Synthesis and spectral data of new 1,2-bis-(2-hetaryl-4-oxothiazolidin-3- yl)ethanes and 1,4-bis-(2-hetaryl-4-oxothiazolidin-3-yl)butanes

Article abstract of DOI:10.1002/jhet.5570430228

New α,ω-bis-(2-hetaryl-4-oxothiazolidin-3-yl)alkanes were prepared via a common two step procedure using N,N-bis-hetarylidenamines condensation with α-mercaptoacetic acid. The used bis-aldimines were obtained from reaction between ethylenediamine or putrescine and benzaldehyde or the isomeric pyridinecarboxyaldehydes. The bis-(2-phenyl-4-oxothiazolidin-3-yl) alkanes were prepared by one-pot three component reaction of diamine, aldehyde and α-mercaptoacetic acid under very mild conditions.

Full text of DOI:10.1002/jhet.5570430228

Synthesis and Spectral Data of New 1,2-Bis-(2-hetaryl-4-oxothiazo-
lidin-3-yl)ethanes and 1,4-Bis-(2-hetaryl-4-oxothiazolidin-3-yl)butanes
Vladimir V. Kouznetsov* and Diego F. Amado
Mar-Apr 2006
447
Laboratorio de Síntesis Orgánica Fina, Centro de Investigación en Biomoléculas, Escuela de Química,
Universidad Industrial de Santander, A.A. 678, Bucaramanga, Colombia
Ali Bahsas and Juan Amaro-Luis
Laboratorio de RMN, Grupo de Productos Naturales, Departamento de Química, Universidad de los Andes,
Mérida 5101, Venezuela
Received January 18, 2005
New α,ω-bis-(2-hetaryl-4-oxothiazolidin-3-yl)alkanes were prepared via a common two step procedure
using N,N-bis-hetarylidenamines condensation with α-mercaptoacetic acid. The used bis-aldimines were
obtained from reaction between ethylenediamine or putrescine and benzaldehyde or the isomeric
pyridinecarboxyaldehydes. The bis-(2-phenyl-4-oxothiazolidin-3-yl)alkanes were prepared by one-pot three
component reaction of diamine, aldehyde and α-mercaptoacetic acid under very mild conditions.
J. Heterocyclic Chem., 43, 447 (2006).
Introduction.
Furthermore, having in mind the polyamine properties in
living systems as well as the already mentioned thiazolidi-
none advantages, the incorporation of a diamine moiety
between two thiazolidinone rings seems to be a good idea
and so does the synthesis of these heterocycles, potentially
promising molecules in the bioactive studies against fungi
and bacteria. Herein, we describe its synthesis and some
physical-chemical properties.
Thiazolidinones are important heterocyclic compounds,
which exhibit a broad range of biological activities [1-4],
including interesting profile as fungicidal [5,6], pesticide
[7], antibacterial [8,9], anticonvulsant [10], antihistaminic
[11], antioxidant [12], anti-inflammatory and antinocicep-
tive [13,14] agents etc. As a consequence many different
protocols have been developed that allow the synthesis of
4-thiazolidinone skeletons. The method more used
employs a two step preparation: reaction of aromatic
ketones (aldehydes) and amines and condensation of the
prepared Schiff bases and α-mercaptoalkanoic acids [1-3].
However, a one-pot three-component reaction of amine,
aldehyde and mercaptoacetic acid is recently emerged as
an efficient synthesis of 4-thiazolidinones [15-18]. In both
cases the reaction is believed to proceed first via an imine
formation followed by attack of sulphur nucleophile on the
imine carbon and finally intramolecular cyclization with
loss of a molecule of water [19,20]. Little is known about
α,ω-bis-(2-hetaryl-4-oxothiazolidin-3-yl)alkanes [1-4].
However, several studies have revealed their anti-inflam-
matory, antihistaminic and analgesic activities [21,22].
Moreover, recently, it was found that some bis-(2-aryl-4-
oxothiazolidin-3-yl)ethanes act as good cyclooxygenase-2
inhibitory agents [23,24].
Results and Discussion.
The N,N-bis-[phenylmethylen(pyridinylmethylene)]-
ethane-1,2-diamines 7-10 and N,N-bis-[phenylmethylen
(pyridinylmethylene)]butene-1,4-diamines 11-14 used in
the preparation of these series were obtained by refluxing
for 7 to 17 hours the solution in dry ethanol of the respec-
tive diamines (ethylenediamine 1 or putrescine 2) and aro-
matic aldehydes (benzaldehyde 3, pyridinecarboxyaldehy-
des 4-6) with the ratio 1:2 of reactants. Almost all bis-
imines were stable solid products which were easily char-
acterized by the strong and sharp absorption band at 1639-
-1
1649 cm corresponding to the C=N bonds.
The condensation of the Schiff bases 7-14 with the α-
mercaptoacetic acid 15 with the ratio 1:2 by stirring in dry
benzene with temperatures between 5 and 10 ºC did not
take more than 20 min and allowed us to get the α,ω-bis-
(2-hetaryl-4-oxothiazolidin-3-yl)alkanes 16-23 as solid
products in good yields (Scheme 1).
Finally, the 1,2-bis-(2-phenyl-4-oxothiazolidin-3-
yl)ethane 16 and the 1,4-bis-(2-phenyl-4-oxothiazolidin-3-
yl)butane 20 were also obtained via the one-pot three-com-
Based on these facts and in continuation of our research
on bioactive heterocycles including thiazolidinone deriva-
tives [25-27], we prepared two new series of 1,2-bis-(4-
oxothiazolidin-3-yl)ethanes and 1,4-bis-(4-oxothiazolidin-
3-yl)butanes with phenyl and pyridinyl fragments.

448
V. V. Kouznetsov, D. F. Amado, A. Bahsas, and J. Amaro-Luis
Vol. 43
ponent condensation by the reaction of diamines (ethyl-
enediamine, putrescine), benzaldehyde and the mercap-
toacetic acid with ratios 1:2.5:2.5 respectively, in refluxing
dry acetonitrile for 12 hours to get solid products, which
can be filtered and recrystallized in ethanol from the reac-
tion mixture (Scheme 1).
the methylene proton H at C-5 because of its interaction
B
with the geminal proton H and a diastereotopic proton
A
H (6´-H ) at the C-1´ of the ethylene fragment. This last
A
A
proton displayed a doublet of doublets or a multiplet at δ
2.55-2.79 ppm because of its interaction with the geminal
proton H (6´-H ) and the proton H at the C-5. The 6´-
B
B
B
H
proton at the C-1´ aliphatic chain suffered the
B
Scheme 1
anisotropic effect from the near amide group or aryl sub-
stituents and it went to down field at δ 3.37-4.01 ppm
appearing overlapped with H as a multiplet. These gemi-
B
nal protons of each methylene group reside in magnetic
1
non-equivalent environments. The H-NMR spectra of the
compounds 20-23 basically displayed similar shifts plus a
multiplet at δ 1.14-1.30 ppm due to the methylene protons
(7-H , 7-H ) of the butane fragment.
A
B
We found also anisochronous chemical shifts along the
whole molecules not only by the ethanic fragment protons
but also the heterocyclic ring protons that proves the exis-
tence of a mixture of isomers.
The cross-peak in the COSY two dimensional spectrum
was very useful in assigning signals. As an example, the
compound 18 displays signals at 2.73 ppm, which present
contours correlated at 3.55 ppm revealing a AA'BB' sys-
tem. The contours corresponding at 3.66 ppm are corre-
lated with the signals displayed at 3.92 ppm, these are het-
The IR spectra of the compounds 16-23 show the typical
C(=O)-N stretching band appearing in the region of 1643-
erocyclic 5-CH signals, an AB system, and the last one
-1
2
1680 cm . The strong and sharp band of the azomethine
(3.92 ppm) is also correlated with the signal at 5.82 ppm,
the chiral proton. In turn there are contours that correlate
this chiral proton with signals of two aromatic protons, a
doublet of doublets at 7.43 and a multiplet at 8.57-8.58
ppm. The remaining aromatic proton contours of the
pyridin-3-yl fragments behave as expected.
The HMQC two dimensional spectrum of 20 presents
contours correlating the carbon signals at 24 ppm and the
proton signals of the multiplet at 1.41-1.43 ppm and the
carbon signal at 42.9 ppm with the multiplets at 2.49-2.51
and 3.51-3.70 ppm, exposing the presence of the alkanic
fragment. The contours correlating the signal at 37.9 ppm
and the multiplets at 3.51-3.70 and 3.81-3.89 ppm belong
bonds was missing, which was a faithful evidence of the
cyclocondensation.
The structure of all the bis-thiazolidinones was also con-
1
13
firmed by H-NMR, C-NMR, DEPT and bi-dimensional
1
1
techniques as H, H-COSY, HMQC and HMBC. These
analyses indicated the magnetic non-equivalence in the
ethanic fragment protons as in the proton of the chiral C-2
at δ 5.74-5.89 ppm. A doublet is displayed due to its inter-
action with the proton H at C-5.
A
According to the gc-ms analysis made to the compound
17, there are two chromatographic peaks with almost equal
retention times (40.30 min, 41.81 min), which are sign of
corresponding racemate (2R,2'R/2S,2'S) and meso-form
(2R,2'S-meso), as has been already proved [21-23]. But not
only the bis-thiazolidinone 17 showed diastereoisomeric
presence, the gc analysis of 16-19 exhibits broad chromato-
graphic peaks, typical for overlapped peaks with very simi-
lar retention times. We were unable to separate these mix-
tures of isomers by conventional column chromatography.
The NMR spectra showed a set of signals for the corre-
sponding protons of thiazolidinone rings and a resonance
system AA'BB' for the ethanic fragment protons of non-
to the diastereotopic 5-CH of the thiazolidinone ring and
2
two smaller contours correlate the signals at 64 and 5.82
ppm, the chiral 2-CH. The aromatic carbons signals
between 126.9 and 128.9 ppm are correlated with the aro-
13
matic proton multiplet signal at 7.32-7.41. The C-nmr
shows the carbonyl carbon signals at 171.2 ppm.
The three-dimensional molecular geometry adopted for
these bis-thiazolidinones depicted in Figure 1 was deduced
from computational geometry programs of the type
HYPERCHEM 7.0 with a molecular mechanic optimiza-
tion MM+. From them, the most probable conformation
acquired for the compounds 18 and 20 can be noted,
named as “exo”- conformation, in which the phenyl groups
are spaced at the maximal distance in a different plane.
1
first-order spectra. The H-NMR spectra of the compounds
16-19 displayed a doublet of doublets at δ 3.84-3.94 ppm
due to the methylene proton H at C-5 because of its inter-
A
action with the geminal proton H and the proton at the
B
chiral C-2; doublet of doublets at δ 3.59-3.71 ppm due to

Mar-Apr 2006
Synthesis and Spectral Data of New 1,2-Bis-(2-hetaryl-4-oxothiazolidin-3-yl)ethanes
449
Figure 1. Structure of compounds 18 and 20.
mp 84-85 ºC; ir (potassium bromide): ν =CH 2848, ν C=N 1647
The antifungal and antibacterial properties of all
obtained α,ω-bis-(2-hetaryl-4-oxothiazolidin-3-yl)alkanes
were not evaluated in full measure due to the poor solubil-
ity of these compounds. However, preliminary assays
showed that compound 23 was active against the fungi
Penicillium notatum with a diameter of inhibition zone of
30 mm per 50 µg, and compound 20 against the bacteria
Bacillus brevis with a diameter of inhibition zone of 10
mm per 100 µg [28].
-1
cm .
Anal. Calcd. for C
H N : C, 70.57%; H, 5.92%; N, 23.51%.
14 14 4
Found: C, 70.65%; H, 6.07%; N, 23.28%
N,N-Bis-(pyridin-4-ylmethylene)ethane-1,2-diamine (10).
This compound was obtained in 71% yield as a white solid, mp
134-135 ºC; ir (potassium bromide): ν =CH 2844, ν C=N 1649
-1
cm ; gc-ms: t = 27.42 min, ms: m/z 238 (molecular ion).
R
Anal. Calcd. for C
H N : C, 70.57%; H, 5.92%; N, 23.51%.
14 14 4
Found: C, 70.69%; H, 6.12%; N, 23.29%
N,N-Bis-(phenylmethylene)butane-1,4-diamine (11).
This compound was obtained in 100% yield as a yellow liquid;
EXPERIMENTAL
-1
General Method. The same experimental techniques were used
as was previously reported [27].
ir (potassium bromide): ν =CH 2925, ν C=N 1645 cm ; gc-ms:
t = 29.28 min, ms: m/z 264 (molecular ion).
R
Anal. Calcd. for C
Found: C, 81.85%; H,7.54%; N, 10.61%.
H N : C, 81.78%; H,7.63%; N, 10.60%.
18 20 2
General Procedure for Reaction of Diamine and Pyridine-
carboxyaldehydes (or Benzaldehyde).
N,N-Bis-(pyridin-2-ylmethylene)butane-1,4-diamine (12).
This compound was obtained in 64% yield as an orange solid, mp
To diamine (1 mmol) in dry ethanol (25-30 ml) was added the
hetaryl aldehyde (2 mmol). The reaction mixture was stirred and
refluxed for 7 to 17 hours. The crystalline solid products were
collected by filtration and washed with heptanes. The liquid
products were concentrated by distilling the ethanol off.
-1
41-42 ºC; ir (potassium bromide): ν =CH 2912, ν C=N 1639 cm .
Anal. Calcd. for C
H N : C, 72.15%; H, 6.81%; N, 21.04%.
16 18 4
Found: C, 72.02%; H, 6.91%; N, 21.03%.
N,N-Bis-(phenylmethylen)ethane-1,2-diamine (7).
N,N-Bis-(pyridin-3-ylmethylene)butane-1,4-diamine (13).
This compound was obtained in 100% yield as a yellow viscous
This compound was obtained in 100% yield as a yellow solid,
-1
mp 37-39 ºC; ir (potassium bromide): ν =CH 2847, ν C=N 1643
liquid; ir (potassium bromide): ν =CH 2933, ν C=N 1647 cm .
-1
cm ; gc-ms: t = 25.05 min, ms: m/z 236 (molecular ion).
Anal. Calcd. for C
H N : C, 72.15%; H, 6.81%; N, 21.04%.
R
16 18 4
Anal. Calcd. for C
H N : C, 81.32%; H, 6.82%; N, 11.85%.
Found: C, 72.23%; H, 6.65%; N, 21.22%.
16 16 2
Found: C, 81.39%; H, 6.77%; N, 11.84%.
N,N-Bis-(pyridin-4-ylmethylene)butane-1,4-diamine (14).
This compound was obtained in 97% yield as a white solid, mp
N,N-Bis-(pyridin-2-ylmethylene)ethane-1,2-diamine (8).
This compound was obtained in 86% yield as a dark red liquid;
-1
73-74 ºC; ir (potassium bromide): ν =CH 2941, ν C=N 1643 cm .
-1
ir (potassium bromide): ν =CH 2916, ν C=N 1649 cm ; gc-ms:
Anal. Calcd. for C
H N : C, 72.15%; H, 6.81%; N, 21.04%.
16 18 4
t = 25.72 min, ms: m/z 238 (molecular ion).
Found: C, 72.01%; H, 6.98%; N, 21.01%.
R
Anal. Calcd. for C
Found: C, 70.47%; H, 6.02%; N, 23.51%.
H N : C, 70.57%; H, 5.92%; N, 23.51%.
14 14 4
General Procedure for Reaction of Bis-aldimines (7-14) with α-
Mercaptoacetic Acid.
N,N'-Bis-(pyridin-3-ylmethylene)ethane-1,2-diamine (9).
This compound was obtained in 100% yield as a yellow solid,
A mixture of the appropriate bis-aldimine (7-14) (4.20
mmoles) and the α-mercaptoacetic acid (8.40 mmoles) was

450
V. V. Kouznetsov, D. F. Amado, A. Bahsas, and J. Amaro-Luis
Vol. 43
stirred in dry benzene in ice cold bath for 15-20 min. The ben-
zene was distilled off and the solid bis-thiazolidinones (16-23)
were obtained from ethanol recrystallization.
31.6 ppm (2C, 5-CH ); COSY correlations [δ /δ (H/H)]: 2.73/3.55
2
H H
(2H , CH CH /2H , CH CH ), 3.66/3.92 (2H , 5-CH /2H , 5-
A
2
2
B
2
2
A
2
B
CH ), 3.92/5.82 (2H , 5-CH /2H, 2-CH), 5.82/7.43 (2H, 2-CH/2H,
2
B
2
Py), 5.82/8.57-8.58 (2H, 2-CH/4H, Py), 7.43/7.78-7.81 (2H, Py/2H,
Py), 7.43/8.57-8.58 (2H, Py/4H, Py), 7.78-7.81/8.57-8.58 (2H,
Py/4H, Py); HMQC correlations [δ /δ (C/H)]: 31.6/3.66 (2C/2H ,
1,2-Bis-(2-phenyl-4-oxo-1,3-thiazolidin-3-yl)ethane (16).
This compound was obtained in 68% yield as a white solid, mp
C
H
A
155-157 ºC; ir (potassium bromide): ν -CH - 2924, ν C(=O)-N
5-CH ), 31.6/3.92 (2C/2H , 5-CH ), 39.5/2.73 (2C/2H , CH CH ),
2
2
B
2
A
2
2
-1
1
1666 cm ; H nmr (DMSO-d ): δ 2.72-2.79 (m, 2H, CH CH ),
3.62-3.64 (m, 2H, CH CH ), 3.71 (d, J= 16.0 Hz, 2H, 5-CH ;
39.5/3.55 (2C/2H , CH CH ), 60.0/5.82 (2C/2H, 2-CH), 123.9/7.43
6
2
2
B
2
2
(2C/2H, Py), 134.7/7.9 (2C/2H, Py), 148.4/8.57-8.58 (2C/2H, Py),
150/8.57-8.58 (2C/2H, Py).
2
2
2
H ), 3.84 (ddd, J= 2.0, 11.0, 16.0 Hz, 2H, 5-CH ; H ), 5.89 (d,
A
2
B
13
J= 2.0 Hz, 2H, 2-CH), 7.30-7.42 (m, 10H, H ); C nmr (100
Anal. Calcd. for C
H N O S : C, 55.94%; H, 4.69%; N,
Ph
18 18 4 2 2
MHz): δ 171.4 (2C=O), 140 (2C, Ph), 128.9 (4C, Ph), 127.2 (4C,
14.50%. Found: C, 56.07%; H, 4.58%; N, 14.76%.
Ph), 127 (2C, Ph), 62.4 (2C, 2-CH), 43.3 (2C, CH CH ), 32 ppm
2
2
1,2-Bis-[2-(pyridin-4-yl)-4-oxo-1,3-thiazolidin-3-yl]ethane (19).
This compound was obtained in 33% yield as a white solid, mp
(2C, 5-CH ); COSY correlations [δ /δ (H/H)]: 2.72-2.79/3.62-
2
H H
3.64 (2H , CH CH /2H , CH CH ), 3.62-3.64/3.84 (2H ,
A
2
2
B
2
2
B
CH CH /2H , 5-CH ), 3.71/3.84 (2H , 5-CH /2H , 5-CH ),
224-225 ºC; ir (potassium bromide): ν -CH - 2933, ν C(=O)-N
2
2
B
2
A
2
B
2
2
-1 1
3.84/5.89 (2H , 5-CH /2H, 2-CH); HMQC correlations [δ /δ
1670 cm ; H nmr (DMSO-d ): δ 2.71 (dd, J= 5.8, 14.0 Hz, 2H,
B
2
C H
6
(C/H)]: 32.0/3.71 (2C/2H , 5-CH ), 32.0/3.84 (2C/2H , 5-CH ),
CH CH ), 3.59-3.63 (m, 4H, 5-CH ; H , CH CH ), 3.85 (dd, J=
A
2
B
2
2
2
2
A
2
2
43.3/2.72-2.79 (2C/2H , CH CH ), 43.3/3.62-3.64 (2C/2H ,
1.8, 16.0 Hz, 2H, 5-CH ; H ), 5.74 (d, J= 1.8 Hz, 2H, 2-CH),
A
2
2
B
2
B
CH CH ), 62.4/5.89 (2C/2H, 2-CH), 127/7.30-7.42 (2C/2H, Ph),
127.2/7.30-7.42 (4C/4H, Ph), 128.9/7.30-7.42 (4C/4H, Ph); gc-
7.31 (dd, J= 1.2, 4.5 Hz, 4H, H ), 8.55 (dd, J= 1.2, 4.5 Hz, 4H,
2
2
Py
13
H
); C nmr (100 MHz): δ 171.2 (2C=O), 150.2 (4C, Py), 149
Py
ms: t = 43.66 min, ms: m/z 384 (molecular ion).
(2C, Py), 121.4 (4C, Py), 60.8 (2C, 2-CH), 40.1 (2C, CH CH ),
R
2
2
Anal. Calcd. for C
N,7.29%. Found: C, 62.29%; H, 5.37%; N,7.01%.
H N O S : C, 62.47%; H, 5.24%;
31.3 ppm (2C, 5-CH ); COSY correlations [δ /δ (H/H)]:
20 20 2 2 2
2
H
H
2.71/3.59-3.63 (2H , CH CH /2H , CH CH ), 2.71/7.31 (2H ,
A
2
2
B
2
2
A
CH CH /4H, Py), 3.59-3.63/3.85 (2H , 5-CH /2H , 5-CH ),
2
2
A
2
B
2
1,2-Bis-[2-(pyridin-2-yl)-4-oxo-1,3-thiazolidin-3-yl]ethane (17).
This compound was obtained in 40% yield as a brown solid,
3.85/5.74 (2H , 5-CH /2H, 2-CH), 5.74/7.31 (2H, 2-CH/4H, Py),
B
2
7.31/8.55 (4H, Py/4H, Py); HMQC correlations [δ /δ (C/H)]:
C
H
mp 167-169 ºC; ir (potassium bromide): ν -CH - 2941, ν C(=O)-
31.3/3.59-3.63 (2C/2H , 5-CH ), 31.3/3.85 (2C/2H , 5-CH ),
2
A
2
B
2
-1
1
N 1680 cm ; H nmr (deuteriumcloroform): δ 2.71 (dd, J= 8.0,
18.0 Hz, 2H, CH CH ), 3.65 (d, J= 16.0 Hz, 2H, 5-CH ; H ),
40.1/2.71 (2C/2H , CH CH ), 40.1/3.59-3.63 (2C/2H ,
A
2
2
B
CH CH ), 60.8/5.74 (2C/2H, 2-CH), 121.4/7.31 (4C/4H, Py),
2
2
2
A
2
2
3.84 (dd, J= 2.0, 16.0 Hz, 2H, 5-CH ; H ), 3.93-4.00 (m, 2H,
150.2/8.55 (4C/4H, Py); ms: m/z 386 (molecular ion).
Anal. Calcd. for C N O S : C, 55.94%; H, 4.69%; N,
2
B
CH CH ), 5.87 (d, J= 2.0 Hz, 2H, 2-CH), 7.22 (ddd, J= 2.0, 5.0,
H
2
2
18 18
4 2 2
8.0 Hz, 2H, H ), 7.28 (dd, J= 2.0, 16.0 Hz, 2H, H ), 7.71 (ddd,
14.50%. Found: C, 55.78%; H, 4.55%; N, 14.63%.
Py
Py
J= 2.0, 8.0, 16.0 Hz, 2H, H ), 8.5 (dd, J= 2.0, 5.0 Hz, 2H, H );
Py
Py
1,4-Bis-(2-phenyl-4-oxo-1,3-thiazolidin-3-yl)butane (20).
This compound was obtained in 44% yield as a white solid, mp
13
C nmr (100 MHz): δ 172.5 (2C=O), 158.6 (2C, Py), 150.1 (2C,
Py), 137.3 (2C, Py), 123.6 (2C, Py), 121.1 (2C, Py), 63.7 (2C, 2-
CH), 39.9 (2C, CH CH ), 32.4 ppm (2C, 5-CH ); COSY correla-
168-170 ºC; ir (potassium bromide): ν -CH - 2931, ν C(=O)-N
2
2
2
2
-1
1
tions [δ /δ (H/H)]: 2.71/3.93-4.0 (2H , CH CH /2H ,
1666 cm
;
H nmr (DMSO-d ): δ 1.41-1.43 (m, 4H,
CH (CH ) CH ), 2.49-2.51 (m, 2H, CH (CH ) ), 3.51-3.70 (m,
H
H
A
2
2
B
6
CH CH ), 2.71/7.28 (2H , CH CH /2H, Py), 3.65/3.84 (2H , 5-
2
2
A
2
2
A
2
2 2
2
2
2 3
CH /2H , 5-CH ), 3.84/5.87 (2H , 5-CH /2H, 2-CH), 7.22/7.28
4H, CH (CH ) , 5-CH ; H ), 3.81-3.89 (m, 2H, 5-CH ; H ), 5.82
2
B
2
B
2
2
2 3
2
A
2
B
13
(2H, Py/2H, Py), 7.22/7.71 (2H, Py/2H, Py), 7.22/8.5 (2H,
Py/2H, Py), 7.28/7.71 (2H, Py/2H, Py), 7.71/8.5 (2H, Py/2H, Py);
HMQC correlations [δ /δ (C/H)]: 32.4/3.65 (2C/2H , 5-CH ),
(d, J= 1.0 Hz, 2H, 2-CH), 7.32-7.41 (m, 10H, H ); C nmr (100
Ph
MHz): δ 171.2 (2C=O), 140.3 (2C, Ph), 128.9 (4C, Ph), 128.9 (4C,
Ph), 126.9 (2C, Ph), 64.0 (2C, 2-CH), 42.9 (2C, CH (CH ) ), 37.9
C
H
A
2
2
2 3
32.4/3.84 (2C/2H , 5-CH ), 39.9/2.71 (2C/2H , CH CH ),
(2C, 5-CH ), 24.0 ppm (2C, CH (CH ) CH ); COSY correlations
B
2
A
2
2
2
2
2 2
2
39.9/3.93-4.0 (2C/2H , CH CH ), 63.7/5.87 (2C/2H, 2-CH),
121.1/7.28 (2C/2H, Py), 123.6/7.22 (2C/2H, Py), 137.3/7.71
[δ /δ (H/H)]: 1.41-1.43/2.49-2.51 (4H, CH (CH ) CH /2H ,
B
2
2
H
H
2
2 2
2
A
CH (CH ) ), 1.41-1.43/3.51-3.70 (4H, CH (CH ) CH /2H ,
2
2 3
2
2 2
2
B
(2C/2H, Py), 150.1/8.5 (2C/2H, Py); gc-ms: t = 40.30 min, t
=
CH (CH ) ), 2.49-2.51/3.51-3.70 (2H , CH (CH ) /2H ,
R1
R2
2
2 3
A
2
2 3
B
41.81 min, ms: m/z 386 (molecular ion).
CH (CH ) ), 3.51-3.70/3.81-3.89 (2H , 5-CH /2H , 5-CH ), 3.81-
2
2 3
A
2
B
2
Anal. Calcd. for C
14.50%. Found: C, 56.05%; H, 4.57%; N, 14.66%.
H N O S : C, 55.94%; H, 4.69%; N,
3.89/5.82 (2H , 5-CH /2H, 2-CH); HMQC correlations [δ /δ
18 18 4 2 2
B
2
C H
(C/H)]: 24.0/1.41-1.43 (2C/4H, CH (CH ) CH ), 37.9/3.51-3.70
2 2 2 2
(2C/2H , 5-CH ), 37.9/3.81-3.89 (2C/2H , 5-CH ), 42.9/2.49-2.51
A
2
B
2
1,2-Bis-[2-(pyridin-3-yl)-4-oxo-1,3-thiazolidin-3-yl]ethane (18).
(2C/2H , CH (CH ) ), 42.9/3.51-3.70 (2C/2H , CH (CH ) ),
A
2
2 3
B
2
2 3
This compound was obtained in 40% yield as a white solid, mp
64.0/5.82 (2C/2H, 2-CH), 126.9/7.32-7.41 (2C/2H, Ph),
128.9/7.32-7.41 (4C/4H, Ph), 128.9/7.32-7.41 (4C/4H, Ph).
198-200 ºC; ir (potassium bromide): ν -CH - 2930, ν C(=O)-N 1670
2
-1
1
cm ; H nmr (DMSO-d ): δ 2.73 (dd, J= 5.8, 14.0 Hz, 2H,
CH CH ), 3.55 (dd, J= 5.8, 14.2 Hz, 2H, CH CH ), 3.66 (d, J= 15.6
Anal. Calcd. for C
H N O S : C, 64.05%; H, 5.86%; N,
6
22 24 2 2 2
6.79%. Found: C, 64.17%; H, 5.77%; N, 6.84%.
2
2
2
2
Hz, 2H, 5-CH , H ), 3.92 (dd, J= 1.4, 15.4 Hz, 2H, 5-CH , H ),
2
A
2
B
1,4-Bis-[2-(pyridin-2-yl)-4-oxo-1,3-thiazolidin-3-yl]butane (21).
This compound was obtained in 50% yield as a yellow solid,
5.82 (d, J= 1.4 Hz, 2H, 2-CH), 7.43 (dd, J= 5.2, 7.9 Hz, 2H, H ),
Py
13
7.78-7.81 (m, 2H, H ), 8.57-8.58 (m, 4H, H ); C nmr (100
Py
Py
MHz): δ 171 (2C=O), 150 (2C, Py), 148.4 (2C, Py), 135.6 (2C, Py),
mp 162-163 ºC; ir (potassium bromide): ν -CH - 2927, ν C(=O)-
2
-1
1
134.7 (2C, Py), 123.9 (2C, Py), 60 (2C, 2-CH), 39.5 (2C, CH CH ),
N 1643 cm
; H nmr (DMSO-d ): δ 1.23-1.30 (m, 4H,
2
2
6

Mar-Apr 2006
Synthesis and Spectral Data of New 1,2-Bis-(2-hetaryl-4-oxothiazolidin-3-yl)ethanes
451
CH (CH ) CH ), 2.49-2.59 (m, 2H, CH (CH ) ), 3.43-3.51 (m,
The appropriate diamine (1.0 mmol) and aldehyde (2.5 mmol)
were stirred and refluxed in acetonitrile for 1 hour, followed by
addition of mercaptoacetic acid (2.5 mmol). The reaction mixture
was stirred and refluxed for 12 more hours. The precipitate prod-
uct was filtered and the filtrate was concentrated. The residue
was taken up with ethanol, where the remainder of product crys-
tallized. After the filtered precipitate was washed with ethanol
and dried to give the bis-thiazolidinones 16 and 20 in 59 and 36%
yields, respectively.
2
2 2
2
2
2 3
2H, CH (CH ) ), 3.55-3.62 (m, 2H, 5-CH ; H ), 3.82 (d, J= 15.0
2
2 3
2
A
Hz, 2H, 5-CH ; H ), 5.79 (d, J= 1.2 Hz, 2H, 2-CH), 7.32-7.36
2
B
(m, 2H, H ), 7.38 (d, J= 8.0 Hz, 2H, H ), 7.37 (m, 2H, H ),
Py
Py
Py
13
8.54 (dd, J= 1.5, 4.5 Hz, 2H H ); C nmr (100 MHz): δ 171.2
Py
(2C=O), 159.3 (2C, Py), 149.7 (2C, Py), 137.4 (2C, Py), 123.5
(2C, Py), 121.0 (2C, Py), 62.6 (2C, 2-CH), 42.2 (2C,
CH (CH ) ), 31.6 (2C, 5-CH ), 23.8 ppm (2C, CH (CH ) CH );
2
2 3
2
2
2 2
2
COSY correlations [δ /δ (H/H)]: 1.23-1.30/2.49-2.59 (4H,
H
H
CH (CH ) CH /2H , CH (CH ) ), 1.23-1.30/3.43-3.51 (4H,
2
2 2
2
A
2
2 3
Acknowledgements.
CH (CH ) CH /2H , CH (CH ) ), 2.49-2.59/3.43-3.61 (2H ,
2
2 2
2
B
2
2 3
A
CH (CH ) /2H , CH (CH ) ), 3.55-3.62/3.82 (2H , 5-
2
2 3
B
2
2 3
A
This work was supported by the grant of Instituto Colombiano
Para el Desarrollo de La Ciencia y La Tecnología “Francisco José
de Caldas” (COLCIENCIAS, Proyecto: 1102-05-11429). The
authors thank to Dr. E. E. Stashenko for providing the gc-ms
spectral data.
CH /2H , 5-CH ), 3.82/5.79 (2H , 5-CH /2H, 2-CH), 7.32-
2
B
2
B
2
7.36/7.38 (2H, Py/2H, Py), 7.32-7.36/7.37 (2H, Py/2H, Py), 7.32-
7.36/8.54 (2H, Py/2H, Py), 7.38/7.37 (2H, Py/2H, Py); HMQC
correlations [δ /δ
(C/H)]: 23.8/1.23-1.30 (2C/4H,
C
H
CH (CH ) CH ), 31.6/3.55-3.62 (2C/2H , 5-CH ), 31.6/3.82
2
2 2
2
A
2
(2C/2H , 5-CH ), 42.2/2.49-2.59 (2C/2H , CH (CH ) ),
B
2
A
2
2 3
REFERENCES AND NOTES
42.2/3.43-3.51 (2C/2H , CH (CH ) ), 62.6/5.79 (2C/2H, 2-CH),
B
2
2 3
121/7.38 (2C/2H, Py), 123.5/7.32-7.36 (2C/2H, Py), 137.4/7.37
(2C/2H, Py), 149.7/8.54 (2C/2H, Py).
[*] FAX 5776-346149 or 90212-224503. E-mail:
kouznet@uis.edu.co
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1,4-Bis-[2-(pyridin-3-yl)-4-oxo-1,3-thiazolidin-3-yl]butane (22).
This compound was obtained in 40% yield as a yellow solid, mp
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6
2
2 2
2
2
2 3
2
2 3
3.65 (d, J= 15.5 Hz, 2H, 5-CH ; H ), 3.94 (dd, J= 1.0, 15.5 Hz, 2H,
2
A
5-CH ; H ), 5.83 (d, J= 1.0 Hz, 2H, 2-CH), 7.41-7.45 (m, 2H, H ),
2
B
Py
13
7.78-7.81 (m, 2H, H ), 8.55-8.58 (m, 4H, H ); C nmr (100
Py
Py
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Py), 134.6 (2C, Py), 124 (2C,Py), 59.6 (2C, 2-CH), 41.9 (2C,
CH (CH ) ), 31.7 (2C, 5-CH ), 23.6 ppm (2C, CH (CH ) CH );
2
2 3
2
2
2 2
2
COSY correlations [δ /δ (H/H)]: 1.14-1.30/2.55-2.60 (4H,
H
H
CH (CH ) CH /2H , CH (CH ) ), 1.14-1.30/3.37-3.43 (4H,
2
2 2
2
A
2
2 3
CH (CH ) CH /2H , CH (CH ) ), 2.55-2.60/3.37-3.43 (2H ,
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2
2 2
2
B
2
2 3
A
CH (CH ) /2H , CH (CH ) ), 3.65/3.94 (2H , 5-CH /2H , 5-
2
2 3
B
2
2 3
A
2
B
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CH ), 3.94/5.83 (2H , 5-CH /2H, 2-CH), 5.83/7.41-7.45 (2H, 2-
2
B
2
CH/2H, Py), 7.41-7.45/7.78-7.81 (2H, Py/2H, Py), 7.41-7.45/8.55-
8.58 (2H, Py/4H, Py), 7.78-7.81/8.55-8.58 (2H, Py/4H, Py); HMQC
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H
2
2 2
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CH ), 31.7/3.65 (2C/2H , 5-CH ), 31.7/3.94 (2C/2H , 5-CH ),
2
A
2
B
2
41.9/2.55-2.60 (2C/2H , CH (CH ) ), 41.9/3.37-3.43 (2C/2H ,
A
2
2 3
B
CH (CH ) ), 59.6/5.83 (2C/2H, 2-CH), 124/7.41-7.45 (2C/2H, Py),
2
2 3
134.6/7.78-7.81 (2C/2H, Py), 148.2/8.55-8.58 (2C/4H, Py),
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Anal. Calcd. for C
H N O S : C, 57.95%; H, 5.35%; N,
20 22 4 2 2
13.52%. Found: C, 58.14%; H, 5.23%; N, 13.44%.
1,4-Bis-[2-(pyridin-4-yl)-4-oxo-1,3-thiazolidin-3-yl]butane (23).
This compound was obtained in 40% yield as a white solid, mp
164-166 ºC; ir (potassium bromide): ν -CH - 2949, ν C(=O)-N
2
-1
1720 cm .
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H N O S : C, 57.95%; H, 5.35%; N,
20 22 4 2 2
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13.33%.
General Procedure for One-Pot Three-Component Reaction of
Diamine with Benzaldehyde and α-Mercaptoacetic Acid.

452
V. V. Kouznetsov, D. F. Amado, A. Bahsas, and J. Amaro-Luis
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