Magnetic dextrin nanobiomaterial: An organic-inorganic hybrid catalyst for the synthesis of biologically active polyhydroquinoline derivatives by asymmetric Hantzsch reaction

Journal Pre-proof Magnetic dextrin nanobiomaterial: An organic-inorganic hybrid catalyst for the synthesis of biologically active polyhydroquinoline derivatives by asymmetric Hantzsch reaction

Ali Maleki, Fereshte Hassanzadeh-Afruzi, Zahra Varzi, Mir Saeed Esmaeili PII:

S0928-4931(19)33139-X

DOI:

https://doi.org/10.1016/j.msec.2019.110502

Reference:

MSC 110502

To appear in:

Materials Science & Engineering C

Received date:

24 August 2019

Revised date:

23 October 2019

Accepted date:

26 November 2019

Please cite this article as: A. Maleki, F. Hassanzadeh-Afruzi, Z. Varzi, et al., Magnetic dextrin nanobiomaterial: An organic-inorganic hybrid catalyst for the synthesis of biologically active polyhydroquinoline derivatives by asymmetric Hantzsch reaction, Materials Science & Engineering C (2019), https://doi.org/10.1016/j.msec.2019.110502

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© 2019 Published by Elsevier.

Journal Pre-proof

Magnetic dextrin nanobiomaterial: An organic-inorganic hybrid catalyst for the synthesis of biologically active polyhydroquinoline derivatives by asymmetric Hantzsch reaction Ali Maleki*, Fereshte Hassanzadeh-Afruzi, Zahra Varzi, Mir Saeed Esmaeili Catalysts and Organic Synthesis Research Laboratory, Department of Chemistry, Iran University of Science and Technology, Tehran 16846-13114, Iran

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*Corresponding author E-mail: [email protected]; Fax: +98-21-73021584; Tel: +98-21-

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73228313 Abstract

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Dextrin is a low molecular weight polysaccharide obtained from natural resources. Due to

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exceptional properties such as chemical structure, having extreme reactive functional groups, low cost, commercial availability, non-toxicity and biocompatibility, it can be introduced as a

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green organocatalyst. The fabrication of hybrid materials from natural polymers and synthetic inorganic materials constructs compounds with new features, abilities and applications.

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Therefore, magnetic dextrin nanobiocomposite was prepared using a simple chemical coprecipitation. Then, it was characterized by Fourier transform infrared (FT‐ IR) spectroscopy,

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energy-dispersive X-ray (EDX) analysis, vibrating sample magnetometer (VSM) curve, scanning electron microscopy (SEM) image, X-ray diffraction (XRD) pattern, thermogravimetric analysis

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(TGA) and inductively-coupled plasma atomic emission spectroscopy (ICP-AES) analysis. Subsequently, to evaluate the catalytic performance of the synthetic hybrid catalyst, it was tested for the synthesis of biologically active polyhydroquinoline derivatives by four-component condensation reactions of aromatic aldehyde, ethyl acetoacetate, dimedone, ammonium acetate in ethanol under refluxing conditions. Experimental observations indicated some advantages of the present method, such as the use of green and biopolymer-based catalyst, simple procedure, mild reaction conditions, short reaction times (15-45 min), appropriate yield of products (7095%) and catalyst reusability after five consecutive runs without considerable catalytic performance decrease.

1

Journal Pre-proof Keywords:

Magnetic

dextrin,

Organic-inorganic

hybrid,

Biomaterial,

Magnetized

polysaccharide, Recyclable catalyst. 1. Introduction In recent research, the design and application of biocompatible and naturally occurring catalysts have become an important study topic in pursuit of green chemistry principles [1]. Polysaccharides are members of family of carbohydrates. Plants, animals, microbials and algal

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are the primary source of polysaccharide origins in the nature [2]. Bio-catalysts in addition to

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being environmentally friendly, have high catalytic activity, prevent undesirable side reactions

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and can stereoselectivity perform the organic reactions in some instances [3]. Dextrin is a low

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molecular weight polysaccharide, which is a hydrolysis product of starch or glycogen. Different types of dextrin are obtainable in terms of the initial source and conditions of hydrolysis, each of

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these types of dextrin has different characteristics and is then used on a specific field [4]. The

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chemical structure of dextrin is composed of a lot of D-glucose units linked by α-(1 → 4) or α-(1 → 6) glycosides bonds (Fig. 1) [5]. This natural polymer has attracted the attention of

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researchers through its unique properties such as its chemical structure, aqueous solution, low

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cost, commercial availability, non-toxicity and biodegradable nature to produce applied materials. Extensive applications of dextrin can be found in some industries such as food, cosmetics, adhesives and textile [6]. An aspect that has remained almost unknown is the catalytic application of this valuable biomaterials. The question that needs to be explained is: Why can dextrin be considered as an organocatalyst in the organic reactions? The presence of extreme reactive functional groups enables this polysaccharide to interact with many of the reaction components of organic reactions by forming hydrogen bonds between its hydroxyl groups and the functional groups

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Journal Pre-proof containing electronegative atoms of starting materials. So, the electrophilic property of these starting materials will be improved and eventually caused to facilitate the reaction. Another excellent characteristic of dextrin is remarkable water absorption capacity. That is why this

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biopolymer can be an appropriate catalyst for those reactions that water is their byproduct.

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Fig. 1. Structure of dextrin polysaccharide

Nanoparticles of magnetic iron oxide have the advantages of both heterogeneous and homogeneous catalysts. In spite of precious benefits of this kind of material such as excellent particle

distribution,

high

surface-to-volume

ratio,

simple

isolation

process

and

superparamagnetic behavior, their ability to agglomerate and oxidize are the adverse points. The organic compounds immobilization on MNPs is considered as a practical solution to overcome this disadvantage [7-11]. The hybrid material is the product of a combination of two or more molecules. When these molecules are attached as nanoscale structural subsets, while retaining 3

Journal Pre-proof the inherent properties of each component, exhibits new features. The structural diversity that exists in these materials enables them to successfully applied in a wide area [12, 13]. Multicomponent reactions (MCRs) are one-pot methods in which most atoms from the beginning material are integrated into the final product. Most outstanding characteristics of MCRs include atomic economy, high efficiency, the convergence, high bond-forming index (BFI) [7, 14-16]. The derivatives of polyhydroquinoline involve a wide range of biomedically significant

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compounds. They possess distinct features of biology and pharmacology for instance,

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geroprotective, vasodilator, antiatherosclerotic, hepatoprotective, antitumor, bronchodilator,

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antidiabetic, calcium channel blockers, anti-inflammatory, and analgesic [17, 18].

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Given the significance of polyhydroquinoline derivatives, several techniques for their synthesis have been revealed and developed. The problem with reported methods is that some weaknesses

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like vigorous reactions condition, unsafe catalysts, and tedious workup methods somewhat

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persist hence, presenting developed and green methods is still a scientific issue. In connection with our recent study on the design natural polymer-based hybrid catalysts [15, 19-

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22], in this study magnetic dextrin was introduced as a green, biocompatible and effectiveness

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organic-inorganic hybrid catalyst. This heterogeneous nanobiocatalyst was prepared, characterized and its application was evaluated for the synthesis of polyhydroquinoline derivatives by asymmetric Hantzsch reaction. Fig. 2 (b) shows how polyhydroquinoline derivatives were synthesized by condensation of aromatic aldehyde, ethyl acetoacetate, dimedone, ammonium acetate in ethanol under refluxing conditions.

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Fig. 2. Preparation of (a) magnetic dextrin and (b) its catalytic application in the synthesis of

2. Experimental

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polyhydroquinoline derivatives.

2.1. General All commercially available chemicals, solvents, reagents and were purchased from SigmaAldrich and Merck company. The melting points of the prepared derivatives were measured by an Electrothermal 9100 apparatus which reported without any correction. The FT-IR spectra were recorded in the range of 400- 4000 cm-1 using Shimadzu IR-470 spectrometer by using KBr pellets.

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H NMR spectra were recorded using the Bruker DRX-500 and 300 Avance

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Journal Pre-proof spectrometer. Elemental analysis was provided by EDX analysis which was recorded by TESCAN4992. The morphology of synthesized nanocomposite was studied by SEM using VEGA2 TESCAN instrument. TGA of prepared nanocomposite was obtained by a STA504. The XRD measurement of the nanocatalyst was recorded with the X′ Pert Pro diffractometer operating with (40 mA, 40 kV) and ICP-AES analysis was performed by Shimadzu ICPS-7000.

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2.2. Synthesis of magnetic dextrin nanocomposite

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As is illustrated in Fig. 2 (a), magnetic dextrin nanocomposite was prepared by in situ chemical

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co-precipitation of ferric and ferrous salts in the presence of dextrin polysaccharide with

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modified methods from literature [23]. Initially, the solution of 2.330 g FeCl3.6H2O and 0.858 g FeCl2.4H2O in 100 mL distilled water was prepared, then 0.55 g dextrin was added gradually to

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the above mixture. The resulting mixture was stirred for 1 h at 90 ºC under N2 atmosphere. To

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provide the alkaline condition, 8 mL ammonium hydroxide (25%) was added drop by drop during 15 min to the above suspension, which stirred intensely. At this stage, the color of the

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reaction mixture changes to dark brown, which indicates the formation of Fe3O4 in the presence

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of dextrin. The reaction continued for about one hour. An external magnet was used to separate the product. The resultant nanocomposite was washed with deionized water (3x20) and ethanol (3x15) to take out any unreacted materials. Then, it was dried at room temperature for 6 h to provide magnetized dextrin.

2.3. General Procedure for Synthesis of Polyhydroquinoline derivatives At first, 5 mg (3.5 wt%) of magnetic dextrin as a heterogeneous catalyst was added to a roundbottomed flask containing an aromatic aldehyde, dimedone, ethyl acetoacetate and ammonium

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Journal Pre-proof acetate with a molar ratio of 1:1:1:1 in 2 mL ethanol. Then, the mixture was refluxed for enough time. After confirming the completion of the reaction by thin layer chromatography (ethyl acetate/n-hexane: 1/2). The magnetic catalyst was easily isolated by an external magnetic. The high pure product was obtained by recrystallization of the crude precipitate from ethanol/water. All the products synthesized in this work were known compounds. Their melting points were

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compared with reported values to confirm their successful formation.

4-(4-chlorophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-

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Ethyl

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2.4. Spectral data of the selected products

carboxylate (5f):

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Dark yellow solid; Melting point = 243-245 °С; FT-IR (KBr): υmax (cm-1) = 1014, 1033, 1070,

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1215, 1382, 1490, 1604, 1647, 1704, 2960, 3076, 3244, 3274. 1H NMR (500 MHz, DMSO-d6):

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δH (ppm) = 0.93 (s, 3H, Me), 1.11 (s, 3H, Me), 1.19 (t, 3H, J = 6.9 Hz, Me), 2.04 (d, 2H, CH2), 2.24 (d, 2H, CH2), 2.30 (s, 3H, Me), 4.05 (q, 2H, J = 6.9 Hz, O-CH2), 4.91 (s, 1H, CH), 7.22-

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7.62 ( 2d, 2H, J = 8.1 Hz, H-Aromatic), 9.18 (s, 1H, NH).

Ethyl 2,7,7‐trimethyl‐5‐oxo‐4‐p‐tolyl‐1,4,5,6,7,8‐hexahydroquinoline‐3‐carboxylate (5k): Light yellow solid; Melting point = 139-141 °С; FT-IR (KBr): υmax (cm-1) = 1033, 1215, 1379, 1492, 1604, 1647, 1701, 2958, 3205, 3276. 1H NMR (300 MHz, CDCl3): δH (ppm) = 0.96 (s, 3H, Me), 1.08 (s, 3H, Me), 1.26 (t, 3H, J = 7.2 Hz, Me), 2.26 (s, 3H, s, Me), 2.22‐2.34 (m, 4H, 2CH2), 2.38 (s, 3H, Me), 4.16 (q, 2H, J = 7.2 Hz, O-CH2), 5.43 (s, 1H, CH), 6.19 (s, 1H, , NH); 6.84 (d, 2H, J= 7.5 Hz, H‐ Aromatic), 7.03 (d, 2H, J= 7.5 Hz, H‐Aromatic).

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Journal Pre-proof 3. Results and discussion Magnetic dextrin nanocomposite was prepared in one-step chemical co-precipitation of ferric and ferrous salts in presence of dextrin as natural precursors under alkaline condition. This magnetized polysaccharide was used as a green, efficient, and heterogeneous catalyst for the first time in organic reactions. To approve the production of nanocomposite and its identification,

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different conventional methods were employed which will be further explained in the following

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sections.

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3.1. Characterization of the prepared catalyst

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3.1.1 EDX analysis

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Elemental analysis was used to study the chemical composition and elementary structure of magnetic dextrin. The existence of C, O and Fe components in the framework of the

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nanocomposite was approved by this analysis. According to the element map and the table

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shown in Fig. 3, the highest atomic percentage belongs to the oxygen element, which is present in the natural polymer of dextrin as an organic part and magnetic nanoparticles as an inorganic

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part of the synthetic catalyst. After oxygen, iron has the highest atomic percent in the catalyst.

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Weight%

Atomic%

C

15.21

25.36

O

49.52

61.99

Fe

35.28

12.65

100

100

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Element

Fig. 3. (a) EDX analysis and (b) elemental mapping images of Fe, O and C components of the magnetic dextrin nanocomposite.

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Journal Pre-proof 3.1.2. FT-IR Analysis The FTIR is a significant instrument for identifying the functional group in the structure of compounds. FT-IR spectra of dextrin and magnetic dextrin nanocomposite are observed in Fig. 4. The FT-IR spectrum of dextrin showed some important absorption bands including: 1. A broad absorption band at 3438 cm−1 is related to the stretching vibration of O–H bond which is abundant in the dextrin polysaccharide backbone.

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2. An absorption band at 2923 cm−1 is attributed to the stretching vibration of aliphatic C–H.

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3. An observed absorption band at 1153 cm-1 is caused by asymmetric stretching vibration of

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glycosidic C–O–C bond.

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4. An appearing absorption band at 1056 cm−1 is assigned to the stretching vibration of the C-O bond on the pyran ring.

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Looking at the two spectrum of dextrin magnetic and dextrin, it is clear that the nanocomposite

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spectrum in addition to dextrin-related absorption bands appear in the 3383 cm−1 (O–H bond), 2928 cm−1 (aliphatic C–H bond), 1053 cm−1 (C–O–C glycosidic bridge) 1026 cm−1 (C-O bond on

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the pyran ring). Two new intensive absorption bands are appeared at 632 cm−1 and 579 cm−1

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which is ascribed to the stretching vibrations of Fe–O bond of Fe3O4 [24].

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Fig. 4. FT-IR spectra of (a) dextrin and (b) the magnetic dextrin.

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3.1.3. VSM magnetization curve

VSM analysis is used to evaluate the synthesized magnetic property of nanocomposite. The magnetic hysteresis loop can be seen in Fig. 5. It is obvious that a synthetic nanocomposite exhibits superparamagnetic behaviour owning to zero values for the magnetic reduced eminence magnetization (Mr) and the coercivity (Hc). The magnetic saturation of this

magnetized

polysaccharide is approximately 60 (emu g-1), which is 19% lower than that reported for the iron oxide nanoparticles [25]. Regarding the presence of natural polymer of dextrin as a non-magnetic

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Journal Pre-proof material in the structure of synthesized nanocomposite, this slight reduction seems reasonable. The point is the nanocomposite is still quickly separated by a magnet and can be retrieved.

100 80

Magnetization (emu/g)

60

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40

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20 0

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-40

-80 -100 -20000

-10000

-5000

0

5000

10000

15000

20000

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-15000

lP

-60

Applied Field (Oe)

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Fig. 5. VSM analysis of the magnetic dextrin.

3.1.4. SEM analysis

SEM picture was used to depict the morphology and particle size distribution of the synthesized nanocatalyst. As is seen in Fig. 6, the SEM results show that there is an aggregation of relatively uniform spherical particles that are well dispersed on the surface of dextrin. The mean particle size of the magnetic dextrin was determined to be 84 nm based on the particle size distribution diagram.

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a

25

Frequency

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20

b

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30

15 10 5 0

45

55

65

75

85

95

105

115

125

135

145

Diameter (nm) Fig. 6. (a) SEM image of the magnetic dextrin and (b) the particle size distribution diagram.

3.1.5. XRD pattern analysis 13

Journal Pre-proof XRD analysis was used to study the crystalline structure of nanocatalyst. As reported in the literature, dextrin has only shown two broad peaks, implying that is amorphous[26]. The XRD pattern of magnetic dextrin nanocomposite was compared to Fe3O4. As shown in Fig. 7, the standard patterns of Fe3O4 with card no. JCPDS, 00-001-111 have some intense characteristic diffraction peak at 2θ = 18.28º, 30.06º, 35.45º, 37.12º, 43.03º, 57.17º and 62.73º. The synthesized nanocomposite pattern displays several peaks at 2θ = 17.53º, 30.1º, 35.52º, 37.87º, 57.40º and

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69.68º that are in accordance with the pattern of Fe3O4. The existence of sharp peaks shows the

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crystalline areas and the wide broad peaks exhibit the amorphous areas in the nanocomposite.

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The semi-crystalline nature of the nanocomposite maybe related to the interaction of the Fe3O4

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with dextrin polymeric chains in the nanocomposite matrix. In other words, the modification of the surface of Fe3O4 with dextrin natural polymer was confirmed. The Scherer equation

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determines that average crystallite size of the prepared catalyst is about 66 nm.

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3.1.6. TGA analysis

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Fig. 7. The XRD pattern of (a) the magnetic dextrin and (b) standard Fe3O4.

To appraise the thermal stability of magnetic dextrin, TGA was used in a range of 20-600 °C in air atmosphere. Fig. 8 showed the curve of weight loss of dextrin and magnetic dextrin nanocomposite. Dextrin a weight loss of 11% at about 200 °C because of the removal of free water. In the temperature range of 237–337 °C, the most decomposition of dextrin was observed with 60% of weight loss. This weight loss might be related to dehydration, with transglucosidation. A residual mass for dextrin at 500 °C was obtained 2%. The curve of weight loss of nanocomposite showed the first weight drop was seen between 60-150 °C as a consequence of the moisture evaporation and the primary degradation of magnetic dextrin was 15

Journal Pre-proof viewed with 13 % weight loss at about 220–325 °C. This weight loss can be caused by selective dehydration, possibly accompanied by transglucosidation. The residual mass until 500 °C for magnetic dextrin was gained about 80%, whereas for pure dextrin at the same temperature, it was less than 5%. It was evident that the nanocomposite weight loss curve occurs at much higher temperatures than pure dextrin. Hence, it was deduced that the fabrication of a hybrid nanocomposite of dextrin polysaccharide with Fe3O4 and the existence of strong intermolecular

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interactions have enhanced significantly its thermal resistance.

Fig. 8. TGA of (a) the magnetic dextrin and (b) dextrin.

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Journal Pre-proof 3.1.7. ICP-AES analysis Furthermore, a dextrin and Fe3O4 content in the prepared nanocomposite was determined with the ICP-AES analysis. The result of this evaluation display that one gram of nanocatalyst composed of 0.72 g (72% w/w) of Fe3O4 and 0.28 g (28% w/w) of dextrin polysaccharide.

3.2. Application of catalyst

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3.2.1. Optimization of the effective parameters

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The synthesis of polyhydroquinoline derivatives via MCRs was chosen to assess the efficiency

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of the prepared hybrid nanocomposite. The four components reaction of 4-chlorobenzaldehyde,

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ethyl acetoateacetate, dimedone and ammonium acetate was tested as a model reaction to determine the optimal conditions. Determinant factors such as temperature, type of catalyst,

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amount of catalyst and solvents, on the reaction were examined. Initially, the model reaction was

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performed at three different temperatures to achieve the best product efficiency, the results (entries 1-3) show that the refluxing conditions leads to higher efficiency for the desired product.

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Then, in order to affect the presence of the catalyst, the reaction was performed without a

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catalyst which produced a low-yield product after about three hours. In next step, the reaction carried out in the presence of same weight percentages of dextrin, Fe3O4 and magnetic dextrin. (entries 4-6). The reaction was slightly facilitated by Fe3O4 and dextrin. But, the synergistic effect of these two materials in the magnetic dextrin hybrid catalyst resulted in a notable catalytic efficiency. Therefore, reactions were followed to investigate the effect of the catalyst content on facilitating the reaction (entries 6-8). The highest reaction efficiency was obtained with 3.5 wt% of nanocatalyst. Different organic solvents such as ethanol, methanol, ethylacetate, n-hexane and

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Journal Pre-proof acetonitrile were used to determine an appropriate solvent for the reaction. The provided information in Table 1 shows that the best result was achieved in ethanol.

Entry

Catalyst

Loading (wt%)

Solvent

Temp. (ºC)

Time (min)

Yieldb (%)

1

-

-

EtOH

r.t.

175

Trace

2

-

-

EtOH

40

180

Trace

3

-

-

EtOH

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170

20

4

Fe3O4

3.5

EtOH

reflux

145

28

5

Dextrin

3.5

EtOH

-p

reflux

120

45

6

Magnetic dextrin

3.5

EtOH

15

95

7

Magnetic dextrin

4.28

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reflux

EtOH

reflux

15

94

8

Magnetic dextrin

7.1

EtOH

reflux

180

Trace

9

Magnetic dextrin

3.5

EtOAc

reflux

75

65

10

Magnetic dextrin

3.5

n-hexane

reflux

135

45

11

Magnetic dextrin

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Table 1. Optimization of the reaction conditions in the MCR of polyhydroquinoline derivatives. a

3.5

CH3CN

reflux

60

65

12

Magnetic dextrin

3.5

MeOH

reflux

55

60

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a

reflux

Reaction conditions: 4-chlorobezaldehyde (1 mmol), ethyl acetoacetate (1 mmol), dimedone (1 mmol),

ammonium acetate (1 mmol), magnetic dextrin (3.5-7.1 wt.%). b

The yields relate to the isolated product.

3.2.2. Investigation of the catalytic activity of magnetic dextrin Appraisal of the generality and limitation of this process for the synthesis of polyhydroquinoline derivatives was done using different aromatic aldehydes ethyl acetoacetate, dimedone, ammonium acetate in optimum condition was studied.

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Journal Pre-proof According to the presented experimental data in Table 2, all aromatic aldehydes whether with electron withdrawing or electron donating substitution generated a high yield of corresponding products between 70-95% and at 15-45 min.

Table 2. Synthesis of polyhydroquinoline derivatives (5a-l) via MCRs using magnetic dextrin

Ar

Product

Time

Yieldb

(min)

(%)

Found

Ref

25

70

202-203

201[27]

30

85

200-202

202-204[28]

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Entry

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nanocatalyst. a

C4H6

2

3-OMeC4H6

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1

Mp (°C)

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3-NO2C4H6

30

90

176-178

175–176[29]

4

4-NO2C4H6

25

80

252-254

255[29]

5

4-BrC4H6

6

4-ClC4H6

7

4-FC4H6

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3

78

259-261

257-258[29]

15

95

242-244

240[27]

40

75

184-186

185-186[28]

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na

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20

20

4-OHC4H6

40

91

232-234

231-233[30]

9

4-OMeC4H6

35

65

259–261

258–260[29]

10

3-OHC4H6

83

216-218

218-220[31]

11

4-MeC4H6

25

86

255-256

255[27]

12

2-ClC4H6

30

65

200-203

201-202[27]

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45

a

Reaction conditions: aromatic aldehydes (1 mmol), ethyl acetoacetate (1 mmol), dimedone (1 mmol),

ammonium acetate (1 mmol), magnetic dextrin (3.5 wt%), EtOH (2 mL), reflux. b

The yields of the isolated products.

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Journal Pre-proof 3.2.3. Recyclability of the magnetic dextrin nanocatalyst The ability to recycle and reuse heterogeneous catalysts is one of their applied features, which is important both from environmental and industrial aspects. Therefore, several experiments were arranged for probing these applied properties of the obtained organic–inorganic hybrid catalyst. The presented results in Fig. 9 show that the product yield was not decreased significantly after five consecutive runs. The catalyst retrieval is considered a useful feature, provided that its

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recovery does not result in a tangible change in its structure. As a result, the FT-IR spectra of the

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obtained catalyst before and after five times use in the reaction was presented in Fig. 10.

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Comparison of two spectra shows that there is no difference between the two spectra. Magnetic

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dextrin retains its structure during repeated experiments and can be used as a stable and retrievable catalyst in other organic reactions. Also, to test structural stability, the XRD analysis

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of the recycled catalyst was carried out and shows that the crystalline phase of the magnetic

95

93

91

2

3

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100 90 80 70 60 50 40 30 20 10 0

90

89

89

4

5

6

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Isolated yield (%)

catalyst (Fig. S5).

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dextrin has not changed after five consecutive reuses in the reaction compared to the fresh

1

Run

Fig. 9. Recycling diagram of the magnetic dextrin nanocatalyst in the synthesis of 5f.

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Fig. 10. FT-IR spectra of (a) the magnetic dextrin before used in the reaction, (b) after five times reusing

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in the reaction.

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The comparison of the catalytic efficiency of the magnetic dextrin with several other catalysts reported in recent literature for the synthesis of a particular derivative of polyhydroquinoline (5f)

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is provided in Table 3. The results demonstrated that the present method, in addition to the use of

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a biocompatible catalyst, has other advantages such as higher performance and lower reaction time than some previous reports.

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Journal Pre-proof Table 3. Comparison of some catalysts with magnetic dextrin nanocatalyst on the model reaction using 4chloro-benzaldehyde, ethyl acetoacetate, dimedone, ammonium acetate. Catalyst

Solvent/conditions

Time (min)

Yielda (%)

[Lit.]

1

BiBr3

EtOH/r.t.

120

86

[32]

2

(DBH or DCH)b

Solvent-Free/130 °C

30

94

[28]

3

La2O3

TFE/r.t.

95

[31]

4

magnetite/chitosan

EtOH/r.t.

75

88

[29]

5

Magnetic dextrin

EtOH/reflux

15

95

This work

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Entry

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The yields of the isolated products.

b

1,3-Di(bromo or chloro)-5,5-dimethylhydantoin.

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a

3.2.4. Mechanism for the synthesis of polyhydroquinoline derivatives

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According to the information provided in the recently reported methods for Hantzsch reaction

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[17, 33], the suggested mechanism showed in Fig. 11. As is observed, in steps 1 and 2, the carbonyl groups of the aromatic aldehyde and ethyl acetoacetate were activated by intermolecular interactions with the catalyst. In one hand, the substance a reacts with dimedone and forms an intermediate c through Knoevenagel condensation. On the other hand, intermediate d is produced during the condensation reaction (imine formation) between the substance b and ammonium acetate. In the next step, a Michael addition between intermediate c and d gave the intermediate e. Subsequently, product 5 is generated by the formation of enamine and an intramolecular nucleophilic reaction.

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Fig. 11. Suggested mechanism for the synthesis of polyhydroquinoline derivatives and the catalytic role of the magnetic dextrin.

4. Conclusions In summary, in this work, the magnetic dextrin was introduced as a novel, green and efficient organic-inorganic hybrid catalyst for the synthesis of biologically active polyhydroquinoline derivatives by asymmetric Hantzsch MCRs. The present polysaccharide-based nanocatalyst approves its ability to generate the products in high yields and short reaction times under mild 25

Journal Pre-proof reaction condition. Magnetic dextrin as a biocompatible recoverable catalyst can play impressive role in reducing chemical waste. This heterogeneous nanobiocomposite catalyst has the promising potential to synthesize other related heterocyclic compounds through MCRs due to unique characteristics especially the abundance of reactive functional groups in its structure. According to the SEM images average particle size of the sample is 84 nm. The VSM analysis verified superparamagnetic property for magnetic dextrin. XRD pattern of prepared catalyst

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indicated that it has a semi-crystalline nature which is a result of the interaction of Fe3O4 with

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dextrin natural polymer. Also, TGA analysis revealed high thermal stability till 600 °C. The

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catalyst recovery results for the synthesis of 5f showed that the yield of the product was not decreased considerably after five consecutive reuses. Given the high recyclability of this

Acknowledgments

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be regarded as a beneficial feature.

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magnetic nanobiocatalyst both in environmental protection and in industrial application, this can

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All authors gratefully acknowledge the partial support from the Research Council of the Iran

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University of Science and Technology (IUST) and the Iran National Science Foundation (INSF).

Conflict of Interest The authors declare no conflict of interest.

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Graphical abstract

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Journal Pre-proof Highlights  Organic-inorganic hybrid showed high synergistic effect between dextrin and Fe3O4.  EDX, FT‐IR, VSM, SEM, XRD, TGA and ICP-AES were used to characterize the catalyst.  Biocompatible nanocatalyst was performed in the synthesis of polyhydroquinolines.

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 It reused several times without considerable reduction in catalytic performance.

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