Synthesis of some thiazolyl and thiadiazolyl derivatives of substituted furan and pyrrole

Article abstract of DOI:10.1002/jhet.5570440104

(Chemical Equation Presented) Four series of substituted furan and pyrrole have been synthesized. The first series was prepared by cyclization of the key intermediates ethyl 5-[(4-substituted thiosemicarbazido)methyl]-2-methylfuran-3- carboxylates 2a-2d and 1-[(4-acetyl-5-methyl-1H-pyrrol-2-yl)methylene]-4- substituted thiosemicarbazides 8a-8d with chloroacetic acid or (ethyl bromoacetate) to afford the corresponding 4-oxo-3-substituted thiazolidin-2-ylidene 3a-3d or 3-substituted thiazolidin-4-one 9a-9d. On the other hand, heating of the intermediates 2a-2d or 8a-8d with acetic anhydride afforded the corresponding (N-substituted acetylamino)-2,3-dihydro-[1,3,4] thiadiazol-2-yl derivatives 4a-4d and [1,3,4]thiadiazol-2-yl-N-substituted acetamide 10a-10d respectively, while cyclization with p-bromophenacyl bromide gave rise to the corresponding 3-substituted thiazol-2-yl-ylidene 5a-5d and 11a-11d respectively. Furthermore, 4-oxo-3-substituted thioureido-thiazolidin-2- yl 6a-6d or 4-oxo-thiazolidin-3-yl-3-substituted thiourea 12a-12d were obtained by reaction of the intermediates 2a-2d or 8a-8d with thioglycolic acid. Some of the synthesized compounds showed promising antimicrobial activities.

Full text of DOI:10.1002/jhet.5570440104

Jan-Feb 2007
21
Synthesis Of Some Thiazolyl And Thiadiazolyl Derivatives Of
Substituted Furan And Pyrrole
Seham Y. Hassan *
Department of Chemistry, Faculty of Science, Alexandria University, Egypt
Received November 29, 2005
S
R1
H2N
R
N
H
N
H
+
CHO
X
H3C
a)R=H
b)R=C6H5
c)R=p-ClC6H4 d)R=p-CH3C6H4
R1
S
R1
S
R
HSCH2COOH
N
N
H3C
X
N
H
N
H
O
X
H3C
HN
N
p-
B
S
r
C6
H4
CO
H
C
t
A c
H2
Br
R
COOH
2
O
2
R1
COOE
2
r
CH
o
N
N
N
Cl
CH
S
Br
R
X
H3C
R1
R
N
CH3
S
N
R1
N
N
N
O
X
H3C
S
X
H3C
N
R
O
H3C
Br
O
Four series of substituted furan and pyrrole have been synthesized. The first series was prepared by
cyclization of the key intermediates ethyl 5-[(4-substituted thiosemicarbazido)methyl]-2-methylfuran-3-
carboxylates 2a-2d and 1-[(4-acetyl-5-methyl-1H-pyrrol-2-yl)methylene]-4-substituted thiosemicarbazides
8a-8d with chloroacetic acid or (ethyl bromoacetate) to afford the corresponding 4-oxo-3-substituted
thiazolidin-2-ylidene 3a-3d or 3-substituted thiazolidin-4-one 9a-9d. On the other hand, heating of the
intermediates 2a-2d or 8a-8d with acetic anhydride afforded the corresponding (N-substituted
acetylamino)-2,3-dihydro-[1,3,4]thiadiazol-2-yl derivatives 4a-4d and [1,3,4]thiadiazol-2-yl-N-substituted
acetamide 10a-10d respectively, while cyclization with p-bromophenacyl bromide gave rise to the
corresponding 3-substituted thiazol-2-yl-ylidene 5a-5d and 11a-11d respectively. Furthermore, 4-oxo-3-
substituted thioureido-thiazolidin-2-yl 6a-6d or 4-oxo-thiazolidin-3-yl-3-substituted thiourea 12a-12d were
obtained by reaction of the intermediates 2a-2d or 8a-8d with thioglycolic acid. Some of the synthesized
compounds showed promising antimicrobial activities.
J. Heterocyclic Chem., 44, 21 (2007).
INTRODUCTION
including anti-inflammatory, antimicrobial, antitumor or
antifungal activities as well as inotropic and chronotropic
activities [4-14]. In addition there have been some reports
concerning biological interest for furans, pyrroles and
their derivatives [2, 15-18]. However; there is a little data
describing compounds containing the two heterocyclic
moieties, thiazoline and furan or pyrrole. Interest in this
class of compounds prompted the synthesis of the several
furanylthiosemicarbazones, pyrrolylthiosemicarbazones,
thiazolidine, thiazolidinone and thiadiazolidine
derivatives as potential antibacterial agents. We aimed at
utilizing a furan or a pyrrole ring as a carrier for the
bacterostatic thiosemicarbazone moiety and investigated
this combination for antibacterial activity. Accordingly a
A wide variety of pharmacological properties have been
shown to be associated with thiazolidone derivatives
which include anesthetic, anticonvulsant and hypnotic
activities [1]. They also display a large variety of
activities such as antibiotic, diuretic, organoleptic, tuber-
culostatic, antileukemik and antiparasitical activities [2].
Recently certain thiadizolines and thiosemicarbazones
have been reported to exhibit antiviral and antibacterial
properties and were evaluated for biological activity
against various microorganisms [3]. Also several of these
derivatives likewise, compounds possessing a thiazoline
moiety often exhibit additional biological activities [19]

22
S. Y. Hassan
Vol 44
Scheme 1
S
C2H5OOC
H3C
H2N
R
N
N
+
H
H
CHO
O
a)R=H
b)R=C6H5
c)R=p-ClC6H4 d)R=p-CH3C6H4
1
C2H5OOC
S
S
C2H5OOC
H3C
H3C
O
HSCH2COOH
B
R
N
N
N
O
N
HN
N
H
H
O
S
p-
H
r
C6
H4
R
CO
6a-6d
A c
CH
2
t
Br
2
O
COOH
2
2a-2d
COOE
2
r
C2H5OOC
H3C
CH
o
H
Cl
N
N
N
C
Br
S
R
N
O
C2H5OOC
H3C
R
CH3
S
N
C2H5OOC
H3C
N
N
N
N
O
O
S
O
R
O
H3C
Br
O
3a-3d
5a-5d
4a-4d
Schemes 1 and 2. The key intermediates ethyl 5-[(4-
substituted thiosemicarbazido)methyl]-2-methylfuran-3-
series of thiazolyl and thiadiazolyl substituted furan and
pyrrole derivatives were designated and synthesized in
our laboratory. Antimicrobial and antifungal activities of
these compounds were measured.
carboxylates, 2a-2d, and 1-[(4-acetyl-5-methyl-1H-pyrrol-
2-yl) methylene]-4-substituted thiosemicarbazides, 8a-8d,
were synthesized by condensation of ethyl 5-formyl-2-
methylfuran-3-carboxylate, 1, [20] or 4-acetyl-5-methyl-
1H-pyrrole-2-carbaldehyde, 7, [21] with thiosemi-
carbazide derivatives. The ir spectra of compounds 2a-2d
RESULTS AND DISCUSSION
Chemistry. The target compounds, 2a-6d and 8a-12d
were synthesized according to the steps outlined in
Scheme 2
H3COC
H3C
S
H2N
R
N
CHO
N
+
H
H
N
H
a)R=H
c)R=p-ClC6H4
b)R=C6H5
d)R=p-CH3C6H4
7
H3COC
H3C
S
R
H
S
N
H3COC
HSCH2COOH
N
H
N
NH
N
O
HN
N
N
H
H3C
S
p-
B
8a-8d
H
r
C6
H4
CO
R
CH
2
t
E
A c
Br
O
2
12a-12d
COOH
2
O
CO
r
2
CH
o
H3COC
H3C
H
N
N
Cl
C
Br
S
R
N
N
H
N
H3COC
H3C
R
CH3
S
H3COC
H3C
N
N
N
S
O
N
H
N
N
H
N
R
O
H3C
O
Br
9a-9d
10a-10d
11a-11d

Jan-Feb 2007
Thiazolyl and Thiadiazolyl Derivatives of Substituted Furan and Pyrrole
23
and 8a-8d showed NH bands at 3134-3440 cm-1, and their
proton nmr spectra showed deuterium exchangeable
singlets due to NH protons at ꢀ 9.07-11.86 ppm.
Treatment of these 4-substituted thiosemicarbazides,
compounds 2 and 8 with chloroacetic acid and fused
sodium acetate or with ethyl bromoacetate afforded 2-
furan-3-carboxylic acid ethyl ester, 5a-5d, and 1-(5-{[4-(4-
bromo-phenyl)-3H-3-substituted thiazol-2-yl-ylidene]hydra-
zono-methyl}-2-methyl-1H-pyrrol-3-yl)-ethanone, 11a-11d,
respectively. Their ir spectra lacked the bands due to NH
and their proton nmr spectra lacked signals characteristic
for NH protons and showed new singlet at ꢀ 6.72-7.64 ppm
attributed to CH thiazol-2-yl-ylidene. Reaction of thiosemi-
carbazone derivatives 2a-2d and 8a-8d with thioglycolic
acid in dry benzene gave rise to the corresponding 2-
methyl-5-[(4-oxo-3-substituted
thiazolidin-2-ylidene)-
hydrazonomethyl]-furan-3-carboxylic acid ethyl ester, 3a-
3d, or 2-[(4-acetyl-5-methyl-1H-pyrrol-2-yl-methylene)-
hydrazono]-3-substituted
thiazolidin-4-one,
9a-9d,
methyl-5-(4-oxo-3-substituted
thio-ureido-thiazolidin-2-
respectively. The ir spectra of compounds 3 and 9 showed
the disappearance of NH bands of substituted thio-
semicarbazone moiety and a new band at 1693-1718 cm-1
attributed to a carbonyl group of thiazolidin-4-one. Their
proton nmr spectra lacked signals characteristic for NH
protons and showed new singlet at ꢀ 3.83-4.06 ppm
attributed to CH2-thiazolidinone. 5-(3-Acetyl-5-(N-substi-
tuted acetylamino)-2,3-dihydro-[1,3,4]thiadiazol-2-yl)-2-
methyl-furan-3-carboxylic acid ethyl ester 4a-4d, and N-[4-
acetyl-5-(4-acetyl-5-methyl-1H-pyrrol-2-yl)-4,5-dihydro-
[1,3,4]thiadiazol-2-yl]-N-substituted acetamide, 10a-10d,
were prepared by heating the corresponding thio-
semicarbazones 2a-2d and 8a-8d with acetic anhydride
respectively. Their ir spectra lacked the bands due to NH
and showed a new band at 1642-1698 cm-1 attributed to an
acetyl group of [1,3,4]-thiadiazol-2-yl. Their proton nmr
spectra lacked signals characteristic for NH protons and
showed new singlet at ꢀ 6.10-6.61 ppm attributed to CH of
1,3,4-thiadiazolyl in addition to signals due to methyl groups
of the CH3CO at 1.28-1.94 ppm. On the other hand, reaction
of thiosemicarbazones 2a-2d and 8a-8d with p-bromo-
phenacyl bromide gave 5-{[4-(4-bromo-phenyl)-3H-3-
substituted thiazol-2-yl-ylidene]hydrazonomethyl}-2-methyl-
yl)-furan-3-carboxylic acid ethyl ester , 6a-6d, or [2-(4-
acetyl-5-methyl-1H-pyrrol-2-yl)-4-oxo-thiazolidin-3-yl]-3-
substituted thioureas 12a-12d. Their ir spectra showed
besides the bands due to NH, a carbonyl absorption band at
1645-1693 cm-1. Their proton nmr spectra showed signals
characteristic for NH protons and showed two new singlets
at ꢀ 3.34-3.46, 6.10-7.97 ppm attributed to CH2 and CH of
4-oxo-thiazolidinyl respectively.
Biological Results. The designed compounds 2a-6d
and 8a-12d have been evaluated for their antimicrobial
activity. The microdilution susceptibility test in Müller-
Hinton Broth (Oxoid) and Sabouraud Liquid Medium
(Oxoid) were used for the determination of antibacterial
and antifungal activity [22,23]. The minimal inhibitory
concentration (MIC) listed in (Table 1) showed that
compounds 3a-3d, and 9a have antifungal activity against
C. albicans comparable to that of Clotrimazole
(Canesten®, Bayer). Other compounds are active against
S. aureus and E. coli. Compound 10a has antimicrobial
activity against S. aureus comparable to that of ampicillin,
while the activity of compounds 2a and 6b is about 50%
of that of ampicillin. Compounds 5b and 6a have
antimicrobial activity against E. coli comparable to that of
Table 1.
Minimal Iinhibitory Concentrations (MIC μg/ml) of Test Compounds
Test compound
E. coli
S. aureus
C. albicans
Test
compound
6d
E. coli
S. aureus
C. albicans
Ampicillin
Clotrimazole
25
---
12.5
…..
25
>200
>200
100
50
50
>200
100
>200
100
>200
>200
>200
>200
100
---
12.5
50
>200
>200
>200
>200
>200
100
>200
100
100
>200
>200
>200
200
>200
12.5
>200
100
100
200
100
>200
100
>200
100
>200
100
>200
100
>200
100
8a
8b
8c
8d
9a
9b
9c
9d
10a
10b
10c
10d
11a
11b
11c
11d
12a
12b
12c
12d
>200
200
100
200
100
>200
200
200
100
>200
100
>200
100
>200
>200
>200
100
>200
>200
>200
2a
2b
2c
2d
3a
3b
3c
3d
4a
4b
4c
4d
5a
5b
5c
5d
6a
6b
6c
200
100
100
200
100
200
100
100
50
>200
>200
>200
>200
12.5
12.5
12.5
12.5
>200
>200
>200
100
>200
>200
>200
>200
>200
>200
>200
12.5
>200
50
50
>200
>200
>200
25
200
100
25
>200
>200
>200
>200
>200
>200
>200
>200
>200
100
>200
25
>200
200
>200

24
S. Y. Hassan
Vol 44
3.34 (s, 3H, COCH3), 6.68 (s, 1H, CH-pyrrole), 6.79 (s, 1H,
CH=N), 10.00 (s, 1H, NH), 11.66 (s, 1H, NH), 11.75 (s, 2H,
2NH).
ampicillin, while the activity of compounds 4a, 4b and 6d
is about 50% of that of ampicillin.
1-((4-Acetyl-5-methyl-1H-pyrrol-2-yl)methylene)-4-phenyl-
thiosemicarbazide (8b). Yield: 78.6%; yellow crystals; mp
210-211ºC (lit. [24] 210ºC); ir: 3334, 3226, 3134 (NH), 1660
(COCH3), 1611 (C=N), 1548, 1339, 1179, 950 cm-1 (NCS amide
EXPERIMENTAL
Chemistry. Reagent quality solvents were used without
purification. Melting points were determined with a Mel-Temp
apparatus and are uncorrected. Magnetic resonance spectra (1H
nmr spectra) were recorded on a Brucker 300 MHz spectrometer
in DMSO-d6. Chemical shift values reported in ꢀ (ppm) relative
to an internal standard (tetramethylsilane). Infrared data were
obtained on a Perkin-Elmer 1600 series Fourier transform
instrument as KBr pellets. Reactions were monitored by tlc on
silica gel-protected aluminum sheets (Type 60 F 254, Merck)
and the spots were detected by exposure to UV-Lamp at ꢁ 254
nm for a few seconds. Elemental analyses were performed in the
Chemistry Department, Faculty of Science, Cairo University.
The antimicrobial tests were carried out at the Pharmaceutical
Department, Faculty of Pharmacy, Alexandria University.
1
I, II, III, IV respectively); H nmr: ꢀ 2.29 (s, 3H, CH3-pyrrole),
3.34 (s, 3H, COCH3), 6.90 (s, 1H, CH-pyrrole), 7.20 (t, 2H, Ar-
H), 7.37 (t, 1H, Ar-H), 7.53 (d, 2H, Ar-H), 7.88 (s, 1H, CH=N),
9.95(s, 1H, NH), 11.77 (s, 1H, NH), 11.86 (s, 1H, NH).
1-((4-Acetyl-5-methyl-1H-pyrrol-2-yl)methylene)-4-(4-chloro-
phenyl)thiosemicarbazide (8c). Yield: 74.7%; yellow crystals;
mp 222-223ºC; ir: 3386, 3224, 3137 (NH), 1660 (COCH3), 1611
(C=N), 1535, 1336, 1195, 922 cm-1 (NCS amide I, II ,III, IV
1
respectively); H nmr:ꢀ 2.29 (s, 3H, CH3-pyrrole), 3.35 (s, 3H,
COCH3), 7.31 (s, 1H, CH-pyrrole), 7.43 (d, 2H, Ar-H), 7.60 (d,
2H, Ar-H), 7.89 (s, 1H, CH=N), 9.97 (s, 1H, NH), 11.75 (s, 1H,
NH), 11.86 (s, 1H, NH). Anal. Calcd for C15H15ClN4OS: C,
53.81; H, 4.52; N, 16.73. Found: C, 54.00; H, 4.35; N, 16.96.
1-((4-Acetyl-5-methyl-1H-pyrrol-2-yl)methylene)-4-p-tolyl-
thiosemicarbazide (8d). Yield 71.2%; yellow crystals; mp 230-
231ºC; ir: 3440, 3204, 3134 (NH), 1661 (COCH3), 1609 (C=N),
1533, 1351, 1140, 942 cm-1 (NCS amide I, II, III, IV
respectively); 1H nmr: ꢀ 2.28 (s, 3H, CH3-pyrrole), 2.47 (s, 3H,
CH3-tolyl), 3.33 (s,3H, COCH3), 6.90 (s, 1H, CH-pyrrole),7.17
(d, 2H, Ar-H),7.38 (d, 2H, Ar-H), 7.87 (s, 1H, CH=N), 9.88 (s,
1H, NH), 11.71 (s, 1H, NH), 11.75 (s, 1H, NH). Anal. Calcd
for C16H18N4OS: C, 61.12; H, 5.77; N, 17.82. Found: C, 60.90;
H, 5.90; N, 17.67.
General Procedure for the Preparation of 2a-2d and 8a-
To a solution of ethyl 5-formyl-2-methylfuran-3-
8d.
carboxylate, 1, or 4-acetyl-5-methyl-1H-pyrrole-2-carbaldehyde,
7, (5 mmol) in ethanol:chloroform (2:1, 25 mL) was added N-
substituted thiosemicarbazide (5 mmol). The reaction mixture
was heated under reflux for 4-8 hours, partially concentrated and
cooled. The solid product was collected by filtration, washed
with ethanol, dried, and recrystallized from ethanol.
Ethyl 2-methyl-5-(thiosemicarbazidomethyl)furan-3-
carboxylate (2a). (72.1% Yield) white crystals; mp 127-128 ºC
(lit. [24] 122ºC); ir: 3392, 3281, 3146 (NH), 1725 (COOEt),
1623 (C=N), 1548, 1333, 1171, 951 cm-1 (NCS amide I, II, III,
IV respectively).
Ethyl 2-methyl 5-((4-(phenylthiosemicarbazido)methyl)-
furan-3-carboxylate (2b). Yield: 77.3%; yellow crystals; mp
160-161ºC; (lit. [24] 158 ºC); ir: 3396, 3352 (NH), 1713
(COOEt), 1625 (C=N), 1533, 1321, 1196, 960 cm-1 (NCS amide
I, II, III, IV respectively).
Ethyl 5-((4-(4-chlorophenyl)thiosemicarbazido)methyl)-2-
methylfuran-3-carboxylate (2c). Yield: 85.8%; white crystals;
mp 185-186ºC; ir: 3313, 3147 (NH), 1717 (COOEt), 1621
(C=N), 1550, 1369, 1129, 933 cm-1 (NCS amide I, II, III, IV
General Procedure for the Preparation of 3a-3d and 9a-
9d. Method A. A mixture of ethyl 5-[(4-substituted thiosemi-
carbazido) methyl]-2-methyl-furan-3-carboxylate, 2a-2d, or 1-
((4-acetyl-5-methyl-1H-pyrrol-2-yl)methylene)-4-substituted
thiosemicarbazide 8a-8d, (1 mmol), chloroacetic acid (1 mmol)
and fused sodium acetate (1.5 mmol) in 20 mL of glacial acetic
acid was refluxed for 4-8 hours. The reaction mixture was
poured into ice-cold water and stored overnight in the
refrigerator. The crude product was collected by filtration,
washed several times with water, dried, and recrystallized from
ethanol.
Method B. To a solution of the ethyl 5-[(4-substituted
thiosemicarbazido) methyl]-2-methylfuran-3-carboxylate, 2a-
2d, or 1-((4-acetyl-5-methyl-1H-pyrrol-2-yl) methylene)-4-
substituted thiosemicarbazide, 8a-8d, (1 mmol) in absolute
ethanol (25 mL) was added ethyl bromoacetate (1 mmol), and
the reaction mixture was heated under reflux for 4-8 hours. The
mixture was concentrated, cooled, and the solid was collected by
filtration, washed with ethanol, dried, and recrystallized from
ethanol.
2-Methyl-5-[(4-oxo-thiazolidin-2-ylidene)-hydrazonomethyl]-
furan-3-carboxylic acid ethyl ester (3a). Yield: 67.7%; yellow
crystals; mp 242-243ºC; ir: 3122 (NH), 1712 (COOEt), 1705
(CO), 1649, 1605 cm-1 (C=N); 1H nmr: ꢀ 1.25 (t, 3H, CH3-ester),
2.59 (s, 3H, CH3-furan), 3.86 (s, 2H, CH2), 4.20 (q, 2H, CH2-
ester), 7.09 (s, 1H, CH-furan), 8.15 (s, 1H, CH=N), 11.94 (s, 1H,
NH). Anal. Calcd for C12H13N3O4S: C, 48.81; H, 4.44; N, 14.23.
Found: C, 49.00; H, 4.21; N, 14.48.
1
respectively); H nmr: ꢀ 1.35 (t, 3H, CH3-ester), 2.65 (s, 3H,
CH3-furan), 4.30 (q, 2H, CH2-ester), 6.98 (s, 1H, CH-furan),
7.35 (d, 2H, Ar-H), 7.57 (d, 2H, Ar-H), 7.76 (s, 1H, CH=N),
9.13 (s, 1H, NH), 10.63 (s, 1H, NH). Anal. Calcd for
C16H16ClN3O3S: C, 52.53; H, 4.41; N, 11.49. Found: C, 52.33;
H, 4.53; N, 11.26.
Ethyl 2-methyl-5-((4-p-tolylthiosemicarbazido)methyl)furan-
3-carboxylate (2d). Yield: 63.7%; white crystals; mp 175-
176ºC; ir: 3328, 3136 (NH), 1711 (COOEt), 1619 (C=N), 1550,
1370, 1129, 945 cm-1 (NCS amide I, II, III, IV respectively); 1H
nmr: ꢀ 1.36 (t, 3H, CH3- ester), 2.36 (s, 3H, CH3-furan), 2.66 (s,
3H, CH3 tolyl), 4.30 (q, 2H, CH2-ester), 6.98 (s, 1H, CH-furan),
7.20(d, 2H, Ar-H), 7.48 (d, 2H, Ar-H), 7.64 (s, 1H, CH=N), 9.07
(s, 1H, NH), 9.68 (s, 1H, NH). Anal. Calcd for C17H19N3O3S: C,
59.11; H, 5.54; N, 12.17. Found: C, 58.91; H, 5.70; N, 11.90.
1-((4-Acetyl-5-methyl-1H-pyrrol-2-yl)methylene)thiosemi-
carbazide (8a). Yield: 66.9%; yellow crystals; mp 230-231ºC
(lit.; [24] 230 ºC); ir: 3410, 3387, 3224, 3136 (NH), 1664
(COCH3), 1614 (C=N), 1548, 1333, 1171, 951 cm-1 (NCS amide
2-Methyl-5-[(4-oxo-3-phenylthiazolidin-2-ylidene)-hydra-
zonomethyl]-furan-3-carboxylic acid ethyl ester (3b). Yield:
78.1%; yellow crystals; mp 168-169ºC; ir: 1713 (COOEt), 1694
(CO), 1633, 1599 cm-1 (C=N); 1H nmr: ꢀ 1.24 (t, 3H, CH3-ester),
1
I, II, III, IV respectively); H nmr: ꢀ 2.26 (s, 3H, CH3-pyrrole),

Jan-Feb 2007
Thiazolyl and Thiadiazolyl Derivatives of Substituted Furan and Pyrrole
25
2.59 (s, 3H, CH3-furan), 4.06 (s, 2H, CH2), 4.20 (q, 2H, CH2-
ester), 7.04 (s, 1H, CH-furan), 7.32 (t , 1H, Ar-H), 7.41 (t, 2H,
Ar-H) , 7.47 (d, 2H, Ar-H), 8.04 (s, 1H, CH=N). Anal. Calcd for
C18H17N3O4S: C, 58.21; H, 4.61; N, 11.31. Found: C, 57.96; H,
4.86; N, 11.12.
2-Methyl-5-[(4-oxo-3-(4-chlorophenyl)thiazolidin-2-ylidene)-
hydrazonomethyl]-furan-3-carboxylic acid ethyl ester (3c).
Yield: 66.5%; yellow crystals; mp 113-114ºC; ir: 1737
(COOEt), 1718 (CO), 1644, 1613 cm-1 (C=N); 1H nmr: ꢀ 1.35 (t,
3H, CH3-ester), 2.66 (s, 3H, CH3-furan), 3.98 (s, 2H, CH2), 4.30
(q, 2H, CH2-ester), 6.99 (s, 1H, CH-furan), 7.29 (d, 2H, Ar-H),
7.48 (d, 2H, Ar-H), 8.01 (s, 1H, CH=N). Anal. Calcd for
C18H16ClN3O4S: C, 53.27; H, 3.97; N, 10.35. Found: C, 53.00;
H, 3.82; N, 10.13.
2-Methyl-5-[(4-oxo-3-p-tolylthiazolidin-2-ylidene)hydrazono-
methyl]furan-3-carboxylic acid ethyl ester (3d). Yield:
77.8%; yellow crystals; mp 162-163ºC; ir: 1726 (COOEt), 1708
(CO), 1643, 1609 cm-1 (C=N); 1H nmr: ꢀ 1.22(t, 3H, CH3-ester),
2.31(s, 3H, CH3-furan), 2.57 (s, 3H, CH3-tolyl), 4.03 (s, 2H,
CH2), 4.19 (q, 2H, CH2-ester), 7.03 (s, 1H, CH-furan), 7.18 (d,
2H, Ar-H), 7.26 (d, 2H, Ar-H), 8.01 (s, 1H, CH=N). Anal.
Calcd for C19H19N3O4S: C, 59.21; H, 4.97; N, 10.90. Found: C,
59.47; H, 4.79; N, 11.12.
attained at room temperature, excess acetic anhydride was
decomposed by water and the mixture was stirred for 30
minutes. The separated product was collected by filtration,
washed with water, dried, and recrystallized from ethanol.
5-(3-Acetyl-5-acetylamino-2,3-dihydro-[1,3,4]-thiadiazol-2-
yl)-2-methyl-furan-3-carboxylic acid ethyl ester (4a). Yield:
76.6%; grey crystals; mp 175-176ºC (lit. [24] 175 ºC); ir: 3147
(NH), 1713 (COOEt), 1661, 1650 (COCH3), 1613 cm-1 (C=N).
5-(3-Acetyl-5-(N-phenylacetylamino)-2,3-dihydro-[1,3,4]-
thiadiazol-2-yl)-2-methyl-furan-3-carboxylic acid ethyl ester
(4b). Yield: 86.7%; buff crystals; mp 120-121ºC(lit. [24] 120
ºC); ir: 1717 (COOEt), 1660, 1645 (COCH3), 1613 cm-1 (C=N).
5-(3-Acetyl-5-(N-(4-chlorophenyl)acetylamino)-2,3-dihydro-
[1,3,4]-thiadiazol-2-yl)-2-methyl-furan-3-carboxylic acid
ethyl ester (4c). Yield: 68.9%; buff crystals; mp 130-131ºC; ir:
1707 (COOEt), 1675, 1655 (COCH3), 1610 cm-1 (C=N); 1H nmr
ꢀ 1.22 (t, 3H, CH3-ester), 1.81, 1.89 (s, 6H, 2 COCH3), 2.47 (s,
3H, CH3-furan), 4.18 (q, 2H, CH2-ester), 6.45 (s, 1H, CH), 6.90
(s,1H, CH-furan), 7.53 (d, 2H, Ar-H), 7.59 (d, 2H, Ar-H). Anal.
Calcd for C20H20ClN3O5S: C, 53.39; H, 4.48; N, 9.34. Found: C,
53.60; H, 4.23; N, 9.56.
5-(3-Acetyl-5-(N-p-tolylacetylamino)-2,3-dihydro-[1,3,4]-
thiadiazol-2-yl)-2-methyl-furan-3-carboxylic acid ethyl ester
(4d). Yield: 69.9%; grey crystals; mp 210-211ºC; ir: 1709
2-[(4-Acetyl-5-methyl-1H-pyrrol-2-ylmethylene)hydra-
zono]thiazolidin-4-one (9a). Yield 71.9%; yellow crystals; mp
239-240ºC; ir: 344, 3133 (NH), 1698 (CO), 1660 (COCH3),
1
(COOEt), 1661, 1654 (COCH3), 1626 cm-1 (C=N); H nmr: ꢀ
1.28 (t, 3H, CH3 ester),1.64 (s, 6H, 2 COCH3), 2.47 (s, 3H,
CH3-furan ), 2.57 (s, 3H, CH3-tolyl), 4.32 (q, 2H, CH2-ester),
6.10 (s, 1H, CH), 7.23 (s, 1H, CH-furan), 7.26 (d, 2H, Ar-H),
7.40 (d, 2H, Ar-H). Anal. Calcd for C21H23N3O5S: C, 58.73; H,
5.40; N, 9.78. Found: C, 58.96; H, 5.29; N, 10.00.
N-[4-Acetyl-5-(4-acetyl-5-methyl-1H-pyrrol-2-yl)-4,5-
dihydro[1,3,4]thiadiazol-2-yl]-acetamide (10a). Yield: 61.6%;
grey crystals; mp 145-146ºC (lit. [24] 145 ºC); ir: 3413, 3240
(NH), 1691, 1677, 1642 (COCH3), 1611 cm-1 (C=N).
1
1619, 1599 cm-1 (C=N); H nmr: ꢀ 2.24 (s, 3H, CH3-pyrrole),
2.33 (s, 3H, COCH3), 3.83 (s, 2H, CH2), 6.78 (s, 1H, CH-
pyrrole), 8.06 (s, 1H, CH=N), 11.55 (s, 1H, NH), 11.78 (s, 1H,
NH). Anal. Calcd for C11H12N4O2S: C, 49.99; H, 4.58; N, 21.20.
Found: C, 49.76; H, 4.73; N, 20.98.
2-[(4-Acetyl-5-methyl-1H-pyrrol-2-ylmethylene)hydrazono]-
3-phenylthiazolidin-4-one (9b). Yield 67.6%; brown crystals;
mp 110-111ºC; ir: 3323 (NH), 1707 (CO), 1650 (COCH3), 1630,
1
1598 cm-1 (C=N); H nmr: ꢀ 2.26 (s, 3H, CH3-pyrrole), 2.30 (s,
N-[4-Acetyl-5-(4-acetyl-5-methyl-1H-pyrrol-2-yl)-4,5-
dihydro-[1,3,4]thiadiazol-2-yl]-N-phenylacetamide (10b).
Yield: 54.6%; yellow crystals; mp 185-186ºC (lit. [24] 185 ºC);
ir: 3344 (NH), 1688, 1660, 1650 (COCH3), 1609 cm-1 (C=N).
N-[4-Acetyl-5-(4-acetyl-5-methyl-1H-pyrrol-2-yl)-4,5-
dihydro-[1,3,4]-thiadiazol-2-yl]-N-(4-chlorophenyl)acetamide
(10c). Yield: 66.8%; buff crystals; mp 105-106ºC; ir: 3353
3H, COCH3), 3.83 (s, 2H, CH2), 7.10 (s, 1H, CH-pyrrole), 7.20
(t, 1H, Ar-H), 7.35 (t, 2H, Ar-H), 7.63 (d, 2H, Ar-H), 7.90 (s,
1H, CH=N), 11.50 (s, 1H, NH). Anal. Calcd for C17H16N4O2S:
C, 59.98; H, 4.74; N, 16.46. Found: C, 59.72; H, 4.90; N, 16.19.
2-[(4-Acetyl-5-methyl-1H-pyrrol-2-ylmethylene)hydra-
zono]-3-(4-chlorophenyl)thiazolidin-4-one (9c). Yield: 74.7%;
buff crystals; mp 239-240ºC; ir: 3399 (NH), 1693 (CO), 1661
(COCH3), 1626, 1600 cm-1 (C=N); 1H nmr: ꢀ 2.20 (s, 3H, CH3-
pyrrole), 2.47 (s, 3H, COCH3), 3.86 (s, 2H, CH2 ), 6.80 (s, 1H,
CH-pyrrole), 7.31 (d, 2H, Ar-H), 7.55 (d, 2H, Ar-H), 7.90 (s,
1H, CH=N), 10.04 (s, 1H, NH). Anal. Calcd for C17H15ClN4O2S:
C, 54.47; H, 4.03; N, 14.95. Found: C, 54.49; H, 4.00; N, 14.92.
2-[(4-Acetyl-5-methyl-1H-pyrrol-2-ylmethylene)hydra-
zono]-3-p-tolylthiazolidin-4-one (9d). Yield: 70.5%; buff
crystals; mp 205-206ºC; ir: 3331 (NH), 1695 (CO), 1654
(COCH3), 1607, 1598 cm-1 (C=N); 1H nmr: ꢀ 2.21 (s, 3H, CH3-
pyrrole), 2.34 (s, 3H, CH3-tolyl), 2.47 (s, 3H, COCH3), 4.06 (s,
2H, CH2), 6.87 (s, 1H, CH-pyrrole), 7.36 (d, 2H, Ar-H), 7.53 (d,
2H, Ar-H), 7.95 (s, 1H, CH=N), 11.02 (s, 1H, NH). Anal. Calcd
for C18H18N4O2S: C, 61.00; H, 5.12; N, 15.81. Found: C, 61.22;
H, 4.96; N, 15.99.
1
(NH), 1689, 1670, 1645 (COCH3), 1599 cm-1 (C=N); H nmr: ꢀ
1.94 (s, 6H, 2 COCH3), 1.97 (s, 3H, CH3-pyrrole), 2.47 (s, 3H,
COCH3 - pyrrole ), 6.20 (s, 1H, CH-thiadiazole), 7.23 (s, 1H,CH),
7.47 (d, 2H, Ar-H), 7.56 (d, 2H, Ar-H), 11.02 (s, 1H, NH).
Anal. Calcd for C19H19ClN4O3S: C, 54.48; H, 4.57; N, 13.37.
Found: C, 54.23; H, 4.73; N, 13.17.
N-[4-Acetyl-5-(4-acetyl-5-methyl-1H-pyrrol-2-yl)-4,5-dihydro-
[1,3,4]-thiadiazol-2-yl]-N-p-tolylacetamide (10d).
Yield:
67.8%; buff crystals; mp 140-141 (dec)ºC; ir: 3334 (NH), 1698,
1665, 1650 (COCH3), 1599 cm-1 (C=N);1H nmr: ꢀ 1.28 (s, 6H, 2
COCH3), 1.65 (s, 3H, CH3-pyrrole), 2.36 (s, 3H, CH3-tolyl), 2.39
(s, 3H, COCH3-pyrrole), 6.61(s, 1H, CH-thiadiazole), 6.77 (s,
1H, CH-pyrrole), 7.10-7.95 (m, 4H, Ar-H), 11.24 (s, 1H, NH).
Anal. Calcd for C20H22N4O3S: C, 60.28; H, 5.56; N, 14.06.
Found: C, 60.40; H, 5.31; N, 14.26.
General Procedure for the Preparation of 4a-4d and 10a-
10d. To a solution of ethyl 5-[(4-substituted thiosemicarbazido)
methyl]-2-methyl-furan-3-carboxylate, 2a-2d, or 1-[(4-acetyl-5-
methyl-1H-pyrrol-2-yl)methylene]-4-substituted thiosemi-
carbazide, 8a-8d (1 mmol) in acetic anhydride (10 mL) was
heated under reflux for 3 hours, after the reaction mixture was
General Procedure for the Preparation of 5a-5d and 11a-
11d. To a solution of ethyl 5-[(4-substituted thiosemicarbazide)
methyl]-2-methyl-furan-3-carboxylate, 2a-2d, or 1-[(4-acetyl-5-
methyl-1H-pyrrol-2-yl) methylene]-4-substituted thiosemi-
carbazide, 8a-8d (1 mmol) in absolute ethanol (25 mL) was
added p-bromophenacyl bromide (1 mmol) and anhydrous

26
S. Y. Hassan
Vol 44
sodium acetate (1.5 mmol), the reaction mixture was heated
under reflux for 4-8 hours, partially concentrated and left to cool
overnight. The solid was collected by filtration, washed with
ethanol, dried, and recrystallized from benzene-petroleum ether.
5-{[4-(4-Bromo-phenyl)-3H-thiazol-2-yl-ylidene]-hydrazono-
methyl}-2-methyl-furan-3-carboxylic acid ethyl ester (5a).
Yield: 71.4%; grey crystals; mp 170-171ºC; ir: 3147 (NH), 1713
CH=N), 11.83 (s, 1H, NH). Anal. Calcd for C23H18BrClN4OS:
C, 53.76; H, 3.53; N, 10.90. Found: C, 53.96; H, 3.45; N, 10.99.
1-(5-{[4-(4-Bromo-phenyl)-3H-3-p-tolylthiazol-2-yl-ylidene]-
hydrazonomethyl}-2-methyl-1H-pyrrol-3-yl)-ethanone (11d).
Yield: 66.9%; buff crystals; mp 180-181ºC; ir: 3343 (NH), 1689
(COCH3), 1633, 1600 cm-1 (C=N); 1H nmr: ꢀ 1.70 (s, 3H, CH3-
pyrrole), 2.21 (s, 3H, CH3-tolyl), 2.32 (s, 3H, COCH3), 7.03 (s,
1H, CH-pyrrole), 7.30 (s, 1H, CH), 7.42 (d, 2H, Ar-H), 7.48 (d,
2H,Ar-H), 7.78 (d, 2H, Ar-H), 7.84 (d, 2H, Ar-H), 8.32 (s, 1H,
CH=N), 12.19 (s, 1H, NH). Anal. Calcd for C24H21BrN4OS: C,
58.42; H, 4.29; N, 11.35. Found: C, 58.24; H, 4.43; N, 11.19.
General Procedure for the Preparation of 6a-6d and 12a-
12d. A mixture of the appropriate ethyl 5-[(4-substituted thio-
semicarbazido) methyl]-2-methylfuran-3-carboxylate, 2a-2d, or
1-[(4-acetyl-5-methyl-1H-pyrrol-2-yl)methylene]-4-substituted
thiosemicarbazide, 8a-8d, (1 mmol) and thioglycolic acid (1.5
mmol) in dry benzene (50 mL) was heated under reflux for 12
hours using water separator. Benzene was evaporated under
reduced pressure and the residue was dissolved in ethanol (15
mL), and then poured into sodium carbonate solution (10 %).
The solid was collected by filtration, washed with water, dried,
and recrystallized from chloroform.
1
(COOEt), 1626, 1600 cm-1 (C=N); H nmr: ꢀ 1.35 (t, 3H, CH3-
ester), 2.62 (s, 3H, CH3-furan), 4.30 (q, 2H, CH2-ester), 6.56 (s, 1H,
CH-furan), 6.82 (s, 1H, CH), 7.26-7.92 (m, 4H, Ar-H), 8.47 (s, 1H,
CH=N), 11.78 (s, 1H, NH). Anal. Calcd for C18H16BrN3O3S: C,
49.78; H, 3.71; N, 9.68. Found: C, 49.54; H, 3.95; N, 9.43.
5-{[4-(4-Bromo-phenyl)-3H-3-phenylthiazol-2-yl-ylidene]-
hydrazonomethyl}-2-methyl-furan-3-carboxylic acid ethyl
ester (5b). Yield: 76.4%; yellow crystals; mp 220-221ºC; ir:
1717 (COOEt), 1640, 1626 cm-1 (C=N); 1H nmr: ꢀ 1.22 (t, 3H,
CH3 ester), 2.47 (s, 3H, CH3-furan), 4.16 (q, 2H, CH2-ester),
6.49 (s, 1H, CH-furan), 6.72 (s, 1H, CH), 6.92-7.60 (m , 9H, Ar-
H), 7.64 (s, 1H, CH=N). Anal. Calcd for C24H20BrN3O3S: C,
56.48; H, 3.95; N, 8.23. Found: C, 56.21; H, 4.21; N, 7.99
5-{[4-(4-Bromo-phenyl)-3H-3-(4-chlorophenyl)thiazol-2-yl-
ylidene]-hydrazonomethyl}-2-methyl-furan-3-carboxylic acid
ethyl ester (5c). Yield: 64.2%; yellow crystals; mp 225-226ºC;
2-Methyl-5-(4-oxo-3-thioureido-thiazolidin-2-yl)-furan-3-
carboxylic acid ethyl ester (6a). Yield: 72.9%; pale yellow
crystals; mp 200-201ºC; ir: 325, 3300, 3153 (NH), 1717
(COOEt), 1668 (CO), 1551, 1346, 1131, 948 cm-1 (NCS amide I,
1
ir: 1717 (COOEt), 1626, 1600 cm-1 (C=N); H nmr: ꢀ 1.22 (t,
3H, CH3 ester), 2.47 (s, 3H, CH3-furan), 4.18 (q, 2H, CH2-ester),
6.51 (s, 1H, CH-furan), 6.85 (s, 1H, CH), 7.29-7.64 (m, 8H, Ar-
H), 7.71 (s, 1H, CH=N). Anal. Calcd for C24H19BrClN3O3S: C,
52.91; H, 3.51; N, 7.71. Found: C, 53.11; H, 3.26; N, 7.96.
5-{[4-(4-Bromo-phenyl)-3H-3-p-tolylthiazol-2-yl-ylidene]-
hydrazonomethyl}-2-methyl-furan-3-carboxylic acid ethyl
ester (5d). Yield: 68.6%; yellow crystals; mp 220-221ºC;
ir:1726 (COOEt), 1626 ,1605 cm-1 (C=N); 1H nmr: ꢀ1.23 (t, 3H,
CH3-ester), 2.25 (s, 3H, CH3-furan), 2.96 (s, 3H, CH3-tolyl),
4.20 (q, 2H, CH2-ester), 6.58 (s, 1H, CH-furan), 6.85(s, 1H,
CH), 7.02-7.79 (m, 8H, Ar-H), 8.46 (s, 1H, CH=N). Anal. Calcd
for C25H22BrN3O3S: C, 57.26; H, 4.23; N, 8.01. Found: C, 57.50;
H, 4.10; N, 8.28.
1
II, III, IV respectively); H nmr: ꢀ1.26 (t, 3H, CH3-ester), 2.50
(s, 3H, CH3-furan), 3.37 (s, 2H, CH2-thiazolidine), 4.22 (q, 2H,
CH2-ester), 7.16 (s, 1H, CH-thiazolidine), 7.87 (s, 1H, CH-
furan), 8.22 (s, 2H, NH2), 11.47 (s, 1H, NH). Anal. Calcd for
C12H15N3O4S2: C, 43.76; H, 4.59; N, 12.76. Found: C, 43.53; H,
4.75; N, 12.51.
2-Methyl-5-(4-oxo-3-phenylthioureido-thiazolidin-2-yl)-
furan-3-carboxylic acid ethyl ester (6b). Yield: 64.1%; yellow
crystals; mp175-176ºC; ir: 3300, 3158 (NH), 1719 (COOEt),
1669 (CO), 1550, 1346, 1138, 940 cm-1 (NCS amide I, II, III, IV
1
respectively); H nmr: ꢀ.1.27 (t, 3H, CH3-ester), 2.50 (s, 3H,
CH3-furan), 3.35 (s, 2H, CH2-thiazolidine), 4.23 (q, 2H, CH2-
ester), 7.16 (s, 1H, CH-thiazolidine), 7.20 (s, 1H, 2-furan), 7.34
(d, 2H, Ar-H), 7.54 (t, 1H, Ar-H), 8.01 (t , 2H, Ar-H), 9.97 (s,
1H, NH), 11.86 (s, 1H, NH). Anal. Calcd for C18H19N3O4S2: C,
53.32; H, 4.72; N, 10.36. Found: C, 53.10; H, 4.98; N, 10.13.
2-Methyl-5-(4-oxo-3-(4-chlorophenyl)thioureido-thiazol-
idin-2-yl)-furan-3-carboxylic acid ethyl ester (6c). Yield:
63.6%; brown crystals; mp 150-151ºC; ir: 3310, 3163 (NH),
1715 (COOEt), 1666 (CO), 1551, 1336, 1139, 944 cm-1 (NCS
1-(5-{[4-(4-Bromo-phenyl)-3H-thiazol-2-yl-ylidene]-hydra-
zonomethyl}-2-methyl-1H-pyrrol-3-yl)-ethanone (11a). Yield:
76.9%; grey crystals; mp 200-201ºC; ir: 3358, 3235 (NH),
1669(COCH3), 1640, 1599 cm-1 (C=N); 1H nmr: ꢀ 2.47 (s, 3H,
CH3-pyrrole), 2.49 (s, 3H, COCH3), 6.83 (s, 1H, CH-pyrrole),
7.32 (s, 1H, CH), 8.06 (d, 2H, Ar-H), 8.26 (d, 2H, Ar-H), 8.43
(s,1H, CH=N), 11.64 (s, 1H, NH), 12.44 (s, 1H, NH). Anal.
Calcd for C17H15BrN4OS: C, 50.63; H, 3.75; N, 13.89. Found: C,
50.41; H, 3.96; N, 13.63.
1
amide I, II, III, IV respectively); H nmr: ꢀ 1.27 (t, 3H, CH3-
1-(5-{[4-(4-Bromo-phenyl)-3H-3-phenylthiazol-2-yl-ylidene]-
hydrazonomethyl}-2-methyl-1H-pyrrol-3-yl)-ethanone (11b).
Yield: 70.9%; buff crystals; mp 118-119ºC; ir: 3363 (NH), 1671
ester), 2.26 (s, 3H, CH3-furan), 3.36 (s, 2H, CH2-thiazolidine),
4.23 (q, 2H, CH2-ester), 7.30 (s, 1H, CH-thiazolidine), 7.40 (d,
2H, Ar-H), 7.50 (d, 2H, Ar-H), 7.90 (s, 1H, CH-furan), 9.90 (s,
1H, NH), 11.86 (s, 1H, NH). Anal. Calcd for C18H18ClN3O4S2:
C, 49.14; H, 4.12; N, 9.55. Found: C, 49.36; H, 3.89; N, 9.76.
2-Methyl-5-(4-oxo-3-p-tolylthioureidothiazolidin-2-yl)-furan-
3-carboxylic acid ethyl ester (6d). Yield: 64.4%; pale yellow
crystals; mp 165-166ºC; ir: 3325, 3135 (NH), 1708 (COOEt),
1661(CO), 1550, 1369, 1127, 942 cm-1 (NCS amide I, II, III, IV
respectively); 1H nmr: ꢀ 1.26 (t, 3H, CH3-ester), 2.27 (s, 3H, CH3-
furan), 2.58 (s, 3H, CH3-tolyl), 3.34 (s, 2H, CH2-thiazolidine), 4.22
(q, 2H, CH2-ester), 7.97 (s, 1H, CH-thiazolidine), 8.23 (s, 1H, CH-
furan), 7.01-7.51 (m, 4H, Ar-H), 9.88 (s, 1H, NH), 11.80 (s, 1H,
NH). Anal. Calcd for C19H21N3O4S2: C, 54.40; H, 5.05; N, 10.02.
Found: C, 54.19; H, 5.25; N, 9.88.
1
(COCH3), 1631,1599 cm-1 (C=N); H nmr: ꢀ 1.24 (s 3H, CH3-
pyrrole), 1.85 (s, 3H, COCH3), 7.16 (d, 2H, Ar-H), 7.32(t, 1H,
Ar-H), 7.44 (t, 2H, Ar-H), 7.54 (s, 1H, CH-pyrrole), 7.56 (d, 2H,
Ar-H), 7.64 (s, 1H, CH), 7.65 (d, 2H, Ar-H), 7.76 (s, 1H,
CH=N), 11.64 (s, 1H, NH). Anal. Calcd for C23H19BrN4OS: C,
57.62; H, 3.99; N, 11.69. Found: C, 57.39; H, 4.16; N, 11.48.
1-(5-{[4-(4-Bromo-phenyl)-3H-3-(4-chlorophenyl)thiazol-
2-yl-ylidene]-hydrazonomethyl}-2-methyl-1H-pyrrol-3-yl)-
ethanone (11c). Yield: 70.1%; buff crystals; mp 120-121ºC; ir:
1
3343 (NH), 1681 (COCH3), 1634, 1609 cm-1 (C=N); H nmr: ꢀ
1.92 (s 3H, CH3-pyrrole), 2.34 (s, 3H, COCH3), 6.75 (s, 1H, CH-
pyrrole), 6.98 (d, 2H, Ar-H), 7.15 (d, 2H, Ar-H), 7.22 (s, 1H,
CH), 7.30 (d, 2H, Ar-H), 7.38 (d, 2H, Ar-H), 7.57 (s, 1H,

Jan-Feb 2007
Thiazolyl and Thiadiazolyl Derivatives of Substituted Furan and Pyrrole
27
[2-(4-Acetyl-5-methyl-1H-pyrrol-2-yl)-4-oxo-thiazolidin-3-
yl]-thiourea (12a). Yield: 60.3%; white crystals; mp 229-
Acknowledgement. Author is very grateful to Dr. Adnan A.
Bekhit, Department of Pharmaceutical, Faculty of Pharmacy,
Alexandria University, Egypt; for performing the antimicrobial
evaluation.
300ºC; ir: 3475, 3344, 3331, 3133 (NH), 1691, 1645 (CO),
1551, 1335, 1186, 948 cm-1 (NCS amide I, II, III, IV
respectively); 1H nmr: ꢀ 2.25 (s, 3H, CH3-pyrrole), 2.35 (s, 3H,
COCH3), 3.37 (s, 2H, CH2-thiazolidine), 6.75 (s, 1H, CH), 7.99
(s, 1H, CH-pyrrole), 9.22 (s, 2H, NH2), 11.44 (m, 2H, 2NH).
Anal. Calcd for C11H14N4O2S2: C, 44.28; H, 4.73; N, 18.78.
Found: C, 44.47; H, 4.49; N, 18.99.
REFERENCES AND NOTES
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[2-(4-Acetyl-5-methyl-1H-pyrrol-2-yl)-4-oxo-thiazolidin-3-
yl]-3-phenylthiourea (12b). Yield: 66.8%; white crystals; mp
238-239ºC; ir: 3458, 3438, 3298 (NH), 1693, 1660 (CO), 1551,
1335, 1186, 948 cm-1 (NCS amide I, II, III, IV respectively); 1H
nmr: ꢀ 2.26 (s, 3H, CH3-pyrrole), 2.45 (s, 3H, COCH3), 3.46 (s, 2H,
CH2-thiazolidine), 6.62 (s, 1H, CH), 6.99 (s, 1H, CH-pyrrole), 7.10
(d, 2H, Ar-H), 7.27 (t, 1H, Ar-H), 7.51 (t, 2H, Ar-H), 9.85 (s, 1H,
1NH), 11.44 (m, 2H, 2 NH). Anal. Calcd for C17H18N4O2S2: C,
54.52; H, 4.84; N, 14.96. Found: C, 54.59; H, 4.80; N, 14.99.
[2-(4-Acetyl-5-methyl-1H-pyrrol-2-yl)-4-oxo-thiazolidin-3-
yl]-3-(4-chlorophenyl)thiourea (12c). Yield: 61.1%; white
crystals; mp 229-300ºC; ir: 3440, 3225, 3173 (NH), 1693, 1661
(CO), 1543, 1356, 1169, 956 cm-1 (NCS amide I, II, III, IV
respectively); 1H nmr: ꢀ 2.16 (s, 3H, CH3-pyrrole), 2.55 (s, 3H,
COCH3) 3.38 (s, 2H, CH2-thiazolidine), 6.10 (s, 1H, CH), 6.19
(s, 1H, CH-pyrrole), 6.40 (d, 2H, Ar-H), 7.02 (d, 2H, Ar-H),
9.22 (s, 1H, NH), 11.44 (m, 2H, 2NH). Anal. Calcd for
C17H17ClN4O2S2: C, 49.93; H, 4.19; N, 13.70. Found: C, 49.90;
H, 4.29; N, 13.59.
[2-(4-Acetyl-5-methyl-1H-pyrrol-2-yl)-4-oxo-thiazolidin-3-
yl]-3-p-tolylthiourea (12d). Yield: 61.8%; white crystals; mp
241-242ºC; ir: 3457, 3389, 3238 (NH), 1693, 1645 (CO), 1562,
1317, 1187, 952 cm-1 (NCS amide I, II, III, IV respectively); 1H
nmr: ꢀ 2.19 (s, 3H, CH3-pyrrole), 2.21 (s, 3H, CH3-tolyl), 2.47 (s,
3H, COCH3), 3.36 (s, 2H, CH2-thiazolidine), 6.10 (s, 1H, CH), 6.30
(s, 1H, CH-pyrrole), 7.06 (d, 2H, Ar-H), 7.40 (d, 2H, Ar-H), 9.89
(s, 1H, NH), 11.14 (m, 2H, 2NH). Anal. Calcd for C18H20N4O2S2:
C, 55.65; H, 5.19; N, 14.42. Found: C, 55.60; H, 5.23; N, 14.38.
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susceptibility test in Müller-Hinton Broth (Oxoid) and
Sabouraud Liquid Medium (Oxoid) were used for the
determination of antibacterial and antifungal activity [22,23].
The utilized test organisms were: Escherichia coli (E. coli)
ATCC 25922 as an example of Gram-negative bacteria,
Staphylococcus aureus (S. aureus) ATCC 19433 as an example
of Gram-Positive bacteria and Candida albicans (C. albicans) as
yeast-like fungi. Ampicillin trihydrate and clotrimazole were
used as standard antibacterial and antifungal agents,
respectively. Solutions of the test compounds, ampicillin
trihydrate and clotrimazole were prepared in DMSO at
concentration of 1600 μg/ml. The twofold dilution of the
compounds were prepared (800, 400,...6.25 μg/ml).
The microorganism suspensions at 106 CFU/ml (Colony
Forming Unit/ml) concentrations were inoculated to the
corresponding wells. Plates were incubated at 36 °C for 24 h to
48 h. The incubation chamber was kept sufficiently humid. At
the end of the incubation period, the minimal inhibitory
concentrations (MIC) were determined.