Efficient "on water" green route heterocyclization of thiosemicarbazones with DMAD

Article abstract of DOI:10.1080/10426507.2015.1073282

A simple, efficient, and eco-friendly procedure for the synthesis of thiazolidin-4-one derivatives in water from cyclocondensation reaction of thiosemicarbazone derivatives and dimethylacetylene dicarboxylate (DMAD) in good yield is reported. The regiochemistry of the cyclized products is established by elemental analysis, IR, NMR, and mass spectral data. A single crystal X-ray diffraction study of a representative compound, 3f, is reported.

Full text of DOI:10.1080/10426507.2015.1073282

Phosphorus, Sulfur, and Silicon and the Related Elements
ISSN: 1042-6507 (Print) 1563-5325 (Online) Journal homepage: http://www.tandfonline.com/loi/gpss20
Efficient “on water” green route heterocyclization
of thiosemicarbazones with DMAD
Rohit Singla, Deepika Gautam, Poonam Gautam & R. P. Chaudhary
To cite this article: Rohit Singla, Deepika Gautam, Poonam Gautam & R. P. Chaudhary
(
2016) Efficient “on water” green route heterocyclization of thiosemicarbazones with
DMAD, Phosphorus, Sulfur, and Silicon and the Related Elements, 191:5, 740-745, DOI:
0.1080/10426507.2015.1073282
1
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Date: 07 May 2016, At: 01:50

PHOSPHORUS, SULFUR, AND SILICON
, VOL. , NO. , –

http://dx.doi.org/./..
Efficient “on water”green route heterocyclization of thiosemicarbazones with DMAD
Rohit Singla, Deepika Gautam, Poonam Gautam, and R. P. Chaudhary
Department of Chemistry, Sant Longowal Institute of Engineering & Technology, Longowal (Sangrur), Punjab, India
ABSTRACT
ARTICLE HISTORY
Received  May 
Accepted  July 
A simple, efficient, and eco-friendly procedure for the synthesis of thiazolidin-4-one derivatives in water
from cyclocondensation reaction of thiosemicarbazone derivatives and dimethylacetylene dicarboxylate
(
DMAD) in good yield is reported. The regiochemistry of the cyclized products is established by elemental
KEYWORDS
Thiazolidin--one;
thiosemicarbazone; DMAD;
X-ray diffraction; eco-friendly
analysis, IR, NMR, and mass spectral data. A single crystal X-ray diffraction study of a representative com-
pound, 3f, is reported.
GRAPHICAL ABSTRACT
1
. Introduction
but still they require toxic organic solvents during product iso-
lation. Therefore, the development of an efficient and versatile
method is still required. On the other hand, ultrasonic reactions
have been increasingly used as clean, green, and environmen-
tally benign routes for the preparation of organic compounds of
synthetic and biological values.12
The use of water as a reaction medium for chemical transforma-
tions has been the subject of organic synthesis due to cost, safety,
and environmental concerns.1–2 Recently, the use of aqueous
media in organic reactions has attracted a great deal of attention.
The variety of interactions between water and substrates such
as hydrogen bonding or interactions related to polarity, acidity
and hydrophobicity make water interesting from an industrial as
Thiazolidin-4-one framework has emerged as one of the
most prolific chemotypes in the recent computational analysis of
medicinal chemistry databases due to its multifarious pharma-
ceutical applications. Thiazolidin-4-one derivatives have been
used as synthetic intermediates, dyes and display diverse biolog-
3
well as laboratory perspective. Sharpless et al. recently defined
as “on water” conditions, using water as a solvent for the reac-
4
tion of water insoluble reactants. A number of synthetic pro-
1
3
14
ical activities such as anticancer, anti-inflammatory, antimi-
tocols for the construction of the thiazolidin-4-one skeleton are
available in the literature which used desiccants such as anhyd.
15
16
17
18
crobial, anticonvulsant, antifungal, antitubercular, anti
19
20
21
HIV, analgesic, antimalarial, HIV reverse transcriptase
5
6
7
8
NaOAc, DCC, ZnCl2, Dean Stark apparatus and molecu-
lar sieves for the removal of water from the reaction mixture.
These methods involve expensive and toxic starting materials,
harsh reaction conditions, long reaction times, and poor yield of
obtained products. Often these reactions are performed in vari-
ous organic solvents posing a serious threat of fire hazard, espe-
cially when they are carried out under microwave irradiation.
Several solvent free protocols9 have been developed recently,
22
23
(
RT) inhibitory activity, COX-2 inhibitory activity, anti-
24
25
hyperglycemic , and insulin reversal activity. Prompted by
these facts and in continuation to our research program on
the synthesis of thiazolidin-4-ones of potential biological rel-
evance2
6–28
we envisaged the environmentally benign ultra-
sound assisted aqueous medium heterocyclization of thiosemi-
carbazones with DMAD and the structural analysis of new
hydrazono thiazolidin-4-ones.
–11
CONTACT R. P. Chaudhary
Punjab-, India.
rpchaudhary@gmail.com
Department of Chemistry, Sant Longowal Institute of Engineering & Technology, Longowal (Sangrur),
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/gpss.
Supplementary data associated with this article include cif file of compound 3f, and NMR spectra of the compounds reported in the article. Supplemental data for this
article can be accessed on the publisher’s website at http://dx.doi.org/./..
©
 Taylor & Francis Group, LLC

PHOSPHORUS, SULFUR, AND SILICON
741
Scheme . Synthetic route to synthesis of thiazolidin--one derivatives 3.
2
. Result and discussion
In the present investigations, on-water synthesis of thiazolidin-
-one derivatives 3 has been accomplished from thiosemicar-
bazones 2 and DMAD (Scheme 1). In one strategy, thiazolidin-
-one derivatives were prepared by stirring a mixture of
by TLC and in some cases the reaction took 30 h for completion.
The effect of ultrasound on the reaction was studied with an aim
to reduce the time period of the reaction and improve the yield
of the product. It was observed that the reaction was completed
within 30–60 min under ultrasonication and yield of the prod-
ucts was reasonably improved. The structure of products, time
period of reaction and yield of the isolated products is reported
in Table 1.
4
4
thiosemicarbazone 2 and DMAD in water at ambient temper-
ature for 24–30 h. In another strategy, thiazolidin-4-ones were
obtained in good yield through ultrasonication of the above
reaction mixture in water for 30–60 min.
The characterization of all the thiazolidin-4-one derivatives
1
13
3
a-l was done by means of elemental analysis, IR, H NMR,
C
Thiosemicarbazone derivatives 2 of aldehydes or ketones
were prepared by stirring a mixture of carbonyl compound 1
and thiosemicarbazide in ethanol containing a catalytic amount
NMR and mass spectral data. The IR spectrum of compound 3a
−1
showed two peaks at 1720 and 1685 cm which was assigned to
two carbonyl groups. Appearance of two singlets at δ 3.77 ppm
29
of conc. HCl by the reported procedure. Thiosemicarbazone
, on stirring with an equimolar amount of DMAD in water at
ambient temperature for 24–30 h, furnished a single product
TLC), which was characterized by spectral data as thiazolidin-
-one 3 and not as thiazinan-4-one 4. The plausible mechanism
1
and δ 6.61 ppm in H NMR spectrum of 3a were assigned to
2
OCH3 group and vinyl proton (=CH), respectively. A broad sig-
13
nal for NH appeared at δ 12.52 ppm. C NMR spectrum of 3a
displayed peaks at δ 166.0 (C=O), δ 165.7 (C=O), and δ 165.4
(
4
(
C=N).
of formation of 3 (route a) and 4 (route b) from condensation of
thiosemicarbazone and DMAD in water is shown in Scheme 2.
In the present investigations, thiazolidin-4-one 3 is the only
product isolated in all the cases under study (TLC). Compound
−1
IR spectrum of 3f exhibited a peak at 1724 cm which
−
1
was assigned to ester carbonyl group. The peak at 1689 cm
−1
was assigned to CONH group. Two peaks at 1630 cm and
−1
1
1
613 cm were assigned to two C=N groups. In the H NMR
4
, if obtained, would behave spectroscopically similar to 3. To
spectrum of 3f, the appearance of a singlet at δ 3.76 ppm was
assigned to the methoxy group and that of a singlet at δ 6.63 ppm
elucidate the isomeric structures and structure of the products
obtained as well as to characterize the products, we used spec-
tral (IR, NMR and Mass) data but rigorous proof came from
the single crystal X-ray structural analyses of 3f. In order to
test the generality of the method, different aldehydes or ketones
13
was assigned to methine (=CH) proton. The C NMR spec-
trum of 3f displayed peaks at δ 165.8 (C=O), δ 165.5 (C=O),
δ 162.3 (C=N), and δ 158.7 (C=N). The mass spectrum of 3f
exhibited a quasi-molecular ion peak at m/z 330.2 (27.7%). The
structure of compound 3f was confirmed by a single crystal
X-ray crystallographic study, which shows cis configuration at
C=C and trans at C=N. The structure of all other products was
(
aliphatic, aromatic and heterocyclic) were used and it was
found that the reaction can tolerate all different types of car-
bonyl compounds. The progress of the reaction was monitored
Scheme . Plausible mechanism for the formation of thiazolidin--one 3 and/or thiazinan--one 4.

742
R. SINGLA ET AL.
Table . Reaction parameters for the synthesis of thiazolidin--one derivatives 3a-l.
Method (a)
Method (b)
Entry Compound , Q = Time (h) Yield (%) Time (min) Yield (%)


a








b


c
d









e
f




Figure . ORTEP diagram of Methyl (E)--((Z)--(((E)-,-dihydronaphthalen-(H)-
ylidene)hydrazono)--oxothiazolidin--ylidene)acetate (3f) with non hydrogen
ellipsoids drawn at % probability level.







g
h








similarly assigned by analytical and spectral data. The analytical
data of all the synthesized compounds was in accordance with
the assigned structures and is in good agreement with calculated
values (within range of ± 0.4%).


i
j








2
.1 Crystallographic study and structural description of
compound 3f


k
l








X-ray diffraction measurements were performed on X Calibur
EOS OXFORD Diffractometer at 293 (2) K. The intensity
data were collected using graphite monochromatic Mo-Kα
a = On water synthesis; b = Ultrasound assisted synthesis.
Table . Crystal data and the structure refinement parameters of compound (3f).
˚
radiation (λ = 0.71073 A). The structure was solved by direct
30
method using the SHELX-97 software package and refined
2
by full-matrix least-squares procedures on F . All nonhydrogen
Compound
f
atoms were refined with anisotropic thermal parameters. The
CCDC no.
Empirical formula
Formula weight

compound 3f crystallized in the monoclinic space group P1,
C H N O S





˚
with Z = 2 and cell parameters a = 7.7206 (7) A, b = 8.5084
.
˚
˚
(
5) A, c = 15.5819 (9) A, α = 82.116 (5)˚, β = 79.399 (6)˚,
Space group
a ( A˚ )
b ( A˚ )
c ( A˚ )
α (˚)
β (˚)
γ (˚)
Volume ( A˚ )
Z
Density (calculated) (Mg/m )
µ (mm
P-
.()
γ = 81.259 (6)˚. In the compound, the C11N2 and C12O1
˚
bond distances of 1.280 (3) and 1.212 (3) A as compared
.()
.()
.()
˚
to literature value of 1.27 and 1.22 A respectively, indicated
the double bond character of these bonds. The bond angles
.()
N2C11N3 and O1C12C13 are 121.5˚ (2) and 124.7˚ (2), respec-
.()
2
tively, which is consistent with the sp hybrid character of

.()

C11 and C12 atoms. The crystallographic data and refine-
ment parameters of 3f are reported in Table 2. The ORTEP
diagram obtained from X-ray structure of 3f is shown in
Figure 1. In the ORTEP diagram, the asymmetric unit of 3f
contains (E)-methyl 2-((Z)-2-((E)-(3,4-dihydronaphthalen-

.
.
−

)
Crystal size (mm)
Color
Temperature (K)
. × . × .
Pale yellow
 ()
Theta range for data collection
Reflections collected
Independent reflections
Data/restraints/parameters
Goodness-of-fit on F
Final R indices [I > σ(I)]]
R indices (all data)
. to .
1
(2H)-ylidene)hydrazono)-4-oxothiazolidin-5-ylidene)acetate
,
,
and one DMF solvate molecule. DMF solvate is included in
…
..
//
the crystal lattice by hydrogen bond between N-H O-C with
bond length 2.7 A. The selected bond lengths and bond angles
.
˚
R = ., wR = .


of compound 3f are listed in Table 3. The crystal packing
diagram of 3f along c axis (Figure S 1) and hydrogen bonding
parameters (Table S 1) (Supplemental Materials).
R = ., wR = .


Largest diff. peak/ hole (e A˚ )
−
−., .

PHOSPHORUS, SULFUR, AND SILICON
743
Table . Selected bond parameters of compound 3f.
.. (E)-Methyl -((Z)--oxo--(propan--ylidenehydrazono)
thiazolidin--ylidene)acetate (a)
Entry
Bond Length ( A˚ )
Entry
Bond Angle(˚)
−1
Yellow solid; mp 198–200°C. IR (cm ) 1720 (C=O), 1685
1
S()-C()
S()-C()
O()-C()
O()-C()
O()-C()
O()-C()
N()-C()
N()-N()
N()-C()
N()-C()
N()-C()
C()-C()
.()
.()
.()
.()
.()
.()
.()
.()
.()
.()
. ()
.()
C()-S()-C()
C()-O()-C()
C()-N()-N()
C()-N()-C()
C()-N()-N()
N()-C()-C()
N()-C()-C()
O()-C()-N()
O()-C()-C()
N()-C()-N()
N()-C()-S()
N()-C()-S()
.()
. ()
. ()
. ()
.()
. ()
. ()
.()
=
=
(
C O), 1620 (C N), H NMR (400 MHz, DMSO-d6) δ;
1
.97–2.02 (m, 6H, 2CH3), 3.77 (s, 3H, OCH3), 6.61 (s, 1H,
13
=
6
CH), 12.52 (br, 1H, NH). C NMR (100 MHz, DMSO-d ) δ;
1
66.0 (C O), 165.7 (C O), 165.4 (C N), 143.2 (thiazole-C5),
=
=
=
1
13.7 (vinyl-CH), 52.0 (OCH3), 24.6 (CH3), 18.4 (CH3). Mass:
+
(M+H ): 242.1 (48%). Anal. Calcd. for C9H11N3O3S: C, 44.80;
. ()
. ()
. ()
H, 4.60; N, 17.42; S, 13.29; found: C, 44.93; H, 4.72; N, 17.55; S,
1
3.40.
. ()
.. (E)-Methyl -((Z)--(cyclopentylidenehydrazono)
-
-oxothiazolidin--ylidene)acetate (b)
−1
Yellow solid; mp 224–26°C. IR (cm ) 1716 (C=O), 1688
1
3
. Experimental
(C=O), 1612 (C=N). H NMR (400 MHz, DMSO-d ) δ; 1.72–
6
1
.77 (m, 4H, 2CH2), 2.42–2.51 (m, 4H, 2CH2), 3.77 (s, 3H,
All the chemicals used were obtained from Sigma and used
without further purification. Melting points were determined
1
3
COOMe), 6.61 (s, 1H, =CH), 12.69 (br, 1H, NH). C NMR
(
100 MHz, DMSO-d6) δ; 179.1 (C=O), 165.8 (C=O), 165.5
1
in open capillaries and are reported uncorrected. H NMR and
(
C=N), 143.1 (thiazole-C5), 113.8 (vinyl-CH), 52.3 (OCH3),
13
C NMR spectra were recorded in DMSO-d6 on BRUKER
+
3
2.8 (CH2), 30.2 (CH2), 24.2 (CH2). Mass: (M+H ): 268.0
AVANCE II 400 MHz spectrometer using tetramethylsilane
TMS) as an internal standard. The chemical shifts are reported
in ppm. IR spectra were recorded on Perkin Elmer (RZX) FTIR
(
17%) .Anal. Calcd. for C11H13N3O3S: C, 49.43; H, 4.90; N,
5.72; S, 12.00; found: C, 49.56; H, 5.01; N, 15.58; S, 12.15.
(
1
−1
spectrometer and the results are reported in cm . Mass spectra
were recorded on a WATERS, Q-TOF MICROMASS (LC-MS) .. (E)-Methyl -((Z)--(cyclohexylidenehydrazono)
--oxothiazolidin--ylidene)acetate (c)
instrument. The elemental analyses of the compounds were per-
−
1
formed on Euro EA 3000 Elemental Analyzer. Thin layer chro- Yellow solid; mp >300°C. IR (cm ) 1722 (C=O), 1686 (C=O),
1
matography (TLC) was performed on silica gel G coated plates 1618 (C=N). H NMR (400 MHz, DMSO-d ) δ; 1.76–1.82
6
and using iodine vapor as visualizing agent. Ultrasonication was (m, 2H, CH ), 1.92–1.98 (m, 4H, 2CH ), 2.46–2.54 (m, 4H,
2
2
done on Cole Parmar CPX500, 20 KHz, 500 Watt instrument. 2CH ), 3.75 (s, 3H, COOMe), 6.60 (s, 1H, =CH), 12.62 (br, 1H,
2
13
X-ray diffraction was performed on X Calibur EOS OXFORD NH). C NMR (100 MHz, DMSO-d ) δ; 179.8 (C=O), 165.1
6
1
Diffractometer. The Supplemental Materials contains sample H (C=O), 164.9 (C=N), 145.1 (thiazole-C5), 112.7 (vinyl-CH),
and 13C NMR spectra for 3a – 3l (Figures S 2 – S 17)
3 2 2 2 2
54.4 (OCH ), 34.9 (CH ), 31.4 (CH ), 24.8 (CH ), 24.2 (CH ).
+
Thiosemicarbazone derivatives 2a-l were obtained from Mass: (M+H ): 282.1 (12%). Anal. Calcd. for C H N O S: C,
12
15
3
3
appropriate aldehyde or ketone and thiosemicarbazone in 51.23; H, 5.37; N, 14.94; S, 11.40; found: C, 51.36; H, 5.48; N,
ethanol by the reported procedure and characterized by their lit- 15.08; S, 11.24.
erature31 melting points.
.. (E)-Methyl -((Z)--((Z)-benzylidenehydrazono)
-
-oxothiazolidin--ylidene)acetate (d)
−1
Yellowish solid; mp 238–240°C. IR (cm ) 1715 (C=O), 1681
1
3
.1 General procedure for the synthesis of 3
=
=
(
C O), 1612 (C N). H NMR (400 MHz, DMSO-d6) δ; 3.78
(
s, 3H, COOCH3), 6.67 (s, 1H, =CH), 7.48–7.51 (m, 3H, Ph),
(
a) On water synthesis
7
.81–7.83 (m, 2H, Ph), 8.53 (s, 1H, N =CH), 12.91 (br, 1H,
A suspension of thiosemicarbazone 2 (1.0 mmol) and
dimethyl acetylene dicarboxylate, DMAD (1.0 mmol) in
water (10 mL) was stirred at ambient temperature for 20–
13
NH). C NMR (100 MHz, DMSO-d6) δ; 165.8 (C=O), 165.7
(
(
C=O), 160.3 (C=N), 158.6 (C=N), 142.8 (thiazole-C5), 133.6
C6H5), 131.2 (C6H5), 128.9 (C6H5), 128.0 (C6H5), 114.2 (vinyl-
30 h. The progress of the reaction was monitored by TLC.
+
CH), 52.4 (OCH3). Mass: (M+H ): 290.2 (25%). Anal. Calcd.
After completion of reaction, the solid obtained was fil-
tered, dried and recrystallized from ethanol: DMF (3:1)
mixture.
for C13H11N3O3S: C, 53.97; H, 3.83; N, 14.52; S, 11.08; found: C,
5
4.12; H, 3.94; N, 14.71; S, 11.21.
(b) Synthesis under Ultrasonication
A suspension of thiosemicarbazone 2 (1.0 mmol) and
dimethyl acetylene dicarboxylate, DMAD (1.0 mmol)
in water (10 mL) was kept in an ultrasound sonicator

.. (E)-Methyl -((Z)--oxo--((Z)-(-phenylethylidene)
hydrazono)thiazolidin--ylidene)acetate (e)
−1
Yellowish solid; mp 222–24°C. IR (cm ) 1718 (C O), 1688
=
1
(
20 KHz) for 30–60 min. The progress of the reaction
=
=
(
C O), 1618 (C N). H NMR (400 MHz, DMSO-d6) δ; 1.98 (s,
was monitored by TLC. After completion of reaction,
the solid obtained was filtered and recrystallized from
ethanol: DMF (3:1) mixture.
=
3
H, CH3) 3.76 (s, 3H, COOCH3), 6.65 (s, 1H, CH), 7.52–7.56
(
m, 3H, Ph), 7.86–7.89 (m, 2H, Ph), 8.55 (s, 1H, N CH), 12.86
=
(
br, 1H, NH). 13C NMR (100 MHz, DMSO-d6) δ; 165.6 (C O),
=

744
R. SINGLA ET AL.
1
65.2 (C=O), 160.5 (C=N), 157.5 (C=N), 143.7 (thiazole-C5), .. (E)-Methyl--((Z)--oxo--((E)-(thiophen
135.6 (C6H5), 132.4 (C6H5), 128.7 (C6H5), 128.3 (C6H5), 114.8
--ylmethylene)hydrazono)
+
(
(
vinyl-CH), 54.6 (OCH3), 25.7 (CH3). Mass: (M+H ): 304.1
thiazolidin--ylidene)acetate (i)
−
1
100%). Anal. Calcd. for C14H13N3O3S: C, 55.43; H, 4.32; N, Yellow fluffy solid; mp 242–44°C. IR (ν cm ): 3447 (NH),
3.85; S, 10.57; found: C, 55.58; H, 4.42; N, 13.96; S, 10.70.
1
1
1731(C=O), 1696 (C=O), 1640 (C=N), 1626 (C=N). H NMR
(
400 MHz, DMSO-d6) δ; 3.79 (s, 3H, OCH3), 6.67 (s, 1H,
CH), 7.19–7.21 (m, 1H, thiophene), 7.59–7.60 (m, 1H, thio-
phene), 7.78–7.79 (m, 1H, thiophene), 8.69 (s, 1H, N =CH),
=
13
1
(
(
2.84 (br, 1H, NH). C NMR (100 MHz, DMSO-d6) δ; 165.8

.. (E)-Methyl -((Z)--((E)-(,-dihydronaphthalen-(H)
C=O), 165.6 (C=O), 162.2 (C=N), 159.3 (C=N), 153.0, 142.8
-
ylidene)hydrazono)--oxothiazolidin--ylidene)
thiazole-C5), 138.2, 133.2, 130.8, 128.2 (thiophene-C), 114.1
acetate (f)
+
−1
(vinyl-CH), 52.4 (OCH3), 35.7, 30.7. Mass: (M+H ): 296.2
Yellow shining crystals; mp 206–08°C. IR (ν cm ): 3157 (NH),
1
(10.6%). Anal. Calcd. For C11H9N3O3S2: C, 44.73; H, 3.07; N,
1
724 (C=O), 1689 (C=O), 1630 (C=N), 1613 (C=N). H NMR
1
4.23; S, 21.71; found: C, 44.86; H, 3.19; N, 14.36; S, 21.84.
(
400 MHz, DMSO-d6) δ; 1.80–1.86 (m, 2H, CH2), 2.8 (t, 2H,
CH2, J = 5.7 Hz), 2.87 (t, 2H, CH2, J = 6.5 Hz), 3.76 (s, 3H,
OCH3), 6.63 (s, 1H, =CH), 7.23 (d, 1H, ArH, J = 7.4 Hz), 7.28–

.. (E)-Methyl--((Z)--((Z)-(furan--ylmethylene)
7
.38 (m, 2H, ArH), 8.10 (d, 1H, ArH, J = 6.8 Hz), 12.9 (br, 1H,
hydrazono)--oxothiazolidin--ylidene)acetate (j)
13
NH). C NMR (100 MHz, DMSO-d6) δ; 165.8 (C=O), 165.5
−1
Yellow solid; mp 226–28°C. IR (ν cm ): 1730 (C=O), 1692
(
C=O), 162.3 (C=N), 158.7 (C=N), 143.0 (thiazole-C5), 141.0,
1
(
C=O), 1638 (C=N), 1630 (C=N). H NMR (400 MHz,
1
31.6, 130.3, 128.8, 126.2, 124.7 (Ar-C), 113.9 (vinyl-CH), 52.3
DMSO-d6) δ; 3.80 (s, 3H, OCH3), 6.68 (s, 1H, =CH), 7.22–
+
(
OCH3), 29.0 (CH2), 27.0 (CH2), 21.7 (CH2). Mass: (M+H ):
7
1
.25 (m, 1H, furan), 7.64–7.67 (m, 1H, furan), 7.88–7.89 (m,
3
30.2 (27.7%). Anal. Calcd. For C16H15N3O3S: C, 58.34; H, 4.59;
13
H, furan), 8.76 (s, 1H, N =CH), 12.9 (br, 1H, NH).
C
N, 12.76; S, 9.74; found: C, 58.46; H, 4.72; N, 12.84; S, 9.86.
NMR (100 MHz, DMSO-d6) δ; 166.7 (C=O), 166.3 (C=O),
1
1
3
62.8 (C=N), 158.6 (C=N), 154.1, 143.4 (thiazole-C5), 138.6,
33.9, 131.6, 129.3 (furan-C), 114.7 (vinyl-CH), 52.8 (OCH3),
+
5.6, 31.2. Mass: (M+H ): 280.0 (45%). Anal. Calcd. For

.. (E)-Methyl--((Z)--((E)-(-methoxy
C11H9N3O4S: C, 47.31; H, 3.25; N, 15.05; S, 11.48; found: C,
-
,-dihydronaphthalen-(H)-ylidene)hydrazono)
-oxothiazolidin--ylidene)acetate (g)
47.44; H, 3.38; N, 15.15; S, 11.61.
-
−1
Yellow shining crystals; mp 198–200°C. IR (ν cm ): 3160 (NH),
1
.. (E)-Methyl--((Z)--((Z)-(,-dimethyl--phenyl-,-
1
720 (C=O), 1688 (C=O), 1626 (C=N), 1618 (C=N). H NMR
dihydro-H-indazol-(H)-ylidene) hydrazono)
(
400 MHz, DMSO-d6) δ; 1.82–1.87 (m, 2H, CH2), 2.83 (t, 2H,
--oxothiazolidin--ylidene)acetate (k)
CH2, J = 5.7 Hz), 2.91 (t, 2H, CH2, J = 6.6 Hz), 3.79 (s, 3H,
OMe), 3.76 (s, 3H, COOCH3), 6.65 (s, 1H, =CH), 7.18 (d, 1H,
ArH, J = 7.0 Hz), 7.29–7.34 (m, 1H, ArH), 7.93 (d, 1H, ArH,
−
1
Dark yellow shining solid; mp 212–14°C. IR (ν cm ): 3260
(
NH), 1728 (C=O), 1692 (C=O), 1636 (C=N), 1620 (C=N).
1
13
H NMR (400 MHz, DMSO-d6) δ; 1.07 (s, 6H, 2CH3), 2.43 (s,
J = 7.0 Hz), 12.8 (br, 1H, NH). C NMR (100 MHz, DMSO-
d6) δ; 166.7 (C=O), 165.3 (C=O), 162.8 (C=N), 159.6 (C=N),
2
=
H, CH2), 3.00 (s, 2H, CH2), 3.89 (s, 3H, OCH3), 6.70 (s, 1H,
CH), 7.43 (m, 1H, ArH), 7.78–7.83 (m, 4H, ArH), 7.95 (s, 1H,
1
43.5 (thiazole-C5), 142.0, 132.6, 130.6, 128.0, 126.8, 123.9 (Ar-
13
N =CH), 12.8 (br, 1H, NH), C NMR (100 MHz, DMSO-d6)
δ; 165.9 (C=O), 158.5 (C=N), 143.6 (C=N), 143.3 (thiazole-
C5), 138.6, 136.2, 129.4, 127.5, 123.0 (C6H5), 116.5 (pyrazole-
C), 113.7 (vinyl-CH), 54.6 (OCH3), 52.3 (OCH3), 29.0 (CH2),
+
2
7.2 (CH2), 22.6 (CH2). Mass: (M ): 359 (85%). Anal. Calcd.
for C17H17N3O4S: C, 56.81; H, 4.77; N, 11.69; S, 8.92; found: C,
CH), 113.7 (vinyl-CH), 52.3 (OCH3), 36.0 (CH2), 33.4 (CH2),
56.96; H, 4.89; N, 11.80; S, 9.06.
+
2
7.9 (CH3). Mass; (M+H ): 424.3 (96.9%). Anal. Calcd. For
C21H21N5O3S: C, 59.56; H, 5.00; N, 16.54; S, 7.57; found: C,
9.64; H, 5.12; N, 16.62; S, 7.71.
5
.. (E)-Methyl--((Z)--((H-fluoren--ylidene)hydrazono)
-
-oxothiazolidin--ylidene)acetate (h)
.. (E)-methyl--((Z)--((Z)-(,-dihydro-H-inden--
ylidene)hydrazono)--oxothiazolidin--ylidene)
acetate (l)
−
1
1
Yellow shining crystals; mp 232–34°C. IR (ν cm ): 1720
(
(
C=O), 1682 (C=O), 1628 (C=N), 1618 (C=N). H NMR
−1
400 MHz, DMSO-d6) δ; 3.79 (s, 3H, OCH3), 6.70 (s, 1H, =CH), Dark yellow solid; mp 214–16°C. IR (ν cm ): 3186 (NH),
1
7
.35–7.38 (m, 2H, ArH), 7.47–7.53 (m, 2H, ArH), 7.78–7.85 1733 (C=O), 1690 (C=O), 1628 (C=N), 1612(C=N). H NMR
(
m, 3H, ArH), 8.57 (d, 1H, ArH, J = 7.6 Hz), 13.13 (br, 1H, (400 MHz, DMSO-d6) δ; 2.92 (t, 2H, CH2, J = 6.9 Hz), 3.01–3.05
13
NH). C NMR (100 MHz, DMSO-d6) δ; 165.7 (C=O), 165.6 (m, 2H, CH2), 3.76 (s, 3H, OCH3), 6.61 (s, 1H, =CH), 7.33 (t,
(
C=O), 162.9 (C=N), 158.0 (C=N), 142.4 (thiazole-C5), 141.6, 1H, ArH, J = 7.7 Hz), 7.41–7.48 (m, 2H, ArH), 7.73 (d, 1H, ArH,
13
1
40.5, 135.6, 131.8, 131.4, 130.9, 129.9, 128.3, 128.2, 122.2, 120.5 J = 7.6 Hz), 12.82 (br, 1H, NH), C NMR (100 MHz, DMSO-
+
(
(
Ar-C), 114.8 (vinyl-CH), 52.4 (OCH3). Mass: (M+H ): 364.1 d6) δ; 172.1 (C=O), 165.8 (C=O), 165.5 (C=N), 157.9 (C=N),
100%). Anal. Calcd. For C19H13N3O3S: C, 62.80; H, 3.61; N, 150.3, 143.1 (thiazole-C5), 136.9, 131.7, 127.0, 125.9, 121.9 (Ar-
1
1.56; S, 8.82; found: C, 62.91; H, 3.75; N, 11.70; S, 9.03.
C), 113.8 (vinyl-CH), 52.3 (OCH3), 28.6 (CH2), 28.0 (CH2).

PHOSPHORUS, SULFUR, AND SILICON
745
+
Mass; (M+H ): 316.1 (100%). Anal. Calcd. For C15H13N3O3S:
13. Zhou, H.; Wu, S.; Zhai, S.; Liu, A.; Sun, Y.; Li, R.; Zhang, Y.; Ekins, S.;
Swaan, P.W.; Fang, B.; Zhang, B.; Yan, B. J. Med. Chem. 2008, 51, 1242-
C, 57.13; H, 4.16; N, 13.33; S, 10.17; found: C, 57.27; H, 4.28; N,
3.42; S, 10.30.
1
251.
1
1
4. Vigorita, M. G.; Ottana, R.; Monforte, F.; Maccari, R.; Monforte, M. T.;
Trovato, A.; Taviano, M. F.; Miceli, N.; Luca, G. D.; Alcaro, S.; Ortuso,
F. Bioorg. Med. Chem. 2003, 11, 999-1006.
4
. Conclusion
1
1
1
5. Bondock, S.; Khalifa, W.; Fadda, A.A. Eur. J. Med. Chem. 2007, 42, 948-
9
54.
The synthesis of some new 2-hydrazono-4-thiazolidinone
derivatives has been accomplished by employing water as a
solvent. The reaction completes in 2–3 days time without an
energy input. The ultrasound assisted synthesis of 2-hydrazono-
6. Archana; Srivastava, V. K.; Kumar, A. Ind. J. Pharm. Sci. 2003, 65, 358-
3
62.
7. Omar, K.; Geronikaki, A.; Zoumpoulakis, P.; Camoutsis, C.; Sokovi c´ ,
M.; C´ iri c´ , A.; Glamo cˇ lija, J. Bioorg. Med. Chem. 2010, 18, 426-432.
4
-thiazolidinone derivatives from thiosemicarbazone derivative
18. Babaoglu, K.; Page, M. A.; Jones, V. C.; McNeil, M. R.; Dong, C.; Nai-
smithc, J. H.; Lee, R. E. Bioorg. Med. Chem. Lett. 2003, 13, 3227-3230.
and DMAD in water occurs within 30–50 min with improved
yields. This method of assembling thiazolidin-4-ones from
thiosemicarbazone and DMAD using water is green method for
synthesis and the products are obtained in good yields.
1
2
2
9. Chen, H.; Yang, T.; Wei, S.; Zhang, H.; Li, R.; Qin, Z.; Li, X. Bioorg. Med.
Chem. Lett. 2012, 22, 7041-7044.
0. Look, G. C.; Schullek, J. R.; Holmes, C. P.; Chinn, J. P.; Gordon, E. M.;
Gallop, M. A. Bioorg. Med. Chem. Lett. 1996, 6, 707-712.
1. Ruiz, F. A. R.; García-Sánchez, R. N.; Estupiñan, S. V.; Gómez-Barrio,
A.; Amado, D. F. T.; Pérez-Solórzano, B. M.; Nogal-Ruiz, J. J.; Martínez-
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Acknowledgments
4
573.
The facilities provided by authorities of Sant Longowal Institute of Engi-
neering and Technology, Longowal are gratefully acknowledged.
2
2
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2
2. Chen, H.; Hao, L.; Zhu, M.; Yang, T.; Wei, S.; Qin, Z.; Zhang, P.; Li, X.
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