Synthesis and antimicrobial activity of new Thiazolidinone derivatives with the use of γ-ferrite catalyst

Article abstract of DOI:10.1155/2012/251450

A series of compounds were synthesized from 3, 3?- (pyridine-2, 6- diyl) bis (2-phenylthiazolidin-4-one (1), which was prepared from a one-pot three component condensation reaction of 2, 6-diamino pyridine, benzaldehyde and thioglycolic acid in the presen

Full text of DOI:10.1155/2012/251450

ISSN: 0973-4945; CODEN ECJHAO
E-Journal of Chemistry
http://www.ejchem.net
2012, 9(2), 825-831
Synthesis and Antimicrobial
Activity of New Thiazolidinone Derivatives
With the use of γ-Ferrite Catalyst
S. P. SHRIVASTAVA, NARESHVARMA SEELAM* and RACHANA RAI
Heterocyclic Research laboratory, Department of Chemistry
Dr. H. S. Gour University, Sagar, M. P, 470003-India
utd_naresh@yahoo.co.in
Received 9 August 2011; Accepted 4 October 2011
Abstract: A series of compounds were synthesized from 3,3′-(pyridine-2,6-
diyl) bis (2-phenylthiazolidin-4-one(1), which was prepared from a one-pot
three component condensation reaction of 2, 6-diamino pyridine, benzaldehyde
and thioglycolic acid in the presence of γ-ferrite as a catalyst. The newly
1
synthesized compounds were characterized by IR, HNMR, 13C NMR spectral
data. All compounds were tested for anti bacterial and anti fungal activities.
Keywords: Pyridine, Azo derivatives, γ-Ferrite, Arylidene derivatives.
Introduction
During the past decade, combinatorial chemistry has provided access to chemical libraries
based on privileged structures1, with heterocyclic structures receiving special attention as
they belong to a class of compounds with proven utility in medicinal chemistry2. There has
been considerable interest in the chemistry of thiazolidin-4-one ring system, which is a core
structure in various synthetic pharmaceuticals displaying a broad spectrum of biological
activities3. Thiazolidinones and their derivatives are an important group of heterocyclic
compounds, having valuable biological activities in the areas of medicine and agriculture4.
Thiazolidinone ring occurs in nature; thus actithiazic acid[(-)2-(5-carboxypentyl)thiazolidin-
4-one)] isolated from streptomyces strains exhibits highly specific in vitro activity against
mycobacterium tuberculosis5. They have found uses, for example, as insecticides,
tuberculostatic6-7,anti-inflammatory8, CNS stimulant, anthelmintic9, CO2+ channel blocker10,
antiviral11, analgesic12, anticonvulsant13, anti platelet activating factor14, anticancer15, and
anti HIV16. 4-Thiazolidinones have also been reported as novel inhibitors of bacterial
enzyme17. In view of these above findings it was thought of interest to accommodate
thiazolidin-4-one and pyridine in a single molecular frame work and screened for their anti
microbial activity.

826 N. VARMA SEELAM et al.
Experimental
The NMR (1H&13C) spectra were recorded at 400 MHz, 100MHz respectively with a Bruker
Avance II 400 instrument. NMR spectra were obtained in solutions of DMSO (d6) and
chemical shifts reported in parts per million (ppm) and TMS as an internal standard. Melting
points were determined in an open capillary and are uncorrected. IR spectra were recorder
on a FT-IR Shimadzu 8400 Spectrophotometer and reported in wave numbers (cm-1).
3,3′-(Pyridine-2,6-diyl)bis(2-phenylthiazolidin-4-one(1)
To a mixture of 2,6-di amino pyridine(l equiv.), benzaldehyde (2 equiv), anhydrous γ-ferrite
(Fe2O3; 4 equiv) was added and the reaction mixture was refluxed with constant stirring in dry
benzene (40ml) for 1/2 h, followed by the addition of thioglycolic acid (2 equiv). The refluxing
and stirring were continued for another 10h. The reaction was monitored by TLC. After the
completion of the reaction, a reddish brown amorphous solid Fe2O3.2H2O/FeO(OH) was removed
by filtration, filtrate was concentrated to dryness under reduced pressure to achieve compound.
Dark brown crystals; yield 74%, m.p: 256°-259°c; IR (KBr,νmax,cm-1) 1698(C=0),
1
1130(C-N), 672(C-S), 1612(C=N), 1597 (C-C), H NMR (δ ppm, DMSO-d6) 3.71 (s, 4H,
S-CH2), 5.18 (s, 2H N-CH),7.32 (m,10H, Ar-H),7.89 (t,1H, pyridine C4), 8.2 (d, 2H,
pyridine C3, C5) 13C-NMR (DMSO, 100 MHz): 172.1, 152, 139.74, 131.04, 127.4, 38.7.
General procedure for the Synthesis of 3,3′-(pyridine-2,6-diyl)bis(5-substituted-
arylidene-2-phenyl)thiazolidin-4-one derivatives (2a-j)
A mixture of compound 1 (l equiv.), aromatic aldehyde (2 equiv.), anhydrous sodium acetate
(2equiv.) in glacial acetic acid (50ml) was heated under reflux for 4 h. Concentrated, cooled
and poured into the crushed ice. The solid thus separated was filtered, washed with water
and recrystallized. All the compounds 2a-j were prepared by the same methodology as
mentioned above. The physical and analytical data of compounds were mentioned in Table 1.
General procedure for the synthesis of 3,3′-(pyridine-2,6-diyl)bis(5-(phenyl
substituted diazenyl)-2-phenyl)thiazolidin-4-one 3(a-c)
To a solution of aniline (0.01 mol) in glacial acetic acid (5 mL) was added conc. HCl (3 mL)
at 0- 5oC. A Solution of Sodium nitrite (1 g in 5 mL of water) was then added drop wise.
The diazonium salt Solution thus prepared was added to a solution of compound"1"
(0.01 mol) in DMF drop wise with stirring below 0°C. The reaction mixture were kept at
room temperature for 2-3 days and then poured in to cold water (200 mL). The resulting
solids were washed with water and recrystallized from suitable solvents. (viz, Ethanol,
methanol). The physical & analytical data of all synthesized compounds were given in Table 1.
3,3′-(Pyridine-2,6-diyl)bis(5-(4-hydroxy arylidene-2-phenyl)thiazolidin-4-one (2a)
IR (KBr, cm-1) νmax=3182.65(O-H), 3120.93(CH in ring), 3057.27(Ar), 1653.05(C=O),
1
1415.80 (C-N), 1600, 1625 (C=C and C=N); H NMR (δ ppm, DMSO-d6), 6.25 (s, 2H,
N-CH), 6.9 (t, 1H, Pyridine C4), 7.35 (s, 2H, CH), 7.6 (m, 18H, Ar-H), 8.0 (s, 2H, OH), 8.21
(d, 2H, C2-H and C5-H in pyridine); 13C NMR (DMSO) δ: 170.8, 155.08, 137.02, 135.8,
132.5, 122.91, 118.2, 114.86.

Synthesis and Antimicrobial Activity of New Thiazolidinone 827
3,3′-(Pyridine-2,6-diyl)bis(5-(arylidene-2-phenyl)thiazolidin-4-one (2b)
IR(KBr, cm-1) νmax=3049(Ar-C-H), 1704(C=0), 1625 (C=C), 1620 (C=N), 1515(C-N),
1H NMR (δ ppm, DMSO–d6), 8.71(m, 20H, Ar-H), 6.20 (s, 2H,N-CH-Ar), 6.92 (t, 1H, C4-H
in Pyridine), 8.19 (d, 2H, C3-H, C5-H in pyridine); 13C NMR (DMSO) δ: 170.79, 156.2,
136.1, 129.8, 109.12.
3,3′-(Pyridine-2,6-diyl)bis(5-(4-N-dimethylaminoarylidene-2-phenyl)thiazolidin-4-
one (2c)
IR (KBr, cm-1) νmax=3423.76(N-H), 3080.42(Ar), 3030.27(CH in alkene), 2931.90(CH3),
1683.91(C=O), 1597.11(C-C), 1417.73 (C-N), 1361.79(3° amine).
3,3′-(Pyridine-2,6-diyl)bis(5-(3,4,5-tri methoxy arylidene-2-phenyl)thiazolidin-4-one (2d)
IR(KBr, cm-1) νmax=3080.42(Ar), 3057.27 (C-H in ring), 2937.68(CH3),1624.12 (C=O),
1
1388.79(C-N), 1230.63 (C-O-C), 702.11(C-S); H NMR (δ ppm, DMS0-d6) 3.86(s, 12H,
3,5-OCH3) 3.79(s, 6H, 4-OCH3) 7.15-7.25(m, 14H, Ar-H), 7.5(d, 2H, 3,5-Pyridine), 7.96
(s, 2H, CH), 8.07 (s, 2H, C-H), 8.30(t, 1H,C4-H in pyridine); 13C NMR (DMSO) δ: 171.3,
158.9, 153.89, 137.2, 131.9, 124.01, 118.7, 114.2, 56.2.
3,3′-(Pyridine-2,6-diyl)bis(5-(4-methoxy arylidene-2-phenyl)thiazolidin-4-one (2e)
IR (KBr, cm-1) νmax=3057.27(Ar), 3030.27(CH in ring), 2933.83(CH3), 1622.19(C=O), 1394.58
1
(C-N), 1219.05(C-O-C), 640.39 (C-S). H NMR (δ ppm, DMSO-d6) 3.73(s,6H,OCH3),7.35
(m,18H,Ar-H), 7.67(t, 1H,C4-H in pyridine),7.9(d,2H,C3-H and C5-H in pyridine),8.09 (s, 2H,C-H);
3,3′-(Pyridine-2,6-diyl)bis(5-(2-chloro arylidene-2-phenyl)thiazolidin-4-one (2f)
IR(KBr, cm-1) νmax= 3082.35(Ar), 3059.20(C-H in heterocyclic ring), 1653.05 (C=O),
1388.79 (C-N), 1089.82 (C-Cl), 702.11(C-S).
3,3′-(Pyridine-2,6-diyl)bis(5-(2-bromo arylidene-2-phenyl)thiazolidin-4-one (2g)
IR(KBr, cm-1) νmax=3058.91(C-H in heterocyclic ring), 3027.18 (Ar), 1638.07(C=O),
1387.12 (C-N), 686.17 (C-S).
3,3′-(Pyridine-2,6-diyl)bis(5-(4-nitro arylidene-2-phenyl)thiazolidin-4-one (2h)
IR(KBr, cm-1) νmax= 3057.93(CH in ring), 3018 (Ar-CH), 1637.11(C=O), 1530.98(N=O),
1387.54(C-N), 701.08(C-S); 1H NMR (δ ppm, DMSO-d6) 5.91(s, 2H, CH), 7.1-7.4(m,18H,Ar-
H), 7.89(t, 1H, C4-H in pyridine), 8.02(s, 2H, CH), 8.35(d, 2H, 3,5-H in pyridine).
3,3′-(Pyridine-2,6-diyl)bis(5-(4-chloro arylidene-2-phenyl)thiazolidin-4-one (2i):
IR(KBr, cm-1) νmax= 3082.35(Ar), 3059.20(C-H in heterocyclic ring), 1653.05 (C=O),
1388.79 (C-N), 1089.82 (C-Cl), 702.11(C-S).
3,3′-(Pyridine-2,6-diyl)bis(5-(2-methoxy arylidene-2-phenyl)thiazolidin-4-one (2j)
IR(KBr, cm-1), νmax=3057.27(Ar), 3030.27(CH in ring), 2933.83(CH3), 1622.19(C=O),
1394.58(C-N), 1219.05(C-O-C), 640.39 (C-S).

828 N. VARMA SEELAM et al.
3,3′-(Pyridine-2,6-diyl)bis(5-((phenyl) di azenyl)-2-phenyl)thiazolidin-4-one (3a)
Brown colour powder; IR(KBr, cm-1) νmax=3038.76(C-H in ring), 3019.91(Ar), 1595.19(N=N)),
1338.22(C-N), 662.03(C=O). 1H NMR(δppm, DMSO-d6) 5.92(s, 2H, CH), 7.05-7.29(m, 20H,
Ar-H), 7.9(t, 1H, C4-Pyridine), 8.2(s, 2H, C5-H in thiazolidinone), 8.5(C3&C5-H in pyridine).
3,3′-(Pyridine-2,6-diyl)bis(5-((4-nitro phenyl) di azenyl)-2-phenyl)thiazolidin-4-one (3b):
IR(KBr, cm-1) νmax=3047.11(C-H in ring), 3029.39(Ar), 1665.82(C=O), 1602.18 (N=N),
1312.26 (C-N), 701.03(C-S); 1H NMR(δppm, DMSO-d6) 6.1(s, 2H,N-CH-Ar), 7.39(m,18H,
Ar), 7.9(t, 1H, C4–H in pyvidine), 8.38(d, 2H, C3,C5-H in pyridine); 13CNMR(DMSO) δ:
171.59, 153.35, 148.71, 135.73, 129.8, 124.21, 119.3, 115.27.
3,3′-(Pyridine-2,6-diyl)bis(5-((4-chloro phenyl) diazenyl)-2-phenyl)thiazolidin-4-
one (3c)
IR (KBr, cm-1) νmax=3051.26(C-H-in-ring), 3032.15(Ar), 1656.43 (C=O), 1599.14 (N=N),
1
1307.69(C-N), 1091.16(C-Cl), 694.78(C-S); H NMR(δ ppm, DMSO-d6) 5.82(s,2H,N-CH-
Ar), 7.52(m,18H,Ar), 7.85(t,1H,C4-H in pyridine), 8.46(d,2H,C3,C5-H in pyridine); 13CNMR
(DMSO) δ: 170.78, 152.73, 135.2, 130.29, 122.91, 118.2, 116.35.
Table 1. Physical and analytical data of compounds 2a-j & 3a-c.
Elementalanalysis
(calcd/found)
Compd
R
Mol.Formula/Mol.wt
C
N
4-OH
H
67 307 C37H27N3O4S2/641.76 C(69.25/69.28), (6.55/6.54)
69 338 C37H27N3O2S2/609.76 C(72.88/72.83), N(4.46/4.45)
2a
2b
2c
2d
2e
2f
4-N-(CH3)2 66 293 C41H37N5O2S2/695.89 C(70.76/70.72), N(10.06/10.02)
3,4,5-(OCH3)3 71 309 C43H39N3O8S2/789.92 C(65.38/65.42) N(5.32/5.36)
4-OCH3
2-Cl
75 341 C39H31N3O4S2/669.81 C(69.93/69.95) N(6.27/6.28)
73 319 C37H25Cl2N3O2S2/678.65 C(65.48/65.48) N(6.19/6.13)
70 354 C37H25Br2N3O2S2/767.55 C(57.90/57.93) N(5.47/5.46)
74 301 C37H25N5O6S2/699.75 C(63.51/63.5) N(10.01/10.07)
69 317 C37H25Cl2N3O2S2/678.65 C(65.48/65.45) N(6.19/6.17)
71 299 C39H31N3O4S2/669.81 C(69.93/69.91), N(6.27/6.23)
79 310 C35H27N7O2S2/641.76 C(65.50/65.53) N(15.28/15.27)
81 327 C35H25N9O6S2/731.76 C(57.45/57.48) N(17.23/17.26)
84 315 C35H25Cl2N7O2S2/710.65 C(59.15/59.14) N(13.80/13.78)
2-Br
2g
2h
2i
4-NO2
4-Cl
2-OCH3
H
2j
3ª
4-NO2
4-Cl
3b
3c
Results and Discussion
The key intermediate 1 was prepared by a one pot three component condensation reaction
involving 2, 6-di amino pyridine, benzaldehyde, and mercaptoacid in the presence of a
γ-ferrite as a catalyst (18). The synthetic route of the compounds is outlined in Scheme-l.
This Thiazolidinone(1) reacted with various araldehydes afforded to bis thiazolidinones and

Synthesis and Antimicrobial Activity of New Thiazolidinone 829
their 5-arylidene derivatives(2a-j) through knoevenagel reaction. In another way
Diazotization of compounds with various aromatic amines yielded azo compounds (3a-c). The
newly synthesized compounds were characterized by FT-IR, NMR (1H, 13C) spectral data.
SHCH2COOH
+
+
OHC
NH2
N
NH2
Gaama-ferrite
N
N
N
S
S
O
O
1
Cl-
CHO
N
N+
R
R
N
N
N
N
N
N
S
S
O
O
S
S
O
O
N
N
N
N
R
R
R
R
3(a-c)
Scheme 1. Synthesis of compound 1, 2a-j and 3a-c.
2(a-j)
Anti Microbial Evaluation
Thirteen of the newly synthesized compounds were evaluated for their in vitro antibacterial
activity against B. subtilis, B. thuringiensis, E. coli and P. aeruginosa, as well as antifungal
activity against B. fabae, F. oxysporam and T. viridae organisms. Agar diffusion method
was used for the determination of the preliminary anti bacterial and antifungal activities.
Streptomycin, Chloramphenicol and Treflucan were used as reference drugs. The results
depicted in Table 2 revealed that most of tested compounds displayed variable inhibitory
effects on the growth of the tested organisms. Regarding the activity of the thiazolidinone
derivatives against bacteria, the results revealed that compounds 2f-2i, 3b, and 3c exhibited
broad spectrum of antibacterial profile against the tested organisms.

830 N. VARMA SEELAM et al.
Table 2. Antimicrobial activity data of compounds 2a-j & 3a-c (MIC, µg/mL).
B.
P.
B.
F.
Trichoder
Compd No
E-Coli
thuringiensis
aeruginosa fabae Oxysporam maviridae
2a
2b
2c
2d
2e
2f
100
100
200
50
200
50
100
100
100
50
50
25
12.5
50
100
25
25
6.25
6.25
-
100
50
100
100
50
100
50
50
100
50
50
50
100
12.5
12.5
25
25
12.5
50
6.25
50
25
100
200
50
200
100
50
25
12.5
6.25
25
50
6.25
50
25
25
50
100
12.5
50
2g
2h
2i
50
50
25
12.5
6.25
100
200
12.5
12.5
50
25
25
25
25
25
50
2j
100
50
100
100
12.5
50
12.5
100
12.5
12.5
-
25
3a
3b
3c
100
25
25
25
6.25
-
12.5
-
Streptomycin 3.125
Chloramphenicol 6.25
6.25
6.25
-
6.25
6.25
-
-
-
-
Treflucan
-
3.125
3.125
3.125
Regarding the activity of thiazolidinones and their 5- arylidenes and their 5- azo
derivatives incorporating pyridine moiety against antifungal strains the results revealed that
compounds 2e, 2j, 3b, and 3c revealed strong growth inhibitory against the tested fungi.
Conclusion
In conclusion, the objective of the present study was to synthesize and investigate the
antimicrobial activities of some new heterocyclic derivatives by the use of γ-ferrite leads
serving as potent antimicrobial agents. Our aim has been verified by the synthesis of two
different groups of structure hybrids comprising basically the pyridine moiety attached to
either arylidene substituted thiazolidinones (or) azo substituted thiazolidinones. The
obtained results clearly revealed that some of the newly synthesized compounds exhibited
better anti microbial activity.
Acknowledgment
The authors are grateful to The Head, Department of Chemistry Dr. H. S. Gour University
Sagar for providing necessary facilities to carry out this work. We sincerely express our
gratitude to Head, Biotechnology laboratory, Department of Botany, Dr. H. S. Gour
University Sagar for providing antimicrobial data. We are grateful to The Director, SAIF,
Panjab University for providing spectral data.
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