most desirable powerful synthetic route in which three or more reactants come together in a single reaction vessel to form a wide range of acyclic or heterocyclic compounds by the one-pot processes\u003csup\u003e29,30\u003c/sup\u003e. MCRs afford extended molecular complexity and diversity from simple starting materials with high atom economy, which have found application in medicinal and natural products chemistry\u003csup\u003e31,32\u003c/sup\u003e. Indeed, the most significant feature of MCRs is generating almost no by-products or simple molecules such as H\u003csub\u003e2\u003c/sub\u003eO or EtOH\u003csup\u003e33\u0026ndash;37\u003c/sup\u003e. Hence, in agreement of the green and sustainable chemistry process, development and the advancement of catalysts to promote MCRs are very important in synthetic and medicinal chemistry\u003csup\u003e38\u0026ndash;40\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAmong the various types of nitrogen-containing heterocycles, derivatives of 3,4-dihydropyrimidin-2(1\u003cem\u003eH\u003c/em\u003e)-one, as biologically-active compounds, have found versatile applications such as anti-bacterial, anti-inflammatory, antihypertensive agents, calcium channel blockers, antitumor compounds\u003csup\u003e41\u0026ndash;47\u003c/sup\u003e. A simple and general protocol for access to 3,4-dihydropyrimidin-2(1\u003cem\u003eH\u003c/em\u003e)-ones involves a three-component one-pot Biginelli cyclocondensation of ethyl acetoacetate, urea and various aldehydes accelerated by different types of catalytic systems such as polymer-supported catalysts\u003csup\u003e48\u003c/sup\u003e, ionic liquids\u003csup\u003e49,50\u003c/sup\u003e, ionic liquid/silica sulfuric acid\u003csup\u003e51\u003c/sup\u003e, metal\u0026minus;organic framework (MOF)\u003csup\u003e52,53\u003c/sup\u003e, montmorillonite clay\u003csup\u003e54\u003c/sup\u003e, magnetic nanoparticles\u003csup\u003e55\u003c/sup\u003e, Lewis acidic zirconium (IV)-salophen perfluorooctanesulfonate or sulfated polyborate\u003csup\u003e56,57\u003c/sup\u003e, nanocrystalline CdS thin film\u003csup\u003e46\u003c/sup\u003e, graphene oxide\u003csup\u003e58,59\u003c/sup\u003e and mesoporous materials\u003csup\u003e60,61\u003c/sup\u003e as well as environmental friendly energy inputs such as ultrasound\u003csup\u003e62\u003c/sup\u003e or microwave irradiation\u003csup\u003e63\u003c/sup\u003e. Most of the reported methods in this regard have the role of heterogeneous catalysts and high value. However, these have problems such as complicated and tedious separation of products and catalysts, toxic reaction conditions, long reaction times and low yields. Therefore, there is still room to develop more environmentally-benign protocols to promote the Biginelli MCR condensation.\u003c/p\u003e \u003cp\u003eIn many previous reports, ethylenediaminetetraacetic acid (EDTA) has been used as an ion exchange and chelating agent for various metal ions\u003csup\u003e64\u0026ndash;66\u003c/sup\u003e, but this compound has a good ability as an inexpensive and non-toxic cross-linker to make strong bonds with organic materials having nucleophilic centers\u003csup\u003e67\u003c/sup\u003e. On the other hand, asparagine is one of the 20 amino acids found in the cells of the human body and is essential for maintaining balance in the central nervous system\u003csup\u003e68\u003c/sup\u003e. Asparagine can act as a biocompatible precursor and bifunctional organocatalyst due to its high natural abundance and cost-effectiveness with acidic and basic sites\u003csup\u003e69,70\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn this research, we herein report the synthesis and characterizations of new asparagine grafted on the EDTA-modified Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e core-shell magnetic nanoparticles (Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine), as a magnetically recoverable nanocatalyst, to promote the Biginelli reaction efficiently at 60\u0026deg;C under solvent-free conditions (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e"},{"header":"Results And Discussion","content":"\u003cdiv class=\"Section2\" id=\"Sec3\"\u003e\n \u003ch2\u003eCharacterization of the Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine nanocatalyst (1)\u003c/h2\u003e\n \u003cp\u003eThe overall procedure for the synthesis of Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine (\u003cstrong\u003e1\u003c/strong\u003e) has been summarized in Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. At first, the obtained magnetic nanoparticles were characterized using different physicochemical techniques such as Fourier transform infrared (FT-IR) spectroscopy, energy-dispersive X-ray (EDX) spectroscopy, field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), X-ray diffraction spectroscopy (XRD), vibrating sample magnetometer (VSM), and thermogravimetric analysis (TGA).\u003c/p\u003e\n \u003cp\u003eThe FT-IR spectroscopy was employed to determine the functional groups and structure of Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e (a), Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e (b), Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS (c), Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA (d) and Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine (e). The results are presented in Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. In the spectra of Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e nanoparticles (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003ea) the bands displayed at 620 cm\u003csup\u003e\u0026minus;1\u003c/sup\u003e and about 3410 cm\u003csup\u003e\u0026minus;1\u003c/sup\u003e are attributed to stretching vibration of Fe\u0026minus;O bond and surface hydroxyl groups, respectively. These peaks were observed in all five samples isolated at the different synthetic stages. In the FT-IR spectrum of Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eb), the absorption bands at 881 and 1036 cm\u003csup\u003e\u0026minus;1\u003c/sup\u003e can be ascribed to the presence of Si\u0026minus;O\u0026minus;Si symmetric and Si\u0026minus;O\u0026minus;Si asymmetric stretching modes, reflecting the coating of silica layer on the magnetite nanoparticles \u003csup\u003e71\u003c/sup\u003e. SP\u003csup\u003e3\u003c/sup\u003e C\u0026ndash;H stretching vibrations about 2922 cm\u003csup\u003e\u0026minus;1\u003c/sup\u003e confirmed the presence of the anchored (3-aminopropyl) triethoxysilane (APTS) group and the band about 1400 cm\u003csup\u003e\u0026minus;1\u003c/sup\u003e is assigned to the bending of \u0026minus;NH groups of Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS MNPs (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003ec) \u003csup\u003e72\u003c/sup\u003e. In the FT-IR spectrum of Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003ed), the peaks at 1635 cm\u003csup\u003e\u0026minus;1\u003c/sup\u003e, 1707 cm\u003csup\u003e\u0026minus;1\u003c/sup\u003e and 1760 cm\u003csup\u003e\u0026minus;1\u003c/sup\u003e corresponding to the C=O vibration of amide, acid and anhydride groups, respectively. In the last step, the peak at 1760 cm\u003csup\u003e\u0026minus;1\u003c/sup\u003e, which belongs to the anhydride group has been removed and new peaks at 1651 cm\u003csup\u003e\u0026minus;1\u003c/sup\u003e and 1737 cm\u003csup\u003e\u0026minus;1\u003c/sup\u003e are attributed to the amide and acid groups in the surface of Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003ee). These results from the FT-IR spectrum confirm that the silica coating and subsequent steps have been successfully performed on the surface of Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e.\u003c/p\u003e\n \u003cp\u003eCompositional analysis of the Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine magnetic nanocatalyst (\u003cstrong\u003e1\u003c/strong\u003e) was carried out using energy-dispersive X-ray spectroscopy (EDX). The EDX spectra of the Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine nanomaterial (\u003cstrong\u003e1\u003c/strong\u003e) are depicted in Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e. In addition, the EDX analysis showed the well-defined peaks related to C, O, N, Si and Fe in the structure of Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine (\u003cstrong\u003e1\u003c/strong\u003e) with the percentages of 40.32, 36.57, 11.69, 6.34 and 5.08, respectively.\u003c/p\u003e\n \u003cp\u003eThe morphology and texture of Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine MNPs (\u003cstrong\u003e1\u003c/strong\u003e) were indicated by FESEM analysis and their photographs were presented in Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e. According to these FESEM photographs, the size and surface shape of nanoparticles are well observed, which proves that the particles are spherical and without agglomeration. The FESEM photographs supported the formation of spherically shaped MNPs, which is in accordance with TEM analysis.\u003c/p\u003e\n \u003cp\u003eThe TEM analysis of the Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine (\u003cstrong\u003e1\u003c/strong\u003e) MNPs in two scales is shown in Fig. \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e. The TEM images demonstrated structural order and the morphology suggested that the magnetite nanoparticles have an average diameter size of 41 nm.\u003c/p\u003e\n \u003cp\u003eThe XRD pattern of Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine (\u003cstrong\u003e1\u003c/strong\u003e) was shown in Fig. \u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e. The reflection peaks were compared with the reference standard patterns related to EDTA (card no. JCPDS, 00-033-1672), Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e (card no. JCPDS, 01-088-0315) and asparagine (card no. JCPDS, 00-031-1542). The sharp peaks in this pattern are generated by combining several peaks. These new sharp peaks are ascribed to the produced Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine MNPs structures after modification reactions by EDTA and asparagine, respectively.\u003c/p\u003e\n \u003cp\u003eThe magnetic properties of MNPs were measured via vibrating sample magnetometery (VSM). The magnetic attributes of Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e and Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine MNPs (\u003cstrong\u003e1\u003c/strong\u003e) were measured out at room temperature by applied magnetic field -1000 to +1000 Oersted. According to data presented in Fig. \u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003e, The values of the magnetization saturation (Ms) for Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e and Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine MNPs (\u003cstrong\u003e1\u003c/strong\u003e) are 73.12 and 20.84 emu/g, respectively. Moreover, the VSM curves of both samples exhibit no hysteresis loops and this property demonstrated that no aggregation occurred in the presence of magnetic fields. A decrease in the magnetic saturation of the Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine was observed after coating with SiO\u003csub\u003e2\u003c/sub\u003e and functionalization with APTS. However, the magnetic saturation of Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine (\u003cstrong\u003e1\u003c/strong\u003e) is sufficient to be recovered by exerting an external magnet.\u003c/p\u003e\n \u003cp\u003eThermal stability of the Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine nanomaterial (\u003cstrong\u003e1\u003c/strong\u003e) was investigated under the air atmosphere over the temperature range of 50 \u0026minus; 800\u0026deg;C (Fig. \u003cspan class=\"InternalRef\"\u003e8\u003c/span\u003e). The Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine MNPs (\u003cstrong\u003e1\u003c/strong\u003e) display three weight loss steps over the temperature range of TGA and the total weight loss of nanocatalyst \u003cstrong\u003e1\u003c/strong\u003e is around 60%. According to obtained results, in the first step 15% weight loss in the range of 150 \u0026minus; 200\u0026deg;C is due to the evaporation of adsorbed water and organic solvents that remain in the nanocatalyst through its preparation processes. In addition, 22% weight loss in the range of 200 \u0026minus; 400\u0026deg;C corresponds to the loss of EDTA\u0026ndash;asparagine moiety. In the last step, the sharp weight loss of 23% at 400-700\u0026deg;C can be assigned to the decomposition of APTS moiety in the MNPs framework. These results also indicate that APTS, EDTA and asparagine has been successfully grafted onto the surface of Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e. Above 700\u0026deg;C only Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e was present.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"Section2\" id=\"Sec4\"\u003e\n \u003ch2\u003eOptimization of conditions in the Biginelli reaction using Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA asparagine nanocatalyst (1)\u003c/h2\u003e\n \u003cp\u003eIn our preliminary experiments, the catalytic activity of as prepared catalyst \u003cstrong\u003e1\u003c/strong\u003e was evaluated in the formation of dihydropyrimidin-2(1\u003cem\u003eH\u003c/em\u003e)-one derivatives by the Biginelli condensation. For this purpose, reaction conditions were optimized using the equimolar mixtures of urea (\u003cstrong\u003e2\u003c/strong\u003e, 1 mmol), 4-chlorobenzaldehyde (\u003cstrong\u003e3a\u003c/strong\u003e, 1 mmol) and ethyl acetoacetate (\u003cstrong\u003e4a\u003c/strong\u003e, 1 mmol) as the model reaction (\u003cstrong\u003eEq.\u0026nbsp;1\u003c/strong\u003e). In a systematic screening, the reaction conditions were investigated precisely by considering of several crucial variables such as catalyst loading, reaction time, solvent and reaction temperature, as given in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. Initially, in the absence of any catalyst and solvent, the progress of model reaction was slow and the yield of the 9-(4-chlorophenyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydroacridine-1,8(2\u003cem\u003eH\u003c/em\u003e,5\u003cem\u003eH\u003c/em\u003e)-dione (\u003cstrong\u003e5a\u003c/strong\u003e) was trace, even after a long time (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e, entry 1). Then, in the presence of very low amount of Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine (\u003cstrong\u003e1\u003c/strong\u003e) loading, as a nanocatalyst, without any solvent at room temperature, a good yield of the desired product \u003cstrong\u003e5a\u003c/strong\u003e was obtained (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e, entry 2). To achieve an excellent yield, the reaction temperature was increased to 60\u0026deg;C (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e, entry 3). Afterward, the model reaction was performed with lower catalyst \u003cstrong\u003e1\u003c/strong\u003e loading under solvent-free conditions as well as polar and non-polar solvents. Furthermore, the effect of temperature and different solvents was investigated (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e, entries 4-13). Also, the model reactions in the presence of EDTA and asparagine were separately investigated, but lower yields of the desired product \u003cstrong\u003e5a\u003c/strong\u003e were isolated (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e, entries 14-15).\u003c/p\u003e\n \u003cp\u003eFollowing the steps of optimizing the reaction conditions, the effect of different solvents and amount of catalyst loadings are summarized in Fig. 9. The model reaction was investigated under solvent-free conditions and different solvents such as EtOH, MeOH, EtOH/H\u003csub\u003e2\u003c/sub\u003eO (1:1), and DMF using Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine nanocatalyst (1) with different loading\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003eof the catalyst\u0026nbsp;1.\u0026nbsp;According\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003eto the obtained findings summarized in\u0026nbsp;Table 1\u0026nbsp;and\u0026nbsp;Fig. 9, the optimum reaction conditions were found to be 10 mg of\u0026nbsp;Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine nanocatalyst (1) loading under solvent-free conditions at 60 \u0026deg;C.\u003c/p\u003e\n \u003cp\u003eAfter the above experiments, the scope of reaction was expanded by using aromatic aldehydes having electron-withdrawing or electron-donating groups under the optimized conditions (\u003cstrong\u003eEq.\u0026nbsp;2\u003c/strong\u003e). The results are summarized in Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. As expected, in this novel magnetic heterogeneous catalytic system the reaction rate of aldehydes with electron-donating groups was slower than electron-releasing ones and required more time to complete the reaction. An alternative variation in this reaction was accomplished by utilizing methyl acetoacetate (\u003cstrong\u003e4b\u003c/strong\u003e) instead of ethyl acetoacetate (\u003cstrong\u003e4a\u003c/strong\u003e) for the synthesis of different Biginelli products. It is worth noting that all the reactions represented very good to excellent yields under solvent-free conditions in short time.\u0026nbsp;\u003c/p\u003e\n \u003ch2\u003eThe proposed mechanism for the synthesis of 3,4-dihydropyrimidin-2(1H)-one derivatives in the presence of Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine nanocatalyst (1)\u003c/h2\u003e\n \u003cp\u003eThe proposed mechanism based on the three-component strategy for the synthesis of 3,4-dihydropyrimidin-2(1\u003cem\u003eH\u003c/em\u003e)-one derivatives catalyzed by Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine nanocatalyst (\u003cstrong\u003e1\u003c/strong\u003e) is presented in Fig. \u003cspan class=\"InternalRef\"\u003e10\u003c/span\u003e. At first, the carbonyl group of aldehyde is activated by Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine (\u003cstrong\u003e1\u003c/strong\u003e) to form intermediate (\u003cstrong\u003eI\u003c/strong\u003e) through the condensation with urea (\u003cstrong\u003e2\u003c/strong\u003e). Afterward, iminium intermediate (\u003cstrong\u003eIII\u003c/strong\u003e) is produced after leaving the H\u003csub\u003e2\u003c/sub\u003eO in the presence of the magnetic nanocatalyst. Meanwhile, intermediate (\u003cstrong\u003eIII\u003c/strong\u003e) reacts with the enol form of the alkyl acetoacetate (\u003cstrong\u003e4\u003c/strong\u003e) and the corresponding intermediate (\u003cstrong\u003eIV\u003c/strong\u003e) is generated. Eventually, intramolecular cyclization occurs which is followed by dehydration of intermediate (\u003cstrong\u003eV\u003c/strong\u003e). At the end of the catalytic cycle, 3,4-dihydropyrimidin-2(1\u003cem\u003eH\u003c/em\u003e)-ones are produced and the catalyst is recycled\u003csup\u003e60\u003c/sup\u003e.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"Section2\" id=\"Sec5\"\u003e\n \u003ch2\u003eGreen chemistry metrics\u003c/h2\u003e\n \u003cp\u003eIn this part of our research, green chemistry metrics for the synthesis of 3,4-dihydropyrimidin-2(1\u003cem\u003eH\u003c/em\u003e)-one by Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine nanocatalyst (\u003cstrong\u003e1\u003c/strong\u003e) were calculated and the results are summarized in Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e\u003csup\u003e79,80\u003c/sup\u003e. Hence, several parameters of the green approach such as environmental factor (E factor), process mass intensity, reaction mass efficiency, carbon efficiency, and atom economy were evaluated and compared to the ideal values\u003csup\u003e81\u003c/sup\u003e. As presented in Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e, all calculated values are close to the ideal values and were reported in supporting information.\u0026nbsp;\u003c/p\u003e\n \u003cdiv class=\"Section3\" id=\"Sec6\"\u003e\n \u003ch2\u003eReusability of the Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine nanocatalyst (1)\u003c/h2\u003e\n \u003cp\u003eOne of the critical scales in catalytic processes is reusability and recyclability of the catalyst. For evaluation of this parameter, the model reaction was examined using Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine (\u003cstrong\u003e1\u003c/strong\u003e) for four runs. At the end of the reaction, the catalyst \u003cstrong\u003e1\u003c/strong\u003e was removed using an external magnet and the recycled catalyst was washed with dry toluene, dried and used in a subsequent model reaction. The obtained results are summarized in Fig. \u003cspan class=\"InternalRef\"\u003e11\u003c/span\u003e. Considering the results of isolated yields of products, the catalytic activity of Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine nanocatalyst (\u003cstrong\u003e1\u003c/strong\u003e) after four runs is slightly reduced, which demonstrates proper conservancy of the catalytic activity after recycling.\u003c/p\u003e\n \u003ch2\u003eComparative study of Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine nanocatalyst (1) and other catalysts for the Biginelli reaction\u003c/h2\u003e\n \u003cp\u003eIn order to compare the optimal catalytic activity and reaction conditions of the Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine nanocatalyst (\u003cstrong\u003e1\u003c/strong\u003e) with previously reported catalysts for the three-component Biginelli reaction, we compared reaction conditions and yield of desired product (\u003cstrong\u003e5a\u003c/strong\u003e) in Table \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e. As it can be observed from data in Table \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e, all catalytic systems are capable of producing the desired product with satisfactory yields but Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine nanocatalyst (\u003cstrong\u003e1\u003c/strong\u003e) in terms of yield and time factors, the reaction temperature, solvent and amount of catalyst loading demonstrates better performance than the other catalysts. Furthermore, additional advantage of this protocol is its easy separation from the crude products by using an external magnet compared to the most of reported heterogeneous catalytic systems.\u0026nbsp;\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e"},{"header":"Experimental","content":"\u003cdiv class=\"Section4\" id=\"Sec8\"\u003e\n \u003ch2\u003eChemicals and Instrumentation\u003c/h2\u003e\n \u003cp\u003eFerric chloride (FeCl\u003csub\u003e3\u003c/sub\u003e.6H\u003csub\u003e2\u003c/sub\u003eO), Ferrous chloride tetrahydrate (FeCl\u003csub\u003e2\u003c/sub\u003e.4H\u003csub\u003e2\u003c/sub\u003eO), (3-aminopropyl) triethoxysilane (APTS, 99%), tetraethyl orthosilicate (TEOS, 99%), ammonia (25 wt%), EDTA (MW = 292.24 g/mol), and asparagine (MW = 132.12 g/mol) were purchased from Merck and used without further purification. Urea, ethyl acetoacetate and aromatic aldehydes were purchased from international chemical companies including Merck and Sigma-Aldrich. The analytical TLC experiments were accomplished using Merck Kieselgel 60 F-254 Al-plates and then visualized by UV light and iodine vapour. Melting points of the products were measured on an Electrothermal 9100 apparatus and uncorrected. The functional groups of the samples were identified by FT-IR spectroscopy on a Perkin Elmer, Frontier FT-MIR spectrometer in the range of 600-4000 cm\u003csup\u003e-1\u003c/sup\u003e using KBr discs. The morphology of the nanocatalyst was observed by FESEM TESCAN-MIRA3 and TEM Philips EM 208S. TGA curves of the Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine (\u003cstrong\u003e1\u003c/strong\u003e) were recorded by Bahr company STA 504. X-ray diffraction (XRD) pattern of the catalyst \u003cstrong\u003e1\u003c/strong\u003e was taken by the Bruker D8 Advance device. The composition of the catalyst was determined by energy-dispersive X-ray (EDX) spectroscopy using a Numerix DXP-X10P instrument. Magnetization measurements were carried out on a BHV-55 vibrating sample magnetometer (VSM). \u003csup\u003e1\u003c/sup\u003eH NMR spectra of the isolated products were recorded at 500 MHz using a Varian-INOVA spectrometer.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"Section3\" id=\"Sec9\"\u003e\n \u003ch2\u003eGeneral procedure for preparation of the magnetic Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e nanoparticles\u003c/h2\u003e\n \u003cp\u003ePreparation of Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e nanoparticles were according to a reported general method \u003csup\u003e83\u003c/sup\u003e. In this procedure, in a 100 mL round-bottomed flask FeCl\u003csub\u003e3\u003c/sub\u003e.6H\u003csub\u003e2\u003c/sub\u003eO (4.6 g, 0.017 mol) and FeCl\u003csub\u003e2\u003c/sub\u003e.4H\u003csub\u003e2\u003c/sub\u003eO (2.3 g, 0.011 mol) were dissolved in deionized water (60 mL) and stirred for 30 min. Subsequently, aqueous NH\u003csub\u003e3\u003c/sub\u003e (10 mL) was added dropwise into the mixture and heated to 40\u0026deg;C under N\u003csub\u003e2\u003c/sub\u003e atmosphere for 2 h. The black solution was poured from the reaction vessel and Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e MNPs precipitates were separated from the solution using an external magnet, washed five times with deionized water and EtOH, and dried in the oven at 50\u0026deg;C for 24 h.\u003c/p\u003e\n \u003cdiv class=\"Section4\" id=\"Sec10\"\u003e\n \u003ch2\u003eGeneral procedure for preparation of the silica-coated magnetic nanoparticles (Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e)\u003c/h2\u003e\n \u003cp\u003eIn accordance to the modified St\u0026ouml;ber method, silica-coated Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e nanoparticles (Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e) were produced by a solvothermal reaction\u003csup\u003e84\u003c/sup\u003e. For this purpose, the Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e MNPs (1.0 g) were dispersed in 30 mL of distilled water and ultrasonicated for 30 min. Then, a mixture of aqueous NH\u003csub\u003e3\u003c/sub\u003e (2 mL) and EtOH (40 mL) were added dropwise to the magnetite mixture and ultrasonicated for 30 min. Then, a mixture of TEOS (2 mL) and EtOH (40 mL) were added slowly to the suspension solution under continuous stirring for 24 h at 60\u0026deg;C. Eventually, the Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e core-shell MNPs were collected using an external magnet, washed with deionized water and EtOH and dried in the oven at 50\u0026deg;C for 5 h.\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv class=\"Section3\" id=\"Sec11\"\u003e\n \u003ch2\u003eModification of the Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003eNPs by (3-aminopropyl) triethoxysilane (Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS)\u003c/h2\u003e\n \u003cp\u003eFe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e core-shell MNPs were modified with (3-aminopropyl) triethoxysilane (APTS) using a typical modified method\u003csup\u003e85\u003c/sup\u003e. Briefly, the Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e NPs (1.0 g) were ultrasonicated in 30 mL dried toluene. Subsequently, APTS (2.0 mL) was added to the magnetic mixture and stirred at 105\u0026deg;C for 24 h. After washing with dry toluene, the obtained MNPs separated and dried at 60\u0026deg;C for 12 h in a vacuum oven to prepare the Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS MNPs.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"Section3\" id=\"Sec12\"\u003e\n \u003ch2\u003ePreparation of the EDTA functionalized magnetic nanoparticles (Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA)\u003c/h2\u003e\n \u003cp\u003eIn a round-bottom flask, magnetic Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS NPs (1.0 g) were added to dry toluene (25 mL) and dispersed with ultrasonic for 15 min. Then, EDTA dianhydride (1.0 g) - synthesized according to Repo et al\u003csup\u003e86\u003c/sup\u003e- and acetic anhydride added to the mixture and stirred at 80\u0026deg;C under N\u003csub\u003e2\u003c/sub\u003e atmosphere for 24 h. The magnetic Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA NPs were washed five times with EtOH followed by drying at 60\u0026deg;C for 6 h in a vacuum oven.\u003c/p\u003e\n \u003ch2\u003ePreparation of the asparagine grafted on the EDTA-modified Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u0026nbsp;\u003c/sub\u003e core-shell magnetic nanoparticles (Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine, 1)\u003c/h2\u003e\n \u003cp\u003eIn the last step, the magnetic Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA NPs were dispersed in 25 mL of dry toluene and asparagine (1.0 g) was added to the magnetic mixture and stirred under reflux conditions and N\u003csub\u003e2\u003c/sub\u003e atmosphere for 24 h. Magnetic precipitates were separated using an external magnet and after drying in the oven, brown powder of Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine nanocatalyst (\u003cstrong\u003e1\u003c/strong\u003e) was obtained.\u003c/p\u003e\n \u003ch2\u003eGeneral procedure for the synthesis of 3,4-dihydropyrimidin-2(1H)-one (5a-5t) catalyzed by Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine nanomaterial (1)\u003c/h2\u003e\n \u003cp\u003eA mixture of urea (\u003cstrong\u003e2\u003c/strong\u003e, 1.0 mmol), aromatic aldehyde (\u003cstrong\u003e3\u003c/strong\u003e, 1.0 mmol), ethyl or methyl acetoacetate (\u003cstrong\u003e4\u003c/strong\u003e, 1.0 mmol), and Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine (\u003cstrong\u003e1\u003c/strong\u003e, 10 mg) were added under solvent-free conditions for an appropriate time indicated in Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. After completion of the reaction, as monitored by TLC [eluent: n-hexane: EtOAc: 3:1], the catalyst was separated using an external magnet and the residue was concentrated to result in the crude product. Finally, the crude product was recrystallized from EtOH to obtain the pure product.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn summary, the novel and thermally stable asparagine grafted on EDTA-modified Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e core-shell magnetic nanoparticles (Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine) was prepared for the first time. The Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine heterogeneouse nanocatalyst was used for highly efficient, facile, and green and sustainable synthesis of 3,4-dihydropyrimidin-2(1\u003cem\u003eH\u003c/em\u003e)-one derivatives in a one-pot and three-component protocol through cyclocondensation of alkyl acetoacetate, urea and various aldehydes under solvent-free conditions. Consistency with the ideal values of green chemistry parameters, easy work up procedure, good to excellent yields in shorter reaction times, fast separation and recyclability of the catalyst are the additional advantages for its application in academic and industrial purposes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAcknowledgements\u003c/h2\u003e \u003cp\u003eWe thank The Research Council of Iran University of Science and Technology (IUST), Tehran, Iran (Grant No 160/19108) for their support. We would also like to acknowledge the support of Iran Nanotechnology Initiative Council (INIC), Iran.\u003c/p\u003e"},{"header":"References","content":"\u003cp\u003e1 Li, C.-J. \u0026amp; Anastas, P. T. Green Chemistry: present and future. \u003cem\u003eChemical Society Reviews\u003c/em\u003e \u003cstrong\u003e41\u003c/strong\u003e, 1413-1414, doi:10.1039/C1CS90064A (2012).\u003c/p\u003e\n\u003cp\u003e2 Sheldon, R. A. Metrics of green chemistry and sustainability: past, present, and future. \u003cem\u003eACS Sustainable Chemistry \u0026amp; Engineering\u003c/em\u003e \u003cstrong\u003e6\u003c/strong\u003e, 32-48 (2018).\u003c/p\u003e\n\u003cp\u003e3 Erythropel, H. C.\u003cem\u003e et al.\u003c/em\u003e The Green ChemisTREE: 20 years after taking root with the 12 principles. \u003cem\u003eGreen chemistry\u003c/em\u003e \u003cstrong\u003e20\u003c/strong\u003e, 1929-1961 (2018).\u003c/p\u003e\n\u003cp\u003e4 Ganesh, K. 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K. \u0026amp; Sillanp\u0026auml;\u0026auml;, M. E. Removal of Co (II) and Ni (II) ions from contaminated water using silica gel functionalized with EDTA and/or DTPA as chelating agents. \u003cem\u003eJournal of hazardous materials\u003c/em\u003e \u003cstrong\u003e171\u003c/strong\u003e, 1071-1080 (2009).\u003c/p\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1.\u0026nbsp;\u003c/strong\u003eOptimization of conditions in the model reaction of urea (\u003cstrong\u003e2\u003c/strong\u003e), 4-chlorobenzaldehyde (\u003cstrong\u003e3a\u003c/strong\u003e), ethyl acetoacetate (\u003cstrong\u003e4a\u003c/strong\u003e), under different conditions in the presence of Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine nanocatalyst (\u003cstrong\u003e1\u003c/strong\u003e).\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e\u003cimg 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\"\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellpadding=\"0\" cellspacing=\"0\" id=\"isPasted\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.523510971786834%\"\u003e\n \u003cp\u003e\u003cstrong\u003eEntry\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.85579937304075%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCatalyst\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.927899686520377%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSolvent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.808777429467085%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTemperature (\u0026deg;C)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.225705329153605%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTime (min)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.658307210031348%\"\u003e\n \u003cp\u003e\u003cstrong\u003eYield\u003csup\u003eb\u003c/sup\u003e (%) 5a\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.523510971786834%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.85579937304075%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.927899686520377%\"\u003e\n \u003cp\u003eSolvent-free\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.808777429467085%\"\u003e\n \u003cp\u003er.t\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.225705329153605%\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.658307210031348%\"\u003e\n \u003cp\u003eTrace\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.523510971786834%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.85579937304075%\"\u003e\n \u003cp\u003eFe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.927899686520377%\"\u003e\n \u003cp\u003eSolvent-free\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.808777429467085%\"\u003e\n \u003cp\u003er.t\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.225705329153605%\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.658307210031348%\"\u003e\n \u003cp\u003e85\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.523510971786834%\"\u003e\n \u003cp\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.85579937304075%\"\u003e\n \u003cp\u003e\u003cstrong\u003eFe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.927899686520377%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSolvent-free\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.808777429467085%\"\u003e\n \u003cp\u003e\u003cstrong\u003e60\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.225705329153605%\"\u003e\n \u003cp\u003e\u003cstrong\u003e20\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.658307210031348%\"\u003e\n \u003cp\u003e\u003cstrong\u003e95\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.523510971786834%\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.85579937304075%\"\u003e\n \u003cp\u003eFe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.927899686520377%\"\u003e\n \u003cp\u003eEtOH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.808777429467085%\"\u003e\n \u003cp\u003er.t\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.225705329153605%\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.658307210031348%\"\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.523510971786834%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.85579937304075%\"\u003e\n \u003cp\u003eFe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.927899686520377%\"\u003e\n \u003cp\u003eEtOH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.808777429467085%\"\u003e\n \u003cp\u003eReflux\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.225705329153605%\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.658307210031348%\"\u003e\n \u003cp\u003e85\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.523510971786834%\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.85579937304075%\"\u003e\n \u003cp\u003eFe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.927899686520377%\"\u003e\n \u003cp\u003eMeOH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.808777429467085%\"\u003e\n \u003cp\u003er.t\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.225705329153605%\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.658307210031348%\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.523510971786834%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.85579937304075%\"\u003e\n \u003cp\u003eFe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.927899686520377%\"\u003e\n \u003cp\u003eMeOH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.808777429467085%\"\u003e\n \u003cp\u003eReflux\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.225705329153605%\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.658307210031348%\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.523510971786834%\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.85579937304075%\"\u003e\n \u003cp\u003eFe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.927899686520377%\"\u003e\n \u003cp\u003eH\u003csub\u003e2\u003c/sub\u003eO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.808777429467085%\"\u003e\n \u003cp\u003er.t\u003c/p\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.225705329153605%\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.658307210031348%\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.523510971786834%\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.85579937304075%\"\u003e\n \u003cp\u003eFe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.927899686520377%\"\u003e\n \u003cp\u003eH\u003csub\u003e2\u003c/sub\u003eO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.808777429467085%\"\u003e\n \u003cp\u003eReflux\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.225705329153605%\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.658307210031348%\"\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.523510971786834%\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.85579937304075%\"\u003e\n \u003cp\u003eFe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.927899686520377%\"\u003e\n \u003cp\u003eEtOH/H\u003csub\u003e2\u003c/sub\u003eO (1:1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.808777429467085%\"\u003e\n \u003cp\u003er.t\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.225705329153605%\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.658307210031348%\"\u003e\n \u003cp\u003e63\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.523510971786834%\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.85579937304075%\"\u003e\n \u003cp\u003eFe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.927899686520377%\"\u003e\n \u003cp\u003eEtOH/H\u003csub\u003e2\u003c/sub\u003eO (1:1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.808777429467085%\"\u003e\n \u003cp\u003eReflux\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.225705329153605%\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.658307210031348%\"\u003e\n \u003cp\u003e70\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.523510971786834%\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.85579937304075%\"\u003e\n \u003cp\u003eFe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.927899686520377%\"\u003e\n \u003cp\u003eDMF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.808777429467085%\"\u003e\n \u003cp\u003er.t\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.225705329153605%\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.658307210031348%\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.523510971786834%\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.85579937304075%\"\u003e\n \u003cp\u003eFe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.927899686520377%\"\u003e\n \u003cp\u003eDMF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.808777429467085%\"\u003e\n \u003cp\u003eReflux\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.225705329153605%\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.658307210031348%\"\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.523510971786834%\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.85579937304075%\"\u003e\n \u003cp\u003eEDTA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.927899686520377%\"\u003e\n \u003cp\u003eSolvent-free\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.808777429467085%\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.225705329153605%\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.658307210031348%\"\u003e\n \u003cp\u003e75\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.523510971786834%\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.85579937304075%\"\u003e\n \u003cp\u003eAsparagine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.927899686520377%\"\u003e\n \u003cp\u003eSolvent-free\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.808777429467085%\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.225705329153605%\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.658307210031348%\"\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup id=\"isPasted\"\u003ea\u003c/sup\u003eReaction conditions: urea (\u003cstrong\u003e2\u003c/strong\u003e, 1 mmol), 4-chlorobenzaldehyde (\u003cstrong\u003e3a\u003c/strong\u003e, 1 mmol), ethyl acetoacetate (\u003cstrong\u003e4a\u003c/strong\u003e, 1 mmol),\u0026nbsp;Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine (\u003cstrong\u003e1\u003c/strong\u003e)\u0026nbsp;and solvent (3 mL, if not otherwise stated). \u003csup\u003eb\u003c/sup\u003eIsolated yield.\u003c/p\u003e\n\u003cp\u003eDue to technical limitations, table 2 is only available as a download in the Supplemental Files section.\u003c/p\u003e\n\u003cp id=\"isPasted\"\u003e\u003cstrong\u003eTable 3\u003c/strong\u003e Measurement of green chemistry metrics for compound \u003cstrong\u003e5a\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.748784440842787%\"\u003e\n \u003cp\u003e\u003cstrong\u003eEntry\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.38735818476499%\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameters of the green approach\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.766612641815236%\"\u003e\n \u003cp\u003e\u003cstrong\u003eIdeal value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.097244732576986%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;Calculated values\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.748784440842787%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.38735818476499%\"\u003e\n \u003cp\u003eE factor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.766612641815236%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.097244732576986%\"\u003e\n \u003cp\u003e0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.748784440842787%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.38735818476499%\"\u003e\n \u003cp\u003eAtom economy (AE %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.766612641815236%\"\u003e\n \u003cp\u003e100%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.097244732576986%\"\u003e\n \u003cp\u003e89.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.748784440842787%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.38735818476499%\"\u003e\n \u003cp\u003eCarbon efficiency (CE %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.766612641815236%\"\u003e\n \u003cp\u003e100%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.097244732576986%\"\u003e\n \u003cp\u003e96%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.748784440842787%\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.38735818476499%\"\u003e\n \u003cp\u003eProcess mass intensity (PMI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.766612641815236%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.097244732576986%\"\u003e\n \u003cp\u003e1.16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.748784440842787%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.38735818476499%\"\u003e\n \u003cp\u003eReaction mass efficiency (RME %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.766612641815236%\"\u003e\n \u003cp\u003e100%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.097244732576986%\"\u003e\n \u003cp\u003e85.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp id=\"isPasted\"\u003e\u003cstrong\u003eTable 4.\u0026nbsp;\u003c/strong\u003eComparative results of catalysts for the synthesis of \u003cstrong\u003e5a\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.208400646203554%\"\u003e\n \u003cp\u003e\u003cstrong\u003eEntry\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.363489499192244%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCatalyst\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.578352180936996%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCatalyst loading\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.678513731825525%\"\u003e\n \u003cp\u003e\u003cstrong\u003eReaction conditions\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.308562197092083%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTime (min)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.862681744749596%\"\u003e\n \u003cp\u003e\u003cstrong\u003eYield (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.208400646203554%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.363489499192244%\"\u003e\n \u003cp\u003eZn(II)-framework\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.578352180936996%\"\u003e\n \u003cp\u003e10 wt %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.678513731825525%\"\u003e\n \u003cp\u003eSolvent-free/60\u0026nbsp;\u0026deg;C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.308562197092083%\"\u003e\n \u003cp\u003e120\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.862681744749596%\"\u003e\n \u003cp\u003e91\u003csup\u003e52\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.208400646203554%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.363489499192244%\"\u003e\n \u003cp\u003ePANI-FeCl\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.578352180936996%\"\u003e\n \u003cp\u003e200 mg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.678513731825525%\"\u003e\n \u003cp\u003eCH\u003csub\u003e3\u003c/sub\u003eCN/ Reflux\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.308562197092083%\"\u003e\n \u003cp\u003e1440\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.862681744749596%\"\u003e\n \u003cp\u003e83\u003csup\u003e82\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.208400646203554%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.363489499192244%\"\u003e\n \u003cp\u003eMCM-41-APS-PMDANHSO\u003csub\u003e3\u003c/sub\u003eH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.578352180936996%\"\u003e\n \u003cp\u003e15 mg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.678513731825525%\"\u003e\n \u003cp\u003eSolvent-free/80\u0026nbsp;\u0026deg;C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.308562197092083%\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.862681744749596%\"\u003e\n \u003cp\u003e96\u003csup\u003e60\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.208400646203554%\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.363489499192244%\"\u003e\n \u003cp\u003eFe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTMS-Fe(OH)\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.578352180936996%\"\u003e\n \u003cp\u003e10 mg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.678513731825525%\"\u003e\n \u003cp\u003eNeat/\u003cspan dir=\"RTL\"\u003e80\u0026nbsp;\u003c/span\u003e\u0026deg;C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.308562197092083%\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e15\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.862681744749596%\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e95\u0026nbsp;\u003c/span\u003e\u003csup\u003e55\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.208400646203554%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.363489499192244%\"\u003e\n \u003cp\u003ezirconium (IV)-salophen perfluorooctanesulfonate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.578352180936996%\"\u003e\n \u003cp\u003e0.05 mmol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.678513731825525%\"\u003e\n \u003cp\u003eSolvent-free/\u003cspan dir=\"RTL\"\u003e9\u003c/span\u003e0\u0026nbsp;\u0026deg;C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.308562197092083%\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e30\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.862681744749596%\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e96\u0026nbsp;\u003c/span\u003e\u003csup\u003e56\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.208400646203554%\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.363489499192244%\"\u003e\n \u003cp\u003eFe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.578352180936996%\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e10\u0026nbsp;\u003c/span\u003emg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.678513731825525%\"\u003e\n \u003cp\u003eSolvent-free/60\u0026nbsp;\u0026deg;C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.308562197092083%\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.862681744749596%\"\u003e\n \u003cp\u003e95 This work\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Core-Shell magnetic nanoparticles, Nano-Ordered catalysts, Multi-Component reactions (MCRs), Heterocycles, Green and sustainable chemistry","lastPublishedDoi":"10.21203/rs.3.rs-971598/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-971598/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eIn this study, the new asparagine grafted on the EDTA-modified Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e core-shell (Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine) magnetic nanoparticles were prepared and their structures were properly confirmed using different spectroscopic, microscopic and magnetic methods or techniques such as FT-IR, EDX, XRD, FESEM, TEM, TGA and VSM. The Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine core-shell nanomaterial was examined, as a highly efficient multifunctional and recoverable nanocatalyst, for the synthesis of a wide range of nitrogen-containing heterocycles and biologically-active 3,4-dihydropyrimidin-2(1\u003cem\u003eH\u003c/em\u003e)-one derivatives under solvent-free conditions. It was proved that Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e@SiO\u003csub\u003e2\u003c/sub\u003e-APTS-EDTA-asparagine MNPs, as a catalyst having excellent thermally and magnetic stability, specific morphology and acidic sites, can activate the Biginelli reaction components. Moreover, environmental-friendliness and nontoxic nature properties of the catalyst, cost effectiveness, low catalyst loading, easy separation of the catalyst from products and short time of reaction are some of the remarkable advantages of this green protocol.\u003c/p\u003e","manuscriptTitle":"Asparagine-EDTA MNPs: A Highly Efficient And Recyclable Magnetic Multifunctional Core-Shell Nanocatalyst For Green Synthesis of Biologically-Active 3,4-Dihydropyrimidin-2(1H)-One Compounds","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-11-01 14:30:19","doi":"10.21203/rs.3.rs-971598/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"77495113-e457-4ba1-be46-fe8289d8f26d","owner":[],"postedDate":"November 1st, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":8234455,"name":"Nanoscience"},{"id":8234456,"name":"General Biochemistry"}],"tags":[],"updatedAt":"2021-11-24T13:44:19+00:00","versionOfRecord":[],"versionCreatedAt":"2021-11-01 14:30:19","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-971598","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-971598","identity":"rs-971598","version":["v1"]},"buildId":"FbvkV6FR0MCFSLy54lSbu","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}