Synthesis and antibacterial activity studies of some 2-(substitutedphenyl)- 3-bis2, 4-(4'-methylphenylamino)-s-triazine-6-ylaminobenzoylamino-5-H-4- thiazolidinone

Article abstract of DOI:10.1155/2012/641547

Some 4-thiazolidinone derivatives 6(a-l) have been prepared bearing s-triazine moiety by the condensation of Schiff bases from bis-2,4 (4'-methyl-phenylamino)-s-triazine-6-ylaminobenzoyl substituted benzylhydrazone 5(a-l) with thioglycolic acid. The structures of synthesized compounds have been characterized by IR, ¹HNMR spectral studies. The synthesized compounds 6(a-l) have been screened for antibacterial activity.

Full text of DOI:10.1155/2012/641547

ISSN: 0973-4945; CODEN ECJHAO
E-Journal of Chemistry
http://www.ejchem.net
2012, 9(2), 988-992
Synthesis and Antibacterial Activity
Studies of Some 2-(Substitutedphenyl)-3-bis2,
4-(4’-methylphenylamino)-s-triazine-6-
ylaminobenzoylamino-5-H-4-thiazolidinone
MUKESH KUMAR AHIRWAR* and S. P. SHRIVASTAVA
Department of Chemistry
Dr. H. S. Gour University Sagar (M.P.), 470003, India
mukesh_phd@yahoo.co.in
Received 31 July 2011; Accepted 4 October 2011
Abstract: Some 4- thiazolidinone derivatives 6(a-l) have been prepared bearing
s-triazine moiety by the condensation of Schiff bases from bis-2,4 (4’-methyl-
phenylamino)-s-triazine-6-ylaminobenzoyl substituted benzylhydrazone 5(a-l)
with thioglycolic acid. The structures of synthesized compounds have been
characterized by IR, 1HNMR spectral studies. The synthesized compounds
6(a-l) have been screened for antibacterial activity.
Keywords: s-Triazine, 4- Thiazolidinone, Antibacterial activity.
Introduction
The survey of literature related to 4- thiazolidinone derivatives show that compounds with
these nuclei have vast medicinal importance. The field ring system is of considerable interest
as it is a core structure in various synthetic pharmaceuticals displaying a broad spectrum of
biological activities1. 4- thiazolidinone a saturated form of thiazole with carbonyl group on
fourth carbon, has been considered as a magic moiety (wonder nucleus) which posseses
almost all types of biological activities2 such as anti HIV3, anticonvulsant4, anticancer5,
antitubercular6, cardioprotective7, antiinflammatory8, antidiabetic9 and antimicrobial10.
Experimental
All the melting points were determined in open capillaries and are uncorrected. The
reactions were monitored on TLC. The IR spetra were recorded in KBr pellets on a perkin-
Elmer 237 spectrophotometer.1HNMR spetra on a Bruker Avance DPX 300 MHz
spectrometer with CDCl3 as a solvent, using TMS as internal reference. Elemental analyses
were carried out on a carlo Elba 1108 model analyzer.

Synthesis and Antibacterial Activity Studies of Some 989
Preparation of 2-(4’-methyl phenyl amino)-s-triazine 1
p-Toluidine (0.01 mole) was added slowly to cyanuric chloride (0.01 mole) in dioxane
o
(30 mL) with constant stirring for 4 h at 0 to 5 C. Then sodium carbonate (0.005 mole)
dissolved in water (10 mL) was added drop wise to neutralize HCl evolved during the
reaction. Finally the contents were poured into ice. The solid separated out was
0
filtered, washed with water, dried and recrystallized from alcohol. m.p 196 C, yield
86%.
Preparation of bis-2,4- (4’-methyl phenyl amino)- s-triazine 2
p-Toluidine (0.01 mole) was added slowly to compound I (0.01 mole) in dioxane
(35 mL) with constant stirring for 6 h at room temperature. Then sodium carbonate
(0.005 mole) dissolved in water (10 mL) was added drop wise to neutralize HCl evolved
during the reaction. Finally the contents were poured into crushed ice. The solid
separated out was filterd, washed with water, dried and recrystallized from alcohol.
0
m.p.179 C.yield 80%.
Preparation of bis 2,4-(4’-methyl phenyl amino)–s-triazin-6-yl-aminoethyl benzoate 3
Ethyl p-aminobenzoate (0.01 mole) and compound 2 (0.01 mole) were dissolved in
dioxane (40 mL). The reaction mixture was refluxed for 6 h, cooled and poured into
crushed ice. Then sodium carbonate (0.005 mole) dissolved in water (10 mL) was
added to neutralize HCl evolved during the reaction. The solid separated out was
0
filtered, washed with water, dried and recrystallized from alcohol. m.p. 219 C yield
78%. IR (KBr, cm-1), 2956(C-H),3102(Ar-H), 1470(C=N), 806(C-N) 3362(N-H),
1680(C=O).
Preparation of bis-2,4-(4’-methylphenylamino)-s-triazine-6-ylaminobenzoyl hydrazone 4
A mixture of compound 3(0.01 mole) in dioxane and hydrazine hydrate (0.01 mole), was
refluxed on a water bath for 6 h. The product was isolated with HCl and crystallized from
dioxane.m.p.198 yield 79 IR (KBr, cm-1), 2908(C-H), 3056(Ar-H), 1498(C=N), 807(C-N),
3356(N-H), 1670(C=O).
Preparation of bis-2,4(4’-methylphenylamino)-s-triazine-6-ylaminobenzoyl substituted
benzylhydrazone 5
A mixture of compound 4 (0.01 mole) and substituted aldehyde (0.01 mole) in dioxane
(15 mL) was refluxed for 4hrs. The product was isolated and crystallized from methanol.
0
m.p.150 C.Yield78%. IR (KBr,cm-1) 2985(C-H), 3056(Ar-H), 3399(N-H), 1420 (C= N),
1675(C=O), 805(C-N). 1HNMR (CDCl3 ,), 6.45 (Sym.multi. 2CH3 subs. Benzene ring 8H),
7.68 (S,4N-H,4H), 2.38 (s,2CH3,6H), 1.95(s,C-H of thiazolidinone), 6.31 (sym.multi.N-H
subs.benzene ring)
Preparation of 2-substitutedphenyl-3-bis-2,4-(4’-methylphenylamino)-s-triazine-6-
ylaminobenzoyl amino-5-H-4- thiazolidinone 6
Thioglycolic acid (0.01 mole) was added to compound 5 (0.01 mole) in dry bezene
(20 mL)and refluxed for 6 h. The product was isolated by washing the upper organic layer
0
with water and sodium bicarbonate solution and crystallized from dioxane. m.p. 197 C
yield 76%. IR(max in cm-1),3456(N-H,3095(Ar-H), 1602(C=C), 1675 (C=O), 750(C-S), 1306
(C=N),802(C-N)675(Ar-Cl). 1HNMR(CDCl3, ), 6.40 (sym. multi., 8H,2CH3 subs.benzene ring),
7.45(s,4H,N-H sub. Benzene ring) 2.38(s, 2CH3, 6H).

990 M. K. AHIRWAR et al.
Reaction Sequence
Cl
Cl
N
0C
N
N
0-5
Dioxane
N
N
+
H2N
CH3
Cl
Cl
N
Cl
NH
H3C
1
25-300
Dioxane
Cl
C
HN2
COOC2H5
NH
COOC2H5
H2N
CH3
Dioxane 4-6 hrs
Reflux
N
N
N
N
CH3
HN
NH
H3C
N
CH3
HN
NH
H3C
N
3
2
Dioxane
NH2.NH2.H2O
R
R
CHO
NH
CONHN=HC
CH3
NH
CONHNH2
CH3
N
N
Dry benzene
H3C
N
N
HN
NH
HN
H3C
NH
N
N
5(a-l)
4
Thioglycolic acid
Dry benzene
CH3COOH/CH3COONa
R
CONH
N
CH
S
NH
O
N
N
C
H2
CH3
HN
NH
H3C
N
6(a-l)
(Scheme -I)
R=a - 2-Cl
d- 2-NO2
e-3- NO2
g -2-
Br
j-2-
OH
Cl
Cl
b- 3-
c- 4-
OH
h- 3-Br k-3-
f- 4-
NO2
i- 4-
Br
l- 4-OH
Table 1. Physical characterization data of synthesized compound 6(a-l).
Elemental analysis
Mol. Yield m.p.
Compd Mol. Formula
C %
H %
N %
Wgt.
%
ºC
Calcd Found Calcd Found Calcd Found
C33H29N8O2ClS 637.145 72 146 62.12 62.11 4.58 4.56 17.58 17.55
C33H29N8O2ClS 637.145 76 146 62.12 62.10 4.58 4.56 17.58 17.56
C33H29N8O2ClS 637.145 74 146 62.12 62.09 4.58 4.55 17.58 17.55
6a
6b
6c
6d
6e
6f
C33H29N9O4S 647.682 68 142 61.10 61.08 4.5
C33H29N9O4S 647.682 69 142 61.10 61.09 4.5
C33H29N9O4S 647.682 78 142 61.10 61.08 4.5
4.3 19.46 19.43
4.3 19.46 19.44
4.4 19.46 19.4
C33H29N8O2BrS 681.595 75 147 58.15 58.13 4.28 4.25 16.44 16.42
C33H29N8O2BrS 681.595 71 147 58.15 58.12 4.28 4.25 16.44 16.41
C33H29N8O2BrS 681.595 73 147 58.15 58.12 4.28 4.25 16.44 16.41
C33H30N8O3S 618.693 77 129 64.06 64.03 4.88 4.86 18.11 18.09
C33H30N8O3S 618.693 71 129 64.06 64.04 4.88 4.87 18.11 18.09
C33H30N8O3S 618.693 78 129 64.06 64.03 4.88 4.86 18.11 18.08
6g
6h
6i
6j
6k
6l

Synthesis and Antibacterial Activity Studies of Some 991
Results and Discussion
The reaction of s-triazine and p-toluidine in the dioxane gave bis -2,4 (4’-methyl phenyl
amino)-s-triazine 2 in two steps. The compound 2 was treated with ethyl p-amino benzoate
in dioxane to get bis 2,4-(4’-methyl phenyl amino)–s-triazine-6’-yl-aminoethylbenzoate 3.
The structure 3 was confirmed by its spectral and analytical studies. The compound 4 was
obtained by reaction of 3 with hydrazine hydrate and characterized by its spectral and
analytical datas. Its IR spectrum revealed the presence of –NH-, NH2, C=O and aromatic
ring at 2274, 3356, 1670 and 3056 cm-1. The compounds 4 was then condensed with
different aromatic aldehydes to get Schiff bases 5. Which on treatment with thioglycolic acid
gave substituted 4- thiazolidinone. Which was characterized by its spectral and analytical
datas, its IR spectrum revealed the presence of =C=O group in five membered ring at 1820 cm-1
the NMR spectrum of 6 in CDCl3 show one singlet at 7.4 δ due to 3NH protons and one
singlet at 2.82 δ due to 2 CH3 group. The two complex multiplets at 6.2 and 4.2δ were
assigned for 8H of two aromatic rings. The thiazolidinone ring characterized by 1H singlet
at 3.2ppm and 2H singlet at 3.4 δ. The C, H, N analysis of the compounds 6a is in good
agreement with the proposed molecular formula, C33H29H8O2ClS. This was also supported
by mass spectrum of the compound which displayed the molecular ion peak at 637.143 and
491.067. All compounds have exhibited good to moderate antibacterial activity.
Antibacterial activity
The synthesized compounds have been screened for antibacterial activities using filter paper
disc diffusion plate11 method. The testing was carried out at concentration 50 ppm and
100 ppm using bacteria like E. Coli, B. subtilis, S. aureus, B. fragilis and K. pneumonie,
.
Streptomycin (for bacteria) was used as standard drug. Most of the synthesized compounds
have found moderate activity (20-24 zone of inhibition) against different strains of bacteria.
Related data have been given in Table 2.
Table 2. Antibacterial activity of the synthesized compounds 6(a-l) against various bacteria
at two different concentrations (ppm).
E. Coli
B.Subtilis
S.aureus
B.Fragilis
K.pneumonie
Compd
Concd, ppm
Concd, ppm
Concd, ppm
Concd, ppm
Concd, ppm
50
100
50
100
50
100
+++
+++
+++
++
50
+
++
+++
+
++
+++
-
++
++
++
100
++
+++
+++
++
+++
++
-
+++
+++
+++
++
50
100
+++ ++++ +++ ++++ ++
+++
+++ +++ ++++ +++
+++ ++++
+++ ++++
+++
_
++
+++
+
++
++
++
6a
6b
6c
6d
6e
6f
6g
6h
6i
++
++
+++
++
+
+
++
_
+++
++
++
++
++
-
++
++
++
++
++
++
+++
+++
+
+++
+++
+++
+++
+++
+
+
+++
++
++
++
+
++
++
+
++
+++
+++ +++
+
+
++
++
+
++
+++
+++
++
++
+++
+++
++
+++
+++
+++
6j
6k
6l
++
++
+++ +++ +++ ++++
+++ ++ +++ ++
++++ +++
++ +++
+++
Std.
+++ ++++ ++++ ++++ +++ ++++ +++ ++++ +++ ++++
Std. streptomycin is used as standard drug. Inhibition diameter in mm:- 0-4(-), 5-9(+),10-14(++), 15-
19(+++), 20-24(++++).

992 M. K. AHIRWAR et al.
Acknowledgment
1
The authors are thankful to SAIF, CDRI Lucknow for providing HNMR spectral data of
synthesized heterocyclic derivatives. We are also thankful to Prof. P. Mehta, Department of
Botany, for his kind assistance in performing antibacterial activity in Botany Department
and, Head Department of Chemistry, Dr. H.S. Gour University, Sagar providing IR spectral
data and laboratory facilities.
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4. Ergene N and Capan G, II Farmaco, 1994, 49, 449.
5. Ebeid M Y, Fathallah O A, El-Zaher M I, Kamel M M, Abdol W A and Anwar M M,
Bull Fac Pharm., 1996, 34, 125.
6. Parekh H H, Parikh A K and Parikh A R, J Sci I.R. Iran, 2004, 15(2), 143.
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