Synthesis of some new thiazolidin-5-one derivatives of pharmaceutical interest

Article abstract of DOI:10.1080/10426500490474932

Condensation of thiazolidin-5-one derivative 1 with different aromatic aldehydes gave the corresponding arylidenes 2a-e. Compound 2e was reacted with urea and thiourea to give the corresponding thiazolo[5,4-d]pyrimidine derivatives 3a,b, respectively. Treatment of compound 1 with phenyl isothiocyanate in basic DMF gave the nonisolable potassium salt of the adduct 4, which underwent heterocyclization upon treatment with chloroacetyl chloride and phenacyl bromide to give the corresponding [2,4′] bisthiazolidinylidenes 5 and 8. Moreover, the reactions of compound 1 with a variety of reagents, e.g., ninhydrin and isatin, were investigated. The structures of these compounds were established by analytical and spectral data.

Full text of DOI:10.1080/10426500490474932

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Phosphorus, Sulfur, and Silicon and the Related
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SYNTHESIS OF SOME NEW THIAZOLIDIN-5-ONE
DERIVATIVES OF PHARMACEUTICAL INTEREST
M. A. Metwally a , E. M. Keshk a , A. Fekry a & H. A. Etman a
a Department of Chemistry, Faculty of Science, Mansoura University , Mansoura, Egypt
Published online: 16 Aug 2010.
To cite this article: M. A. Metwally , E. M. Keshk , A. Fekry & H. A. Etman (2004) SYNTHESIS OF SOME NEW THIAZOLIDIN-5-
ONE DERIVATIVES OF PHARMACEUTICAL INTEREST, Phosphorus, Sulfur, and Silicon and the Related Elements, 179:10,
2067-2079, DOI: 10.1080/10426500490474932
To link to this article: http://dx.doi.org/10.1080/10426500490474932
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Phosphorus, Sulfur, and Silicon, 179:2067–2079, 2004
ꢀC
Copyright Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500490474932
SYNTHESIS OF SOME NEW THIAZOLIDIN-5-ONE
DERIVATIVES OF PHARMACEUTICAL INTEREST
M. A. Metwally, E. M. Keshk, A. Fekry, and H. A. Etman
Department of Chemistry, Faculty of Science, Mansoura
University, Mansoura, Egypt
(Received January 26, 2004; accepted March 23, 2004)
Condensation of thiazolidin-5-one derivative 1 with different aromatic
aldehydes gave the corresponding arylidenes 2a–e. Compound 2e was
reacted with urea and thiourea to give the corresponding thiazolo[5,4-
d]pyrimidine derivatives 3a,b, respectively. Treatment of compound 1
with phenyl isothiocyanate in basic DMF gave the nonisolable potas-
sium salt of the adduct 4, which underwent heterocyclization upon
treatment with chloroacetyl chloride and phenacyl bromide to give the
corresponding [2,4ꢁ] bisthiazolidinylidenes 5 and 8. Moreover, the re-
actions of compound 1 with a variety of reagents, e.g., ninhydrin and
isatin, were investigated. The structures of these compounds were es-
tablished by analytical and spectral data.
Keywords: Bisthiazolidinylidene-5,5ꢁ-dione; isothiocyanates; thiazo-
lidin-5-ones
INTRODUCTION
Diverse biological activities such as bactericidal,1,2 fungicidal,3,4
insecticidal,5,6 anticonvulsant,7–9 tuberculostatic,10,11 herbicidal,12,13
antiviral,14,15 and antiprotozoal16 have been found with thiazolidi-
none derivatives. The diversity of biological and physiological activi-
ties of organic sulfur heterocycles may be attributed to the presence
of the N C S fragment, which is characteristic of thiazoles, thiazo-
lines, and thiazolidines.17 This encouraged us to investigate the syn-
thesis of some new thiazolidin-5-one derivatives of pharmaceutical
interest.
Address correspondence to M. A. Metwally, Department of Chemistry, Faculty of Sci-
ence, Mansoura University, Mansoura, Egypt. E-mail: mamegs@mans.edu.eg
2067

2068
M. A. Metwally et al.
RESULTS AND DISCUSSION
3-Phenyl-2-phenyliminothiazolidin-5-one (1)18 was prepared by the re-
action of diphenylthiourea and chloroacetyl chloride in DMF containing
1
a quantitative amount of KOH. IR, H NMR, and 13C NMR analyses
1
confirmed the chemical structure of compound 1. The H NMR spec-
trum of 1 showed a singlet signal at δ 3.85 corresponding to the methy-
lene protons and a multiplet signal at δ 6.85–7.50 due to the aromatic
protons.
A series of 4-arylidene-3-phenyl-2-phenyliminothiazolidin-5-ones
2a–e was synthesized by condensation of compound 1 with a variety of
aromatic aldehydes in ethanol containing a catalytic amount of piperi-
dine (Scheme 1). Assignment of the products 2a–e was based on their
elemental analyses, IR, 1H NMR, 13C NMR, and MS spectral data. The
IR spectra of 2a–e revealed absorption bands at 1713–1698 cm−1 (C O)
1
and 1641–1633 cm−1 (C N). The H NMR spectra of 2a–e showed the
disappearance of the characteristic for singlet CH2 of the thiazolidinone
ring in 1 at δ 3.85.
SCHEME 1
Compound 2e was refluxed with urea and thiourea in ethanol–
sodium ethoxide to give the corresponding thiazolo[5,4-d]pyrimidine
derivatives 3a,b, respectively (Scheme 1). The structures of the

Thiazolidin-5-One Derivatives
2069
products 3a,b were established from their analytical and spectral data.
The IR spectrum of compound 3a showed absorption bands at 3322 cm−1
(NH), 1673 cm−1 (C O), and 1640 cm−1 (C N). The 1H NMR spectrum
of compound 3b revealed signals for two paraffinic protons, methoxy,
and aromatic protons at δ 2.60–2.70, 3.85, and 6.85–8.00, respectively,
in addition to broad signal at δ 9.60 for NH proton.
The base promoted nucleophilic addition of 3-phenyl-2-phenylimino-
thiazolidin-5-one (1) to an equimolar amount of phenyl isothio-
cyanate in DMF containing potassium hydroxide and afforded the
corresponding, nonisolable intermediate potassium sulphide salt 4.
In situ heterocyclization of 4 was achieved by the reaction with
chloroacetyl chloride to furnish the corresponding 3,3ꢁ-diphenyl-2ꢁ-
phenylimino[2,4ꢁ]bisthiazolidinylidene-5,5ꢁ-dione (5) (Scheme 2). The
structure of 5 was confirmed by analytical and spectral data. The IR
spectrum revealed an intense bands at 1737, 1685 cm−1 (2 C O), and
1625 cm−1 (C N). The 1H NMR spectrum of 5 showed a singlet signal
at δ 3.80 due to the methylene protons and multiplet at δ 6.60–7.60 due
to aromatic protons.
SCHEME 2
The condensation of 5 with p-anisaldehyde gave the correspond-
ing product 4-(4ꢁ-methoxybenzylidene)-3,3ꢁꢁ -diphenyl-2ꢁꢁ-phenylimino-
[2,4ꢁꢁ]bisthiazolidin- ylidene-5,5ꢁꢁ-dione (6). The structure of the latter

2070
M. A. Metwally et al.
1
product was supported by analytical and spectral data. The H NMR
spectrum of 6 showed singlet signal at δ 3.90 for OCH3 protons, a mul-
tiplet at δ 6.90–7.80 for aromatic protons, and a singlet signal at δ 8.00
for the olefinic proton.
The active methylene of the [2,4ꢁ]bisthiazolidinylidene-5,5ꢁ-dione
5 was coupled with 4-methylbenzenediazonium chloride in ethanol
buffered with sodium acetate at 0–5◦C to yield the corre-
sponding monohydrazone product 3,3ꢁꢁ-diphenyl-2ꢁꢁ-phenylimino-4-(4ꢁ-
tolylhydrazono)[2,4ꢁꢁ]bisthiazolidinylidene-5,5ꢁꢁ-dione (7). The struc-
ture of the product 7 was assigned on the basis of the elemental analysis
and spectral data. The IR spectrum exhibited bands at 3250 cm−1 (NH),
1718, 1695 cm−1 (2 C O), and 1634 cm−1 (C N). The 1H NMR spectrum
revealed a singlet signal at δ 2.30 corresponding to CH3 protons and a
multiplet in the region of δ 6.80–7.90 for the aromatic protons, in addi-
tion to a broad signal at δ 8.60 for the NH proton.
Subsequent treatment of 4 with equimolar amount of phenacyl bro-
mide furnished 3,4,3ꢁ-triphenyl-2ꢁ-phenylimino-2ꢁ,3ꢁ-dihydro-3H-[2,4ꢁ]-
bisthiazolyliden-5ꢁ-one (8) (Scheme 2). The structure of the latter
product was established via inspection of its spectral data. The
1H NMR spectrum revealed a multiplet signal in the region δ 6.70–
7.60 corresponding to the aromatic protons together with the olefinic
proton.
On the other hand, compound 1 was reacted with ninhydrin in
ethanol containing a catalytic amount of triethylamine to yield 2-(5ꢁ-
oxo-3ꢁ-phenyl-2ꢁ-phenyliminothiazolidin-4ꢁ-ylidene)indan-1,3-dione (9)
(Scheme 3). The structure of the latter product was established on the
basis of its analytical and spectral data. The IR spectrum showed bands
at 1711 cm−1 (C O), 1688 (2 C O), and 1635 cm−1 (C N).
Furthermore, compound 1 was condensed with isatin in glacial acetic
acid to yield 3-(5ꢁ-oxo-3ꢁ-phenyl-2ꢁ-phenyliminothiazolidin-4ꢁ-ylidene)-
1,3-dihydro-indol-2-one (10). The latter product was established from
the correct elemental analysis and spectral data. The IR spectrum
showed bands at 3181 cm−1 (NH), 1711, 1688 cm−1 (2 C O), and
1634 cm−1 (C N). The 1H NMR spectrum of 10 revealed the presence of
a multiplet signal corresponding to the aromatic protons at δ 6.90–7.75.
Treatment of compound 10 with paraformaldehyde and piperidine
or morpholine in absolute ethanol afforded the corresponding Mannich
products 11a,b (Scheme 3). Assignment of the products was based on
their analytical and spectral data. The 1H NMR spectrum for compound
11a showed a multiplet signal in the region δ 1.35–1.55 for three methy-
lene groups, at δ 2.55 for two methylene groups, a singlet signal at δ
4.50 for one methylene group, and a multiplet signal for the aromatic
protons at δ 6.90–7.60.

Thiazolidin-5-One Derivatives
2071
SCHEME 3
1-Acetyl-3-(5ꢁ-oxo-3ꢁ-phenyl-2ꢁ-phenyliminothiazolidin-4ꢁ-ylidene)
-
1,3-dihydroindol-2-one (12) was synthesized by treatment of the
thiazolidin-4-ylidene derivative 10 with acetic anhydride and sodium
acetate at 80◦C. The spectral data of the amide 12 were consistent with
1
its structure. The H NMR spectrum displayed a singlet at δ 2.30 for
CH3 protons and a multiplet at δ 6.90–7.70 for the aromatic protons.
Compound 10 was reacted with chloroacetyl chloride in DMF con-
taining catalytic amount of triethylamine to give the corresponding
chloroacetyl derivative 13. The structure of 13 was confirmed by the
1
IR, H NMR, and MS spectral data. The IR spectrum revealed an in-
tense broad band at 1700 cm−1 corresponding to the carbonyl groups
and 1638 cm−1 (C N).
Moreover, compound 10 was treated with p-toluenesulphonyl chlo-
ride in pyridine to give the corresponding sulphonyl derivative 14. The
spectral data of 14 were consistent with its structure. The IR spectrum
showed a broad band in the region 1699 cm−1 (2 C O) and a strong
band at 1634 cm−1 (C N).
The medicinal applications of spiro-2-oxoindolines as muscle re-
laxants and anti-inflammatory agents is well known.19,20 Several
spiro-2-oxoindoline derivatives have been reported to exhibit analgesic

2072
M. A. Metwally et al.
activity21 and were also platelet-aggregation inhibitors.22 Based
on the above facts, we investigated the Michael addition reaction
of the thiazolidin-5-one derivative 1 with 3-dicyanomethylidene-2-
oxoindoline to obtain the spiro-2-oxoindoline derivative 15. The struc-
ture of the spiro-2-oxoindoline 15 was secured by its elemental analysis
and spectral data (see the Experimental section below).
EXPERIMENTAL
All melting points were uncorrected. Elemental analyses were carried
out in the microanalytical unit, Faculty of Science, University of Cairo,
Egypt. IR spectra were recorded on a Mattson 5000 Fourier transform
infrared (FTIR) spectrometer. 1H NMR and 13C NMR spectra were mea-
sured on a Bruker WP 300 in CDCl3, DMSO-d6, or CF3COOD as solvent
using TMS as an internal standard. Mass spectra were recorded on a
Finnigan MAT 212 instrument.
3-Phenyl-2-phenyliminothiazolidin-5-one (1)
A mixture of diphenylthiourea (2.29 g, 0.01 mol) and chloroacetyl chlo-
ride (2.27 g, 0.02 mol) was stirred in DMF (25 ml) containing (0.56 g,
0.01 mol) KOH for 10 h. The reaction mixture was poured onto crushed
ice. The precipitate that formed was filtered off, dried, and recrystal-
lized (ethanol) to give compound 1 as buff crystals, m.p. 170–171◦C,
lit.18 m.p. 172–173◦C. Yield, 84%. IR (KBr) (ν, cm−1): 1724 (C O), 1637
1
(C N). H NMR (CDCl3) δ 3.85 (s, 2H, CH2), 6.85–7.50 (m, 10H, Ar-
H). 13C NMR (CDCl3) ppm 32.75, 120.76 (2C), 124.53, 127.86 (2C),
128.88, 129.04 (2C), 129.24 (2C), 134.56, 147.89, 154.89, 171.29. MS
(m/z, %): 268 (M+, 100), 194 (38), 149 (65), 104 (40), 77 (25). C15H12N2OS
(268.33) requires C, 67.14; H, 4.51; N, 10.44. Found: C, 67.05; H, 4.42; N,
10.34.
4-Arylidene-3-phenyl-2-phenyliminothiazolidin-5-ones
(2a–e)
A mixture of compound 1 (2.68 g, 0.01 mol) and appropriate aldehyde
(0.01 mol) in ethanol (20 ml) containing a catalytic amount of piperi-
dine was refluxed for 4 h. The mixture was cooled, and the solid prod-
ucts formed were filtered, dried, and recrystallized (ethanol) to afford
compounds 2a–e.

Thiazolidin-5-One Derivatives
2073
4-Benzylidene-3-phenyl-2-phenyliminothiazolidin-5-one
(2a)
Yellow crystals. m.p. 200–202◦C. Yield, 73%. IR (KBr) (ν, cm−1): 1713
1
(C O), 1641 (C N). H NMR (DMSO-d6) δ 7.10–7.80 (m, 15H, Ar-H),
8.05 (s, 1H, olefinic CH). C22H16N2OS (356.44) requires C, 74.13; H,
4.52; N, 7.86. Found: C, 74.26; H, 4.40; N, 7.74.
4-(4ꢀ-Hydroxybenzylidene)-3-phenyl-2-
phenyliminothiazolidin-5-one (2b)
Yellow crystals. m.p. >300◦C. Yield, 84%. IR (KBr) (ν, cm−1): 1698
(C O), 1639 (C N). 1H NMR (CDCl3/CF3COOD) δ 6.95–7.70 (m, 14H,
Ar-H), 8.15 (s, 1H, olefinic CH). 13C NMR (CDCl3/CF3COOD) ppm
110.80, 117.17 (2C), 124.13, 125.12 (2C), 127.75 (2C), 129.76, 130.79
(2C), 131.15 (2C), 131.26, 132.40, 133.53, 133.76 (2C), 142.77, 160.38,
164.58, 170.91. MS (m/z, %): 372 (M+, 35), 194 (13), 150 (100), 121(9),
77(15). C22H16N2O2S (372.44) requires C, 70.95; H, 4.33; N, 7.52. Found:
C, 70.78; H, 4.45; N, 7.63.
4-(4ꢀ-Chlorobenzylidene)-3-phenyl-2-
phenyliminothiazolidin-5-one (2c)
Yellow crystals. m.p. 179–180◦C. Yield, 78%. IR (KBr) (ν, cm−1): 1708
(C O), 1634 (C N). 1H NMR (CDCl3) δ 7.00–7.60 (m, 14H, Ar-H), 8.10
(s, 1H, olefinic CH). C22H15ClN2OS (390.89) requires C, 67.60; H, 3.87;
N, 7.17. Found: C, 67.73; H, 3.91; N, 7.08.
4-(4ꢀ-Dimethylaminobenzylidene)-3-phenyl-2-
phenyliminothiazolidin-5-one (2d)
Yellow crystals. m.p. > 300◦C. Yield, 91%. IR (KBr) (ν, cm−1): 1711
(C O), 1633 (C N). 1H NMR (DMSO-d6) δ 3.10 (s, 6H, N(CH3)2), 6.90–
7.60 (m, 14H, Ar-H), 8.00 (s, 1H, olefinic CH). MS (m/z, %): 399 (M+,
13), 177 (100), 77 (13). C24H21N3OS (399.51) requires C, 72.15; H, 5.30;
N, 10.52. Found: C, 72.34; H, 5.42; N, 10.61.
4-(4ꢀ-Methoxybenzylidene)-3-phenyl-2-
phenyliminothiazolidin-5-one (2e)
Yellow crystals. m.p. 210–212◦C; Yield, 84%. IR (KBr) (ν, cm−1): 1712
1
(C O), 1641 (C O). H NMR (CDCl3) δ 3.80 (s, 3H, OCH3), 6.80–7.55
(m, 14H, Ar-H), 7.80 (s, 1H, olefinic CH). 13C NMR (CDCl3) ppm 55.32,
114.49 (2C), 118.19, 121.05 (2C), 124.70, 126.23, 128.00 (2C), 128.79,
129.20 (4C), 131.30, 131.88 (2C), 134.71, 148.27, 151.22, 160.83, 166.58.
C23H18N2O2S (386.47) requires C, 71.48; H, 4.69; N, 7.25. Found: C,
71.60; H, 4.80; N, 7.37.

2074
M. A. Metwally et al.
2H-Thiazolo[5,4-d]pyrimidines (3a,b)
A mixture of compound 2e (3.86 g, 0.01 mol) and urea or thiourea
(0.01 mol) in EtONa/EtOH (prepared by dissolving 0.23 g of Na in 30 ml
absolute EtOH) was refluxed for 3 h. The reaction mixture was cooled,
poured onto crushed ice, left to cool, and neutralized with dilute HCl.
The solid that was formed was filtered off, dried, and recrystallized
(ethanol) to give 3a,b, respectively.
7-(4ꢀ-Methoxyphenyl)-1-phenyl-2-phenylimino-1,6,7,7a-
tetrahydro-2H-thiazolo[5,4-d]pyrimidin-5-one (3a)
Yellow crystals. m.p. 165–166◦C; Yield, 48%. IR (KBr) (ν, cm−1): 3322
(NH), 1673 (C O), 1640 (C N). 1H NMR (DMSO-d6) δ 2.55–2.70 (m, 2H,
CH-CH), 3.80 (s, 3H, OCH3), 6.80–8.00 (m, 14H, Ar-H), 8.50 (br. s, 1H,
NH). C24H20N4O2S (428.51) requires C, 67.27; H, 4.70; N, 13.07. Found:
C, 67.41; H, 4.84; N, 13.20.
7-(4ꢀ-Methoxyphenyl)-1-phenyl-2-phenylimino-1,6,7,7a-
tetrahydro-2H-thiazolo[5,4-d]pyrimidine-5-thione (3b)
Green crystals, m.p. 185–187◦C; Yield, 54%. IR (KBr) (ν, cm−1): 3313
1
(NH), 1638 (C N). H NMR (DMSO-d6) δ 2.60–2.70 (m, 2H, CH CH),
3.85 (s, 3H, OCH3), 6.85–8.00 (m, 14H, Ar-H), 9.60 (br. s, 1H, NH). MS
(m/z, %): 444 (M+, 4), 429 (2), 369 (32), 310 (25), 299 (15), 234 (62),
164 (100), 140 (74). C24H20N4OS2 (444.57) requires C, 64.84; H, 4.53;
N, 12.60. Found: C, 64.63; H, 4.66; N, 12.73.
3,3ꢀ-Diphenyl-2ꢀ-phenylimino[2,4ꢀ]bithiazolidinylidene-
5,5ꢀ-dione (5)
A mixture of compound 1 (2.68 g, 0.01 mol), KOH (0.56 g, 0.01 mol), and
phenyl isothiocyanate (1.35 g, 0.01 mol) was stirred in DMF (20 ml) at
0–5◦C for 10 h. Simultaneously chloroacetyl chloride (1.13 g, 0.01 mol)
was added dropwise, and stirring was continued for 4 h. The reaction
mixture was poured onto crushed ice. The precipitate that was formed
was filtered off, dried, and recrystallized (ethanol) to afford compound 5
as brown crystals, m.p. 198–200◦C. Yield, 64%. IR (KBr) (ν, cm−1): 1737
(C O), 1685 (C O), 1625 (C N). 1H NMR (CDCl3) δ 3.80 (s, 2H, CH2),
6.60–7.60 (m, 15H, Ar-H). 13C NMR (CDCl3) ppm 31.90, 93.79, 121.14
(2C), 124.27, 128.00 (2C), 128.65 (2C), 129.10 (2C), 129.36 (2C), 129.79
(2C), 130.56, 131.63, 133.17, 134.36, 145.58, 147.71, 151.76, 166.76,
172.66. MS (m/z, %): 443 (M+, 95), 384 (18), 249 (20), 221 (100), 179 (57),
135 (13), 103 (19), 77 (23). C24H17N3O2S2 (443.54) requires C, 64.99; H,
3.86; N, 9.47. Found: C, 64.83; H, 3.95; N, 9.59.

Thiazolidin-5-One Derivatives
2075
4-(4ꢀ-Methoxybenzylidene)-3,3ꢀꢀ-diphenyl-2ꢀꢀ-
phenylimino[2,4ꢀꢀ]bithiazolidinylidene-5,5ꢀꢀ-dione (6)
A mixture of compound 5 (4.43 g, 0.01 mol) and p-methoxybenzaldehyde
(1.22 g, 0.01 mol) in ethanol (30 ml) containing a catalytic amount of
piperidine was refluxed for 4 h. The reaction mixture was left to cool.
The solid formed was filtered off, dried, and recrystallized (ethanol)
to give compound 6 as orange crystals, m.p. 96–97◦C; Yield: 78%.
1
IR (KBr) (ν, cm−1): 1702 (C O), 1679 (C O), 1610 (C N). H NMR
(CDCl3/CF3COOD) δ 3.90 (s, 3H, OCH3), 6.90–7.80 (m, 19H, Ar-H), 8.00
(s, 1H, olefinic CH). MS (m/z, %): 561 (M+, 8), 368 (12), 339 (20), 281
(12), 207 (27), 149 (40), 57 (100). C32H23N3O3S2 (561.67) requires C,
68.43; H, 4.13; N, 7.48. Found: C, 68.62; H, 4.32; N, 7.57.
3,3ꢀꢀ-Diphenyl-2ꢀꢀ-phenylimino-4-(4ꢀ-tolylhydrazono)
[2,4ꢀꢀ]-bithiazolidinylidene-5,5ꢀꢀ-dione (7)
A solution of compound 5 (4.43 g, 0.01 mol) in ethanol (25 ml) and
sodium acetate (4 g) was stirred in ice-bath at 0–5◦C. A diazotized so-
lution of p-toluidine (0.01 mol) was added to the stirred solution over a
period 30 min, and stirring was continued for 2 h with cooling. The re-
action mixture was left in an ice bath and the solid formed was filtered
off, dried, and recrystallized (ethanol) to afford compound 7 as dark
red crystals, m.p. 120–121◦C. Yield, 70%. IR (KBr) (ν. cm−1): 3250(NH),
1
1718 (C O), 1695 (C O), 1634 (C N). H NMR (CDCl3) δ 2.30 (s, 3H,
CH3), 6.80–7.90 (m, 19H, Ar-H), 8.60(NH). C31H23N5O2S2 (561.68) re-
quires C, 66.29; H, 4.13; N, 12.47. Found: C, 66.10; H, 4.00; N, 12.56.
3,4,3ꢀ-Triphenyl-2ꢀ-phenylimino-2ꢀ,3ꢀ-dihydro-3H-
[2,4ꢀ]bisthiazolyliden-5ꢀ-one (8)
To a cold suspension of finally divided KOH (0.56 g, 0.01 mol) in DMF
(20 ml) was added the thiazolidin-5-one derivative 1 (2.68 g, 0.01 mol),
followed by phenyl isothiocyanate (1.35 g, 0.01 mol). The mixture was
stirred at room temperature overnight, then treated with phenacyl bro-
mide (1.99 g, 0.01 mol) and left to stand at room temperature for 24 h.
The mixture was poured into cold water. The solid product that sep-
arated was filtered off, washed with water, dried, and recrystallized
(ethanol) to give compound 8 as white crystals, m.p. 150–152◦C. Yield,
1
48%. IR (KBr) (ν, cm−1): 1659 (C O), 1619 (C N). H NMR (CDCl3)
δ 6.70–7.60 (m, 21H, 20 Ar-H and olefinic CH). C30H21N3OS2 (503.64)
requires C, 71.54; H, 4.20; N, 8.34. Found: C, 71.39; H, 4.34; N, 8.45.

2076
M. A. Metwally et al.
2-(5ꢀ-Oxo-3ꢀ-phenyl-2ꢀ-phenyliminothiazolidin-4ꢀ-ylidene)
indan-1,3-dione (9)
A mixture of compound 1 (2.68 g, 0.01 mol) and ninhydrin (1.78 g,
0.01 mol) in ethanol (30 ml) containing a catalytic amount of triethy-
lamine was refluxed for 4 h, and then was left to cool overnight. The
solid formed was filtered off, dried, and recrystallized (ethanol) to give
compound 9 as brown crystals, m.p. 105–107◦C. Yield, 44%. IR (KBr) (ν,
1
cm−1): 1711 (C O), 1688 (2 C O), 1635 (C N). H NMR (DMSO-d6) δ
7.10–7.85 (m, 14H, 14 Ar-H). C24H14N2O3S (410.44) requires C, 70.23;
H, 3.44; N, 6.83. Found: C, 70.07; H, 3.28; N, 6.74.
3-(5ꢀ-Oxo-3ꢀ-phenyl-2ꢀ-phenyliminothiazolidin-4ꢀ-ylidene)-
1,3-dihydro-indol-2-one (10)
A mixture of compound 1 (2.68 g, 0.01 mol) and isatin (1.47 g, 0.01 mol)
in glacial acetic acid (30 ml) was refluxed for 3 h, left to cool at room
temperature, and then poured into cold water. The solid formed was
filtered off, dried, and recrystallized from AcOH:EtOH (2:1) to af-
ford 10 as orange crystals, m.p. 229–230◦C. Yield, 85%. IR (KBr) (ν,
cm−1): 3181 (NH), 1711 (C O), 1688 (C O), 1634 (C N). 1H NMR
(CDCl3/CF3COOD) δ 6.90–7.75 (m, 14H, Ar-H). MS (m/z, %): 397 (M+,
20), 268 (19), 194 (100), 175 (56), 149 (23), 120 (28), 104 (32), 91 (32), 77
(81). C23H15N3O2S (397.45) requires C, 69.50; H, 3.80; N, 10.57. Found:
C, 69.65; H, 3.94; N, 10.70.
3-(5ꢀ-Oxo-3ꢀ-phenyl-2ꢀ-phenyliminothiazolidin-4ꢀ-ylidene)-
1,3-dihydro-indol-2-ones (11a,b)
A mixture of compound 10 (3.97 g, 0.01 mol), paraformaldehyde (0.31 g,
0.01 mol), and piperidine or morpholine (0.01 mol) in absolute ethanol
(30 ml) was refluxed in a water bath for 5 h. The reaction mixture was
evaporated to its half volume and kept at room temperature overnight.
The solid obtained was filtered off, dried, and recrystallized (ethanol)
to give 11a,b.
3-(5ꢀ-Oxo-3ꢀ-phenyl-2ꢀ-phenyliminothiazolidin-4ꢀ-ylidene)-
1-piperidin-1-yl-methyl-1,3-dihydroindol-2-one (11a)
◦
Red crystals. m.p. 143–145 C. Yield, 55%. IR (KBr) (ν, cm−1): 1692
(broad, 2 C O), 1638 (C N).1H NMR (CDCl3/CF3COOD) δ 1.35–1.55
(m, 6H, 3CH2), 2.55 (m, 4H, 2CH2), 4.50 (s, 2H, CH2), 6.90–7.60 (m,
14H, Ar-H). C29H26N4O2S (494.61) requires C, 70.42; H, 5.30; N, 11.33.
Found: C, 70.30; H, 5.42; N, 11.40.

Thiazolidin-5-One Derivatives
2077
1-Morpholin-4-ylmethyl-3-(5ꢀ-oxo-3ꢀ-phenyl-2ꢀ-
phenyliminothiazolidin-4ꢀ-ylidene)-1,3-dihydroindol-2-
one (11b)
Red crystals. m.p. 154–155◦C. Yield, 63%. IR (KBr) (ν, cm−1): 1702
(broad, 2 C O), 1638 (C N). 1H NMR (DMSO-d6) δ 2.60 (m, 4H, 2CH2),
3.50 (m, 4H, 2CH2), 4.45 (s, 2H, CH2), 7.00–7.70 (m, 14H, Ar-H). MS
(m/z, %): 496 (M+, 5), 397 (43), 310 (5), 194 (84), 174 (37), 149 (17),
120 (11), 104 (20), 100 (100), 77 (35). C28H24N4O3S (496.58) requires C,
67.72; H, 4.87; N, 11.28. Found: C, 67.85; H, 4.90; N, 11.35.
1-Acetyl-3-(5ꢀ-oxo-3ꢀ-phenyl-2ꢀ-phenyliminothiazolidin-
4ꢀ-ylidene)-1,3-dihydroindol-2-one (12)
A mixture of compound 10 (3.97 g, 0.01 mol) and sodium acetate (0.5 g)
in acetic anhydride (10 ml) was heated in a water bath (at 80◦C) for
6 h, left to cool, and poured into ice-cold water. The solid formed was
filtered off, dried, and recrystallized (ethanol) to afford compound 12
as red crystals, m.p. 263–264◦C. Yield, 76%. IR (KBr) (ν, cm−1): 1712
1
(broad, 3 C O), 1643 (C N). H NMR (DMSO-d6) δ 2.30 (s, 3H, CH3),
6.90–7.70 (m, 14H, Ar-H). C25H17N3O3S (439.49) requires C, 68.32; H,
3.90; N, 9.56. Found: C, 68.49; H, 3.77; N, 9.45.
1-(2-Chloroacetyl)-3-(5ꢀ-oxo-3ꢀ-phenyl-2ꢀ-
phenyliminothiazolidin-4ꢀ-ylidene)-1,3-dihydroindol-2-
one (13)
A mixture of compound 10 (3.97 g, 0.01 mol) and chloroacetyl chloride
(1.13 g, 0.01 mol) in DMF containing a catalytic amount of triethylamine
was stirred at room temperature for 2 h and was then poured into ice-
cold water. The solid formed was filtered off, dried, and recrystallized
from EtOH:DMF (3:1) to yield the chloroacetyl derivative 13 as orange
crystals, m.p. 270–271◦C. Yield, 68%. IR (KBr) (ν, cm−1): 1700 (broad, 3
C O), 1638 (C N). 1H NMR (DMSO-d6) δ 4.15 (s, 2H, CH2), 7.10–7.90
(m, 14H, Ar-H). C25H16ClN3O3S (473.93) requires C, 63.36; H, 3.40; N,
8.87. Found: C, 63.53; H, 3.22; N, 9.00.
3-(5ꢀ-Oxo-3ꢀ-phenyl-2ꢀ-phenyliminothiazolidin-4ꢀ-ylidene)-
1-(toluene-4-sulphonyl)-1,3-dihydroindol-2-one (14)
A mixture of compound 10 (3.97 g, 0.01mol) and p-toluenesulphonyl
chloride (1.90 g, 0.01 mol) in pyridine (20 ml) was stirred at room tem-
perature for 4 h. The reaction mixture was poured into ice-cold water
and neutralized with acetic acid. The formed solid product was filtered

2078
M. A. Metwally et al.
off, dried, and recrystallized from ethanol to yield compound 14 as red
crystals, m.p. 280–282◦C. Yield, 77%. IR (KBr) (ν, cm−1): 1699 (broad, 2
C O), 1634 (C N). 1H NMR (DMSO-d6) δ 2.40 (s, 3H, CH3), 7.05–7.80
(m, 18H, Ar-H). MS (m/z, %): 551 (M+, 5), 397 (41), 194 (100), 175 (50),
146 (13), 120 (10), 77 (20). C30H21N3O4S2 (551.64) requires C, 65.32; H,
3.84; N, 7.62. Found: C, 65.20; H, 3.95; N, 7.51.
Spiro-pyrano[3,2-d]thiazole-2-oxoindoline Derivative (15)
A mixture of 1 (2.68 g, 0.01 mol) in ethanol (30 ml), 3-dicyano-
methylidene-2-oxoindoline (1.96 g, 0.01 mol), and a few drops of piperi-
dine was refluxed for 4 h and then left to cool overnight. The result-
ing solid product was filtered off, dried, and recrystallized (ethanol) to
yield 15 as yellow crystals, m.p. 258–259◦C. Yield, 54%. IR (KBr) (ν,
1
cm−1): 3394, 3311 (NH2 and NH), 2197 (CN), 1705 (C O). H NMR
(CDCl3/CF3COOD) δ 7.10–7.90 (m, 14H, Ar-H). MS (m/z, %): 463 (M+,
4), 354 (4), 306 (100), 278 (82), 234 (25), 180 (10), 119 (22), 77 (65).
C26H17N5O2S (463.51) requires C, 67.37; H, 3.70; N, 15.11. Found: C,
67.50; H, 3.78; N, 15.22.
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