Nano n -propylsulfonated magnetic γ-Fe2O3 as an efficient and reusable catalyst for the synthesis of thioamides

Article abstract of DOI:10.1080/17415993.2013.765429

One-pot three-component reactions of aldehydes, amines, and sulfur are carried out in the presence of nano n-propylsulfonated magnetic γ-Fe2O3 as a catalyst for the synthesis of biologically interesting thioamide derivatives. The value of this catalytic method lies in its mild reaction catalyst and conditions, good yields, and ease of handling.

Full text of DOI:10.1080/17415993.2013.765429

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Nano n-propylsulfonated magnetic
γ-Fe2O3 as an efficient and reusable
catalyst for the synthesis of thioamides
Zhikui Yin a & Bin Zheng b
a School of Pharmacy, Xinxiang Medical University, Xinxiang,
Henan, 453003, People's Republic of China;
b Department of Parasitology, Xinxiang Medical University,
Xinxiang, Henan, 453003, People's Republic of China
Version of record first published: 12 Feb 2013.
To cite this article: Zhikui Yin & Bin Zheng (2013): Nano n-propylsulfonated magnetic γ-Fe2O3 as
an efficient and reusable catalyst for the synthesis of thioamides, Journal of Sulfur Chemistry,
DOI:10.1080/17415993.2013.765429
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Journal of Sulfur Chemistry, 2013
http://dx.doi.org/10.1080/17415993.2013.765429
Nano n-propylsulfonated magnetic γ-Fe2O3 as an efficient and
reusable catalyst for the synthesis of thioamides
Zhikui Yina* and Bin Zhengb
aSchool of Pharmacy, Xinxiang Medical University, Xinxiang, Henan 453003, People’s Republic of China;
bDepartment of Parasitology, Xinxiang Medical University, Xinxiang, Henan 453003, People’s Republic of
China
(Received 10 October 2012; final version received 1 January 2013)
One-pot three-component reactions of aldehydes, amines, and sulfur are carried out in the presence of nano
n-propylsulfonated magnetic γ -Fe2O3 as a catalyst for the synthesis of biologically interesting thioamide
derivatives. The value of this catalytic method lies in its mild reaction catalyst and conditions, good yields,
and ease of handling.
SO3H
O
nano
SO3H
O
γ-Fe2O3
S
O
SO3H
R1
+
Ar
N
ArCHO + R1NHR2
S8
DMF,100°C
R2
Keywords: thioamides; amines; nano n-propylsulfonated γ -Fe2O3; γ -Fe2O3; synthesis
1. Introduction
Thioamide derivatives have attracted considerable attention in the recent years because of their
wide range of pharmaceutical activities such as antifungal (1), anticonvulsant (2), antithyroid (3),
and antioxidant (4) activities. In addition, they also find wide applications as intermediates in the
synthesis of five- and six-membered heterocycles (5) and active pharmaceutical ingredients such
as fentiazac, fenclosic acid, and febuxostate (6). Therefore, the synthesis of thioamide derivatives
has aroused great interest in the organic and medicinal communities.
There are several methods available for the preparation of thioamide derivatives including
thionation of amides using PSCl3 (thiophosphoryl chloride) or TsCl (4-toluenesulfonyl chloride)
mediated Beckmann rearrangement (7), basic catalyzed Willgerodt–Kindler reaction (8), via
the Kindler reaction in the presence of sulfated tungstate (9), and thionation of amides using
thionating reagents (10). Despite, the importance of these reported protocols may suffer from
drawbacks such as the use of expensive reagents, harsh reaction conditions, prolonged reaction
times, cumbersome product isolation procedures, and low yields. Hence, the exploration of a
mild, efficient, and synthetic protocol for the thioamide derivatives is highly desirable.
*Corresponding author. Email: yinzhikui2004@163.com
© 2013 Taylor & Francis

2
Z. Yin and B. Zheng
Magnetic nanoparticles are receiving increasing interest in the recent years (11). The magnetic
nature of these particles allows for easy recovery and recycling of the catalysts by an external
magnetic field, which may optimize operational cost and enhance the product’s purity. Moreover,
magnetic nanoparticles can be functionalized easily through appropriate surface modifications,
which are able to load various functionalities (12).
As a part of our endeavors toward the development of efficient and environmentally benign
synthetic methodologies using economic and eco-friendly heterogeneous catalysts, we now report
a highly efficient procedure for the preparation of thioamide derivatives via a one-pot, three-
component reaction of aldehydes, amines, and sulfur using nano n-propylsulfonated γ -Fe2O3
(NPS-γ -Fe2O3) as an efficient and reusable catalyst in DMF (Scheme 1). NPS-γ -Fe2O3 was easily
prepared as described (13) by the reaction of nano γ -Fe2O3 with 1,3-propanesultone (Scheme 2).
SO3H
O
nano
SO3H
O
γ-Fe2O3
S
O
SO3H
R1
+
Ar
N
ArCHO + R1NHR2
S8
DMF, 100°C
R2
2
3
4
1
Scheme 1. Synthesis of thioamide derivatives using NPS-γ -Fe2O3.
SO3H
O
O
O
O
O
nano
γ-Fe2O3
OH
OH
OH
S
SO3H
SO3H
nano
γ-Fe2O3
O
Toluene, reflux
nano n-propylsulfonated γ-Fe2O3
Scheme 2. Synthesis of NPS-γ -Fe2O3.
2. Results and discussion
The one-pot synthesis of thioamides was achieved by the three-component reaction of aldehydes,
amines, and sulfur in the presence of NPS-γ -Fe2O3 as a heterogeneous catalyst (Scheme 1). To
find optimum conditions, the synthesis of thiobenzanilide (4a) was used as a model reaction.
Therefore, a mixture of benzaldehyde (1 mmol), aniline (1 mmol), and sulfur (1.2 mmol) was
heated on the oil bath at different temperatures in the presence of various amounts of NPS-
γ -Fe2O3 as a catalyst in DMF (Table 1). As can be seen from this table, the efficiency of the
reaction is mainly affected by the amount of the catalyst. The optimal amount of the catalyst was
200 mg/mmol and a higher amount of the catalyst did not increase the yield noticeably. Also, the
yields increased as the reaction temperature was raised and at 100◦C, the product 4a was obtained
in high yield.
The effects of solvents such as CH2Cl2, EtOH, CH3CN, DMSO, H2O, and solvent-free con-
ditions were also studied, but in comparison with DMF, the reaction times were longer and the
yields were considerably lower (Table 2).
To show the generality of this method, a range of thioamides were prepared under the opti-
mized reaction conditions (Table 3). Also, aromatic aldehydes with substituents carrying either

Journal of Sulfur Chemistry
Table 1. Amounts of catalyst and temperature optimization for the synthesis of thiobenzanilide.a
3
Entry
NPS-γ -Fe2O3 (mg/mmol)
T (◦C)
Time (h)
Yield (%)b
1
2
3
4
5
6
7
8
9
–
50
100
100
100
100
100
100
100
50
80
90
110
120
24
10
10
8
6
6
13
51
69
79
92
90
91
29
56
82
89
90
100
150
200
250
300
200
200
200
200
200
6
24
12
6
6
6
10
11
12
Notes: aReaction conditions: benzaldehyde (1 mmol), aniline (1 mmol), and sulfur (1.2 mmol), DMF (10 mL).
bIsolated yield.
Table 2. Solvent optimization for the synthesis thiobenzanilide.a
Entry
Solvent
Temperature (◦C)
Time (h)
Yield (%)b
1
2
3
4
5
6
7
CH2Cl2
EtOH
CH3CN
DMSO
H2O
Reflux
Reflux
Reflux
100
Reflux
100
12
12
10
8
24
6
49
53
59
68
0
DMF
Neat
92
73
40
6
Notes: aReactionconditions: benzaldehyde(1mmol), aniline(1 mmol), andsulfur (1.2mmol),
NPS-γ -Fe2O3 (200 mg).
bIsolated yield.
Table 3. Preparation of thioamides.a
Entry
Ar
R1
R2
Product
Time (h)
Yield (%)b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
C6H5
C6H5
C6H5
C6H5
C6H5
H
c-Hex
C6H5
4-Cl-C6H4
4-Me-C6H4
2-Cl-C6H4
H
H
H
H
C6H5
H
H
H
H
H
H
H
H
H
H
H
H
H
H
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
7
6
6
6
6
6
8
8
8
8
6
6
7
7
80c
92
92 (89, 85, 84)d
89
91
92
C6H5
4-Cl-C6H4
4-NO2-C6H4
4-MeOC6H4
3-NO2-C6H4
4-MeO-C6H4
4-MeO-C6H4
4-pyridyl
2-thiophenyl
78c
72c
69c
71c
90
4-MeO-C6H4
C6H5
87
91
85
C6H5
Notes: aReaction conditions: aldehyde (1 mmol), amine (1 mmol), sulfur (1.2 mmol), DMF (10 mL); NPS-γ -Fe2O3 (200 mg);
100◦C.
bIsolated yield.
cAmmonia as ammonium acetate.
dYields after three times of catalyst recovery.
electron-donating or electron-withdrawing group and various amines reacted successfully and
gave the expected products in good to excellent yields in a relatively short reaction time.
The recovery and reuse of a catalyst are highly preferable for a greener process. Thus, the
recyclability of NPS-γ -Fe2O3 was investigated using benzaldehyde, aniline, and sulfur as model

4
Z. Yin and B. Zheng
substrates. The catalyst was easily separated by the use of an external magnet after the reaction,
and was then washed with EtOH and dried for 30 min at 110◦C. The recovered NPS-γ -Fe2O3
was reused without any significant deactivation even after three runs.
3. Conclusion
In summary, we have developed an efficient one-pot, three-component reaction of aldehydes,
amines, and sulfur for the direct construction of a library of thioamide deverivates catalyzed by
NPS-γ -Fe2O3 in DMF. Product separation and catalyst recycling are easily accomplished with
the assistance of the external magnet; the catalyst can be recycled at least three times.
4. Experimental
4.1. General
1H NMR and 13C NMR spectra were determined on a Bruker AV-400 spectrometer (100 MHz for
13C NMR) at room temperature using tetramethylsilane as an internal standard solution (DMSO-
d6); coupling constants (J) were measured in Hz; elemental analysis were performed by aVario-III
elemental analyzer; melting points were determined on a XT-4 binocular microscope and were
uncorrected; commercially available reagents were used throughout, without further purification
unless otherwise stated.
4.2. Synthesis of NPS-γ-Fe2O3
NPS-γ -Fe2O3 is prepared by the reported procedure (13). FeCl2·4H2O (9.25 mmol) and
FeCl3·6H2O (15.8 mmol) were dissolved in deionized water (150 mL) under Ar atmosphere
at room temperature. A NH4OH solution (25%, 50 mL) was then added dropwise to the stirring
mixture at room temperature to reach the reaction pH to 11. The resulting black dispersion was
continuously stirred for 1 h at room temperature and then heated to reflux for 1 h to yield a brown
dispersion. The magnetic nanoparticles were then purified by a repeated centrifugation, decanta-
tion, and redispersion cycle for three times. The as-synthesized sample was heated at 2◦C min−1
up to 200◦C and then kept in the furnace for 3 h to give a reddish-brown powder. The sulfonation of
maghemite nanoparticles was conducted using nano Fe2O3 (6 g), which was suspended in 600 mL
of 0.1 M toluene solution of 1,3-propanesultone and the colloidal solution was refluxed for 48 h.
The sulfonated nano γ -Al2O3 was isolated and purified by repeated washing and centrifugation.
4.3. General procedure for the preparation of 4
To a mixture of aldehyde (1 mmol), amine (1 mmol) or ammonium acetate, sulfur (1.2 mmol)
and DMF (10 mL), NPS-Fe2O3 (200 mg) were added. The mixture was stirred at 100◦C for the
appropriate time (Table 3). After the completion of the reaction (TLC), the reaction mixture was
diluted with EtOAc. The catalyst was separated by an external magnet, washed with EtOH, dried,
and re-used for a consecutive run under the same reaction conditions. The organic layer was
washed with saturated aq. NH4Cl solution, water, dried over Na2SO4, and concentrated under
reduced pressure to obtain crude product, which was purified by chromatography on a silica
gel with hexane–ethyl acetate (8:2) as an eluent to obtain pure products. All the products were

Journal of Sulfur Chemistry
5
1
known compounds and were characterized by IR, H NMR, elemental analysis, and compared
with reported values (7–10).
Acknowledgment
We are pleased to acknowledge the financial support from Xinxiang Medical University.
References
(1) Shekarchi, M.; Pirali-Hamedani, M.; Navidpour, L.; Adib, N.; Shafiee, A. J. Iran Chem. Soc. 2008, 5, 150–158.
(2) Kulandasamy, R.; Adhikari, A.V.; Stables, J.P. Bull. Korean Chem. Soc. 2010, 31, 3318–3326.
(3) (a) Chernov’yants, M.S.; Dolinkin, A.O. J. Struct. Chem. 2010, 51, 1176–1190; (b) Corban, G.J.; Hadjikakou, S.K.;
Tsipis, A.C.; Kubicki, M.; Bakas, T.; Hadjiliadis, N. New J. Chem. 2011, 35, 213–224.
(4) Chernovyants, M.S.; Aleshina, N.V. J. Anal. Chem. 2012, 67, 214–218.
(5) Hisano, T.; Yabuta, Y. Chem. Pharm. Bull. 1973, 21, 511–517.
(6) Lednicer, D. Strategies for Organic Drug Synthesis and Design; John Wiley Press: Hoboken, 2009; Chapter 8, pp
298–299.
(7) (a) Pathak, U.; Pandey, L.K.; Mathur, S.; Suryanarayana, M.V.S. Chem. Commun. 2009, 5409–5411; (b) Liu, L.-F.;
An, N.; Pi, H.-J.; Ying, J.; Du, W.; Deng, W.-P. Synlett 2011, 7, 978–981.
(8) Okamoto, K.; Yamamoto, T.; Kanbara, T. Synlett 2007, 17, 2687–2690.
(9) Pathare, S.P.; Chaudhari, P.S.; Akamanchi, K.G. Appl. Catal. A: Gen. 2012, 425–426, 125–129.
(10) (a) Scheeren, J.W.; Ooms, P.H.J.; Nivard, R.J.F. Synthesis 1973, 3, 149–150; (b) Curphey, T.J. J. Org. Chem. 2002,
67, 6461–6473; (c) Steliou, K.; Mrani, M. J. Am. Chem. Soc. 1982, 104, L3104–L3106; (d) Pathak, U.; Pandey,
L.K.; Tank, R. J. Org. Chem. 2008, 73, 2890–2893.
(11) (a) Lu, A.H.; Salabas, E.L.; Schueth, F. Angew Chem. Int. Ed. 2007, 46, 1222–1244; (b) Somorjai, G.A.; Park, J.Y.
Angew Chem. Int. Ed. 2008, 47, 9212–9228.
(12) (a) Megia-Fernandez, A.; Ortega-Munoz, M.; Lopez-Jaramillo, J.; Hernandez- Mateo, F.; Santoyo-Gonzalez, F. Adv.
Synth. Catal. 2010, 352, 3306–3320; (b) Wang, B.G.; Ma, B.C.; Wang, Q.O.; Wang, W. Adv. Synth. Catal. 2010, 352,
2923–2928; (c) Firouzabadi, H.; Iran-poor, N.; Gholinejad, M.; Hoseini, J. Adv. Synth. Catal. 2011, 35, 125–132; (d)
Amali, A.J.; Rana, R.K. Green Chem. 2009, 11, 1781–1786; (e) Oliveira, R.L.; Kiyohara, P.K.; Rossi, L.M. Green
Chem. 2010, 12, 144–149; (f) Zeng, T.Q.;Yang, L.; Hudson, R.; Song, G.H.; Moores, A.R.; Li, C.J. Org. Lett. 2011,
13, 442–445.
(13) Sobhani, S.; Parizi, Z.P.; Razavi, N. Appl. Catal. A: Gen. 2011, 409–410, 162–166.