Arginine-based surface modification of nanostarch, a catalytic carbohydrates in synthesis of heteroaryl sulfides

Article abstract of DOI:10.1016/j.molstruc.2019.05.017

Novel arginine-functionalized starch-based nanoparticles (Arg-SNPs)were synthesized and characterized by Fourier transforms infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDAX), X-ray diffraction (

Full text of DOI:10.1016/j.molstruc.2019.05.017

Accepted Manuscript
Arginine-based surface modification of nanostarch, a catalytic carbohydrates in
synthesis of heteroaryl sulfides
Zohre Zarnegar, Homeyra Rostami Monjezi, Javad Safari
PII:
S0022-2860(19)30571-X
10.1016/j.molstruc.2019.05.017
MOLSTR 26524
DOI:
Reference:
To appear in:
Journal of Molecular Structure
Received Date:
Accepted Date:
18 March 2019
07 May 2019
Please cite this article as: Zohre Zarnegar, Homeyra Rostami Monjezi, Javad Safari, Arginine-
based surface modification of nanostarch, a catalytic carbohydrates in synthesis of heteroaryl
sulfides, Journal of Molecular Structure (2019), doi: 10.1016/j.molstruc.2019.05.017
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ACCEPTED MANUSCRIPT
OH
O
Si
Si
Cl
Cl
OMe
MeO Si
OMe
O
Toluene
SNP
Cl
OH
SNP
O
24 h , reflux
O
OH
O
Si
Cl
SNP
O
Cl-SNP
OH
NH2
HN
NH
NH
O
O
NH
NH
O
Si
Si
Arginine
Toluene
O
N
OH
SNP
O
H
NH2
O
NH
Si
NH
HN
NH2
Arg-SNP
OH
O

ACCEPTED MANUSCRIPT
Arginine-based surface modification of nanostarch, a catalytic carbohydrates
in synthesis of heteroaryl sulfides
Zohre Zarnegar,b Homeyra Rostami Monjezi,a Javad Safaria *
aDepartment of Organic Chemistry, Faculty of Chemistry, University of Kashan, Kashan,
87317-51167, I.R. Iran.
bResearch Affiliate, Department of Chemistry, University of Payame Noor, P.O. BOX 19395-
4697, Tehran-IRAN
E-mail: safari_jav@yahoo.com; safari@kashanu.ac.ir
Abstract
Novel arginine-functionalized starch-based nanoparticles (Arg-SNPs) were synthesized and
characterized by Fourier transforms infrared spectroscopy (FT-IR), scanning electron microscopy
(SEM), energy dispersive X-ray spectroscopy (EDAX), X-ray diffraction (XRD) and thermos-
gravimetric analyses (TGA) techniques. Arg-SNP was used as a highly efficient and
macromolecule-supported recyclable nanocatalyst for the one-pot reaction between thiourea and
iodine with various substituted methylcarbonyls to afford the corresponding diheteroaryl
thioethers in high-to-quantitative yields. The nanocatalyst was recycled at least five times without
significant decrease in the catalytic activity.
Keywords: Diheteroaryl thioethers, Arginine, Starch, heterogeneous catalyst, nanoparticles,
Thiourea.
.
1. Introduction
In recent years, the use of green techniques has been used to reduce environmental pollution with
a variety of catalysts [1]. A green chemistry process should also not cause environmental pollution.
Therefore, the application of heterogenized homogeneous catalysts or reagents is based on the
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principles of green chemistry. Carbon based nanoparticles are a important class of nanosupports
that are used for immobilization of homogeneous species for example carbon-based nanoparticles
modified with various L-amino acids in insulin amyloid formation [2], nitrogen (N)-doped carbon
nanodots as fluorophores for selective and sensitive fluorescence detection of nitrite in water [3],
aminoguanidine carbon dots as antibacterial activity againsts [4], and etc. [5]. Moreover,
development of polymeric carbohydrates as one of the most practical carbon derivatives have
received significant attentions for synthesis of heterogenized homogeneous catalysts such as
cellulose, chitosan, chitin, starch, and collagen fiber [6]. Among biocompatible polymers, starch
and its modified structure have been widely investigated as green and valuable catalysts and
suitable bio-supports for development of heterogeneous catalysts due to its high reactivity,
efficient selectivity, low price, structure diversity and environmental friendly nature [7]. In this
context, different types of homogeneous catalysts have been immobilized on the starch and used
in catalytic reactions such as Pd stabilized by starch-halloysite hybrid for coupling reactions [6],
Au nanoparticles immobilized on starch polymer and their use in homocoupling phenylboronic
acid [8], Sulfonated starch nanoparticles for synthesis of xanthenes [4], Ziegler–Natta supports
based on iron oxide/cassava starch for in situ ethylene polymerization [9], Sb2S3-CeO2/chitosan-
starch for photo-degradation of toxic herbicide compound [10] and etc. [11]. On the other hand,
starch nanoparticles (SNPs) have attracted great attention because of their nano-size, large surface
area, unique biodegradable, good biocompatibility, biological activity and adsorptive properties.
These valuable natural materials have been developed for food industry, biomedical fields, fat
replacer, water treatment agent, composites filler, and catalytic nanosystems [4,7]. Therefore, SNP
can be a better and more suitable option than starch for catalytic activity. There is no example of
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the use of SNP as a green support for the immobilization of arginine amino acid for the synthesis
of thioether derivatives.
Currently, the synthesis of diheteroaryl thioethers as a significant type of sulfur-containing organic
compounds is an important area of research due to their pharmaceutical and biological properties
[12-14]. Representative examples of diaryl thioethers with biological activity and pharmaceutical
applications are shown in Fig. 1. They are also known as important intermediates in for the
synthesis of valuable organic chemical compounds [15]. Therefore, many protocols have been
developed for the synthesis of diaryl thioethers for example metal-catalyzed arylation of thiols
[16,17], metal-catalyzed reactions with disulfides [18-20], sulfenylation of organometallic
reagents [21], and condensation methyl ketones and thiourea in the presence of iodine [22].
<Fig. 1>
However, these methods often require drastic reaction conditions, the use of transition metal
catalysts, elevated temperatures, long reaction times, and less available starting materials such as
arenethiols [14,23]. Therefore, the development of inexpensive, straightforward, convenient, and
mild methodology is desirable for the preparation of heteroaryl thioethers especially by using
stable, highly active, and green catalysts and readily available starting materials.
In the present study, we report a new approach for the synthesis of biocompatible heterogeneous
catalyst based on immobilization of arginine amino acid on the starch nanoparticles. The resulting
system, Arg-SNP, was used as an efficient and heterogeneous catalyst for the effective synthesis
of the diheteroaryl thioethers via one-pot reaction of methylcarbonyls, thiourea and iodine in
DMSO (Schemes 1). The recyclability of Arg-SNP up to five reaction runs was also examined.
< Schemes 1>
2. Experimental Section
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2.1. Materials and apparatus
All commercially available reagents were used without further purification and purchased from
Merck and Aldrich Company in high purity. Melting points were specified on an Electrothermal
MK3 apparatus using an open-glass capillary and are uncorrected. FT-IR spectra were recorded as
KBr pellets with a Perkin-Elmer 550 spectrometer. 1HNMR and 13C NMR spectra were obtained
in the DMSO‐d6 solvent with a Bruker DRX‐400 and Bruker Avance spectrometer at 400 and 100
MHz, respectively. Starch nanoparticles was specified using a Holland Philips Xpert X-ray powder
diffraction (XRD) diffractometer (CuK, radiation, λ= 0.154056 nm), at a scanning speed of 2°/min
from 10° to 100° (2θ). Thermal gravimetric analysis (TGA) was performed on a mettler STA4000
system at a heating rate of 10 K min-1 under N2 atmosphere. The elemental analyses (C, H, N)
were obtained from a Carlo ERBA Model EA 1108 analyzer. The morphological characteristics
of polymeric nanoparticles were investigated by a scanning electron microscope (SEM, XL-EM-
10C) analysis operating at an accelerating voltage of 20 kV under high vacuum.
2.2. Synthesis of Arg-SNPs
The SNPs were prepared by nanoprecipitation method [7]. In a typical procedure, 8.2 g of starch
was added in 35 mL of distillated water and the mixture was heated at 90 °C for 1 h. Then, 150 mL
of absolute ethanol was dropped slowly into the resulted mixture to complete gelatinization of corn
starch by vigorous stirring. The obtained mixture was cooled at the room temperature and another
35 mL of absolute ethanol was added drop-wise to the resulting suspensions for another hour under
vigorous mechanical stirring. The suspensions were centrifuged and the formed nanoparticles were
washed three times using absolute ethanol to remove the water. The SNPs were dried at 50 °C to
remove ethanol. The chloropropyl grafted SNP (Cl-SNP) was synthesized through
functionalization of SNPs with organosilane precursor 3-chloropropyltrimethoxysilane. The
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details are as follows: in 50 ml round-bottom flask, 2.5 g of SNPs were dispersed in 5 mL of
toluene. Then, 5 mL (25 mmol) of 3-chloropropyltrimethoxysilane were added to the reaction
mixture and refluxed for 24 h. After this time, Cl-SNPs were collected by filtration and washed
several times with ethanol to remove the precursor residue. The modified SNPs were dried at 100
ºC for 8 h. Finally, for immobilization of arginine on functionalized SNPs, 1 g of Cl-SNP was
dispersed in 30 ml of toluene and 1.5 g (8.6 mmol) of amino acid was added to solution in the
presence of NEt3 (1.2 mmol) and stirred under reflux conditions for 48 h. The resulting mixture
was filtered, washed with toluene and chloroform and dried in oven at 110 °C for 6 h to produce
the Arg-SNPs.
2.3. General procedure for the synthesis of diheteroaryl thioethers
A mixture of methyl ketone (1 mmol), thiourea (2 mmol), iodine (1 mmol), and Arg-SNP (0.02 g)
was stirred at 40 °C in DMSO solvent. After the completion of reaction (monitored by TLC;
hexane / AcOEt 1:1), the bio-heterogeneous nanocatalyst was separated by filtration and the
organic layer was extracted with saturated sodium thiosulfate / water and ethyl acetate solution.
the solvent was removed under reduced pressure. The pure product was recrystallized by hot
ethanol in high yield. All diheteroaryl thioethers were characterized by physical data and
spectroscopic techniques.
Spectral data for diheteroaryl thioethers
5,5'-thiobis(4-phenylthiazol-2-amine) (3a)
1
IR spectrum (KBr cm-1) 3272 (NH2), 3109 (NH2), 1624 (C=C), 1513 (C=N), 773 (S-C=N); H
NMR (400 MHz, DMSO) δ (ppm) 7.30 (m, J=5 Hz, Ar-H), 7.63 (s,4H,NH2), 7.95 (m, J=5 Hz, Ar-
H).
5,5'-thiobis(4-(4-hydroxyphenyl)thiazol-2-amine) (3b)
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IR spectrum (KBr cm-1) 3112 (OH), 3109 (NH2), 3098 (NH2), 1613 (C=C), 1540 (C=N), 741 (S-
C=N); 1H NMR (400 MHz, DMSO) δ (ppm) 76.67 (d, J=10Hz, Ar-H), 7.58 (s,4H,NH2), 7.71 (d,
J=10 Hz, Ar-H) , 9.7 (s,2H,OH).
5,5'-thiobis(4-(2-hydroxyphenyl)thiazol-2-amine) (3c)
Copper color solid, Rf (Petrolyom ether:Ethyl acethat, 1:1):0.04, UV (nm): 330; IR spectrum (KBr
1
cm-1) 3430 (OH), 3317 (NH2), 3182 (NH2), 1610 (C=C), 1526 (C=N), 751 (S-C=N); H NMR
(400 MHz, DMSO) δ (ppm) 6.67 (t, J=10Hz, Ar-H), 6.78 (d, 2H,Ar-H), 7.56 (t, J=10 Hz, Ar-H),
7.65 (d, J=10 Hz, Ar-H), 7.76 (s,4H,NH2 ), 10.43 (s,2H,OH); 13C NMR (100MHz, DMSO) δ (ppm)
110.1, 120.1, 121.1, 131.0, 132.1, 154.0, 154.9, 159.1, 169.1; Anal. Calcd. for C18H14N4O2S3: C,
52.16; H, 3.40; N, 13.52; O, 7.72; S, 23.20%. Found: C, 52.12; H, 3.38; N, 13.54; O, 7.74; S,
23.25%.
5,5'-thiobis(4-(4-bromophenyl)thiazol-2-amine) (3d)
IR spectrum (KBr cm-1) 3364 (NH2), 3185 (NH2), 1665 (C=C), 1510 (C=N), 1454 (N-H Bending
aromatic), 718 (S-C=N); 1H NMR (400 MHz, DMSO) δ (ppm) 7.32 (S, 4H, NH2), 7.62 (d, J= 10
Hz, 4H, Ar-H), 7.73 (d, J=10 Hz, Ar-H).
5,5'-thiobis(4-(4-chlorophenyl)thiazol-2-amine) (3e)
IR spectrum (KBr cm-1) 3295 (NH2), 1647 (C=C), 1512 (C=N), 1461 (N-H Bending aromatic),
718 (S-C=N); 1H NMR (400 MHz, DMSO) δ (ppm) 7.55 (S, 4H, NH2), 7.34 (d, J=4 Hz, 4H, Ar-
H), 7.70 (d, J=4 Hz, Ar-H).
5,5'-thiobis(4-(p-tolyl)thiazol-2-amine) (3f)
IR spectrum (KBr cm-1) 3355 (NH2), 3281 (NH2), 1624 (C=C), 1502 (C=N), 1463 (N-H Bending
aromatic), 717 (S-C=N); 1H NMR (400 MHz, DMSO) δ (ppm) 2.18 (6H.CH3), 7.40 (S, 4H, NH2),
7.12 (d, J= 30 Hz, 4H, Ar-H), 7.54 (d, J= 30Hz, 4H, Ar-H).
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5,5'-thiobis(4-(m-tolyl)thiazol-2-amine) (3g)
IR spectrum (KBr cm-1) 3317 (NH2), 3190 (NH2), 1626 (C=C), 1501 (C=N), 1468 (N-H Bending
aromatic), 717 (S-C=N); 1H NMR (400 MHz, DMSO) δ (ppm) 2.50 (6H.CH3), 7.08 (s, 4H, NH2),
7.17 (d, J= 10 Hz, 2H, Ar-H), 7.41 (t, J= 10Hz, 2H, Ar-H), 7.63 (d, J=10 ,2H, Ar-H), 7.81 (s, 2H,
Ar-H).
5,5'-thiobis(4-(4-methoxyphenyl)thiazol-2-amine) (3h)
IR spectrum (KBr cm-1) 3287 (NH2), 3113 (NH2), 1637 (C=C), 1519 (C=N), 1458 (N-H Bending
aromatic), 726 (S-C=N); 1H NMR (400 MHz, DMSO) δ (ppm) 3.37 (OCH3), 6.84 (d, J= 10 Hz,
4H, Ar-H), 7.31 (S, 4H, NH2), 7.59 (d, J= 10 Hz, 4H, Ar-H).
5,5'-thiobis(4-(4-nitrophenyl)thiazol-2-amine) (3i)
Copper color solid, Rf (Petrolyom ether:Ethyl acethat, 1:1):0.02, UV (nm): 268; IR spectrum (KBr
cm-1) 3413 (NH2), 3402 (NH2), 1341 (NO2), 1639 (C=C), 1507 (C=N), 1451 (N-H Bending
aromatic), 758 (S-C=N); 1H NMR (400 MHz, DMSO) δ (ppm) 7.54 (s, 4H, NH2), 7.09 (d, J=10
Hz, 4H, Ar-H), 7.72 (d, J= 10 Hz, 4H, Ar-H); Anal. Calcd. for C18H12N6O4S3: C, 45.76; H, 2.56;
N, 17.79; O, 13.54; S, 20.36%. Found: C, 45.79; H, 2.50; N, 17.83; O, 13.55; S, 20.38%.
5,5'-thiobis(4-(4-morpholinophenyl)thiazol-2-amine) (3j)
Orange solid, Rf (Petrolyom ether:Ethyl acethat, 1:1):0.02, UV (nm): 378; IR spectrum (KBr cm-
1) 3371 (NH2), 3174 (NH2), 1608 (C=C), 1505 (C=N), 1451 (N-H Bending aromatic), 758 (S-
C=N); 1H NMR (400 MHz, DMSO) δ (ppm) 7.67 (d,4H, Ar-H), 7.31 (s, 4H, NH2), 6.91 (d, 4H,
Ar-H); 13C NMR (100MHz, DMSO) δ (ppm) 48.2, 66.4, 114.0, 123.5, 128.4, 148.0, 153.1, 157.1,
168.2; Anal. Calcd. for C26H28N6O2S3: C, 56.50; H, 5.11; N, 15.20; O, 5.79; S, 17.40%. Found: C,
56.55; H, 5.16; N, 15.02; O, 5.84; S, 17.45%.
Results and discussion
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3.1. Catalyst characterization
The Arg-SNPs were synthesized according to the Scheme 2. The structure of amino acid modified
SNPs is identified by types of techniques such as FT-IR, XRD, SEM, EDAX, and TGA. Next, the
performance of the Arg-SNPs is evaluated for the synthesis of heteroaryl sulfides.
< Scheme 2>
The FT-IR spectrum of SNPs in Fig. 2. is in good accordance with the previous reports [7] and
exhibited the characteristic bands at 3420 cm−1, OH stretching, 2926 cm−1, C-H vibration, 1646
cm−1, OH bending vibration, 1156 and 1023 cm−1, C-O bond stretching vibration of glucose units.
Arg-SNP spectrum in Fig. 2(b) has signals at 3302 and 3067 cm−1 that they confirm the existence
of the NH2 and O–H stretching vibrations in the amino acid. The band stretching near 2943 and
2863 cm−1 can be attributed to the presence of C–H groups. The signal appeared at 1623 cm−1are
attributed to the COO- stretching vibrations. The vibration band at 1135 cm−1 is attributed to
asymmetrical stretching of C=N that it overlaps with Si-O absorption bands.
< Fig. 2. >
The morphology of the SNPs and modified SNPs were studied by SEM technique. The SEM in
Fig. 3 (a) was showed a spherical-shape nanostructure for SNPs with a relatively regular size of
about 20-30 nm. As depicted in Fig. 3(b) the synthesized Arg-SNPs have a homogeneous surface
with a spherical structureafter modification.
< Fig. 3. >
The EDAX analysis was performed for characterization of Arg-SNPs. As shown in Fig. 4, the
EDAX image of the functionalized starch confirms the presence of Si, O, C and N. The presence
of Si and N atoms can be attributed to the organosilane precursor and amino acid.
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< Fig. 4. >
The XRD pattern of pristine starch and its modified nanostructures are displayed in Fig. 5. The
three characteristic peaks of the pure starch are shown at 2θ = 15.38°, 17.20°, and 23.29° related
to the high degree of crystallinity of polymeric carbohydrate. The broad peaks in the XRD of SNPs
are attributed to the increased amorphous nature of their nanostructures. The characteristic peaks
of Arg-SNPs are observed at 2θ = 11.20°, 17.23°, 18.48°, 19.32°, 19.67° and 20.62° that the sharp
bands in their ranges can show the new orientation of the plates of particles [24].
< Fig. 5. >
TGA-DTA diagrams SNPs and Arg-SNPs are presented in Fig. 6. The thermogram of SNP is also
depicted in Fig. 6(a). The weight loss below 200°C could be assigned the evaporation of adsorbed
water. The other observed weight loss at 280-500°C is related to the degradation of starch. The
DTA diagram in Fig. 6(a) indicates, SNPs were decomposed in two steps at 314 and 493 °C which
are followed by an exothermic process. These exothermic systems can be due to the loss of water
and the decomposition of organic polymer, respectively. In Fig. 6(b), the TGA of Arg-SNP is also
depicted that this curve is almost like the thermogram of SNP. The comparison of the DTA of Arg-
SNP and SNP indicated that the former showed higher thermal stability and degradation started at
higher temperature.
< Fig. 6. >
3.2. Catalytic activity
The performance of the Arg-SNP as a green nanocatalyst was investigated for the synthesis of
diheteroaryl thioethers. Initially, the treatment of acetophenone, thiourea and iodine in the presence
of Arg-SNP as catalyst was selected as a model reaction. Then, the reaction variables were
optimized. The results are listed in Table 1. After examining the amount of catalyst, reaction
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temperature and suitable solvent for the process, the optimum reaction conditions were found to be use
of 0.02 g amount of Arg-SNP in the DMSO as solvent at 40 °C. In the following, the catalytic
activity of arginine and SNP for promoting the model product was investigated. It was found that
the desired products were furnished 65 and 40% for homogeneous and heterogeneous catalyst,
respectively. Although the catalytic activity of arginine was higher than the SNP, but also it was
homogeneous with tedious work-up. It can be concluded that use of nano-supported homogeneous
catalyst such as Arg-SNP is more effective than use of any of them. This can confirm the synergism
between homogeneous catalyst and support. The nano-size and large surface area of the
support makes the homogenous catalyst readily available to the substrates. Also, experiments
showed that when alanine and valine are stabilized on starch, they have a more catalytic effect than
homogenous species. But their activity is less than Arg-SNP. In the absence of the nanocatalyst,
the reaction did not show good results for the synthesis of the desired diheteroaryl thioether.
< Table 1. >
After the optimization of all the reaction parameters, the scope of this protocol was evaluated by
using a series of different methylcarbonyls with the variety of substituents on their rings were used.
The obtained results are shown in Table 2. The nature and position of the substituent groups in the
aromatic ring of the starting methyl ketone did not have much effect on the yield of the final
product and all of the used methylcarbonyls afforded the expected products in good to excellent
yields.
< Table 2 >
The plausible mechanism of the catalytic reaction is shown in Scheme 3. Immobilized arginine
can act as a bi-functional organocatalyst due to the existence of both Lewis base (NH2) and
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Brønsted acidic (COOH) sites. At the outset, supported amino acid as a Lewis acid can activate
the carbonyl group of the aromatic methyl ketone. The reaction between activated methyl ketone
and I2 leads to the α-iodocarbonyl product (1aa). Also, thiourea can convert to thiol (2a) by Lewis
base in amino acid and react with the iodinated methyl ketone to form intermediate (A). Then,
catalytic promoted dehydrogenation gives species (4a). 2-aminothiazoles (4a) can convert to
iodinated thiazole (5a) in the presence of I2. Intermediate (5a) gives species (B) via condensation
reaction with thiourea, which would undergo a hydrolysis reaction to form intermediate (6a). At
the end of this process, intermediate (6a) can condense with intermediate (5a) to form the desired
product (3a).
<scheme 3>
Moreover, the recyclability and reusability of the Arg-SNPs was evaluated in the condensation
model reactions by comparing the yields of products by using fresh and reused nanocatalysts. The
obtained results are presented in Fig. 7. To this purpose, upon the end of the first reaction run, the
nanocatalyst was filtered, washed with EtOH and acetone, air-dried and used for the next run. This
cycle was repeated for 5 consecutive runs without a considerable loss of catalytic activity. The
EDAX analysis and SEM photograph of the recycled catalyst shows no change in its structure
(Fig. 8).
<Fig. 7>
<Fig. 8>
Conclusion
In this study, a novel arginine-functionalized heterogeneous polymeric nanocatalyst was
introduced for the one-pot cyclocondensation reaction of aromatic methyl ketones and thiourea in
the presence of iodine under mild reaction conditions. The present method can be classified as a
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new approach for the preparation of diheteroaryl thioethers. This procedure includes further
important aspects like excellent yields, the use of green catalytic system, reusability of the
nanocatalyst, the easy workup procedure, high atom economy, and environmentally benign
reaction conditions.
Acknowledgments
The authors gratefully acknowledge the financial support from the University of Kashan for
supporting this work by Grant NO. (256722/29).
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Figure captions
Table 1. Optimization of reaction conditions for the model reaction.
Table 2. Synthesis of diheteroaryl thioethers using Arg-SNP.
Scheme 1. Synthesis of diheteroaryl thioether derivatives by Arg-SNP.
Scheme 2. The procedure for the synthesis of Arg-SNPs.
Scheme 3. Plausible mechanism of the catalytic reaction for the synthesis of diheteroaryl
thioethers.
Fig. 1. Representative examples of the bioactive diaryl sulfides
Fig. 2. The FTIR spectra of (a) SNPs and (b) Arg-SNPs.
Fig. 3. The SEM analyses of (a) SNPs and (b) Arg-SNPs.
Fig. 4. The EDAX spectrum of Arg-SNPs.
Fig. 5. The XRD patterns of pristine starch and its nanostructures.
Fig. 6. TGA-DTA diagrams of (a) SNPs and (b) Arg-SNPs.
Fig. 7. The recyclability of the nanocatalyst.
Fig. 8. (a) SEM and (b) EDAX of recovered nanocatalyst.
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Table 1. Optimization of reaction conditions for the model reaction.a
S
S
S
S
O
H2N
NH2
Conditions
+
I2
+
N
H2N
NH2
N
Ph
Ph
Ph
Entry
Catalyst (g)
Solvent
Temp (°C)
Yield (%)b
1
2
0.006
0.01
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
EtOH
40
40
40
40
40
30
50
60
80
40
40
40
40
40
40
90
90
3
0.02
96
4
0.025
0.03
95
5
92
6
0.02
trace
80
7
0.02
8
0.02
15
9
0.02
trace
15
10
11
12
13
14
15
16
17
18
19
20
21
0.02
0.02
CHCl3
CH3CN
H2O
trace
trace
trace
trace
65
0.02
0.02
0.02
CH2Cl2
DMSO
0.02 (Arg)
0.02 (Val)
0.02 (Val-SNP)
0.02 (Ala)
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
40
40
40
40
40
40
60
88
58
70
40
40
0.02 (Ala-SNP)
0.02 (SNP)
-
aAcetophenone (1 mmol), thiourea (2 mmol), I2 (1 mmol), catalyst, and solvent (3 ml) for 5 h.
bIsolated yield of the pure compound
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Table 2. Synthesis of diheteroaryl thioethers using Arg-SNP.a
Entry
1
R
Product Yield (%)b Mp (oC)
Mp (Lit.)c
H
3a
3b
3c
3d
3e
3f
96
72
70
79
76
97
91
98
90
99
211-213
159-161
155-158
229-231
229-231
212-214
199-201
204-207
218-219
290-292
208.9-212.6
2
3
4-OH
2-OH
157.2-162.8
New
231
4
4-Br
5
4-Cl
233
6
4-Me
214
7
3-Me
3g
3h
3i
200
8
4-OMe
4-NO2
4-Morpholin
206
9
New
New
10
3j
aMethyl ketone (1 mmol), thiourea (2 mmol), I2 (1 mmol), Arg-SNP (0.02 g), and
DMSO (3 ml) for 5 h.
bIsolated yield of the pure compound
c[22]
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H
N
O
N
NH
COOH
OH
N
Me
S
S
S
N
N
Me
Vortioxetine antidepressant
Nicotinic acethylcholine receptor ligand
HIV -1 integrase inhibitor
N
S
S
OMe
OMe
Cl
O
Ph
N
S
N
S
OMe
N
H
MeO
N
S
N
N
CO2Me
N
HO
Cl
MeO
N
H
Cathespine-D-inhibitor
Protein tyrosine phosphatase inhibitor
MCF-7 growth inhibitor
Fig. 1. Representative examples of the bioactive diaryl sulfides.
19

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(b)
(a)
Fig. 2. The FTIR spectra of (a) SNPs and (b) Arg-SNPs.
20

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(a)
(b)
Fig. 3. The SEM analyses of (a) SNPs and (b) Arg-SNPs.
21

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Fig. 4. The EDAX spectrum of Arg-SNPs.
22

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Arg-SNP
SNP
Starch
Fig. 5. The XRD patterns of pristine starch and its nanostructures.
23

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(a)
(b)
Fig. 6. TGA-DTA diagrams of (a) SNPs and (b) Arg-SNPs.
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100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
96
94
93
93
91
1
2
3
4
5
Run
Fig. 7. The recyclability of the nanocatalyst.
25

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(a)
(b)
Fig. 8. (a) SEM and (b) EDAX of recovered nanocatalyst.
26

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R
N
NH2
O
S
S
S
Arg-SNP
+
S
I2
CH3
+
H2N
NH2
DMSO, 40°C
R
NH2
N
R
Scheme 1: Synthesis of diheteroaryl thioether derivatives by Arg-SNP.
27

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OH
O
O
Si
Si
Cl
Cl
OMe
O
Toluene
SNP
MeO Si
OMe
Cl
OH
SNP
O
24 h , reflux
O
OH
Si
Cl
SNP
O
Cl-SNP
OH
NH2
HN
NH
NH
O
O
NH
NH
O
Si
Si
Arginine
Toluene
O
N
OH
SNP
O
H
NH2
O
NH
Si
NH
HN
NH2
Arg-SNP
OH
O
Scheme 2. The procedure for the synthesis of Arg-SNPs.
28