Synthesis and biological activity of 4-thiazolidinone derivatives of phenothiazine

Article abstract of DOI:10.2298/JSC100924152S

A new series of N-[3-(10H-phenothiazin-10-yl)propyl]-2-(substituted phenyl)-4-oxo-5-(substituted benzylidene)-3-thiazolidinecarboxamide, 5a-s were synthesized. The reaction of thioglycolic acid with N-[3-(10H-phenothiazin- 10-yl)propyl]-N'-[(substituted phenyl)methylidene]urea, 3a-s in the presence of anhydrous ZnCl2 afforded the new heterocyclic compounds N-[3- -(10H-phenothiazin-10-yl)propyl]-2-(substituted phenyl)-4-oxo-3- thiazolidinecarboxamide, 4a-s. The latter product on treatment with several selected substituted aromatic aldehydes in the presence of C2H5ONa underwent the Knoevenagel reaction to yield 5a-s. The structure of compounds 1, 2, 3a-s, 4a-s and 5a-s were confirmed by IR, 1H-NMR, 13C-NMR and FAB mass spectroscopy and by chemical analysis. All the above compounds were screened for their antimicrobial activity against some selected bacteria and fungi and for their antituberculosis activity, the compounds were screened against the bacterium Mycobacterium tuberculosis. Copyright 2012 (CC) SCS.

Full text of DOI:10.2298/JSC100924152S

J. Serb. Chem. Soc. 77 (1) 17–26 (2012)
UDC 547.869+547.789+542.913:615.28–188
JSCS–4245
Original scientific paper
Synthesis and biological activity of 4-thiazolidinone derivatives
of phenothiazine
RITU SHARMA*, PUSHKAL SAMADHIYA, SAVITRI D. SRIVASTAVA
and SANTOSH K. SRIVASTAVA
Synthetic Organic Chemistry Laboratory, Department of Chemistry, Dr. H. S. Gour
University (A Central University), Sagar-470003, India
(Received 24 September 2010, revised 24 April 2011)
Abstract: A new series of N-[3-(10H-phenothiazin-10-yl)propyl]-2-(substituted
phenyl)-4-oxo-5-(substituted benzylidene)-3-thiazolidinecarboxamide, 5a–s
were synthesized. The reaction of thioglycolic acid with N-[3-(10H-phenothia-
zin-10-yl)propyl]-N’-[(substituted phenyl)methylidene]urea, 3a–s in the pre-
sence of anhydrous ZnCl2 afforded the new heterocyclic compounds N-[3-
-(10H-phenothiazin-10-yl)propyl]-2-(substituted phenyl)-4-oxo-3-thiazolidine-
carboxamide, 4a–s. The latter product on treatment with several selected sub-
stituted aromatic aldehydes in the presence of C2H5ONa underwent the Knoe-
venagel reaction to yield 5a–s. The structure of compounds 1, 2, 3a–s, 4a–s
1
and 5a–s were confirmed by IR, H-NMR, 13C-NMR and FAB mass spectros-
copy and by chemical analysis. All the above compounds were screened for their
antimicrobial activity against some selected bacteria and fungi and for their
antituberculosis activity, the compounds were screened against the bacterium
Mycobacterium tuberculosis.
Keywords: synthesis; phenothiazine; 4-oxothiazolidine; antimicrobial; antitu-
bercular.
INTRODUCTION
Thiazolidines have been shown to possess various remarkable biological ac-
1
2
3
4
tivities such as analgesic, amoebicidal, nematocidal, anaesthetic, mosquito-
5
6
7–12
13–14
-repеllent, anti-HIV, anticancer, antibacterial,
antifungal,
EGFR and HER-2 kinase inhibitor, antiproli-
etc. Phenothiazine is also a bioactive heterocyclic compound of
antiinflam-
16–19
24,25
20–22
23
matory,
ferative,
antitubercular,
pharmaceutical importance and possesses different biological activities viz. anti-
26,27
28
29
30
bacterial,
antifungal, antitubercular, and anti-inflammatory. In the pre-
sent study, compounds 1, 2, 3a–s, 4a–s and 5a–s were synthesized as shown in
Scheme 1. The starting material, phenothiazine with 1-bromo-3-chloropropane un-
*Corresponding author. E-mail: ritusharmaic@rediffmail.com
doi: 10.2298/JSC100924152S
Available online at www.shd.org.rs/JSCS/
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2012 Copyright (CC) SCS

18
SHARMA et al.
S
S
S
NH2CONH2
BrCH2CH2CH2Cl
N
N
N
H
1
2
CH2CH2CH2NHCONH2
CH2CH2CH2Cl
ArCHO
S
N
3(a-s)
CH2CH2CH2NHCON=CHAr
S
HSCH2COOH+ZnCl2
N
S
ArCHO+C2H5ONa
CH CH CH NHCO
N
CHAr
S
2
2
2
N
5(a-s)
O
CH2CH2CH2NHCON
CHAr
CHAr1
S
4(a-s)
O
Ar= substituted phenyl ring
Compound
Ar = Ar1
Compound
Ar = Ar1
Compound
Ar = Ar1
3a, 4a, 5a
3b, 4b, 5b
3c, 4c, 5c
3d, 4d, 5d
3e, 4e, 5e
3f, 4f, 5f
C6H5
3h, 4h, 5h
3i, 4i, 5i
3j, 4j, 5j
3k, 4k, 5k
3l, 4l, 5l
4-NO2C6H4
3-NO2C6H4
2-NO2C6H4
4-CH3OC6H4
3-CH3OC6H4
3o, 4o, 5o 3-CH3OC6H4
3p, 4p, 5p 2-CH3OC6H4
4-ClC6H4
3-ClC6H4
2-ClC6H4
4-BrC6H4
3-BrC6H4
2-BrC6H4
3q, 4q, 5q
3r, 4r, 5r
3s, 4s, 5s
4-HOC6H4
3-HOC6H4
2-HOC6H4
3m, 4m, 5m 2-CH3OC6H4
3n, 4n, 5n 4-CH3C6H4
3g, 4g, 5g
Scheme 1. Reaction scheme for synthesis of compounds 1–5.
derwent an nucleophilic substitution reaction yielding 10-(3-chloropropyl)-10H-
phenothiazine, compound 1. Compound 1 on reaction with urea afforded N-[3-
(10H-phenothiazin-10-yl)propyl]urea, compound 2. Compound 2 on reaction
with several selected substituted benzaldehydes underwent a condensation reac-
tion to afford N-[3-(10H-phenothiazin-10-yl)propyl]-N’-[(substituted phenyl)-
methylidene]urea, compounds 3a–s. The reaction of thioglycolic acid with com-
pounds 3a–s in the presence of anhydrous ZnCl gave new heterocyclic com-
2
pounds N-[3-(10H-phenothiazin-10-yl)propyl]-2-(substituted phenyl)-4-oxo-3-
-thiazolidinecarboxamide, compounds 4a–s. Compounds 4a–s on treatment with
various selected substituted benzaldehydes in the presence of C H ONa under-
2
5
went a Knoevenagel condensation reaction to yield the final products N-[3-(10H-
-phenothiazin-10-yl)propyl]-2-(substituted phenyl)-4-oxo-5-(substituted benzyli-
dene)-3-thiazolidine-carboxamide, compounds 5a–s. The structures of all the
newly synthesized compounds 1, 2, 3a–s, 4a–s and 5a–s were confirmed by IR,
1
13
H-NMR, C-NMR and FAB mass spectroscopy and by chemical analysis. All
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SYNTHESIS AND BIOLOGICAL ACTIVITY OF 4-THIAZOLIDINONE DERIVATIVES OF PHENOTHIAZINE
19
the above compounds were screened for their antimicrobial activity against some
selected bacteria and fungi and antituberculosis activity against Mycobacterium
tuberculosis.
EXPERIMENTAL
Melting points were taken in open capillaries and are uncorrected. The progress of the
reactions was monitored on silica gel-G coated TLC plates using MeOH : CHCl3 (1:9). The
spot was visualized by exposing the dry plate to iodine vapour. The IR spectra were recorded
in KBr discs on a Shimadzu 8201 PC FTIR spectrophotometer (νmax in cm–1) and the 1H- and
13C-NMR spectra were measured on a Bruker DRX-300 spectrometer in CDCl3 at 300 and 75
MHz, respectively, using TMS as an internal standard. All chemical shifts are reported on
δ scales. The FAB mass spectra were recorded on a Jeol SX–102 mass spectrometer. Elemen-
tal analyses were realised on a Carlo Erba-1108 analyzer. The analytical data of all the
compounds were highly satisfactory. For column chromatographic purification of the pro-
ducts, Merck silica Gel 60 (230–400 Mesh) was used. The employed reagent grade chemicals
were purchased from commercial sources and further purified before use.
Synthesis of 10-(3-chloropropyl)-10H-phenothiazine, compound 1
Phenothiazine (0.301 mol) and 1-bromo-3-chloropropane (0.301 mol) in ethanol (100
ml) were stirred on a magnetic stirrer for 5.0 h at room temperature. Completion of the reac-
tion was monitored on silica gel-G coated TLC plates. The product was filtered and purified
over a silica gel packed column chromatography using CHCl3:CH3OH (8:2 v/v) as the eluant
(120 ml). The purified product was dried under vacuum and recrystallized from acetone to
yield compound 1 (Fig. 1).
9
4
5
5a
S
4a
6
7
3
2
10
8a
1a
11
N
1
8
12
Cl
1
13
Fig. 1. Structure of compound 1.
Synthesis of N-[3-(10H-phenothiazin-10-yl)propyl]urea, compound 2
Compound 1 (0.20 mol) and urea (0.20 mol) in ethanol (100 ml) were stirred on a mag-
netic stirrer for 4.0 h at room temperature. The completion of the reaction was monitored by
silica gel-G coated TLC plates. The product was filtered and purified over a silica gel packed
column chromatography using CHCl3:CH3OH (8:2 v/v) as eluant (120 ml). The purified pro-
duct was dried under vacuo and recrystallized from ethanol to yield compound 2 (Fig. 2).
9
4
5
S
5a
4a
1a
6
7
3
2
10
8a
O
N
1
8
12
'
1
11
'
N
'
3
2
13
H
2
NH2
Fig. 2. Structure of compound 2.
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2012 Copyright (CC) SCS

20
SHARMA et al.
Synthesis of N-[3-(10H-phenothiazin-10-yl)propyl]-N’-(phenylmethylidene)urea, compound 3a
Compound 2 (0.026 mol) and benzaldehyde (0.026 mol) in ethanol (100 ml) in the pre-
sence of 2–4 drops glacial acetic acid were first stirred on a magnetic stirrer for 2.0 h at room
temperature followed by refluxing on a steam bath at 80–90 °C for 3.3 h. The completion of
the reaction was monitored using silica gel-G coated TLC plates. The product was filtered,
cooled and purified over a silica gel packed column chromatography using CH3OH:CHCl3
(7:3 v/v) as eluant (90 ml). The purified product was dried under vacuum and recrystallized
from acetone at room temperature to furnish compound 3a (Fig. 3).
Compounds 3b–s (Fig. 3) were synthesized using a similar method.
4
3
9
4a
S
5
5a
2
6
1a
1
O
X
16
17
N
8a
10
12
7
'
'
8
1
3
'
11
2
18
N
N
CH
14
15
H
13
20
19
3(a-s)
Fig. 3. Structure of compounds 3a–s.
Synthesis of 4-oxo-N-[3-(10H-phenothiazin-10-yl)propyl]-2-(phenyl)-3-thiazolidine-carbox-
amide, compound 4a
Compound 3a (0.0129 mol) and thioglycolic acid (0.0129 mol) in methanol (50 ml) in
the presence of ZnCl2 were first stirred on a magnetic stirrer for 2.0 h at room temperature
followed by refluxing on a steam bath at 70–90 °C for 6.0 h. The completion of the reaction
was monitored using silica gel-G coated TLC plates. The product was filtered, cooled and
purified over a silica gel packed column chromatography using CH3OH:CHCl3 (7:3 v/v) as
eluant (80 ml). The purified product was dried under vacuum and recrystallized from ethanol
at room temperature to furnish compound 4a (Fig. 4).
Compounds 4b–s (Fig. 4) were synthesized using a similar method.
16
17
X
3
4
9
4a
15
18
2
O
'
S
5a
5
"
"
3
14
19
2
1
1a
'
1
N
CH
12
2
6
HN
N
8a
10
"
4
S
"
11
8
7
1
13
O
"
4(a-s)
5
Fig. 4. Structure of compounds 4a–s.
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2012 Copyright (CC) SCS

SYNTHESIS AND BIOLOGICAL ACTIVITY OF 4-THIAZOLIDINONE DERIVATIVES OF PHENOTHIAZINE
21
Synthesis of 4-oxo-N-[3-(10H-phenothiazin-10-yl)-propyl]-2-phenyl-5-(phenylmethylidene)-
-3-thiazolidinecarboxamide, compound 5a
Compound 4a (0.008 mol) and benzaldehyde (0.008 mol) in ethanol (50 ml) in the pre-
sence of CH3CH2ONa were first stirred on a magnetic stirrer for 2.0 h at room temperature
followed by refluxing on a steam bath at 80–90 °C for 5.0 h. Completion of the reaction was
monitored using silica gel-G coated TLC plates. The product was filtered, cooled and purified
by a silica gel packed column chromatography using CH3OH:CHCl3 (7:3 v/v) as eluant (70
ml). The purified product was dried under vacuum and recrystallized from ethanol at room
temperature to furnish compound 5a.
Compounds 5b–s were synthesized using a similar method.
Biological study
The antibacterial, antifungal and antitubercular activities of compounds 1, 2, 3a–s, 4a–s
and 5a–s were assayed in vitro against selected bacteria, i.e., Escherichia coli, Bacillus sub-
tilis, Staphylococus aureus, and selected fungi, Aspergillus flavus, Aspergillus niger and Can-
dida albicans H37Rv strain. The inhibition zone (mm) of compounds 1, 2, 3a–s, 4a–s and 5a–s
were determined using the filter paper disc diffusion method31 (antibacterial and antifungal
activity) at two concentration of 50 and 100 ppm and the percentage activity of compounds 1,
2, 3a–s, 4a–s and 5a–s were determined using the L. J. medium (conventional) method (anti-
tubercular activity) at 25 and 50 μg mL-1 and lower concentrations. Streptomycin and griseo-
fulvin were used as the standard for the antibacterial and antifungal activity, respectively, and
for the antitubercular activity, isoniazid and rifampicin were taken as standards.
RESULTS AND DISCUSSION
The analytical and spectral data of the synthesized compounds are given in
the Supplementary material to this paper.
The reaction of 1-bromo-3-chloropropane with phenothiazine was performed
in ethanol as solvent to afford compound 1. The spectroscopic analyses of com-
pound 1 showed absorption peaks for N–CH, C–Cl and C–S–C at 1272, 774 and
–1
687 cm in the IR spectrum. The IR spectrum confirms the formation of com-
pound 1. This fact was also supported by the disappearance of NH absorption of
the phenothiazine.
Compound 1 on reaction with urea under continuous stirring at room tem-
perature yielded compound 2. In the spectroscopic analyses of compound 2, three
absorption peaks were found in the IR spectrum for NH, NH and CO at 3342,
2
–1
3412 and 1655 cm , respectively while the absorption of C–Cl found in the
spectrum of 1 had disappeared. This clearly indicated that compound 1 under-
1
went substitution reaction with urea. This fact was also supported by the H- and
13
1
C-NMR spectra as two signals appeared in the H-NMR spectrum for NH and
NH at δ 5.83 and 5.99 ppm, respectively. The formation of compound 2 was
2
13
fully supported by the signal for the CO group at δ 163.4 ppm in the C-NMR
spectrum. All the facts together were strong evidence for the synthesis of com-
pound 2.
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22
SHARMA et al.
Substituted benzaldehydes underwent condensation reaction with compound
2, resulting in the formation of Schiff bases N=CH, which was confirmed by the
1
13
IR, H-NMR and C-NMR spectra of compounds 3a–s. In the IR spectra, an ab-
–1
sorption was found in the range 1531–1584 cm , while a strong signal appeared
in the range of δ 7.84–8.34 and 143–158.4 ppm in the H-NMR and C-NMR
1
13
spectra of compounds 3a–s, respectively. These facts were also supported by the
1
disappearance of the signal for NH present in the H-NMR spectrum of com-
2
pound 2.
Compounds 3a–s on reaction with an equimolar amount of thioglycolic acid
in the presence of ZnCl underwent a reaction whereby a five-membered thiazo-
2
lidinone ring was formed, compounds 4a–s. Compounds 4a–s showed a characte-
–1
ristic absorption for a cyclic carbonyl group in the range 1725–1758 cm in the
1
IR spectra. The H-NMR spectra of compounds 4a–s clearly indicated the
presence of the active methylene group in the thiazolidine ring by exhibiting a
13
signal in the range δ 3.26–3.68 ppm. The C-NMR spectra of compounds 4a–s
also supported the fact that a cyclic carbonyl group was present by the signal that
appeared in the range δ 160.4–178.8 ppm. These facts were supported by a) the
disappearance of the N=CH proton and b) the appearance of a N–CH proton in
1
the range of δ 5.23–5.82 ppm in the H-NMR spectra of compounds 4a–s.
Compounds 4a–s underwent a Knoevenagel condensation reaction with sub-
stituted benzaldehydes in the presence of alkali metal alkoxide (C H ONa) to
2
5
1
afford compounds 5a–s. In the H-NMR spectra of compounds 5a–s, the two me-
thylene protons of compounds 4a–s were absent and a new signal for C=CH ap-
peared in the range δ 6.32–6.77 ppm and in the C-NMR spectra of compounds
13
5a–s, two new signals for C=CH and C=CH appeared in the δ range 134.6–143.2
and 140.1–149.2 ppm, respectively. All these facts clearly confirmed the syn-
thesis of all the final products.
Biological study
The results of the antimicrobial (antibacterial, antifungal and antitubercular)
activities are summarized in Table I. All the compounds 1, 2, 3a–s, 4a–s and 5a–s
were screened for their antimicrobial activity against selected strains of bacteria
and fungi and antitubercular activity against M. tuberculosis (H37Rv strain). The
investigation of antimicrobial data revealed that compounds 5c, 5d, 5e, 5f, 5h, 5i
and 5j displayed high activity, compounds 4h, 4j, 5b, 5g and 5q showed mode-
rate activity and the other compounds showed less activity against all the strains
compared with standard drugs.
The compounds exhibited a structure–activity relationship (SAR) because
the activity of compounds varies with substitution. The nitro group-containing
compounds 5h, 5i and 5j showed higher activity than the chloro group- (5c and
5d) or the bromo group-containing compounds (5e and 5f). In addition, the
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SYNTHESIS AND BIOLOGICAL ACTIVITY OF 4-THIAZOLIDINONE DERIVATIVES OF PHENOTHIAZINE
23
chloro- and bromo-derivatives also had a higher activity than the other tested
compounds. Based on the SAR, it could be concluded that the activity of com-
pounds depended on the electron withdrawing nature of the substituent groups.
The sequence of the activity is following:
NO > Cl > Br > OCH < OH > CH
3
2
3
TABLE I. Antibacterial, antifungal (inhibition zone in mm) and antitubercular activity of
compounds 1, 2, 3a–s, 4a–s and 5a–s
Antitubercular
activity, %
Antibacterial activity
Antifungal activity
C.
M. tuberculosis
Compound
B. subtilis E. coli S. aureus A. niger A. flavus
albicans H37Rv strain
c / ppm
c / μg mL-1
50 100 50 100 50 100 50 100 50 100 50 100
25
13
10
18
25
27
30
28
27
25
32
35
38
25
28
23
20
24
25
28
30
32
20
25
30
30
30
32
30
30
32
35
50
20
18
22
32
34
35
40
50
52
65
68
66
40
42
43
38
35
38
50
52
55
35
55
60
60
68
70
75
70
68
70
1
2
–
2
7
7
9
–
–
5
7
4
2
7
6
–
5
9
8
8
4
4
6
7
–
3
9
5
6
13
3a
3b
3c
3d
3e
3f
3g
3h
3i
12 10 14 11 13
12 10 15
10 20 11 18 13 19 10 17 13 17 11 14
12 19 12 16 10 16 11 17 13 17 11 14
10 13 14 17 12 19 13 20 14 20 13 17
8
9
21
20 10 21 11 20
21 20
9
22 10 21
9
8
6
18
14
13
8
6
8
15
13
12
8
6
9
16
17
14
10 24
7
9
13 26 10 24 13 27 10 18 12 25 14 22
11 23 20 10 25 10 17 11 26 12 23
13 27 10 24 12 26 10 18 10 24 11 22
9
3j
3k
3l
7
8
8
4
5
5
9
10
12
13
10
7
6
6
7
5
6
5
8
9
10
13
14
12
8
9
13
14
8
7
6
4
6
4
8
8
7
12
13
12
11
10
7
15
13
14
7
6
7
6
5
6
7
7
9
13
14
12
13
12
10
13
12
13
6
7
6
5
6
5
6
7
8
13
13
14
9
11
9
8
7
6
4
7
6
8
9
14
12
10
10
10
11
14
14
3m
3n
3o
3p
3q
3r
3s
4a
4b
4c
4d
4e
4f
8
14
14
15
10 16
9
13 10 15
15 10 14
15 20 13 19 14 20 10 15 12 20 10 14
14 23 10 21 13 21 10 17 11 17 12 18
10 27 10 28 12 27 11 20 10 19 11 21
12 26 11 27 12 29 11 20
10 29 10 27 10 28 21
8
8
17 12 19
17 10 19
9
10 28 11 30 13 30 12 24 13 20 13 21
4g
4h
4i
17 30
8
31 10 30
7
20
8
9
9
21 10 22
18 30 15 28 10 30 11 24
10 22 13 24 12 28 10 12
12 24 15 30 13 27 12 28 10 22
20
19
8
8
9
22
20
24
4j
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24
SHARMA et al.
TABLE I. Continued
Antitubercular
activity, %
Antibacterial activity
Antifungal activity
C.
M. tuberculosis
Compound
B. subtilis E. coli S. aureus A. niger A. flavus
albicans H37Rv strain
c / ppm
c / μg mL-1
50 100 50 100 50 100 50 100 50 100 50 100
25
30
32
30
29
28
30
33
34
33
22
32
36
32
30
30
29
32
27
28
28
30
31
22
18
20
24
27
25
100
50
50
53
50
41
42
45
70
70
65
45
74
80
80
78
79
76
82
83
81
60
63
65
45
49
47
76
70
65
100
4k
4l
10 14
11 15
9
8
22 10 20
20 10 21
8
8
8
7
7
7
21
20
15
13
13
16
9
8
7
9
8
7
17
15
14
13
12
13
7
6
7
7
8
8
21
15
13
13
10
14
4m
4n
4o
4p
4q
4r
4s
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
9
8
9
8
14 10 16
8
8
7
8
18
14
13
15
10
13
14
8
8
9
12
14
17
16 26 18 30 14 29 14 25 12 22 13 25
17 24 15 30 15 27 13 24 13 21 10 21
12 20 11 22 10 21 11 23 10 18 10 22
18 25 07 22 10 23 07 15 07 12 10 14
15 29 10 30 15 29 12 20 10 20 14 21
13 34 12 32 14 31 15 24 17 25 14 23
15 32 10 31 13 32 11 23 10 21 13 22
12 33 12 31 15 31 10 22 12 23 15 23
11 31 11 31 14 32 11 22 11 21 14 23
20 27 10 28 10 28 10 19 10 20 10 20
22 35 19 33 12 34 18 24 09 24 12 25
20 34 10 32 12 35 12 25 10 23 12 24
24 36 11 33 10 33 13 25 11 22 10 24
08 28 09 21 08 27 11 18 10 14 11 17
11 26 12 23 12 25 10 16 12 15 12 16
13 27 15 25 14 26 13 15 13 15 12 12
14 18 14 17 16 22 10 15 10 13 10 14
12 19 14 15 15 20 09 14 09 12 11 15
14 20 15 18 14 19 08 12 10 18 09 15
12 29 13 28 12 30 14 20 13 16 12 21
13 28 14 24 13 27 13 18 13 17 13 20
11 30 12 21 11 29 12 18 10 15 11 19
28 37 26 34 27 35 20 26 18 25 19 26
5m
5n
5o
5p
5q
5r
5s
Standard
Streptomycin
Griseofulvin
Standardsa
a
Standards for the antitubercular activity, isoniazid and rifampicin, showed 100 % activity at both tested con-
centrations
CONCLUSIONS
The present research study reports the successful synthesis of all the newly
synthesized compounds 1, 2, 3a–s, 4a–s and 5a–s. Some of the synthesized com-
pounds displayed good biological activities while the others showed lower anti-
microbial and antitubercular activities.
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2012 Copyright (CC) SCS

SYNTHESIS AND BIOLOGICAL ACTIVITY OF 4-THIAZOLIDINONE DERIVATIVES OF PHENOTHIAZINE
25
SUPPLEMENTARY MATERIAL
Аnalytical and spectral data of synthesized compounds are available electronically from
http://www.shd.org.rs/JSCS/, or from the corresponding author on request.
Acknowledgements. The authors are thankful to SAIF, Central Drugs Research Institute,
Lucknow (India) for providing the spectral and analytical data of the compounds. We are
thankful to the Head, Department of Biotechnology, Dr. H. S. Gour University (A Central
University), Sagar (India) for the antimicrobial (antibacterial and antifungal) results and the
Microcare Laboratory and Tuberculosis Research Centre, Surat, Gujarat (India) for the anti-
tuberculosis activity results. We are also thankful to the Head, Department of Chemistry, Dr.
H. S. Gour University (A Central University), Sagar (India) for providing the facilities for the
realisation oft the work.
И З В О Д
СИНТЕЗА И БИОЛОШКА АКТИВНОСТ 4-ТИАЗОЛИДИНОНСКИХ ДЕРИВАТА
ФЕНОТИАЗИНА
RITU SHARMA, PUSHKAL SAMADHIYA, SAVITRI D. SRIVASTAVA и SANTOSH K. SRIVASTAVA
Synthetic Organic Chemistry Laboratory, Department of Chemistry, Dr. H.S. Gour University (A Central
University), Sagar-470003, India
Синтетисана је серија нових деривата N-[3-(10H-фенотиазин-10-ил)-пропил]-2-(супсти-
туисани фенил)-4-оксо-5-(супституисани бензилиден)-3-тиазолидин-карбоксамида 5a–s. Ре-
акција тиогликолне киселине и N-[3-(10H-фенотиазин-10-ил)-пропил]-N’-[(супституисани
фенил)-метилиден]-уреа 3a–s, у присуству анхидрованог ZnCl2 даје нова хетероциклична
једињења N-[3-(10H-фенотиазин-10-ил)-пропил]-2-(супституисани фенил)-4-oксo-3-тиазоли-
дин-карбоксамиде, 4a–s. Добијени производи у реакцији са одабраним супституисаним аро-
матични алдехидима, у присуству C2H5ONa подлежу Кневенагеловој реакцији и дају једи-
1
њења 5a–s. Једињења 1, 2, 3a–s, 4a–s и 5a–s потвргнуте су IR, H-NMR, 13C-NMR, FAB MS
инструменталним анализама и елементалној анализи. Испитана је антибактеријска, антифун-
гална и антитуберкулозна активност према M. tuberculosis синтетисаних једињења.
(Примљено 24. септембра 2010, ревидирано 24. априла 2011)
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