Mo@GAA-Fe3O4MNPs: a highly efficient and environmentally friendly heterogeneous magnetic nanocatalyst for the synthesis of polyhydroquinoline derivatives

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Mo@GAA-Fe₃O₄MNPs: a highly eﬃcient and

environmentally friendly heterogeneous magnetic

nanocatalyst for the synthesis of

Cite this: RSC Adv., 2021, 11, 10497

polyhydroquinoline derivatives

a

*

Mehraneh Aghaei-Hashjin, Asieh Yahyazadeh and Esmayeel Abbaspour-

b

*

Gilandeh

Polyhydroquinolines were eﬃciently obtained from a sequential four-component reaction between

dimedone or 1,3-cyclohexandione, ethyl acetoacetate, or methyl acetoacetate as b-ketoester,

a

aldehydes, and ammonium acetate, under the catalysis of Mo@GAA-Fe₃O₄MNPs as a green, eﬀective,

recyclable, and environmentally friendly nanocatalyst. Due to its magnetic nature the prepared catalyst

can be easily separated from the reaction mixture by an external magnet and reused several times

without signiﬁcant changes in catalytic activity and reaction eﬃciency. The catalyst was characterized

using energy dispersive X-ray spectroscopy (EDX), X-ray diﬀraction (XRD), thermogravimetric analysis

(TGA), Fourier transform infrared spectroscopy (FTIR), vibrating sample magnetometry (VSM), scanning

electron microscopy (SEM), and transmission electron microscopy (TEM).

Received 16th January 2021

Accepted 3rd March 2021

DOI: 10.1039/d1ra00396h

rsc.li/rsc-advances

Nowadays, remarkable attention has been paid to the use of

magnetic nanoparticles (MNPs), as a bridge between homoge-

1. Introduction

neous and heterogeneous catalysts, by scientic and industrial

researchers because of their potential importance in modern

chemical research.¹⁰Some excellent physical and chemical

features of MNPs such as separation by an external magnet,

superparamagnetism, high surface area, and strong adsorption

ability¹¹have expanded their utilization in the removal of heavy

metal ions in wastewater,^12–14catalysis,¹⁵and drug delivery.¹⁶

However, some of the MNPs features such as a tendency to

oxidize and accumulate during reactions, high initial chemical

activity, and high surface area to volume ratio will reduce their

catalytic activity and magnetic nature during the reaction

period.^17,18Thus, to overcome this drawback and increase their

chemical stability for the special application, functionalization

and modication of their surface with organic or inorganic

supports are necessary.

Molybdenum as a d-block transition metal has various

oxidation states from –I to +VI and it has a signicant role in the

life evolution. Despite the little amount of molybdenum on the

earth's crust, it could be known as an oxotransferases for the

active places and cofactors of several enzymes that catalyzes the

oxygen and electron transfer reactions on the layers of nitrogen,

carbon, and sulfur.^19,20Mo(VI) is one of the main oxidation states

that obtains a formal double bond between the metal and the

oxo ligand via the donating s and p bonds. There is a wide

range of reports on the fabricated complexes using dioxomo-

lybdenum(^VI) obtained from varying the type and denticity of

the remaining anionic ligands.^21–24Among those, MoO₂(acac)₂

In recent decades, the preparation of environmentally friendly

catalysts with recoverability and reusability are the main chal-

lenges amongst researchers in organic chemistry. Chemical

reactions can be accelerated in the presence of homogeneous or

heterogeneous catalysts, each of which has its advantages and

disadvantages. Homogeneous catalysts, due to the greater

interaction with the substrates compared to their heteroge-

neous counterparts, can generate a uniform layer with the

starting materials in the organic solvent of the reaction which

increases their activity and selectivity during the corresponding

reaction.^1–6However, the main problem when using these

catalysts is related to the diﬃculty in separating and reusing

them, which can be largely solved by using heterogeneous types.

Heterogeneous catalysts, despite their lower eﬃciency, can

exhibit suitable recyclability by centrifugation or ltration and

can be reused several times without a signicant decrease in

their catalytic behavior. Functionalization of the heterogeneous

supports via a strong connection with homogeneous catalysts

increase their eﬃciency while maintaining their simplicity in

recovery and separation.⁷

Nanocatalysts exhibit high catalytic activity, which is

provided by their large surface area, and this signicantly

increases the contact between reactants and catalyst.^8,9

^aChemistry Department, University of Guilan, Rasht 41335-1914, Iran

^bYoung Researchers and Elites Club, Ardabil Branch, Islamic Azad University, Ardabil,

Iran. E-mail: abbaspour1365@yahoo.com

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is one of the most famous and major dioxomolybdenum(VI) Energy-dispersive X-ray spectroscopy (EDX) was carried out on

complexes used as a catalyst for the organic transformations a FE-SEM (MIRA III, Detector of SAMX, France). Powder X-ray

including epoxidation of alkenes and the oxidation of diﬀraction (XRD) was performed using Cu-Ka radiation (l ¼

suldes.^25,26Also, the coordination of molybdenum complexes 1.54 A) on a Philips-PW1730 in the 2q range of 10 –80 . Ther-

by the organic groups (including oxygen, nitrogen, and sulfur) mogravimetric analyses (TGA) were performed using a Linseis

stabilized on the surfaces of magnetic nanoparticles has been SATPT 100 thermoanalyzer at a heating rate of 10 ^ꢀC min^ꢁ1

ꢀ

˚

used in many catalytic systems.^27–30

under nitrogen atmosphere over a temperature range of 25–

Multicomponent reactions (MCRs), as a versatile synthetic 700 ^ꢀC. The Fourier-transform infrared (FT-IR) spectra were

strategy, combine at least three or more reactants^31–34via recorded on a Perkin Elmer PXI spectrum, using pellets of the

a single synthetic operation to generate several covalent bonds materials diluted with KBr in the range of 400–4000 cm^ꢁ1. The

into structurally complex organic molecules containing most magnetic features of the catalyst were determined using

atoms of the available starting materials.³⁵Currently, MCRs are a vibrating sample magnetometer (VSM; MDK Co. Kashan, Iran)

taken into consideration in the sustainable synthetic strategies, in the magnetic eld range of ꢁ15 000 Oe to 15 000 Oe at room

via which we can easily generate high compatibility with green temperature. Scanning electron microscopy (SEM) images were

chemistry due to their unique advantages, such as concomitant recorded using an SEM-LEO 1430VP analyzer. Transmission

step economy, mild conditions, atom economy, and high electron microscopy (TEM) was utilized on a Zeiss-EM 900

convergence. Over the past decades and due to their various instrument.

important applications in combinatorial chemistry,³⁶agro-

chemistry,³⁷medicinal chemistry,^38–40polymer chemistry,³¹and

2.1. Synthesis of Fe₃O₄nanoparticles (MNPs)

natural product synthesis,⁴¹MCRs have received considerable

In the rst step, a solution of FeCl₂$4H₂O (0.86 g) and FeCl₃-

attention among organic chemists.

$6H₂O (2.36 g) were dissolved in deionized water (40 mL). The

1,4-Dihydropyridine (1,4-DHP) core as an important class of

mixture was heated to 90 ^ꢀC, and mechanical stirring was done

nitrogen-containing heterocycles found in the nature have

for 30 min under an argon atmosphere. Then, 10 mL of

attracted considerable synthetic eﬀorts over the past decade

ammonia solution (25%) was added dropwise to the resulting

because of their diversity of biological functions, including

mixture and stirred for another 20 min under argon ow. The

antitubercular,⁴²neuroprotectant,⁴³antimicrobial,⁴⁴insecti-

precipitates were washed with distilled water and collected

cidal,⁴⁵antiviral,⁴⁶antihypertension,⁴⁷anticancer,⁴⁸and antiox-

using a magnet. The product was dried under vacuum

idant^49,50activities. Amongst them, polyhydroquinoline

conditions.

derivatives are very interesting heterocyclic molecules due to

their pharmacological properties such as anti-inammatory,

antimalarial, antibacterial, anti-asthmatic, and tyrosine kinase

2.2. Synthesis of Fe₃O₄@SiO₂(SCMNPs)

inhibiting agents.^51–53Many procedures have been developed for In a typical method, 1.0 g of obtained Fe₃O₄nanoparticles was

the preparation of polyhydroquinolines using catalysts such as dispersed in a mixture of 60 mL ethanol, 20 mL deionized water,

ionic liquids,⁵⁴microwaves,⁵⁵reuxing at high temperature,⁵⁶and 2 mL ammonia solution (25%) by sonication for 10 min.

metal triates,⁵⁷ceric ammonium nitrate (CAN),⁵⁸trimethylsilyl Then, 0.45 mL of tetraethylorthosilicate (TEOS) was added into

chloride (TMSCl),⁵⁹HY-zeolite,⁶⁰FeF₃,⁶¹silica perchloric acid the reaction system, sonicated for another 10 min, and stirred at

(HClO₄–SiO₂),⁶²triuoroethanol,⁶³montmorillonite K-10,⁶⁴ambient temperature for 14 h. The resultant precipitate was

iodine,⁶⁵autoclave,⁶⁶NiFe₂O₄MNPs,⁶⁷heteropoly acid,⁶⁸L- magnetically collected by a permanent magnetic eld, washed

proline,⁶⁹PTSA-SDS,⁷⁰NiCuMgFe₂O₄MNPs,⁷¹polymers,⁷²three times with a mixture of ethanol and water (1 : 1), and

Sc(OTf)₃,⁷³{Fe₃O₄@SiO₂@(CH₂)₃Im}C(NO₂)₃,⁷⁴Yb(OTf)₃,⁵⁷Fe₃- dried in a vacuum oven.

O₄-adenine-Ni,⁷⁵BINOL-phosphoric acid derivatives,⁷⁶and Cu-

SPATB/Fe₃O₄.⁷⁷Although most of these procedures oﬀer

2.3. Functionalization of SCMNPs by 3-

distinct merits, some of these procedures suﬀer from one or

more limitations, such as generating a large amount of waste,

low yields of the desired product, poor recovery of the catalyst,

long reaction times, and hard reaction conditions. Therefore, to

avoid these limitation based on the green chemistry protocols,

the discovery of simple, eﬃcient, versatile, and environmentally

friendly processes for the synthesis of polyhydroquinolines is

still favored.

aminopropyltriethoxysilane (Amp@SCMNPs)

1 g of core–shell Fe₃O₄@SiO₂nanoparticles was suspended in

20 mL of dry toluene by ultrasonication. Aer treatment for

20 min, 2 mL of 3-aminopropyltriethoxysilane (Amp) was added

to the solution and reuxed under an argon atmosphere. Aer

24 h, the Amp@SCMNPs were collected using a permanent

magnet, washed with ethanol and distilled water several times,

and then dried under vacuum.

2. Experimental

2.4. Functionalization of Amp@SCMNPs by glutaraldehyde

(imine@SCMNPs)

All of the chemical substances used in this work were purchased

from Merck, Aldrich, and Fluka Chemical Companies and used 2 g of prepared Amp@SCMNPs nanoparticles was added to

without further purication. Melting points of the products 100 mL ethanol and dispersed for 30 min under ultrasonic

were determined with an Electrothermal 9100 apparatus. irradiation. Then, 4 mmol of glutaraldehyde was added into the

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reaction solution and reuxed for 24 h. The prepared solid

product (imine@SCMNPs) was then magnetically isolated and

washed several times with ethanol to remove unreacted

glutaraldehyde; nally, it was dried under vacuum.

2.7. General procedure for the preparation of

polyhydroquinolines

Firstly, Mo@GAA-Fe₃O₄MNPs (10 mg) was poured into the

reaction mixture of dimedone or 1,3-cyclohexandione (1 mmol),

ethyl acetoacetate, or methyl acetoacetate (1 mmol), aldehydes

(1 mmol), and ammonium acetate (1.2 mmol), and the reaction

mixture was heated for a specic time. Upon completion of the

reaction, the catalyst was easily extracted using an external

magnetic eld; the resulting product was collected by ltration,

rinsed, and recrystallized with ethanol to give pure

polyhydroquinolines.

2.5. Synthesis of GAA/imine@SCMNPs

1 g of the obtained imine@SCMNPs was dispersed in 25 mL

DMF by the ultrasonic bath for 30 min. Then, 0.85 mmol of

guanidineacetic acid (GAA) was added to the reaction solution.

Aer the stirrer process for 8 h, the resulting substance was

separated by a permanent magnet, rinsed with ethanol several

times, and dried under vacuum.

3. Results and discussion

3.1. FTIR analysis Mo@GAA-Fe₃O₄MNPs

FTIR spectroscopy is one of the main techniques for the quali-

2.6. Synthesis of Mo@GAA-Fe₃O₄MNPs

tative determination of the molecular structures in diﬀerent

MoO₂(acac)₂was prepared using the literature method.⁷⁸2 g of species and the identication of existing functional groups in

GAA/imine@SCMNPs were added into 150 mL ethanol and the structure. Fig.

1 shows FTIR spectra for SCMNPs,

a solution of MoO₂(acac)₂(4 mmol) in 70 mL ethanol was added Amp@SCMNPs, imine@SCMNPs, GAA/imine@SCMNPs, and

to this reaction solution and reuxed for 12 h. Aer magnetic Mo@GAA-Fe₃O₄MNPs. In the case of SCMNPs, the band at

separation, the resulting solid product was washed with 585 cm^ꢁ1, from the Fe–O bond, veries that the Fe₃O₄lattice is

dichloromethane to remove the unreacted MoO₂(acac)₂and was formed. The presence of a broad peak at 3406 cm^ꢁ1is due to the

dried under vacuum (Scheme 1).

O–H stretching vibrations, which are attached to the Fe₃O₄

Scheme 1 The Mo@GAA-Fe₃O₄MNPs synthesis.

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Fig. 1 FTIR spectra of SCMNPs, Amp@SCMNPs, imine@SCMNPs, GAA/imine@SCMNPs, and Mo@GAA-Fe₃O₄MNPs.

surface. The above-mentioned structure has the symmetric stretching vibrations, which conrmed the successful covalent

stretching vibrations of Si–O–Si at around 1030 cm^ꢁ1and attachment of 3-aminopropyltriethoxysilane (Amp) to the

twisting bonds of Si–O–H and H–O–H at 1630 cm^ꢁ1, indicating SCMNPs surface. Also, vibrations at 796 and 853 cm^ꢁ1were

that the Fe₃O₄nanoparticles (MNPs) contain silica layers. In the probably attributed to the asymmetric stretching and in plane

FT-IR spectrum of the Amp@SCMNPs can be observed the bending of Si–O–Si group, respectively. In about the imi-

peaks for C–H (2938 cm^ꢁ1), and NH₂(3250, and 3427 cm^ꢁ1

)

ne@SCMNPs, the peak at 1636 cm^ꢁ1is assigned to the

Fig. 2 TGA curves of (a) SCMNPs, (b) GAA/imine@SCMNPs, and (c) Mo@GAA-Fe₃O₄MNPs.

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3.2. TGA analysis of Mo@GAA-Fe₃O₄MNPs

TGA analysis can be used to determine the loading amount of

the organic groups on the synthetic substrates. This measures

the mass variations as a function of the temperature and time

under a controlled atmosphere and indicates the thermal

stability of the sample on a plot. The TGA analysis curves of

SCMNPs, GAA/imine@SCMNPs, and Mo@GAA-Fe₃O₄MNPs are

shown in Fig. 2. All samples underwent a small weight loss

ꢀ

below 200 C due to water thermodesorption from the surface

(drying). Another weight loss up to 700 ^ꢀC was found in TGA

curve of SCMNPs, which can be related to the release of hydroxyl

ions from the nanoparticles and volatilization. In the TGA

curves of GAA/imine@SCMNPs and Mo@GAA-Fe₃O₄MNPs,

another weight loss can be seen up to 650 ^ꢀC, which can be

attributed to the decomposition of the functionalized organic

groups.

3.3. XRD analysis of Mo@GAA-Fe₃O₄MNPs

Fig.

3 XRD patterns of (a) Fe₃O₄, (b) GAA/imine@SCMNPs, (c)

Identication of the crystalline materials using X-ray is one of

the most common and important analysis techniques. As the X-

ray region is located between gamma and ultraviolet, useful

data could be obtained from this spectral region including the

crystalline structure, the material type, and the nanoparticle

size. The XRD patterns for Fe₃O₄(a), GAA/imine@SCMNPs (b),

Mo@GAA-Fe₃O₄MNPs (c) and recovered Mo@GAA-Fe₃O₄MNPs

(d) are depicted in Fig. 3. The X-ray diﬀraction patterns of Fe₃O₄

magnetic nanoparticles display six diﬀraction peaks at 2q ¼

30.5^ꢀ, 35.7^ꢀ, 43.8^ꢀ, 53.6^ꢀ, 57.5^ꢀ, and 63.1^ꢀ(indexed as (220),

(311), (400), (422), (511), and (440) reection, associated with

the crystalline structure of the spinel magnetic core). In addi-

tion, GAA/imine@SCMNPs and Mo@GAA-Fe₃O₄MNPs have

also similar diﬀraction peaks, indicating an unchanged

Mo@GAA-Fe₃O₄MNPs, and recovered Mo@GAA-Fe₃O₄MNPs (d).

stretching vibrations of the C]N bond, revealing the func-

tionalization of the Amp@SCMNPs with glutaraldehyde groups.

The bands at 1457 and 1626 cm^ꢁ1of the FTIR spectrum of GAA/

imine@SCMNPs can be assigned to the C–N and COO stretch-

ing vibrations. Also, a broad band about 3000–3400 cm^ꢁ1can be

ascribed to the acidic OH stretching vibrations. The peak

observed at 950 cm^ꢁ1corresponds to the MoO₂group, which

indicates the formation of the Mo@GAA-Fe₃O₄MNPs. More-

over, the FTIR spectra of the catalyst show a frequency shi for

some bonds, indicating the coordination of the metal with the

desired bonds.

Fig. 4 VSM patterns of (a) Fe₃O₄, (b) SCMNPs, and (c) Mo@GAA-Fe₃O₄MNPs.

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crystalline structure of the above-mentioned products. It is attributed to the functionalization of the Fe₃O₄core by silica

necessary to mention that the XRD pattern of recovered layers, organic molecules, and metal groups.

Mo@GAA-Fe₃O₄MNPs aer the rst recovery and reuse do not

show any change in crystalline structure.

3.5. SEM analysis of Mo@GAA-Fe₃O₄MNPs

The obtained images from the SEM technique could be used to

study the morphology, uniformity, and physical properties of

nanoparticle surfaces. High magnications are obtained by this

3.4. VSM analysis of Mo@GAA-Fe₃O₄MNPs

Magnetic properties and the behavior of the achieved nano- device to precisely investigate the material details. As shown in

particles are investigated by the VSM analysis. An external Fig. 5, Fe₃O₄and SCMNPs are nearly spherical with a smooth

magnetic eld is applied to evaluate the magnetization ability of surface and their mean particle sizes are 19 and 26 nm,

the magnetic nanoparticles. The VSM analysis of the synthe- respectively. The obtained results clearly showed that the

sized (a) Fe₃O₄, (b) SCMNPs, and (c) Mo@GAA-Fe₃O₄MNPs were SCMNPs particles have grown compared to the Fe₃O₄. Accord-

shown in Fig. 4. The saturation magnetization values (M_s) of ing to the represented images for GAA/imine@SCMNPs and

magnetic materials revealed signicant diﬀerences, which are Mo@GAA-Fe₃O₄MNPs, the average size of the above-mentioned

50.63 and 47.16 emu g^ꢁ1for bare Fe₃O₄and SCMNPs, respec- nanoparticles are in the range of 30–37 nm. The modication by

tively, while for catalyst, the diﬀerence is 28.99 emu g^ꢁ1. As can organic and metallic groups can result in the growth and

be seen, the value of M_sfor the catalyst decreased, which can be accumulation of the nanoparticles.

Fig. 5 SEM image of (a) Fe₃O₄, (b) SCMNPs, (c) GAA/imine@SCMNPs, and (d) Mo@GAA-Fe₃O₄MNPs.

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Fig. 6 TEM image of Mo@GAA-Fe₃O₄MNPs.

Fig. 7 EDX spectra of (a) GAA/imine@SCMNPs and (b) and Mo@GAA-Fe₃O₄MNPs.

Fig. 8 SEM image of Mo@GAA-Fe₃O₄MNPs nanocatalyst and corresponding quantitative EDX element mapping of C, N, O, Fe, Si, and Mo.

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spectra of the GAA/imine@SCMNPs and Mo@GAA-Fe₃O₄MNPs

is shown in Fig. 7a and b, respectively. In the case of GAA/

imine@SCMNPs, the presence of carbon, nitrogen, oxygen,

iron, and silicon was conrmed (Fig. 7a). Also in Fig. 7b, the

presence of the molybdenum element indicates coordination of

Mo with nitrogen and oxygen electron pairs and thus the

successful synthesis of the Mo@GAA-Fe₃O₄MNPs. In addition,

Fig. 8 shows the elemental map of the Mo@GAA-Fe₃O₄MNPs

nanocatalyst, which exhibits the presence of C, N, O, Fe, Si, and

Mo elements.

To synthesize new catalysts for certain organic processes,^79–84

the synthesis of potentially active polyhydroquinoline deriva-

tives (5) was investigated with various substituents from the

reaction between dimedone or 1,3-cyclohexandione (1), ethyl

acetoacetate, or methyl acetoacetate (2), aldehydes (3), and

ammonium acetate (4) under solvent-free conditions using

Mo@GAA-Fe₃O₄MNPs as a novel, eco-friendly, reusable, and

promising nanocatalyst (Scheme 2).

Scheme

polyhydroquinolines.

2

Mo@GAA-Fe₃O₄

MNPs-catalyzed

synthesis

of

3.6. TEM analysis of Mo@GAA-Fe₃O₄MNPs

The catalytic activity of the Mo@GAA-Fe₃O₄MNPs was

surveyed in the preparation of polyhydroquinoline derivatives.

Firstly, the condensation reaction of dimedone, ethyl acetoa-

cetate, 4-chlorobenzaldehyde, and ammonium acetate in the

presence of Mo@GAA-Fe₃O₄MNPs was chosen as a model

reaction. To optimize the reaction conditions, the synthesis of

polyhydroquinolines we studied under various reaction condi-

tions, including solvent, temperature, and the amount of cata-

lyst. To optimize the reaction solvent, H₂O, EtOH, THF, CH₂Cl₂,

CH₃CN, toluene, cyclohexane, and solvent-free conditions were

tested (Entries 1–8). The results are summarized in Table 1,

showing that carrying out the reaction in the absence of solvent

led to the formation of the desired product 5p in the highest

In TEM analysis, a focused electron beam is used for obtaining

the images. In this technique, some information from the inner

structure could be obtained by transmitting a high-energy

electron beam through a thin sample. Fig. 6 shows the TEM

image of Mo@GAA-Fe₃O₄MNPs. TEM images indicate that the

diameter of the obtained catalyst is about 28–35 nm and it has

a nearly spherical morphology with a narrow particle size

distribution.

3.7. EDX and elemental mapping analysis of Mo@GAA-

Fe₃O₄MNPs

One of the main techniques to identify the elemental compo- yield (Entry 8). However, a good yield of the product was

sition of the sample or a part of it is the EDX analysis. The EDX

Table 1 Optimization one-pot four-component condensation of dimedone, ethyl acetoacetate, 4-chlorobenzaldehyde, and ammonium

acetate, under diﬀerent conditions^a

Entry

Solvent

Catalyst (mg)

Temp. (^ꢀC)

Time (min)

Yield^b(%)

1

2

3

4

5

6

7

8

H₂O

EtOH

THF

CH₂Cl₂

CH₃CN

Toluene

Cyclohexane

—

10

—

5

15

20

10

Reux

90

100

80

60

40

25

100

50

45

83

18

25

35

39

40

96

—

81

95

92

95

88

76

65

21

86

88

160

360

220

360

200

12

100

35

12

20

40

9

10

11

12

13

14

15

16

17

18

19

90

120

25

10

10 (imine@SCMNPs)

10 (GAA/imine@SCMNPs)

90

25

a

Reaction conditions: dimedone (1 mmol), ethyl acetoacetate (1 mmol), 4-chlorobenzaldehyde (1 mmol), and ammonium acetate (1.2 mmol) and

required amount of the catalyst. ^bIsolated yield.

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Table 2 Preparation of polyhydroquinoline derivatives using desired catalyst^a

Entry

RCHO (3)

Product

Time (min)

Yield^b(%)

M.P. (Obsd) (^ꢀC)

M.P. (Lit) (^ꢀC)

1

13

93

222–224

221–223 (ref. 85)

2

3

15

20

93

92

253–256

208–211

256–257 (ref. 85)

208–211 (ref. 86)

4

5

6

17

13

15

90

93

236–238

257–259

219–221

238–240 (ref. 87)

257–259 (ref. 88)

220–222 (ref. 89)

7

8

20

90

93

223–225

269–272

222–223 (ref. 90)

270–274 (ref. 91)

9

15

95

256–258

256–259 (ref. 88)

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Table 2 (Contd.)

Entry

10

RCHO (3)

Product

Time (min)

Yield^b(%)

M.P. (Obsd) (^ꢀC)

M.P. (Lit) (^ꢀC)

14

94

239–241

240–241 (ref. 91)

11

12

15

18

94

91

234–236

202–205

234–235 (ref. 91)

204–205 (ref. 91)

13

14

15

20

13

15

88

95

90

231–235

201–203

207–208

233–234 (ref. 91)

202–204 (ref. 57)

206–208 (ref. 92)

16

12

96

243–245

244–246 (ref. 93)

17

18

14

92

89

240–242

245–247

241–243 (ref. 57)

244–246 (ref. 92)

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Table 2 (Contd.)

Entry

19

RCHO (3)

Product

Time (min)

Yield^b(%)

M.P. (Obsd) (^ꢀC)

M.P. (Lit) (^ꢀC)

15

91

218–221

218–220 (ref. 92)

20

21

20

18

92

89

210–213

259–262

211–212 (ref. 72)

260–261 (ref. 57)

22

18

94

205–207

204–206 (ref. 57)

23

24

20

90

88

247–249

237–240

246–248 (ref. 57)

238–240 (ref. 94)

25

45

72

148–150

147–148 (ref. 57)

a

Reaction conditions: dimedone or 1,3-cyclohexandione (1 mmol), ethyl acetoacetate or methyl acetoacetate (1 mmol), aldehydes (1 mmol),

ammonium acetate (1.2 mmol) and catalyst (10 mg) at 90 ^ꢀC. ^bIsolated yields.

obtained in EtOH aer 50 min from the start of the reaction and 11–12). It was found that using 10 mg of the Mo@GAA-

(Entry 2). To study the role of catalyst amount, the model Fe₃O₄MNPs is appropriate to carry out the reaction under

reaction was performed in the presence of 5, 10, 15, and 20 mg solvent-free conditions with a 96% yield. Aerward, the inu-

of Mo@GAA-Fe₃O₄MNPs (Entries 8 and 10–12). These obser- ence of temperature on the model reaction was investigated.

vations showed that carrying out the reaction in the absence of The reaction was carried out under diﬀerent temperatures (25,

ꢀ

the catalyst gave any yield for the desired product (Entry 9). The 40, 60, 80, 90, and 100 C) (Entries 8 and 13–17), and the best

reaction in presence of 5 mg of the catalyst provided a good result was achieved at 90 ^ꢀC under solvent-free conditions

yield of the product (Entry 10), while 10, 15, and 20 mg gave (Entry 8). Finally, when the model reaction was done in the

excellent-to-high yields of the corresponding product (Entries 8 existence of 10 mg of imine@SCMNPs, GAA/imine@SCMNPs

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Scheme 3 Proposed mechanism for the synthesis of polyhydroquinoline derivatives.

under the optimized conditions, the product yield were 86 and methyl acetoacetate, a wide range of aldehydes, and ammonium

88%, respectively (Entries 18–19). Comparing the product eﬃ- acetate (Table 2). Aromatic aldehydes with electron-donating or

ciencies for the inputs of 8 and 18–19, it could be fully under- electron-withdrawing groups tolerate smooth transformation to

stood that the coordination of the compound Mo@GAA-Fe₃O₄the corresponding products without the formation of by-

MNPs by free electron pair of nitrogen with the molybdenum products at better yields and in short reaction times. The

complex increased the catalytic activity.

reaction was also carried out with aliphatic aldehyde instead of

Utilizing the optimal reaction conditions, various poly- aromatic aldehyde but did not aﬀord the title products in

hydroquinolines were prepared by the four-component reaction considerable amounts (5y).

of dimedone, or 1,3-cyclohexandione, ethyl acetoacetate or

Fig. 9 The recycling of Mo@GAA-Fe₃O₄MNPs as catalysts under solvent-free conditions in the synthesis of 5p.

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Table 3 Comparison of the results of the production of products 5n

Catalyst

loading

Entry

Catalyst and conditions

Time (h)

Yield (%)

Ref.

1

2

3

4

5

6

7

8

Yb(OTf)₃/EtOH/r.t.

5 mol%

2 mol%

8 mg

2 mol%

10 mol%

25 mg

30 mg

10 mol%

75 mg

5

1.5

33 min

1

5

4

30 min

4

20 min

13 min

90

88

96

90

92

93

94

92

95

57

95

96

97

98

99

73

(NH₄)₆[Mn^IVMo₉O₃₂]/EtOH/r.t.

MgMnO₃/solvent-free/100 ^ꢀ

FePO₄/EtOH/reux

La₂O₃/TFE/r.t.

C

L-Proline/EtOH/reux

Sc(OTf)₃/EtOH/r.t.

Cu(^II)-DCC-CMK-3/solvent-free/80 ^ꢀ

C

100

101

102

This work

9

10

11

Al₂(SO₄)₃/EtOH/reux

Aluminized polyborate/solvent-free/100 ^ꢀC

Mo@GAA-Fe₃O₄MNPs/solvent-free/90 ^ꢀ

C

10 mg

The plausible mechanism for the synthesis of poly- any signicant changes in the reaction eﬃciency. Moreover,

hydroquinoline derivatives using Mo@GAA-Fe₃O₄MNPs has high yields of products, short reaction times, lower loading of

been shown in Scheme 3. The metallic parts of the catalyst play the catalyst, clean procedure, easy work-up, and heterogeneous

a noticeable role in this organic transformation. Initially, Mo reaction conditions are several advantages of this straightfor-

groups of the catalyst activate the C]O functional groups of ward and eﬃcient strategy.

aldehyde and facilitate the condensation with dimedone or 1,3-

cyclohexandione and aﬀord intermediate A. Then, Mo groups of

the catalyst also activate C]O functional groups of ethyl ace-

toacetate or methyl acetoacetate and increase the activity of this

group. The condensation of ethyl acetoacetate or methyl ace-

Conﬂicts of interest

There are no conicts to declare.

toacetate and ammonium acetate resulted in intermediate B.

The Michael addition of intermediate A with intermediate B

resulted in intermediate C. The achieved compound is unstable

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Article Doi

Mo@GAA-Fe3O4MNPs: a highly efficient and environmentally friendly heterogeneous magnetic nanocatalyst for the synthesis of polyhydroquinoline derivatives

DOI: 10.1039/d1ra00396h

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