One-pot, solvent-free facile stereoselective synthesis of rhodanine–furan hybrids from renewable resources

Article abstract of DOI:10.1080/17415993.2019.1702196

In this study, a one-pot, solvent-free stereoselective reaction was started between primary amines, carbon disulfide, ethyl bromoacetate, and furan derivatives derived from sugars at room temperature, which was completed within 10 min to produce rhodanine–furan hybrid molecules in good to high yields. The presence of the chloromethyl group in products derived from chloromethylfurfural (CMF) made it possible for the substitution of other functional groups such as amine group.

Full text of DOI:10.1080/17415993.2019.1702196

Journal of Sulfur Chemistry
ISSN: 1741-5993 (Print) 1741-6000 (Online) Journal homepage: https://www.tandfonline.com/loi/gsrp20
One-pot, solvent-free facile stereoselective
synthesis of rhodanine–furan hybrids from
renewable resources
Leila Sabahi-Agabager & Farough Nasiri
To cite this article: Leila Sabahi-Agabager & Farough Nasiri (2019): One-pot, solvent-free facile
stereoselective synthesis of rhodanine–furan hybrids from renewable resources, Journal of Sulfur
Chemistry, DOI: 10.1080/17415993.2019.1702196
To link to this article: https://doi.org/10.1080/17415993.2019.1702196
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JOURNAL OF SULFUR CHEMISTRY
https://doi.org/10.1080/17415993.2019.1702196
One-pot, solvent-free facile stereoselective synthesis of
rhodanine–furan hybrids from renewable resources
Leila Sabahi-Agabager and Farough Nasiri
Department of Applied Chemistry, University of Mohaghegh Ardabili, Ardabil, Iran
ABSTRACT
ARTICLE HISTORY
Received 10 November 2019
Accepted 3 December 2019
In this study, a one-pot, solvent-free stereoselective reaction was
started between primary amines, carbon disulfide, ethyl bro-
moacetate, and furan derivatives derived from sugars at room
temperature, which was completed within 10 min to produce rhoda-
nine–furan hybrid molecules in good to high yields. The presence of
the chloromethyl group in products derived from chloromethylfur-
fural (CMF) made it possible for the substitution of other functional
groups such as amine group.
KEYWORDS
5-arylidene rhodanines;
furans; solvent-free reaction;
multicomponent reactions
(MCRs); biomass
Introduction
To optimize the biological activity of synthetic molecules, it is essential to have a dif-
ferent design of the molecules. The synthesis of hybrid molecules is a way to achieve
this goal, which has been further considered in recent decades to improve the biolog-
ical activity of synthetic compounds [1]. Sugars represent a renewable source for the
production of furan derivatives. The furan scaffold consists of several bioactive natu-
ral products such as furanolactones, furano-flavonoids, and furanocoumarins. The furan
CONTACT Farough Nasiri
nasiri@uma.ac.ir
Department of Applied Chemistry, University of Mohaghegh
Ardabili, P.O. Box 56199-11367, Ardabil, Iran.
This article makes reference to supplementary material available on the publisher’s website at
https://doi.org/10.1080/17415993.2019.1702196
© 2019 Informa UK Limited, trading as Taylor & Francis Group

2
L. SABAHI-AGABAGER AND F. NASIRI
derivatives have been reported to show more than 18 various pharmacologically activities
[2]. High remedial properties of furan-containing drugs have motivated organic chemists
to synthesize various furan derivatives. On the other hand, the arylidene rhodanine-based
compounds are considerable heterocyclic molecules with diverse pharmacological activi-
ties such as anticancer [3], anti-bacterial [4], anti-diabetic [5], antifungal [6], and anti-HIV
[7]. These molecules also inhibit numerous targets such as aldose reductase [8], hepatitis
C virus (HCV) NS3 protease [9], PRL-3 [10], and UDPN-acetylmuramate/L-alanine lig-
ase [11]. Recently, rhodanine-based molecule supported on nanomagnetic particles has
also been used to remove heavy metal contamination [12] or used as a catalyst for organic
transformations [13,14].
Due to the above observations, we were interested in the synthesis of hybrid molecules
containing furan and rhodanine moieties (5-arylidene rhodanines) by the reaction of
furanaldehydes (furfural and other furanaldehyde derivatives obtained from sugar), car-
bon disulfide, ethylbromoacetate, and primary amines. Among most of the reported
synthesis methods used to generate arylidene rhodanines, the Knoevenagel condensation
between rhodanine units and aldehydes has been done frequently through a separate step
in the presence of an appropriate base [15–26]. Recently, a few reports have been pub-
lished regarding the four-component synthesis of arylidene rhodanines. In these reports,
ultrasonic or microwave conditions have been used to facilitate the reaction [27,28] or the
reaction has been performed in ionic liquid [29] and to the best of our knowledge, there
is no report about the one-pot solvent-free synthesis of arylidene rhodanines. To develop
easy and green synthesis of arylidene rhodanines without isolation of reaction interme-
diates or purification step, and in continuation of our research on one-pot solvent-free
synthesis of heterocyclic compounds [30–33], this study was conducted to report a one-
pot solvent-free reaction between primary amines 1, carbon disulfide, ethyl bromoacetate,
and renewable furan derivatives 2 in the presence of a catalytic amount of triethylamine to
produce rhodamine-furan hybrids 3 in good to high yields within 10 minutes.
Results and discussion
The one-pot reaction between phenethyl amine 1a, carbon disulfide, ethyl bromoacetate,
and chloromethylfurfural (CMF) 2a was selected as a model reaction to produce rhoda-
nine–furan hybrid 3a (Scheme 1). At first, to achieve an efficient procedure, the one-pot
methods reported in the literature were used for the synthesis of the compound 3a. As
illustrated in Scheme 2, when the reaction was carried out by the Azizi’s method [27] in
PEG and the presence of 300 mol% of KOH and ultrasonic condition, the reaction yield
was negligible. Also, when the reaction was performed according to the Mermer’s method
[28] in water and the presence of 300 mol% of triethylamine and ultrasonic condition, the
reaction yield was only 20%. The deletion of ultrasonic condition in the recent reaction
[28] reduced reaction yield to 14%. When the reaction was carried out in solvent-free con-
dition with an equimolar ratio of reactant and in presence of 20 mol% of triethylamine, 3a
created with a yield of 33% within 10 min (Table 1, entry 1). The increase in the amount
of triethylamine did not influence on yield of 3a (Table 1, entries 1, 2). In this reaction,
bromoethylacetate was added to the mixture of phenethylamine and CS2, and the reac-
tion mixture was stirred by a glass rod for 2 minutes. Then, CMF and triethylamine were
added respectively to the mixture and mixing was continued, and progress of the reaction

JOURNAL OF SULFUR CHEMISTRY
3
Scheme 1. One-pot reaction between phenetyl amine, CS2, CMF, and ethyl bromoacetate.
Scheme 2. Synthesis of 3a through a number of methods reported in the literature.
Table 1. Optimization of the reaction conditions for the synthesis of compound 3a.
Molar ratio of reactants to CMF
Entry
Phenethylamine
CS2
Ethylbromoacetate
Et3N
Time
Yield% of 3a
1
2
1
1
1
1
2
1
1
1
1
2
1
1
1
1
2
0.2
0.4
0.2a
0.2
0.4
0.5
0.6
10 min
10 min
1 day
10 min
10 min
10 min
10 min
33
33
3
Trace
4b
5
–
c
40
63
62
6
7
2.5
3
2.5
3
2.5
3
aWhen triethylamine was added to the reaction mixture before adding CMF.
bThe reaction was carried out at 60°C.
cThe reaction afforded a complex oily mixture.
was monitored by the TLC. After 8 min, the reaction was completed. The product was eas-
ily separated by adding ethanol to the reaction mixture. In this reaction, the progress of
the reaction was significantly influenced by the order of the reactant addition. When tri-
ethylamine was added to the reaction mixture before adding CMF, the reaction yield was
negligible after 24 hours (Table 1, entry 3). Also, this reaction was sensitive to tempera-
ture, and when the reaction was carried out at 60°C, the reaction afford a complex mixture

4
L. SABAHI-AGABAGER AND F. NASIRI
Scheme 3. One-pot, solvent-free stereoselective reaction between phenetyl amine, CS2, CMF, and ethyl
bromoacetate.
(Table 1, entry 4). To obtain the optimum reaction conditions in terms of reactant amount,
the model reaction was checked in the presence of different ratios of reactant relative to
CMF. As shown in Table 1, reasonable reaction yield was gained when the reaction was
carried out using 2.5 times of reactant and 50 mol% of trimethylamine relative to CMF at
room temperature (Table 1, entries 5–7).
As shown in Scheme 3, two possible stereoisomers (3a and 3aꢀ) can be formed in this
reaction. These isomers can be detected from each other based on the chemical shift of
1
olefinic hydrogen in the H NMR. In the Z-form (3a), methine proton is located in the
deshielding region of adjacent carbonyl group. This proton appears at about 7.0–8.0 ppm,
while in the E-form (3aꢀ), this proton should appear at about less than 6.5 ppm [15]. The1H
NMR chemical shift of methine proton in products of this reaction appears in a range of
7.4–7.6 ppm, showing that only Z isomer has been produced. The reason for the forma-
tion of 3 in Z-form is due to the high degree of thermodynamic stability of Z-form in this
compound [3]. Structures of the produced 5-arylidene rhodanines derivatives were deter-
mined based on their IR, 1H NMR, 13C NMR, and mass spectroscopic data. For example,
the 1H NMR spectrum of 3c showed three singlets (δ = 2.32, 4.63, and 5.28 ppm) related
to the methyl, CH2N, and CH2Cl protons, respectively. Protons of the furan ring showed
two doublets (δ = 6.55 and 6.78 ppm, 3JHH = 3.5 Hz). The methine proton of 3c appeared
as a singlet at δ = 7.44 ppm, revealing that the compound 3c is produced as only Z-form
[15]. Also, aromatic protons of 3c produced two doublets at δ = 7.13 and δ = 7.36 ppm
(3JHH = 7.7 Hz). Also, the 13C NMR spectrum of 3c showed 15 distinct signals confirm-
ing the proposed structure. Mass spectrum of 3c illustrated a molecular ion peak at the
expected m/z value, i.e. 363 (Table 2).
To generalize the reported method to other aldehydes, we examined this procedure for
benzaldehyde. The yield of desired product was about 60%, indicating that this method
can be extended to other aldehydes as well.
A proposed mechanism for this reaction is shown in Scheme 4. The reaction proceeds
through an initial addition of the amine1 to carbon disulfide to afford zwitterionic interme-
diate I [34] which then reacts with ethyl bromoacetate with the loss of one HBr molecule to
convert it into the intermediate II. Intermediate II undergoes an intramolecular cycliza-
tion to produce rhodanine III with diverse R1 groups with loss of the ethanol molecule.
Condensation of rhodanine III with furan derivatives 2 in the presence of NEt3 gave the
rhodanine–furan hybrids 3.
Chlorine atom in the compounds 3a–3d has potential for substitution with various
functional groups. The amino group is one of the most important functional group in

JOURNAL OF SULFUR CHEMISTRY
5
bioactive compounds, which by converting to ammonium salts, makes it possible to sol-
ubilize organic compounds in an aqueous medium. Compound 3a easily reacted with
hexamethylenetetramine to produce intermediate 4 (Scheme 5) which was converted to its
Table 2. One-pot, solvent-free stereoselective synthesis of rhodanine–furan hybrids 3a–3j.
Entry
1
R1
R2
Product
Yield (%)a
63
PhCH2CH2
CH2Cl
2
3
PhCH2
CH2Cl
65
59
4-Me-PhCH2
CH2Cl
4
5
CH3OCH2CH2
CH2Cl
63
PhCH2CH2
CH2OH
75
(continued).

6
L. SABAHI-AGABAGER AND F. NASIRI
Table 2. Continued.
Entry
R1
R2
Product
Yield (%)a
45
6
7
PhCH2
CH2OH
4-Me-PhCH2
CH2OH
60
8
9
CH3OCH2CH2
CH2OH
48
64
PhCH2CH2
H
10
PhCH2
H
57
aIsolated yields.
ammonium salt of rhodanine–furan hybrid 5 by treating with acidic ethanol at reflux con-
dition [35]. The 1H NMR spectrum of 5 showed a triplet (δ = 2.95 ppm, 3JHH = 9.0 Hz)
related to CH2-Ar protons, and the two methylene protons of CH2-N moieties overlapped
with each other at δ = 4.20–4.24 ppm. One of the two protons of the furan ring showed a
doublet at δ 6.86 ppm with 3JHH = 3.5 Hz, and other proton of the furan ring overlapped
with aromatic proton signals at δ = 7.19–7.30 ppm. The methine proton appeared as a
singlet at δ = 7.59 ppm. The NH3+ protons of 5 resulted as a broad singlet at δ 8.87 ppm.
This resonance disappeared after the addition of D2O to the DMSO solution of 5. In addi-
tion, the 13C NMR spectrum of 5 showed 15 distinct signals confirming the proposed

JOURNAL OF SULFUR CHEMISTRY
7
Scheme 4. A proposed mechanism for the formation of rhodanine–furan hybrids through the reaction
between primary amines, CS2, furan derivatives, and ethyl bromoacetate.
Scheme 5. Synthesis of ammonium salt of rhodanine–furan hybrid 5.
structure. Mass spectrum of 5 displayed a (M+-HCl) peak at m/z 344, corresponding with
the proposed structure.
Conclusion
The present one-pot solvent-free and stereoselective reaction between primary amines,
carbon disulfide, ethylbromoacetate, and furfural derivatives derived from sugars provided
a novel series of furan–rhodanine hybrids in good to high yields within 10 minutes. The
presence of the chloromethyl group in products derived from CMF made it possible for
the substitution of other functional groups such as amine group. Also, the simplicity of the
present procedure and facility of the product isolation made it an interesting alternative to
more complex methods.
Experimental section
General information
Thin layer chromatography was carried out using commercially available Merck F254
aluminum backed silica plates and Silica gel (60 meshes) was used for column chromatog-
raphy. Melting points (un-corrected) were measured with a Stuart SMP-3 apparatus. IR
spectra of products were measured with an FTIR Perkin Elmer RXI. NMR spectra were

8
L. SABAHI-AGABAGER AND F. NASIRI
recorded with a Bruker DRX-250 AVANCE instrument (250.1 MHz for 1H and 62.5 MHz
for13C) or INOVA-500 (500 MHz for 1H and 125 MHz for 13C) with CDCl3 or DMSO as
the solvent. Chemical shifts are given in ppm (δ) relative to internal TMS, and coupling
constants (J) are reported in Hertz (Hz). 5-(Chloromethyl)furfural was prepared from
powdered sugar according to the published procedure [36]. 5-(Hydroxymethyl)furfural
was prepared from fructose according to the published procedure [37]. Other starting
materials and solvents were obtained from Merck (Germany) and were used without
further purification.
General procedure for the preparation of 3-alkyl-5-((5-(hydroxymethyl)furan-2-yl)
methylene)-2-thioxothiazolidin-4-one (3a–j)
To a mixture of amine (2.5 mmol) and CS2 (2.5 mmol) was added ethyl bromoacetate
(2.5 mmol). The contents were admixed by glass rod at room temperature for 2 minutes.
Then furanaldehyde derivative (1 mmol) and NEt3 (0.5 mmol) were added to the mixture
and mixing was continued for 8 min. After the reaction completed, ethanol (when the alde-
hyde reactant was CMF) or water (when the aldehyde reactant was HMF or furfural) was
added to the reaction mixture and the product was collected by filtration.
(Z)-5-((5-(Chloromethyl)furan-2-yl)methylene)-3-phenethyl-2-thioxothiazolidin-
4-one (3a)
Yellow powder; mp: 144–147°C; 0.229 g, yield: 63%. IR (KBr) (υmax/cm−1): 3036,
1699, 1613, 1352, 1329, 1261, 1165. Ms: m/z (%) = 363 (M+, 32), 328 (18), 259
1
(39), 172 (61), 137 (100), 83 (32). H NMR (250 MHz, CDCl3): δ ppm 3.00 (t, 2H,
3
3JHH = 8.0 Hz, CH2Ar), 4.32 (t, 2H, JHH = 8.0 Hz, NCH2), 4.63 (s, 2H, CH2Cl), 6.55
3
3
(d, 1H, JHH = 3.5 Hz, CHFuran), 6.78 (d, 1H, JHH = 3.5 Hz, CHFuran), 7.29–7.40 (m,
5H, Ar), 7.43 (s, 1H, =CH); 13C NMR (62.5 MHz, CDCl3): δ ppm 33.0 (CH2Ph),
36.9 (CH2Cl), 45.6 (CH2N), 112.9 and 117.6 (2CHFuran), 119.1 (CH=CRhodanin), 121
(CH=CRhodanin), 126.8 (CH), 128.6 (2CH), 128.9 (2CH), 137.5 (CAr), 150.6 and 154.7
(2CFuran), 167.2 (C=O) and 194.1 (C=S).
(Z)-3-Benzyl-5-((5-(chloromethyl)furan-2-yl)methylene)-2-thioxothiazolidin-4
-one (3b)
Yellow powder; mp: 139–143°C; 0.226 g, yield: 65%. IR (KBr) (υmax/cm−1): 3035, 1702,
1610, 1301, 1187, 695, 529. MS (m/z, %): 349 (M+, 53), 314 (25), 172 (58), 137 (100),
91 (56), 65 (25). 1H NMR (500.1 MHz, CDCl3): δ ppm 4.63 (s, 2H, CH2N), 5.31 (s, 2H,
3
3
CH2Cl), 6.55 (d, 1H, JHH = 3.5 Hz, CHFuran), 6.78 (d, 1H, JHH = 3.5 Hz, CHFuran),
7.28–7.34 (m, 3H, Ar), 7. 44 (s, 1H, =CH), 7.45–7.48 (m, 2H, Ar); 13C NMR (125.7 MHz,
CDCl3): δ ppm 37.0 (CH2Cl), 47.6 (CH2N), 113.1 (CHFuran), 117.9 (CHFuran), 119.3
(CH=CRhodanin), 122.1 (CH=CRhodanin), 128.2 (CH), 128.7 (2CH), 129.0 (2CH), 135.0
(CAr), 150.7 (CFuran), 154.9 (CFuran), 167.6 (C =O) and 194.3 (C =S).
(Z)-3-(4-Methyl-benzyl)-5-((5-(chloromethyl)furan-2-yl)methylene)-2-thioxothiaz
olidin-4-one (3c)
Yellow powder; mp: 158–160°C; 0.214 g, yield: 59%. IR (KBr) (υmax/cm−1): 1702, 1609,
1341, 1306, 1184, 1044. MS (m/z, %): 363 (M+, 53), 329 (21), 172 (31), 137 (53), 105 (100),
1
63 (61). H NMR (500.1 MHz, CDCl3): δ ppm 2.32 (s, 3H, CH3), 4.63 (s, 2H, NCH2),
5.28 (s, 2H, CH2Cl), 6.55 (d, 1H, 3JHH = 3.5 Hz, CHFuran), 6.78 (d, 1H, 3JHH = 3.5 Hz,

JOURNAL OF SULFUR CHEMISTRY
9
CHFuran), 7.13 (d, 2H, 3JHH = 7.7 Hz, Ar), 7.36 (d, 2H, 3JHH = 7.7 Hz, Ar), 7.43 (s, 1H,
=CH); 13C NMR (125.7 MHz, CDCl3): δ ppm 21.3 (CH3), 37.0 (CH2Cl), 47.4 (CH2N),
113.1 (CHFuran), 117.8 (CHFuran), 119.3 (CH=CRhodanin), 122.2 (CH=CRhodanin), 129.0
(2CH), 129.4 (2CH), 132.0 (C), 138.0 (C), 150.7 (CFuran), 154.9 (CFuran), 167.6 (C =O) and
194.3 (C =S).
(Z)-5-((5-(Chloromethyl)furan-2-yl)methylene)-3-(2-methoxyethyl)-2-thioxothiaz
olidin-4-one (3d)
Yellow powder; mp: 134–140°C; 0.200 g, yield: 63%. IR (KBr) (υmax/cm−1): 1710, 1608,
1327, 1221, 1126, 1105. MS (m/z, %): 317 (M+, 15), 282 (16), 258.9 (24), 172 (39),
1
137 (100), 63 (25). H NMR (500.1 MHz, CDCl3): δ ppm 3.36 (s, 3H, CH3O), 3.70 (t,
3
3
2H, JHH = 5.8 Hz, NCH2), 4.35 (t, 2H, JHH = 5.8 Hz, OCH2), 4.63 (s, 2H, CH2Cl),
3
3
6.56 (d, 1H, JHH = 3.6 Hz, CHFuran), 6.78 (d, 1H, JHH = 3.6 Hz, CHFuran), 7. 44 (s,
1H, =CH); 13C NMR (125.7 MHz, CDCl3): δ ppm 37.0 (CH2Cl), 43.6 (CH2N), 59.0
(CH3O), 68.4 (CH2O), 113.1(CHFuran), 117.7 (CHFuran), 119.2 (CH=CRhodanin), 121.9
(CH=CRhodanin), 150.6 (CFuran), 154.7 (CFuran), 167.5 (C =O) and 194.5 (C =S).
(Z)-5-((5-(Hydroxymethyl)furan-2-yl)methylene)-3-phenethyl-2-thioxothiazolidin
-4-one (3e)
Yellow powder; mp: 108–109°C; 0.259 g, yield: 75%. IR (KBr) (υmax/cm−1): 3422, 1700,
1607, 1328, 1256, 1166, 1023, 805, 697. MS (m/z, %): 345 (M+, 34), 241 (37), 154 (100). 1H
NMR (500.1 MHz, CDCl3): δ ppm 1.76 (s, 1H, OH), 3.01 (t, 2H, 3JHH = 10.0 Hz, CH2-Ar),
4.33 (t, 2H, 3JHH = 10.0 Hz, N–CH2), 4.73 (s, 2H, CH2-OH), 6.51 (d, 1H, 3JHH = 3.5 Hz,
3
CHFuran), 6. 81 (d, 1H, JHH = 3.5 Hz, CHFuran), 7.23–7.35 (m, 5H, Ar), 7. 42 (s, 1H,
=CH);13C NMR (125.7 MHz, CDCl3): δ ppm 32.9 (CH2Ph), 45.5 (CH2-N), 57.6 (CH2-
OH), 111.1 (CHFuran), 118.0 (CHFuran), 119.5 (CH=CRhodanin), 120.6 (CH=CRhodanin),
126.6 (CH), 128.5 (2CH), 128.8 (2CH), 137.4 (CAr), 149.7 (CFuran), 159.0 (CFuran), 167.1
(C =O) and 194.0 (C =S).
(Z)-3-Benzyl-5-((5-(hydroxymethyl)furan-2-yl)methylene)-2-thioxothiazolidin-4-
one(3f)
Yellow powder; mp: 150–152°C; 0.148 g, yield: 45%. IR (KBr) (υmax/cm−1): 3422, 1702,
1607, 1302, 1190, 1007. MS (m/z, %): 329 (M+-2, 4), 311 (11), 134 (24), 91 (45), 63 (100).1H
NMR (500.1 MHz, CDCl3): δ ppm 2.25 (s, 1H, OH), 4.69 (s, 2H, CH2N), 5.30 (s, 2H,
3
3
CH2OH), 6.45 (d, 1H, JHH = 3.5 Hz, CHFuran), 6.78 (d, 1H, JHH = 3.5 Hz, CHFuran),
7.28–7.34 (m, 3H, Ar) 7. 44 (s, 1H, =CH), 7.45–7.47 (m, 2H, Ar);13C NMR (125.7 MHz,
CDCl3): δ ppm 47.4 (CH2N), 57.6 (CH2OH), 111.2 (CHFuran), 118.3 (CHFuran), 119.8
(CH=CRhodanin), 120.6 (CH=CRhodan1in), 128.1 (CH), 128.6 (2CH), 128.9 (2CH), 134.9
(CAr), 149.8 (CFuran), 159.4 (CFuran), 167.6 (C =O) and 194.2 (C =S).
(Z)-3-(4-Methyl-benzyl)-5-((5-(hydroxymethyl)furan-2-yl)methylene)-2-thioxothi
azolidin-4-one (3g)
Yellow powder; mp: 177–180°C; 0.207 g, yield: 60%. IR (KBr) (υmax/cm−1): 3424, 1699,
1608, 1342, 1305, 1188, 1022. MS (m/z, %): 345 (M+, 29), 154 (44), 105 (43), 63 (100). 1H
NMR (500.1 MHz, CDCl3): δ ppm 2.31 (s, 3H, CH3), 3.96 (s, 1H, OH), 4.70 (s, 2H, NCH2),
5.26 (s, 2H, CH2OH), 6.47 (d, 1H, 3JHH = 3.5 Hz, CHFuran), 6.77 (d, 1H, 3JHH = 3.5 Hz,
CHFuran), 7.12 (d, 2H, JHH = 7.8, Ar), 7.36 (d, 2H, JHH = 8.0, Ar), 7. 41 (s, 1H,
=CH); 13C NMR (125.7 MHz, CDCl3): δ ppm 21.2 (CH3), 47.2 (CH2N), 57.7 (CH2OH),

10
L. SABAHI-AGABAGER AND F. NASIRI
111.2(CHFuran), 118.2 (CHFuran), 119.6 (CH=CRhodanin), 120.8 (CH=CRhodanin), 129.0
(2CH), 129.2 (2CH), 131.9. (C), 137.9 (C), 149.8 (CFuran), 159.2 (CFuran), 167.6 (C =O),
194.2 (C =S).
(Z)-5-((5-(Hydroxymethyl)furan-2-yl)
azolidin-4-one (3h)
methylene)-3-(2-methoxyethyl)-2-thioxothi
Yellow powder; mp: 94–95°C; 0.144 g, yield: 48%. IR (KBr) (υmax/cm−1): 3423, 1705, 1606,
1340, 1328, 1219, 1187, 1163, 1020. MS (m/z, %): 299 (M+, 20), 241 (25), 154 (54), 137
1
(21), 78 (91), 63 (100). H NMR (500.1 MHz, CDCl3): δ ppm 2.42 (s, 1H, OH), 3.35
(s, 3H, CH3O), 3.69 (t, 2H, 3JHH = 5.8 Hz, NCH2), 4.32 (t, 2H, 3JHH = 5.8 Hz, OCH2),
4.69 (s, 2H, CH2OH), 6.48 (d, 1H, 3JHH = 3.5 Hz, CHFuran), 6.77 (d, 1H, 3JHH = 3.5 Hz,
CHFuran), 7. 38 (s, 1H, =CH);13C NMR (125.7 MHz, CDCl3): δ ppm 43.4 (CH2-N),
57.6 (CH2-OH), 58.9 (CH3-O), 68.3 (CH2-O), 111.2(CHFuran), 118.3 (CHFuran), 119.7
(CH=CRhodanin), 120.5 (CH=CRhodanin), 149.8 (CFuran), 159.5 (CFuran), 167.6 (C =O)
and 194.6 (C =S).
(Z)-5-((Furan-2-yl)methylene)-3-phenethyl-2-thioxothiazolidin-4-one (3i)
Yellow powder; 0.202 g, yield: 64%, mp: 151–152°C [27].
(Z)-3-Benzyl-5-((furan-2-yl)methylene)-2-thioxothiazolidin-4-one (3j)
Yellow powder; 0.172 g, yield: 57%, mp: 140–142°C [29].
Procedure for the preparation of hydrochloride salt of (Z)-5-((5-(aminomethyl)furan-
2-yl)methylene)-3-phenethyl-2-thioxothiazolidin-4-one (5)
To a boiling solution of 3a (364 mg, 1 mmol) in chloroform (6 mL) was added hexam-
ethylenetetramine (196 mg, 1.4 mmol), and the reaction mixture was heated for 4 h under
reflux condition. The obtained hexamethylenetetraammonium salt was filtered and dis-
solved in 4 mL ethanol. Then concentrated HCl (10.0 equiv.) was added to the reaction
mixture and the mixture was heated at reflux condition. After 2 hours, compound 5 par-
ticipate as a yellow powder. Mp: 209–210°C (decomposition); 0.141 g, yield: 37%. IR (KBr)
(υmax/cm−1): 2864 (br), 1682, 1599, 1329, 1179. MS (m/z, %): 344 (M+-36, 81), 240 (48),
3
153 (100), 96 (52).1H NMR (500.1 MHz, DMSO): δ ppm 2.95 (t, 2H, JHH = 9.0 Hz,
3
CH2Ar), 4.20–4.24 (m, 4H, NCH2), 6.86 (d, 1H, JHH = 3.5 Hz, CHFuran), 7.19–7.22
(m, 4H, CHFuran and Ar), 7.27–7.30 (m, 2H, Ar), 7.59 (s, 1H, =CH), 8.87 (bs, 3H,
NH3 exchange with D2O). 13C NMR (125.7 MHz, DMSO): δ ppm 32.2 (CH2Ph), 35.2
(CH2N), 45.3 (CH2NH3), 114.2 (CHFuran), 118.4 (CHFuran), 119.8 (CH=CRhodanin), 121.4
(CH=CRhodanin), 126.7 (CH), 128.6 (2CH), 128.7 (2CH), 137.6 (CAr), 149.7 (CFuran), 153.4
(CFuran), 166.5 (C =O) and 194.4 (C =S).
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
This research was supported by the Iran National Science Foundation (INSF) under grant No.
96004838.

JOURNAL OF SULFUR CHEMISTRY
11
Supporting information
1H NMR,13C NMR, and Mass spectra of all new compounds associated with this article
can be found in the online version.
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