Synthesis of new series of N-3-[-{2-(substituted phenyl-4- oxo-5-(substituted benzylidene)-1,3-thiazolidine}-carbamyl]-propyl-2- aminothiazole and their biological importance

Article abstract of DOI:10.1007/s12039-011-0123-2

Synthesis of new series of N-3-[-{2-(substituted phenyl-4-oxo-5- (substituted benzylidene)-1,3-thiazolidine}-carbamyl]-propyl-2-aminothiazole, 5(a-s) have been developed. The cycloaddition reaction of thioglycolic acid with N-{3-(substituted benzylidine-c

Full text of DOI:10.1007/s12039-011-0123-2

c
J. Chem. Sci. Vol. 123, No. 5, September 2011, pp. 631–644. ꢀ Indian Academy of Sciences.
Synthesis of new series of N-3-[-{2-(substituted phenyl-4-
oxo-5-(substituted benzylidene)-1,3-thiazolidine}-carbamyl]-
propyl-2-aminothiazole and their biological importance
PUSHKAL SAMADHIYA∗, RITU SHARMA, SANTOSH K SRIVASTAVA and
SAVITRI D SRIVASTAVA
Synthetic Organic Chemistry Laboratory, Department of Chemistry, Dr. H S Gour University (A Central
University), Sagar, India 470 003
e-mail: pushkalsamadhiya@rediffmail.com
MS received 4 December 2010; revised 7 May 2011; accepted 11 May 2011
Abstract. Synthesis of new series of N-3-[-{2-(substituted phenyl-4-oxo-5-(substituted benzylidene)-1,3-
thiazolidine}-carbamyl]-propyl-2-aminothiazole, 5(a–s) have been developed. The cycloaddition reaction of
thioglycolic acid with N-{3-(substituted benzylidine-carbamyl)-propyl}-2-aminothiazole, 3(a–s) in the pres-
ence of anhydrous ZnCl2 afforded new heterocyclic compounds N1-3-[-{2-(substituted phenyl-4-oxo-1,3-
thiazolidine}-carbamyl]-propyl-2-aminothiazole 4(a–s). The latter product on treatment with several selected
substituted aromatic aldehydes in the presence of C2H5ONa undergoes Knoevenagel reaction to yield 5(a–s).
The structure of compounds 1, 2, 3(a–s), 4(a–s) and 5(a–s) were confirmed by IR, 1H NMR, 13C NMR, FAB
mass and chemical analysis. All final compounds were screened for their antimicrobial activity against some
selected bacteria and fungi and antituberculosis study against M. tuberculosis, gave acceptable activity.
Keywords. Synthesis; aminothiazole; thiazolidinone; antimicrobial; antitubercular.
1. Introduction
5-substituted benzylidine-1,3-thiazolidine}-carbamyl]-
propyl-2-aminothiazoleas shown in scheme 1. The
starting material, 2-aminothiazole with 1-bromo-3-
chloropropane undergoes electrophilic substitution
reaction yielded N-(3-chloropropyl)-2-aminothiazole,
compound 1. The compound 1 on the reaction with urea
afforded N1-{3-(aminocarbamyl)-propyl}-2-aminothia-
zole, compound 2. The compound 2 on reaction with
Thiazolidinone has an important role as a widely ex-
ploited pharmacophore in medicinal chemistry having
varied biological activity such as antifungal,1 anti-
bacterial,2,3 antimycobacterial,4 antipsychotic,5 anti-
inflammatory6 have been found to be associated with
thiazolidinone derivatives. Substituted thiazolidine de-
rivatives represent important key intermediates for the several selected substituted benzaldehydes under-
synthesis of pharmacologically active drug. Thiazoles goes condensation reaction to afford N-{3-(substituted
are amongst the most frequently encountered hetero- benzylidine-carbamyl)-propyl}-2-aminothiazole, com-
cycles in compounds of biological interest along with pound 3(a–s). The cycloaddition reaction of thiogly-
many other applications. They have been shown to pos- colic acid with compound 3(a–s) in the presence of
sess abroad spectrum of biological activity depending anhydrous ZnCl2 gave new heterocyclic compounds
on their particular structure. Anticonvulsants7, anti- N-3-[-{2-(substituted phenyl-4-oxo-1,3-thiazolidine}-
inflammatory8 activities are observed in thiazole deri- carbamyl]-propyl-2-aminothiazole, compound 4(a–s).
vatives. Some synthetic thiazoles have exhibited a The compound 4(a–s) on treatment with various
range of biological activities such as antimicrobial,9 selected substituted benzaldehydes in the presence of
biological activities,10 antibacterial, antifungal.11–13 C2H5ONa undergo Knoevenagel condensation reaction
Some recent studies have shown the synthesis of some yielded compound 5(a–s). The structure of compounds
new thiazoles candidates used as antimicrobial and 1, 2, 3(a–s), 4(a–s) and 5(a–s) were confirmed by IR,
1H NMR, 13C NMR, FAB mass and chemical analy-
anticancer agent. We have decided to synthesize
sis. All the above compounds were screened for their
a new series of N-3-[-{2-substituted phenyl-4-oxo-
∗For correspondence
631

632
Pushkal Samadhiya et al.
NH2CONH2
BrCH2CH2CH2Cl
N
N
S
S
N
S
NHCH2CH2CH2NHCONH2
NHCH2CH2CH2Cl
NH2
1
2
ArCHO
N
S
HSCH2COOH+ZnCl2
NHCH CH CH NHCO
N
CHAr
N
S
2
2
2
S
4(a-s)
NHCH2CH2CH2NHCON=CHAr
O
3(a-s)
ArCHO+C2H5ONa
N
S
NHCH CH CH NHCO
N
CHAr
S
2
2
2
5(a-s)
O
CHAr1
Ar = Ar1 = substituted phenyl ring
Scheme 1. Synthesis of compounds 1, 2, 3(a–s), 4(a–s) and 5(a–s).
antimicrobial activity against some selected bacte- room temperature. The reaction mixture was continu-
ria and fungi and antituberculosis study against M. ously stirred on a magnetic stirrer for about 8 h. The
tuberculosis.
product was filtered and purified over a column chro-
matography. The purified product was recrystallized
from ethanol at room temperature to yield compound 1.
2. Materials and methods
Melting points were taken in open capillaries and are
uncorrected. Progress of reaction was monitored by sil-
ica gel-G coated TLC plates in MeOH: CHCl3 system
(1:9). The spot was visualized by exposing dry plate in
iodine vapours. IR spectra were recorded in KBr disc on
a Schimadzu 8201 PC, FTIR spectrophotometer (νmax
in cm−1) and 1H and 13C NMR spectra were measured
on a Brucker DRX-300 spectrometer in CDCl3 at 300
and 75 MHz respectively using TMS as an internal stan-
dard. All chemical shifts were reported on δ scales. The
FAB mass spectra were recorded on a Jeol SX–102
mass spectrometer. Elemental analyses were performed
on a Carlo Erba–1108 analyzer. The analytical data of
all the compounds were satisfactory. For column chro-
matographic purification of the products, Merck silica
Gel 60 (230–400 Mesh) was used. The reagent grade
chemicals were purchased from the commercial sources
and further purified before use.
2.2 Method for synthesis of compound 2
A mixture of compound 1 and urea (1:1 mole) was dis-
solved in methanol at room temperature. The reaction
mixture was continuously stirred on a magnetic stirrer
for about 8 h. The product was filtered and purified over
a column chromatography. The purified product was
recrystallized from ethanol at room temperature to yield
compound 2.
2.3 General method for the synthesis
of compound 3(a–s)
A mixture of compound 2 and substituted benzaldehy-
des (1:1 mole) was dissolved in methanol at room tem-
perature and allowed to react. The reaction mixture was
first continuously stirred on a magnetic stirrer for about
2 to 3 h then kept on a steam bath for about 1.30–
4.15 h. The products were cooled and filtered. The prod-
ucts were purified over a column chromatography and
2.1 Method for synthesis of the compound 1
A mixture of 2-aminothiazole and 1-bromo-3-chloro- recrystallized from ethanol at room temperature to yield
propane (1:1 mole) was dissolved in methanol at compound 3(a–s).

Synthesis and biological importance of thiazolidines
633
2.4 General method for the synthesis
of compounds 4(a–s)
used in ppm. All the final synthesized compounds
5(a–s) have been screened in vitro for their antibacte-
rial activity against B. subtilis, E. coli and S. aureus
and antifungal activity against A. niger, A. flavus and
C. albicans. Standards for antibacterial and antifun-
gal activity streptomycin and griseofulvin were used
respectively. Standards also screened under the similar
conditions for comparison. The antitubercular activ-
ity was screened against the M. tuberculosis. For the
antitubercular activity isoniazid and rifampicin were
used as standard and also screened under the similar
conditions.
A mixture of compound 3(a–s) and thioglycolic acid
(1:1 mole) dissolved in methanol was allowed to react
in the presence of catalytic amount of ZnCl2. The
reaction mixture was first continuously stirred on a
magnetic stirrer for about 2 to 3.5 h then kept on
steam bath for about 1.45–4.15 h at 80–90◦C. The prod-
ucts were cooled and filtered at room temperature. The
filtered products were purified over column chromatog-
raphy and recrystallized from ethanol at room tempera-
ture to yield compound 4(a–s).
3.1 Antibacterial activity
2.5 General method for the synthesis
of compound 5(a–s)
The above synthesized compound 5(a–s) were screened
against some selected bacteria and examined for the
inhibition of growth of the organism. The concen-
trations of the compounds were given in ppm. The
diameter of the inhibition zones in (mm) are given in
table 1.
A mixture of compound 4(a–s) and substituted ben-
zaldehydes (1:1 mole) was dissolved in methanol in the
presence of alkali metal alkoxide (C2H5ONa) and allow
to react. The reaction mixture was first continuously
stirred on a magnetic stirrer for about 2 to 3.5 h then
kept on steam bath for about 1.45–4.15 h at 80–90◦C.
The products were cooled and filtered at room tem-
perature. The filtered products were purified over col-
umn chromatography and recrystallized from ethanol
at room temperature to yield final products compound
5(a–s).
3.2 Antifungal activity
The above synthesized compound 5(a–s) were screened
against selected fungi and determined their minimal
inhibition zones in (mm) were presented in table 2 and
concentrations of the compounds were given in ppm.
3. Biological study
3.3 Antitubercular activity
Series of newly synthesized compounds were active
against selected microorganisms. The minimal inhibi-
tion diameters were determined using the filter paper
disc diffusion method and the concentrations have been
The above synthesized compound 5(a–s) were screened
against M. tuberculosis using L. J. medium (Conven-
tional) method at 50 μg/mL and lower concentrations
Table 1. Antibacterial activity of compounds 5(a–s).
Compound
B. subtilis
E. coli
50 100
ppm ppm ppm
S. aureus
Compound
B. subtilis
E. coli
50 100
ppm ppm ppm
S. aureus
50
100
ppm
50
100
ppm
50
100
ppm
50
100
ppm
ppm
ppm
5a
5b
5c
5d
5e
5f
5g
5h
5i
10
15
13
15
12
11
20
22
20
24
25
32
34
33
30
30
28
29
27
27
37
07
10
12
10
12
11
10
09
10
11
26
22
30
30
31
28
27
26
25
25
24
34
10
15
14
13
15
14
10
12
12
10
27
23
32
30
27
31
28
27
29
26
25
35
5k
5l
08
11
13
14
12
14
12
13
11
-
25
24
25
18
19
20
25
23
22
-
09
12
15
14
14
15
13
14
12
-
18
19
19
13
12
11
15
17
15
-
08
12
14
16
15
14
12
13
11
-
20
28
26
27
20
19
18
21
20
-
5m
5n
5o
5p
5q
5r
5s
-
5j
Streptomycin 28
Streptomycin 28
37
26
34
27
35

634
Pushkal Samadhiya et al.
Table 2. Antifungal activity of compounds 5(a–s).
Compound
A. niger
50 100
ppm ppm ppm ppm ppm
A. flavus
50 100
C. albicans
Compound
A. niger
50 100
ppm ppm ppm ppm ppm
A. flavus
50 100
C. albicans
50
100
ppm
50
100
ppm
5a
5b
5c
5d
5e
5f
5g
5h
5i
07
12
10
11
10
11
10
08
12
13
15
22
24
23
22
20
18
19
17
17
32
07
10
12
10
12
11
10
09
10
11
20
12
20
20
21
18
17
16
15
15
14
35
10
14
14
13
15
14
10
12
12
10
24
14
24
22
21
21
20
22
20
21
20
36
5k
5l
11
10
13
10
09
08
14
13
12
-
15
14
15
15
14
12
15
18
22
-
10
12
13
10
09
10
13
13
10
-
18
19
19
13
12
11
15
17
15
-
11
12
12
10
11
09
12
13
11
-
20
18
16
17
15
13
12
14
16
-
5m
5n
5o
5p
5q
5r
5s
5j
Griseofulvin 22
Griseofulvin 22
32
20
35
24
36
using M. tuberculosis H37Rv strain. The results are NMR (δ): 2.24 (m, 2H, CH2CH2CH2), 3.46 (m, 2H,
shown in table 3. The standard antitubercular drugs CH2CH2CH2-NH), 4.25 (m, 2H, N-CH2CH2CH2),
isoniazid and rifampicin were taken as standards.
5.63 (t, J = 4.60 Hz, 1H, NHCO), 5.96 (s, 2H, NH2),
7.76 (t, J = 5.10 Hz, 1H, NH), 6.76 (d, 1H, J =
4.82 Hz, C5H of thiazole), 7.18 (d, 1H, J = 4.82 Hz,
C4H of thiazole);13C NMR (δ): 32.9 (CH2CH2CH2),
39.6 (CH2CH2CH2NH), 44.8 (N-CH2CH2CH2), 109.5
(C5 of thiazole), 138.6 (C4 of thiazole), 163.8 (CO),
168.2 (C2 of thiazole); Mass(FAB): 200M+.
3.3a N-(3-chloropropyl)-2-aminothiazole (1): Yield:
63%; m.p. 77–79◦C; Anal. Calcd for C6H9N2SCl:
C, 40.79, H, 5.13, N, 15.85%; found C, 40.74, H,
5.09, N, 15.80%; IR (cm−1): 748 (C–Cl), 886 (C–
S), 1339 (N-CH2), 1568 (C=C), 2888, 3046 (CH),
3482 (NH); 1H NMR (δ): 2.30 (m, 2H, CH2CH2CH2),
3.46(t, 2H, J = 7.41 Hz, CH2CH2CH2–Cl), 4.23 (m,
2H, N–CH2CH2CH2), 6.90 (t, J = 5.10 Hz, 1H, NH),
6.76 (d, 1H, J = 4.36 Hz, C5H of thiazole), 7.18
(d, 1H, J = 4.36 Hz, C4H of thiazole),13C NMR
(δ): 32.6 (CH2CH2CH2), 41.8 (CH2CH2CH2-Cl), 46.6
(N-CH2CH2CH2), 109.5 (C5 of thiazole), 139.5 (C4 of
thiazole), 169.6 (C2 of thiazole), Mass (FAB): 176M+.
3.3c N-{3-(benzylidencarbamyl)-propyl}-2-aminothi-
azole (3a): Yield: 61%; m.p. 67-68◦C; Anal. Calcd
for C14H16N4OS: C, 58.31, H, 5.59, N, 19.42%; found
C, 58.27, H, 5.52, N, 19.37%; IR: 3369 (NH), 1664
1
(C=O), 1558 (N=CH); H NMR (δ): 2.26 (m, 2H,
CH2CH2CH2), 3.42 (t, 2H, J = 7.40 Hz, CH2CH2CH2-
N), 4.22 (t, 2H, J = 7.40 Hz,N-CH2CH2CH2), 5.58 (t,
J = 4.60 Hz, 1H, NHCO), 7.24 (d, 1H, J = 4.84 Hz,
3.3b N-{3-(aminocarbamyl)-propyl}-2-aminothiazole C4H of thiazole), 6.62 (d, 1H, J = 4.84 Hz, C5H of
(2): Yield: 72%; m.p.58–60◦C; Anal. Calcd for thiazole), 7.78 (t, J = 5.10 Hz, 1H, NH), 7.86 (s,
C7H12N4OS: C, 41.98, H, 6.03, N, 27.97%; found 1H, N=CH), 6.30–7.21 (m, 5H, Ar-H); 13C NMR
C, 41.89, H, 5.97, N, 27.88%; IR: 872 (C-S), 1232 (δ): 32.8 (CH2CH2CH2), 39.7 (CH2CH2CH2-N), 45.6
(C-N), 1642 (C=O), 3378 (NH), 3424 (NH2); 1H (N-CH2CH2CH2), 113.6 (C5 of thiazole), 140.5 (C4 of
Table 3. Antitubercular activity of compounds 5(a–s).
Compound
% Activity
Compound
% Activity
Compound
% Activity
Compound
% Activity
25 ppm 50 ppm
25 ppm 50 ppm
25 ppm 50 ppm
25 ppm 50 ppm
5a
5b
5c
5d
22
32
33
32
30
45
82
80
80
78
5f
5g
5h
5i
5j
30
29
32
27
28
79
76
82
83
81
5k
5l
5m
5n
5o
28
30
31
22
18
60
63
65
45
49
5p
5q
5r
5s
20
24
27
25
-
47
56
60
55
-
5e
-
Standard
100
100
Standard
100
100
Standard
100
100
Standard
100
100

Synthesis and biological importance of thiazolidines
635
thiazole), 144.5 (N=CH), 162.7 (CO), 169.7 (C2 of thiazole), 126.5, 128.7, 128.5, 129.5, 132.4, 139.5 (6C,
thiazole), 124.5, 125.8, 127.6, 129.7, 131.5, 137.6 (6C, Ar); Mass (FAB): 322M+.
Ar); Mass (FAB): 288M+.
3.3g N-{3-(4-bromobenzylidencarbamyl)-propyl}-2-
3.3d N-{3-(4-chlorobenzylidencarbamyl)-propyl}-2-
aminothiazole (3e): Yield: 68%; m.p. 75–77◦C; Anal.
aminothiazole (3b): Yield: 63%; m.p. 80–82◦C;
Anal. Calcd for C14H15N4OSCl: C, 52.08, H, 4.68,
N, 17.35%; found C, 52.05, H, 4.65, N, 17.30%;
Calcd for C14H15N4OSBr: C, 45.78, H, 4.11, N,
15.25%; found C, 45.74, H, 4.06, N, 15.19%; IR: 639
1
(C-Br), 1555 (N=CH), 1678 (C=O), 3388 (NH); H
IR: 3375 (NH), 1675 (C=O), 1565 (N=CH), 742
NMR(δ): 2.35 (m, 2H, J = 7.39 Hz, CH2CH2CH2),
3.52 (m, 2H, CH2CH2CH2-NH), 4.26 (m, 2H, N-
CH2CH2CH2), 5.69 (t, J = 4.60 Hz, 1H, NHCO),
7.04 (d, 1H, J = 4.78 Hz, C5H of thiazole), 7.27
(d, 1H, J = 4.78 Hz, C4H of thiazole), 7.78 (t, J =
5.10 Hz, 1H, NH), 7.94 (s, 1H, N=CH) 7.19–7.69 (m,
4H, Ar-H); 13C NMR (δ): 33.4 (CH2CH2CH2), 43.7
(CH2CH2CH2-NH), 46.8 (N-CH2CH2CH2), 112.7 (C5
of thiazole), 140.9 (C4 of thiazole), 150.6 (N=CH),
164.1 (CO), 169.5 (C2 of thiazole), 123.5, 126.5, 129.2,
132.8, 133.6, 137.6 (6C, Ar); Mass (FAB): 367M+.
1
(C–Cl); H NMR (δ): 2.35 (m, 2H, J = 7.43 Hz,
CH2CH2CH2), 3.52 (m, 2H, CH2CH2CH2-N), 4.33
(m, 2H, N-CH2CH2CH2), 5.57 (t, J = 4.60 Hz, 1H,
NHCO), 7.40 (d, 1H, J = 4.86 Hz, C4H of thiazole),
7.20 (d, 1H, J = 4.86 Hz, C5H of thiazole), 7.05 (t,
J = 5.10 Hz, 1H, NH), 7.95 (s, 1H, N=CH), 6.70–7.80
(m, 4H, Ar-H); 13C NMR (δ): 34.7 (CH2CH2CH2),
41.5 (CH2CH2CH2-NH), 47.5 (N-CH2CH2CH2), 115.5
(C5 of thiazole), 143.9 (C4 of thiazole), 151 (N=CH),
166.5 (CO), 172.5 (C2 of thiazole), 125.5, 128.5, 129.5,
130.4, 134.3, 140.5 (6C, Ar); Mass (FAB): 322M+.
3.3h N-{3-(3-bromobenzylidencarbamyl)-propyl}-2-
aminothiazole (3f): Yield: 64%; m.p. 72–73◦C; Anal.
Calcd for C14H15N4OSBr: C, 45.78, H, 4.11, N,
15.25%; found C, 45.72, H, 4.04, N, 15.22%; IR: 642
3.3e N-{3-(3-chlorobenzylidencarbamyl)-propyl}-2-
aminothiazole (3c): Yield: 65%; m.p.84–87◦C; Anal.
Calcd for C14H15N4OSCl: C, 52.08, H, 4.68, N,
17.35%; found C, 52.04, H, 4.64, N, 1.25%; IR: 745
1
(C-Br), 1563 (N=CH), 1679 (C=O), 3366 (NH); H
1
(C–Cl), 1560 (N=CH), 1674 (C=O), 3375(NH); H
NMR (δ): 2.39 (m, 2H, CH2CH2CH2), 3.50 (m, 2H,
CH2CH2CH2–NH), 4.28 (m, 2H, N-CH2CH2CH2),
5.55 (t, J = 4.60 Hz, 1H, NHCO), 7.07 (d, 1H, J =
4.82 Hz, C5H of thiazole), 7.29 (d, 1H, J = 4.82 Hz,
C4H of thiazole), 7.75 (t, J = 5.10 Hz, 1H, NH), 7.88
(s, 1H, N=CH), 7.23–7.90 (m, 4H, Ar-H); 13C NMR
(δ): 41.3 (CH2CH2CH2), 49.4 (CH2CH2CH2-N), 47.1
(N-CH2CH2CH2), 112.6 (C5 of thiazole), 141.5 (C4 of
thiazole), 151.6 (N=CH), 163.9 (CO), 172.4 (C2 of
thiazole), 124.1, 126.7, 129.2, 131.5, 137.7, 141.2 (6C,
Ar); Mass (FAB): 367M+.
NMR (δ): 2.44 (m, 2H, J = 7.42 Hz, CH2CH2CH2),
3.50 (m, 2H, CH2CH2CH2-N), 3.85 (m, 2H, N-
CH2CH2CH2), 5.62 (t, J = 4.60 Hz, 1H, NHCO), 7.15
(d, 1H, J = 4.84 Hz, C5H of thiazole), 7.30 (d, 1H, J =
4.84 Hz, C4H of thiazole), 7.74 (t, J = 5.10 Hz, 1H,
NH), 7.95 (s, 1H, N=CH), 7.3–7.5 (m, 4H, Ar-H); 13
C
NMR (δ): 33.5 (CH2CH2CH2), 43.5 (CH2CH2CH2-N),
47.1 (N-CH2CH2CH2), 113 (C5 of thiazole), 141.8 (C4
of thiazole), 147.5 (N=CH), 164 (CO), 170 (C2 of
thiazole), 126.5, 128.5, 130.5, 132.5, 136.3, 137.5 (6C,
Ar); Mass (FAB): 322M+.
3.3f N-{3-(2-chlorobenzylidencarbamyl)-propyl}-2- 3.3i N-{3-(2-bromobenzylidencarbamyl)-propyl}-2-
aminothiazole (3d): Yield: 66%; m.p. 81–82◦C; aminothiazole (3h): Yield: 62%; m.p. 70–71◦C; Anal.
Anal. Calcd for C14H15N4OSCl: C, 52.08, H, 4.68, N, Calcd for C14H15N4OSBr: C, 45.78, H, 4.11, N,
17.35%; found C, 52.1, H, 4.60, N, 17.36%; IR: 742 15.25%; found C, 45.74, H, 4.05, N, 15.18%; IR: 632
1
1
(C–Cl), 1565 (N=CH), 1675 (C=O), 3380 (NH); H (C-Br), 1554 (N=CH), 1672 (C=O), 3378 (NH); H
NMR (δ): 2.45 (m, 2H, CH2CH2CH2), 3.45 (m, 2H, NMR (δ): 2.30 (m, 2H, CH2CH2CH2), 3.41 (m, 2H,
CH2CH2CH2-NH), 3.78 (m, 2H, N-CH2CH2CH2), CH2CH2CH2-NH), 4.27 (m, 2H, N-CH2CH2CH2), 5.69
5.85 (t, J = 4.60 Hz, 1H, NHCO), 7.12 (d, 1H, J = (t, J = 4.60 Hz, 1H, NHCO), 7.06 (d, 1H, J = 4.83 Hz,
4.81 Hz, C5H of thiazole), 7.35 (d, 1H, J = 4.81 Hz, C5H of thiazole), 7.28 (d, 1H, J = 4.83 Hz, C4H of
C4H of thiazole), 7.77 (t, J = 5.10 Hz, 1H, NH), 7.85 thiazole), 7.70 (t, J = 5.10 Hz, 1H, NH), 8.02 (s,
(s, 1H, N=CH), 7.5–7.8 (m, 4H, Ar-H); 13C NMR 1H, N=CH), 7.21–7.73 (m, 4H, Ar-H); 13C NMR(δ):
(δ): 33.5 (CH2CH2CH2), 44.5 (CH2CH2CH2-N), 47.8 35.9 (CH2CH2CH2), 42.1 (CH2CH2CH2-NH), 51.4
(N-CH2CH2CH2), 111.5 (C5 of thiazole), 141.5 (C4 of (N-CH2CH2CH2), 109.7 (C5 of thiazole), 139.9 (C4
thiazole), 150.5 (N=CH), 164.3 (CO), 170.3 (C2 of of thiazole), 152 (N=CH), 164.1 (CO), 171.6 (C2 of

636
Pushkal Samadhiya et al.
thiazole), 126.8, 128.5, 129.5, 131.7, 133.9, 145.4 (6C, 165 (CO), 171.5 (C2 of thiazole), 122.8, 125.6, 127.8,
Ar); Mass (FAB): 367M+.
133.7, 137.9, 149.6 (6C, Ar); Mass (FAB): 333M+.
3.3m N-{3-(4-methoxybenzylidencarbamyl)-propyl}-
2-aminothiazole (3l): Yield: 61%; m.p. 75–77◦C;
Anal. Calcd for C15H18N4O2S: C, 56.58, H, 5.69, N,
17.59%; found C, 56.50, H, 5.61, N, 17.56%; IR: 1564
(N=CH), 2949 (OCH3), 3359 (NH); 1H NMR (δ): 2.16
(m, 2H, CH2CH2CH2), 3.38 (m, 2H, CH2CH2CH2-
NH), 3.59 (s, 3H, OCH3), 4.23 (t, 2H, m, 2H, N-
CH2CH2CH2), 5.68 (t, J = 4.60 Hz, 1H, NHCO), 7.10
(d, 1H, J = 4.82 Hz, C5H of thiazole), 7.39 (d, 1H, J =
4.82 Hz, C4H of thiazole), 7.84 (t, J = 5.10 Hz, 1H,
NH), 7.95 (s, 1H, N=CH), 7.24–7.88 (m, 4H, Ar-H);
13C NMR (δ): 35.2 (CH2CH2CH2), 44.6 (CH2CH2CH2-
NH), 47.6 (N-CH2CH2CH2), 51.7 (OCH3), 109.8 (C5
of thiazole), 139.5 (C4 of thiazole), 154.8 (N=CH),
162.5 (CO), 169.6 (C2 of thiazole), 114.7, 117.6, 126.8,
128.7, 130.6, 159.9 (6C, Ar); Mass (FAB): 318M+.
3.3j N-{3-(4-nitrobenzylidencarbamyl)-propyl}-2-
aminothiazole (3i): Yield: 65%; m.p. 80–81◦C;
Anal. Calcd for C14H15N5O3S : C, 50.44, H, 4.53, N,
21.00%; found C, 50.35, H, 4.48, N, 20.90%; IR: 849
(C-N), 1532 (N=O), 1578 (N=CH), 1677 (C=O),
1
3378 (NH); H NMR (δ): 2.37 (m, 2H, J = 7.45 Hz,
CH2CH2CH2), 3.57 (m, 2H, CH2CH2CH2-N), 4.24
(m, 2H, N-CH2CH2CH2), 5.81 (t, J = 4.60 Hz, 1H,
NHCO), 7.20 (d, 1H, J = 4.83 Hz, C5H of thiazole),
7.45 (d, 1H, J = 4.83 Hz, C4H of thiazole), 7.80 (t, J =
5.10 Hz, 1H, NH), 8.10 (s, 1H, N=CH), 7.22–7.91 (m,
4H, Ar-H); 13C NMR (δ): 38.9 (CH2CH2CH2), 44.3
(CH2CH2CH2-N), 48.3 (N-CH2CH2CH2), 114.7 (C5
of thiazole), 141.6 (C4 of thiazole), 155.4 (N=CH),
165.4 (CO), 171.9 (C2 of thiazole), 122.4, 124.9, 128.7,
129.5, 138.8, 147.9 (6C, Ar); Mass (FAB): 333M+.
3.3n N-{3-(2-methoxybenzylidencarbamyl)-propyl}-
2-aminothiazole (3m): Yield: 63%; m.p. 68–69◦C;
Anal. Calcd for C15H18N4O2S: C, 56.58, H, 5.69,
N, 17.59%; found C, 56.54, H, 5.62, N, 17.53%;
IR: 3366 (NH), 2940 (OCH3), 1558 (N=CH);1H
NMR (δ): 2.14 (m, 2H, CH2CH2CH2), 3.42 (m, 2H,
CH2CH2CH2-NH), 3.64 (s, 3H, OCH3), 4.14 (m, 2H,
N-CH2CH2CH2), 5.64 (t, J = 4.60 Hz, 1H, NHCO),
7.28 (d, 1H, J = 4.80 Hz, C4H of thiazole), 6.82
(d, 1H, J = 4.80 Hz, C5H of thiazole), 7.68 (t, J =
5.10 Hz, 1H, NH), 7.79 (s, 1H, N=CH), 7.22–7.92
(m, 4H, Ar-H); 13C NMR (δ): 38.1 (N-CH2CH2CH2),
42.8 (CH2CH2CH2), 49.7 (CH2CH2CH2-NH), 54.7
(OCH3), 161.1 (CO), 153.5 (N=CH), 170.2 (C2 of
thiazole), 109.4 (C5 of thiazole), 138.3 (C4 of thiazole),
112.3, 116.8, 122.7, 128.5, 137.7, 159.9 (6C, Ar); Mass
(FAB): 318M+.
3.3k N-{3-(3-nitrobenzylidencarbamyl)-propyl}-2-
aminothiazole (3j): Yield: 61%; m.p. 77–79◦C; Anal.
Calcd for C14H15N5O3S: C, 50.44, H, 4.53, N, 21.00%;
found C, 50.37, H, 4.45, N, 20.92%; IR: 3371 (NH),
1668 (C=O), 1528 (N=O), 1574 (N=CH), 844 (C-N);
1H NMR (δ): 2.35 (m, CH2CH2CH2), 3.56 (m, 2H,
CH2CH2CH2-NH), 4.32 (m, 2H, N-CH2CH2CH2),
5.78 (t, J = 4.60 Hz, 1H, NHCO), 7.40 (d, 1H, J =
4.87 Hz, C4H of thiazole), 7.18 (d, 1H, J = 4.87 Hz,
C5H of thiazole), 7.87 (t, J = 5.10 Hz, 1H, NH), 8.07
(s, 1H, N=CH), 7.21–7.86 (m, 4H, Ar-H); 13C NMR
(δ): 39.7 (CH2CH2CH2), 45.2 (CH2CH2CH2-NH),
51.1 (N-CH2CH2CH2), 112.6 (C5 of thiazole), 140 (C4
of thiazole), 154.7 (N=CH), 165.2 (CO), 171.3 (C2 of
thiazole), 122.3, 125.2, 128.4, 133.4, 137.5, 150.5 (6C,
Ar); Mass (FAB): 333M+.
3.3l N-{3-(2-nitrobenzylidencarbamyl)-propyl}-2- 3.3o N-{3-(3-methoxybenzylidencarbamyl)-propyl}-
aminothiazole (3k): Yield: 60%; m.p. 72–74◦C; Anal. 2-aminothiazole (3m): Yield: 64%; m.p. 70–72◦C;
Calcd for C14H15N5O3S: C, 50.44, H, 4.53, N, 21%; Anal. Calcd for C15H18N4O2S: C, 56.58, H, 5.69, N,
found C, 50.40, H, 4.47, N, 20.95%; IR: 847 (C-N), 17.59%; found C, 56.52, H, 5.64, N, 17.50%; IR: 1554
1538 (N=O), 1572 (N=CH), 1664 (C=O), 3358 (N=CH), 2947 (OCH3), 3368 (NH); 1H NMR (δ): 2.11
(NH); 1H NMR (δ): 2.34 (m, 2H, J = 7.51 Hz, (m, 2H, CH2CH2CH2), 3.42 (m, 2H, CH2CH2CH2-
CH2CH2CH2), 3.45 (m, 2H, CH2CH2CH2-N), 4.29 NH), 3.68 (s, 3H, OCH3), 4.18 (m, 2H, N-
(m, 2H, N-CH2CH2CH2), 5.73 (t, J = 4.60 Hz, 1H, CH2CH2CH2), 5.69 (t, J = 4.60 Hz, 1H, NHCO), 7.11
NHCO), 7.16 (d, 1H, J = 4.88 Hz, C5H of thiazole), (d, 1H, J = 4.82 Hz, C5H of thiazole), 7.29 (d, 1H, J =
7.31 (d, 1H, J = 4.88 Hz, C4H of thiazole), 7.82 (t, J = 4.82 Hz, C4H of thiazole), 7.72 (t, J = 5.10 Hz, 1H,
5.10 Hz, 1H, NH), 8.11 (s, 1H, N=CH), 7.26–7.99 (m, NH), 7.96 (s, 1H, N=CH), 7.41–7.82 (m, 4H, Ar-H);
4H, Ar-H); 13C NMR (δ): 40.2 (CH2CH2CH2), 47.1 13C NMR (δ): 36.2 (CH2CH2CH2), 44.6 (CH2CH2CH2-
(CH2CH2CH2-N), 52.3 (N-CH2CH2CH2), 111.7 (C5 NH), 48.7 (N-CH2CH2CH2), 54.5 (OCH3), 109..8 (C5
of thiazole), 139.8 (C4 of thiazole), 155.7 (N=CH), of thiazole), 137..8 (C4 of thiazole), 153.9 (N=CH),

Synthesis and biological importance of thiazolidines
637
161.9 (CO), 168.2 (C2 of thiazole), 112.8, 117.9, 123.6, of thiazole), 124.3, 126.4, 128.7, 130.8, 134.7, 137.8
129.7, 138.9, 160.5 (6C, Ar); Mass (FAB): 318M+. (6C, Ar); Mass (FAB): 302M+.
3.3p N-{3-(4-methylbenzylidencarbamyl)-propyl}-2- 3.3s N-{3-(4-hydroxybenzylidencarbamyl)-propyl}-2-
aminothiazole (3n): Yield: 62%; m.p. 64–65◦C; Anal. aminothiazole (3q): Yield: 61%; m.p. 72–74◦C; Anal.
Calcd for C15H18N4OS: C, 59.58, H, 5.99, N, 18.52%; Calcd for C14H15N4O2S: C, 55.24, H, 4.96, N, 18.40%;
found C, 59.50, H, 5.92, N, 18.48%; IR: 1552 (N=CH), found C, 55.19, H, 4.90, N, 18.30%; IR: 1559 (N=CH),
1
1
2927 (CH3), 3352 (NH); H NMR (δ): 2.09 (m, 2H, 3382 (NH), 3470 (OH); H NMR (δ): 2.29 (m, 2H,
CH2CH2CH2), 3.34 (m, 2H, CH2CH2CH2-NH), 2.60 CH2CH2CH2), 3.47 (m, 2H, CH2CH2CH2-NH), 4.29
(s, 3H, CH3), 4.02 (m, 2H, N-CH2CH2CH2), 5.68 (t, (m, 2H, N-CH2CH2CH2), 4.17 (s, 1H, OH), 5.82 (t, J =
J = 4.60 Hz, 1H, NHCO), 6.81 (d, 1H, J = 4.88 Hz, 4.60 Hz, 1H, NHCO), 7.15 (d, 1H, J = 4.81 Hz, C5H
C5H of thiazole), 7.14 (d, 1H, J = 4.88 Hz, C4H of of thiazole), 7.36 (d, 1H, J = 4.81 Hz, C4H of thi-
thiazole), 7.69 (t, J = 5.10 Hz, 1H, NH), 7.84 (s, 1H, azole), 7.84 (t, J = 5.10 Hz, 1H, NH), 8.07 (s, 1H,
N=CH), 7.29–7.79 (m, 4H, Ar-H); 13C NMR (δ): 24.9 N=CH), 7.22–7.99 (m, 4H, Ar-H); 13C NMR (δ):
(CH3), 34.4(CH2CH2CH2), 43.3 (CH2CH2CH2-NH), 39.9 (CH2CH2CH2), 45.1 (CH2CH2CH2-NH), 51.1
46.7 (N-CH2CH2CH2), 151.7 (N=CH), 160.8 (CO), (N-CH2CH2CH2), 110.7 (C5 of thiazole), 138.6 (C4 of
171.2 (C2 of thiazole), 109.5 (C5 of thiazole), 139.8 (C4 thiazole), 156.3 (N=CH), 164.7 (CO), 169.1 (C2 of
of thiazole), 125.8, 127.4, 129.8, 130.7, 134.9, 139.6 thiazole), 116.7, 118.9, 126.9, 129.8, 130.7, 154.8 (6C,
(6C, Ar); Mass (FAB): 302M+.
Ar); Mass (FAB): 304M+.
3.3q N-{3-(3-methybenzylidencarbamyl)-propyl}-2- 3.3t N-{3-(3-hydroxybenzylidencarbamyl)-propyl}-2-
aminothiazole (3o): Yield: 61%; m.p. 61–62◦C; aminothiazole (3r): Yield: 66%; m.p. 70–71◦C;
Anal. Calcd for C15H18N4OS: C, 59.58, H, 5.99, N, Anal. Calcd for C14H15N4O2S: C, 55.24, H, 4.96, N,
18.52%; found C, 59.52, H, 5.90, N, 18.45%; IR: 1545 18.40%; found C, 55.20, H, 4.88, N, 18.36%; IR: 1564
1
1
(N=CH), 2920 (CH3), 3347 (NH); H NMR (δ): 2.60 (N=CH), 3379 (NH), 3462 (OH); H NMR (δ): 2.28
(s, 3H, CH3), 2.05 (m, 2H, CH2CH2CH2), 3.45 (m, 2H, (m, 2H, CH2CH2CH2), 3.48 (m, 2H, CH2CH2CH2-
CH2CH2CH2-NH), 3.78 (m, 2H, N-CH2CH2CH2), 5.40 N), 4.28 (m, 2H, N-CH2CH2CH2), 4.26 (s, 1H, OH),
(t, J = 4.60 Hz, 1H, NHCO), 6.88 (d, 1H, J = 4.86 Hz, 5.96 (t, J = 4.60 Hz, 1H, NHCO), 7.05 (d, 1H, J =
C5H of thiazole), 7.25 (d, 1H, J = 4.86 Hz, C4H of 4.90 Hz, C5H of thiazole), 7.34 (d, 1H, J = 4.90 Hz,
thiazole), 7.65 (t, J = 5.10 Hz, 1H, NH), 7.80 (s, 1H, C4H of thiazole), 7.87 (t, J = 5.10 Hz, 1H, NH), 8.01
N=CH), 7.32–7.85 (m, 4H, Ar-H); 13C NMR (δ): 21.9 (s, 1H, N=CH), 7.26–8.14 (m, 4H, Ar-H); 13C NMR
(CH3), 39.1 (CH2CH2CH2), 52.1 (CH2CH2CH2-NH), (δ): 38.4 (CH2CH2CH2), 46.7 (CH2CH2CH2-N), 53.4
45.7 (N-CH2CH2CH2), 109.8 (C5 of thiazole), 140.1 (N-CH2CH2CH2), 111.2 (C5 of thiazole), 139.6 (C4 of
(C4 of thiazole), 151 (N=CH), 159.5 (CO), 171 (C2 of thiazole), 154.2 (N=CH), 163.7 (CO), 168.1 (C2 of
thiazole), 125.2, 129.6, 128.5, 129.8, 134.3, 137.4 (6C, thiazole), 113.4, 115.8, 119.9, 129.4, 138.8, 155.7 (6C,
Ar); Mass(FAB): 302M+.
Ar); Mass (FAB): 304M+.
3.3r N-{3-(2-methylbenzylidencarbamyl)-propyl}-2- 3.3u N-{3-(2-hydroxybenzylidencarbamyl)-propyl}-2-
aminothiazole (3p): Yield: 64%; m.p. 57–58◦C; aminothiazole (3s): Yield: 65%; m.p. 78–80◦C; Anal.
Anal. Calcd for C15H18N4OS: C, 59.58, H, 5.99, N, Calcd for C14H15N4O2S: C, 55.24, H, 4.96, N, 18.40%;
18.52%; found C, 59.55, H, 5.93, N, 18.46%; IR: 1555 found C, 55.20, H, 4.92, N, 18.32%; IR: 1565 (N=CH),
1
1
(N=CH), 2910 (CH3), 3345 (NH); H NMR (δ): 2.63 3381 (NH), 3468 (OH); H NMR (δ): 2.21 (m, 2H,
(s, 3H, CH3), 2.05 (m, 2H, CH2CH2CH2), 3.40 (m, 2H, CH2CH2CH2), 3.44 (m, 2H, CH2CH2CH2-NH), 4.26
CH2CH2CH2-NH), 3.70 (m, 2H, N-CH2CH2CH2), 5.55 (m, 2H,N-CH2CH2CH2), 4.28 (s, 1H, OH), 5.83 (t,
(t, J = 4.60 Hz, 1H, NHCO), 6.85 (d, 1H, J = 4.82 Hz, J = 4.60 Hz, 1H, NHCO), 7.12 (d, 1H, J = 4.89 Hz,
C5H of thiazole), 7.22 (d, 1H, J = 4.82 Hz, C4H of C5H of thiazole), 7.39 (d, 1H, J = 4.89 Hz, C4H of
thiazole), 7.67 (t, J = 5.10 Hz, 1H, NH), 7.75 (s, 1H, thiazole), 7.79 (t, J = 5.10 Hz, 1H, NH), 7.97 (s, 1H,
N=CH), 7.24–7.75 (m, 10H, Ar-H);13C NMR (δ): 22.9 N=CH), 7.25–8.06 (m, 4H, Ar-H); 13C NMR (δ):
(CH3), 35.2 (CH2CH2CH2), 42.3 (CH2CH2CH2-NH), 38.4 (CH2CH2CH2), 47.3 (CH2CH2CH2-NH), 52.1
46.5 (N-CH2CH2CH2), 105.2 (C5 of thiazole), 139.4 (N-CH2CH2CH2), 109.6 (C5 of thiazole), 140.2 (C4 of
(C4 of thiazole), 155.5 (N=CH), 160.2 (CO), 169.5 (C2 thiazole), 151.3 (N=CH), 164.1 (CO), 168.3 (C2 of

638
Pushkal Samadhiya et al.
thiazole), 112.7, 123.4, 124.3, 127.7, 131.5, 154.9 (6C, 2H, S-CH2), 5.49 (d, 1H, N-CH), 6.98 (d, 1H, J =
Ar); Mass (FAB): 304M+.
4.98 Hz, C5H of thiazole), 7.38 (d, 1H, J = 4.98 Hz,
C4H of thiazole), 6.72–7.86 (m, 4H, Ar-H); 13C NMR
(δ): 54 (CH2-S), 63.2 (N-CH), 113.5 (C5 of thiazole),
139.4 (C4 of thiazole), 173.6 (CO, cyclic), 171.3 (C2 of
thiazole), 126.4, 127.8, 128.5, 129.2, 130.5, 139 (6C,
Ar); Mass (FAB): 397M+.
3.4 Compounds 4(a–s)
3.4a N-3-[-{-(2-phenyl-4-oxo-1,3-thiazolidine}-car-
bamyl]-propyl-2-aminothiazole (4a): Yield: 62%; m.p.
75–77◦C; Anal. Calcd for C16H18N4O2S2: C, 53.01, H,
5.00, N, 15.45%; found C, 52.97, H, 4.95, N, 15.41%;
IR: 674 (C-S-C), 1329 (C-N), 1735 (CO cyclic), 2930
3.4e N-3-[-{2-(4-bromophenyl-4-oxo-1,3-thiazolidine}-
carbamyl]-propyl-2-aminothiazole (4e): Yield: 62%;
m.p. 80–82◦C; Anal. Calcd for C16H17N4O2S2Br: C,
43.54, H, 3.88, N, 12.69%; found C, 43.51, H, 3.82,
N, 12.66%; IR: 670 (C-S-C), 741 (C-Br), 1324 (C-
1
(S-CH2); H NMR: 3.49 (s, 2H, S-CH2), 5.32 (d, 1H,
N-CH), 6.96 (d, 1H, J = 4.90 Hz, C5H of thiazole), 7.35
(d, 1H, J = 4.90 Hz, C4H of thiazole), 6.74–7.69 (m,
4H, Ar-H); 13C NMR (δ): 52.6 (CH2-S), 63.5 (N-CH),
109.5 (C5 of thiazole), 140.1 (C4 of thiazole), 171.6
(CO, cyclic), 172 (C2 of thiazole), 125.4, 126.4, 127,
128.2, 130, 137.2 (6C, Ar); Mass (FAB): 362M+.
1
N), 1732 (CO cyclic), 2931 (S-CH2); H NMR: 3.59
(s, 2H, S-CH2), 5.41 (d, 1H, N-CH), 6.86 (d, 1H,
J = 4.89 Hz, C5H of thiazole), 7.41 (d, 1H, J = 4.89 Hz,
C4H of thiazole), 6.81–7.79 (m, 4H, Ar-H); 13C NMR
(δ): 52.4 (CH2-S), 65.1 (N-CH), 113.3 (C5 of thiazole),
138.2 (C4 of thiazole), 172.6 (CO, cyclic), 170.6 (C2 of
thiazole), 126.5, 127.9, 128.5, 129.4, 130.9, 139.2 (6C,
Ar); Mass (FAB): 441M+.
3.4b N-3-[-{2-(4-chlorophenyl)-4-oxo-1,3-thiazolidine-
carbamyl}-propyl-2-aminothiazole (4b): Yield: 63%;
m.p. 92–93◦C; Anal. Calcd for C16H17N4O2S2Cl: C,
48.41, H, 4.31, N, 14.11% found C, 48.39, H, 4.27,
N, 14.08%; IR: 671 (C-S-C), 743 (C–Cl), 1325 (C-N),
3.4f N-3-[-{2-(3-bromophenyl-4-oxo-1,3-thiazolidine}-
carbamyl]-propyl-2-aminothiazole (4f): Yield: 65%;
m.p. 87–88◦C; Anal. Calcd for C16H17N4O2S2Br: C,
43.54, H, 3.88, N, 12.69%; found C, 43.49, H, 3.81,
N, 12.67%; IR: 672 (C-S-C), 742 (C-Br), 1327 (C-N),
1738 (CO cyclic), 2981 (S-CH2); 1H NMR: 3.51 (s, 2H,
S-CH2), 5.45 (d, 1H, N-CH), 6.87 (d, 1H, J = 4.91 Hz,
C5H of thiazole), 7.37 (d, 1H, J = 4.91 Hz, C4H of
thiazole), 6.65–7.79 (m, 4H, Ar-H); 13C NMR (δ): 55.7
(CH2-S), 65.6 (N-CH), 113.4 (C5 of thiazole), 140.3
(C4 of thiazole), 172.4 (CO, cyclic), 169.5 (C2 of thia-
zole), 126.7, 127.5, 128, 128.7, 129.3, 138.5 (6C, Ar);
Mass (FAB): 441M+.
1
1736 (CO cyclic), 2933 (S-CH2); H NMR: 3.52 (s,
2H, S-CH2), 5.46 (d, 1H, N-CH), 6.96 (d, 1H, J =
4.91 Hz, C5H of thiazole), 7.41 (d, 1H, J = 4.91 Hz,
C4H of thiazole), 6.71–7.84 (m, 4H, Ar-H); 13C NMR
(δ): 53.5 (CH2-S), 64.3 (N-CH), 112.6 (C5 of thiazole),
138.1 (C4 of thiazole), 174 (CO, cyclic), 170.5 (C2 of
thiazole), 126.7, 127.5, 128.3, 129.4, 130.1, 138.6 (6C,
Ar); Mass (FAB): 397M+.
3.4c N-3-[-{2-(3-chlorophenyl)-4-oxo-1,3-thiazolidine-
carbamyl}-propyl-2-aminothiazole (4c): Yield: 62%;
m.p. 88–89◦C; Anal. Calcd for C16H17N4O2S2Cl: C,
48.41, H, 4.31, N, 14.11%; found C, 48.36, H, 4.25,
N, 14.10%; IR: 675 (C-S-C), 746 (C–Cl),1329 (C-
3.4g N-3-[-{2-(2-bromophenyl-4-oxo-1,3-thiazolidine}-
carbamyl]-propyl-2-aminothiazole (4g): Yield: 67%;
m.p. 89–91◦C, Anal. Calcd for C16H17N4O2S2Br: C,
43.54, H, 3.88, N, 12.69%; found C, 43.48, H, 3.84,
N, 12.66%; IR: 677 (C-S-C), 748 (C-Br), 1322 (C-N),
1
N), 1738 (CO cyclic), 2932 (S-CH2); H NMR: 3.51
(s, 2H, S-CH2), 5.42 (d, 1H, N-CH), 6.89 (d, 1H,
J = 4.95 Hz, C5H of thiazole), 7.38 (d, 1H, J = 4.95 Hz,
C4H of thiazole), 6.81–7.82 (m, 4H, Ar-H); 13C NMR
(δ): 55.6 (CH2-S), 63.2 (N-CH), 113.4 (C5 of thiazole),
139.4 (C4 of thiazole), 173.5 (CO, cyclic), 171 (C2 of
thiazole), 125.4, 126, 127.7, 128.6, 129.4, 137 (6C,
Ar); Mass (FAB): 397M+.
1
1740 (CO cyclic), 2937 (S-CH2); H NMR: 3.46 (s,
2H, S-CH2), 5.41 (d, 1H, N-CH), 6.87 (d, 1H, J =
4.88 Hz, C5H of thiazole), 7.35 (d, 1H, J = 4.88 Hz,
C4H of thiazole), 6.77–7.91 (m, 4H, Ar-H); 13C NMR
(δ): 54.5 (CH2-S), 63.3 (N-CH), 109.6 (C5 of thiazole),
3.4d N-3-[-{2-(2-chlorophenyl-4-oxo-1,3-thiazolidine}- 138.3 (C4 of thiazole), 170.2 (CO, cyclic), 169.6 (C2 of
carbamyl]-propyl-2-aminothiazole (4d): Yield: 68%; thiazole), 126.4, 127.2, 128.7, 129.1, 129.9, 137.6 (6C,
m.p. 85–86◦C; Anal. Calcd for C16H17N4O2S2Cl: C, Ar); Mass (FAB): 441M+.
48.41, H, 4.31, N, 14.11%; found C, 48.38, H, 4.28,
N, 14.05%; IR: 676 (C-S-C), 748 (C–Cl), 1325 (C-N), 3.4h N-3-[-{2-(4-nitrophenyl-4-oxo-1,3-thiazolidine}-
1
1735 (CO cyclic), 2936 (S-CH2); H NMR: 3.55 (s, carbamyl]-propyl-2-aminothiazole (4h): Yield: 66%;

Synthesis and biological importance of thiazolidines
639
m.p. 83–85◦C; Anal. Calcd for C16H17N5O4S2: C, (CO, cyclic), 171.2 (C2 of thiazole), 126, 127.5, 128,
47.16, H, 4.20, N, 17.18%; found C, 47.14, H, 4.12, 128.8, 129.6, 138 (6C, Ar); Mass (FAB): 392M+.
N, 17.15%; IR: 669 (C-S-C), 841 (C-NO), 1324 (C-
1
N), 1516 (NO2), 1736 (CO cyclic), 2928 (S-CH2); H
3.4l N-3-[-{2-(3-methoxyphenyl-4-oxo-1,3-thiazoli-
NMR: 3.44 (s, 2H, S-CH2), 5.38 (d, 1H, N-CH), 6.87
dine}-carbamyl]-propyl-2-aminothiazole (4l): Yield:
61%; m.p. 80–81◦C; Anal. Calcd for C17H18N4O3S2:
C, 52.04, H, 4.51, N, 14.28%; found C, 51.99, H, 4.46,
N, 14.23%; IR: 669 (C-S-C), 1331 (C-N), 1734 (CO
(d, 1H, J = 4.94 Hz, C5H of thiazole), 7.36 (d, 1H, J =
4.94 Hz, C4H of thiazole), 6.78–7.84 (m, 4H, Ar-H);
13C NMR (δ): 51.7 (CH2-S), 623.5 (N-CH), 113.3 (C5
of thiazole), 138.1 (C4 of thiazole), 170.7 (CO, cyclic),
169.2 (C2 of thiazole), 125.1, 126.4, 127.1, 128.7,
129.9, 137.4 (6C, Ar); Mass (FAB): 407M+.
1
cyclic), 2981 (S-CH2), 2961 (OCH3); H NMR: 3.32
(s, 2H, S-CH2), 3.58 (s, 2H, OCH3), 5.38 (d, 1H, N-
CH), 6.87 (d, 1H, J = 4.86 Hz, C5H of thiazole), 7.37
(d, 1H, J = 4.86 Hz, C4H of thiazole), 6.87–7.81 (m,
4H, Ar-H); 13C NMR (δ): 53 (CH2-S), 64.6 (N-CH),
112.5 (C5 of thiazole), 140.4 (C4 of thiazole), 169.7
(CO, cyclic), 170.1 (C2 of thiazole), 125.1, 127.2,
128.7, 129.2, 130.6, 137.2 (6C, Ar); Mass (FAB):
392M+.
3.4i N-3-[-{2-(3-nitrophenyl-4-oxo-1,3-thiazolidine}-
carbamyl]-propyl-2-aminothiazole (4i): Yield: 62%;
m.p. 87-89◦C; Anal. Calcd for C16H17N5O4S2: C,
47.16, H, 4.20, N, 17.18%; found C, 47.14, H, 4.11,
N, 17.16%; IR: 679 (C-S-C), 866 (C-NO),1325 (C-N),
1
1529 (NO2), 1732 (CO cyclic), 2927 (S-CH2); H
NMR: 3.41 (s, 2H, S-CH2), 5.36 (d, 1H, N-CH), 6.85
(d, 1H, J = 4.92 Hz, C5H of thiazole), 7.39 (d, 1H, J =
4.92 Hz, C4H of thiazole), 6.68–7.77 (m, 4H, Ar-H);
13C NMR (δ): 55.7 (CH2-S), 62 (N-CH), 110.7 (C5 of
thiazole), 139.8 (C4 of thiazole), 169.8 (CO, cyclic),
168.5 (C2 of thiazole), 126.5, 127.8, 128.6, 129.6,
130.5, 139.5 (6C, Ar); Mass (FAB): 407 M+.
3.4m N-3-[-{2-(2-methoxyphenyl-4-oxo-1,3-thiazoli-
dine}-carbamyl]-propyl-2-aminothiazole (4m): Yield:
62%; m.p. 77–78◦C; Anal. Calcd for C17H18N4O3S2:
C, 52.04, H, 4.51, N, 14.28%; found C, 52.02, H, 4.44,
N, 14.21%; IR: 676 (C-S-C), 1328 (C-N), 1736 (CO
1
cyclic), 2939 (S-CH2), 2959 (OCH3); H NMR: 3.38
(s, 2H, S-CH2), 3.54 (s, 2H, OCH3), 5.38 (d, 1H, N-
CH), 6.85 (d, 1H, J = 4.89 Hz, C5H of thiazole), 7.39
(d, 1H, J = 4.89 Hz, C4H of thiazole), 6.78–7.84 (m,
4H, Ar-H); 13C NMR (δ): 53.4 (CH2-S), 62.7 (N-CH),
110.6 (C5 of thiazole), 139 (C4 of thiazole), 169.2 (CO,
cyclic), 171.2 (C2 of thiazole), 126, 127, 128.5, 129.6,
130, 131.5, 139.4 (6C, Ar); Mass (FAB): 392M+.
3.4j N-3-[-{2-(2-nitrophenyl-4-oxo-1,3-thiazolidine}-
carbamyl]-propyl-2-aminothiazole (4j): Yield: 63%;
m.p. 80-81◦C; Anal. Calcd for C16H17N5O4S2: C,
47.16, H, 4.20, N, 17.18%; found C, 47.12, H, 4.14,
N, 17.13%; IR: 677 (C-S-C), 842 (C-NO),1325 (C-
1
N), 1532 (NO2),1735 (CO cyclic), 2927 (S-CH2); H
NMR: 3.38 (s, 2H, S-CH2), 5.31 (d, 1H, N-CH), 6.86
(d, 1H, J = 4.98 Hz, C5H of thiazole), 7.34 (d, 1H, J =
4.98 Hz, C4H of thiazole), 6.82–7.68 (m, 4H, Ar-H);
13C NMR (δ): 53.4 (CH2-S), 62.6 (N-CH), 110.7 (C5
of thiazole), 138.5 (C4 of thiazole), 169.7 (CO, cyclic),
170.2 (C2 of thiazole), 126.1, 127.2, 128.2, 128.6, 129,
138.2 (6C, Ar); Mass (FAB): 407M+.
3.4n N-3-[-{2-(4-methylphenyl-4-oxo-1,3-thiazoli-
dine}-carbamyl]-propyl-2-aminothiazole (4n): Yield:
64%; m.p. 174–175◦C; Anal. Calcd for C17H20N4O2S2:
C, 54.25, H, 5.31, N, 14.89%; found C, 54.21, H, 5.29,
N, 14.86%; IR: 672 (C-S-C), 1327 (C-N), 1738 (CO
1
cyclic), 2981 (S-CH2), 2976 (CH3); H NMR: 2.85
(s, 3H, CH3), 3.34 (s, 2H, S-CH2), 5.28 (d, 1H, N-
CH), 6.89 (d, 1H, J = 4.83 Hz, C5H of thiazole),
7.35 (d, 1H, J = 4.83 Hz, C4H of thiazole), 6.79–7.81
(m, 4H, Ar-H); 13C NMR (δ): 25.6 (CH3), 53.2 (CH2-
S), 63.6 (N-CH), 111.7 (C5 of thiazole), 138.1 (C4 of
thiazole), 169.2 (CO, cyclic), 167.4 (C2 of thiazole),
124, 125.2, 127.4, 129.4, 130.4, 131.2, 137.4 (6C, Ar);
Mass (FAB): 376M+.
3.4k N-3-[-{2-(4-methoxyphenyl-4-oxo-1,3-thiazoli-
dine}-carbamyl]-propyl-2-aminothiazole (4k): Yield:
65%; m.p. 78-79◦C; Anal. Calcd for C17H18N4O3S2:
C, 52.04, H, 4.51, N, 14.28%; found C, 52.01, H,
4.48, N, 14.25%; IR: 670 (C-S-C), 1324 (C-N), 1736
1
(CO cyclic), 2928 (S-CH2), 2968 (OCH3); H NMR:
3.38 (s, 2H, S-CH2), 3.67 (s, 3H, OCH3), 5.38 (d, 1H,
N-CH), 6.85 (d, 1H, J = 4.82 Hz, C5H of thiazole),
7.35 (d, 1H, J = 4.82 Hz, C4H of thiazole), 6.89–7.87
(m, 4H, Ar-H); 13C NMR (δ): 54 (CH2-S), 62 (N-CH),
110.7 (C5 of thiazole), 138.4 (C4 of thiazole), 168.7
3.4o N-3-[-{2-(3-methylphenyl-4-oxo-1,3-thiazoli-
dine}-carbamyl]-propyl-2-aminothiazole (4o): Yield:
63%; m.p. 67–68◦C; Anal. Calcd for C17H20N4O2S2:
C, 54.25, H, 5.31, N, 14.89%; found C, 54.19, H, 5.26,

640
Pushkal Samadhiya et al.
N, 14.85%; IR: 667 (C-S-C), 1324 (C-N), 1739 (CO 167 (C2 of thiazole), 124, 125.4, 126.2, 128.6, 130, 139
1
cyclic), 2924 (S-CH2), 2968 (CH3); H NMR: 2.78 (6C, Ar); Mass (FAB): 378M+.
(CH3), 3.32 (s, 2H, S-CH2), 5.25 (d, 1H, N-CH), 6.82
(d, 1H, J = 4.84 Hz, C5H of thiazole), 7.38 (d, 1H, J =
3.4s N-3-[-{2-(2-hydroxyphenyl-4-oxo-1,3-thiazoli-
4.84 Hz, C4H of thiazole), 6.75–7.69 (m, 4H, Ar-H);
dine}-carbamyl]-propyl-2-aminothiazole (4s): Yield:
13C NMR (δ): 25.3(CH3), 52.2 (CH2-S), 60.4 (N-CH),
61%; m.p. 80–81◦C; Anal. Calcd for C16H18N4O3S2:
108.2 (C5 of thiazole), 136.4 (C4 of thiazole), 168.7
C, 50.79, H, 4.76, N, 14.81%; found C, 50.72, H, 4.71,
(CO, cyclic), 169.1 (C2 of thiazole), 124.6, 126.8,
N, 14.75%; IR: 667 (C-S-C), 1322 (C-N), 1733 (CO
127.9, 129.4, 130.8, 132.5, 140.2 (6C, Ar); Mass
1
cyclic), 2928 (S-CH2), 3456 (OH); H NMR: 3.29
(FAB): 376M+.
(s, 2H, S-CH2), 4.78 (s, 1H, OH), 5.15 (d, 1H, N-CH),
6.83 (d, 1H, J = 4.90 Hz, C5H of thiazole), 7.27 (d, 1H,
J = 4.90 Hz, C4H of thiazole), 6.71–7.64 (m, 4H, Ar-
3.4p N-3-[-{2-(2-methylphenyl-4-oxo-1,3-thiazoli-
H); 13C NMR (δ): 50.5 (CH2-S), 59.2 (N-CH), 107.4
dine}-carbamyl]-propyl-2-aminothiazole (4p): Yield:
(C5 of thiazole), 136.1 (C4 of thiazole), 168.1 (CO,
62%; m.p. 70–72◦C; Anal. Calcd for C17H20N4O2S2:
cyclic), 166 (C2 of thiazole), 124.6, 126.7, 128.5, 129.3,
C, 54.25, H, 5.31, N, 14.89%; found C, 54.18, H, 5.22,
131.2, 137 (6C, Ar); Mass (FAB): 378M+.
N, 14.81%; IR: 669 (C-S-C), 1324 (C-N), 1733 (CO
1
cyclic), 2922 (S-CH2),2956 (CH3); H NMR: 2.68
(CH3), 3.21 (s, 2H, S-CH2), 5.18 (d, 1H, N-CH), 6.89
(d, 1H, J = 4.87 Hz, C5H of thiazole), 7.31 (d, 1H, J =
4.87 Hz, C4H of thiazole), 6.76–7.68 (m, 4H, Ar-H);
13C NMR (δ): 25.8 (CH3), 52.7 (CH2-S), 63.4 (N-CH),
112.7 (C5 of thiazole), 140.1 (C4 of thiazole), 168.2
(CO, cyclic), 171 (C2 of thiazole), 124.5, 125.8, 127.9,
128.6, 129, 137.8 (6C, Ar); Mass (FAB): 376M+.
3.5 Compounds 5(a–s)
3.5a N-3-[-{2-phenyl-4-oxo-5-benylidene-1,3-thiazoli-
dine}-carbamyl]-propyl-2-aminothiazole (5a): Yield:
64%; m.p. 71–73◦C; Anal. Calcd for C23H22N4O2S2: C,
61.30, H, 4.92, N, 12.43%; found C, 61.27, H, 4.85, N,
1
12.39%; IR: 1608 (C=CH), 2968 (C=CH); H NMR:
6.40 (s, 1H, C=CH), 6.91 (d, 1H, J = 4.88 Hz, C5H of
thiazole), 7.27 (d, 1H, J = 4.88 Hz, C4H of thiazole),
6.71–7.92 (m, 10H, Ar-H); 13C NMR (δ): 110.4 (C5 of
thiazole), 138.4 (C4 of thiazole), 143.2 (C=CH), 146.2
(C=CH), 169.2 (C2 of thiazole), 124.8, 125.3, 126.1,
126.8, 127.2, 127.6, 128.2, 128.6, 129, 130.4, 137.6,
138.2 (12C, Ar); Mass (FAB): 490M+.
3.4q N-3-[-{2-(4-hydroxyphenyl-4-oxo-1,3-thiazoli-
dine}-carbamyl]-propyl-2-aminothiazole (4q): Yield:
66%; m.p. 79–81◦C; Anal. Calcd for C16H18N4O3S2:
C, 50.79, H, 4.76, N, 14.81%; found C, 50.77, H, 4.74,
N, 14.79%; IR: 668 (C-S-C), 1324 (C-N), 1732 (CO
1
cyclic), 2925 (S-CH2), 3482 (OH); H NMR: 3.35 (s,
2H, S-CH2), 4.92 (s, 1H, OH), 5.27 (d, 1H, N-CH),
6.82 (d, 1H, J = 4.91 Hz, C5H of thiazole), 7.35 (d,
1H, J = 4.91 Hz, C4H of thiazole), 6.77–7.71 (m,
4H, Ar-H); 13C NMR (δ): 53.2 (CH2-S), 63.4 (N-CH),
110.5 (C5 of thiazole), 138.4 (C4 of thiazole), 169.7
(CO, cyclic), 168 (C2 of thiazole), 124.4, 125.2, 127.2,
128.6, 129.6, 137.8 (6C, Ar); Mass (FAB) : 378M+.
3.5b N-3-[-{2-(4-chorophenyl)-4-oxo-5-(4-chloroben-
zylidene)-1,3-thiazolidine}-carbamyl]-propyl-2-amino-
thiazole (5b): Yield: 62%; m.p. 89–91◦C; Anal. Calcd
for C23H20N4O2S2Cl2: C, 53.17, H, 3.88, N, 10.78%;
found C, 53.12, H, 3.81, N, 10.74%; IR: 769 (C–Cl),
1
1615 (C=CH), 2981 (C=CH); H NMR: 6.45 (s, 1H,
C=CH), 6.92 (d, 1H, J = 4.81 Hz, C5H of thiazole),
7.32 (d, 1H, J = 4.81 Hz, C4H of thiazole), 6.85–7.72
(m, 8H, Ar-H); 13C NMR (δ): 110.2 (C5 of thiazole),
139.4 (C4 of thiazole), 143.1 (C=CH), 146.5 (C=CH),
170 (C2 of thiazole), 125.1, 126.3, 126.7, 127, 127.8,
128, 128.9, 129, 130.5, 131.2, 138.4, 139.2 (12C, Ar);
Mass (FAB): 519M+.
3.4r N-3-[-{2-(3-hydroxyphenyl-4-oxo-1,3-thiazoli-
dine}-carbamyl]-propyl-2-aminothiazole (4r): Yield:
63%; m.p. 85–87◦C; Anal. Calcd for C16H18N4O3S2:
C, 50.79, H, 4.76, N, 14.81%; found C, 50.75, H, 4.72,
N, 14.73%; IR: 668 (C-S-C), 1325 (C-N), 1733 (CO
1
cyclic), 2988 (S-CH2), 3477 (OH); H NMR: 3.31 (s,
2H, S-CH2), 4.94 (s, 1H, OH), 5.18 (d, 1H, N-CH), 6.85
(d, 1H, J = 4.94 Hz, C5H of thiazole), 7.22 (d, 1H, J =
4.94 Hz, C4H of thiazole), 6.75–7.68 (m, 4H, Ar-H);
13C NMR (δ): 51.4 (CH2-S), 60.2 (N-CH), 108.2 (C5
of thiazole), 137.4 (C4 of thiazole), 168.1 (CO, cyclic),
3.5c N-3-[-{-5-(3-chlorobenzylidene)-2-(3-chloro-
phenyl)-4-oxo-1,3-thiazolidine}-carbamyl]-propyl-2-
aminothiazole (5c): Yield: 61%; m.p. 84–85◦C; Anal.
Calcd for C23H20N4O2S2Cl2: C, 53.17, H, 3.88, N,

Synthesis and biological importance of thiazolidines
641
10.78%; found C, 53.14, H, 3.78, N, 10.73%; IR: 775 127.5, 128.2, 128.7, 131, 132.5, 138.4, 140.2 (12C,
1
(C–Cl), 1625 (C=CH), 2983 (C=CH); H NMR: 6.49 Ar); Mass (FAB): 608M+.
(s, 1H, C=CH), 7.02 (d, 1H, J = 4.85 Hz, C5H of
thiazole), 7.36 (d, 1H, J = 4.85 Hz, C4H of thiazole),
3.5g N-3-[-{2-(2-bromophenyl-4-oxo-5-(2-bromoben-
6.71–7.63 (m, 8H, Ar-H); 13C NMR (δ): 51.7 (CH2-
S), 63.6 (N-CH), 109.7 (C5 of thiazole), 140.1 (C4 of
zylidene)-1,3-thiazolidine}-carbamyl]-propyl-2-amino-
thiazole (5g): Yield: 65%; m.p. 80–81◦C; Anal. Calcd
thiazole), 144.6 (C=CH), 148.3 (C=CH), 172 (C2 of
for C23H20N4O2S2Br2: C, 45.40, H, 3.31, N, 9.20%;
thiazole), 123.2, 124.5, 125.4, 125.8, 126, 126.7, 127.3,
found C, 45.31, H, 3.26, N, 9.16%; IR: 639 (C-Br),
1
128.5, 129, 129.8, 138.2, 139.7 (12C, Ar); Mass (FAB)
1620 (C=CH), 2989 (C=CH); H NMR: 6.50 (s, 1H,
519M+.
C=CH), 6.98 (d, 1H, J = 4.85 Hz, C5H of thiazole),
7.37 (d, 1H, J = 4.85 Hz, C4H of thiazole), 6.79–7.75
(m, 8H, Ar-H); 13C NMR (δ): 113.5 (C5 of thiazole),
3.5d N-3-[-{2-(2-chlorophenyl-4-oxo-5-(2-chloroben-
142.3 (C4 of thiazole), 144.1 (C=CH), 147.3 (C=CH),
zylidene)-1,3-thiazolidine}-carbamyl]-propyl-2-amino-
173 (C2 of thiazole), 122.3, 124.3, 125.3, 126.6, 127.4,
128.6, 129.3, 130.4, 131.7, 132.2, 137.5, 138 (12C,
thiazole (5d): Yield: 63%; m.p. 81–82◦C; Anal. Calcd
for C23H20N4O2S2Cl2: C, 53.17, H, 3.88, N, 10.78%;
Ar); Mass (FAB): 608M+.
found C, 53.11, H, 3.82, N, 10.76%; IR: 762 (C–Cl),
1
1618 (C=CH), 2983 (C=CH); H NMR: 6.47 (s, 1H,
3.5h N-3-[-{2-(4-nitrophenyl)-4-oxo-5-(4-nitroben-
C=CH), 6.97 (d, 1H, J = 4.80 Hz, C5H of thiazole),
zylidene)-1,3-thiazolidine}-carbamyl]-propyl-2-amino-
7.36 (d, 1H, J = 4.80 Hz, C4H of thiazole), 6.71–7.63
(m, 8H, Ar-H); 13C NMR (δ): 107.9 (C5 of thiazole),
136.2 (C4 of thiazole), 144.6 (C=CH), 143.2 (C=CH),
172 (C2 of thiazole), 124.2, 125.6, 126.3, 127, 127.8,
128.4, 128.6, 130, 130.8, 131.2, 138.6, 140.1 (12C, Ar);
Mass (FAB): 519M+.
thiazole (5h): Yield: 61%; m.p. 77–79◦C; Anal. Calcd
for C23H20N6O6S2: C, 51.10, H, 3.72, N, 15.54%;
found C, 51.07, H, 3.69, N, 15.51%; IR: 852 (C-NO),
1
1522 (NO2), 1622 (C=CH), 2990 (C=CH); H NMR:
6.52 (s, 1H, C=CH), 7.06 (d, 1H, J = 4.92 Hz, C5H
of thiazole), 7.42 (d, 1H, J = 4.92 Hz, C4H of thia-
zole), 6.89–7.81 (m, 8H, Ar-H); 13C NMR (δ): 57.4
(CH2-S), 64 (N-CH), 111.6 (C5 of thiazole), 141.2 (C4
of thiazole), 145.3 (C=CH), 147.3 (C=CH), 172 (C2
of thiazole), 122.7, 123.5, 125.3, 126, 126.8, 127.2,
127.9, 128.7, 129.3, 130.6, 137.4, 138.4 (12C, Ar);
Mass (FAB): 540M+.
3.5e N-3-[-{2-(4-bromophenyl-4-oxo-5-(4-bromoben-
zylidene)-1,3-thiazolidine}-carbamyl]-propyl-2-amino-
thiazole (5e): Yield: 62%; m.p. 78–79◦C; Anal. Calcd
for C23H20N4O2S2Br2: C, 45.40, H, 3.31, N, 9.20%;
found C, 45.33, H, 3.25, N, 9.18%; IR: 635 (C-Br),
1
1627 (C=CH), 2986 (C=CH); H NMR: 6.43 (s, 1H,
C=CH), 6.90 (d, 1H, J = 4.89 Hz, C5H of thiazole),
7.31 (d, 1H, J = 4.89 Hz, C4H of thiazole), 6.80–7.77
(m, 8H, Ar-H); 13C NMR (δ): 110.9 (C5 of thiazole),
138.1 (C4 of thiazole), 144.3 (C=CH), 146.8 (C=CH),
170 (C2 of thiazole), 120.4, 121.3, 124.7, 125.3, 126.8,
127.2, 127.7, 128.3, 130.2, 131, 137.4, 139.1 (12C,
Ar); Mass (FAB) 608M+.
3.5i N-3-[-{2-(3-nitrophenyl-4-oxo-5-(3-nitrobenzyl-
idene)-1,3-thiazolidine}-carbamyl]-propyl-2-aminothi-
azole (5i): Yield: 65%; m.p. 75–76◦C; Anal. Calcd
for C23H20N6O6S2: C, 51.10, H, 3.72, N, 15.54%;
found C, 51.08, H, 3.66, N, 15.49%; IR: 859 (C-NO),
1
1518 (NO2), 1628 (C=CH), 2985 (C=CH); H NMR:
6.51 (s, 1H, C=CH), 7.03 (d, 1H, J = 4.94 Hz, C5H
of thiazole), 7.41 (d, 1H, J = 4.94 Hz, C4H of thi-
azole), 6.87–7.86 (m, 8H, Ar-H); 13C NMR (δ): 56
(CH2-S), 63.2 (N-CH), 112 (C5 of thiazole), 140.2 (C4
of thiazole), 144.3 (C=CH), 147.2 (C=CH), 173 (C2
of thiazole), 120.7, 122.4, 123.3, 125.1, 125.9, 127.8,
128.9, 129.4, 131.3, 132.2, 135.4, 136.2 (12C, Ar);
Mass (FAB) 540M+.
3.5f N-3-[-{2-(3-bromophenyl-4-oxo-5-(3-bromoben-
zylidene)-1,3-thiazolidine}-carbamyl]-propyl-2-amino-
thiazole (5f): Yield: 66%; m.p. 79–81◦C; Anal. Calcd
for C23H20N4O2S2Br2: C, 45.40, H, 3.31, N, 9.20%;
found C, 45.34, H, 3.24, N, 9.15%; IR: 641 (C-Br),
1
1624 (C=CH), 2987 (C=CH); H NMR: 6.49 (s, 1H,
C=CH), 6.98 (d, 1H, J = 4.87 Hz, C5H of thiazole),
7.37 (d, 1H, J = 4.87 Hz, C4H of thiazole), 6.78–7.79
(m, 8H, Ar-H); 13C NMR (δ): 113.1 (C5 of thiazole),
140.4 (C4 of thiazole), 142.1 (C=CH), 147 (C=CH),
173 (C2 of thiazole), 121.7, 123.4, 125.4, 126.3, 127.1,
3.5j N-3-[-{2-(2-nitrophenyl-4-oxo-5-(2-nitrobenzyl-
idene)-1,3-thiazolidine}-carbamyl]-propyl-2-aminothi-
azole (5j): Yield: 62%; m.p. 81–82◦C; Anal. Calcd
for C23H20N6O6S2: C, 51.10, H, 3.72, N, 15.54%;

642
Pushkal Samadhiya et al.
found C, 51.04, H, 3.64, N, 15.46%; IR: 863 (C-NO), 118.6, 120.5, 121.3, 124.1, 126.3, 127, 128.4, 129.3,
1
1526 (NO2), 1625 (C=CH), 2988 (C=CH); H NMR: 136, 155.3, 157.2 (12C, Ar); Mass (FAB) 511M+.
6.49 (s, 1H, C=CH), 6.98 (d, 1H, J = 4.93 Hz, C5H
of thiazole), 7.37 (d, 1H, J = 4.93 Hz, C4H of thia-
3.5n N-3-[-{2-(4-methylphenyl-4-oxo-5-(4-methyl-
zole), 6.88–7.81 (m, 8H, Ar-H); 13C NMR (δ): 56.1
(CH2-S), 63.2 (N-CH), 112.6 (C5 of thiazole), 141.2
benzylidene)-1,3-thiazolidine}-carbamyl]-propyl-2-
aminothiazole (5n): Yield: 62%; m.p. 69–71◦C;
(C4 of thiazole), 145 (C=CH), 147.3 (C=CH), 172 (C2
Anal. Calcd for C25H26N4O2S2: C, 62.76, H, 5.43, N,
of thiazole), 123.3, 124.6, 125.6, 126, 126.8, 127.2,
11.71%; found C, 62.72, H, 5.41, N, 11.68 IR: 1588
1
128.4, 128.7, 129.4, 132.5, 137, 139.7 (12C, Ar); Mass
(C=CH), 2979 (C=CH) 1341 (CH3); H NMR: 2.81
(FAB): 540M+.
(s, 3H, CH3) 6.42 (s, 1H, C=CH), 6.93 (d, 1H, J =
4.87 Hz, C5H of thiazole), 7.36 (d, 1H, J = 4.87 Hz,
C4H of thiazole), 6.79–7.67 (m, 8H, Ar-H); 13C NMR
3.5k N-3-[-{2-(4-methoxyphenyl-4-oxo-5-(4-methoxy-
(δ): 107.5 (C5 of thiazole), 137.1 (C4 of thiazole), 140.5
benzylidene)-1,3-thiazolidine}-carbamyl]-propyl-2-ami-
nothiazole (5k): Yield: 65%; m.p. 74–76◦C; Anal.
Calcd for C25H26N4O4S2: C, 58.82, H, 5.09, N, 10.98%;
found C, 58.77, H, 5.06, N, 10.95%; IR: 1596 (C=CH),
(C=CH), 144.2 (C=CH), 171 (C2 of thiazole), 122.9,
124.3, 125.2, 126.2, 127.4, 128.6, 129.6, 130, 133.8,
134.6, 135.2, 137.6 (12C, Ar); Mass (FAB) 479M+.
1
2985 (C=CH), 2970 (OCH3); H NMR: 3.63 (s, 3H,
3.5o N-3-[-{2-(3-methylphenyl-4-oxo-5-(3-methyl-
benzylidene)-1,3-thiazolidine}-carbamyl]-propyl-2-
aminothiazole (5o): Yield: 65%; m.p. 61–63◦C; Anal.
Calcd for C25H26N4O2S2: C, 62.76, H, 5.43, N, 11.71%;
found C, 62.73, H, 5.39, N, 11.65%; IR: 1592 (C=CH),
OCH3), 6.47 (s, 1H, C=CH), 6.98 (d, 1H, J = 4.88 Hz,
C5H of thiazole), 7.38 (d, 1H, J = 4.88 Hz, C4H of
thiazole), 6.82–7.78 (m, 8H, Ar-H); 13C NMR (δ): 51.6
(CH2-S), 63.2 (N-CH), 109.6 (C5 of thiazole), 138.1
(C4 of thiazole), 142.1 (C=CH), 146.5 (C=CH), 170
(C2 of thiazole), 110.7, 112.4, 113.2, 114.5, 124.5,
125.9, 127, 128.6, 129, 138.1, 154.8, 157.3 (12C, Ar);
Mass (FAB) 511M+.
1
2977 (C=CH), 1325 (CH3); H NMR: 2.86 (s, 3H,
CH3), 6.38 (s, 1H, C=CH), 6.91 (d, 1H, J = 4.86 Hz,
C5H of thiazole), 7.30 (d, 1H, J = 4.86 Hz, C4H of
thiazole), 6.80–7.71 (m, 8H, Ar-H); 13C NMR (δ): 52.5
(CH2-S), 62 (N-CH), 110.7 (C5 of thiazole), 138.1 (C4
of thiazole), 142.4 (C=CH), 144.3 (C=CH), 168 (C2
of thiazole), 122.4, 124.5, 125.6, 126.5, 127.6, 128.2,
128.7, 130.4, 131, 132.8, 135.9, 137.2 (12C, Ar); Mass
(FAB) 479M+.
3.5l N-3-[-{2-(3-methoxyphenyl-4-oxo-5-(3-methoxy-
benzylidene)-1,3-thiazolidine}-carbamyl]-propyl-2-
aminothiazole (5l): Yield: 60%; m.p. 75–76◦C; Anal.
Calcd for C25H26N4O4S2: C, 58.82, H, 5.09, N, 10.98%;
found C, 58.76, H, 5.04, N, 10.93%; IR: 1592 (C=CH),
1
2982 (C=CH), 2977 (OCH3); H NMR: 3.67 (s, 3H,
3.5p N-3-[-{2-(2-methylphenyl-4-oxo-5-(2-methyl-
benzylidene)-1,3-thiazolidine}-carbamyl]-propyl-2-
aminothiazole (5p): Yield: 63%; m.p. 65–66◦C; Anal.
Calcd for C25H26N4O2S2: C, 62.76, H, 5.43, N, 11.71%;
found C, 62.69, H, 5.38, N, 11.66%; IR: 1590 (C=CH),
OCH3), 6.40 (s, 1H, C=CH), 6.96 (d, 1H, J = 4.91 Hz,
C5H of thiazole), 7.38 (d, 1H, J = 4.91 Hz, C4H of thi-
azole), 6.87–7.79 (m, 8H, Ar-H); 13C NMR (δ): 110.7
(C5 of thiazole), 138.1 (C4 of thiazole), 142.5 (C=CH),
144.7 (C=CH), 168.6 (C2 of thiazole), 114.2, 116.3,
118.4, 120.3, 122.5, 123.6, 125.4, 127.4, 128, 136.6,
158.1, 160.2 (12C, Ar); Mass (FAB) 511M+.
1
2980 (C=CH), 1338 (CH3); H NMR: 2.79 (s, 3H,
CH3) 6.41 (s, 1H, C=CH), 6.88 (d, 1H, J = 4.90 Hz,
C5H of thiazole), 7.35 (d, 1H, J = 4.90 Hz, C4H of thi-
azole), 6.81–7.75 (m, 8H, Ar-H); 13C NMR (δ): 109.2
(C5 of thiazole), 135.4 (C4 of thiazole), 140.5 (C=CH),
145.4 (C=CH), 170 (C2 of thiazole), 123.5, 124.6,
125.3, 126.4, 127.6, 128, 128.7, 129.6, 132.5,135.8,
136, 139.1 (12C, Ar); Mass (FAB) 479M+.
3.5m N-3-[-{2-(2-methoxyphenyl-4-oxo-5-(2-methoxy-
benzylidene)-1,3-thiazolidine}-carbamyl]-propyl-2-
aminothiazole (5m): Yield: 61%; m.p. 72–73◦C;
Anal. Calcd for C25H26N4O4S2: C, 58.82, H, 5.09, N,
10.98%; found C, 58.71, H, 5.01, N, 10.94%; IR: 1597
(C=CH), 2983 (C=CH) 2969 (OCH3); 1H NMR: 3.61
(s, 3H, OCH3), 6.47 (s, 1H, C=CH), 6.93 (d, 1H, J = 3.5q N-3-[-{2-(4-hydroxyphenyl-4-oxo-5-(4-hydro-
4.96 Hz, C5H of thiazole), 7.33 (d, 1H, J = 4.96 Hz, xybenzylidene)-1,3-thiazolidine}-carbamyl]-propyl-2-
C4H of thiazole), 6.82–7.77 (m, 8H, Ar-H); 13C NMR aminothiazole (5q): Yield: 65%; m.p. 79–81◦C; Anal.
(δ):, 109.4 (C5 of thiazole), 139 (C4 of thiazole), 142.6 Calcd for C23H22N4O4S2: C, 57.26, H, 4.56, N, 11.61%;
(C=CH), 147.4 (C=CH), 171 (C2 of thiazole), 115.3, found C, 57.22, H, 4.54, N, 11.57%; IR: 1625 (C=CH),

Synthesis and biological importance of thiazolidines
643
2978 (C=CH), 3612 (OH); 1H NMR: 4.82 (s, 1H, OH), been disappeared. This is clearly indicated that com-
6.34 (s, 1H, C=CH), 6.89 (d, 1H, J = 4.92 Hz, C5H of pound 1 gives the substitution reaction with urea. This
thiazole), 7.36 (d, 1H, J = 4.92 Hz, C4H of thiazole), was also supported by 1H and 13C NMR spectra because
6.71–7.62 (m, 8H, Ar-H); 13C NMR (δ): 108.6 (C5 of two signals appeared in the 1H NMR spectrum for NH
thiazole), 136.2 (C4 of thiazole), 139.3 (C=CH), 143.4 and NH2 at δ 5.63 and 5.96 ppm respectively. The for-
(C=CH), 169 (C2 of thiazole), 116.5, 120.3, 122.8, mation of the compound 2 was fully supported by a CO
123.2, 124.2, 126.8, 127.6, 128.7, 130.5, 137, 155.6, group gives a signal at δ 163.8 ppm in the 13C NMR
157.4 (12C, Ar); Mass (FAB) 581M+.
spectrum. All these are strong evidences for the synthe-
sis of compound 2. Substituted benzaldehydes give the
condensation reaction with compound 2 resultant the
production of Schiff bases N=CH took placed which
3.5r N-3-[-{2-(3-hydroxyphenyl-4-oxo-5-(3-hydroxy-
benzylidene)-1,3-thiazolidine}-carbamyl]-propyl-2-
aminothiazole (5r): Yield: 61%; m.p. 73–74◦C; Anal.
Calcd for C23H22N4O4S2: C, 57.26, H, 4.56, N, 11.61%;
found C, 57.22, H, 4.51, N, 11.54%; IR: 1624 (C=CH),
2979 (C=CH), 3626 (OH); 1H NMR: 4.91 (s, 1H, OH),
6.38 (s, 1H, C=CH), 6.86 (d, 1H, J = 4.85 Hz, C5H of
thiazole), 7.37 (d, 1H, J = 4.85 Hz, C4H of thiazole),
6.76–7.69 (m, 8H, Ar-H); 13C NMR (δ): 108.4 (C5 of
thiazole), 137.1 (C4 of thiazole), 141.3 (C=CH), 143.3
(C=CH), 168.5 (C2 of thiazole), 117.2, 118.5, 122,
123.7, 124.2, 125, 12.6, 127.1, 130, 136.5, 154.6, 156.9
(12C, Ar); Mass (FAB) 581M+.
1
was confirmed by IR, H NMR and 13C NMR spec-
tra of compound 3(a–s). In the IR spectra an absorp-
tion found in the range of 1552–1589 cm−1 while a
strong signal appeared in the range of δ 7.78–8.24 and
1
δ 145–155.4 ppm in the H NMR and 13C NMR spec-
tra of compound 3(a–s) respectively. The facts also sup-
ported by the disappearance of the signal of NH2 in
the 1H NMR spectra. The compound 3(a–s) on reaction
with equimolar amount of thioglycolic acid in the pres-
ence of ZnCl2 (act as a catalyst) in the trace amount
gives the cycloaddition reaction and produced a five-
membered thiazolidinone ring, 4(a–s). The compound
4(a–s) showed a characteristic absorption of the cyclic
carbonyl group in the range of 1736–1758 cm−1 in the
3.5s N-3-[-{2-(2-hydroxyphenyl-4-oxo-5-(2-hydroxy-
benzylidene)-1,3-thiazolidine}-carbamyl]-propyl-2-
aminothiazole (5s): Yield: 62%; m.p. 75–76◦C; Anal.
Calcd for C23H22N4O4S2: C, 57.26, H, 4.56, N, 11.61%;
found C, 57.20, H, 4.51, N, 11.52%; IR: 1632 (C=CH),
2977 (C=CH), 3618 (OH); 1H NMR: 4.87 (s, 1H, OH),
6.35 (s, 1H, C=CH), 6.86 (d, 1H, J = 4.80 Hz, C5H of
thiazole), 7.25 (d, 1H, J = 4.80 Hz, C4H of thiazole),
6.69–7.65 (m, 8H, Ar-H); 13C NMR (δ): 107.6 (C5 of
thiazole), 132.1 (C4 of thiazole), 139.3 (C=CH), 140.2
(C=CH), 165 (C2 of thiazole), 120.4, 122.7, 123.4,
124.1, 125.7, 126.6, 127.6, 128.4, 129.2, 137.7, 153.9,
155.2 (12C, Ar); Mass (FAB) 581M+.
1
IR spectra. The H NMR spectra drawn attention and
clearly indicate the presence of the active methylene
group in the thiazolidine ring in the range of δ 3.26–
3.49 ppm. The 13C NMR spectra of compound 4(a–s)
also supported the fact that cyclic carbonyl group
present and a signal appeared in the range of δ 165.4–
175.2 ppm. These were supported by two evidences that
are; (i) disappearance of N=CH proton and (ii) appear-
ance of N–CH proton in the range of δ 5.23–5.47 ppm
1
in the H NMR spectra of compound 4(a–s). Com-
pound 4(a–s) underwent the Knoevenagel condensation
reaction with substituted benzaldehydes in the pres-
ence of alkali metal alkoxide (C2H5ONa) to afford com-
pound 5(a–s). In the 1H NMR spectra of the compound
5(a–s), we found the disappearance of two methy-
lene protons of compounds 4(a–s) and an appearance
4. Results and discussion
The reaction of 1-bromo-3-chloro-propane with 2- of a new signal for C=CH in the range of δ 6.44–
1
aminothiazole afforded a product compound 1. The 6.77 ppm in the H NMR and two new signals for
spectroscopic analyses of compound 1 showed absorp- C=CH and C=CH appeared in the range of δ 135.7–
tion peaks for N–CH and C–Cl at 1339 and 748 cm−1 143.2 and δ 141.1–149.2 ppm in the 13C NMR spectra
respectively in the IR spectrum and confirms the of the compounds 5(a–s). These facts clearly confirmed
formation of compound 1. The compound 1 on the reac- the synthesis of all final products. Compounds 5(a–s)
tion with urea with continuous stirring at room tempera- were synthesized and screened for their antibacterial
ture yielded compound 2. In the spectroscopic analyses and antifungal activity against some selected bacte-
of compound 2 we found three absorption peaks in IR ria and fungi respectively and antitubercular activity
spectrum for NH, NH2 and CO at 3378, 3424 cm−1 and against M. tuberculosis (H37Rv strain). The investiga-
1642 cm−1 respectively while absorption of C–Cl has tion of antimicrobial and antitubercular data revealed

644
Pushkal Samadhiya et al.
that the compounds (5c), (5d), (5e), (5f), (5h), (5i) and Institute Lucknow (India) for providing spectral and
(5j) have shown more activity in the series, the com- analytical data of the compounds. We are thankful
pounds (5b), (5g) and (5s) showed moderate activity to Head of the Department of Biotechnology, Dr.
and rest of the compounds showed less activity against H S Gour, University, Sagar (India) for antimicrobial
all the strains compared with standard drugs.
(antibacterial and antifungal) analysis of samples.
Our investigations have shown that the compounds Microcare Laboratory and Tuberculosis Research
have a structure–activity relationship because activity Centre, Gujarat is also thanked for the help to study
of compounds varied with substitution. Nitro group antituberculosis activity.
containing compounds (5h, 5i and 5j) showed higher
activity than chloro (5c, 5d), or bromo group contain-
ing compounds (5e, 5f). Chloro and bromo derivatives
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Acknowledgements
The authors are thankful to Sophisticated Analytical
Instrument Facilities (SAIF), Central Drugs Research