Synthesis and biological evaluation of novel methylene-bis-thiazolidinone derivatives as potential nematicidal agents

Article abstract of DOI:10.1002/jhet.5570450409

(Chemical Equation Presented) In a one pot procedure, a series of novel methylene-bis-thiazolidinone derivatives 5 and 6 was prepared by condensation of 5-(3-formyl-4-methoxybenzyl)-2-methoxybenzaldehyde 3 with mercapto acids and primary aromatic amines 4

Full text of DOI:10.1002/jhet.5570450409

Jul-Aug 2008
999
Synthesis and Biological Evaluation of Novel Methylene-bis-
thiazolidinone Derivatives as Potential Nematicidal Agents
A. Srinivas, A. Nagaraj, and Ch. Sanjeeva Reddy*
Department of Chemistry, Kakatiya University, Warangal 506 009, India,
Email: chsrkuc@yahoo.co.in
Received May 6, 2007
HOOCH2C
O
HS CHCOOH
CH2COOH
N
S
R
OMe
MeO
ZnCl2, PhMe
S
N
CH2COOH
CHO
5a-g
OMe
CHO
MeO
O
R-NH2
R
+
2
O
4
ZnCl2, PhMe
S
N
R
3
HS-CH2-COOH
OMe
MeO
S
N
6a-g
R
O
In a one pot procedure, a series of novel methylene-bis-thiazolidinone derivatives 5 and 6 was prepared
by condensation of 5-(3-formyl-4-methoxybenzyl)-2-methoxybenzaldehyde 3 with mercapto acids and
primary aromatic amines 4 in presence of ZnCl2 under both microwave irradiation and conventional
heating conditions. High yields are achieved even on a gram scale, while reaction times are considerably
shortened under microwave irradiation compared to conventional heating conditions. Characterization of
new compounds has been done by means of IR, NMR, MS and elemental analysis. The nematicidal and
antibacterial activity of the compounds has also been evaluated.
J. Heterocyclic Chem., 45, 999 (2008).
INTRODUCTION
with trioxane in the presence of a mixture of acetic acid
and conc. sulphuric acid [18]. Treatment of 2 with MeI in
presence of K2CO3 in DMF at room temperature gave the
desired intermediate 5-(3-formyl-4-methoxybenzyl)-2-
methoxybenzaldehyde 3 (Scheme 1).
Thiazolidinone and its derivatives are known to possess
significant pharmacological [1] and biological activities [2]
like sedative [3], anti-inflammatory [4], antitubercular [5],
anticancer [6], antitumor [7], anti-HIV [8], antibacterial [9],
antifungal [10], analgesis, hypotermic [11], anestetic [12]
nematicidal [13] and CNS stimulant [14]. Furthermore,
thiazolidinones have been used for the treatment of cardiac
diseases [15], diabetic complications like cataract,
nephropathy, neuropathy [16] and selective anti-platelet
The one-pot synthesis of methylene-bis-thiazolidinone
derivatives 5a-g and 6a-g was carried out by the
condensation-cyclization reaction between 5-(3-formyl-4-
methoxybenzyl)-2-methoxybenzaldehyde 3, primary aro-
matic amine 4 and a suitable mercapto acid in the presence
of ZnCl2 under microwave irradiation/ conventional heating
(Scheme 2). In the “classical” method, the reactions were
performed in dry toluene at reflux for a long time (2-4 h),
often leading to degradation processes and consequent low
yields of isolated products, whereas with the application of
microwave-assisted technology, the reaction is completed
in only 5-7 minutes and the compounds, isolated by
conventional work-up, are obtained in satisfactory yields,
often higher than those achieved by the traditional methods
(Table 1). The structures of synthesized compounds were
confirmed by IR, NMR, MS and elemental analyses.
Further the compounds were subject to nematicidal and
antibacterial testing.
activating factor [17].
Moreover, the thiazolidinone
derivatives are also employed in the synthesis of cyanine
dyes, which are used in the photographic film industry [18].
Led by the above facts, we report here the microwave-
assisted synthetic route for the synthesis of some new
heterocycles incorporating two thiazolidinone moieties in
order to prepare molecules having enhanced biological
activity and to have them evaluated for their nematicidal
and antibacterial activity.
RESULTS AND DISCUSSION
The 5-(3-formyl-4-hydroxybenzyl)-2-hydroxybenzalde-
hyde 2 was prepared by the reaction of salicylaldehyde 1

1000
A. Srinivas, A. Nagaraj, and Ch. Sanjeeva Reddy,
Vol 45
Scheme 1
OHC
HO
CHO
OH
OHC
OMe
MeI, K2CO3
DMF / r.t
Trioxane
H2SO4 / AcOH
OH
OMe
CHO
CHO
1
2
3
Scheme 2
HOOCH2C
O
HS CHCOOH
CH2COOH
N
S
R
OMe
MeO
ZnCl2, PhMe
S
CH2COOH
CHO
N
5a-g
OMe
MeO
O
R-NH2
R
+
2
O
CHO
4
ZnCl2, PhMe
S
N
R
3
HS-CH2-COOH
OMe
MeO
S
N
6a-g
R
O
Table 1
Synthesis of Compounds 5(a-g) and 6(a-g)
Reaction time
Mol. formula
Yield %
Compd.
R
A (h)
B (min)
A
B
5a
5b
5c
5d
5e
5f
5g
6a
6b
6c
6d
6e
6f
C6H5
C37H34N2O8S2
3.5
2.5
3.0
2.0
2.5
3.0
2.0
3.5
2.5
3.0
2.5
2.0
3.0
2.5
5
6
6
5
5
5
3
5
6
7
5
5
5
4
62
71
69
63
68
79
80
63
65
61
70
67
77
79
80
89
82
86
88
86
91
79
82
79
81
82
87
90
4-Cl-C6H4
4-NO2-C6H4
2-CH3-C6H4
4-CH3-C6H4
3-OH-C6H4
4-OH-C6H4
C6H5
4-Cl-C6H4
4-NO2-C6H4
2-CH3-C6H4
4-CH3-C6H4
3-OH-C6H4
4-OH-C6H4
C37H32Cl2N2O8S2
C37H32N4O12S2
C39H38N2O8S2
C39H38N2O8S2
C37H34N2O10S2
C37H34N2O10S2
C33H30N2O4S2
C33H28Cl2N2O4S2
C33H28N4O8S2
C35H34N2O4S2
C39H38N2O8S2
C33H30N2O6S2
C33H30N2O6S2
6g
A: conventional heating. B: microwave irradiation.
Antibacterial Activity. Compounds 5a-g and 6a-g
were screened for their antibacterial activity using the
tube dilution method [19] by measuring the minimum
inhibitory concentration (MIC) in μg/mL against four
interesting biological activity however, with a degree of
variation.
Compounds in series 5 and 6, which contain 4-Cl / 3-
OH, displayed good antibacterial activity against all the
organisms. Compounds 5b and 6f were highly active
against B. subtilis, S. aureus and S. pyogenes, compound
5f was highly active against B. subtilis, S. aureus, E. coli,
compound 6b was highly active against B. subtilis, E. coli,
S. pyogenes and the compound 5c was highly active
against E. coli and S. pyogenes. Compounds 6a and 6d did
not exhibit any activity against E. coli even at 100 μg/mL
representative
Staphylococcus
organisms
aureus,
viz
Bacillus
subtilis,
and
Escherichia
coli
Staphylococcus pyogenes. Standard antibacterial agents,
such as Streptomycin and Neomycin, were also screened
under identical conditions for comparison. The minimum
inhibitory concentrations are given in Table 2. It has been
observed that the test compounds however exhibited an

Jul-Aug 2008
Synthesis and Biological Evaluation of Novel Methylene-bis-thiazolidinone Derivatives
1001
Table 2
Antibacterial and Nematicidal Activity of 5a-g and 6a-g
Antibacterial Activity
Nematicidal Activity
LD50 value (ppm)
Minimum inhibition concentration (MIC, μg/mL)
Compd
B. subtilis
S. aureus
E. coli
S. pyogenes
D.myceliophagus
C.elegans
5a
5b
5c
5d
5e
5f
5g
6a
6b
6c
6d
6e
6f
50
12.5
25
25
12.5
25
50
50
12.5
50
50
25
25
100
50
12.5
25
10
30
50
25
12.5
25
50
12.5
12.5
25
50
25
25
25
12.5
12.5
50
50
12.5
50
10
30
940
360
440
610
1070
210
420
710
400
490
1030
910
360
660
--
960
400
390
650
1010
320
670
650
350
510
1050
970
240
540
--
25
100
12.5
50
50
12.5
25
50
50
12.5
50
10
30
50
12.5
100
--
12.5
25
--
50
25
50
6g
Streptomycin
Neomycin
10
30
--
--
was washed with 2 N NaOH solution, dried over Na2SO4.
Evaporation of the solvent gave compound 3. The structure of
compound 3 was confirmed by its spectral data and compared
with the data reported in the literature [21].
concentration. The alkyl substituted derivatives displayed
moderate levels of antibacterial activity (Table 2).
Nematicidal Activity. The compounds 5a-g and 6a-g
were also screened for their nematicidal activity against
Ditylenchus myceliophagus and Caenorhabditis elegans
by aqueous in vitro screening technique [20] at various
concentrations. The results have been expressed in terms
of LD50 i.e. median lethal dose at which 50% nematodes
became immobile (dead). The screened data reveal that
compound 5f and 6f are the most effective against D.
myceliophagus and C. elegans with LD50 value of 210 and
240 ppm, respectively (Table 2).
General procedure for the synthesis of methylene-bis-
thiazolidinones (5a-g). To a stirred mixture of 3 (1.42 g, 0.005
mol), appropriate aromatic amine 4 (0.015 mol) and thiomalic
acid (4.5 g, 0.03 mol) in dry toluene (5 mL), ZnCl2 (1.36 g, 0.01
mol) was added after 2 min and irradiated in a microwave oven
at 280 W for 4-7 minutes at 110 °C. After cooling, the filtrate
was concentrated to dryness under reduced pressure, the residue
was taken up in ethyl acetate, and the resulting solution was
washed with brine solution. The organic phase was dried over
Na2SO4, filtered, the filtrate was concentrated under reduced
pressure to dryness, and the crude product was purified by
column chromatography on silica gel using methanol/
dichloromethane as eluent. The purity of the products was
checked by TLC using methanol/dichloromethane (1:9) as
solvent. Under conventional method the same reaction mixture
in toluene (30 mL) was refluxed at 110 °C for the appropriate
time (Table 1).
EXPERIMENTAL
All chemicals and solvents were of analytical grade and used
as purchased. Evaporations were performed at reduced pressure
below 40°C. The reactions and purifications were monitored by
tlc on aluminium sheets coated with silica gel 60 F254 (Merck),
column chromatography on silica gel 60 (Merck). Melting
points were taken using a Fisher-Johns melting point instrument
and are uncorrected. IR spectra were obtained on a Perkin-
Elmer FTIR 5000 spectrophotometer, using KBr pellets. 1H
NMR and 13C NMR spectra were obtained with Varian Gemini
(1H: 300 MHz, 13C: 75 MHz) spectrometer and the chemical
shifts were reported as parts per million (ꢀ ppm) down field
from internal tetramethylsilane and coupling constants (J) in Hz.
Mass spectra were obtained on a VG Micromass 7070H
spectrometer. Elemental analyses were performed on a Perkin-
Elmer 240 CHN elemental analyzer.
2-[2-(5-3-[5-(Carboxymethyl)-4-oxo-3-phenyl-1,3-thiazolan-
2-yl]-4-methoxybenzyl-2-methoxyphenyl)-4-oxo-3-phenyl-1,3-
thiazolan-5-yl]acetic acid (5a). mp 201-203 °C; IR (KBr): ꢁ
3130-2890, 3021, 2980, 1724, 1716, 1610, 1480, 1410, 1224,
1
688 cm-1; H NMR (DMSO-d6): ꢀ 2.37 (4H, d, CH2), 3.36 (2H,
s, CH2), 4.12 (6H, s, OCH3), 4.67 (2H, t, CH), 6.16 (2H, s, CH-
S). 6.70-7.32 (16H, m, ArH), 11.41 (2H, s, COOH); 13C NMR
(DMSO-d6): ꢀ 36.4, 41.0, 45.3, 54.2, 61.7, 107.8, 121.3, 123.6,
127.1, 128.4, 130.3, 134.7, 135.9, 138.5, 152.7, 166.9, 170.9;
MS: m/z 698 (M+). Anal. calcd for C37H34N2O8S2: C, 63.60; H,
4.90; N, 4.01. Found: C, 63.42; H, 4.77; N, 4.00.
5-(3-Formyl-4-methoxybenzyl)-2-methoxybenzaldhyde
(3). To a solution of 2 (2.56 g, 0.01 mol) and K2CO3 (5.60 g,
0.04 mol) in DMF (16 mL), MeI (4.25 g, 1.9 mL, 0.03 mol) was
added. The mixture was stirred at room temperature for 12 h
(tlc, EtOAc: Pet-ether, 2:1) then the mixture was poured in water
(30 mL), and extracted with Et2O (3ꢀ20 mL). The organic phase
2-[2-(5-3-[5-(Carboxymethyl)-3-(4-chlorophenyl)-4-oxo-1,3-
thiazolan-2-yl]-4-methoxybenzyl-2-methoxyphenyl)-3-(4-
chlorophenyl)-4-oxo-1,3-thiazolan-5-yl]acetic acid (5b). mp
249-251 °C; IR (KBr): ꢁ 3140-2900, 3010, 2980, 1720, 1700,
1
1605, 1479, 1410, 1220, 746, 688 cm-1; H NMR (DMSO-d6): ꢀ
2.37 (4H, d, CH2), 3.36 (2H, s, CH2). 4.12 (6H, s, OCH3), 4.67

1002
A. Srinivas, A. Nagaraj, and Ch. Sanjeeva Reddy,
Vol 45
(2H, t, CH), 6.16 (2H, s, CH-S). 6.70-7.10 (6H, m, ArH), 7.20
(4H, d, J = 8.71 Hz, ArH), 7.51 (4H, d, J = 8.71 Hz, ArH), 11.39
(2H, s, COOH); 13C NMR (DMSO-d6): ꢀ 36.4, 41.1, 45.2, 54.2,
61.3, 107.8, 121.3, 123.1, 127.9, 128.7, 130.7, 134.6, 135.3,
138.9, 153.4, 167.2, 170.9; MS: m/z 728 (M+). Anal. calcd for
C37H32Cl2N2O8S2: C, 57.89; H, 4.20; N, 3.65. Found: C, 57.70;
H, 4.17; N, 3.61.
(CDCl3): ꢀ 2.37 (4H, d, CH2), 3.36 (2H, s, CH2). 4.12 (6H, s,
OCH3), 4.67 (2H, s, CH), 6.20 (2H, s, CH-S). 6.70-7.10 (10H,
m, ArH), 7.28 (4H, d, J = 8.87 Hz, ArH), 8.24 (2H, s, OH), 9.21
(2H, s, COOH); 13C NMR (CDCl3): ꢀ 36.6, 41.1, 45.4, 54.7,
62.4, 108.1, 114.7, 123.1, 123.9, 124.7, 133.2, 134.9, 135.2,
154.1, 160.1, 167.2, 170.1; MS: m/z 730 (M+).. Anal. calcd for
C37H34N2O10S2: C, 60.81; H, 4.69; N, 3.83. Found: C, 60.62; H,
4.58; N, 3.71.
2-[2-(5-3-[5-(Carboxymethyl)-3-(4-nitrophenyl)-4-oxo-1,3-
thiazolan-2-yl]-4-methoxybenzyl-2-methoxyphenyl)-3-(4-
nitrophenyl)-4-oxo-1,3-thiazolan-5-yl]acetic acid (5c). mp
249-251 °C; IR (KBr): ꢁ 3140-2900, 3010, 2980, 1720, 1700,
General procedure for the synthesis of methylene-bis-
thiazolidinones (6a-g). To a stirred mixture of 3 (1.42 g, 0.005
mol), aromatic amine 4 (0.015 mol) and thioglycolic acid (2.76 g,
0.03 mol) in dry toluene (5 mL), ZnCl2 (1.36 g, 0.01 mol) was
added after 2 min and irradiated in a microwave oven at 280 W
for 4-7 minutes at 110 °C. After cooling, the filtrate was concen-
trated to dryness under reduced pressure and the residue was
taken-up in ethyl acetate. The ethyl acetate layer was washed
with brine, 5% sodium bicarbonate solution and finally with
brine. The organic layer was dried over Na2SO4 and evaporated
to dryness at reduced pressure. The crude product thus obtained
was purified by column chromatography on silica gel with
hexane-ethyl acetate as eluent. The purity of the products was
checked by TLC using ethyl acetate/hexane (4:6). Under
conventional method the same reaction mixture in toluene (30
mL) was refluxed at 110 °C for the appropriate time (Table 1).
2-{2-Methoxy-5-[4-methoxy-3-(4-oxo-3-phenyl-1,3-thiazo-
lan-2-yl)benzyl]phenyl}-3-phenyl-1,3-thiazolan-4-one (6a).
mp 129-131 °C; IR (KBr): ꢁ 3015, 2985, 1716, 1610, 1475,
1415, 1224, 686 cm-1; 1H NMR (DMSO-d6): ꢀ 3.36 (2H, s, CH2),
3.77 (4H, s, CH2) 4.11 (6H, s, OCH3), 6.07 (2H, s, CH-S), 6.70-
7.40 (16H, m, ArH); 13C NMR (DMSO-d6): ꢀ 35.9, 41.1, 54.1,
63.2, 109.1, 123.6, 125.2, 128.4, 129.7, 130.3, 134.3, 135.9,
138.9, 152.0, 171.1; MS: m/z 582 (M+). Anal. Calcd. for
C33H30N2O4S2: C, 68.02; H, 5.19; N, 4.81. Found: C, 67.93; H,
5.11; N, 4.77.
1
1605, 1479, 1410, 1220, 746, 688 cm-1; H NMR (DMSO-d6): ꢀ
2.37 (4H, d, CH2), 3.36 (2H, s, CH2), 4.11 (6H, s, OCH3), 4.67
(2H, t, CH), 6.16 (2H, s, CH-S). 6.70-7.10 (6H, m, ArH), 7.81
(4H, d, J = 9.08 Hz, ArH), 8.11 (4H, d, J = 9.08 Hz, ArH), 11.39
(2H, s, COOH); 13C NMR (DMSO-d6): ꢀ 36.6, 41.1, 45.7, 54.6,
61.7, 108.4, 122.3, 123.6, 127.9, 128.3, 131.9, 134.9, 139.2,
143.2, 154.1, 167.3, 170.7; MS: m/z 788 (M+). Anal. calcd for
C37H32N4O12S2: C, 56.34; H, 4.09; N, 7.10. Found: C, 56.27; H,
4.00; N, 7.05.
2-[2-(5-3-[5-(Carboxymethyl)-3-(2-methylphenyl)-4-oxo-
1,3-thiazolan-2-yl]-4-methoxybenzyl-2-methoxyphen-yl)-3-
(2-methylphenyl)-4-oxo-1,3-thiazolan-5-yl]acetic acid (5d).
mp 245-247 °C; IR (KBr): ꢁ 3140-2950, 3010, 2995, 1715,
1700, 1610, 1480, 1410, 1224, 686 cm-1; 1H NMR (DMSO-d6): ꢀ
2.10 (6H, s, CH3), 2.36 (4H, d, CH2), 3.36 (2H, s, CH2). 4.11
(6H, s, OCH3), 4.67 (2H, t, CH), 6.16 (2H, s, CH-S). 6.70-7.50
(14H, m, ArH), 11.40 (2H, s, COOH); 13C NMR (DMSO-d6): ꢀ
18.3, 36.6, 41.1, 45.4, 54.9, 62.3, 108.3, 122.3, 123.6, 127.8,
128.2, 129.1, 130.1, 132.7, 135.9, 136.4, 139.2, 154.1, 167.3,
170.2; MS: m/z 726 (M+). Anal. calcd for C39H38N2O8S2: C,
64.45; H, 5.27; N, 3.85. Found: C, 64.39; H, 5.12; N, 3.82.
2-[2-(5-3-[5-(Carboxymethyl)-3-(4-methylphenyl)-4-oxo-
1,3-thiazolan-2-yl]-4-methoxybenzyl-2-methoxyphenyl)-3-
(4-methylphenyl)-4-oxo-1,3-thiazolan-5-yl]acetic acid (5e).
mp 182-184 °C; IR (KBr): ꢁ 3140-2950, 3011, 2990, 1715,
1698, 1610, 1475, 1412, 1224, 684 cm-1; 1H NMR (DMSO-d6): ꢀ
2.05 (6H, s, CH3), 2.36 (4H, d, CH2), 3.36 (2H, s, CH2). 4.10
(6H, s, OCH3), 4.66 (2H, s, CH), 6.19 (2H, s, CH-S). 6.70-7.10
(6H, m, ArH), 7.16 (4H, d, J = 8.33 Hz, ArH), 8.23 (4H, d, J =
8.33 Hz, ArH), 11.40 (2H, s, COOH); 13C NMR (DMSO-d6): ꢀ
19.4, 36.6, 41.1, 45.3, 54.9, 62.5, 108.9, 117.7, 123.3, 124.8,
129.7, 133.2, 135.7, 136.1, 138.7, 153.2, 167.3, 170.1; MS: m/z
726 (M+). Anal. calcd for C39H38N2O8S2: C, 64.45; H, 5.27; N,
3.85. Found: C, 64.36; H, 5.19; N, 3.78.
3-(4-Chlorophenyl)-2-(5-{3-[3-(4-chlorophenyl)-4-oxo-1,3-
thiazolan-2-yl]-4-methoxybenzyl}-2-methoxyphenyl)-1,3-
thiazolan-4 -one (6b). mp 214-216 °C; IR (KBr): ꢁ 3015,
1
2987, 1714, 1605, 1481, 1410, 1221, 746, 690 cm-1; H NMR
(CDCl3): ꢀ 3.36 (2H, s, CH2), 3.77 (4H, s, CH2) 4.11 (6H, s,
OCH3), 6.06 (2H, s, CH-S), 6.70-7.10 (6H, m, ArH), 7.21 (4H,
d, J = 8.71 Hz, ArH), 7.52 (4H, d, J = 8.71 Hz, ArH); 13C NMR
(CDCl3): ꢀ 35.9, 41.1, 54.3, 63.7, 109.3, 121.8, 123.5, 127.6,
128.7, 132.1, 135.3, 136.3, 138.7, 152.9, 171.1; MS: m/z 652
(M+). Anal. calcd for C33H28Cl2N2O4S2: C, 60.83; H, 4.33; N,
4.30. Found: C, 60.71; H, 4.25; N, 4.22.
2-[2-(5-3-[5-(Carboxymethyl)-3-(3-hydroxyphenyl)-4-oxo-
1,3-thiazolan-2-yl]-4-methoxybenzyl-2-methoxyphen-yl)-3-
(3-hydroxyphenyl) 4-oxo-1,3-thiazolan-5-yl]acetic acid (5f).
2-(2-Methoxy-5-{4-methoxy-3-[3-(4-nitrophenyl)-4-oxo-
1,3-thiazolan-2-yl]benzyl}phenyl)-3-(4-nitrophenyl)-1,3-thia-
zolan-4-one (6c). mp 197-199 °C; IR (KBr): ꢁ 3016, 2992,
-
1
1695, 1610, 1510, 1318, 1479, 1410, 1224, 682 cm-1; H NMR
mp 209-211 °C; IR (KBr): ꢁ 3540, 3140-2960, 3014, 2985,
1714, 1705, 1605, 1478, 1412, 1220, 680 cm-1; 1H NMR
(CDCl3): ꢀ 2.36 (4H, d, CH2), 3.36 (2H, s, CH2). 4.11 (6H, s,
OCH3), 4.68 (2H, t, CH), 6.18 (2H, s, CH-S). 6.70-7.10 (14H, m,
ArH), 8.24 (2H, s, OH), 9.21 (2H, s, COOH); 13C NMR
(CDCl3): ꢀ 36.6, 41.2, 45.7, 54.9, 62.4, 108.2, 109.9, 112.6,
114.3, 123.4, 125.1, 130.1, 132.6, 135.9, 136.1, 153.2, 160.3,
167.3, 170.2; MS: m/z 730 (M+). Anal. calcd for C37H34N2O10S2:
C, 60.81; H, 4.69; N, 3.83. Found: C, 60.76; H, 4.61; N, 3.78.
2-[2-(5-3-[5-(Carboxymethyl)-3-(4-hydroxyphenyl)-4-oxo-
1,3-thiazolan-2-yl]-4-methoxybenzyl-2-methoxyphen-yl)-3-
(4-hydroxyphenyl)-4-oxo-1,3-thiazolan-5-yl]acetic acid (5g).
mp 241-243 °C; IR (KBr): ꢁ 3450, 3140-2960, 3011, 2990,
1720, 1690, 1606, 1470, 1410, 1226, 680 cm-1; 1H NMR
(DMSO-d6): ꢀ 3.36 (2H, s, CH2), 3.77 (4H, s, CH2) 4.12 (6H, s,
OCH3), 6.08 (2H, s, CH-S), 6.70-7.10 (6H, m, ArH), 7.77 (4H,
d, J = 9.08 Hz, ArH), 8.11 (4H, d, J = 9.08 Hz, ArH); 13C NMR
(DMSO-d6): ꢀ 35.3, 41.1, 54.1, 63.3, 109.2, 123.9, 126.1, 128.3,
133.1, 135.7, 136.1, 138.9, 142.1, 152.5, 171.2; MS: m/z 674
(M+). Anal. calcd for C33H28N4O8S2: C, 58.92; H, 4.20; N, 8.33.
Found: C, 58.10; H, 4.11; N, 8.20.
2-(2-Methoxy-5-{4-methoxy-3-[3-(2-methylphenyl)-4-oxo-
1,3-thiazolan-2-yl]benzyl}phenyl)-3-(2-methylphenyl)-1,3-
thiazolan-4-one (6d). mp 179-181 °C; IR (KBr): ꢁ 3014,
2990, 1705, 1610, 1482, 1410, 1224, 692 cm-1; 1H NMR
(DMSO-d6): ꢀ 2.0 (6H, s, CH3), 3.36 (2H, s, CH2), 3.79 (4H,
s, CH2) 4.13 (6H, s, OCH3), 6.10 (2H, s, CH-S), 6.70-7.60

Jul-Aug 2008
Synthesis and Biological Evaluation of Novel Methylene-bis-thiazolidinone Derivatives
1003
(14H, m, ArH); 13C NMR (DMSO-d6): ꢀ 16.4, 35.4, 41.1,
54.3, 64.9, 109.2, 121.7, 124.1, 125.4, 126.9, 127.8, 129.3,
132.1, 133.7, 135.0, 138.9, 152.5, 171.1; MS: m/z 612 (M+).
Anal. calcd for C35H34N2O4S2: C, 68.83; H, 5.61; N, 4.59.
Found: C, 68.71; H, 5.51; N, 4.50.
REFERENCES AND NOTES
[1a] Patel, R. B.; Desai, P. S.; Desai, K. R.; Chikhalia, K. H.
Indian J. Chem. 2006, 45B, 773. b) Bishnoi, A.; Krishna, S.; Tripathi, C.
K. M. Indian J. Chem. 2006, 45B, 2136. c) Venkateshwarlu, P.;
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2-(2-Methoxy-5-{4-methoxy-3-[3-(4-methylphenyl)-4-oxo-
1,3-thiazolan-2-yl]benzyl}phenyl)-3-(4-methylphenyl)-1,3-
thiazolan-4-one (6e). mp 180-182 °C; IR (KBr): ꢁ 3012, 2988,
1698, 1612, 1475, 1410, 1220, 689 cm-1; 1H NMR (DMSO-d6): ꢀ
2.02 (6H, s, CH3), 3.36 (2H, s, CH2), 3.80 (4H, s, CH2) 4.13 (6H,
s, OCH3), 6.07 (2H, s, CH-S), 6.70-7.10 (6H, m, ArH), 7.15 (4H,
d, J = 8.33 Hz, ArH), 7.39 (4H, d, J = 8.33 Hz, ArH); 13C NMR
(DMSO-d6): ꢀ 19.7, 35.6, 41.1, 54.5, 64.2, 109.2, 113.4, 122.1,
124.3, 128.7, 133.7, 135.1, 136.9, 139.8, 152.3, 171.1; MS: m/z
612 (M+). Anal. calcd for C35H34N2O4S2: C, 68.83; H, 5.61; N,
4.59. Found: C, 68.73; H, 5.50; N, 4.52.
3-(3-Hydroxyphenyl)-2-(5-{3-[3-(3-hydroxyphenyl)-4-oxo-
1,3-thiazolan-2-yl]-4-methoxybenzyl}-2-methoxyphenyl)-1,3-
thiazo lan-4-one (6f). mp 205-207 °C; IR (KBr): ꢁ 3535,
3015, 2982, 1690, 1615, 1478, 1412, 1221, 686 cm-1; 1H
NMR (CDCl3): ꢀ 3.36 (2H, s, CH2), 3.81 (4H, s, CH2) 4.11
(6H, s, OCH3), 5.40 (2H, s, OH), 6.07 (2H, s, CH-S), 6.70-
7.14 (14H, m, ArH); 13C NMR (CDCl3): ꢀ 35.3, 41.1, 54.1,
64.2, 107.6, 109.7, 113.3, 115.0, 123.8, 124.1, 129.8, 133.9,
135.3, 152.9, 158.3, 171.9; MS: m/z 616 (M+). Anal. calcd
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64.31; H, 4.86; N, 4.50.
3-(4-Hydroxyphenyl)-2-(5-{3-[3-(4-hydroxyphenyl)-4-oxo-
1,3-thiazolan-2-yl]-4-methoxybenzyl}-2-methoxyphenyl)-1,3-
thiazolan-4-one (6g). mp 259-261 °C; IR (KBr): ꢁ 3541, 3012,
2986, 1710, 1614, 1476, 1412, 1221, 689 cm-1; 1H NMR
(CDCl3): ꢀ 3.36 (2H, s, CH2), 3.80 (4H, s, CH2) 4.14 (6H, s,
OCH3), 5.15 (2H, s, OH), 6.09 (2H, s, CH-S), 6.70-7.10 (10H,
m, ArH), 7.39 (4H, d, J = 8.86 Hz, ArH); 13C NMR (CDCl3): ꢀ
35.9, 41.1, 54.4, 64.3, 109.2, 114.9, 122.1, 123.2, 125.0, 133.8,
134.1, 136.4, 151.1, 155.2, 171.5; MS: m/z 616 (M+). Anal.
calcd for C33H30N2O6S2: C, 64.48; H, 4.92; N, 4.56. Found: C,
64.40; H, 4.82; N, 4.51.
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Acknowledgements. The authors are grateful to the Director,
Indian Institute of Chemical Technology, Hyderabad, India for
NMR and MS spectral analysis; to the Head, Department of
Microbiology, Kakatiya University, Warangal for his valuable
suggestions.