A highly efficient magnetic solid acid nanocatalyst for the synthesis of new bulky heterocyclic compounds

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PAPER

A highly eﬃcient magnetic solid acid nanocatalyst

for the synthesis of new bulky heterocyclic

compounds

Cite this: RSC Adv., 2016, 6, 47298

*

Masoud Nasr-Esfahani, Zahra Raﬁee, Morteza Montazerozohori and Hassan Kashi

Fe₃O₄nanoparticles were prepared and coated with 3-aminopropyltriethoxysilane (APTES). The formed

amine-surfaced Fe₃O₄@APTES NPs were further chemically modiﬁed with maleic anhydride (MAH) to

generate Fe₃O₄@APTES$MAH NPs. This catalyst was characterized by FT-IR, X-ray diﬀraction (XRD),

scanning electron microscopy (SEM), transmission electron microscopy (TEM), thermogravimetric

analysis (TG), energy dispersive X-ray analyzer (EDAX), vibrating sample magnetometry (VSM) and the

dynamic light scattering (DLS) measurement technique. The catalyst showed high thermal stability and

good reusability. Some new bulky heterocyclic compounds such as bis(2,4,5-triarylimidazole), bis(1,4-

dihydropyridine), bis(1,8-dioxooctahydroxanthene) and bis(1,8-dioxo-decahydroacridine) derivatives were

synthesized using 4,4⁰-(alkylazanediyl)dibenzaldehyde as substrate and Fe₃O₄@APTES or

Fe₃O₄@APTES$MAH as catalyst. The high purity products were isolated and the catalyst was easily

separated with a simple work-up with magnetic ﬁeld and was recycled several times without noticeable

loss of reactivity under the described reaction conditions.

Received 29th January 2016

Accepted 4th May 2016

DOI: 10.1039/c6ra02749k

www.rsc.org/advances

molecules or surfactants functionalized Fe₃O₄NPs can be simply

divided to oil-soluble^22,23or water-soluble.^24,25For biomedical

Introduction

and many chemical applications, it is necessary to obtain water

dispersible NPs.

Magnetic iron oxide (Fe₃O₄) nanoparticles have been widely

used as a heterogeneous catalyst for the synthesis of heterocy-

clic compounds such as a-aminophosphonates,¹2,3-dihy-

droquinazolin-4(1H)-ones,²dihydropyrimidinone,³pyrans,⁴1,4-

dihydropyridines,⁵calix(4)resorcinarenes,⁶xanthenes,⁷acri-

dines,⁸imidazoles,⁹Aza-Sakurai reaction¹⁰and Strecker reac-

tion.¹¹This compound has been investigated for various

applications in biomedical sciences including detoxication of

biological uids, anti-cancer drug delivery, food analysis, envi-

ronmental treatment and magnetic resonance imaging

(MRI).^12–19

The magnetic iron oxide NPs have intrinsic instability over

longer periods, because they have hydrophobic surfaces and in

the absence of any proper surface coating, and the hydrophobic

interactions between the NPs will cause them to aggregate and

therefore, form large clusters, resulting in increased particle size

and to reduce the surface energy.²⁰Also magnetic particles lose

their magnetism over time because bare iron oxide nano-

particles are easily oxidized in the air because of their high

chemical activity, especially Fe₃O₄and g-Fe₂O₃NPs.²¹Therefore,

it is important to develop a proper protection strategy to chem-

ically stabilize bare iron oxide nanoparticles against damage

during or aer the subsequent application. According to the

surface characteristics of the functionalized nanoparticles, small

3-Aminopropyltriethyloxysilane (APTES) agent was mostly

employed for providing the amino group.²⁶This agent is

considered as a candidate for modication on the surface of

Fe₃O₄NPs. The high density of the surface functional group of

NH₂, allowing for connecting to other targeting biomolecules

and display well dispersion and stability in aqueous solvents,

with retention of their physical characteristics of super-

paramagnetism with high saturation magnetization.²⁷The

functional group of NH₂was reacted with other group and new

catalysts such as Pd(^II)–phosphine complexes,²⁸Fe₃O₄-APTES-N-

(2-aminoethyl)acrylamide,²⁹

Fe₃O₄–APTES–quinuclidine,³⁰

magnetic nanoparticles-crown,³¹polyaniline/Fe₃O₄,³²Nap-

roxen–APTES–Fe₃O₄,³³Fe₃O₄–APTES–PEG³⁴and Fe₃O₄–APTES–

TCNP³⁵were synthesized. Some of these catalysts like Fe₃O₄@

APTES$Ac, Fe₃O₄@APTES$SAH,³⁶Fe₃O₄–APTES$SO₃H^37,38are

acidic and Fe₃O₄@APTS–Py,³⁹MNP–NMe₂, MNP–NH₂(ref. 40)

and Fe₃O₄@APTES@Ni(OH)₂(ref. 41) are basic catalysts.

1,4-Dihydropyrdines have been reported as neurotropic,⁴²

anticancer,⁴³antidiabetic⁴⁴and glycoprotein inhibitors agents.⁴⁵

Various clinically used cardiovascular agents such as nicardi-

pine, amlodipine, nifedipine, and other related derivatives are

dihydropyridyl compounds eﬀective in the treatment of hyper-

tension.⁴⁶Recently, studies showed that 1,4-dihydropyridine

derivatives with lipophilic groups have considerable antituber-

cular activity against M. tuberculosis H37Rv.^47,48

Department of Chemistry, Yasouj University, Yasouj 75918-74831, Iran. E-mail:

manas@yu.ac.ir

47298 | RSC Adv., 2016, 6, 47298–47313

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1,8-Dioxooctahydroxanthenes are an important class of

RSC Advances

The imidazole derivatives especially triarylimidazole have

heterocyclic compounds. They have been found in a large many biological activities, for example, pharmaceuticals,⁶⁶act

number of naturally occurring molecules. Due to their wide- as B-Raf kinase,⁶⁷inhibitors of p38 MAP kinase,⁶⁸antitumorals⁶⁹

ranging therapeutic and biological properties such as anti- and glucagon receptors.⁷⁰

viral,⁴⁹antibacterial⁵⁰and photodynamic therapy,⁵¹the

synthesis of these compounds has attracted the attention of dures for the preparation of these types of compounds by using

chemical and pharmaceutical researchers. of new catalyst are active ongoing research area, and there will

Therefore, the development of versatile and eﬃcient proce-

Bucricaine, Proavine and Amsacrine are acridine derivatives be a scope for further improvement toward low reaction times,

and used topically for surface anesthesia of eye, bacteriostatic improved yields and milder reaction conditions.

and antineoplastic respectively.^52,53In addition, 1,8-dioxo-

In this study, we want to report synthesis of new magnetically

decahydroacridines used as laser dyes, photoinitiators, anti- recoverable Brønsted acidic catalyst for the preparation of some

tumor, antimalaria, fungicidal and widely prescribed as calcium new bulky heterocyclic compounds. For this purpose, we

b-blockers.^54–59

present a simple APTS-assisted hydrothermal approach to

2-Pyridones attracted attention due to their applications as synthesizing APTS-coated Fe₃O₄NPs with reactive surface

bioactive compounds for example as antibacterial,⁶⁰antifungal,⁶¹amine groups. The surface-reactive amine groups of Fe₃O₄NPs

as a promising class of HIV-1 non-nucleoside reverse transcrip- were further carboxylated by reacting with MAH (Fe₃O₄@

tase inhibitors,⁶²antibiotics,⁶³sedative⁶⁴and cardiotonic agents.⁶⁵APTES$MAH). The catalyst was characterized by X-ray

Scheme 1 Synthesis of new bulky heterocyclic compounds using 4,4-(alkylazanediyl)dibenzaldehyde as the substrate in the presence of Fe₃-

O₄@APTES$MAH NPs (Cat. A) or Fe₃O₄@APTES (Cat. B) as catalyst.

This journal is © The Royal Society of Chemistry 2016

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diﬀraction (XRD), transmission electron microscopy (TEM), the solid. Then it was collected by ltration, washed with water

Fourier transform infrared spectrometry (FT-IR), thermog- and dried to give the pure product.

ravimetry analysis (TGA), dynamic light scattering (DLS)

N-Butyl-4-(4,5-diphenyl-1H-imidazol-2-yl)-N-(4-(4,5-diphenyl-

diagrams and vibrating scanning magnetometry (VSM). In the 1H-imidazol-2-yl)phenyl)aniline (3). Pale yellow solid; mp: 86–

following some bulky heterocyclic compounds such as 1,4- 88 ^ꢀC; yield: 78% (0.49 g); IR (KBr, cm^ꢁ1): 3316, 3062, 2925,

1

dihydropyrdine, 1,8-dioxooctahydroxanthene, 1,8-dioxo-decahy- 2885, 1660, 1592, 1450, 1322, 1211, 1172; H NMR (400 MHz,

droacridine, 2-pyridone and imidazole derivatives were CDCl₃) d (ppm): 9.91 (2H, s, N–H), 8.00 (12H, d, J ¼ 7.2 Hz, Ar-

prepared using Fe₃O₄@APTES or Fe₃O₄@APTES$MAH NPs as H), 7.69 (4H, t, J ¼ 7.4 Hz, Ar-H), 7.54 (12H, t, J ¼ 7.7 Hz, Ar-H),

catalyst (Scheme 1).

3.87 (2H, t, J ¼ 7.5 Hz, N–CH₂), 1.70–1.59 (2H, m, CH₂), 1.42–

1.27 (2H, m, CH₂), 0.97 (3H, t, J ¼ 7.3 Hz, CH₃); ¹³C NMR (100

MHz, CDCl₃) d (ppm): 194.61, 134.93, 132.99, 131.61, 130.10,

130.06, 129.94, 129.05, 128.65, 120.73, 54.90, 45.75, 41.65,

10.70; anal. calcd C₄₆H₃₉N₅: C 83.48, H 5.94, N 10.58; found: C

83.29, H 5.90, N 10.53.

Experimental

Chemicals were purchased from Merck or Aldrich. FT-IR spectra

were recorded from KBr discs on a JASCO FT-IR-680. NMR

spectra were taken with a Bruker 400 MHz Ultrashield spec-

trometer at 400 MHz (¹H) and 100 MHz (¹³C) using CDCl₃or

DMSO-d₆as the solvent with TMS as the internal standard.

Thermal degradation of catalyst was carried out in the range 28–

4-(4,5-Diphenyl-1H-imidazol-2-yl)-N-(4-(4,5-diphenyl-1H-imi-

dazol-2-yl)phenyl)-N-hexylaniline (4). Brown solid; mp: 140–142

^ꢀC; yield: 68% (0.47 g); IR (KBr, cm^ꢁ1): 3324, 3059, 2925, 2859,

1

1670, 1602, 1457, 1320, 1218, 1180; H NMR (400 MHz, CDCl₃)

d (ppm): 10.31 (2H, s, N–H), 7.96 (4H, t, J ¼ 8.4 Hz, Ar-H), 7.54

(8H, d, J ¼ 7.97 Hz, Ar-H), 7.34 (12H, t, J ¼ 7.84 Hz, Ar-H), 7.10

(4H, t, J ¼ 7.35 Hz, Ar-H), 3.79 (2H, t, J ¼ 7.7 Hz, N–CH₂), 1.76–

1.68 (2H, m, CH₂), 1.36–1.25 (6H, m, 3CH₂), 0.90 (3H, t, J ¼ 6.8

Hz, CH₃); ¹³C NMR (100 MHz, CDCl₃) d (ppm): 189.78, 140.85,

136.46, 132.42, 131.06, 130.25, 130.05, 127.84, 120.11, 116.80,

51.54, 31.99, 31.50, 26.56, 22.63, 14.02; anal. calcd C₄₈H₄₃N₅: C

83.57, H 6.28, N 10.15; found: C 83.41, H 6.24, N 10.09.

ꢁ1

ꢀ

800 C at a heating rate of 10 C min under nitrogen atmo-

sphere using thermogravimetric analyzer-TG-209 F3, Netzsch,

Germany. Energy dispersive X-ray spectroscopy analyses (EDAX)

were carried out on a PHILIPS XL30, operated at a 20 kV

accelerating voltage. The optical rotation was obtained with

Jasco p-1030 polarimeter. Surface morphology and particle size

were studied using a KYKY-EM-32000 SEM instrument and the

X-ray diﬀraction (XRD) patterns of polymer and catalyst were

recorded using an XRD (Bruker, D8 Advance, Rheinstetten,

Germany) with a copper target at 40 kV and 35 mA and Cu Ka

Synthesis of compounds 5 and 6

ꢁ1

ꢀ

˚

(l ¼ 1.54 A) in the range of 10–80 at the speed of 0.05 min

.

A mixture of 4,4-(butylazanediyl)dibenzaldehyde (1, 1 mmol,

0.28 g), 5,5-dimethyl-1,3-cyclohexanedione (4 mmol, 0.56 g),

Fe₃O₄@APTES$MAH NPs (0.06 g) and 2 mmol amine (ammo-

nium acetate, 0.15 g or aniline, 0.19 g) into a 25 mL round

bottomed ask was heated at 70 ^ꢀC in ethanol–water (8 mL, v/v

¼ 1) for 55 or 48 min (for compounds 5 or 6, respectively). The

reaction mixture was cooled to room temperature and solid

catalyst separated by a magnet. The reaction mixture was

concentrated on a rotary evaporator under reduced pressure

and the obtained solid product was recrystallized in ethanol.

9,9-((Butylazanediyl)bis(1,4-phenylene))bis(3,3,6,6-tetramethyl-

3,4,6,7,9,10-hexahydroacridine-1,8(2H,5H)-dione) (5). Yellow

Magnetic characterization was carried out on a vibrating sample

magnetometer (MDKB) at room temperature and the melting

points were determined using an electrothermal digital melting

point apparatus and are uncorrected. Reaction courses and

product mixtures were monitored by thin layer chromatography

(TLC).

Preparation of the catalyst

Fe₃O₄@APTES (500 mg) was dispersed in ethanol (5 mL) using

ultrasonic bath for 30 min. Subsequently, maleic anhydride

(1.47 g) was dissolved in DMSO (5 mL) and added dropwise over

a period of 20 min at room temperature under vigorous stirring.

The mixture was stirred for 24 h and the functionalized nano-

particles were separated by centrifugation. Then the solid

catalyst was washed with dry CH₂Cl₂and was subsequently

separated using centrifugation and nally dispersed in ethanol.

solid; mp: 231–233 C; yield: 80% (0.58 g); IR (KBr, cm^ꢁ1): 3428,

ꢀ

2956, 2869, 1631, 1612, 1506, 486, 1222; ¹H NMR (400 MHz,

DMSO-d₆) d (ppm): 8.81 (2H, s, NH), 7.12 (4H, d, J ¼ 8.5, Ar-H),

6.73 (4H, d, J ¼ 8.5, Ar-H), 5.03 (2H, s, 2 ꢂ CH), 3.70 (2H, t, J ¼

6.5 Hz, N–CH₂), 2.33 (4H, d, 2 ꢂ CH₂, J ¼ 18 Hz), 2.21 (4H, d, 2 ꢂ

CH₂, J ¼ 16.3 Hz), 2.06 (8H, s, 4 ꢂ CH₂), 1.54–1.51 (2H, m, CH₂),

1.29–1.24 (2H, m, CH₂), 1.09 (12H, s, 4 ꢂ CH₃), 1.00 (12H, s, 4 ꢂ

CH₃), 0.88 (3H, t, J ¼ 5.5 Hz); ¹³C NMR (100 MHz, CDCl₃) d (ppm):

Synthesis of compounds 3 and 4

A mixture of ammonium acetate (8 mmol, 0.62 g) and benzoin 198.68 (C]O), 151.39 (C]C), 147.07, 128.43, 120.26, 119.96 (Ar-

(2 mmol, 0.42 g) was dissolved in ethanol–water mixture (8 mL, C), 115.19 (C]C), 60.42 (4 ꢂ CH₂), 58.50 (CH₂), 50.79 (4 ꢂ

1 : 1, v/v) and to the reaction mixture 1 mmol of dialdehyde (1, CH₂), 32.74 (2 ꢂ CH), 29.43 (4 ꢂ C(CH₃)₂), 27.33 (CH₂), 21.08 (8 ꢂ

0.281 g, or 2, 0.309 g) and Fe₃O₄@APTES$MAH NPs (0.08 g) were CH₃), 18.45 (CH₂), 14.14 (CH₃); anal. calcd C₅₀H₆₁N₃O₄: C 78.19, H

added. Then, the reaction mixture was heated at 70 ^ꢀC for 130 or 8.01, N 5.47, O 8.33; found: C 78.03, H 7.95, N 5.43.

145 min (3 or 4, respectively). The reaction mixture was cooled

9,9-((Butylazanediyl)bis(1,4-phenylene))bis(3,3,6,6-tetra-

to room temperature and solid catalyst separated by a magnet. methyl-10-phenyl-3,4,6,7,9,10-hexahydroacridine-1,8(2H,5H)-

The reaction mixture was poured into ice-water (5 mL) to obtain dione) (6). Pale yellow solid; mp: 169–171 ^ꢀC; yield: 77% (0.71 g);

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IR (KBr, cm^ꢁ1): 3062, 2960, 1596, 1571, 1494, 1243; ¹H NMR (400 CH₃), 0.94 (3H, t, J ¼ 6.7 Hz, CH₃); ¹³C NMR (100 MHz, CDCl₃)

MHz, CDCl₃) d (ppm): 7.61 (2H, d, J ¼ 8.78 Hz, Ar-H), 7.86 (4H, t, d (ppm): 190.23 (C]O), 189.28 (–C]O, aldehyde), 160.02 (C]

J ¼ 7.86 Hz, Ar-H), 7.18 (4H, d, J ¼ 7.74 Hz, Ar-H), 7.13 (4H, t, J ¼ C), 145.93, 131.79, 130.16, 129.42, 128.51, 127.59, 127.20,

7.35 Hz, Ar-H), 6.68–6.64 (4H, m, Ar-H), 5.31 (2H, s, CH), 3.69 125.62, 123.84, 120.51, 115.73, 115.15 (Ar-C), 113.25 (C]C),

(2H, t, J ¼ 7.67 Hz, N–CH₂), 2.38 (8H, s, 4 ꢂ CH₂), 2.05 (8H, s, 4 50.33 (2 ꢂ CH₂), 47.08 (CH₂), 46.47 (2 ꢂ CH₂), 43.76 (CH), 31.37

ꢂ CH₂), 1.32–1.18 (4H, m, 2 ꢂ CH₂), 1.03 (24H, s, 8 ꢂ CH₃), 0.87 (2 ꢂ C(CH₃)₂), 29.75 (CH₂), 27.38 (4 ꢂ CH₃), 20.31 (CH₂), 13.96

(3H, t, J ¼ 7.74 Hz, CH₃), ¹³C NMR (100 MHz, CDCl₃) d (ppm): (CH₃); anal. calcd C₄₀H₄₄N₂O₃: C 79.97, H 7.38, N 4.66, O 7.99;

195.36 (C]O), 160.01 (C]C), 139.14, 139.04, 129.17, 124.29, found: C 79.83, H 7.35, N 4.64.

122.92, 122.87, 122.80, 122.75 (Ar-C), 110.73 (–C]C), 50.12 (4 ꢂ

CH₂), 41.99 (CH₂), 41.93 (CH₂), 32.25 (4 ꢂ CH₂), 27.92 (2 ꢂ CH),

Synthesis of compound 9

29.55 (4 ꢂ C(CH₃)₂), 29.09 (CH₂), 28.03 (8 ꢂ CH₃), 20.07 (CH₂),

13.85 (CH₃); anal. calcd C₆₂H₆₉N₃O₄: C 80.92, H 7.56, N 4.57, O

6.95; found: C 80.79, H 7.53, N 4.54.

Into a 25 mL round bottomed ask, the mixture of 4,4⁰-(hex-

ylazanediyl)dibenzaldehyde 2 (1 mmol, 0.31 g), ammonium

acetate (1.5 mmol, 0.12 g) and methyl acetoacetate (4 mmol,

0.46 g) and Fe₃O₄@APTES$MAH NPs (0.05 g) was heated at

70 ^ꢀC under solvent free conditions. Aer completion of the

reaction (40 min), the mixture was cooled to room temperature

and then ethanol (5 mL) was added to the resulting mixture and

catalyst separated by a magnet. Aer evaporation of solvent, the

solid product was ltered and recrystallized from ethanol to

give the pure products.

Synthesis of compounds 7 and 8

Into a 25 mL round bottomed ask, a mixture of 4,4⁰-(butyla-

zanediyl)dibenzaldehyde 1 (1 mmol, 0.28 g), 5,5-dimethyl-1,3-

cyclohexanedione (2 mmol, 0.28 g), Fe₃O₄@APTES$MAH NPs

(0.03 g) and 1 mmol amine (ammonium acetate, 0.08 g or

aniline, 0.09 g) was reuxed in ethanol–water mixture (8 ml, v/v

¼ 1) for 40 or 45 min (for compounds 7 or 8, respectively). The

reaction mixture was cooled to room temperature and solid

catalyst separated by a magnet. The reaction mixture was

concentrated using a rotary evaporator under reduced pressure

and the solid product was recrystallized in ethanol.

4-(Butyl(4-(3,3,6,6-tetramethyl-1,8-dioxo-1,2,3,4,5,6,7,8,9,10-

decahydroacridin-9-yl)phenyl)amino)benzaldehyde (7). Pale

yellow solid; mp: 161–163 ^ꢀC; yield: 68% (0.36 g); [a]²_D⁰¼ +109.2^ꢀ

(c ¼ 0.21 g mL^ꢁ1, CHCl₃); IR (KBr, cm^ꢁ1): 3066, 3028, 2956,

2871, 1643, 1608, 1608, 1484, 1220; ¹H NMR (400 MHz, DMSO-

d₆) d (ppm): 9.71 (1H, s, CHO), 8.32 (1H, s, NH), 7.81 (2H, d, J ¼

8.1, Ar-H), 7.08 (2H, d, J ¼ 8.5, Ar-H), 6.91 (2H, d, J ¼ 8.1, Ar-H),

6.40 (2H, d, J ¼ 8.5, Ar-H), 4.73 (1H, s, CH), 4.14 (1H, q, J ¼ 5.3

Hz, N–CH₂), 3.75 (1H, q, J ¼ 7.6 Hz, N–CH₂), 2.52 (2H, d, CH₂, J

¼ 18 Hz), 2.45 (2H, d, CH₂, J ¼ 16.3 Hz), 2.16 (4H, s, 2 ꢂ CH₂),

Tetramethyl 4,4⁰-((hexylazanediyl)bis(4,1-phenylene))bis(2,6-

dimethyl-1,4-dihydropyridine-3,5-dicarboxylate) (9). Brown

solid; mp: 92–94 C; yield: 86% (0.61 g); IR (KBr, cm^ꢁ1): 3338,

ꢀ

3091, 2950, 2927, 2854, 1697, 1506, 1488, 1432, 1305, 1216,

1118, 1097; ¹H NMR (400 MHz, CDCl₃) d (ppm): 7.11 (4H, d, J ¼

8.5 Hz, Ar-H), 6.78 (4H, d, J ¼ 8.5 Hz, Ar-H), 5.83 (2H, s, N–H),

4.95 (2H, s, CH), 3.68 (12H, s, 4 ꢂ O–CH₃), 3.57 (2H, t, J ¼ 7.7

Hz, N–CH₂), 2.34 (12H, s, 4 ꢂ CH₃), 1.61 (2H, brs, CH₂), 1.24–

1.36 (6H, m, 3CH₂), 0.88 (3H, t, J ¼ 6.6 Hz, CH₃); ¹³C NMR (100

MHz, CDCl₃) d (ppm): 168.27, 146.32, 144.05, 139.89, 128.24,

120.24, 104.03, 52.36, 51.02, 38.32, 31.66, 29.71, 26.75, 22.70,

19.56, 14.05; anal. calcd C₄₀H₄₉N₃O₈: C 68.65, H 7.06, N 6.00, O

18.29; found: C 68.50, H 7.02, N 5.96.

Synthesis of compounds 10 and 11

1.56–1.48 (2H, m, CH₂), 1.34–1.26 (2H, m, CH₂), 1.10 (6H, s, 2 ꢂ A mixture of 4,4⁰-(butylazanediyl)dibenzaldehyde 1 (1 mmol,

CH₃), 1.00 (6H, s, 2 ꢂ CH₃), 0.90 (3H, t, J ¼ 5.5 Hz); ¹³C NMR 0.28 g), 5,5-dimethyl-1,3-cyclohexanedione (4 mmol 0.56 g for

(100 MHz, DMSO-d₆) d (ppm): 194.22 (C]O), 191.05 (–C]O, 10; 2 mmol 0.28 g for 11) and Fe₃O₄@APTES$MAH NPs (0.08 g

aldehyde), 149.54 (C]C), 152.14, 148.65, 138.12, 130.85, 128.76, for 10; 0.04 g for 11) into a 25 mL round bottomed ask, was

127.29, 119.62, 113.81 (Ar-C), 112.80 (C]C), 50.12 (2 ꢂ CH₂), heated in an oil bath at 70 ^ꢀC under solvent-free conditions.

46.16 (CH₂), 40.86 (2 ꢂ CH₂), 39.71 (CH), 31.85 (2 ꢂ C(CH₃)₂), Aer completion of the reaction (35 min, 10; 45 min, 11) the

29.09 (CH₂), 28.03 (4 ꢂ CH₃), 20.07 (CH₂), 13.85 (CH₃); anal. resulting solid was cooled and dichloromethane (5 mL) added

calcd C₃₄H₄₀N₂O₃: C 77.83, H 7.68, N 5.34, O 9.15; found: C and stirred for a few minutes. Then, the catalyst was separated

77.71, H 7.63, N 5.30.

by magnet. The remained solution was kept overnight and the

4-(Butyl(4-(3,3,6,6-tetramethyl-1,8-dioxo-10-phenyl-1,2,3,4,5, crude product recrystallized from ethanol to aﬀord the pure

6,7,8,9,10-decahydroacridin-9-yl)phenyl)amino)benzaldehyde

product.

20

ꢀ

(8). Orange solid; mp: 106–109 C; yield: 70% (0.42 g); [a]_D

¼

9,9⁰-((Butylazanediyl)bis(1,4-phenylene))bis(3,3,6,6-tetra-

+71.5^ꢀ(c ¼ 0.33 g mL^ꢁ1, CHCl₃); IR (KBr, cm^ꢁ1): 2956, 2923, methyl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2H)-dione) (10).

1

ꢀ

2869, 1642, 1592, 1508, 1448, 1249; H NMR (400 MHz, CDCl₃) Green-blue solid; mp: 225–227 C; yield: 82% (0.63 g); IR (KBr,

d (ppm): 9.74 (1H, s, CHO), 7.66 (2H, d, J ¼ 8.8 Hz, Ar-H), 7.38– cm^ꢁ1): 2958, 2930, 1665, 1623, 1509, 1359, 1197, 1137; ¹H NMR

7.17 (4H, m, Ar-H), 7.12 (1H, d, J ¼ 5.5 Hz, Ar-H), 6.96 (2H, d, J ¼ (400 MHz, CDCl₃) d (ppm): 7.09 (4H, d, J ¼ 8.5 Hz, Ar-H), 6.76

8.5, Ar-H), 6.88 (2H, d, J ¼ 8.6 Hz, Ar-H), 6.70 (2H, d, J ¼ 8.5 Hz, (4H, d, J ¼ 8.5 Hz, Ar-H), 4.70 (2H, s, CH), 3.53 (2H, t, J ¼ 7.5 Hz,

Ar-H), 5.49 (1H, s, CH), 3.71 (1H, t, J ¼ 7.6 Hz, N–CH₂), 3.62 (1H, N–CH₂), 2.48 (8H, s, 4 ꢂ CH₂), 2.23 (8H, s, 4 ꢂ CH₂), 1.53 (2H,

t, J ¼ 7.6 Hz, N–CH₂), 2.45 (2H, d, J ¼ 13.4 Hz, CH₂), 2.38 (2H, d, m, CH₂), 1.26 (2H, m, CH₂), 1.11 (12H, s, 4 ꢂ CH₃), 1.01 (12H, s,

J ¼ 16.0 Hz, CH₂), 2.26 (4H, s, 2 ꢂ CH₂), 1.39–1.33 (2H, m, CH₂), 4 ꢂ CH₃), 0.88 (3H, t, J ¼ 7.3 Hz, CH₃); ¹³C NMR (100 MHz,

1.28–1.24 (2H, m, CH₂), 1.14 (6H, s, 2 ꢂ CH₃), 1.11 (6H, s, 2 ꢂ CDCl₃) d (ppm): 196.57 (C]O), 162.13 (C]C), 146.2, 136.4,

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128.8, 120.31 (Ar-C), 115.83 (C]C), 50.83 (4 ꢂ CH₂), 40.87 0.32 g), malononitrile (2 mmol, 0.13 g) in methanol (10 mL) was

(CH₂), 32.23 (4 ꢂ CH₂), 30.77 (2 ꢂ CH), 29.55 (4 ꢂ C(CH₃)₂), divided into two equal parts. Into the rst part in a 25 mL round

29.20 (CH₂), 27.50 (8 ꢂ CH₃), 20.20 (CH₂), 13.91 (CH₃); anal. bottomed ask, suspension of Fe₃O₄@APTES (0.1 g) in meth-

calcd C₅₀H₅₉NO₆: C 77.99, H 7.72, N 1.82, O 12.47; found: C anol (5 mL) was added and reuxed for 8 h. The reaction

77.83, H 7.68, N 1.80.

mixture was cooled to room temperature and solid catalyst

4-(Butyl(4-(3,3,6,6-tetramethyl-1,8-dioxo-2,3,4,5,6,7,8,9-octa- separated by a magnet. The reaction mixture was concentrated

hydro-1H-xanthen-9-

yl)phenyl)amino)benzaldehyde

(11). under reduced pressure and then water (5 mL) was added. The

Orange solid; mp: 72–74 ^ꢀC; yield: 69% (0.36 g); [a]²_D⁰¼ +23.5^ꢀ(c obtained solid product was ltered oﬀ, dried and recrystallized

¼ 0.3 g mL^ꢁ1, CHCl₃); IR (KBr, cm^ꢁ1): 2963, 2935, 2871, 1728, from ethanol.

1

1663, 1623, 1509, 1359, 1195, 1145; H NMR (400 MHz, CDCl₃)

Into the second part of the above mixture, catalytic amount

d (ppm): 9.91 (1H, s, CHO), 7.81 (2H, d, J ¼ 8.4 Hz, Ar-H), 7.09 of triethylamine (0.2 mL) in methanol (10 mL) was added and

(2H, d, J ¼ 8.5 Hz, Ar-H), 6.91 (2H, d, J ¼ 8.5, Ar-H), 6.76 (2H, d, J heated under reux conditions for 4 h. The reaction mixture was

¼ 8.5 Hz, Ar-H), 4.73 (1H, s, CH), 3.53 (2H, t, J ¼ 7.5 Hz, N–CH₂), kept at room temperature for 1 h and then 5 mL cold water was

2.48 (4H, s, 2 ꢂ CH₂), 2.19 (4H, s, 2 ꢂ CH₂), 1.51 (2H, m, CH₂), added. Then the solid product was isolated and recrystallized

1.25 (2H, m, CH₂), 1.11 (6H, s, 2 ꢂ CH₃), 1.01 (6H, s, 2 ꢂ CH₃), from ethanol.

0.88 (3H, t, J ¼ 7.3 Hz, CH₃); ¹³C NMR (100 MHz, CDCl₃)

Method B. A solution of compound 12 (1 mmol, 0.57 g) and

d (ppm): 201.20 (–C]O, aldehyde), 197.54 (C]O), 162.95 (C] malononitrile (2 mmol, 0.13 g) in 1,4-dioxane (15 mL) and

C), 148.65, 138.12, 130.85, 128.65, 127.29, 113.81(Ar-C), 112.80 dimethylformamide (7 mL) was divided into two equal parts. In

(C]C), 50.05 (2 ꢂ CH₂), 46.10 (CH₂), 40.86 (2 ꢂ CH₂), 37.71 a 25 mL round bottomed ask into the rst part of the solution,

(CH), 31.85 (2 ꢂ C(CH₃)₂), 29.09 (CH₂), 28.18 (4 ꢂ CH₃), 20.07 Fe₃O₄@APTES (0.1 g) was added and heated at 70 ^ꢀC for 9 h. The

(CH₂), 13.83 (CH₃); anal. calcd C₃₄H₃₉NO₄: C 77.68, H 7.48, N reaction mixture was cooled to room temperature and solid

2.66, O 12.17; found: C 77.52, H 7.44, N 2.63.

catalyst separated by a magnet and the residual was poured into

ice/water containing 2 drops of hydrochloric acid. The solid

products were collected and recrystallized from 1,4-dioxane.

Into second part of the solution, triethylamine (0.2 mL) was

added and heated under reux for 5 h. Then the mixture was

cooled and poured into ice/water containing 2 drops of

concentrated HCl. The solid products were collected and

recrystallized from 1,4-dioxane (Scheme 4).

Synthesis of compound 12

A solution of 2-cyano-N-phenylacetamide (14, 2 mmol, 0.32 g)

and 4,4⁰-(butylazanediyl)dibenzaldehyde (1, 1 mmol, 0.28 g) in

1,4-dioxane (10 mL) was divided into two equal parts. Into the

rst part in a 25 mL round bottomed ask, Fe₃O₄@APTES (0.1 g)

was added and heated at 70 ^ꢀC for 7 h, cooled to room

temperature and solid catalyst was separated by a magnet. The

residual solution was poured into the mixture of ice-water

containing two drops of HCl and the solid product was

collected by ltration and recrystallized from 1,4-dioxane. Into

the second part of the solution, triethylamine (0.2 mL) was

added and the reaction mixture was heated under reux

conditions for 4 h. The reaction mixture was poured into the

mixture of ice-water and two drops of HCl. The solid product

was collected by ltration and recrystallized from 1,4-dioxane.

3,3⁰-((Butylazanediyl)bis(1,4-phenylen))bis(2-cyano-N-phe-

nylacrylamide) (12). Orange solid, mp: 140–142 ^ꢀC; yields: part 1,

0.43 g, 75%; part 2, 0.50 g, 88%; IR (KBr, cm^ꢁ1): 3328, 3056, 2956,

4,4⁰-((Butylazanediyl)bis(4,1-phenylene))bis(6-amino-2-oxo-

1-phenyl-1,2-dihydropyridine-3,5-dicarbonitrile)

(13).

Pale

ꢀ

brown solid; mp: 154–157 C; yields: method A: part 1, 0.313 g

45%; part 2, 0.502 g 72%; method B: part 1, 0.278 g 40%; part 2,

0.453 g 65%; IR (KBr, cm^ꢁ1): 3270, 3208, 3052, 2956, 2260, 2211,

1

1668, 1600, 1508, 1488, 1392, 1187; H NMR (400 MHz, CDCl₃)

d (ppm): 7.72 (4H, brs, 2NH₂), 7.53 (8H, d, J ¼ 7.9 Hz, Ar-H), 7.40

(8H, t, J ¼ 7.8 Hz, Ar-H), 7.23 (2H, t, J ¼ 7.3, Ar-H), 3.76 (2H, t, J ¼

7.0 Hz, N–CH₂), 1.32–1.37 (2H, m, CH₂), 1.16–1.23 (2H, m, CH₂),

0.89 (3H, t, J ¼ 7.0 Hz, CH₃); ¹³C NMR (100 MHz, CDCl₃)

d (ppm): 160.99, 149.95, 149.88, 147.16, 138.34, 130.32, 128.89,

128.62, 123.85, 120.53, 119.16, 119.06, 115.93, 74.76, 45.64,

26.71, 19.52, 13.79; anal. calcd C₄₂H₃₁N₉O₂: C 72.71, H 4.50, N

18.17, O 4.61; found: C 72.58, H 4.48, N 18.10.

1

2927, 2206, 1675, 1590, 1535, 1504, 1438, 1313, 1180, 827; H

NMR (400 MHz, CDCl₃) d (ppm): 9.85 (1H, s, N–H), 9.82 (1H, s, N–

H), 8.28 (1H, s, CH]C), 8.26 (1H, s, CH]C), 7.91–7.86 (4H, dd, J₁

¼ 11.0 Hz, J₂¼ 8.8 Hz, Ar-H), 7.76 (4H, dd, J₁¼ 14.0 Hz, J₂¼ 8.7

Hz, Ar-H), 7.32 (4H, t, J ¼ 7 Hz, Ar-H), 7.11 (4H, dd, J₁¼ 10.1 Hz, J₂

¼ 8.9 Hz), 7.03 (2H, d, J ¼ 8.8 Hz), 3.79 (2H, t, J ¼ 7.7 Hz, N–CH₂),

1.61–1.66 (2H, m, CH₂), 1.31–1.34 (2H, m, CH₂), 0.89 (3H, t, J ¼

5.8 Hz, CH₃); ¹³C NMR (100 MHz, CDCl₃) d (ppm): 190.55, 152.66,

133.04, 131.61, 129.21, 125.94, 121.94, 120.97, 120.73, 120.42,

119.79, 52.33, 29.67, 20.21, 13.84; anal. calcd C₃₆H₃₁N₅O₂: C,

76.44; H, 5.52; N, 12.38; O, 5.66; found: C 76.30, H 5.49, N 12.33.

Results and discussion

Because of the high surface energy, the naked Fe₃O₄nano-

particles are generally unstable and aggregate easily and alter

magnetic properties. In addition, Fe₃O₄nanoparticles are

highly susceptible to be oxidized to g-Fe₂O₃nanoparticles in the

presence of oxygen.⁷¹To overcome such limitations, various

surface modication methods have been developed to modify

the surface of naked Fe₃O₄nanoparticles.^72,73With proper

surface modication, the stability and dispersity of Fe₃O₄

nanoparticles could be improved, and the oxidation process

Synthesis of compound 13

Method A. A mixture of 4,4⁰-(butylazanediyl)dibenzaldehyde from Fe₃O₄nanoparticles to g-Fe₂O₃nanoparticles could be

1 (1 mmol, 0.28 g), 2-cyano-N-phenylacetamide (14, 2 mmol, greatly slowed down.

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Fe₃O₄MNPs were prepared using procedure described in the in DMSO and the functionalized nanoparticles were separated

literature⁷⁴and subsequently were coated with 3-amino- using centrifugation (Scheme 2). MAH contains carboxylic acid

propyltriethoxysilane to achieve amino functionalized magnetic groups so, it can activate the electrophilic compounds by

nanoparticles Fe₃O₄@APTES MNPs.²⁶

hydrogen bonding and lone pairs.

MAH was used for further modication of Fe₃O₄@APTES

As can be seen in Scheme 2, Fe₃O₄as a Lewis acid and the

MNPs. A very useful property of the MAH moieties is their free carboxyl groups on the surface of MAH provide the solid

spontaneous reactivity towards primary amines, which can be acid catalyst and play a signicant role in increasing the elec-

easily modied surface NPs. Each MAH ring yields a free trophilic character of the dialdehyde and so can activate the

carboxylic group aer reaction with the amine. This was carbonyl group of aldehyde to decrease the energy of transition

resulting in NPs with increased stability, e.g. in a biological state for the nucleophilic attack. Considering the super-

environment.⁷⁵For preparation of Fe₃O₄@APTES$MAH paramagnetic properties and the ease chemical modication,

magnetic nanoparticles, the dispersed Fe₃O₄@APTES in this solid acid catalyst can use in many organic reactions as

ethanol was dropwise added to a solution of maleic anhydride a solid acidic catalyst.

Characterization and stability of the catalyst

Fig. 1 indicates the FT-IR spectra of the unmodied Fe₃O₄

nanoparticles (Fig. 1a), modied Fe₃O₄nanoparticles by 3-

aminopropyltriethyoxysilane (Fig. 1b) and Fe₃O₄@APTES$MAH

(Fig. 1c). The corresponding absorption bands of these

compounds are listed in Table 1. The sharp and revealing band

at around 579–585 cm^ꢁ1are relates to Fe–O bond.⁷⁶The bands

around 1633 and 3438 cm^ꢁ1are due to the hydroxyl groups on

the Fe₃O₄nanoparticles are observed in Fig. 1a. The Fe–O

stretching vibration near 580 cm^ꢁ1, O–H stretching vibration

near 3428 cm^ꢁ1, O–H deformed vibration near 1633 cm^ꢁ1, Si–O

stretching at 1029 and 1122 cm^ꢁ1, –CH₂stretching at 2852 cm^ꢁ1

were observed for Fe₃O₄@APTES (Fig. 1b). The band at 3428

cm^ꢁ1was probably attributed to the free amino groups, which is

overlapped by the O–H stretching vibration (Fig. 1b). These

results provided the evidence that the g-amino-

propyltriethyoxysilane was successfully attached to the surface

of Fe₃O₄nanoparticles.⁷⁷Fig. 1c shows the FT-IR spectrum of

Scheme 2 Synthesis route for the maleic anhydride coated magnetite

nanoparticles.

Fe₃O₄@APTES$MAH nanoparticles. The main characteristics

Fig. 1 FT-IR spectra of unmodiﬁed Fe₃O₄nanoparticles (a), modiﬁed Fe₃O₄nanoparticles by g-aminopropyltriethyoxysilane (b) and Fe₃O₄@-

APTES$MAH (c).

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Table 1 EDAX quantiﬁcation element normalized

Fe₃O₄@APTES

Wt%

Fe₃O₄@APTES$MAH

Element

Series

At%

Wt%

At%

Carbon

Nitrogen

Oxygen

Silicon

Iron

K-series

9.13

1.47

31.52

1.72

19.48

2.70

50.50

1.57

12.14

1.38

34.62

1.94

23.86

2.32

51.10

1.63

56.16

25.75

49.92

21.09

bands are assigned as follow: the band at 3396 cm^ꢁ1is attrib- ¼ 35.5844^ꢀwas respectively estimated around 17.7 nm and 20.2

utable to N–H stretching mode, which is overlapped by the O–H nm, due to the agglomeration of Fe₃O₄inside nanospheres and

stretching vibration, –C]CH and –CH₂stretching at 3085 and surface growth of amine and acid on the shell.

2890 cm^ꢁ1respectively, C]O stretching mode for acid and

Fig. 4 shows the morphology of Fe₃O₄@APTES$MAH as ob-

amide at 1716 and 1646 cm^ꢁ1and C]C stretching vibration at tained by scanning electron microscopy (SEM) micrograph (a),

1628 cm^ꢁ1. The bands around 1430 and 1252 cm^ꢁ1have been transmission electron microscopy (TEM) (b), and dynamic light

attributed to C–N and C–O stretching mode for amide and acid. scattering (DLS) diagrams (c).

The bands at 1027 and 582 cm^ꢁ1are assigned to the oxygen–

silicon and oxygen–iron stretching vibration.

As shown in Fig. 4a and b, the TEM and SEM images show

that Fe₃O₄@APTES$MAH nanoparticles were spherical with

The XRD patterns of Fe₃O₄@APTES and Fe₃O₄@APTES$MAH a mean diameter of 20 nm, with uniform size, and showed good

nanoparticles (Fig. 2) indicate their cubic structures. The posi- dispersity. Also, it shows spherical morphology aer being

tion and relative intensities of all peaks conrm well with coated Fe₃O₄with APTES shell and maleic anhydride. In short

standard XRD pattern of Fe₃O₄(Fig. 3) indicating retention of the SEM and TEM images indicate the successful coating of the

the crystalline cubic spinel structure during functionalization of magnetic Fe₃O₄particles.

Fe₃O₄nanomagnetic. The XRD patterns of the particles show six

The particle size of the synthesized Fe₃O₄@APTES$MAH

characteristic peaks reveal a cubic iron oxide phrase (2q ¼ 30.1, nanoparticles was also determined using DLS measurement

35.5, 43.0, 53.5, 57.2, 62.7, 73.9). As it can be seen in Fig. 2, the technique. Dynamic light scattering is a technique for charac-

following peak signals at (220), (311), (400), (422), (511), (440) terizing the size of colloidal dispersions which utilizes the

and (533) planes of Fe₃O₄crystals, respectively, which coincides illumination of a suspension of particles or molecules under-

with JCPD 00-001-1111 standard. The size of Fe₃O₄@APTES and going Brownian motion by a laser beam. The technique of

Fe₃O₄@APTES$MAH was also determined by X-ray line broad dynamic light scattering has been widely employed for sizing

using the Debye–Scherrer formula given as D ¼ 0.9l/b cos q, magnetic nanoparticles in liquid phase.^78,79

where D is the average crystalline size, l the X-ray wavelength

Fig. 4c shows the typical DLS size distribution graph by

˚

used (1.5406 A for Cu Ka) and b is the angular line width at half intensity of the synthesized Fe₃O₄@APTES$MAH. The size

maximum intensity and q is the Bragg's angle. The average size distribution by intensity shows an average width peak in the

of Fe₃O₄@APTES and Fe₃O₄@APTES$MAH nanoparticles for 2q range 20 to 80 nm. The average size of Fe₃O₄@APTES$MAH is

Fig. 2 The X-ray diﬀraction pattern of (a) Fe₃O₄@APTES NPs and (b) Fe₃O₄@APTES$MAH NPs.

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Fig. 3 Pattern of Fe₃O₄@APTES$MAH NPs and standard pattern of magnetite.

Fig. 4 SEM micrograph (a), TEM image (b) and DLS diagram of Fe₃O₄@APTES$MAH (c).

around 38 nm. Polydispersity index (PDI) for this sample is 0.37

For stability investigation of the materials, thermogravi-

which is an indication of size polydispersity of synthesized metric analysis was used. Fig. 5a–c shows the typical TGA curve

Fe₃O₄@APTES$MAH nanospheres.

of Fe₃O₄and two modied compounds of it. The organic

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materials of the samples are completely burned to generate gas and d shows the dispersion of Fe₃O₄@APTES$MAH in ethanol

products at the elevated temperature. The weight loss of around and its separation process, respectively. In the absence of an

ꢀ

5% below 150 C for the samples (Fig. 5a and b) is apparently external magnetic eld, the dispersion of Fe₃O₄@APTES$MAH

owing to loss of adsorbed water or the water that formed from was homogeneous and stable in ethanol. However, this

the condensation of hydroxyl groups. The weight loss between compound was collected easily by applying an external

150 and 600 ^ꢀC in Fig. 5c was assigned to the breaking of magnetic eld. It is very important that a magnetic compound

covalent amide bonds and decomposition of acidic catalyst should possess suﬃcient magnetic properties for easy

(about 24%). At higher temperature, Fe₃O₄-amine decomposed separation.

and iron oxide is formed. Thus, the TGA curve conrmed the

successful functionalization of magnetic nanoparticles Fe₃- show in Fig. 7 and Table 1 for Fe₃O₄@APTES (a) and Fe₃O₄@-

O₄@APTES with maleic anhydride. APTES$MAH (b). The presence of iron and oxygen can be seen in

Also energy dispersive X-ray spectroscopy (EDAX) results

The magnetization curves of the magnetic nanoparticles samples, with iron abundance more than oxygen. Also maleic

compounds were measured at room temperature with anhydride adsorption on the surface of Fe₃O₄–APTES nano-

a vibrating sample magnetometry (VSM). As shown in Fig. 6, the particles is conrmed by the increase in carbon atomic and

saturation magnetizations for Fe₃O₄@APTES (Fig. 6a) and Fe₃- weight percents.

O₄@APTES$MAH (Fig. 6b) were found to be 53.01 emu g^ꢁ1and

39.76 emu g^ꢁ1, respectively. The saturation magnetization

decreased during the function modication process, indicating

Catalytic synthesis of bulky heterocyclic compounds

The dialdehydes 1 and 2 were synthesized using the Vilsmeyer

reaction according to the literature (Scheme 3).^80,811-Bromo-

butane or 1-bromohexane was reacted with diphenylamine in

the presence of sodium hydroxide in DMSO to give N-butyl-N-

phenylaniline or N-hexyl-N-phenylaniline, respectively. Under

nitrogen atmosphere, POCl₃was added to DMF, then the amine

was added to this solution, and the resulting mixture was stir-

red. Aer cooling and basied with sodium hydroxide solution,

the resulting mixture was extracted and puried by column

chromatography to give 4,4⁰-(hexylazanediyl)dibenzaldehyde (1)

and 4,4⁰-(butylazanediyl)dibenzaldehyde (2).

the reaction of maleic anhydride with amino group and prob-

ably with reducing of amino aﬀects the magnetic ability. Fig. 6c

Table 2 shows the results of the synthesis of (1,8-dioxo-

decahydroacridine), bis(1,8-dioxooctahydroxanthene), bis(1,4-

dihydropydidine), bis(2,4,5-triarylimidazole), bis(2-cyano-N-

phenylacrylamide) and bis(dihydropyridine-3,5-dicarbonitrile)

derivatives in the presence of modied magnetic nano-

particles. As shown, compounds 3–8 were synthesized in

ethanol–water as solvent and, compounds 9–11 under solvent-

free conditions at low temperature with good eﬃciency. The

synthesis of compounds 12 and 13 needs a basic catalyst,

Fig. 5 Thermal gravimetric analysis curves of Fe₃O₄(a), Fe₃O₄@APTES

(b) and Fe₃O₄@APTES$MAH (c).

Fig. 6 Magnetization curves at 300 K for Fe₃O₄@APTES NPs (a), Fe₃O₄@APTES$MAH NPs (b), dispersion and separation of Fe₃O₄@APTES$MAH in

ethanol without external magnetic ﬁeld (c), and with external magnetic ﬁeld (d).

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Fig. 7 EDAX results of Fe₃O₄@APTES (a) and Fe₃O₄@APTES$MAH nanoparticles (b).

method was more eﬃcient than second procedure (Table 2,

entry 11).

For a comparable study on the catalyst eﬀects in reaction

eﬃciencies, synthesis of compounds 3–11 were carried out in

the presence of Fe₃O₄@APTES as catalyst (Table 3). It was

observed that the reactions using Fe₃O₄@APTES$MAH give

excellent yields of products with lower reaction times as

compared with the reactions applying Fe₃O₄@APTES that

shows low yields. These observations conrm that coating of

Fe₃O₄by APTS does not lead to an acidic catalyst that is

necessary for the titled reactions. Therefore, it is obvious that

supported MAH moiety induce required acidic character on the

catalyst surface leading to eﬃcient progress of the design

reactions as shown in Table 3.

It is noteworthy that the catalyst was simply recovered by

magnet without any acidic or basic workup even aer its ve

uses. Aer completion of the reaction of 4,4⁰-(hexylazanediyl)

dibenzaldehyde 2, ammonium acetate and Fe₃O₄@APTES$MAH

for the synthesis of compound 9 at 70 ^ꢀC, the catalyst was

Scheme 3 Synthesis of 4,4⁰-(alkylazanediyl)dibenzaldehyde.

therefore, triethylamine as a homogeneous catalyst and Fe₃-

O₄@APTES as a heterogeneous catalyst were used for this

purpose (Scheme 4).

Although these compounds in the presence of triethylamine

were synthesized with high eﬃciency, Fe₃O₄@APTES is

heterogeneous in the reaction mixture and separate easy by

simple magnet. The compound 13 was synthesized using two

methods (one-pot, method A and two-step, method B) that rst

Table 2 Synthesis of compounds 3–13 catalyzed by modiﬁed magnetic nanoparticles

Entry

Comp.

Solvent

Catalyst (g)

Time (min)

Yield (%)

Mp (^ꢀC)

1

2

3

4

5

6

7

8

9

10

3

4

5

6

7

8

9

10

11

12

Ethanol–water

Solvent-free

1,4-Dioxane

Fe₃O₄@APTES$MAH (0.08)

Fe₃O₄@APTES$MAH (0.06)

Fe₃O₄@APTES$MAH (0.03)

Fe₃O₄@APTES$MAH (0.05)

Fe₃O₄@APTES$MAH (0.08)

Fe₃O₄@APTES$MAH (0.04)

Triethylamine (0.2 mL)

Fe₃O₄@APTES (0.1)

130

145

55

48

40

45

40

35

45

4 (h)

5 (h)

8 (h)

5 (h)

8 (h)

78

68

80

77

68

70

86

82

69

88

75

72

55

65

50

86–88

140–142

231–233

169–171

161–163

106–109

92–94

225–227

72–74

140–142

11

13 method A

13 method B

Methanol

Triethylamine (0.2 mL)

Fe₃O₄@APTES (0.1)

Triethylamine (0.2 mL)

Fe₃O₄@APTES (0.1)

154–157

1,4-Dioxane

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Scheme 4 Synthesis of compound 13 by multicomponent reaction.

Table 3 Eﬃciency comparison of Fe₃O₄@APTES$MAH as a new catalyst and Fe₃O₄@APTES

Catalyst (g)/time (min)/yield (%)

Fe₃O₄@APTES$MAH

Entry

Comp.

Solvent

Fe₃O₄@APTES

Mp (^ꢀC)

1

2

3

4

5

6

7

8

9

3

4

5

6

7

8

9

10

11

Ethanol–water

Solvent-free

0.08/130/78

0.08/145/68

0.06/55/80

0.06/48/77

0.03/40/68

0.03/45/70

0.05/40/86

0.08/35/82

0.04/45/69

0.1/130/12

0.1/145/10

0.1/55/15

0.1/48/15

0.1/40/12

0.1/45/10

0.1/40/16

0.1/35/16

0.1/45/15

86–88

140–142

231–233

169–171

161–163

106–109

92–94

Solvent-free

225–227

72–74

Fig. 8 Recyclability of Fe₃O₄@APTES$MAH in the synthesis of bis(1,4-

dihydropyridine) (9).

Fig. 9 EDAX results of reused Fe₃O₄@APTES$MAH nanoparticles.

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Table 4 Reused catalyst EDAX quantiﬁcation element normalized

(Fig. 7b) and that recovered aer use exhibited similar EDAX

patterns (Fig. 9), indicating that the structural properties of the

catalyst were not aﬀected by the reaction medium.

Fe₃O₄@APTES$MAH

reused

Infrared and UV diﬀusion/reectance spectra of catalyst

before and aer reaction are exhibited at Fig. 10 and 11,

respectively. The IR peaks appeared at catalyst spectrum aer

reaction are well in agreement with those obtained for fresh

catalyst that conrmed the structure of the catalyst remained

unchanged aer recycling (Fig. 10). Moreover UV diﬀusion/

reectance spectrum of fresh catalyst shows ve absorption

bands in the range of 200–600 nm at 224, 249, 277, 310 and 353

nm wavelengths. As found in Fig. 11b, the used catalyst spec-

trum also show those electronic transition bands suggesting no

notable change in catalyst molecular structure.

Fig. 12 shows DLS of catalyst aer the rst recovery. In

compare between Fig. 4c and 12 can be seen that the catalyst

particles have not changed and agglomeration not occurred

during the reaction.

In order to show the ability of our method with respect to

previous reports, some of our results in comparison to some

Element

Series

Wt%

At%

Carbon

Nitrogen

Oxygen

Silicon

Iron

K-series

12.01

1.41

34.47

1.88

23.73

2.40

51.03

1.59

50.23

21.25

recovered from the reaction mixture and recovered catalyst was

washed with chloroform and dried. The recovered catalyst was

added to fresh substrates under the same experimental condi-

tions for ve runs without a signicant decrease in the product

yield and its catalytic activity (Fig. 8).

The EDAX elemental microanalysis results for the reused

Fe₃O₄@APTES$MAH in the synthesis of bis(1,4-dihydropyridine)

(9) is presented in Fig. 9 and Table 4. Both the fresh catalyst

Fig. 10 FT-IR spectra of (a) reused catalyst (b) fresh catalyst.

Fig. 11 UV diﬀusion/reﬂectance spectrum of (a) fresh catalyst; (b) reused catalyst.

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Fig. 12 DLS of reused catalyst.

Table 5 Comparison of eﬃciency of various catalysts in the synthesis of 1,4-dihydropyrdine, 1,8-dioxooctahydroxanthene, 1,8-dioxo-deca-

hydroacridine, 2-pyridone and imidazole model compounds

Entry

Compound

Catalyst

Conditions

Time (min)

Yield (%)

Ref.

Cellulose sulfonic acid

DABCO-bromine

Fe₃O₄NPs

Solvent-free, 110 ^ꢀ

H₂O, reux

C

300

60

30

94

90

86

90

82

83

7

Solvent-free, 100 ^ꢀ

Fe₃O₄@APTES$MAH

Solvent-free, 70 ^ꢀ

C

30

—

1

Amberlyst-15

FSG Hf(NPf₂)₄

Fe₃O₄NPs

EtOH/reux

300

360

25

81

49

85

92

84

85

8

C₂H₅OH/H₂O, reux

Solvent-free, 120 ^ꢀ

Solvent-free, 70 ^ꢀ

C

Fe₃O₄@APTES$MAH

35

—

2

NO

Ultrasonic

40

300

5

87

92

93

86

87

5

Alumina sulfuric acid

Fe₃O₄NPs

Fe₃O₄@APTES$MAH

CH₃OH, 70 ^ꢀ

C

Solvent-free, 80 ^ꢀ

Solvent-free, 70 ^ꢀ

C

10

—

3

BO₃H₃

Ceric ammonium nitrate

Fe₃O₄NPs

C₂H₅OH/H₂O ultrasonic

55

70

30

94

87

88

90

88

89

9

C₂H₅OH/H₂O 65 ^ꢀ

C

Solvent-free, 80 ^ꢀ

Solvent-free, 70 ^ꢀ

C

Fe₃O₄@APTES$MAH

—

4

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Table 6 Catalytic activity of Fe₃O₄@APTES$MAH in various organic reactions compared with Fe₃O₄NPs

Fe₃O₄@APTES$MAH

Fe₃O₄NPs

Condition

Entry

1

Product

Condition

Time

Yield (%)

86

Time

Yield (%)

48

Ref.

Solvent-free 50 ^ꢀC

30 (min)

Solvent-free 50 ^ꢀ

C

30 (min)

—

2

3

CH₃CN 50 ^ꢀ

C

10 (h)

67

Neat RT^a

24 (h)

65

90

CH₃CN 60 ^ꢀ

8 (h)

70

90

Neat RT^a

20 (h)

65

85

91

92

4

CH₃CN reux

80 (min)

PEG₄₀₀70 ^ꢀC^a

90 (min)

a

The amount of catalyst: 0.023 g.

other methods are summarized in Table 5. To compare between and run in the presence of Fe₃O₄@APTES$MAH (Scheme 5) and

the eﬀect of magnetic nanoparticles (Fe₃O₄NPs), modied then the results were compared with those reported using Fe₃O₄

magnetic nanoparticles (Fe₃O₄@APTES$MAH) and other cata- NPs in the literature. As shown in Table 6, in all designed

lysts, benzaldehyde was used as a model substrate. As shown in reactions, the catalyst of Fe₃O₄@APTES$MAH (as Brønsted acid)

Table 3 by using Fe₃O₄@APTES$MAH, the reaction carried out catalyzed the reactions with more ratios of yield/time with

in a moderate temperature with high eﬃciency and the yield/ respect to Fe₃O₄(as Lewis acid). With regard to the above

time ratio of the present method is better or comparable with comparative reactions, it seems that the Fe₃O₄@APTES$MAH

the other reported results.

can be recommended as a new Brønsted acid for many organic

Furthermore, to show the catalytic activity of the Fe₃O₄@- reactions that need the acid catalyst.

APTES$MAH as compared with Fe₃O₄NPs in other cases, some

organic reactions such as acylal synthesis (entry 1), epoxide

reaction with indole (entry 2), aminolysis of epoxide (entry 3)

Conclusions

and N-formylation of amine (entry 4) in Table 6, were selected

Fe₃O₄NPs are an eﬃcient acidic catalyst for synthesis of

numerous heterocyclic compounds. When Fe₃O₄was coated

with g-aminopropyltriethyoxysilane (Fe₃O₄–APTES) not only

reduced acidic properties but also used as a base catalyst. This

assertion is proved for synthesis of compounds 12 and 13

(Method A) in the presence of this catalyst. Although the eﬀect

of this catalyst is lower than triethylamine (longer times and

lower yields). In summary, we showed that maleic anhydride

reacted with NH₂coated Fe₃O₄nanoparticles and produced

acidic catalyst that was a novel and eﬀective heterogeneous and

magnetic catalyst for the one-pot synthesis of heterocyclic

compounds. The present method requires remarkably small

amounts of non-toxic and environmentally friendly Fe₃O₄–

APTES$MAH as a catalyst. In addition we introduced magneti-

cally nanocatalyst that could be reused in 5 successive runs with

no signicant structural change and loss of activity.

Acknowledgements

Scheme 5 Diﬀerent comparative reactions.

We are grateful to the Yasouj University for nancial assistance.

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RSC Adv., 2016, 6, 47298–47313 | 47313

Article Doi

A highly efficient magnetic solid acid nanocatalyst for the synthesis of new bulky heterocyclic compounds

DOI: 10.1039/c6ra02749k

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Article abstract of DOI:10.1039/c6ra02749k

Full text of DOI:10.1039/c6ra02749k

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