Synthesis of some novel 5-(Arylidene)-2-imino-3(pyridin-2-yl)thiazolidin-4- one derivatives

Article abstract of DOI:10.1080/10426500802387401

Treatment of 2-aminopyridine (1) with chloroacetyl chloride in dry benzene gave 2-chloro-N-(pyridin-2-yl)acetamide (3), which on further reaction with potassium thiocyanate gave 2-imino-3-(pyridin-2-yl)thiazolidin-4-one (4) as an intermediate compound for the synthesis of pyridin-2-yl substituted 2-imino-thiazolidine-4-one derivatives. Cyclocondensation reaction of (4) with a series of aromatic aldehydes gave 5-arylidene derivatives of pyridin-2-yl substituted 2-imino-thiazolidine-4-ones 5a-j. 1H and 13C NMR spectroscopy, as well as elemental analyses, were used for the identification of these new compounds.

Full text of DOI:10.1080/10426500802387401

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Phosphorus, Sulfur, and Silicon
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Synthesis of Some
Novel 5-(Arylidene)-2-
imino-3(pyridin-2-
yl)thiazolidin-4-one Derivatives
Akbar Mobinikhaledi a , Naser Foroughifar a
Somayeh Faghihi a
&
a Chemistry Department , Arak University , Arak,
Iran
Published online: 22 Jun 2009.
To cite this article: Akbar Mobinikhaledi , Naser Foroughifar & Somayeh Faghihi
(2009) Synthesis of Some Novel 5-(Arylidene)-2-imino-3(pyridin-2-yl)thiazolidin-4-
one Derivatives, Phosphorus, Sulfur, and Silicon and the Related Elements, 184:7,
1837-1842, DOI: 10.1080/10426500802387401
To link to this article: http://dx.doi.org/10.1080/10426500802387401
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Phosphorus, Sulfur, and Silicon, 184:1837–1842, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802387401
Synthesis of Some Novel 5-(Arylidene)-2-imino-3-
(pyridin-2-yl)thiazolidin-4-one Derivatives
Akbar Mobinikhaledi, Naser Foroughifar,
and Somayeh Faghihi
Chemistry Department, Arak University, Arak, Iran
Treatment of 2-aminopyridine (1) with chloroacetyl chloride in dry benzene gave
2-chloro-N-(pyridin-2-yl)acetamide (3), which on further reaction with potassium
thiocyanate gave 2-imino-3-(pyridin-2-yl)thiazolidin-4-one (4) as an intermediate
compound for the synthesis of pyridin-2-yl substituted 2-imino-thiazolidine-4-one
derivatives. Cyclocondensation reaction of (4) with a series of aromatic aldehydes
gave 5-arylidene derivatives of pyridin-2-yl substituted 2-imino-thiazolidine-4-ones
1
5a–j. H and 13C NMR spectroscopy, as well as elemental analyses, were used for
the identification of these new compounds.
Keywords Benzylidene; pyridine; thiazolidin-4-one
INTRODUCTION
The thiazolidin-4-one nucleus has been reported to possess broad and
diverse pharmacological activities.1−9 In view of the many biological ac-
tivities of thiazolidin-4-ones, their synthesis has attracted considerable
attention in recent years. Several modified preparative methods have
been reported for the preparation of simple thiazoles.6−10 However, to
date there have been no reports on the synthesis of derivatives with the
thiazolidin-4-one nucleus attached to a pyridine ring, which may show
interesting biological activities. Due to incessant interest in the chem-
istry of substituted thiazolidin-4-ones, substantial attention should
be paid to the synthesis of novel pyridin derivatives, particularly of
pyridin-2-yl substituted 2-imino-thiazolidin-4-one derivatives. In view
of these reports, we present in this article the synthesis of some novel
5-arylidene derivatives of pyridin-2-yl substituted 2-iminothiazolidin-
4-ones.
Received 10 March 2008; accepted 5 August 2008.
Address correspondence to Akbar Mobinikhaledi, Chemistry Department, Arak Uni-
versity, Dr. Beheshti Ave., Arak 38156-879, Iran. E-mail: akbar mobini@yahoo.com
1837

1838
A. Mobinikhaledi et al.
RESULTS AND DISCUSSION
2-Aminopyridine was reacted with chloroacetyl chloride to give 2-
chloro-N-(pyridin-2-yl)acetamide 3. Reaction of 3 with potassium
thiocyanate under reflux conditions afforded 2-imino-3-(pyridin-2-yl)
thiazolidin-4-one 4 as an intermediate for the synthesis of 5-(arylidene)-
2-imino-3-(pyridin-2-yl)thiazolidin-4-one derivatives 5 as shown in
Scheme 1.
O
O
+
Cl
Cl
Cl
N
NH
2
N
N
H
3
1
2
KSCN
O
O
O
R
N
N
N
N
S
R
HN
S
HN
4
5
R
H
R
5
5
f
g
h
i
4-Br
2-Cl
4-Cl
a
b
c
d
e
2-NO2
4-NO2
4-OCH3
4-CH3
5-Br-2-OH
4-OH
j
SCHEME 1
The yields of the products after recrystallization from ethanol were
1
in the order of 54%–80%. The H and 13C NMR spectra as well as the
elemental analyses data of all synthesized compounds are consistent
with the expected structures. The 1H NMR spectra of the 5-(arylidene)-
2-imino-3-(pyridin-2-yl)thiazolidin-4-one derivatives 5 consist of a mul-
tiplet and a singlet resulting from the aromatic protons and the NH

Synthesis of New Thiazolidin-4-one Derivatives
1839
group, respectively. The signal of the =CH− moiety appears in the
same range as those of the aromatic protons.
EXPERIMENTAL
Melting points were determined with an electrothermal digital melt-
ing point apparatus Mettler Toledo Type FP62 and are uncorrected. 1H
and 13C NMR spectra were recorded with a Bruker Avance (300 MHz)
spectrometer in DMSO-d6 solutions using TMS as internal standard.
Microanalyses were performed with an Elemental Analyzer (Elemen-
tal, Vario EL III) at the Arak University. Reactions were monitored
by thin layer chromatography using silica gel F254 aluminum sheets
(Merck). All chemicals used were reagent grade and were used without
further purification.
Preparation of 2-Chloro-N-(pyridin-2-yl)acetamide (3)
Chloroacetyl chloride (0.02 mol, 1.6 mL) was slowly added to a solution
of 2-aminopyridine (0.01 mol, 0.94 g) in dry benzene, which was kept
at 0–5◦C. The reaction mixture was refluxed for 5 h, and the excess of
solvent was removed under vacuum. The residue was washed with 5%
aqueous solution of NaHCO3 (20 mL) and then with water (20 mL).
The crude product was recrystallized from ethanol (15–20 mL) to give
1
pink crystals. Yield: 88% (1.5 g), mp 124–126◦C. H NMR (DMSO-d6,
300 MHz): δ = 4.35 (s, 2H, CH2), 7.12–8.34 (m, 4H, arom-H), 10.79 (s,
1H, NH). 13C NMR (DMSO-d6, 75 MHz): δ = 43.9, 114.0, 120.3, 138.8,
148.4, 151.8, 165.9.
Preparation of 2-Imino-3-(pyridine-2-yl)thiazolidin-4-one (4)
A mixture of 2-chloro-N-(pyridin-2-yl)acetamide 3 (0.01 mol, 1.71 g),
potassium thiocyanate (0.02 mol, 1.94 g), and acetone (30 mL) was
refluxed for 8 h. The excess of solvent was then removed under vacuum.
The solid product was filtered and washed with water (30–40 mL).
Recrystallization from ethanol (15–20 mL) gave pure orange crystals.
1
Yield: 76% (1.48 g), mp 245–247◦C. H NMR (DMSO-d6, 300 MHz):
δ = 3.84 (s, 2H, CH2), 7.12–8.39 (m, 4H, arom-H), 11.96 (s, 1H, NH).
13C NMR (DMSO-d6, 75 MHz): δ = 35.8, 118.1, 120.1, 139.1, 147.1,
156.3, 167.6, 179.0.

1840
A. Mobinikhaledi et al.
Synthesis of 5-(Arylidene)-2-imino-3-(pyridin-2-yl)
thiazolidin-4-ones (5): General Procedure
A solution of sodium acetate (0.002 mol, 0.16 g) in acetic acid (5 mL)
was added slowly to a solution of 2-imino-3-(pyridin-2-yl)thiazolidin-4-
one 4 (0.001 mol, 0.20 g) in acetic acid (5–10 mL). The resulting mix-
ture was stirred for 5 min, and then the respective aromatic aldehyde
(0.002 mol) was added. The mixture was refluxed for 5–24 h depending
on the aldehyde used. The precipitate was filtered, washed with water
(20 mL), and then recrystallized from ethanol (10–15 mL).
5-Benzylidene-2-imino-3-(pyridin-2-yl)thiazolidin-4-one (5a)
Orange crystals. Yield: 61% (0.17 g), mp 278–280◦C. 1H NMR
(DMSO-d6, 300 MHz): δ = 7.20–8.52 (m, 10H, arom-H, CH ), 12.47 (s,
1H, NH). 13C-NMR (DMSO-d6, 75 MHz): δ = 119.6, 120.7, 126.9, 129.7,
130.5, 131.4, 134.2, 139.4, 147.5, 156.3, 157.5, 157.9, 170.0. Anal. Calcd.
for C15H11N3OS: C, 64.04; H, 3.94; N, 14.94%. Found: C, 64.33; H, 4.22;
N, 14.81%.
5-(2-Nitrobenzylidene)-2-imino-3-(pyridin-2-yl)thiazolidin-4-
one (5b)
1
Light yellow crystals. Yield: 64% (0.21 g), mp 289–290◦C. H NMR
(DMSO-d6, 300 MHz): δ = 7.20–8.42 (m, 9H, arom-H, CH ), 12.57 (s,
1H, NH). 13C NMR (DMSO-d6, 75 MHz): δ = 119.7, 120.8, 125.8, 127.6,
130.0, 130.2, 131.0, 131.6, 134.8, 139.4, 147.4, 148.3, 156.0, 157.0, 169.1.
Anal. Calcd. for C15H10N4O3S: C, 55.21; H, 3.09; N, 17.17%. Found: C,
55.50; H, 3.15; N, 17.28%.
5-(4-Nirobenzylidene)-2-imino-3-(pyridin-2-yl)
thiazolidin-4-one (5c)
1
Light yellow crystals. Yield: 76% (0.25 g), mp 345–346◦C. H NMR
(DMSO-d6, 300 MHz): δ = 7.23–8.51 (m, 9H, arom-H, CH ), 12.59 (s,
1H, NH). Anal. Calcd. for C15H10N4O3S: C, 55.21; H, 3.09; N, 17.17%.
Found: C, 55.02; H, 3.27; N, 17.44%.
5-(4-Methoxybenzylidene)-2-imino-3-(pyridin-2-yl)thiazolidin-
4-one (5d)
1
Light yellow crystals. Yield: 67% (0.21 g), mp 268–270◦C. H NMR
(DMSO-d6, 300 MHz): δ = 3.84 (s, 3H, CH3), 7.12–8.51 (m, 9H, arom-H,
CH ), 12.37 (s, 1H, NH). 13C NMR (DMSO-d6, 75 MHz): δ = 55.9,
114.7, 115.3, 119.6, 120.5, 123.7, 126.7, 131.5, 132.5, 139.3, 147.5,

Synthesis of New Thiazolidin-4-one Derivatives
1841
156.4. 161.0. 169.0. Anal. Calcd. for C16H13N3O2S: C, 61.72; H, 4.21; N,
13.50%. Found: C, 61.51; H, 4.43; N, 13.73%.
5-(4-Methylbenzylidene)-2-imino-3-(pyridin-2-yl)thiazolidin-4-
one (5e)
Yellow crystals. Yield: 58% (0.17 g), mp 269–271◦C. 1H NMR (DMSO-
d6, 300 MHz): δ = 3.34 (s, 3H, CH3), 7.20–8.52 (m, 9H, arom-H, CH ),
12.42 (s, 1H, NH). Anal. Calcd. for C16H13N3OS: C, 65.06; H, 4.44; N,
14.23%. Found: C, 65.23; H, 4.50; N, 14.11%.
5-(4-Bromobenzylidene)-2-imino-3-(pyridin-2-yl)thiazolidin-4-
one (5f)
Cream crystals. Yield: 75% (0.27 g), mp 320–321◦C.1H NMR (DMSO-
d6, 300 MHz): δ = 7.21–8.51 (m, 9H, arom-H, CH ), 12.50 (s, 1H, NH).
Anal. Calcd. for C15H10BrN3OS: C, 50.01; H, 2.80; N, 11.66%. Found:
C, 50.21; H, 2.72; N, 11.81%.
5-(2-Chlorobenzylidene)-2-imino-3-(pyridin-2-yl)thiazolidin-4-
one (5g)
Yellow crystals. Yield: 54% (0.17 g), mp 298–300◦C.1H NMR (DMSO-
d6, 300 MHz): δ = 7.20–8.49 (m, 9H, arom-H, CH ), 12.57 (s, 1H, NH).
Anal. Calcd. for C15H10ClN3OS: C, 57.05; H, 3.19; N, 13.31%. Found: C,
56.86; H, 3.47; N, 13.20%.
5-(4-Chlorobenzylidene)-2-imino-3-(pyridin-2-yl)thiazolidin-4-
one (5h)
Cream crystals. Yield: 61% (0.19 g), mp 303–305◦C.1H NMR (DMSO-
d6, 300 MHz): δ = 7.21–8.52 (m, 9H, arom-H, =CH−), 12.49 (s, 1H, NH).
Anal. Calcd. for C15H10ClN3OS: C, 57.05; H, 3.19; N, 13.31%. Found: C,
57.16; H, 3.23; N, 13.48%.
5-(5-Bromo-2-hydroxybenzylidene)-2-imino-3-(pyridin-2-
yl)thiazolidin-4-one (5i)
Orange crystals. Yield: 73% (0.27 g), mp 263–264◦C. 1H NMR
(DMSO-d6, 300 MHz): δ = 6.92–8.48 (m, 8H, arom-H, CH ), 10.79 (s,
1H, OH), 12.44 (s, 1H, NH). 13C NMR (DMSO-d6, 75 MHz): δ = 110.9,
118.6, 119.7, 120.7, 123.6, 125.0, 126.9, 130.9, 134.2, 135.3, 139.3, 147.4,
156.3, 156.7. 169.7. Anal. Calcd. for C15H10BrN3O2S: C, 47.89; H, 2.68;
N, 11.17%. Found: C, 47.91; H, 2.50; N, 11.36%.

1842
A. Mobinikhaledi et al.
5-(4-Hydroxybenzylidene)-2-imino-3-(pyridin-2-yl)thiazolidin-
4-one (5j)
Yellow crystals. Yield: 81% (0.24 g), mp 308–309◦C.1H NMR (DMSO-
d6, 300 MHz): δ = 6.93–8.52 (m, 9H, arom-H, =CH−), 10.26 (s, 1H,
OH), 12.32 (s, 1H, NH). 13C NMR (DMSO-d6, 75 MHz): δ = 116.7, 119.5,
120.4, 122.5, 125.2, 132.0, 132.8, 139.2, 147.5, 156.5, 157.9, 159.9, 170.1.
Anal. Calcd. for C15H11N3O2S: C, 60.59; H, 3.73; N, 14.13%. Found: C,
60.50; H, 3.85; N, 13.90%.
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