One-pot synthesis of 1,3-thiazolidin-4-one using Bi(SCH2COOH) 3 as catalyst

Article abstract of DOI:10.1016/j.cclet.2013.03.019

A catalytic multi-component reaction involving aromatic amine, aromatic aldehydes, mercapto acid as substrates and Bi(SCH₂COOH)₃ as catalyst under solvent free conditions, afforded thiazolidin-4-one in good yields. The efficiency of the catalyst was proved with a variety of substrates, ranging from electron-deficient to electron-rich aldehydes.

Full text of DOI:10.1016/j.cclet.2013.03.019

Chinese Chemical Letters 24 (2013) 389–391
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Chinese Chemical Letters
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Original article
One-pot synthesis of 1,3-thiazolidin-4-one using Bi(SCH2COOH)3 as catalyst
b,
Naser Foroughifar a, , Sattar Ebrahimi
*
*
a Faculty of Chemistry, North Tehran Branch, Islamic Azad University, Tehran, Iran
b Department of Chemistry Malayer Branch, Islamic Azad University, Malayer, Iran
A R T I C L E I N F O
A B S T R A C T
Article history:
A catalytic multi-component reaction involving aromatic amine, aromatic aldehydes, mercapto acid as
substrates and Bi(SCH2COOH)3 as catalyst under solvent free conditions, afforded thiazolidin-4-one in
good yields. The efficiency of the catalyst was proved with a variety of substrates, ranging from electron-
deficient to electron-rich aldehydes.
Received 17 December 2012
Received in revised form 28 February 2013
Accepted 5 March 2013
Available online 11 April 2013
ß 2013 Naser Foroughifar, Sattar Ebrahimi. Published by Elsevier B.V. on behalf of Chinese Chemical
Society. All rights reserved.
Keywords:
Thiazolidin-4-one
Mercapto acid
Multicomponent
Thioglycolic acid
1. Introduction
2. Experimental
The purity of compounds was checked by thin layer chroma-
tography (TLC) using n-hexane/ethyl acetate (1/1, v/v) as an eluent.
Multi-component reactions (MCRs) and improvement of the
methods for multi-component reactions have been of considerable
interest in current day research. As a one-pot reaction, MCRs
permit rapid access to combinatorial libraries of complex
molecules, especially in drug discovery [1]. The thiazolidin-4-
one ring system is a core structure found in various synthetic
pharmaceutical compounds, displaying a broad spectrum of
biological activities [2–7]. Consequently, several synthetic meth-
ods have been developed for the synthesis of 4-thiazolidinones.
The main synthetic routes to thiazolidin-4-ones involve cyclo-
condensation of azomethines (Schiff’s base) with mercaptoacetic
acid [8]. There are also reports using chemical agents, such as N-
methylpyridinium tosylate [9] as desiccant, to assist the formation
of thiazolidinone derivatives. The use of [BmIm]OH [10], Hunig’s
base [11], and Baker’s yeast [12] has also been reported to expedite
the cyclo-condensation of the azomethines and thioglycolic acid.
However, these methodologies suffer from one or more dis-
advantages, such as costly dehydrating agents, require prolonged
heating and tedious work-up. Therefore, it was thought worth-
while to develop a new method for the cyclo-condensation. As a
result, we showed that aromatic amine, aromatic aldehydes, and 2-
mercaptoacetic acid, under solvent free conditions gave thiazoli-
din-4-one.
IR spectra were acquired on
a galaxy series FT-IR 5000
spectrophotometer as KBr discs. NMR spectra were recorded on
Bruker spectrophotometer (300 MHz) in DMSO-d6 using TMS as an
internal standard. Elemental analyses for C, H, N and S were
performed on a Vario EL III elemental analyzer.
2.1. General procedure for the synthesis of thiazolidine-4-one 4a–k
Aromatic aldehydes 1a–f (1 mmol), aromatic amine 2a–d
(1 mmol), thioglycolic acid 3 (1.2 mmol), and catalyst (10 mol%)
were mixed. The reaction mixture was then heated (70 8C) for 2 h.
The progress of the reaction was monitored by TLC using n-hexane/
ethyl acetate (1/1). After the completion of the reaction, the
reaction mixture extracted with ethylacetate (3 ꢀ 5 mL) and the
organic layer washed with 5% sodium bicarbonate. The organic
layer was then dried over anhydrous Na2SO4, concentrated, and
recrystallized from n-hexane/ethyl acetate to afford the purified
product.
2.2. Representative spectral data
2.2.1. 2-(2-Nitrophenyl)-3-p-tolylthiazolidin-4-one (4i)
IR (KBr, cmꢁ1):
n
3034 (aromatic CH stretch.), 2928 (aliphatic
CH stretch.), 1725 (C55O), 1550 (C55C), 1530, 1350 (NO2); 1H NMR
(300 MHz, DMSO-d6): 7.99 (d, 1H, J = 8.1 Hz, Harom.), 7.69–7.73
(m, 2H, Harom.), 7.49–7.54 (m, 1H, Harom.), 7.33 (d, 2H., J = 8.3 Hz,
* Corresponding authors.
d
E-mail addresses: n_forougifar@iau-tnb.ac.ir, n_forougifar@yahoo.com
(N. Foroughifar), seyonesi@gmail.com, seyonesi@iau-malayer.ac.ir (S. Ebrahimi).
1001-8417/$ – see front matter ß 2013 Naser Foroughifar, Sattar Ebrahimi. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
http://dx.doi.org/10.1016/j.cclet.2013.03.019

390
N. Foroughifar, S. Ebrahimi / Chinese Chemical Letters 24 (2013) 389–391
Table 1
Table 2
Thiazolidin-4-one 4a-k.
Optimization of the reaction condition for product 4a.
Entry
R2
R1
Yields (%)
Mp (found)
Mp (reported)
[13]
Entry
Catalyst
Time (h)
T (8C)
Yields (%)
1
2
3
4
5
6
–
24
2
rt
7
7
4a
4b
4c
4d
4e
4f
4-Me
H
4-Me
H
90
75
75
88
90
70
70
86
85
79
76
120–122
130–132
110–112
123–124
129
119–120
131–132
106–107
110–111
129–130
115–117
133–134
102–103
–
–
70
70
70
70
80
Cat. (5 mol%)
Cat. (10 mol%)
Cat. (15 mol%)
Cat. (10 mol%)
2
30
81
80
80
4-Me
H
H
2
4-Cl
H
2
4-Cl
H
3
4-Me
Ph
118–119
162–164
105–106
134–136
151–152
176–178
4g
4h
4i
4-NO2
H
[(cShem_)1DT$FI]G
4-NO2
2-NO2
3-NO2
3-NO2
4-Me
4-Me
H
S
O
Cat.
solvent free
O
4j
–
HS
CHO +
R2
+
N
NH2
R1
R1
OH
4k
–
1a-f
3
2a-d
R1= H, 4-Me, 4-Cl, 2-NO2, 3-NO2, 4-NO2
4a-k
R2
R2= H, 4-Me, 4-Cl, 4-NO2
HOOC
S
S
COOH
Bi
S
Harom.), 7.10 (d, 2H, Harom., J = 8.2 Hz), 6.75 (s, 1H, S–CH–N), 4.00 (d,
1H, J = 15.7 Hz, CH2), 3.80 (d, 1H, J = 15.8 Hz, CH2), 2.20 (s, 3H, CH3);
Calcd. for: C16H14N2O3S: C 61.13, H 4.49, N 8.91, S 10.20; Found: C
60.92, H 4.42, N 8.80, S 10.27.
Cat:
COOH
Scheme 1. Synthesis of thiazolidinon-4-one 4a–k.
2.2.2. 2-(3-Nitrophenyl)-3-p-tolylthiazolidin-4-one (4j)
IR (KBr, cmꢁ1):
n
3051 (aromatic CH stretch.), 2956 (aliphatic
CH stretch.), 1731 (C55O), 1521, 1346 (NO2); 1H NMR (300 MHz,
DMSO-d6): 8.23 (s, 1H, Harom.), 8.07 (d, 1H, J = 7.8 Hz, Harom.), 7.90
d
in the product yield observed (entry 2, Table 2). Then we repeated
the reaction in the presence of catalyst and also evaluated the
amount of catalyst required for this transformation using 5 mol%
and we obtained 30% yields. Maximum yield (81%) was obtained
when the reaction was carried out with 10 mol% of the catalyst.
Any further increase of catalyst loading does not affect the yield
(entry 5, Table 2). The reaction temperature was also examined and
70 8C was found to be the optimum temperature. Reducing the
temperature from 70 8C led to a significant decrease in the yield of
the desired product 4a.
We further examined a wide variety of aromatic aldehydes with
various substituents to establish the utility of this reaction. Ortho-,
meta- and para-substituted aromatic aldehydes undergo this one-
pot multi-component synthesis with aromatic amine and thiogly-
colic acid to afford 1,3-thiazolidin-4-ones 4a–k in good yields
(d, 1H, J = 7.4 Hz, Harom.), 7.59 (t, 1H, J = 7.9 Hz, Harom.), 7.20 (d, 2H,
J = 8.0 Hz, Harom.), 7.09 (d, 2H, J = 8.0 Hz, Harom.), 6.68 (s, 1H, S–CH–
N), 4.00 (d, 1H, J = 15.7 Hz, CH2), 3.90 (d, 1H, J = 15.6 Hz, CH2), 2.19
(s, 3H, CH3); Calcd. for: C16H14N2O3S: C 61.13, H 4.49, N 8.91, S
10.20; Found: C 60.95, H 4.44, N 8.79, S 10.08.
2.2.3. 2-(3-Nitrophenyl)-3-phenylthiazolidin-4-one (4k)
IR (KBr, cmꢁ1):
n
3044 (aromatic CH stretch.), 2936 (aliphatic
CH stretch.), 1730 (C55O), 1540, 1347 (NO2); 1H NMR (300 MHz,
DMSO-d6): 8.24 (s, 1H, Harom.), 8.07 (d, 1H, J = 8.1 Hz, Harom.), 7.90
d
(d, 1H, J = 7.7 Hz, Harom.), 7.59 (t, 1H, J = 7.8 Hz, Harom.), 7.28–7.36
(m, 4H, Harom.), 7.13–7.17 (m, 1H, Harom.), 6.72 (s, 1H, S–CH–N),
4.10 (d, 1H, J = 15.7 Hz, CH2), 3.93 (d, 1H, J = 15.7 Hz, CH2);
C
15H12N2O3S: C 59.99, H 4.03, N 9.33, S 10.68; Found: C 59.71, H
3.93, N 9.11, S 10.48.
(Scheme 1 and Table 1). Aryl aldehydes bearing electron
withdrawing and donating functionalities smoothly undergo
cyclo-condensation to the respective thiazolidin-4-ones with good
yields. Reaction profile is very clean and no side products are
formed.
3. Results and discussion
Herein, we report a novel and facile synthesis of 1,3-thiazolidin-
4-one in good yields. In a one-pot procedure, compounds 4a–k
(Table 1) were obtained in the course of a three component
reaction with aromatic aldehyde 1a–f, aromatic amine 2a–d and
mercaptoacetic acid 3 using 2,20,200-bismuthinetriyltris(sulfane-
diyl)triacetic acid [Bi(SCH2COOH)3] at an ambient temperature
under solvent free conditions within 2 h.
1H NMR spectra of all synthesized compounds reveal a
singlet signal at region
d 6.67–7.75 attributed to the resonance
of the methine proton (S–CH–N). The appearance of the IR
absorption signals due to the carbonyl group of the synthesized
compounds 4a–k, clearly confirmed the formation of thiazoli-
din-4-ones.
A proposed mechanism for the reaction is outlined in Scheme 2.
Based on this mechanism, it is highly probable that the carbonyl
groups of aldehydes and acid have to be activated, which occurs
when the carbonyl oxygen is coordinated by catalyst. Therefore, it
may be proposed that the catalyst facilitates the formation of imine
intermediate [A] by increasing the electrophilicity of the carbonyl
group of the aldehyde.
Initially, we condensed p-toluidine (1.0 mmol), 4-methylben-
zaldehyde (1 mmol), thioglycolic acid (1.2 mmol) under solvent
free conditions. They were stirred at room temperature for 24 h in
the absence of the catalyst but led to very poor yields (entry 1,
Table 2).
To enhance the yield of the desired product the temperature of
the reaction was increased to 70 8C, with no appreciable increment
[(Scheme_2)TD$FIG]
OH
Catalyst
S
NH2
O
H
N Ph
O
HSCH 2COOH
O
Catalyst
N
Ph
C
PhNH2
S
B
A
Scheme 2. Postulated mechanism for thiazolidin-4-one synthesis.

N. Foroughifar, S. Ebrahimi / Chinese Chemical Letters 24 (2013) 389–391
391
[4] X. Zhang, X. Li, D. Li, et al., Ionic liquid mediated and promoted eco-friendly
preparation of thiazolidinone and pyrimidine nucleoside–thiazolidinone hybrids
and their antiparasitic activities, Bioorg. Med. Chem. Lett. 19 (2009) 6280–6283.
[5] A. Mobinikhaledi, N. Foroughifar, M. Kalhor, et al., Synthesis and antifungal
activity of novel 2-benzimidazolylimino-5-arylidene-4-thiazolidinones J, Hetero-
cycl. Chem. 47 (2010) 77–80.
[6] X. Jin, C.J. Zheng, M.X. Song, et al., Synthesis and antimicrobial evaluation of l-
phenylalanine-derived C5-substituted rhodanine and chalcone derivatives con-
taining thiobarbituric acid or 2-thioxo-4-thiazolidinone, Eur. Med. Chem. 56
(2012) 203–209.
4. Conclusion
For the first time, a novel, facile, one-pot three component
method for the synthesis of substituted thiazolidin-4-one cata-
lyzed by 10 mol% of catalyst has been developed in good yield.
Compared to the previously reported methods, mild reaction
conditions, easy work-up, clean reaction profile, shorter reaction
times, and wide range of applicable substrates are key advantages
of this methodology.
[7] X.J. Sun, W.L. Dong, W.G. Zhao, Z.M. Li, Synthesis, crystal structure and biological
activities of 2-substituted-3-aryl-4-thiazolidinone(thiazolidinethione) deriva-
tives, Chin. J. Org. Chem. 27 (2007) 1374–1380.
[8] B. Chandrasekhar, b-Mercaptoalkanoic carboxylic esters: versatile synthons in
heterocyclic chemistry, J. Sulfur Chem. 29 (2008) 187–240.
Acknowledgment
[9] D. Gautam, P. Gautam, R.P. Chaudhary, N-methylpyridinium tosylate catalyzed
green and efficient synthesis of some novel 2,4-disubstituted thiazoles and 4-
thiazolidinones, Chin. Chem. Lett. 23 (2012) 1221–1224.
[10] S.G. Patil, R.R. Bagul, M.S. Swami, et al., Synthesis of 5-benzylidene-3-(3-fluoro-4-
yl-morpholin-4-yl-phenylimino)thiazolidin-4-one derivatives catalyzed by
[BmIm]OH and their anti-microbial activity, Chin. Chem. Lett. 22 (2011)
883–886.
We are thankful to North Tehran Branch, Islamic Azad
University for their financial support.
References
[11] V. Gududuru, V. Nguyen, J.T. Dalton, D.D. Miller, Efficient microwave enhanced
synthesis of 4-thiazolidinones, Synlett (2004) 2357–2358.
[12] U.R. Pratap, D.V. Jawale, M.R. Bhosle, R.A. Mane, Saccharomyces cerevisiae cata-
lyzed one-pot three component synthesis of 2,3-diaryl-4-thiazolidinones, Tetra-
hedron Lett. 52 (2011) 1689–1691.
[1] S. Samai, G.C. Nandi, R. Kumar, M.S. Singh, Multicomponent one-pot solvent-free
synthesis of functionalized unsymmetrical dihydro-1H-indeno[1,2-b]pyridines,
Tetrahedron Lett. 50 (2009) 7096–7098.
[2] Y.X. Li, X. Zhai, W.K. Liao, et al., Design, synthesis and biological evaluation of new
rhodacyanine analogues as potential antitumor agents, Chin. Chem. Lett. 23
(2012) 415–418.
[3] D. Bhambi, V.K. Salvi, J.L. Jat, S. Ojha, G.L. Talesara, Synthesis and antimicrobial
activity of some new indole containing isoxazolines and phthalimidoxy deriva-
tives of thiazolidinone and thiohydantoin, J. Sulfur Chem. 28 (2007) 155–163.
[13] A. Bolognese, G. Correale, M. Manfra, et al., Thiazolidin-4-one formation. Mecha-
nistic and synthetic aspects of the reaction of imines and mercaptoacetic acid
under microwave and conventional heating, Org. Biomol. Chem.
2809–2813.
2 (2004)