Synthesis and antimicrobial of certain new thiazolidinone, thiazoline, and thiophene derivatives

Article abstract of DOI:10.1080/10426500903074858

2-Cyano-N-(9,10-dioxo-9,10-dihydro-anthracen-2-yl)-acetamide (1) was utilized as a key intermediate for the synthesis of thiazolidin-4-one 2 and thiocarbamoyl 5 derivatives via reaction with 2-sulfanylacetic acid and phenyl isothiocyanate, respectively. Compound 5 reacted with different α-halo compounds to give thiazolidin-5-one 4, thiazolidine 7a,b, thiazolidin-4-one 8, and thiophene derivatives 10a,b. Thiazoline 6 and tetrahydro-benzothiophene 12 derivatives were obtained via a one-pot reaction of compound 1 with phenyl isothiocyanate/sulfur and cyclohexanone/sulfur, respectively. Representative compounds of the synthesized products were evaluated as antimicrobial agents. Some of these compounds exhibited promising activities. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426500903074858

This article was downloaded by: [Acadia University]
On: 17 May 2013, At: 12:18
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Phosphorus, Sulfur, and Silicon and the
Related Elements
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/gpss20
Synthesis and Antimicrobial of Certain
New Thiazolidinone, Thiazoline, and
Thiophene Derivatives
M. A. Gouda a , M. A. Berghot a , A. I. Shoeib a & A. M. Khalil a
a Department of Chemistry, Faculty of Science, Mansoura University,
Mansoura, Egypt
Published online: 02 Jul 2010.
To cite this article: M. A. Gouda , M. A. Berghot , A. I. Shoeib & A. M. Khalil (2010): Synthesis and
Antimicrobial of Certain New Thiazolidinone, Thiazoline, and Thiophene Derivatives, Phosphorus,
Sulfur, and Silicon and the Related Elements, 185:7, 1455-1462
To link to this article: http://dx.doi.org/10.1080/10426500903074858
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation
that the contents will be complete or accurate or up to date. The accuracy of any
instructions, formulae, and drug doses should be independently verified with primary
sources. The publisher shall not be liable for any loss, actions, claims, proceedings,
demand, or costs or damages whatsoever or howsoever caused arising directly or
indirectly in connection with or arising out of the use of this material.

Phosphorus, Sulfur, and Silicon, 185:1455–1462, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500903074858
SYNTHESIS AND ANTIMICROBIAL OF CERTAIN NEW
THIAZOLIDINONE, THIAZOLINE, AND THIOPHENE
DERIVATIVES
M. A. Gouda, M. A. Berghot, A. I. Shoeib, and A. M. Khalil
Department of Chemistry, Faculty of Science, Mansoura University,
Mansoura, Egypt
2-Cyano-N-(9,10-dioxo-9,10-dihydro-anthracen-2-yl)-acetamide (1) was utilized as a key in-
termediate for the synthesis of thiazolidin-4-one 2 and thiocarbamoyl 5 derivatives via reac-
tion with 2-sulfanylacetic acid and phenyl isothiocyanate, respectively. Compound 5 reacted
with different α-halo compounds to give thiazolidin-5-one 4, thiazolidine 7a,b, thiazolidin-
4-one 8, and thiophene derivatives 10a,b. Thiazoline 6 and tetrahydro-benzothiophene
12 derivatives were obtained via a one-pot reaction of compound 1 with phenyl isothio-
cyanate/sulfur and cyclohexanone/sulfur, respectively. Representative compounds of the
synthesized products were evaluated as antimicrobial agents. Some of these compounds
exhibited promising activities.
Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental
file.
Keywords Aminoanthraquinone; antimicrobial activity; thiazole; thiazolidinone; thiazoline;
thiophene
INTRODUCTION
Many biological properties for 2-amino-9,10-anthraquinone derivatives have been re-
ported, such as antitumor and anti-HIV activities.1 The synthesis and antimicrobial activities
of thiazole2,3 and thiophene4,5 compounds are well documented; however the 2-amino-9,10-
anthraquinone derivatives possessing these nuclei are little known.6 Therefore, our aim in
this work was to synthesize some new thiazolidinone, thiazole, and thiophene derivatives in-
corporating the 2-amino-9,10-anthraquinone moiety, starting from 2-cyano-N-(9,10-dioxo-
9,10-dihydroanthracen-2-yl)acetamide in order to investigate their antimicrobial activity.
RESULTS AND DISCUSSION
Chemistry
The synthetic procedures adopted to obtain the target compounds are depicted in
Schemes 1–4, and compounds 2, 4, 5, 7a,b, and 8 prefer the (E) form rather than the
Received 18 February 2009; accepted 28 May 2009.
We offer our thanks to Prof. Dr. Yhia A. O. Ellazeik and Dr. Ehab Ali Metwally for carrying out the
microbiology screening, Botany Department, Faculty of Science, Mansoura University, Mansoura, Egypt.
Address correspondence to M. A. Gouda, Department of Chemistry, Faculty of Science, Mansoura Univer-
sity, El-Gomhoria St., Mansoura 35516, Egypt. E-mail: dr mostafa chem@yahoo.com
1455

1456
M. A. GOUDA ET AL.
O
S, PhNCS
O
NH2
DMF / EtOH
NH
Ph
N
S
TEA
S
O
6
O
O
O
HS
COOH
O
O
S
O
CN
Pyridine
N
NH
NH
H
O
1
2
O
O
KOH / DMF
PhNCS
CN
NH
PhHN
O
S-K+
Cl
3
Cl
O
DM
O
F
dil. HCl
O
O
O
O
N
CN
SH
CN
NH
NH
Ph
O
PhHN
S
5
O
4
Scheme 1
O
O
O
R
OEt
O
O
Cl
Cl
O
O
CN
S
CN
5
NH
NH
Ph
EtO
H
/ D
MF
EtOH / DMF
O
Ph
N
N
S
8
O
R
7a, R= CH3
7b, R= Ph
Scheme 2
(Z) form due to stabilization by π–π interaction (π–π stacking) between the phenyl
group and anthraquinone moiety. 2-Cyano-N-(9,10-dioxo-9,10-dihydro-anthracen-2-yl)-
acetamide (1) was prepared according to the previously reported procedure.7 Thus, reac-
tion of compound 1 with 2-sulfanylacetic acid through modification of this reported pro-
cedure8–10 afforded (E)-N-(9,10-dioxo-9,10-dihydroanthracen-2-yl)-2-(4-oxothiazolidin-
2-ylidene)acetamide (2) (Scheme 1). Compound 2 was characterized by the presence of a
strong absorption band at 1716 cm−1 in the IR spectrum, specific for the thiazolidinone.
1
Another piece of evidence for cyclization, in the H NMR spectrum, is the presence of a
singlet signal, equivalent to two protons at δ 3.73 ppm, which represents the C-5 protons
of the thiazolidinone nucleus. The 13C NMR spectrum of compound 2 revealed signals at
δ 157.46 and 92.44 ppm due to C-4 and C-5 of the thiazolidinone nucleus, respectively.

THIAZOLIDINONE, THIAZOLINE, AND THIOPHENE DERIVATIVES
1457
R
O
Cl
O
NH2
O
5
EtOH / DMF
TEA
NH
PhHN
10a, R= CH3
O
O
S
R
10b, R= Ph
O
O
O
O
O
R
O
-HCl
CN
S
+
CN
SH
Cl
NH
NH
PhHN
O
O
PhHN
R
5
NHEt3Cl
O
O
O
O
O
N
C
S
N
NH
PhHN
NH
O
O
O
PhHN
S
R
R
9a, R= CH3
9b, R= Ph
NHEt3
NH
O
O
O
O
O
NH2
1,3-H+migration
H
NH
NH
O
O
O
PhHN
S
PhHN
S
R
R
10a, R= CH3
10b, R= Ph
Scheme 3
O
O
O
O
O
NH
O
O
NH2
S
1
CN
Sulfur
NH
NH
O
NH
O
12
11
Scheme 4
The synthesis of 2-cyano-N-(9,10-dioxo-9,10-dihydroanthracen-2-yl)-2-(5-oxo-3-
phenylthiazolidin-2-ylidene)-acetamide (4) and (E)-2-cyano-N-(9,10-dioxo-9,10-dihydro-
anthracen-2-yl)-3-phenylamino-3-sulfanylacrylamide (5) were achieved as previously de-
scribed method.11 Treatment of acetamide 1 with phenyl isothiocyanate, in dry dimethylfor-
mamide in the presence of an equivalent amount of potassium hydroxide, produced the
potassium 2-cyano-3-(9,10-dioxo-9,10-dihydroanthracen-2-ylamino)-3-oxo-1-(phenyla-
mino)-prop-1-ene-1-thiolate (3). Cyclization of the potassium salt 3 with chloroacetyl chlo-
ride in dry dimethylformamide gave (E)-2-cyano-N-(9,10-dioxo-9,10-dihydroanthracen-
2-yl)-2-(5-oxo-3-phenylthiazolidin-2-ylidene)acetamide (4), whereas acidification of such
potassium salt 3 librated the β-sulfonylacetamide 5 (Scheme 1).

1458
M. A. GOUDA ET AL.
The structure of compound 4 was based on analytical and spectral data. The IR
spectrum showed four absorption bands at 3300, 2191, 1720, and 1670 (br) cm−1 due
1
to NH, CN, and four carbonyl functional groups. Its H NMR spectrum revealed the
appearance of a singlet signal, equivalent to two protons at 4.13 ppm due to C5 protons of
thiazolidinone nucleus. N-(9,10-Dioxo-9,10-dihydroanthracen-2-yl)-4-amino-3-phenyl-2-
thioxo-2,3-dihydrothiazole-5-carboxyamide (6) was obtained by reacting 1 with sulfur and
phenyl isothiocyanate following the reported reaction conditions12 (Scheme 1).
Refluxing of compound 5 in a mixture of DMF/EtOH with chloroacetone, phenacyl
chloride, and/or ethyl chloroacetate led to the formation of 2-cyano-N-(9,10-dioxo-9,
10-dihydroanthracen-2-yl)-2-(4-methyl/phenyl-3-phenylthiazol-2(3H)-ylidene)acetamides
7a,b and 2-cyano-N-(9,10-dioxo-9,10-dihydroanthracen-2-yl)-2-(4-oxo-3-phenyl-thiazoli-
din-2-ylidene)acetamide (8), respectively (Scheme 2).
The IR spectra of compounds 7a,b and 8 showed the presence of an NH group
in 3356–3404 cm−1 region, a cyano group in the 2175–2002 cm−1 region, and three
carbonyl groups in 1664–1669, 1646–1640 cm−1 regions. The IR of compound 8 also
showed an absorption band at 1734 due to the carbonyl group of thiazolidin-4-one nucleus.
1
The H NMR of compound 7a,b shows two singlet signals, equivalent to one proton at
7.03 and 7.12 ppm, respectively, due to C-5 proton of thiazoline nucleus. In addition,
the 13C NMR spectrum of compound 7b reveals a signal at δ 98.95 ppm corresponding
1
to C-5 of thiazoline ring. Moreover, the H NMR spectrum of compound 8 displayed a
singlet signal, equivalent to two protons at 4.05 ppm, which represents the C-5 protons of
thiazolidin-4-one. In continuation of our work on the synthesis of biologically interesting
heterocyclic molecules containing thiophene moiety,13 several thiophene derivatives have
been synthesized with a view to evaluating their antimicrobial activities.
Thus, refluxing of compound 5 in DMF/EtOH containing a catalytic amount
of triethylamine, chloroacetone, and/or phenacylchloride revealed formation of N-
(9,10-dioxo-9,10-dihydro-anthracen-2-yl)-5-acetyl(or benzoyl)-4-amino-2-phenylamino-
thiophene-3-carboxamides 10a,b. The IR spectra of compounds 10a,b were characterized
by the disappearance of CN group and the appearance of NH2 and CO bands. In addition,
the 1H NMR of compound 10a showed three singlet signals at 2.26, 10.36, and 11.98 ppm
due to CH3, NHPh and NHC O protons, respectively.
Finally, N-(9,10-dioxo-9,10-dihydro-anthracen-2-yl)-3-amino-4,5,6,7-tetrahydroben-
zo[b]thiophene-3-carboxamide (12) was obtained by the reaction of compound 1 with
cyclohexanone and sulfur in a mixture of DMF/EtOH containing a catalytic amount of mor-
pholine. The reaction may be explained via the intermediacy of 2-cyano-2-cyclohexylidene-
N-(9,10-dioxo-9,10-dihydroanthracen-2-yl)-acetamide (11) (Scheme 4). The structure of
compound 12 was established on the basis of its elemental analysis and spectral data; its 1H
NMR spectrum displayed a four multiplet signals at 1.71, 2.47, 2.64, and 7.87–8.47 ppm
due to the tetrahydrobenzene and anthraquinone moieties, respectively, and another two
broad signals at 6.80 and 9.57 ppm corresponding to NH2 and NH groups, respectively.
Moreover, 13C NMR spectrum revealed signals at δ 26.15, 24.52, 23.35, and 22.99 due to
tetrahydrobenzene nucleus.
Antimicrobial Evaluation
Twelve compounds were screened in vitro for their antimicrobial activity against
two bacterial strains: Staphylococcus epidermidis and Pseudomonas auregenosa, and two
fungi: Alternaria solani and Fusarium solani, using cup-plate method by measuring the

THIAZOLIDINONE, THIAZOLINE, AND THIOPHENE DERIVATIVES
1459
zone of inhibition according to a standard procedure.14 The results are presented in the
Supplemental Materials (available online).
In conclusion, we have reported in this article a simple and convenient route for the
synthesis of some new heterocyclic derivatives based on anthraquinone for antimicrobial
evaluation.
EXPERIMENTAL
All melting points were recorded on Gallenkamp electric melting point apparatus
and are uncorrected. The IR spectra υ (cm−1) (KBr) were recorded on a Perkin Elmer
1
Infrared Spectrophotometer Model 157. The H NMR spectra were obtained on a Varian
Spectrophotometer at 500 MHz, using TMS as an internal reference and DMSO-d6 as
solvent. The 13C NMR spectra were recorded on a JEOL-ECA500 (National Research
Center, Egypt). The mass spectra (EI) were recorded on 70 eV with Kratos MS equipment
and/or a Varian MAT 311 A spectrometer. Elemental analyses (C, H, and N) were carried
out at the Microanalytical Center of Cairo University, Giza, Egypt. 2-Cyano-N-(9,10-dioxo-
9,10-dihydro-anthracen-2yl)acetamide was prepared according to the procedures reported
in the literature.7
(E)-N-(9,10-Dioxo-9,10-dihydroanthracen-2-yl)-2-(4-oxothiazolidin-
2-ylidene)acetamide (2)
To 2-cyano-N-(9,10-dioxo-9,10-dihydroanthracen-2-yl)acetamide (1) (0.58 g, 2
mmol) in pyridine (20 mL), 2-sulfanylacetic acid (0.184 g, 2 mmol) was added. The
reaction mixture was heated under reflux for 7 h, then left to cool to room temperature. The
separated crystalline product was filtered, washed with ethanol, dried, and recrystallized
from DMF/ethanol to give compound 2 as brown crystals, 75% yield; mp 298◦C. Analysis:
Calcd. For C19H12N2O4S (364.37): C, 62.63; H, 3.32; N, 7.69; Found C, 62.83%; H,
3.40%; N, 7.82%. IR (cm−1) (KBr): 3337, 3290 (2NH); 1719, 1663, 1654 (3C O). MS
(m/z) (I%): 318 (2.1) M+-CH2S; 317 (1.8); 291 (0.4); 290 (96); 274 (33.9); 223 (3.2);
1
168 (15.0); 126 (31.1); 78 (93.2). H NMR (DMSO-d6) δ: 3.73 (s, 2H, thiazolidinone,
CH2); 5.82 (s, 1H, CH); 7.87–8.43(m, 7H, Ar–H of anthraquinone ring); 10.48 (s, 1H,
NH); 11.66 (s, H, NH). 13C NMR (DMSO-d6) δ: 183.18, 181.86, 174.95, 166.42, 157.47,
145.97, 134.74, 133.57, 129.09, 127.63, 127.28, 127.17, 123.63, 115.65, 92.44.
(E)-2-Cyano-N-(9,10-dioxo-9,10-dihydroanthracen-2-yl)-2-(5-oxo-3-
phenylthiazolidin-2-ylidene)acetamide (4)
To a cold suspension of finally divided KOH (0.112 g, 2 mmol) in dry dimethylfor-
mamide (10 mL), the cyanoacetamide derivative 1 (0.58 g, 2 mmol) followed by phenyl
isothiocyanate (0.24 mL, 2 mmol) were added. The mixture was stirred at room tempera-
ture for 12 h, and then cooled again to 0◦C, treated with the chloroacetyl chloride, and left
to stand at room temperature for 24 h. Then the mixture was poured into ice-cold water.
The resulting precipitate was filtered off, dried, and crystallized from DMF/ethanol gave
compound 4, brown crystals, 60% yield; mp 310◦C. Analysis: Calcd. For C26H15N3O4S
(465.48): C, 67.09; H, 3.25; N, 9.03; Found C 67.20,%; H 3.39,%; N 9.25,%. IR (cm−1
(KBr): 3300 (NH); 2081 (CN); 1720–1670 (4C O). MS (m/z) (I%): 464 (46.2) M+-1;
)

1460
M. A. GOUDA ET AL.
463 (46.2); 296 (15.4); 294 (46.2); 241 (100); 131 (46.2); 74 (61.5). 1H NMR (DMSO-d6)
δ: 4.13 (s, 2H, thiazolidin-5-one); 7.20–8.83 (m, 7H, Ar–H) and 11.50 (s, 1H, NH).
(E)-2-Cyano-N-(9,10-dioxo-9,10-dihydroanthracen-2-yl)-3-phenylamino-
3-sulfanylacrylamide (5)
To a cold suspension of finally divided KOH (0.22 g, 4 mmol) in dry dimethylfor-
mamide (10 mL), the cyanoacetamide derivative 1 (1.16 g, 4 mmol) followed by phenyl
isothiocyanate (0.48 mL, 4 mmol) were added. The mixture was stirred at room tempera-
ture over night, then poured into ice-cold water and acidified with 0.1 N HCl to a pH 3–4.
The resulting precipitate was filtered off, dried, and crystallized from aqueous ethanol to
give compound 5, as reddish brown crystals; 72% yield, mp 244◦C. Analysis: Calcd. For
C24H15N3O3S (425.46): C, 67.75; H, 3.55; N, 9.88; Found C, 67.62%; H, 3.46%; N, 9.87%.
IR (cm−1) (KBr): 3294 (br. NH), 2548 (SH), 2201 (CN) and 1672, 1637 (3 C O). MS
(m/z) (I%): 425 (M+, 2.5), 291 (15.00), 265 (47.00), 251 (17.5), 223 (100.0), 164 (42.5),
1
76 (67.5). H NMR (DMSO-d6) δ: 6.91–8.80 (m, 14H, Ar–H, SH, NH-Ph) and 11.71 (s,
1H, NH).
N-(9,10-Dioxo-9,10-dihydroanthracen-2-yl)-4-amino-3-phenyl-2-thioxo-
2,3-dihydrothiazole-5-carboxyamide (6)
To a suspension of compound 1 (0.58 g, 2 mmol) in ethanol (20 mL), finely divided
sulfur (0.064 g, 2 mmol), triethylamine (0.28 mL, 2 mmol), phenyl isothiocyanate (0.24
mL, 2 mmol), and dimethylformamide (5 mL) were added. The reaction mixture was stirred
at 60◦C for 4 h, then left to cool at room temperature. The separated product was filtered,
washed with ethanol, dried, and crystallized from DMF/benzene (2:1) to give compound
6; brown crystals; 70% yield, mp 270◦C. Analysis: Calcd. For C24H15N3O3S2 (457.52): C,
63.00; H, 3.30; N, 9.18; Found C, 63.28%; H, 3.47%; N, 9.33%. IR (cm−1) (KBr): 3412,
3325 (br., NH); 1674 (3 C O) and 1324 (C S). MS (m/z) (I%): 264 (M+-C8H8N2S2,
12.0), 263 (38.6), 224 (15.8), 223 (100), 195 (16.5), 167 (25.3), 142 (82.3), 114 (44.9), 86
(50.0), 68 (90.5), 50 (22.2). 1H-NMR (DMSO-d6) δ: 7.69–8.55 (m, 14H, 12Ar–H, NH2),
11.02 (s, 1H, NH).
Synthesis of (E)-2-Cyano-N-(9,10-dioxo-9,10-dihydroanthracen-2-yl)-2-
(4-methyl/phenyl-3-phenylthiazol-2(3H)-ylidene)acetamides 7a,b and
(E)-2-Cyano-N-(9,10-dioxo-9,10-dihydroanthracen-2-yl)-2-(4-oxo-3-phenyl-
thiazolidin-2-ylidene)acetamide (8)
To compound 5 (0.85 g, 2 mmol) in dimethylformamide (20 mL) and chloroacetone
(0.16 mL, 2 mmol), phenacyl chloride (0.23 mL, 2 mmol), or ethyl chloroacetate (0.21 mL,
2 mmol) was added. The reaction mixture was heated under reflux for 6 h, then cooled and
neutralized with saturated sodium acetate solution. The resulting precipitate was filtered
off, dried, and crystallized from DMF/ethanol to give compounds 7a,b and 8, respectively.
7a: Red crystals, 55% yield, mp >320◦C; Analysis: Calcd. For C27H17N3O3S
(463.51): C, 69.96; H, 3.70; N, 9.07; Found C, 70.05%; H, 3.91%; N, 9.14%. IR (cm−1
)
(KBr): 3404 (NH); 2175 (CN); 1664–1646 (3C O). MS (m/z) (I%): 463 (M+, 32.5), 344
(17.50), 340 (12.50), 339 (17.50), 291 (20.0), 241 (100), 192 (17.5), 139 (35.0), 105 (22.5),

THIAZOLIDINONE, THIAZOLINE, AND THIOPHENE DERIVATIVES
1461
73 (80.0). 1H-NMR (DMSO-d6) δ: 1.88 (s, 3H, CH3), 7.03 (s, 1H, C5-H, thiazoline ring),
7.56–8.51 (m, 12H, Ar–H), 9.53 (s, 1H, NH).
7b: Brown crystals; 60% yield, mp 175◦C; Analysis: Calcd. For C32H19N3O3S
(525.58): C, 73.13; H, 3.64; N, 8.00; Found C, 73.06%; H, 3.51%; N, 7.84%. IR (cm−1
)
(KBr): 2180 (CN); 1669 (3C O). MS (m/z) (I%): 525 (M+, 17.1), 304 (28.0), 303 (59.8),
1
278 (1.2), 167 (12.2), 134 (31.7), 89 (26.8), 51 (100). H NMR (DMSO-d6) δ: 7.12 (s,
1H, C5-H, thiazoline ring), 7.38–8.47 (m, 17H, Ar–H), 11.20 (br., 1H, NH). 13C NMR
(DMSO-d6) δ: 183.98, 181.85, 166.84, 155.21, 145.49, 142.88, 140.62, 138.33, 137.11,
135.40, 134.98, 134.91, 134.84, 134.72, 134.53, 134.23, 133.57, 133.50, 131.00, 130.42,
130.07, 129.098, 129.58, 128.96, 128.55, 127.14, 127.02, 125.09, 124.70, 123.51, 121.56,
121.42, 118.58, 117.39, 116.22, 110.83 and 98.95.
8: Brown crystals, 75% yield, mp 285◦C; Analysis: Calcd. For C26H15N3O4S
(465.48): C, 67.09; H, 3.25; N, 9.03; Found C, 67.27%; H, 3.41%; N, 9.24%. IR (cm−1
)
(KBr): 3356 (NH); 2202 (CN); 1734–1665 (4C O). MS (m/z) (I%): 398 (M+-CH2 C O,
1
16.5), CN; 397 (0.9), 352 (0.8), 326 (13.1), 153 (6.1), 77 (100). H NMR (DMSO-d6) δ:
4.05 (s, 2H, CH2, thiazolidinone), 7.48–8.48 (m, 12H, Ar–H), 10.14 (s, 1H, NH).
5-Acetyl-4-amino-N-(9,10-dioxo-9,10-dihydroanthracen-2-yl)-2-
(phenylamino)thiophene-3-carboxamide (10a) and 4-Amino-5-
benzoyl-N-(9,10-dioxo-9,10-dihydroanthracen-2-yl)-2-
(phenylamino)thiophene-3-carboxamide (10b)
To compound 5 (0.85 g, 2 mmol) in dimethylformamide (20 mL), chloroacetone (0.16
mL, 2 mmol) or phenacyl chloride (0.23 mL, 2 mmol) and triethylamine (0.2 mL) were
added. The reaction mixture was heated under reflux for 6 h, then cooled and neutralized
with saturated sodium acetate solution. The resulting precipitate was filtered off, dried, and
crystallized from the DMF/methanol to give 10a and 10b.
10a: Brown crystals, 60% yield, mp 290◦C; Analysis: Calcd. For C27H19N3O4S
(481.52): C, 67.35; H, 3.98; N, 8.73; Found C, 67.52%; H, 4.08%; N, 8.94%. IR (cm−1
)
1
(KBr): 3416 (br), 3321, 3259 (NH), 1667 (3C O). H NMR (DMSO-d6) δ: 2.26 (s, 3H,
CH3), 7.17–8.7 (m, 14H, Ar-H, NH2), 10.36, 11.98 (2s, 2H, 2NH).
10b: Brown crystals, 65% yield mp 185◦C; Analysis: Calcd. For C32H21N3O4S
(543.59): C, 70.70; H, 3.89; N, 7.73; Found C, 70.93%; H, 3.95%; N, 7.94%. IR (cm−1
)
(KBr): 3379 (br); 3313 (br) (NH); 1668 (br) (3C O). 1H NMR (DMSO-d6) δ: 7.18–8.65
(m, 19H, Ar-H, NH2), 9.57, 9.82 (2s, 2H, 2NH).
2-Amino-N-(9,10-dioxo-9,10-dihydroanthracen-2-yl)-4,5,6,7-tetrahydro-
benzo[b]thiophene-3-carboxamide (12)
To compound 1 (0.58 g, 2 mmol) in absolute ethanol (20 mL), morpholine (0.52 mL,
6 mmol), cyclohexanone (0.19 mL, 2 mmol), and sulfur (0.06 g, 2 mmol) were added.
The reaction mixture was heated under reflux for 3 h. The separated crystalline product
was filtered, dried, and recrystallized from DMF/EtOH (1:2) to give compound 12. Brown
crystals, 60% yield, mp 290◦C; Analysis: Calcd. For C23H18N2O3S (402.47): C, 68.64; H,
4.51; N, 6.96; Found C, 68.80%; H, 4.73%; N, 7.08%. IR (cm−1) (KBr): 3436 (br.), 3303
(NH), 1761–1667 (3C O). MS (m/z) (I%): 403 (M+ +1, 5.3), 402 (M+, 20.4), 401 (3.3),
249 (9.0), 223 (37.1), 179 (100.0), 125 (44.9), 91 (30.2), 50 (31.0). 1H NMR (DMSO-d6)

1462
M. A. GOUDA ET AL.
δ: 1.66–1.73 (m, 4H, C5-H2, C6-H2 of cyclohexene ring), 2.47 (M, 2H, C4-H2 of cyclohexane
ring), 2.64 (m, 2H, C7-H2 of cyclohexene ring; 6.80 (s, NH2), 7.87–8.47 (m, 7H, Ar–H of
anthraquinone ring), 9.57 (s, 1H, NH). 13C NMR (DMSO-d6) δ: 183.06, 181.79, 164.80,
145.78, 135.01, 134.64, 134.49, 133.60, 130.38, 128.72, 127.76, 127.21, 127.31, 124.50,
26.15, 24.52, 23.35 and 22.99.
REFERENCES
1. L. Lain-Tze and Y. Jinun-Ban (Industrial Technology Research Institute, Taiwan), U.S. Pat. Appl.
Publ. 9 (2003), 2003149092, A1, 20030807.
2. K. Tsuji and H. Ishikawa, Bio Org. Med. Chem. Lett., 4, 1601 (1994).
3. S. Bondock, W. Khalifa, and A. A. Fadda, Eur. J. Med. Chem., 42(7), 948 (2007).
4. M. R. P. Queiroz, I. C. F. R. Ferreira, Y. De Gaetano, G. Kirsch, R. C. Calhelha, and L. M.
Estevinho, Bio Org. Med. Chem., 14(20), 6827 (2006).
5. R. M. Mohareb, K. A. El-Sharkawy, and S. M. Sherif, Acta Pharm., 58(4), 429 (2008).
6. M. A. Berghot, M. A. Hanna, and M. M. Girges, Pharmazie, 47(5), 340 (1992).
7. D. R. Tatke and S. Seshadri, Indian J. Chem., 22B(12), 1197 (1983).
8. S. M. Rida, N. S. Habib, E. A. M. Badawey, H. T. Y. Fahmy, and H. A. Ghozlan, Arch. Pharm.
(Weinheim), 328(4), 325 (1995).
9. M. H. Elngdi, M. A. Khalifa, M. K. Ibraheim, and M. R. Elmoghayer, J. Heterocycl. Chem., 18,
877 (1981).
10. S. M. Rida, F. A. Ashour, S. A. M. El-Hawash, M. M. El-Semary, M. H. Badr, and M. A. Shalaby,
Eur. J. Med. Chem., 40(9), 949 (2005).
11. L. Bukowski, M. Janowiec, Z. Zwolska-Kwiek, and Z. Andrzejczyk, Die Pharm., 53(6), 373
(1998).
12. E. A. M. Badawy, A. A. Hazza, S. M. Rida, and H. T. Y. Fahmy. Arech. pharm. (Weinheim), 325,
565 (1992).
13. M. A. Berghot, A. M. Khalil, and M. A. Gouda, Mansoura Sci. Bull., 32(1), 59 (2005).
14. R. Cruickshank, J. P. Duguid, B. P. Marion, and R. H. A. Swain, Medical Microbiology, 12th
Ed., Vol. II, (Churchill Livingstone, London, 1975), p. 196.