Document Type : Original Article


Department of Chemistry, Firoozkooh Branch, Islamic Azad University, Firoozkooh, Iran


Amine functionalized SiO2@Fe3O4 as an efficient, green, and recyclable catalyst was synthesized using a simple approach. Then, the catalytic activity of the amine-functionalized SiO2@Fe3O4 was evaluated in the metal-free green synthesis of Knoevenagel condensation from the various aromatic aldehydes and malononitrile in water to gives the corresponding 2-(aryl) methylenemalononitrile derivatives in excellent yields with a relatively low catalyst loading. Short reaction times, commercial availability of the starting materials, being environmentally friendly, reusability of catalyst, high yields, low cost, and easy work-up are the attractive features of the present work. The reusability of the catalyst was investigated for the product 3a. After separation with an external magnet, the recycled catalyst can be reused in 7 consecutive runs. The yield of the product reduced from 97 to 91% over 7 times.

Graphical Abstract

Amine functionalized SiO2@Fe3O4 as a green and reusable magnetic nanoparticles system for the synthesis of Knoevenagel condensation in water


Main Subjects


In recent years, much attention has been paid to developing environmentally friendly chemical synthesis using non-toxic reagents, solvents, and catalysts. Generally, ideal methods for synthesizing heterocyclic compounds were defined as one in which the target compound is generated via a one-pot reaction and in the quantitative yield. Moreover, starting materials are readily available and inexpensive in resource-effective and environmentally benign routes. In this context, one-pot synthesis played as an efficient, simple, and significant method for constructing nanoscale inorganic/organic hybrid functional materials [13].

Over the past decades, Fe3O4 or γ-Fe2O3 core-shell magnetic nanoparticles have received progressive attention by playing the role of catalyst in organic synthesis. This was due to their commercial availability, the high surface area, environmental stability, inexpensiveness, superparamagnetic properties, ease of handling, eco-friendly nature, high stability, low cost, convenience, and cost-effective synthesis. Also, they have been used in various areas such as environmental remediation [4], magneto thermal therapy [5, 6], MRI contrast agent [7], bioseparation [8], biomolecular sensing [9, 10], enzyme and protein separations [11], drug delivery [12, 13], and data storage [14].

Knoevenagel condensation is highly interesting as demonstrating various application in drugs (like pioglitazone, atorvastatin, and coartem) [1516], total synthesis [17, 18], construction one-step of molecules (like (S)-(+)-3-aminomethyl 5-methylhexanoic acid) [19, 20]. Although a variety of procedures have been reported for the synthesis of Knoevenagel condensation such as L-Proline [21], NUC-2 [22], iron [23], MgAl-LDH/ZIF-8 [24], ethylenediammonium diacetate [25], magnesium oxide (MgO) [26], KGCN-RGO [27], hydroquinone and benzoquinone [28], Silica-l-proline [29], MOF [30], phosphane [31], Fe3O4@SiO2-3N [32], Nmm-based ionic liquids [33], Montmorillonite KSF [34], composite oxides [35, 36], Ce(III) and Lu(III) MOFs [37], papain [38], nickel MOF [39], organic compounds [40], lipase [41], and DABCO [42]. However, many of these procedures suffer from drawbacks such as toxic solvents, tedious steps for the catalyst preparation, expensive reagents and catalysts, long reaction times,harsh reaction conditions, and tedious work-up procedures. Therefore, the development of new methods and catalysts is still in demand.

Hence, we report herein amine-functionalized SiO2@Fe3O4 as a green and reusable catalytic system for the efficient synthesis of Knoevenagel condensation (Scheme 1). 

Scheme 1. Synthesis of Knoevenagel condensation


Materials and methods

All the materials were purchased from Sigma-Aldrich, Merck (Germany), and Fluka (Switzerland) and were used without further purification. Melting points were determined with an electrothermal 9100 melting point apparatus. Fourier transform infrared (FT-IR) spectra were recorded on a Bruker Equinox 55 spectrometer using potassium bromide disks. All products were identified by comparing their physical and spectra data with those reported in the literature.

Preparation of amine-functionalized SiO2@Fe3O4

We synthesized the amine-functionalized SiO2@Fe3O4 according to a previous report [43] and characterized by various analyses such as FT-IR, TEM, SEM, XRD, and VSM.

General procedure for the synthesis 2-(aryl) methylenemalononitrile derivatives

A mixture of various aldehyde (1 mmol) and malononitrile (1 mmol) in the presence of catalyst (0.05 g) in water (2 mL) was stirred at room temperature for the specified period. After completing the reaction (monitored by TLC), the catalyst was removed by magnetic separation and washed with CH2Cl2 to the remove the residual product and dried for reuse. The crude products were recrystallized from EtOH to obtain pure Knoevenagel derivatives.

Results and Discussion

The amine-functionalized SiO2@Fe3O4 was synthesized by a simple approach. To prepare the catalyst, Fe3O4 was first modified with SiO2 to afford the SiO2@Fe3O4. Then, the treatment of SiO2@Fe3O4 prepared with APTES gives the corresponding superparamagnetic amine functionalized SiO2@Fe3O4 (Scheme 2) [43]. Then, the catalyst characterized by various analyses such as FT-IR, TEM, SEM, and XRD.

Scheme 2. Schematic for the synthesis of amine-functionalized SiO2@Fe3O4

The FT-IR spectra of amine-functionalized SiO2@Fe3O4 step by step were studied in the range 500–4000 cm−1 (Figure 1ac). As illustrated in Figure 1a, the absorption bands at 650 cm-1 are related to the Fe‒O vibrations. After coating SiO2 on the iron oxide, the existence of Si‒O of the SiO2@Fe3O4 group in structure was determined by a peak at 1108 cm−1. Finally, after the reaction between SiO2@Fe3O4 and APTES, new bands according to NH2 and -CH (sp3) were observed at 3478 and 2956 cm-1, respectively (Figure 1c).  

Figure 1. FT-IR spectra of a) Fe3O4, b) SiO2@Fe3O4, and c) amine functionalized SiO2@Fe3O4

To the determination the particle size, morphology, and particle aggregation mode of the amine-functionalized SiO2@Fe3O4, FESEM and TEM analyses were studied (Figures 2a,b). The average size of coated particles was less than 45 nm, and the sphere-like shape was changed due to the complex coating. In the TEM image, the nanometer-sized nature and the core-shell structure of the amine-functionalized SiO2@Fe3O4 were obvious.

The X-ray diffraction (XRD) analysis was used to determine the crystalline and the size of amine-functionalized SiO2@Fe3O4 (Figure 3). The intense Bragg's peaks were observed at 2θ=30.6, 37.4, 44.5, 58.4, 63.2°, which are the plates (220), (311), (400), (422), (511), and (440) respectively. These peaks are related to the crystal planes in the Fe3O4 lattice and according to the standard XRD pattern of cubic Fe3O4 (JCPDS 88-0866) [44].

The magnetic behavior of amine-functionalized SiO2@Fe3O4 was investigated using the VSM analysis (Figure 4). As can be seen, the specific saturation magnetizations of amine-functionalized SiO2@Fe3O4 is measured to be 32 emu g-1.

To explore the practicability of our investigation, a model reaction was performed between benzaldehyde (1a) and malononitrile (2) using various amounts of catalyst and various solvents at room temperature to gives the corresponding 3a. The model reaction was evaluated using various amounts of catalyst (0.01, 0.03, 0.05, 0.07, and 0.1 g) at room temperatures and a various solvents such as H2O, EtOH, MeOH, CH2Cl2, and THF. When the reaction was carried out without amine-functionalized SiO2@Fe3O4, the product was obtained in a trace amount (Table 1, entry 1). Increasing the reaction yield in the presence of catalyst was obtained (Table 1, entry 2-6).

Figure 2. The a) SEM, and b) TEM analysis for the amine functionalized SiO2@Fe3O4

Figure 3. XRD analysis for the amine functionalized SiO2@Fe3O4

Figure 4. VSM analysis for the amine-functionalized SiO2@Fe3O4

When the catalyst was gradually increased to 0.05 g in water as green solvent, the reaction was completed in a short time, and the product yield was obtained to 96% (Table 1, entry 4). After optimized reaction conditions, using 0.05 g of catalyst in water at room temperature was the best condition for the reaction.

To study the generality and scope of the magnetic nanocatalyst, we extended our study with various aromatic aldehydes with electron-withdrawing groups and electron-donating groups with malononitrile to give 2-(aryl)methylenemalononitrile derivatives 3a–m in optimized conditions (Table 2). As shown in Table 2, all desired products were produced in good to excellent yields in short reaction times without formation of any by-products.

Table 1. Effect of different amounts of catalyst and solvent at room temperaturea

a Reaction conditions: benzaldehyde (1 mmol), malononitrile (1 mmol), catalyst, and solvent (2 mL)

b Isolated yields

As expected, it is recyclable and could be reused without any significant activity loss. For this purpose, the reaction between 4-nitrobenzaldehyde (1 mmol) and malononitrile (1 mmol) in the presence of a catalyst (0.05 g) in water (2 mL) at room temperature has been investigated. Upon completion of the reaction, amine-functionalized SiO2@Fe3O4 can be easily separated and recovered with a permanent external magnet and then reused in the next run. The results have revealed that the recovered catalyst does not significantly lose its activity after 7 times, and the nano catalyst's catalytic activity was nearly the same as that of the freshly used catalyst (Figure 5a). After 7 runs, the TEM and FT-IR analyses for the catalyst were investigated (Figures 5b,c). As shown in Figure 5b,c the functional groups, morphology, and size are the same with fresh catalyst.

Table 2. Synthesis of 2-(aryl)methylenemalononitrile derivativesa

a Reaction conditions: various aldehyde (1 mmol), malononitrile (1 mmol), and catalyst (0.05 g) in water (2 mL) at room temperature

b Isolated yields

Figure 5. a) Reusability of amine-functionalized SiO2@Fe3O4, b) TEM image, and c) FT-IR spectra after 7 recycling experiment


In this work, we have reported an efficient and green catalytic system including amine-functionalized SiO2@Fe3O4 for the one-pot metal-free green synthesis of Knoevenagel condensation in high yields. The amine-functionalized SiO2@Fe3O4 was evaluated using FT-IR, SEM, TEM, XRD, and VSM analysis. The presented method is a safe, clean procedure and avoids using any toxic solvents. Other advantages of this method are simplicity in process, ease of work-up, and simple product separation. Moreover, this catalytic system could be reused for seven consecutive runs without any significant catalytic activity loss.


We gratefully acknowledge the Islamic Azad University of Firoozkooh because of spiritual support.

How to cite this manuscript: Fatemeh Sheikholeslami-Farahani*. Amine functionalized SiO2@Fe3O4 as a green and reusable magnetic nanoparticles system for the synthesis of Knoevenagel condensation in water. Asian Journal of Nanoscience and Materials, 5(2) 2022, 132-143. DOI: 10.26655/AJNANOMAT.2022.2.5

[1]. a) Dömling A. Chem. Rev., 2006, 106:17 [Crossref], [Google Scholar], [Publisher] b) Amini I., Azizkhani V., Ezzatzadeh E., Pal K., Rezayati S., Fekri M.H., Shirkhani P. Asian J. Green Chem., 2020, 4:51 [Crossref], [Publisher] c) Ramezanpour S., Bigdeli Z., Rominger F. Asian J. Green Chem., 2020, 4:87 [Crossref], [Publisher] d) Hakimi F., Oreyzi F.S., Bani Fatemeh F., Golrasan E. Asian J. Green Chem.,  2020, 4:134 [Crossref], [Publisher] e) Nakkalwar S.L., Kasralikar H.M., Kaminwar N.S., Patwari S.B., Jadhav V.B. Asian J. Green Chem., 2020, 4:159 [Crossref], [Publisher] f) Ravanshad S., Asvar H., Fouladi F., Pourkazemi A., Shamsizadeh M., Khalili M., Merajoddin M., Zare A. Asian J. Green Chem.,  2020, 4:173 [Crossref], [Publisher] g) Hakimi F., Mirjalili F., Fallah-Mehrjardi M. Asian J. Green Chem., 2020, 4:13 [Crossref], [Publisher] h) Hakimi F., Dehghan Niri M., Banitaba S.H., Golrasan E. Asian J. Green Chem., 2020, 4:239 [Crossref], [Publisher] i) Ezzatzadeh E., Sheikholeslami-Farahani F., Yadollahzadeh K., Rezayati S. Combinatorial Chemistry & High Throughput Screening, 2021, 4:1465 [Crossref], [Google Scholar], [Publisher]
[2]. a) Gu Y.L. Green Chem., 2012, 14:2091 [Crossref], [Google Scholar], [Publisher] b) Atashrooz J., Zare A. Asian J. Green Chem., 2022, 4:317 [Crossref], [Google Scholar], [Publisher] c) Pagore V.P., Jadhav V.B., Bajad P.N., Pawar R.P. Asian J. Green Chem., 2020, 4:379 [Crossref], [Publisher] d) Duguta G., Kumar Mukka S., Sriram Yelike H., Rajanna Kamatala C., Sudhakar Mukka S. Asian J. Green Chem., 2020, 4:457 [Crossref], [Publisher] e) khanivar R., Zare A., Sadeghi-Takallo M. Asian J. Green Chem., 2021, 5:1 [Crossref], [Google Scholar], [Publisher] f) Singha R., Brahman D., Sinha B., Ghosh P. Asian J. Green Chem., 2021, 5:91 [Crossref], [Publisher] g) Elageed E.H.M., Mohammed A.A.A., Gao G., Suleman N.M. Asian J. Green Chem., 2021, 5:125 [Crossref], [Google Scholar] h) Ezzatzadeh E., Hossaini Z. Applied Organometalic Chemistry, 2020, 34:e5596 [Crossref], [Google Scholar], [Publisher] i) Seifi Mansour S., Ezzatzadeh E., Safarkar R. Asian J. Green Chem., 2019, 3:353 [Crossref],  [Publisher] j) Ezzatzadeh E., Hossaini Z., Rostamian R., Vaseghi S., Mousavi S.F. Journal of Heterocyclic Chemistry, 2017, 54:2906 [Crossref], [Google Scholar], [Publisher]
[3]. a) Hajinasiri R., Rezayati S. Z. Naturforsch. 2013, 68b:818-822 [Crossref], [Google Scholar], [Publisher] b) Baghernejad B., Salimifar S. Asian J. Green Chem., 2021, 5:196 [Crossref], [Publisher] c) Ranjan Dasgupta H., Mukherjee S., Ghosh P. Asian J. Green Chem., 2021, 5:235 [Crossref], [Publisher] d) Baghernejad b., Ghapanvari H. Asian J. Green Chem., 2021, 5:271 [Crossref], [Publisher] e) Hakimi Saryazdi F., Golrasan E., Heidari S. Asian J. Green Chem., 2021, 5:325 [Crossref], [Publisher] f) Baghernejad B., Talebi M. Asian J. Green Chem., 2021, 5:368 [Crossref], [Publisher] g) Ezzatzadeh E. Asian J. Nanosci. Mater., 2021, 4:125 [Crossref], [Publisher]
[4]. Lu A., Schmidt W., Matoussevitch N., Bonnemann H., Spliethoff B., Tesche B., Bill E., Kiefer W., Schuth F. Angew. Chem., 2004, 116:4403 [Crossref], [Google Scholar], [Publisher]
[5]. Hiergeist R., Andra W., Buske N., Hergt R., Hilger I., Richter U., Kaiser W. J. Magn. Magn. Mater., 1999, 201:420 [Crossref], [Google Scholar], [Publisher]
[6]. Jordan A., Scholz R., Wust P., Fahling H., Felix R. J. Magn. Magn. Mater., 1999, 201:413 [Crossref], [Google Scholar], [Publisher]
[7]. Weissleder R., Bogdanov A., Neuwelt E.A., Papisov M. Adv. Drug Delivery Rev. 1995, 16:321 [Crossref], [Google Scholar], [Publisher]
[8]. Wang D., He J., Rosenzweig N., Rosenzweig Z. Nano Lett., 2004, 4:409 [Crossref], [Google Scholar], [Publisher]
[9]. Perez J.M., Simeone F.J., Saeki Y., Josephson L., Weissleder R. J. Am. Chem. Soc. 2003, 125:10192 [Crossref], [Google Scholar], [Publisher]
[10]. Graham D.L., Ferreira H.A., Freitas P.P. Trends Biotechnol. 2004, 22:455 [Crossref], [Google Scholar], [Publisher]
[11]. Meyer A., Hansen D.B., Gomes C.S.G., Hobley T.J., Thomas O.R.T., Franzreb M. Biotechnol. Prog. 2005, 21:244 [Crossref], [Google Scholar], [Publisher]
[12]. Pankhurst Q.A., Connolly J., Jones S.K., Dobson J. J. Phys. D: Appl. Phys., 2003, 36:R167 [Google Scholar], [Publisher]
[13]. Campo A.D., Sen T., Lellouche J.P., Bruce I.J. J. Magn. Magn. Mater., 2005, 293:33 [Crossref], [Google Scholar], [Publisher]
[14]. Hyeon T. Chem. Commun., 2003, 927 [Crossref], [Google Scholar], [Publisher]
[15]. Ying A., Wang L., Qiu F., Hu H., Yang J. C R Chimie, 2015, 18:223 [Crossref], [Google Scholar], [Publisher]
[16]. Beutler U., Fuenfschilling P.C., Steinkemper A. Org Process Res Dev., 2007, 11:341 [Crossref], [Google Scholar], [Publisher]
[17]. Mandal M., Yun H., Dudley G.B., Lin S., Tan D.S., Danishefsky S.J. J Org Chem., 2005, 70:10619 [Crossref], [Google Scholar], [Publisher]
[18]. Horeischi F., Biber N., Plietker B. J Am Chem Soc., 2014, 136:4026 [Crossref], [Google Scholar], [Publisher]
[19]. Hoekstra M.S., Sobieray D.M., Schwindt M.A., Mulhern T.A., Grote T.M., Huckabee B.K., Hendrickson V.S., Franklin L.C., Granger E.J., Karrick G.L. Org Process Res Dev., 1997, 1:26 [Crossref], [Google Scholar], [Publisher]
[20]. Roy B.N., Singh G.P., Lathi P.S., Agrawal M.K., Mitra R., Pise V.S. Indian J Chem B. 2012, 51:1470 [Crossref], [Google Scholar], [Publisher]
[21]. Madhava Reddy M., Sivaramakrishna A. ChemistrySelect, 2020, 5:4816 [Crossref], [Google Scholar], [Publisher]
[22]. Chen H., Fan L., Zhang X. ACS Appl. Mater. Interfaces, 2020, 12:54884 [Crossref], [Google Scholar], [Publisher]
[23]. Huang L.S., Lai Y H. Applied Organometalic Chemistry, 2019, 33:e4910 [Crossref], [Google Scholar], [Publisher]
[24]. Li P., Zeng H.C. ACS Appl. Mater. Interfaces, 2016, 43:29551 [Crossref], [Google Scholar], [Publisher]
[25]. Sub C., Chen Z.C., Zheng Q.G. Synthesis, 2003, 4:0555 [Crossref], [Google Scholar], [Publisher]
[26]. Sadgar A.L., Deore T.S., Jayaram R.V. ACS Omega, 2020, 5:12224 [Crossref], [Google Scholar], [Publisher]
[27]. Bahuguna A., Kumar A., Chhabra T., Kumar A., Krishnan V. ACS Appl. Nano Mater., 2018, 1:6711 [Crossref], [Google Scholar], [Publisher]
[28]. Takakura R., Koyama K., Kuwata M., Yamada T., Sajiki H., Sawama Y. Org. Biomol. Chem., 2020, 18:6594 [Crossref], [Google Scholar], [Publisher]
[29]. Vaid R., Gupta M. Monatshefte für Chemie - Chemical Monthly, 2015, 146:645 [Crossref], [Google Scholar], [Publisher]
[30]. Taher A., Lee D.J., Lee B.K., Lee I.M. Synlett, 2016, 27:1433 [Crossref], [Google Scholar], [Publisher]
[31]. Yadav J.S., Subba Reddy B.V., Basak A.K., Visali B., Venkat Narsaiah A., Nagaiah K. European Journal of Organic Chemistry, 2004, 2004:546 [Crossref], [Google Scholar], [Publisher]
[32]. de Resende Filho J.B.M., Pires G.P., de Oliveira Ferreira J.M.G., Teotonio E.E.S., Vale J.A. Catalysis Lett., 2017, 147:167 [Crossref], [Google Scholar], [Publisher]
[33]. Xu H., Pan L., Fang X., Liu B., Zhang W., Lu M., Xu Y., Ding T., Chang H. Tetrahedron Lett., 2017, 58:2360 [Crossref], [Google Scholar], [Publisher]
[34]. Bigi F., Chesini L., Maggi R., Sartori G. J Org Chem., 1999, 64:1033 [Crossref], [Google Scholar], [Publisher]
[35]. Gawande M.B., Jayaram R.V. Catal Commum., 2006, 7:931 [Crossref], [Google Scholar], [Publisher]
[36]. Wei Y., Zhang S., Yin S., Zhao C., Luo S., Au C. Catal Commum., 2011, 12:1333 [Crossref], [Google Scholar], [Publisher]
[37]. Almási M., Zelenák V., Opanasenko M., Císarová, I. Catal Today, 2015, 243:184 [Crossref], [Google Scholar], [Publisher]
[38]. Hu W., Guan Z., Deng X., He Y. Biochimie, 2012, 94:656 [Crossref], [Google Scholar], [Publisher]
[39]. Almási M., Zelenák V., Opanasenko M., Cejka J. Dalton Trans., 2014, 43:3730 [Crossref], [Google Scholar], [Publisher]
[40]. Prout F.S., Abdel-Latif A.A., Kamal M.R. J Chem Eng Data., 1963, 4:597 [Crossref], [Google Scholar], [Publisher]
[41]. Ding Y., Xiang X., Gu M., Xu H., Huang H., Hu, Y. Bioprocess and Biosystems Engineering, 2016, 39:125 [Crossref], [Google Scholar], [Publisher]
[42]. Abaee M.S., Cheraghi S. Turk J Chem., 2014, 38:650 [Crossref], [Google Scholar], [Publisher]
[43]. Singh P., Yadav P., Mishra A., Awasthi S.K. ACS Omega, 2020, 5:4223 [Crossref], [Google Scholar], [Publisher]
[44]. Mirzaee M., Bahramian B., Gholampour P., Teymouri S., Khorsand T. Appl. Organomet. Chem., 2019, 33:e4792 [Crossref], [Google Scholar], [Publisher]
[45]. Kalantari F., Rezayati S., Ramazani A., Aghahosseini H., Ślepokura K., Lis T. ACS Applied Nano Materials, 2022, 5:1783 [Crossref], [Google Scholar], [Publisher]