Sulfonated chitosan encapsulated magnetically Fe3O4 nanoparticles as effective and reusable catalyst for ultrasound-promoted rapid, three-component synthesis of spiro-4H-pyrans

Article abstract of DOI:10.1007/s13738-018-1399-7

Abstract: A facile one-pot protocol for synthesis of spiro-4H-pyrans using sulfonated chitosan-coated Fe₃O₄ nanoparticles (Fe₃O₄@CS-SO₃H NPs) as an efficient catalyst under ultrasonic condition has been developed. First, the Fe₃O₄@CS NPs were prepared from the reaction of chitosan with Fe₃O₄ NPs. Then, the treatment of Fe₃O₄@CS NPs with chlorosulfonic acid leads to the formation of Fe₃O₄@CS-SO₃H NPs which exerts excellent catalytic activity toward one-pot, three-component synthesis of spiro-4H-pyran derivatives. The core–shell structure and the composition of produced magnetic nanocatalyst were characterized by FT-IR, XRD, VSM, SEM and EDX techniques. Graphical Abstract: [Figure not available: see fulltext.].

Full text of DOI:10.1007/s13738-018-1399-7

Journal of the Iranian Chemical Society
https://doi.org/10.1007/s13738-018-1399-7
ORIGINAL PAPER
Sulfonated chitosan encapsulated magnetically Fe O nanoparticles
3
4
as effective and reusable catalyst for ultrasound-promoted rapid,
three-component synthesis of spiro-4H-pyrans
Hossein Naeimi · Sepideh Lahouti1
1
Received: 18 November 2017 / Accepted: 13 May 2018
©
Iranian Chemical Society 2018
Abstract
A facile one-pot protocol for synthesis of spiro-4H-pyrans using sulfonated chitosan-coated Fe O nanoparticles (Fe O @
3
4
3
4
CS-SO H NPs) as an efficient catalyst under ultrasonic condition has been developed. First, the Fe O @CS NPs were
3
3
4
prepared from the reaction of chitosan with Fe O NPs. Then, the treatment of Fe O @CS NPs with chlorosulfonic acid
3
4
3
4
leads to the formation of Fe O @CS-SO H NPs which exerts excellent catalytic activity toward one-pot, three-component
3
4
3
synthesis of spiro-4H-pyran derivatives. The core–shell structure and the composition of produced magnetic nanocatalyst
were characterized by FT-IR, XRD, VSM, SEM and EDX techniques.
Electronic supplementary material The online version of this
article (https://doi.org/10.1007/s13738-018-1399-7) contains
supplementary material, which is available to authorized users.
*
Hossein Naeimi
naeimi@kashanu.ac.ir
1
Department of Organic Chemistry, Faculty of Chemistry,
University of Kashan, Kashan 87317-51167,
Islamic Republic of Iran
Vol.:(0
1
123456789)
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Journal of the Iranian Chemical Society
Graphical Abstract
Keywords Spiro-4H-pyran · Magnetic nanoparticles · Fe O @CS-SO H NPs · Chitsan · Ultrasonic irradiation
3
4
3
Introduction
presentation of a versatile and facile pathway for a large
variety of syntheses in organic chemistry. Therefore, a large
number of organic reactions can be performed under ultra-
sonic irradiation in high yields, short reaction times and
mild conditions [15, 16]. The considerable features of the
ultrasound approach are improved reaction rates, formation
of purer products in high yields, easier manipulation and
considered as processing help in terms of energy protection
and waste minimization compared with traditional methods
[17, 18].
An increasing attention has recently been considered on the
synthesis of chitosan (CS) coated Fe O NPs [1–6]. As an
3
4
ideal patronage material, CS has its special set of properties
including availability, safety, non-toxicity, biocompatibil-
ity, biodegradability, low immunogenicity, and antibacte-
rial properties [7–10]. Specifically, the amine and hydroxyl
groups in chitosan arrange as active sites for numerous
absorb chemical modifications [11]. Recently published
complete books and papers [12–14] show chemical appli-
cations of ultrasounds. Sonochemistry is a new route and
Multicomponent reactions [19] (MCR’s) leading to
interesting heterocyclic scaffolds must appear as powerful
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Journal of the Iranian Chemical Society
tools for delivering the molecular diversity required in
combinatorial approaches for the synthesis of bioactive
compounds and producing varied chemical libraries of
drug-like molecules for biological screening [20, 21]. The
spiropyran derivatives have attracted strong interest due
to their useful biological and pharmacological properties
such as anticoagulant, spasmolytic, diuretic, anticancer,
and antianaphylactin characteristics [22–31]. Spiropyrans,
in particular, have potential applications as photochromic
materials in data registration, storage, transfer and in other
industrial fields [32, 33]. Some reports on the multicompo-
nent-based spiropyrans have appeared employing P-TSA,
HAuCl ·3H O, InCl , NH Cl, L-proline and ZnCl as the
(XRD) diffractometer (CuK, radiation, λ= 0.154056 nm),
at a scanning speed of 2°/min from 10° to 100° (2θ). A
BANDELIN ultrasonic HD 3200 with probe model KE 76,
with the diameter of 6 mm, was used to produce ultrasonic
irradiation and homogenizing the reaction mixture. Piezo-
electric crystal of this kind of probe normally works in the
range of 700 kHz, however using some proper clamps, the
output frequency of piezoelectric crystal have controlled
and reduced to 20 kHz. Therefore, the induced frequency
of probe to the reaction mixture is equal to 20 kHz. A
thermal method was used for the calibration of ultrasonic
power. Melting points are determined in open capillaries
using an Electrothermal Mk3 apparatus and are uncor-
rected. The purity determination of the substrates and
reaction monitoring were accomplished by TLC on silica-
gel poly gram SILG/UV 254 plates (from Merck Com-
pany). FE-SEM images of the products were visualized
by a Sigma ZEISS, Oxford Instruments Field Emission
Scanning Electron Microscope. The magnetic properties
of nanoparticles have been measured with a vibrating
sample magnetometer (VSM, PPMS-9T) at 300 K in Iran
(University of Kashan).
4
2
3
4
2
catalysts [27, 34–36]. Although these methods are avail-
able, they do not have enough scope for an efficient, high
yielding, and mild approach to attain spiropyran deriva-
tives. Indole and indoline fragments are important moieties
of a large number of a diversity of natural products and
medicinal factors and some of indolines, spiro-annulated
with heterocycles in the 3-position, have shown high bio-
logical activity [24, 37, 38]. The spirooxindole system is
the core structure of many pharmacological agents and
natural alkaloids [35, 39]. Thus, a number of procedures
have been reported for the preparation of spirooxindole-
fused heterocycles [40, 41].
Typical experimental procedure for the preparation
of chitosan‑coated magnetic nanoparticles, Fe O @
3
4
In continuation of our ongoing researches toward sonica-
tion and catalytic reactions [42–50], we report herein a clean
synthesis of spiro-4H-pyran derivatives from a wide variety
of isatin or acenaphthoquinone, malononitrile and different
CS NPs
Fe O NPs are prepared by chemical co-precipitation of
3
4
3
+
2+
Fe and Fe ions with 2:1 molar ratio, in the presence
of chitosan, followed by the hydrothermal treatment. Spe-
cifically 1 mmol of chitosan (medium molecular weight:
100,000–300,000) is dissolved in 25 mL of 0.05 M ace-
tic acid solution; to which FeCl ·6H O (0.5 mmol) and
1
,3-dicarbonyl compounds in the presence of Fe O @CS-
3
3 4
SO H NPs under ultrasound irradiation. The high yields, and
possibility of easy recovering of the catalyst are the most
advantages of this method.
3
2
FeCl ·4H O (0.25 mmol) are added. This resulting solution
2
2
is mechanically stirred for 6 h at 80 °C, under N atmos-
2
Experimental
phere. Consequently, 6 mL of 25% NH OH is injected
4
drop wise into the reaction mixture with constant stirring.
After 30 min, the mixture is cooled to room temperature
and chitosan coated over magnetic nanoparticles are sepa-
rated by an external magnet. First washed with distilled
water, then ethanol, and finally dried under vacuum at room
temperature.
Chemicals and apparatus
The chemicals used in this work were obtained from Fluka
and Merck Chemical Companies and were used without
purification. FT-IR spectra were obtained with potassium
−
1
bromide pellets in the range 400–4000 cm with a Per-
1
13
kin–Elmer 550 spectrometer. H NMR and C NMR spec-
tra were recorded with a Bruker DRX-400 spectrometer
Preparation of sulfo chitosan encapsulated nano
iron oxide (Fe O @CS‑SO H NPs)
3
4
3
at 400 and 100 MHz, respectively in DMSO-d solvent.
6
NMR spectra were reported as parts per million (ppm)
downfield from tetramethylsilane as internal standard.
The used abbreviations are: singlet (s), doublet (d), triplet
Fe O @CS NPs (10 mg) is dispersed in dry CH Cl (2 mL)
3 4 2 2
in an ultrasonic bath for 20 min, then chloro sulfonic acid
(0.3 mL) is added drop-wise over a period of 10 min at
(
t) and multiplet (m). Nanostructures were characterized
room temperature under N atmosphere. Subsequently,
2
using a Holland Philips Xpert X-ray powder diffraction
the mixture is mechanically stirred for 15 min until HCl
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Journal of the Iranian Chemical Society
gas evolution is stopped. Finally, functionalized magnetic
Fe O @CS-SO H NPs is separated by an external mag-
2-Amino-2′,9-dioxo-9H-spiro[indeno[2,1-b]pyran-4,3′-indol
ine]-3-carbonitrile (4c)
3
4
3
net, washed several times with dry CH Cl , until a neutral
2
2
pH level is achieved, then dried under vacuum at room
Brown solid, (mp . 293–295 °C); IR (KBr) ν: 3415, 3275,
rep
temperature.
3126, 2832, 2175, 1725, 1656, 1611, 1454, 1391, 1253,
−
1; 1
1
154, 1053, 904 cm
H NMR (DMSO-d , 400 MHz) δ:
6
Typical procedure for the synthesis
of spiro‑4H‑pyrans
10.96 (s, 1H, NH), 7.98 (d, J =8.0 Hz, 2H, ArH), 7.71 (s,
1H, ArH), 7.56 (d, J=8.8 Hz, 1H, ArH), 7.36 (s, 1H, ArH),
7
.32 (s, 1H, ArH), 7.21 (s, 1H, ArH), 6.97 (s, 2H, NH ), 6.77
2
1
3
A mixture of isatins or acenaphthoquinone (1 mmol), malo-
nonitrile (1 mmol), 1,3-dicarbonyl compounds (1 mmol) and
Fe O @CS-SO H NP (20 mg) in aqueous ethanol (5:1, v/v)
(s, 1H, ArH); C NMR (DMSO-d , 100 MHz) δ: 182.01,
6
168.73, 159.51, 157.84, 148.07, 141.03, 139.05, 136.02,
134.06, 130.02, 129.18, 127.74, 127.10, 126.12, 125.33,
120.45, 117.48, 111.80, 56.23, 23.56.
3
4
3
(
5 mL) was sonicated at room temperature. After completion
of the reaction as indicated by TLC, the catalyst was sepa-
rated from the reaction mixture by an external magnet. The
residual was filtered and the precipitate washed with ethanol.
Then the crude products were purified by recrystallization
from ethanol and the pure products were characterized by
physical and spectral data.
2-Amino-5′-chloro-2′,9-dioxo-9H-spiro[indeno[2,1-b]pyran-
4,3′-indoline]-3-carbonitrile (4d)
Brown solid, (mp . 296–298 °C); IR (KBr) ν: 3325, 3211,
rep
3140, 2817, 2154, 1723, 1632, 1607, 1452, 1389, 1223,
−
1; 1
1
1
168, 1034, 897 cm
H NMR (DMSO-d , 400 MHz) δ:
6
0.79 (s, 1H, NH), 7.90 (d, J =8.0 Hz, 2H, ArH), 7.83 (s,
Representative spectral data
1H, ArH), 7.60 (d, J=8.8 Hz, 1H, ArH), 7.45 (s, 1H, ArH),
7
.18 (s, 1H, NH ) 6.94 (s, 1H, NH ), 6.73 (s, 1H, ArH);
2 2
1
3
2
-Amino-7,7-dimethyl-2′,5-dioxo-5,6,7,8-tetrahydrospiro[c
C NMR (DMSO-d , 100 MHz) δ: 178.01, 170.73, 156.51,
6
hromene-4,3′-indoline]-3-carbonitrile (4a)
152.84, 144.07, 140.03, 138.05, 135.02, 132.06, 131.02,
1
28.18, 127.65, 127.09, 126.88, 124.33, 122.45, 116.48,
White solid, (mp . 258–263 °C)/(mp 268–270 °C)
113.80, 58.23, 43.18.
rep
lit
[
51–55], IR (KBr) ν: 3434, 2980, 2134, 1678, 1645, 1463,
−
1; 1
1
1
234, 1089, 964, cm
H NMR (DMSO-d , 400 MHz) δ:
6
Ethyl-2′-amino-3′-cyano-6′-methyl-2-oxospiro[indoline-3,4′
0.51 (s, 1H, NH), 6.97–7.50 (m, 3H, ArH), 6.76 (s, 2H,
-
pyran]-5′-carboxylate (4e)
NH ), 6.52 (S, 1H, ArH), 2.90 (q, J= 5.1 Hz, 4H, 2CH ),
2
2
1
3
1
1
1
4
.10 (s, 6H, 2CH ); C NMR (DMSO-d , 100 MHz) δ:
3
6
White solid, (mp . 251–253 °C)/(mp 255–259 °C) [51];
rep
lit
85.18, 168.80, 167.23, 161.81, 157.65, 141.32, 133.12,
25.41, 122.41, 120.62, 116.38, 110.32, 88.68, 62.61, 51.32,
7.85, 33.09, 22.39, 21.11, 12.69.
IR (KBr) ν: 3453, 3268, 3129, 2195, 1718, 1622, 1594,
−
1. 1
1
468, 1386, 1295, 1243, 1032, 943 cm
6
H NMR (DMSO-
d , 400 MHz) δ: 11.20 (s, 1H, NH),7.55 (d, J=6.8 Hz, 2H,
ArH), 7.14 (d, J = 8.4 Hz, 2H, NH ), 6.81 (d, J = 8.4 Hz,
2
2
H, ArH), 3.33 (q, 2H, CH O), 2.32 (s, 3H, CH ), 2.07 (t,
2
3
2
-Amino-5′-chloro-7,7-dimethyl-2′,5-dioxo-5,6,7,8-tetrahy
1
3
J=7.2 Hz, 3H, CH ). C NMR (DMSO-d , 100 MHz) δ:
3
6
drospiro[chromene-4,3′-indoline]-3-carbonitrile (4b)
1
1
5
86.28, 173.17, 154.62, 153.61, 145.81, 137.22, 133.64,
27.28, 121.06, 119.54, 115.14, 111.01, 106.31, 69.94,
4.18, 42.63, 17.24.
White solid, (mp . 278–280 °C)/(mp 293–295 °C) [53,
rep
lit
5
1
4]; IR (KBr) ν: 3345, 3264, 3121, 2956, 2164, 1723,
−
1; 1
653, 1615, 1443, 1376, 1246, 1154, 1053, 915 cm
H
NMR (DMSO-d , 400 MHz) δ: 10.54 (s, 1H, NH), 7.32 (d,
Ethyl-2′-amino-5-chloro-3′-cyano-6′-methyl-2-oxospiro[ind
oline-3,4′-pyran]-5′-carboxylate (4 h)
6
J=8.0 Hz, 1H, ArH), 7.22 (s, 2H, NH ), 7.10 (s, J=8.8 Hz,
2
1
2
H, ArH), 7.03 (s, 1H, ArH), 6.78 (t, J=8.8 Hz, 1H, ArH),
.39 (d, 2H, CH ), 2.14 (d, 2H, CH ), 1.01 (s, 3H, CH ), 0.97
White solid, (mp . 255–259 °C)/(mp 255–257 °C) [51];
2
2
3
rep
lit
1
3
(
s, 3H, CH ); C NMR (DMSO-d , 100 MHz) δ: 193.01,
IR (KBr) ν: 3374, 3312, 3170, 2208, 1714, 1656, 1591,
3
6
−
1. 1
1
1
2
79.77, 161.51, 157.86, 145.02, 134.42, 127.15, 126.72,
21.18, 119.14, 113.70, 111.12, 54.33, 52.48, 42.80, 34.00,
7.76, 25.22.
1456, 1376, 1278, 1219, 1065, 954 cm
6
H NMR (DMSO-
d , 400 MHz) δ: 11.36 (s, 1H, NH), 7.76 (d, J=6.8 Hz, 1H,
ArH), 7.64 (s, 2H, NH ), 6.95 (d, J = 8.4 Hz, 2H, ArH),
2
1
3

Journal of the Iranian Chemical Society
2
3
1
1
4
.32 (q, 2H, CH O), 2.16 (s, 3H, CH ), 2.07 (t, J = 7.2 Hz,
2′-Amino-2,9′-dioxo-2H,9′H-spiro[acenaphthylene-1,4′-ind
eno[2,1-b]pyran]-3′-carbonitrile (7b)
2
3
1
3
H, CH ). C NMR (DMSO-d , 100 MHz) δ: 178.28,
3
6
63.17, 158.61, 157.21, 141.81, 134.22, 131.64, 128.23,
23.06, 121.54, 115.18, 113.01, 104.31, 68.94, 55.18,
3.63, 15.24.
Light yellow solid, (mp . > 300 °C)/(mp .>300 °C) [56];
rep
lit
IR (KBr) ν: 3319, 2750, 2212, 1710, 1578, 1274, 1175,
−
1; 1
9
70 cm
H NMR (DMSO-d , 400 MHz) δ: 8.42–8.56
6
(
m, 4H, ArH), 8.21 (s, 2H, NH ) 7.88–7.99 (m, 3H, ArH),
2
2
′-Amino-5-chloro-2,5′-dioxo-5′H-spiro[indoline-3,4′-pyran
1
3
7
.63–7.75 (m, 3H, ArH); C NMR (DMSO-d , 100 MHz)
6
o[3,2-c]chromene]-3′-carbonitrile (5a)
δ: 210.69, 186.48, 165.14, 162.64, 146.82, 145.56, 144.64,
1
1
1
413.4, 141.93, 136.93, 134.15, 133.67, 132.27, 132.06,
32.01, 131.51, 130.16, 130.14, 128.14, 124.74, 123.46,
22.86, 66.59, 65.10.
White solid, (mp . > 300 °C)/(mp .>300 °C) [51]; IR
rep
lit
(
KBr) υ: 3469, 3352, 3218, 2936, 2188, 1718,1659, 1601,
−1; 1
1
447, 1373, 1242, 1172, 1088, 969 cm
H NMR (DMSO-
d , 400 MHz) δ: 10.80 (s, 1H, NH), 7.93 (d, J=7.6 Hz, 1H,
6
Ethyl-2′-amino-3′-cyano-6′-methyl-2-oxo-2H-spiro[acenap
hthylene-1,4′-pyran]-5′-carboxylate (7c)
ArH), 7.74–7.77 (m, 2H, ArH), 7.45–7.56 (d, J=7.3 Hz, 2H,
ArH), 7.41 (s, 1H, NH ), 7.23 (d, J=8.1 Hz, 1H, NH ), 6.85
2
2
1
3
(
d, J=7.3 Hz, 1H, ArH); C NMR (DMSO-d , 100 MHz)
6
Light yellow solid, (mp . > 300°C)/(mp .>300 °C) [56];
rep
lit
δ: 174.91, 159.06, 157.39, 154.43, 151.30, 142.01, 134.72,
IR (KBr) ν: 3425, 2952, 2218, 1729, 1634, 1565, 1378,
1
1
32.71, 127.74, 125.10, 124.77, 124.40, 121.65, 116.71,
15.64, 111.71, 110.59, 104.69, 53.36, 49.85.
−
1. 1
1
4
7
2
356, 1285, 1143, 1082, 923 cm
H NMR (DMSO-d ,
6
00 MHz) δ: 8.39–8.44 (m, 3H, ArH), 8.16 (s, 2H, NH ),
2
.92-8.00 (m, 3H, ArH), 3.54 (q, 2H, J = 7.0 Hz, CH O),
2
2
′-Amino-2,5′-dioxo-5′H-spiro[indoline-3,4′-pyrano[3,2-c]
1
3
.35 (s, 3H, CH ), 2.08 (t, 3H, J=7.0 Hz, –CH ); C NMR
3
3
chromene]-3′-carbonitrile (5b)
(
DMSO-d , 100 MHz) δ: 201.19, 168.32, 163.09, 153.40,
6
1
1
1
47.85, 134.35, 133.02, 131.54, 131.49, 130.61, 129.79,
27.33, 123.71, 121.89, 119.37, 97.59, 78.45, 58.99, 54.65,
7.10,15.82.
White solid, (mp . 286–288 °C)/(mp . 293–294 °C) [51,
rep
lit
5
1
5]; IR (KBr) υ: 3457, 3284, 3167, 2921, 2265, 1717, 1660,
−
1; 1
606, 1533, 1486, 1381, 1246, 1162, 1079, 960 cm
H
NMR (DMSO-d , 400 MHz) δ: 10.68 (s, 1H, NH), 7.84 (d,
6
2
′-Amino-2,5′-dioxo-2H,5′H-spiro[acenaphthylene-1,4′-pyr
J = 7.8 Hz, 1H, ArH), 7.74 (t, J = 7.3 Hz, 1H, ArH), 7.67
ano[3,2-c]chromene]-3′-carbonitrile (7d)
(
(
t, J=7.3 Hz, 1H, ArH) 7.55 (t, J=7.8 Hz, 1H, ArH), 7.49
d, J = 8.7 Hz, 1H, ArH), 7.37 (t, J = 7.8 Hz, 2H, ArH),
Light yellow solid, (mp . > 300 °C)/(mp . 293–295 °C)
rep
lit
7
6
.22 (t, J=7.8 Hz, 1H, NH ), 7.14 (d, J=7.4 Hz, 1H, NH )
2 2
[
51]; IR (KBr) ν: 3313, 3262, 2128, 1727, 1643, 1496, 1334,
1
3
.96 (s, 1H, ArH) 6.84 (s, 1H, ArH); C NMR (DMSO-
−
1; 1
1
8
7
229, 1083, 899 cm
H NMR (DMSO-d , 400 MHz) δ:
6
d , 100 MHz) δ: 175.26, 159.64, 157.49, 153.24, 151.13,
6
.39–8.46 (m, 3H, ArH), 8.17 (d, J = 7.3 Hz, 1H, ArH),
1
1
4
40.19, 133.49, 131.91, 128.92, 125.11, 124.18, 123.87,
21.71, 117.34, 117.10, 111.57, 110.78, 104.51, 54.91,
5.63.
.90–8.00 (m, 3H, ArH), 7.81 (d, J=7.3 Hz, 1H, ArH), 7.63
13
(
s, 1H, ArH), 7.36 (s, 2H, NH ) 5.58 (s, 1H, ArH); C NMR
2
(
DMSO-d , 100 MHz) δ: 197.35, 186.87, 178.49, 153.11,
6
1
1
1
51.24, 140.11, 133.76, 132.32, 130.38, 129.87, 129.54,
28.95,128.25, 127.65, 127.18, 126.97, 124.28, 122.75,
21.19, 116.26, 110.25, 59.75, 57.36.
2
′-Amino-6′,6′-dimethyl-2,8′-dioxo-5′,6′,7′,8′-tetrahydro-2H
-spiro[acenaphthylene-1,4′-chromene]-3′-carbonitrile (7a)
Light yellow solid, (mp . 259–262 °C)/(mp . 268–270 °C)
rep
lit
[
56]; IR (KBr) υ: 3368, 3287, 2832, 2162, 1717, 1653, 1498,
Results and discussion
−
1; 1
1
8
254, 1075, 956 cm
H NMR (DMSO-d , 400 MHz) δ:
6
.44 (d, 1H, ArH), 8.18 (s, 2H, J=7.4 Hz, NH ), 7.91–8.00
2
Preparation and characterization of Fe O @CS‑SO H
3
4
3
(
m, 3H, ArH), 2.32 (d, 4H, 2CH ), 2.22 (s, 3H, CH ), 2.08
2 3
NPs
1
3
(
s, 3H, CH ); C NMR (DMSO-d , 100 MHz) δ: 208.61,
3
6
1
1
1
94.34, 174.62, 168.65, 141.20, 140.76, 138.15, 134.57,
33.14, 129.78, 126.93, 122.51, 120.40, 118.83, 116.25,
14.05, 56.92, 54.09, 49.75, 33.09, 25.52, 22.20.
The Fe O @CS-SO H NPs was prepared according to a
3
4
3
modified procedure in the literature (Scheme 1). The het-
erogeneous catalyst, Fe O @CS-SO H NPs, is fully char-
3
4
3
acterized by FT-IR, XRD, VSM, SEM and EDX.
1
3

Journal of the Iranian Chemical Society
Scheme 1 Preparation steps of
Fe O @CS-SO H NPs
3
4
3
Fig. 2 XRD pattern of Fe O @CS-SO H NPs
3
4
3
−
1
at 1630 cm is assigned to N–H bending vibration and
−
1
that of 1382 cm to C–O stretching of primary alco-
holic groups in chitosan. The biosorption bands around
Fig. 1 IR spectra of a chitosan (CS), b Fe O @CS NPs, c Fe O @
3
4
3
4
CS-SO H NPs
3
−
1
1
088 cm display the stretching vibration of the C–O
bonds (Fig. 1a). In Fe O @CS NPs, absorptions of chi-
3
4
−
1
The FT-IR spectra scrutiny of chitosan, Fe O @CS
tosan appear along with a peak at 569 cm which cor-
responds to the stretching vibration of Fe-O groups; indi-
cating that the magnetic Fe O NPs is coated by chitosan.
3
4
NPs, and Fe O @CS-SO H NPs, are instructive (Fig. 1).
3
4
3
The FT-IR spectrum of chitosan shows a broad band at
3
4
−
1
−1
3
434 cm which corresponds to the stretching vibrations
Two new bands located at 2910 and 2869 cm and the
−
1
−1
of N-H and O-H groups. Peaks appearing at 2920 cm
band at 1645 cm can be attributed to the aliphatic C–H
are characteristic of C-H stretching vibration. The band
and N–H stretching vibrations, respectively. These bands
1
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Journal of the Iranian Chemical Society
8
6
4
2
0
-
-
-
-
2
4
6
8
-10000 -8000 -6000 -4000 -2000
0
2000 4000 6000 8000 10000
Applied Field(Oe)
Fig. 5 Particle size distribution histogram of Fe O @CS-SO H NPs
3
4
3
Fig. 3 Magnetization versus applied for Fe O @CS-SO H NPs
3
4
3
Fig. 6 The energy dispersive X-ray (EDX) of Fe O @CS-SO H NPs
3
4
3
Fig. 4 SEM image of Fe O @CS-SO H NPs
3
4
3
The magnetic properties of the as-synthesized
Fe O CS-SO H NPs are measured at room temperature.
3
4
3
are attributed to the characteristic absorptions of the chi-
tosan attached on the ferrite surface (Fig. 1b). The FT-IR
spectrum of Fe O @CS-SO H NPs shows the stretching
The negligible coactivity in the magnetization curves
indicates that the Fe O @CS-SO H NPs are super para-
3
4
3
magnetic. A typical magnetization loop appears with the
saturation magnetization (Ms) 73.2 emu/g (Fig. 3). There-
fore, catalyst shows high permeability in magnetization
which facilitates magnetic separation with a conventional
magnet.
3
4
3
and out-of-plane bending of acidic O–H groups as two
−
1
broad bands at 2800–3500 and 884 cm , respectively.
Finally, S–O stretching bands of –SO H in O–SO H
3
3
−
1
and NH–SO H groups appeared at 1153 and 1057 cm ,
3
respectively (Fig. 1c).
The size and structure of the Fe O @CS-SO H NPs
3
4
3
Fe O @CS-SO H NPs are studied by means of X-ray
are estimated using SEM (Fig. 4). The SEM image shows
uniformly dispersed spherical particles, along with weak
agglomerations.
3
4
3
analysis (XRD). The sharp peaks in the XRD patterns con-
firm the good crystallinity of the prepared samples (Fig. 2).
The results are in agreement with standard patterns of
inverse cubic spinel magnetite (Fe O ) crystal structure,
The particle size distribution histogram was provided and
evaluated using scanning electron microscopy (SEM) image,
and the resulting histogram is illustrated in Fig. 5. The his-
togram showed narrow and mean average particle diameters
of 19.4 nm± 1.3 nm for Fe O @CS-SO H NPs.
3
4
showing six diffraction peaks at 2θ about 31.21°, 36.73°,
3.41°, 53.73°, 57.33° and 63.85° corresponding to (230),
321), (400), (422), (450) and (511). No impurity in the
XRD patterns suggests the formation of pure Fe O nano-
4
(
3
4
3
The elemental compositions are calculated from the
energy dispersive X-ray (EDX). The elemental composi-
tions of Fe O @CS-SO H NPs are 69.60, 17.94, 9.00, 2.94
3
4
particles. The small and weak broad bands in the range of
5°–28° can show the existence of amorphous sulfonated
chitosan.
2
3
4
3
and 0.52% for Fe, O, S, C, N, respectively. This meant the
1
3

Journal of the Iranian Chemical Society
Scheme 2 Various synthesized
spirooxindoles in the presence
of Fe O @CS-SO H NPs
3
4
3
chitosan was coated onto the surface of the Fe O nanopar-
was obtained in excellent yield (96%) and better reaction
time compared with the other solvents.
3
4
ticles (Fig. 6).
It is noteworthy that in some of the above solvents, with
non-polar solvents such as chloroform and tetrahydrofuran
(THF) due to the low solubility of starting materials, the
reaction yield was low and at the end of the reaction, the
starting materials were recovered along with the product.
Therefore, aqueous ethanol was chosen as the best solvent
for this reaction (Table 1, entry 5).
Investigation of catalyst activity in the synthesis
of spiro‑4H‑pyrans
In this research, the spiro-4H-pyrans were prepared from
the reaction of isatin or acenaphthoquinone, malononitrile
and various 1,3-dicarbonyl compounds in the presence of
Fe O @CS-SO H NPs as catalyst under ultrasonic irradia-
We examined this reaction in the presence of several
additives. The results are summarized in Table 2. It was
found that when the reaction was carried out without
any additives only trace product was detected (Table 2,
entry1). Also, when the reaction was carried out using
p-toluene sulfonic acid (p-TSA), it could not catalyze this
3
4
3
tion (Scheme 2).
To achieve suitable conditions for the synthesis of
spiro-4H-pyran 4a, various solvent conditions and
amounts of catalysts have been investigated in the reac-
tion of isatin (1a, 1 mmol), malononitrile (2, 1 mmol),
and dimedone (3a, 1 mmol) in the presence of Fe O @CS-
reaction (Table 2, entry 7). Some bases such as NaHCO
3
4
3
SO H NPs catalyst as a model reaction (Scheme 3). As can
and L-proline can catalyze this reaction with moderate
yields (Table 2, entries 2 and 3). When some Lewis acids,
for example ZnCl , InCl and FeCl .6H O were used in
3
be seen in Table 1, the result was obtained with Fe O @
3
4
CS-SO H NPs (20 mg) as a catalyst in various solvents
3
2
3
3
2
including aqueous ethanol, acetonitrile, ethanol, water,
tetrahydrofuran (THF) and chloroform under ultrasonic
irradiation (35 W). As shown in Table 1, when the reaction
was carried out in the presence of Fe O @CS-SO H NPs
this reaction system, the products were obtained in mod-
erate yields (Table 2, entries 4–6). The model reaction
was performed using Fe O and chitosan, which gave
3
4
the desired product in 60% and 54% yield, respectively
3
4
3
as catalyst in aqueous ethanol, the expected product 4a
(Table 2, entries 8 and 9). The best result was obtained
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Journal of the Iranian Chemical Society
Scheme 3 Plausible mechanism for the synthesis of spiro-4H-pyran
Table 1 Influence of the solvent on the product 4aa
Table 2 Effect of different catalysts on the model reaction
Entry Catalyst Time (min) Yield (%) Ref.
Entry
Solvent
Time (min)
Yield (%)b
1
2
3
4
5
6
EtOH
15
15
25
20
5
79
62
51
55
96
73
1
2
3
4
5
6
7
8
9
1
None
60
20
25
35
25
35
40
35
30
5
Trace
65
68
63
85
51
Trace
60
54
96
–
35
38
36, 37
36
36, 37
37
–
CH CN
NaHCO3
L-proline
ZnCl2
3
CHCl3
THF
EtOH/H O
InCl3
2
H O
12
FeCl .6H O
2
3
2
p-TSA
a
Reaction conditions: isatin (1.0 mmol), malononitrile (1.0 mmol),
dimedone (1.0 mmol), and Fe O @CS-SO H NPs (20 mg)
Fe O
3
4
3
4
3
b
Chitosan
Fe O @CS-SO H NP
–
Isolated yield
0
This work
3
4
3
when Fe O @CS-SO H NP was used according to the
3
4
3
yield and the reaction time (Table 2, entry 10). Therefore,
Fe O @CS-SO H NP was chosen as a catalyst for this
(Table 3). It was observed that there occurred a reduc-
tion in overall reaction time and an increase in yield by
increasing the amount of Fe O @CS-SO H NPs up to
3
4
3
reaction.
We grinded the starting material with varying amounts
of Fe O @CS-SO H NPs ranging from 5 to 50 mg
3
4
3
20 mg (Table 3 entry 3). Further increase in the amount of
3
4
3
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Journal of the Iranian Chemical Society
Table 3 Effect of different amounts of Fe O @CS-SO H NPs in the
effective spiro reaction in the frequency of 35 kHz. It was
demonstrated that in this method, ultrasound irradiation can
be played an important role on the product yield and reac-
tion time.
3
4
3
model reaction
Entry
Catalysta
Time (min)
Yield (%)b
1
2
3
4
5
6
5
15
20
30
40
50
30
20
15
9
5
5
65
79
96
96
96
96
Ultrasound enhances the chemical reactions in a solu-
tion through the generation of cavitations micro bubbles.
The cavities are believed to act as a micro reactor: as the
molecules enter the micro bubbles and the high tempera-
ture and pressure produced during cavitations break their
chemical bonds thus reacting with other species.
The sonication of isatins (1a–b), malononitrile (2) and
1,3-dicarbonyl compounds (3a–d) at room temperature was
carried out. The obtained products (4a–5b) were shown in
Table 5.
a
Amount of Fe O @CS-SO H NPs (mg)
Isolated yield
3
4
3
b
In addition, investigations were shown that this protocol
could be extended to a three-component coupling reaction
involving an equimolar amount of acenaphthoquinone (6),
malononitrile (2) and 1,3-dicarbonyl compounds (3a–d).
Under these conditions, the desired spiro acenaphthylenes
Table 4 The effect of ultrasound frequency on spiro-4H-pyrans
Entry Condition Frequency (KHz) Time (min) Yield (%)a
1
2
3
4
5
6
Silent
US
US
US
US
None
20
30
35
40
360
20
15
5
5
5
–
75
80
96
96
96
(
7a–d) were also produced in good yields under ultrasound
irradiation. The results of the investigation are presented in
Table 6.
The formation of racemate spiro-4H-pyrans can be
explained by Knoevenagel condensation and Michael
addition followed by cyclization, as shown in Scheme 3.
Initially, it protonates the carbonyl group of isatin, which
then condenses with acidic CH group of malononitrile 2
through a fast Knoevenagel condensation to afford isatil-
idene malononitrile derivative A. The Michael addition of
dimedone enol form to compound A creates intermediate
B which obtains the compound C via enolization; then by
the cyclization of hydroxyl group of C to the cyano moiety
to afford D. Finally, the desired product E was produced by
the tautomerization of compound D (Scheme 3). It is clear
that adsorption of isatin 1 is improved on the Fe O @CS-
US
45
aIsolated yield
Fe O @CS-SO H NPs affected neither the reaction time
3
4
3
nor the yield of the product. Thus, we concluded that the
best result was obtained with 20 mg amount of Fe O @
3
4
CS-SO H NPs.
3
Moreover, to investigate the effects of ultrasonic irradia-
tion and to evaluate and compare conventional heating or
silent condition with ultrasound assisted method, we con-
tinued our efforts under different conditions. The results are
listed in Table 4 (entry 1 vs. other entries). It is notable that
the corresponding products were obtained in excellent yields
and short reaction times under sonication. While no reaction
were performed at room temperature in the absence of ultra-
sonic irradiation and longer reaction time (Table 4, entry 1).
When the frequency was 35 kHz, the yield increased
product 4a to 96% yield and the reaction time is reduced to
3
4
SO H NPs catalyst by the effects of nanocatalyst surface
3
and also ultrasonic irradiation. Additionally, ultrasound
can increase mass transfer of isatin between 1,3-dicarbonyl
compounds and malononitrile via the acoustic cavitation
effect.
The reusability is one of the important properties of this
catalyst. After the completion of the reaction, the Fe O @
3
4
5
min (Table 4, entry 4). Using 45 kHz did not change reac-
CS-SO H NPs catalyst was separated by an external magnet.
3
tion yield a considerable amount (96% in the same time).
Experiments performed at constant transmitted power but
variable frequency (35, 40 and 45 kHz) show the same trend.
These facts mean that there is an optimum frequency for
The catalyst was then washed with ethyl acetate, air-dried
and used directly with fresh substrates under identical condi-
tions without further purification. It was found that the cata-
lyst could be reused for the five repeated cycles without any
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Journal of the Iranian Chemical Society
Table 5 Synthesis of compound
Entry
1
R
1
Reactant
Product
Time
5
Yield(%)b
(
4a–5b) in presence of Fe O @
3
4
CS-SO H NPs catalyst
3
4
a
H
96
4
b
2
3
Cl
H
6
7
95
93
4
c
4
d
4
5
Cl
H
5
6
94
91
4
e
4
5
h
a
6
7
Cl
Cl
5
4
93
94
5
b
8
H
4
97
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Journal of the Iranian Chemical Society
Table 5 (continued)
Entry
1
R
1
Reactant
Product
Time
Yield(%)b
4
a
H
5
96
4
b
2
3
Cl
H
6
7
95
93
4
c
4
d
4
5
Cl
H
5
6
94
91
4
e
4
5
h
a
6
7
Cl
Cl
5
4
93
94
5
b
8
H
4
97
Under ultrasonic irradiation
The reaction condition: isatins (1a–b), malononitrile (2) and 1,3-dicarbonyl (3a–d) at room temperature
a
Isolated yields
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Journal of the Iranian Chemical Society
Table 6 Synthesis of compounds (7a–d) from the presence of
Fe O @CS-SO H NPs catalyst
3
4
3
Entry
Reactant
Yield
%)b
Product
Time(min)
(
1
5
92
94
90
96
7
a
Fig. 7 Reusability of Fe O @CS-SO H NPs
3
4
3
2
3
4
5
6
4
7
b
appreciable loss of its activity as shown in Fig. 7. It could
thus be concluded that the Fe O @CS-SO H NPs with high
3
4
3
activity and good reusability could be a satisfying catalyst
for these reactions.
7
7
c
The SEM images of Fe O @CS-SO H NPs catalyst
3
4
3
before use in the reaction and after five times of reuse was
shown the same particle size (Fig. 8). Interestingly, the shape
and size of the nanoparticles remained unchanged before and
after the reaction. We believe that, this is also the possible
reason for the extreme stability of the Fe O @CS-SO H NPs
d
3
4
3
presented herein.
Table 6 (continued)
Entry
Reactant
Yield
Product
Time(min)
%)b
Conclusion
(
We have reported efficient and environmentally friendly pro-
cedure for the synthesis of spiro-4H-pyran via condensation
of isatin or acenaphthoquinone, malononitrile and different
1
5
92
94
90
96
7
a
1
,3-dicarbonyl compounds using Fe O @CS-SO H NPs as
3 4 3
a magnetic heterogeneous catalyst under ultrasound irradia-
tion. This method offers several advantages including ease of
separation and recovery, higher yields, safety, mild reaction
conditions, short reaction times, simple workup procedure
and recyclability of the magnetic nanocatalyst, as well as
the ability to tolerate a large range of substitutions in the
reagents. In general, improvements in rates and yield of the
reactions were observed by carrying out the reactions under
ultrasound irradiation.
2
3
4
5
6
4
7
b
7
7
c
d
Temperature under ultrasonic irradiation
The reaction condition: acenaphthoquinone, malononitrile (2) and
1
,3-dicarbonyl (3a-d) at room
a
Isolated yield
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Journal of the Iranian Chemical Society
Fig. 8 SEM Images of Fe O @
3
4
CS-SO H NPs before use (a)
3
and after five times reuse (b)
Acknowledgements The authors are grateful to University of Kashan
23. H.R. Safaei, M. Shekouhy, S. Rahmanpur, A. Shirinfeshan, Green
for supporting this work by Grant no. 159148/73.
Chem. 14, 1696 (2012)
2
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