Synthesis and Antimicrobial activity of Some
Heterocyclic compounds which containing sulfur atoms
Mohamed Abd El-Latif Zein *
* Chemistry department, Faculty of Science, Damanhour University, Damanhour, Egypt.
E-Mail: [email protected] & [email protected]
Abstract
2-(substituted)-[1-(5-methylthiophen-2-yl)ethylidene]hydrazinecarbothioamide (2 and 4a,b),
2-[1-(5-methylthiophen-2-yl)ethylidene]-N-(4-oxo-5,6-dihydro-4H-1,3-thiazin-2-yl)
hydrazinecarbothioamide (3) and 3-[1-(5-methylthiophen-2-yl)ethylidene]amino-2-thioxoimidazolidin4-one
(5)
were
synthesized
ethylidene]hydrazinecarbothioamide
via
the
with
ethyl
reaction
of
chloroacetate,
2-[1-(5-methylthiophen-2-yl)
ethyl-β-chloropropionate
and
bromomethylheterolyl ketones under different conditions. Treatment of 5 with ethyl-βchloropropionate, diethyl oxalate and aryl diazonium salts afforded the corresponding 1-substitutedimidazolidin-2-thione derivative (6) and 5-substituted-imidazolidin-2-thione derivatives (7 and 8). The
prepared compounds also exhibited antimicrobial activity
Keywords: Thiophene, Thioxoimidazolidinone, hydrazine, carbothioamide, Antimicrobial
1- Introduction
In 1966, a novel antienteroviral agent,
myocarditis [1,2]. It is under development by
pleconaril [Fig-1] , was made available for
Viropharma, Inc. for the treatment of severe
treatment of life threatening enteroviral
enteroviral infection in phase 2 clinical trials.
infections, such as meningitis, encephalitis,
Unfortunately, pleconaril has been found to
have limited activity against Enterovirus
World Research Journal of Organic chemistry
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Synthesis and Antimicrobial activity of Some Heterocyclic compounds which containing sulfur atoms
71(EV 71) at concentrations tested in vitro. In
structural
requirements
for
anti-EV
71
our laboratory, many structurally related
activity. Previously, we reported that the
imidazolidinones were recently [2, 3] found to
biphenyl analogues A and B [Fig-2] with
have strong activity against EV 71. SAR
either a phenyl or 4-chlorophenyl moieties at
studies demonstrated that an aryl substituent
the Para position bestowed the best potency to
at the Para position of the phenoxyl ring and a
this class of compounds [4].
pyridine containing imidazolidinone are key
As an extension of our previous work
the reaction of 2-acetyl-5-methylthiophene
[5-11], this paper reported the preparation of
with
some
activity was evaluated against most of the
sulfur
Heterocycles
containing
thiosemicarbazide.
The
thiophene imidazolidinone moieties with
antibacterial and antifungal.
expected biological activity, using 2-[1-(5-
2-Materials and Methods.
methylthiophen-2-
biological
Melting points were determined in
yl)ethylidene]hydrazinecarbothioamide 1 as a
Capillaries with a Thomas Uni-melt apparatus
key starting material which was obtainable in
uncorrected. IR spectra were recorded on
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Mohamed Abd El-Latif Zein
a Perkin-Elmer 1420 spectrometer and a
30.05. Found: C, 44.91; H, 5.01; N, 19.42; S,
Biorad FTS7 (KBr) [Table-2]. NMR spectra
29.85.
were recorded on a general electric QE300
2-(2-[1-(5-methylthiophen-2-
instrument and chemical shifts are given with
yl)ethylidene]hydrazinecarbothioamido)ac
respect to TMS [Table-3]. Mass spectra were
etic acid (2).
obtained on a Jeol JMSD-300 spectrometer
2-[1-(5-methylthiophen-2-yl)ethylidene]-N-
operating at 70 eV. Microanalyses were
(4-oxo-5,6-dihydro-4H-1,3-thiazin-2-
conducted using an elemental analyzer 1106
yl)hydrazinecarbothioamide (3).
[Table-1].
A
mixture
of
1(0.01
2-[1-(5-methylthiophen-2-
ethylchloroacetate
yl)ethylidene]hydrazinecarbothioamide
chloropropionate (0.01 mol) in methoxide
(1):
(30ml) was heated under reflux for 4 hr. the
A
mixture
ethyl-β-
2-acetyl-5-
reaction mixture was cooled and acedified
mol),
with dilute hydrochloric acid (2%). The crude
thiosemicarbazide (0.01 mol) in methanol (30
product was filtered off, washed with water,
ml) was heated under reflux for 2 hr, and then
dried and purified by recrystallization with
cooled. The solid formed was filtered off,
ethanol to give compound 2 and 3.
dried and purified by recrystallization with
Compound 2 (EtOH) as yellow crystals yield
methanol to give 1 as colourless crystals,
65
yield 85%, m.p: 180 οC; IR (KBR): 3456,
3177(NH), 3300-2850(br.OH), 1711(C=O),
3176(NH2), 3240(NH), 1630(C=N), 1605,
1632(C=N),
1592(C=C), 1422(C=S), 1000,800(C-S)cm-1;
1102,1007(C-O),
1
NMR
methylthiophene
of
and/or
mol),
(0.01
H-NMR(DMSO-d6):
δ1.5(s,
3H,
CH3),
%,m.p:
215
ο
C
;
IR(KBr):
1572(C=C),
3296,
1409(C=S),
1000,800(C-S)cm-1.
(DMSO-d6):
δ1.42(s,
3H,
1
H-
CH3),
δ2.1(s, 3H, CH3), δ6.5 (d, 1H,Thiophene-H),
δ2.12(s, 3H, CH3), δ4.57(d, 2H, CH2), δ
δ7.6(d, 1H, Thiophene-H), δ7.25(s, 1H, NH),
7.02(d, 1H, Thiophene-H), δ 8.21 (d, 1H,
δ8.77(s, 2H, NH2), ppm. MS (m/z, %):
Thiophene-H), δ 8.57(s, 1H, NH-CH2), δ
213(M+,
194(25.50),
10.21(s,
138(25.40),
1H,OH)ppm. MS (m/z, %): 271(M+, 37.10),
37.10),
181(21.80),
198(29.40),
153(11.60),
1H,
124(41.40), 116(56.20), 97(100), 89(5.80),
256(10.11),
75(8.50),
212(12.85),
60(11.80).
Anal.
Calcd.
For
C8H11N3S2: C, 45.07; H, 5.16; N, 19.71; S,
=N-NH-CS),
254(31.12),
153(73.11), 138(34.28), 133(57.91),
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12.42(s,
226(21.84),
197(65.17),
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δ
174(100),
Synthesis and Antimicrobial activity of Some Heterocyclic compounds which containing sulfur atoms
197(84.12),
74(12.65),
59(44.26).
under reflux for 6 hr, then cooled and poured
Anal.Calcd. for C10H13N3O2S2: C, 44.28; H,
into water. The resulting solid was filtered
4.79; N, 15.49; S, 23.62. Found: C, 44.11; H,
off, washed with water, dried and purified by
4.52; N, 15.23; S, 23.35.
recrystallization from a suitable solvent to
Compound 3 (ethanol) as yellow crystals
give 4 and 5.
yield 85% , m.p: 265
3229(NH),
1585(C=C),
1685(C=O),
ο
C; IR (KBr):
1630(C=N),
1000,800(C-S)cm-1;
1
H-
2-[1-(5-methylthiophen-2-yl)ethylidene]-N(2-oxo-2-(pyridine-4yl)ethylhydrazinecarbothioamide
as
(4a),
ο
NMR(DMSO-d6): δ1.41(s, 3H, CH3), δ2.25(s,
yellow crystals, yield 75%, m.p:245 C; IR
3H, CH3),
δ 2.93-3.08(t, 2H, COCH2-), δ
(KBr): 3235(NH), 1682(C=O), 1630(C=N),
3.38-3.58(t, 2H, S-CH2-), δ 7.11 (d, 1H,
1602(C=C), 1463(C=S), 1000,800(C-S)cm-1.
Thiophene-H), δ 7.81 (d, 1H, Thiophene-H), δ
1
9.61(s, 1H, NH)ppm. MS (m/z,%): 267(M+,
δ2.08(s, 3H, CH3), δ4.61(s, 2H, NHCH2CO),
30.70), 252(41.20), 170(100), 153(22.30),
δ6.65 (d, 1H, Thiophene-H), δ7.11(d, 1H,
138(76.50), 129(32.00), 114(15.00), 97(98) .
Thiophene-H), δ7.55-8.29(m, 4H, pyridine-
Anal.Calcd. for C11H13N3OS2: C, 49.44; H,
H),
4.87; N, 15.73; S, 23.97. Found: C, 49.21; H,
=NNHCS)ppm. MS (m/z, %): 332(M+,
4.11; N, 15.29; S, 23.68.
25.35), 317(15.28), 254(17.14), 235(45.82),
2-[1-(5-methylthiophen-2-yl)ethylidene]-N-
226(10.94),
(2-oxo-2-
194(75.18),
179(33.28),
153(57.91),
(Aroyl)ethylhydrazinecarbothioamide
138(75.43),
135(16.55),
120(28.24),
(4a,b).
106(47.22), 97(63.54), 78(29.18).
3-[1-(5-methylthiophen-2-
Calcd. for C15H16N4OS2: C, 54.19; H, 4.85;
yl)ethylidene]amino-2-thioxoimidazolidin-
N, 16.85; S, 19.29. Found: C, 54.03; H, 4.51;
4-one (5)
N, 16.39; S, 18.97.
A mixture of 1 (0.01 mol), ω-bromo
H-NMR (DMSO-d6): δ1.27(s, 3H, CH3),
δ9.51(s, 1H, NHCH2), δ11.22(s, 1H,
212(48.33),
197(100),
Anal.
2-[1-(5-methylthiophen-2-yl)ethylidene]-N-
methyl heterolyl ketones( such as ω-bromo
(2-oxo-2-(thiophen-2-
methyl H-pyridyl ketone and ω-bromomethyl-
yl)ethylhydrazinecarbothioamide
2-thinoyl ketone) and ethyl chloro acetate
yellow
(0.01mol) in methanol (50 ml) in presence of
m.p:125οC;IR(KBr): 3300(NH), 1675(C=O),
crystals,
yield
fused sodium acetate (0.03 mol) was heated
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(4b),as
60%,
Mohamed Abd El-Latif Zein
1631(C=N),
1603(C=C),
-1
1412(C=S),
1
Ethyl-3-(3-[1-(5-methylthiophen-2-
1000,800(C-S) cm . H-NMR (DMSO-d6):
yl)ethylidene]amino-4-oxo-2-
δ1.51(s, 3H, CH3), δ2.21(s, 3H, CH3), δ
thioxoimidazolidin-1-yl)propanoate (6).
4.87(s, 2H, NHCH2CO), δ 6.54(d, 1H,
A mixture of 5 (0.01 mol ), ethyl
Thiophene-H), δ 7.40(m, 2H, Thiophene-H),
propionate (0.01mol) and fused sodium
δ 7.81(d, 1H, Thiophene-H), δ 7.98(d, 1H,
acetate (0.03 mol) in dimethyl formamide
Thiophene-H),
δ 9.58(s, 1H, NHCH2), δ
(30ml) was heated under reflux for 6 hr, then
11.33(s, 1H, =NNHCS)ppm. MS (m/z, %):
cooled and poured into water. The solid
+
337(M ,
45.87),
254(65.81),
obtained was filtered off, washed with water,
212(32.11),
dried and purified by recrystallization from
184(100),
ethanol to give 6 as yellow crystals, yield
138(86.43),
80%,m.p:270 οC; IR(KBr):1745(CO of ester),
125(13.51), 111(27.24), 97(83.58), 83(19.18).
1707(CO of imide), 1620(C=N), 1408(C=S),
Anal. Calcd. For C14H15N3OS3: C, 49.82; H,
1263, 1199(C-O), 1000,800(C-S)cm-1.
4.48; N, 12.45; S, 28.50. Found: C, 49.29; H,
NMR (DMSO-d6): δ1.30 (t, 3H, CH3),
4.18; N, 12.36; S, 28.23.
δ1.65(s, 3H, CH3), δ2.22 (s, 3H, CH3),
3-[1-(5-methylthiophen-2-
δ2.65(t, 2H, CH2CO), δ3.81(t, 2H, NCH2),
yl)ethylidene]amino-2-thioxoimidazolidin-4-
δ4.21-4.56(q,
one (5), as orange crystals, yield 70%;
NCH2CO), δ6.82 (d, 1H, Thiophene-H),
m.p:260 οC; IR (KBr):3225(NH), 1705(C=O),
δ7.25(d, 1H, Thiophene-H) ppm. MS (m/z,
1625(C=N),
%): 353(M+, 43.70), 338(11.25), 324(65.24),
240(14.82),
199(12.10),
153(63.28),
322(18.23),
226(19.54),
197(72.54),
140(17.91),
1603(C=C),
1411(C=S),
2H,
OCH2),
δ4.84(s,
1
H-
2H,
1000,800(C-S) cm-1. 1H-NMR (DMSO-d6):
308(21.30),
280(37.12),
266(32.00),
δ1.22(s, 3H, CH3), δ2.18(s, 3H, CH3),
256(64.01),
252(98.00),
215(17.54),
δ4.42(s, 2H, NHCH2CO), δ6.65 (d, 1H,
138(100), 101(32.28), 97(87.45),87(12.48),
Thiophene-H), δ7.31(d, 1H, Thiophene-H),
73(26.13),45(11.24).
δ9.53(s, 1H, NH)ppm. MS (m/z, %): 253(M+,
C15H19N3O3S2: C, 50.97; H, 5.42; N, 11.89; S,
38.14), 238(11.20), 156(64.81), 138(100),
18.14. Found: C, 49.88; H, 5.32; N, 11.75; S,
115(44.50),
17.97.
97(81.54).
Anal.Calcd.
for
Anal.
Calcd.
For
C10H11N3OS2: C, 47.41; H, 4.38; N, 16.59; S,
Ethyl-2-(1-[1-(5-methylthiophen-2-
25.31 Found: C, 47.10; H, 4.22; N, 16.18; S,
yl)ethylidene]amino-5-oxo-2-
25.08.
thioxoimidazolidin-4-yl)-2-oxoacetate (7)
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A mixture of 5 (0.01 mol), diethyl oxalate
ο
(0.01mol) and sodium metal (0.03 mol) in
added dropwise with stirring during 45 min.
xylene (50 ml) was heated under reflux for 4
After addition the mixture was stirred for
hr. the reaction mixture was cooled and
further 30 min and then left for 2 hr in a
poured into ice-dilute
refrigerator. The precipitated product was
HCl. The organic layer was extracted and
collected, washed with water, dried, and
evaporated.
purified by recrystallization with methanol to
The
solid
obtained
was
crystallized from toluene to give 7 as pale
yellow crystals, yield 60%,m.p: 215
ο
C;
C) of the diazonium salt (0.02 mol) was
give 8.
3-[1-(5-methylthiophen-2-
IR(KBr): 3235(NH), 1740-1701(br. CO of
yl)ethylidene]amino-5-(phenyldiazenyl)-2-
ester and amide), 1630(C=N), 1602(C=C),
thioxoimidazolidin-4-one
1463(C=S),
1086(C-O),
crystals, yield 70%, m.p:110 οC; IR(KBr):
H-NMR (DMSO-d6):
3285(NH), 1702(C=O), 1630(C=N), 1602,
δ1.42 (t, 3H, CH3), δ1.61(s, 3H, CH3-C=N),
1585(C=C), 1428(C=S), 1000,800(C-S)cm-1.
δ2.33(s, 3H, CH3-thiophene), δ4.01-4.21(q,
1
2H,OCH2), δ4.63(s,1H,CHCO), δ6.74 (d, 1H,
δ2.32(s, 3H, CH3), δ3.98 (s, 1H, COCHN),
Thiophene-H), δ7.54(d, 1H, Thiophene-H),
δ6.63 (d, 1H, Thiophene-H), δ7.12(d, 1H,
δ9.11(s, 1H, NH)ppm. MS (m/z, %): 353(M+,
Thiophene-H),
28.54), 338(16.82), 324(15.33), 308(42.81),
δ9.20(s, 1H, NH)ppm. MS (m/z, %): 357(M+,
280(57.22),
28.70), 342(18.37), 280(65.24), 260(28.15),
1234,
1000,800(C-S)cm-1.
1138,
1
256(13.24),
252(68.31),
(8a)
as
orange
H-NMR (DMSO-d6): δ1.36(s, 3H, CH3),
δ7.51-7.93(m,
ArH),
215(78.24), 138(89.12), 101(56.28), 97(100),
252(100),
73(57.41),
for
105(68.77), 97(57.56), 77(42.57). Anal.Calcd.
C14H15N3O4S2: C, 47.58; H, 4.28; N, 11.89; S,
for C16H15N5OS2: C, 53.76; H, 4.23; N, 19.59;
18.15. Found: C, 47.11; H, 3.98; N, 11.56; S,
S, 17.94. Found: C, 53.55; H, 3.89; N, 19.33;
17.95.
S, 17.68.
5-arylazo-3-[1-(5-methylthiophen-2-
5-(2-chlorophenyldiazenyl)-3-[1-(5-
yl)ethylidene]amino-2-thioxoimidazolidin-
methylthiophen-2-yl)ethylidene]amino-2-
4-one (8a, b)
thioxoimidazolidin-4-one
45(24.54).
Anal.
Calcd.
A solution of 5 (0.01 mol) in aqueous
219(42.13),
5H,
(8b)
crystals, yield 85%, m.p:95
138(64.01),
as
yellow
ο
C;IR(KBr):
sodium hydroxide (50 ml, 10%) was a chilled
3325(NH), 1710(C=O), 1631(C=N), 1603,
in ice to 0-5 οC. A cold aqueous solution (0-5
1588(C=C), 1423(C=S), 1000,800(C-S)cm-1.
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Mohamed Abd El-Latif Zein
1
H-NMR (DMSO-d6): δ1.05(s, 3H, CH3),
280(12.29),
δ1.98(s, 3H, CH3), 3.97 (s, 1H, COCHN),
139(19.28),
δ6.22 (d, 1H, Thiophene-H), δ7.18(d, 1H,
97(32.28). Anal.Calcd. for C16H14ClN5OS2:
Thiophene-H),
ArH),
C, 49.04; H, 3.60; N, 17.87; Cl,9.06; S, 16.34.
10.19(s, 1H, NH)ppm. MS (m/z, %): 391(M+,
Found: C, 48.87; H, 3.32; N,17.59; Cl, 8.79;
43.70), 376(31.25), 356(85.24), 294(21.30),
S, 16.15.
7.31-7.93(m,
4H,
253(29.44),
138(78.54),
252(100),
111(54.21),
[Table-1]: Elemental Analysis
Compd.
C%
H%
N%
S%
Cl%
No.
formula
Calculd.
found
Calculd.
found
Calculd.
found
Calculd.
found
Calculd.
found
1
C8H11N3S2
45.07
44.91
5.16
5.01
19.71
19.42
30.05
29.85
-
-
2
C10H13N3O2S2
44.28
44.11
4.79
4.52
15.49
15.23
23.62
23.35
-
-
3
C11H13N3OS2
49.44
49.21
4.87
4.11
15.73
15.29
23.97
23.68
-
-
4a
C15H16N4OS2
54.19
54.03
4.85
4.51
16.85
16.39
19.29
18.97
-
-
4b
C14H15N3OS3
49.82
49.29
4.48
4.18
12.45
12.36
28.50
28.23
-
-
5
C10H11N3OS2
47.41
47.10
4.38
4.22
16.59
16.18
25.31
25.08
-
-
6
C15H19N3O3S2
50.97
49.88
5.42
5.32
11.89
11.75
18.14
17.97
-
-
7
C14H15N3O4S2
47.58
18.15
4.28
3.98
11.89
11.56
18.15
17.95
-
-
8a
C16H15N5OS2
53.76
53.55
4.23
3.89
19.59
19.33
17.94
17.68
-
-
8b
C16H14ClN5OS2
49.04
48.87
3.60
3.32
17.87
17.59
16.34
16.15
9.06
8.79
[Table-2]: IR Values by cm-1
No.
1
NH2
3456, 3176
2
3
4a
4b
5
NH
OH
3240
3296, 33003177 2850
3229
3235
3300
3225
6
7
3235
8a
8b
3285
3325
C=O
1711
1685
1682
1675
3225
1745,1707
17401701
1702
1710
C=N
3240
C=C
1605, 1592
C=S
1422
C-S
1000,800
1632
1632
1409
1000,800 1102,1007
1630
1630
1631
1625
1585
1602
1631
1625
1463
1412
1411
1000,800
1000,800
1000,800
1000,800
1408
1000,800
1620
1630
1602
1463
1000,800
1630
1631
1602, 1585
1603, 1588
1428
1423
1000,800
1000,800
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C-O
1263,
1199
1234,
1138
Synthesis and Antimicrobial activity of Some Heterocyclic compounds which containing sulfur atoms
[Table-3]: 1H-NMR spectra data (DMSO-d6): Chemical shifts δ(ppm) from TMS, J(Hz).
No.
CH3-C=N
1.5(s, 3H)
1
1.42(s, 3H)
CH3C-S
2.1(s,
3H)
2.12(s,
3H)
CH2
Thiophene-H
NH
NH2
6.5(d,1H)& 7.6(d,1H)
7.25(s, 1H)
8.77(
s,2H)
4.57(d, 2H)
7.02(d,1H)&
8.21(d,1H)
8.57(s,
1H,NHCH2) &
10.21(s,
1H, =NNH-CS)
2
1.41(s, 3H)
2.25(s,
3H)
2.93-3.08(t, 2H, COCH2)& 3.38-3.58(t, 2H, SCH2-)
7.11(d,1H)&
7.81(d,1H)
9.61(s, 1H)
1.27(s, 3H)
2.08(s,
3H)
4.61(d, 2H)
6.65(d,1H),7.11(d,1H)
&
δ7.55-8.29(m, 4H,
pyridine-H),
1.51(s, 3H)
2.21(s,
3H)
4.87(s, 2H)
6.54(d,1H),7.40(m,2H)
,
7.81(d,
1H)&7.98(d,1H)
1.22(s, 3H)
2.18(s,
3H)
2.22(s,
3H)
4.42(s, 2H)
6.65(d,1H)&
7.31(d,1H)
6.82(d,1H)&
7.25(d,1H)
9.51(s, 1H,
NHCH2) &
11.22(s,
1H,
=NNHCS)
9.58(s, 1H,
NHCH2) &
11.33(s,
1H,
=NNHCS)
9.53(s, 1H)
3
4a
4b
5
1.30(t,
3H)&1.65(s,3
H)
6
1.42(t,3H)&1.6
1(s,3H)
7
1.36(s,3H)
8a
1.05(s, 3H)
8b
2.33(s,
3H,
CH3thioph
ene)
2.32(s,
3H)
1.98(s,
3H)
δ2.65(t, 2H, CH2CO),
δ3.81(t, 2H, NCH2),
δ4.21-4.56(q, 2H, OCH2),
δ4.84(s, 2H, NCH2CO)
δ4.01-4.21(q, 2H,OCH2)& 6.74(d,1H)&7,54(d,1H
δ4.63(s,1H,CHCO)
)
δ3.98 (s, 1H, COCHN)
3.97 (s, 1H, COCHN)
9.11(s,1H)
6.63 (d, 1H), 7.12(d,
9.20(s,1H)
1H)& 7.51-7.93(m, 5H,
ArH)
6.22 (d, 1H), δ7.18(d,
10.19(s,
1H) &7.31-7.93(m, 4H, 1H)
ArH)
World Research Journal of Organic chemistry
ISSN: 2320-3374 & E-ISSN: 2320-5679, Volume 2, Issue 1, 2013
Bioinfo Publications
OH
12.42
(s,1H
)
Mohamed Abd El-Latif Zein
yl)ethylidene]hydrazinecarbothioamide
3- Result and Discussion
(1)
with ω-bromo-methylarylketones (such as 4The reaction of 2-[1-(5methylthiophen-2-
ω-bromo-methylketone)
yl)ethylidene]hydrazinecarbothioamide
with
pyridyl- ω -bromomethylketone and 2-thinyl-
ethylchloroacetate
and
and
(1)
chloroacetate in presence of fused sodium
ethyl-β-
acetate in methanol under reflux, yielded the
propionate in methoxide under reflux gave the
corresponding
corresponding
yl)ethylidene]-N-(2-oxo-2-
2-(2-[1-(5-methylthiophen-2-
2-[1-(5-methylthiophen-2-
yl)ethylidene]hydrazinecarbothioamido)acetic
(Aroyl)ethylhydrazinecarbothioamide
acid
and
(2)
and
ethyl
2-[1-(5-methylthiophen-2-
(4a,b)
3-[1-(5-methylthiophen-2-
yl)ethylidene]-N-(4-oxo-5,6-dihydro-4H-1,3-
yl)ethylidene]amino-2-thioxoimidazolidin-4-
thiazin-2-yl)hydrazinecarbothio-amide
one (5), [Scheme-1].
Treatment
of
(3).
2-[1-(5-methylthiophen-2-
[Scheme-1]
World Research Journal of Organic chemistry
ISSN: 2320-3374 & E-ISSN: 2320-5679, Volume 2, Issue 1, 2013
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Synthesis and Antimicrobial activity of Some Heterocyclic compounds which containing sulfur atoms
Alkylation of compound 5 with ethyl-β-
corresponding
ethyl-2-(1-[1-(5-
chloropropionate in presence of fused sodium
methylthiophen-2-yl)ethylidene]amino-5-oxo-
acetate in dimethyl formamide under reflux
2-thioxoimidazolidin-4-yl)-2-oxoacetate
led to the formation of ethyl-3-(3-[1-(5-
Diazotization [10,11] of aromatic amines
methylthiophen-2-yl)ethylidene]amino-4-oxo-
(such as aniline and 2-chloroaniline) followed
2-thioxoimidazolidin-1-yl)propanoate
by coupling with sodium salt of 5 gave the
(6,Scheme 2). Heating [6] of (5)
corresponding
with diethyl oxalate in Xylene in the presence
methylthiophen-2-yl)ethylidene]amino-2-
of sodium metal under reflux gave the
thioxoimidazolidin-4-one (8a, b [Scheme-2]).
5-arylazo-3-[1-(5-
[Scheme-2]
World Research Journal of Organic chemistry
ISSN: 2320-3374 & E-ISSN: 2320-5679, Volume 2, Issue 1, 2013
Bioinfo Publications
(7).
Mohamed Abd El-Latif Zein
by measuring the zone of inhibition. The
4-The Antimicrobial activity
Synthesized
compounds
screening results given in [Table-4] indicated
were
assayed against Gram positive bacteria (such
that
as Bacillus subtilis, Streptococcus penumonia
antimicrobial activities against one or the
and Staphylococcus aureas), Gram negative
other type of bacteria and fungi. Compound 3,
bacteria (such as E.coli and Pesudomonas)
4a,4b, 6, 7, 8a and 8b showed higher activity
and Fungi (such as Aspergillus niger and
against bacteria and fungi, Also, compounds 2
Penicillium) following Vincent and Vincent
and 5 were most moderate activity against
filter
bacteria and fungi.
paper
compounds
disc
method
[12,13].
were
tested
at
The
all
the
compounds
exhibited
100μg/ml
concentration and the activity was determined
[Table-4] The Antimicrobial activity of some synthesized compounds.
2
3
4a
4b
5
6
-
+++
+++
+++
-
+
+++ +++
+++
+
++
+++
+
+
+++
+++ +++
+++
++
+++
+++
+++
++
+++
+++ +++
++
E.coli
+
+++
++
+++
++
+++
+++ +++
+++
Pesudomonas sp.
-
+++
+++
+++
-
+++
++
++
+++
Antifungal
Aspergillus niger
++
++
+++
+++
++
+++
+++ +++
+++
Activity
Penicillium sp.
+
+++
+++
++
+
+++
++
+++
Bacillus subtilis
Gram
Streptococcus
Positive
penumonia
Bacteria
Staphylococcus
aureas
Gram
Negative
Bacteria
7
8a
++
8b
Note:(- )No antimicrobial activity, (+) Mild activity, (++) Moderate activity, (+++) Marked activity.
5-conclusion
The Antimicrobial data revealed that with
slight modifications in the structure one can
plan for the drug design.
World Research Journal of Organic chemistry
ISSN: 2320-3374 & E-ISSN: 2320-5679, Volume 2, Issue 1, 2013
Bioinfo Publications
Synthesis and Antimicrobial activity of Some Heterocyclic compounds which containing sulfur atoms
[11] J.A.Hasanen, H.K.Ibrahim, M.A.Zein
References
[1] D.C.Pevear, T.M. Tull, M.E. Seipel, J.M
G.roarke, (1999) Antimicrob. Agents
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World Research Journal of Organic chemistry
ISSN: 2320-3374 & E-ISSN: 2320-5679, Volume 2, Issue 1, 2013
Bioinfo Publications