Nanostarch: a novel and green catalyst for synthesis of 2-aminothiazoles

Article abstract of DOI:10.1007/s00706-016-1805-8

Abstract: In this work, starch nanoparticles as a green and cheap catalyst were obtained based on the precipitation of amorphous starch in ethanol. It was found that starch nanoparticles are efficient catalyst for the synthesis of 2-aminothiazoles using methylcarbonyl compounds and thiourea as precursors. The use of green and biodegradable nanostarch makes this present methodology quite simple, shorter reaction times and milder conditions, and more convenient and economically viable compared to catalyzed methods reported in the literature. Graphical abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s00706-016-1805-8

Monatsh Chem
DOI 10.1007/s00706-016-1805-8
ORIGINAL PAPER
Nanostarch: a novel and green catalyst for synthesis
of 2-aminothiazoles
1
1
Javad Safari
•
Masoud Sadeghi
Received: 7 October 2015 / Accepted: 20 June 2016
Ó Springer-Verlag Wien 2016
Abstract In this work, starch nanoparticles as a green and
cheap catalyst were obtained based on the precipitation of
amorphous starch in ethanol. It was found that starch
nanoparticles are efficient catalyst for the synthesis of
Introduction
Starch like most natural polymers (such as chitin, chitosan,
cellulose), is a natural, renewable, biocompatible, and
biodegradable polymer that produced by many plants as a
source of stored energy. Starch is the second most abundant
natural polymer after cellulose. It has low cost and easily can
be extracted from various plant parts, such as plant roots,
stalks, seeds, and variety staple crops such as corn, potato,
wheat, rice. Starch or amylum is a carbohydrate that consists
of glucose monomer units that has two type arrangement,
amylose and amylopectin. Amylose is a linear polymer of
glucose units that are connected to each other through a-link
2
-aminothiazoles using methylcarbonyl compounds and
thiourea as precursors. The use of green and biodegradable
nanostarch makes this present methodology quite simple,
shorter reaction times and milder conditions, and more
convenient and economically viable compared to catalyzed
methods reported in the literature.
Graphical abstract
(1–4). There are about 1.6 % of the glucose units connected
by a-link (1–6) and they are attached to the main structure of
amylose, which leads to the branched structure of amylose
(Scheme 1). Amylopectin is a large and branched polysac-
charide that the main structure of molecule is similar to
amylose. In total, starch is formed from 20 to 30 % amylose
and 70 to 80 % amylopectin [1–3].
The use of starch (or carbohydrates in general) as a
catalyst has attracted much attention in recent years [4–6].
The main reasons for this attention are the cost, availability
and biodegradability properties of carbohydrates.
Keywords Methylcarbonyl Á 2-aminothiazoles Á
Nanostarch Á Nanoparticle Á Iodine
Starch nanoparticles (NPs) have unique properties dif-
ferent from the bulk properties because of their nanometric
size [7]. In recent year, new processes have been intro-
duced to produce starch NPs, such as the precipitation of
amorphous starch [8, 9], enzymatic hydrolysis and com-
bining complex formation [10], microfluidization [11],
ultrasonic irradiation [12], and ionic liquid [13]. There are
a number of reports that have presented the use of func-
tionalized starch NPs for organic reactions. However, to
the best our knowledge, there are no similar applications
for starch NPs as the catalyst in organic reactions [14–17].
&
Javad Safari
safari@kashanu.ac.ir;
safari_jav@yahoo.com
1
Laboratory of Organic Chemistry Research, Department of
Organic Chemistry, College of Chemistry and Biochemistry,
University of Kashan, Kashan 87317-51167,
Islamic Republic of Iran
123

J. Safari, M. Sadeghi
Scheme 1
Scheme 2
Fig. 1 a FT-IR spectra of starch (blue) and b starch NPs (red)
2
-aminothiazoles have a special place in organic syn-
thesis due to the medical and pharmaceutical applications
18, 19]. In the meantime, 2-aminothiazoles has been
[
considered as a special case in recent years. There are
various synthetic ways for preparation of 2-aminothiazoles
[
20–35]. The most straightforward and easy way for the
synthesis of 2-aminothiazoles is the use of methylcarbonyl
compounds and thiourea as the raw materials. The fol-
lowing protocols use acetophenone and thiourea as
precursors for the synthesis of 2-aminothiazole: CuO/I2
Fig. 2 SEM image of synthesized starch NPs
[
[
36], NaICl [37], O /KI/[Bmim]OTf [38], and CBr /Et N
2 2 4 3
39].
In recent paper, our group propose starch NPs for the
spectrums because of the chemical similarity of the two
species. However, minor differences are visible due to the
different particle size.
synthesis of 2-aminothiazole in satisfied yield and fairly
short time (Scheme 2).
SEM image of synthesized starch NPs is shown in Fig. 2
the synthesized NPs have a good average diameter
(70 nm).
Results and discussion
The X-ray diffraction (XRD) patterns of the starch and
starch NPs are shown in Fig. 3. The original starch gives
three characteristic peaks at 2h = 11 (weak diffraction
peak), 14 (strong diffraction peak), and 27 (strong
diffraction peak) indicating the high degree of crystallinity
of starch. However, there are no similar peaks in the
diffractograms of the starch NPs. The broad peaks in the
X-ray diffraction of starch NPs are attributed to the
increased amorphous nature of the starch NPs. The XRD of
the starch NPs is characteristic of an amorphous polymer.
To investigate the feasibility of the synthetic method for
the synthesis of 2-aminothiazoles, initial experiments were
In the first of study, starch was modified to starch NPs by a
precipitation process. The structural organization of starch
NPs was investigated by FT-IR, SEM and XRD.
The FT-IR of starch and starch NPs were taken with
KBr pellets and shown in Fig. 1. The characterization
-
1
peaks in the starch spectrum are 3409 cm
(–OH
(C–H stretching) 1020 and
0158 cm (C–O stretching). The characteristic absorp-
tion peaks in the FT-IR spectrum of starch NPs include
-
1
stretching), 2926 cm
-
1
1
-
1
-1
3
427 cm (–OH group), 2932, 1026 and 1155 cm (C–O
stretching). There is not much difference between two
1
23

Nanostarch: a novel and green catalyst for synthesis of 2-aminothiazoles
solvent and amounts of catalyst were used. In addition, the
optimal temperature conditions were screened. The results
indicate that DMSO is more efficient than other solvents
such as EtOH, CH CN and EtOAc. The varying amounts of
3
starch NPs were employed, and 10 mg was used as the best
catalyst amount under the reaction conditions (Table 1,
entry 10).
After determining the optimal conditions, we surveyed
more substrates, and achieved the satisfactory results,
which were prepared are summarized in Table 2.
Generally, a-hydrogen in aldehydes, b-ketoesters, and
b-diketones has higher acid strength than ketones. The less
pKa substrates, resulting in the more formation of the enol
and more a-iodocarbonyl intermediate (Scheme 3). As
expected, the methylcarbonyl substrates contain more
acidic hydrogen (such as b-ketoesters entries 7, 8, and 9, b-
diketone entry 10), showed better results than the cases
containing less acidic hydrogen (such as entries 2–5).
The plausible mechanism for the formation of the
Fig. 3 X-ray diffraction patterns of the starch (a) and starch NPs (b)
2
-aminothiazoles is shown in Scheme 4. It is clear from the
performed using acetophenone, thiourea and iodine as
reactants at 80 °C. A reaction model was carried out, to
compare starch and starch NPs catalytic properties. The
results were indicated, starch NPs have better efficiency
than bulk case (Table 1, entry 3).
structure of starch that there are many hydroxyl groups (–
OH) on the structure of starch. These hydroxyl groups can
activate the methylcarbonyl substrates in the reaction by
hydrogen bonding. The hydrogen bonding between the
hydroxyl groups on the starch and the carbonyl group in the
methylcarbonyl compounds is a key factor in the produc-
tion of a-iodocarbonyl, nucleophilic attack of thiourea
species at the a-position of a-iodocarbonyl, and the ring
closure of thiazole. Studies showed that in the absence of a
suitable catalyst, the a-iodocarbonyl species is not pro-
duced with a good yield [36].
With regard to the Table 1, starch NPs was selected as
the main catalyst and all reactions were carried out utiliz-
ing starch NPs. After that it was decided to search for the
optimal conditions for the desired reaction. The various
Table 1 Optimization of the reaction conditions
In summary, we have demonstrated a simple and effi-
cient protocol for the synthesis of 2-aminothiazoles using
starch NPs as the catalyst. We have used methylcarbonyl
compounds and thiourea as precursors. This method is very
quick, and avoids the use of expensive reagents and high
temperature.
Entry
Nanocatalyst/mg
Solvent
Temperature/°C
Yield/%
1
2
3
4
5
6
7
8
9
–
–
80
80
80
80
80
80
80
80
80
80
80
70
90
65 [40]
58
50 (bulk starch)
EtOH
EtOH
DMSO
Experimental
Materials
50
50
50
50
40
30
20
10
5
65
75
CH
3
CN
55
EtOAc
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
60
Chemicals were purchased from the Merck and Fluka
chemical companies in high purity. All of the materials
were of commercial reagent grade.
80
75
90
10
11
12
13
92
Apparatus
90
10
10
85
Melting points were determined using an Electrothermal
80
9100 apparatus and are uncorrected. FT-IR spectra were
recorded as KBr pellets on a Shimadzu FT-IR-8400S
1 13
spectrometer. HNMR (400 MHz) and CNMR spectra
Reaction condition: acetophenone (1 eq), thiourea (1 eq), iodine
1 eq), and solvent stirred at 80 °C for 1 h
(
123

J. Safari, M. Sadeghi
Table 2 Starch NPs catalyzed synthesis of 2-aminothiazoles
1
2
Entry
R
R
M.p. /°C
Lit. m.p. /°C
Yield /%
1
2
3
4
5
6
7
8
9
H
H
89–90
90–92 [29]
95
92
85
96
88
84
90
96
96
97
Ph
H
151–153
161–162
285–286
88–91
148–150 [35]
162–163 [35]
286–287 [35]
79–92 [29]
4-Cl-Ph
H
4-NO
2
-Ph
H
3-Me-Ph
2-OH-Ph
4-OH-Ph
H
H
138–139
198–200
177–179
225–226
148–149
139–140 [29]
198–200 [35]
177–178 [29]
224–226 [29]
148–150 [29]
H
CH
CH
CH
3
3
3
COOEt
COOMe
COOCH
1
0
2 2
CH=CH
Reaction condition: acetophenone (0.5 mmol), thiourea (0.5 mmol), iodine (0.5 mmol), starch NPs (10 mg) and DMSO (2 mL) stirred at 80 °C
for 1 h
constant stirring for 1 h to complete gelatinization of corn
Scheme 3
starch, 150 mL of absolute ethanol was added drop-wise to
the previous solution with constant stirring. The resulting
suspensions containing nanoparticle were cooled at the
room temperature and another 35 mL of absolute ethanol
was added drop-wise to the suspensions for 1 h with con-
stant stirring. The suspensions were centrifuged and the
prepared starch NPs were washed using absolute ethanol to
remove the water. The starch NPs was dried at 50 °C to
remove ethanol.
were obtained using a Bruker DRX-400 AVANCE spec-
trometer. Analytical thin-layer chromatography (TLC) was
accomplished on 0.2 mm precoated plates of silica gel
0 F-254 (Merck) or neutral alumina oxide gel 60F 254
Merck). Morphological characteristics of the nanostruc-
Procedure for preparation of 2-aminothiazole
by starch NPs
6
(
tures were characterized using a scanning electron
microscope (SEM, EVO LS 10, Zeiss, Carl Zeiss Inc.,
Germany) operating at an accelerating voltage of 20 kV
under high vacuum.
A mixture of methylcarbonyl (0.5 mmol), thiourea
(0.5 mmol), iodine (0.5 mmol), DMSO (2 mL) and 10 mg
Starch NPs were stirred at 80 °C. After completion of the
reaction (monitored by TLC, petroleum:ethyl acetate, 4:1),
the reaction was quenched by the addition of 10 mL dis-
tilled water. The aqueous solution was extracted with
EtOAc (3 9 10 mL) and the combined extract was dried
with anhydrous Na SO . The solvent was vacuumed, and
Procedure for preparation of starch NPs
2
4
Starch NPs were prepared using precipitation of amorphous
starch. 8.2 g of starch was added into 35 mL of distilled
water and then the mixture was heated at 90 °C. After
finally, the resulting precipitate was recrystallized by
EtOH.
1
23

Nanostarch: a novel and green catalyst for synthesis of 2-aminothiazoles
Scheme 4
Acknowledgments We gratefully acknowledge the financial support
from the Research Council of the University of Kashan for supporting
this work by Grant No. 363022/5.
18. Das D, Sikdar P, Bairagi M (2015) Eur J Med Chem 109:89–98
19. Smith B, Chang HH, Medda F, Gokhale V, Dietrich J (2012)
Bioorg Med Chem Lett 22:3567–3570
2
0. Aoyama T, Murata S, Arai I, Araki N, Takido T, Suzuki Y,
Kodomari M (2006) Tetrahedron 62:3201–3213
2
2
1. Wipf P, Venkatraman S (1996) J Org Chem 61:8004–8005
2. Wang Y, Zhao F, Chi Y, Zhang WX, Xi Z (2014) J Org Chem
References
7
9:11146–11154
3. Chen B, Guo S, Guo X, Zhang G, Yu Y (2015) Org Lett
7:4698–4701
1
2
. Angellier H, Choisnard L, Molina-Boisseau S, Ozil P (2004)
Dufresne. Biomacromol 5:1545–1551
. BeMiller JN, Whistler RL (2009) Starch: Chemistry and tech-
nology, 3rd; food science and technology. Academic Press, New
York
2
2
1
4. Donohoe TJ, Kabeshov MA, Rathi AH, Smith IED (2012) Org
Biomol Chem 10:1093–1101
5. Ishiwata Y, Togo HF (2008) Synlett (17):2637–2641
6. de Kimpe N, de Cock W, Keppens M, de Smaele D (1996) J
Heter Chem 33:179–1183
2
2
3
. Bul e´ on A, Colonna P, Planchot V, Ball S (1998) Int J Biol
Macromol 23:85–112
4
5
6
. Hatamjafari F (2013) Helvitica Chim Acta 96:1560–1563
. Shaabani A, Rahmati A, Badri Z (2008) Catal Commun 9:13–16
. Wan Y, Lin W, Chen XM, Shen Y, Xin HQ, Xu HH, Yuan R,
Pang LL, Ma R, Yue CH, Yin W, Bo RC, Wu H (2009) Lett Org
Chem 6:456–461
2
2
2
3
3
7. Kumar D, Kumar NM, Patel G, Gupta S, Varma RS (2011)
Tetrahedron Lett 52:1983–1986
8. Madhav B, Murthy SN, Kumar BA, Ramesh K, Nageswar Y
(
2012) Tetrahedron Lett 53:3835–3838
9. Meshram HM, Thakur PB, Babu BM, Bangade VM (2012)
Tetrahedron Lett 53:5265–5269
7
. Le Corre D, Bras J, Dufresne
1:1139–1153
A (2010) Biomacromol
1
0. Miyamoto K, Nishi Y, Ochiai
4
M (2005) Angew Chem
8
9
. Ma X, Jian R, Chang PR, Yu J (2008) Biomacromol 9:3314–3320
. Tan Y, Xu K, Li L, Liu C, Song C, Wang P (2009) ACS Appl
Mater Interfaces 1:956–959
4:6896–6899 (International ed. in English)
1. Safari J, Abedi-Jazini Z, Zarnegar Z, Sadeghi M (2015) J Nano
Res 17:495
1
1
0. Kim JY, Lim ST (2009) Carbohydr Polym 76:110–116
1. Liu D, Wu Q, Chen H, Chang PR (2009) J Colloid Inter Sci
3
3
3
2. Singh H, Singh P, Deep K (1983) Tetrahedron 39:1655–1660
3. Sv eˇ tl ´ı k J, Ture cˇ ek F (1984) Tetrahedron Lett 25:3901–3904
4. Xie L, Wu Y, Yi W, Zhu L, Xiang J, He W (2013) J Org Chem
3
39:117–124
1
1
1
2. Haaj SB, Magnin A, Boufi S (2014) RSC Adv 4:42638–42646
3. Zhou G, Luo Z, Fu X (2014) Ind Crops Products 52:105–110
4. Doi S, Clark JH, Macquarrie DJ, Milkowski K (2002) Chem
Commun (22):2632–2633
7
8:9190–9195
3
3
5. Yadav JS, Reddy BS, Rao YG, Narsaiah AVF (2008) Tetrahe-
dron Lett 49:2381–2383
6. Zhu YP, Yuan JJ, Zhao Q, Lian M, Gao QH, Liu MC, Yang Y,
Wu AX (2012) Tetrahedron 68:173–178
7. Ghodse SM, Telvekar VN (2015) Tetrahedron Lett 56:472–474
8. ZhaoJ,XuJ,ChenJ,HeM,WangX(2015)Tetrahedron71:539–543
9. Keshari T, Kapoorr R, Yadav LDS (2015) Tetrahedron Lett
56:5623–5627
0. Yen M (2004) Dyes Pigments 63:1–9
1
1
1
5. Kumar S, Verma S, Jain SL (2015) Tetrahedron Lett
5
6:2430–2433
6. Verma S, Le Bras J, Jain SL, Muzart J (2013) Dalton Trans
2:14454–14459
3
3
3
4
7. Verma S, Tripathi D, Gupta P, Singh R, Bahuguna GM,
Shivakumar LN, Chauhan RK, Saran S, Jain SL (2013) Dalton
Trans 42:11522–11527
4
123