One-pot synthesis of 1,3-thiazolidin-4-one using ammonium persulfate as catalyst

Article abstract of DOI:10.1080/17415993.2016.1223298

Ammonium persulfate can be used as a homogeneous catalyst for three-component one-pot synthesis of some 1,3-thiazolidin-4-one derivatives from aldehydes, amines and mercaptoacetic acid under solvent-free conditions with good yields. The characterization o

Full text of DOI:10.1080/17415993.2016.1223298

Journal of Sulfur Chemistry
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One-pot synthesis of 1,3-thiazolidin-4-one using
ammonium persulfate as catalyst
Sattar Ebrahimi
To cite this article: Sattar Ebrahimi (2016): One-pot synthesis of 1,3-thiazolidin-4-
one using ammonium persulfate as catalyst, Journal of Sulfur Chemistry, DOI:
10.1080/17415993.2016.1223298
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Date: 02 September 2016, At: 23:47

JOURNAL OF SULFUR CHEMISTRY, 2016
http://dx.doi.org/10.1080/17415993.2016.1223298
SHORT COMMUNICATION
One-pot synthesis of 1,3-thiazolidin-4-one using ammonium
persulfate as catalyst
Sattar Ebrahimi
Department of Chemistry, Malayer Branch, Islamic Azad University, Malayer, Iran
ABSTRACT
ARTICLE HISTORY
Received 31 January 2016
Accepted 7 August 2016
Ammonium persulfate can be used as a homogeneous catalyst for
three-component one-pot synthesis of some 1,3-thiazolidin-4-one
derivatives from aldehydes, amines and mercaptoacetic acid under
solvent-free conditions with good yields. The characterization of
products was generally achieved by IR and NMR techniques. Inex-
pensive catalyst, high yields, simple product isolation and high atom
economy are the noteworthy aspects of the protocols.
KEYWORDS
Thiazolidin-4-one; APS;
ammonium persulfate;
thioglycolic acid;
mercaptoacetic acid
1. Introduction
4-Thiazolidinones derivatives are an important class of compounds in medicinal
chemistry. The 4-thiazolidinone ring system is a core structure in various synthetic
pharmaceutical compounds, displaying broad medicinal and biological activities. Deriva-
tives of 4-thiazolidinone have been demonstrated to possess anti-histaminic,[1] anti-
HIV,[2] antituberculotic,[3] antifungal,[4] antiviral,[5] anticancer [6] and antimicrobial
activities.[7,8] Several synthetic methods have been reported for the synthesis of 4-
thiazolidinones. The main synthetic routes to 1,3-thiazolidin-4-ones involve three com-
ponents (an aldehyde, an amine and mercaptoacetic acid), either in a one- or a
two-step process.[9] There are also some reports using chemical agents, such as N-
methylpyridinium tosylate [10] as desiccant, to assist the formation of thiazolidi-
none derivatives. The use of [BmIm]OH,[11] Hunig’s base,[12] nano-CdZr4(PO4)6,[13]
Bi(SCH2COOH)3 [14] and Baker’s yeast [15] has also been reported to expedite the
cyclocondensation reaction of the azomethines and thioglycolic acid. However, these
methodologies suffer from one or more disadvantages, such as tedious work-up, require
CONTACT Sattar Ebrahimi
seyonesi@gmail.com
© 2016 Informa UK Limited, trading as Taylor & Francis Group

2
S. EBRAHIMI
prolonged heating and costly dehydrating agents. Therefore, it was thought worthwhile
to develop a new method for cyclocondensation. As a result, we showed that aromatic
aldehydes, aromatic amine and thioglycolic acid, under solvent-free conditions, gave
4-thiazolidinones.
2. Results and discussion
In continuation of our research work in the development of expedient methodologies for
the synthesis of 1,3-thiazolidinones,[14,16] an attempt has been made here to develop a
one-pot synthetic method for the synthesis of 4-thiazolidinones.
Our studies were initiated by the cyclocondensation reaction of p-toluidine 1a, ben-
zaldehyde 2a and thioglycolic acid. The reaction was tested under a variety of different
conditions. The results are summarized in Table 1. The reaction was tested in various sol-
vents, such as H2O, CH3CN, EtOH and THF, but solvent-free conditions were found to be
optimal in terms of isolated yields and reaction rates. After this determination, we exam-
ined the reaction efficiency using different types of catalysts and at different temperatures
under solvent-free conditions. 2-Phenyl-3-(p-toly) thiazolidin-4-one (4a) was obtained in
84% yield when the reaction was run at 90°C in the presence of 10 mol% of APS. The
solvent-free condensation was also tested at 90°C without catalyst but the reaction did
not significantly proceed even after long reaction times (12 h). To enhance the yield of the
desired product, the temperature of the reaction was increased to 100°C but no appreciable
improvement in the product yield was observed.
As shown in Table 2, a series of aromatic aldehydes bearing electron-withdrawing or
electron-donating substituents such as nitro, halide and methoxy gave the corresponding
Table 1. Optimization of the reaction conditions for product 4a.
Entry
Reaction conditions
T (°C)
Yields (%)
1
2
3
4
5
6
7
No catalyst, 12 h
Cat (2 mol%), 60 min
Cat (3 mol%), 60 min
Cat (5 mol%), 60 min
Cat (10 mol%), 60 min
Cat (10 mol%), 90 min
No catalyst, 12 h
rt
90
90
90
90
–
35
60
68
84
100
90
85
trace
Table 2. Thiazolidin-4-one derivatives 4a–4k.
Mp (°C)
Mp (°C)
Entry
ArNH2
Ar’CHO
Product
Yields (%)
84
[found]
[reported]
1
109–111
110–112 [14]
2
78
121–123
115–117 [17]
(continued).

JOURNAL OF SULFUR CHEMISTRY
3
Table 2. Continued.
Mp (°C)
[found]
Mp (°C)
[reported]
Entry
ArNH2
Ar’CHO
Product
Yields (%)
90
3
122–124 125–127 [13]
4
5
75
92
110–111 105–106 [14]
176–177 176–178 [14]
6
7
75
80
128–130 131–132 [17]
127–128 119–120 [17]
8
92
150–151 151–152 [14]
134–136 134–136 [14]
9
85
88
10
165–166
132–135
–
–
11
73

4
S. EBRAHIMI
Scheme 1. The synthetic pathway of thiazolidinon-4-ones.
product in good yields. Different functional groups were also introduced in the ortho
position, indicating that the method is not sensitive to steric or electronic variation of
ortho substituents. To demonstrate the scope and limitation of the procedure, heterocyclic
amines, such as 4H-1,2,4-triazol-3-amine and nicotinohydrazide, were also examined and
the results are summarized in Table 2 (Scheme 1).
3. Conclusion
In conclusion, I have developed a simple, efficient and green method for the synthesis of
a variety of thiazolidin-4-one derivatives using ammonium persulfate under solvent-free
conditions. The method offers many advantages over the reported methods, such as shorter
reaction time, cleaner reaction profile, easy isolation and good yield of the products.
4. Experimental
4.1. General
Purity of the compound was checked by thin-layer chromatography using EtOH/n-hexane
(1:1 v/v) as an eluent. IR spectra were prepared on a galaxy series FT-IR 5000 spectropho-
tometer using KBr discs. NMR spectra were recorded on a Brucker spectrophotometer
(300 MHZ) in DMSO-d6 using TMS as an internal standard. C, H, N and S analyses were
performed on a Vario EL III elemental analyzer.
4.2. General procedure for preparation of 4a–4k
A mixture of aromatic aldehydes 1a–1g (1 mmol), aromatic amine 2a–2d (1 mmol), thio-
glycolic acid 3 (1.0 mmol) and APS (10 mol%) was heated (90°C) for 60 min. After the
completion, 5 mL of H2O was added and the reaction mixture was extracted with ethy-
lacetate (2 × 5 mL) and the organic layer was washed with 5% sodium bicarbonate. The
organic layer was dried over anhydrous Na2SO4, concentrated and recrystallized from
n-hexane/ethyl acetate to afford the pure product 4a–4k.
4.2.1. Selected data
N-(2-(2-chlorophenyl)-4-oxothiazolidin-3-yl)nicotinamide (4j, Table 2):
IR (KBr, cm−1): 3120 (NH), 3040 (aromatic CH stretch.), 2974 (aliphatic CH stretch.),
1731 (C O), 1680 (C O), 1610 (C N); 1H NMR (300 MHZ, DMSO-d6): δ 11.16 (1H, s, NH)
8.74 (s, 1H, Harom.), 7.59–7.67 (m, 3H, Harom.), 7.39–7.46 (m, 4H, Harom.), 6.28 (s, 1H,
S–CH–N), 3.98 (d, 1H, CH, J = 15.8 Hz), 3.75 (d, 1H, CH2, J = 15.3 Hz). Anal. Calcd. for

JOURNAL OF SULFUR CHEMISTRY
5
C15H12ClN3O2S: C, 53.98%; H, 3.62%; N, 12.59%; S, 9.60%. Found: C, 53.78%; H, 3.51%;
N, 12.64%; S, 9.57%.
2-(4-nitrophenyl)-3-(4H-1,2,4-triazol-3-yl)thiazolidin-4-one (4k, Table 2):
IR (KBr, cm−1): 3175 (NH), 3085 (aromatic CH stretch.), 2965 (aliphatic CH stretch.),
1730 (C O), 1545, 1346 (NO2); 1H NMR (300 MHz, DMSO-d6): δ 8.15–8.18 (m, 3H, Harom.
CHtriazole), 7.85 (br, 1H, NH), 7.65 (d, 2H, Harom., J = 8.5 Hz), 6.55 (s, 1H, S–CH–N), 4.11
(d, 1H, CH, J = 16.1 Hz), 3.52 (d, 1H, CH2, J = 15.6 Hz). Anal. Calcd. for C11H9N5O3S:
C, 45.36%; H, 3.11%; N, 24.04%; S, 11.01%. Found: C, 45.51%; H, 3.21%; N, 24.16%; S,
10.92%.
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
We are thankful to Islamic Azad University, Malayer Branch, for providing of financial and technical
supports of this work.
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