A convenient synthesis of some new 5-substituted-4-thioxo-thiazolidinones and fused thiopyrano[2,3-d]thiazole derivatives

Article abstract of DOI:10.1080/10426500701849105

The new Z-5-arylmethylene-4-thioxo-thiazolidine derivatives have been synthesized by condensation of ω -(4-formylphenoxy)acetophenone derivatives with 4-thioxo-thiazolidine derivatives, in good yields. The cycloaddition of the newly synthesized compounds

Full text of DOI:10.1080/10426500701849105

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Phosphorus, Sulfur, and Silicon
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A Convenient Synthesis of
Some New 5-Substituted-4-
Thioxo-Thiazolidinones
and Fused Thiopyrano[2,3-
d]thiazole Derivatives
Nadia Hanafy Metwally a
a Department of Chemistry, Faculty of Science ,
University of Cairo , Giza, Egypt
Published online: 12 Aug 2008.
To cite this article: Nadia Hanafy Metwally (2008) A Convenient Synthesis of Some
New 5-Substituted-4-Thioxo-Thiazolidinones and Fused Thiopyrano[2,3-d]thiazole
Derivatives, Phosphorus, Sulfur, and Silicon and the Related Elements, 183:9,
2073-2085, DOI: 10.1080/10426500701849105
To link to this article: http://dx.doi.org/10.1080/10426500701849105
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Phosphorus, Sulfur, and Silicon, 183:2073–2085, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500701849105
A Convenient Synthesis of Some New
5-Substituted-4-Thioxo-Thiazolidinones and Fused
Thiopyrano[2,3-d]thiazole Derivatives
Nadia Hanafy Metwally
Department of Chemistry, Faculty of Science, University of Cairo,
Giza, Egypt
The new Z-5-arylmethylene-4-thioxo-thiazolidine derivatives have been synthesized
by condensation of ω-(4-formylphenoxy)acetophenone derivatives with 4-thioxo-
thiazolidine derivatives, in good yields. The cycloaddition of the newly synthesized
compounds to N-arylmaleimides, N-phenyl-1,2,4-triazole-3,5-dione, ethyl acrylate
and ω-nitrostyrene has been studied. Under thermal reaction conditions [4 + 2] cy-
cloaddition proceeds with complete site- and regioselectivity to yield the new fused
thiopyrano[2,3-d]thiazole derivatives.
Keywords 4-Thioxo-thiazolidine derivatives; 5-[(4-benzoylmethoxy)phenylmethylene]-
4-thioxo-thiazolidines; ω-(4-formylphenoxy)acetophenones; thiopyrano[2,3-d]-thiazole
derivatives
INTRODUCTION
As a part of the general interest in heterocyclic synthesis, which
has been explored for developing pharmaceutically important com-
pounds, thiazolidinones have been studied extensively due to their
ready accessibility, diverse chemical reactivity and broad spectrum
of biological activity.1–13 Recently, it was established, that the modi-
fied 5-substituted thiazolidinone derivatives exhibited diverse pharma-
cological activities.14–17In addition, heterocyclic systems having both
thiazolidine and thiopyrano moieties have important applications in
the field of medicinal chemistry.18–20 Our objective is that 4-thioxo-
thiazolidinones are synthetic precursors of thiopyrano[2,3-d]thiazole
compounds, which could imitate some pharmacologically important
molecular fragments of thiazolidinones. In continuation of our previ-
ous studies on 4-thioxo-thiazolidines,21–28 I report here the synthesis
Received 3 September 2007; accepted 24 October 2007.
Address correspondence to Nadia Hanafy Metwally, Department of Chemistry, Faculty
of Science, University of Cairo, Giza, Egypt. E-mail: nhmmohamed@yahoo.com
2073

2074
N. H. Metwally
of some new thiopyrano[2,3-d]thiazole derivatives, starting from ω-(4-
formylphenoxy)acetophenone derivatives and 4-thioxo-thiazolidinone
derivatives.
RESULTS AND DISCUSSION
The etherification of ω-bromoacetophenone derivatives 1a-d
with 4-hydroxybenzaldehyde (2) in refluxing acetone and in the
presence of anhydrous K2CO3, afforded the corresponding ω-(4-
formylphenoxy)acetophenone derivatives 3a-d in almost quantitative
yields (Scheme 1). The structure of the isolated products 3a-d were
deduced from elemental analyses and spectral data. For example, the
IR spectrum of 3a showed an absorption band near 2848, 2763 cm−1
,
due to aldehydic CH group and 1681–1683 cm−1, due to two C O
groups, in addition to other absorptions correlated to the assigned
1
structures. Furthermore, the H NMR spectrum of the same product
revealed a singlet signal at δ = 5.76 attributed to the active methylene
protons and a singlet signal at δ = 9.87 attributed to aldehydic proton.
Also, the mass spectrum showed correct molecular ion peak at m/z 240
(M+) beside some of the abundant fragments. Elemental analyses are
in agreement with the structures 3a-d (cf. Experimental).
The aldehydes 3a-d were allowed to condense with 4-thioxo-
thiazolidin-2-one (4a) and /or 2,4-dithioxo-thiazolidine (4b) in glacial
acetic acid and in the presence of anhydrous sodium acetate to afford 5-
arylmethylene-4-thioxo-thiazolidine derivatives 5a-h, respectively, in
good yields. The structures of products 5a-h were established via their
elemental analyses and spectral data. For example, the IR spectrum of
5a showed absorption bands at 3055 and 1700–1702 cm−1 due to NH
and two C O groups, and in addition to other absorptions correlated
to the assigned structure. Its 1H NMR spectrum revealed a singlet sig-
nal at δ = 5.72 due to methylene protons, a singlet signal at δ = 8.07
due to olefinic proton and a D2O-exchangeable signal at δ = 13.73 at-
tributed to NH proton, beside the other expected signals. The mass
SCHEME 1

Thioxo-Thiazolidinones and Fused Thiazole Derivatives
2075
SCHEME 2
spectrum of 5a showed correct molecular ion peak at m/z 355 (M+). In
addition, an evidence to support the structural assignment was gained
from the 13C NMR spectrum of the same compound, which showed two
characteristic signals at δ 70.32 and 195.07 attributed to methylene
and carbonyl carbon atoms. In addition, two characteristic signals at
δ = 170.55 and 193.89 corresponding to carbonyl and thiocarbonyl car-
bon atoms of thiazolidine ring, respectively, beside the other expected
signals (cf. Experimental). From these data the Z-configuration was
assigned to structures 5 on the basis that the olefinic proton of the Z-
configured isomer is more deshielded by the thioxo group of the thiazole
moiety compared with the E-isomer and appears at lower field (δ ∼ 8.0–
8.50 ppm) relative to the E-isomer29–31 (δ ∼ 7.30–7.80 ppm) (cf. Scheme
2 and Experimental).
Next, my study is extended to explore the utility of compounds 5a,e in
Diels-Alder reaction with different dienophiles. Thus, heating equimo-
lar amounts of the deeply colored 5a,e and N−arylmaleimides 6a-c
under reflux in toluene gave colorless 1:1 adducts. The IR spectrum
of the isolated product 7b taken as typical example of the prepared
series, showed absorption bands at 1677 cm−1 and 1716 cm−1, corre-
sponding to CO groups. Furthermore, the 1H NMR data of this adduct
showed two doublets at δ = 3.88 and 3.95 with J values 5.6 and 8.6 Hz
attributed to H-6, in addition to two doublets at δ = 4.45 and 5.24 with
J values 5.6 and 8.6 Hz, respectively, corresponding to H-5 and H-7,
beside the other expected signals. Based on the coupling constant, the
cis-configurations32 was assigned to the cycloadducts 7b. Based on the
elemental analyses and spectral data, structures 7a-f were assigned to
these adducts (cf. Scheme 3 and Experimental).
Similarly, the reaction of 5a,e with N-phenyl-1, 2, 4-triazole-3,5-
dione (8) in refluxing toluene afforded the 1:1 adducts 9a,b (cf.
Scheme 4). The structures of the isolated adducts 9a,b were deduced
from their elemental analyses and spectral data (cf. Experimental).

2076
N. H. Metwally
SCHEME 3
Also, the cycloaddition of 5a,e with ethyl acrylate (10a) and ω-
nitrostyrene (10b) in refluxing toluene gave the thiazolothiopyrano
cycloadducts, 11a-d (cf. Scheme 5). The structures of 11a-d were as-
1
signed based on their elemental analyses and spectral data. The H
NMR spectra of compounds 11a,b revealed in each case one doublet
at δ ∼ 4.45 corresponding to H-7 and two doublets at ∼ 3.28 and 3.37
corresponding to H-5ax and H-5eq in addition to multiplet at δ ∼ 3.04–
3.15 corresponding to H-6. The formation of compounds 11a-d can be
explained in terms of [4 + 2] cycloaddition to thiocarbonyl system (cf.
Experimental).
EXPERIMENTAL
Melting points were determined on an electrothermal (9100) appara-
tus and are uncorrected. The IR spectra were recorded as KBr pellets
1
on a Perkin Elmer 1430 spectrophotometer. H NMR and 13C NMR
spectra were recorded in deuterated dimethylsulfoxide at 300 MHz
on a Varian Gemini NMR spectrometer using tetramethylsilane as
SCHEME 4

Thioxo-Thiazolidinones and Fused Thiazole Derivatives
2077
SCHEME 5
internal reference, and results are expressed as δ values. Mass spec-
tra were taken on a Shimadzu GCMS-QP 1000 Ex mass spectrometer
at 70 eV. Elemental analyses were carried out at the Microanalysis Cen-
ter of Cairo University, Giza, Egypt. The starting compounds 4a and
4b were prepared according to the reported literature.33,34
ω-(4-Formylphenoxy)acetophenone Derivatives 3a-d—General
Procedure
ω-Bromoacetophenone derivatives 1a-d (10 mmol) was added to a mix-
ture of 4-hydroxybenzaldehyde (2) (1.22 g, 10 mmol) and anhydrous
K2CO3 (2.90 g, 30 mmol) in dry acetone (30 ml). The mixture was re-
fluxed on a water bath for 6 h, left to cool, poured into cold water, filtered
off, and recrystallized from ethanol to afford pale brown crystals.
ω-(4-Formylphenoxy)acetophenone (3a)
Yield (98%); m.p. 117◦C; IR (cm−1) ν 2848, 2763 (aldehydic CH) and
1
1681–1683 (C O); H NMR (DMSO) δ 5.76 (s, 2H, CH2), 7.16 (d, 2Hb,
J = 9.0, Hz, ArH’s), 7.57 (t, 2Hd, J = 7.2 Hz, ArH’s), 7.70 (t, 1He, J =
7.4 Hz, ArH’s), 7.88 (d, Ha, J = 8.7 Hz, ArH’s), 8.04 (d, 2Hc, J = 7.2
Hz, ArH’s), 9.87 (s, 1H, CHO); MS (m/z): 240 (M+, 5.7%), 121 (4.9%),
105 (100%), 91 (16.4%), 77 (36.7%), 61 (4.6%), and 50 (18.6%). Anal. for
C15H12O3 (240.25) calcd.: C, 74.99; H, 5.03. Found: C, 74.87; H, 5.16.
ω-(4-Formylphenoxy)-4-methylacetophenone (3b)
Yield (92%); m.p. 105◦C; IR (cm−1) ν 2859, 2789 (aldehydic CH) and
1
1698–1700 (C O); H NMR (DMSO) δ 2.37 (s, 3H, CH3), 5.70 (s, 2H,
CH2), 7.15 (d, 2Hb, J = 9.0 Hz, ArH’s), 7.39 (d, 2Hd, J = 6.1 Hz, ArH’s),
7.85 (d, 2Ha, J = 8.7 Hz, ArH’s), 7.92 (d, 2Hc, J = 8.4 Hz, ArH’s), 9.87

2078
N. H. Metwally
(s, 1H, CHO). MS (m/z): 254 (M+, 6.3%), 119 (100%), 91 (36.4%), 77
(17.4%), and 61 (2.1%). Anal. for C16H14 O3 (254.28) calcd.: C, 75.57; H,
5.55. Found: C, 75.71; H, 5.38.
ω-(4-Formylphenoxy)-4-bromoacetophenone (3c)
Yield (97%); m.p. 122◦C; IR (cm−1) ν 2832, 2762 (aldehydic CH) and
1
1706–1710 (C O); H NMR (DMSO) δ 5.76 (s, 2H, CH2), 7.18 (d, 2Hb,
J = 9.0 Hz, ArH’s), 7.71 (d, 2Hd, J = 8.6 Hz, ArH’s), 7.88 (d, 2Ha, J =
8.8 Hz, ArH’s), 8.01 (d, 2Hc, J = 8.2 Hz, ArH’s), 9.01 (s, 1H, CHO).
MS (m/z): 320 (M+1, 12.9%), 183 (100%), 169 (8.1%), 155 (23.7%), 105
(14.6%), 90 (19.9%), 77 (23.2%), 63 (13.2%), and 50 (37.7%). Anal. for
C15H11BrO3 (319.15) calcd.: C, 56.45; H, 3.47; Br, 25.04 . Found: C, 56.28;
H, 3.32, Br, 25.20.
ω-(4-Formylphenoxy)-4-chloroacetophenone (3d)
Yield (94%); m.p. 128◦C; IR (cm−1) ν 2865, 2782 (aldehydic CH) and
1
1708–1710 (C O); H NMR (DMSO) δ 5.77 (s, 2H, CH2), 7.19 (d, 2Hb,
J = 9.0 Hz, ArH’s), 7.68 (d, 2Hd, J = 8.6 Hz, ArH’s), 7.84 (d, 2Ha, J =
8.6 Hz, ArH’s), 8.04 (d, 2Hc, J = 8.2 Hz, ArH’s), and 8.98 (s, 1H, CHO).
Anal. for C15H11 ClO3 (274.04) calcd.: C, 65.58; H, 4.04; Cl, 12.91. Found:
C, 65.43; H, 4.17; Cl, 12.78.
Condensation of 3a-d with 4-Thioxo-thiazolidin-2-one (4a)
and/or 2,4-Dithioxo-thiazolidine (4b)—General Procedure
To a solution of 4a or 4b (10 mmol) in glacial acetic acid (25 ml) and
anhydrous sodium acetate (1.64 g, 20 mmol) was added the appropriate
aldehyde 3a-d (10 mmol). The reaction mixture was refluxed for 30 min.
on a water bath, cooled and then poured into cold water. The solid so
formed was filtered off and recrystallized from EtOH/dioxane to give
orange or reddish crystals of 5a-d.
Z-5-[4-(Benzoylmethoxy)phenylmethylene]-4-thioxo-
thiazolidin-2-one(5a)
Yield (75%); m.p. 198◦C; IR (cm−1) υ 3055 (NH) and 1700–1702
(C O); 1H NMR (DMSO) δ 5.72 (s, 2H, CH2), 7.14 (d, 2Hb, J = 9.3 Hz,
ArH’s), 7.56 (d, 2Ha, J = 7.5 Hz, Ar’s), 7.60 (t, 2Hd, J = 8.7 Hz, ArH’s),
7.69 (t, 1He, J = 7.5 Hz, ArH’s), 8.02 (d, 2Hc, J = 7.2 Hz, Ar’s), 8.07 (s,
1H, CH), 13.73 (brs, NH, exchangeable with D2O). 13C NMR (DMSO-d6,)
δ 70.32 (CH2), 115.18, 126.31, 127.15, 127.87, 128.84, 132.71, 133.90,
134.18, 136.15, 160.27, 170.55 (C O), 193.89 (C = S) and 195.07 (C O).
MS m/z (%): 355 (M+, 19.3%), 235 (7.5%), 193 (4.4%), 181 (3.1%), 165

Thioxo-Thiazolidinones and Fused Thiazole Derivatives
2079
(2.7%), 149 (3.5%), 106 (8.3%), 105 (100%), 89 (7.5%), and 77 (47.5%).
Anal. for C18H13NO3S2 (355.43) calcd.: C, 60.83; H, 3.69; N, 3.94; S,
18.04. Found: C, 60.68; H, 3.57; N, 3.78; S, 17.89.
Z-5-[4-(4-Methylbenzoylmethoxy)phenylmethylene]-4-thioxo-
thiazolidin-2-one(5b)
Yield (72%), m.p. 170◦C; IR (cm−1) υ 3120 (NH) and 1690 (C O); 1H
NMR (DMSO) δ 3.36 (s, 3H, CH3), 5.72 (s, 2H, CH2), 7.12 (d, 2Hb, J =
8.8 Hz, ArH’s), 7.53–7.62 (m, 4Ha,d, ArH’s), 7.98 (d, 2Hc, J = 7.6 Hz,
ArH’s), 8.0 (s, 1H, CH), and 13.71 (brs, NH, exchangeable with D2O).
Anal. for C19H15NO3S2 (369.46) calcd.: C, 61.77; H, 4.09; N, 3.79; S,
17.36. Found: C, 61.63; H, 4.21; N, 3.62; S, 17.50.
Z-5-[4-(4-Bromobenzoylmethoxy)phenylmethylene]-4-thioxo-
thiazolidin-2-one(5c)
Yield (80%); m.p. 227◦C; IR (cm−1) υ 3175 (NH) 1686 and 1690 (C O);
1H NMR (DMSO) δ 5.74 (s, 2H, CH2), 7.12 (d, 2Hb, J = 8.8 Hz, ArH’s),
7.66 (d, 2Ha, J = 8.4 Hz, ArH’s), 7.77 (d, 2Hd, J = 8.2 Hz, ArH’s), 7.82 (d.,
2Hc, J = 8.4 Hz, ArH’s), 8.02 (s, 1H, CH), and 13.70 (brs, NH, exchange-
able with D2O). Anal. for C18H12BrNO3S2 (434.33) calcd.: C, 49.78; H,
2.78; Br, 18.40; N, 3.22; S, 14.77. Found: C, 49.91; H, 2.90; Br, 18.24; N,
3.37; S, 14.63.
Z-5-[4-(4-Chlorobenzoylmethoxy)phenylmethylene]-4-oxo-
thiazolidin-2-one(5d)
Yield (82%), m.p. 218◦C; IR (cm−1) υ 3183 (NH), 1687 and 1690
(C O); 1H NMR (DMSO) δ 5.73 (s, 2H, CH2), 7.14 (d, 2Hb, J = 9.0
Hz, ArH’s), 7.60 (d, 2Ha, J = 8.2 Hz, Ar’s), 7.74 (d, 2Hd, J = 8.4 Hz,
ArH’s), 8.88 (d, 2Hc, J = 8.2 Hz, Ar’s), 8.04 (s, 1H, CH), and 13.73 (brs,
NH, exchangeable with D2O). Anal. for C18H12ClNO3S2 (389.88) calcd.:
C, 55.45; H, 3.10; Cl, 9.09; N, 3.59; S, 16.45. Found: C, 55.57; H, 3.23;
Cl, 9.23; N, 3.42; S, 16.58.
Z-5-[4-(Benzoylmethoxy)phenylmethylene]-2,4-dithioxo-
thiazolidine(5e)
Yield (83%); m.p. 202◦C; IR (cm−1) υ 3100 (NH) and 1690 (C O); 1H
NMR (DMSO) δ 5.73 (s, 2H, CH2), 7.12 (d, 2Hb, J = 8.8 Hz, ArH’s), 7.53
(d, 2Ha, J = 7.4, Ar’s), 7.59 (t, 2Hd, J = 7.4 Hz, ArH’s), 7.70 (t, 1He, J =
7.6 Hz, ArH’s), 8.0 (d, 2Hc, J = 7.2 Hz, Ar’s), 8.08 (s, 1H, CH), 13.70 (brs,
NH, exchangeable with D2O). Anal. for C18H13NO2S3 (371.50) calcd.:
C, 58.20; H, 3.53; N, 3.77; S, 25.89. Found: C, 58.33; H, 3.70; N, 3.64; S,
25.77.

2080
N. H. Metwally
Z-5-[4-(4-Methylbenzoylmethoxy)phenylmethylene]-2,4-
dithioxo-thiazolidine(5f)
Yield (78%); m.p. 215◦C; IR (cm−1) υ 3126 (NH) and 1690 (C O); 1H
NMR (DMSO) δ 3.37 (s, 3H, CH3), 5.72 (s, 2H, CH2), 7.12 (d, 2Hb, J =
9.0 Hz, ArH’s), 7.55–7.66 (m, 4Ha,d, ArH’s), 7.97 (d, 2Hc, J = 7.8 Hz,
ArH’s), 8.02 (s, 1H, CH), 13.68 (brs, NH, exchangeable with D2O). MS
m/z (%): 385 (21.3%), 252 (10.9%), 193 (5.2%), 177 (5.2%), 191 (2.1%),
177 (5.8%), 165 (4.3%), 150 (6.3%), 105 (28.6%), 119 (100%), 91 (36.3%),
and 77 (17.1%). Anal. for C19H15NO2S3 (385.52) calcd.: C, 59.19; H, 3.92;
N, 3.63; S, 24.95. Found: C, 59.33; H, 3.75; N, 3.49; S, 24.78.
Z-5-[4-(4-Bromobenzoylmethoxy)phenylmethylene]-2,4-
dithioxo-thiazolidine(5g)
Yield (83%); m.p. 242◦C; IR (cm−1) υ 3177 (NH) and 1690 (C O); 1H
NMR (DMSO) δ 5.72 (s, 2H, CH2), 7.12 (d, 2Hb, J = 8.8 Hz, ArH’s), 7.60
(d, 2Ha, J = 7.6 Hz, ArH’s), 7.74 (d, 2Hd, J = 8.4 Hz, ArH’s), 7.88 (d., 2Hc,
J = 8.4 Hz, ArH’s), 8.07 (s, 1H, CH), and 13.64 (brs, NH, exchangeable
with D2O). Anal. for C18H12BrNO2S3 (450.39) calcd.: C, 48.0; H, 2.69;
Br, 17.74; N, 3.11; S, 21.36. Found: C, 48.18; H, 2.54; Br, 17.90; N, 3.28;
S, 21.49.
Z-5-[4-(4-Chlorobenzoylmethoxy)phenylmethylene]-2,4-
dithioxo-thiazolidine(5h)
Yield (87%); m.p. 230◦C; IR (cm−1) υ 3187 (NH) and 1690 (C O); 1H
NMR (DMSO)δ 5.75 (s, 2H, CH2), 7.15 (d, 2Hb, J = 8.6 Hz), 7.58 (d,
2Ha, J = 7.8 Hz), 7.70 (d, 2Hd, J = 7.8 Hz), 8.02 (d, 2Hc, J = 8.2 Hz),
8.04 (s, 1H, CH), and 13.65 (brs, NH, exchangeable with D2O). Anal.
for C18H12ClNO2S3 (405.94) calcd.: C, 53.26; H, 2.98; Cl, 8.73; N, 3.45;
S, 23.70. Found: C, 53.39; H, 2.86; Cl, 8.88; N, 3.29; S, 23.58.
Reactions of 5a,e with N-arylmaleimides,
N-phenyl-1,2,4-triazole-3,5-dione, Ethyl Acrylate and
ω-Nitrostyrene—General Procedure
A solution of equimolecular amounts (10 mmol) of 5a,e, and the appro-
priate dienophile in toluene (30 ml) was refluxed for 1 h. The solid so
formed was filtered off and crystallized from the appropriate solvent.
7-[4-(Benzoylmethoxy)phenyl]-N-phenyl-5,6-
dihydrothiopyrano[2,3-d]thiazolidin-2-oxo-5,6-
dicarboximide (7a)
White crystals (EtOH/dioxane); yield (57%); m.p. 218◦C; IR (cm−1) υ
1
3186 (NH), 1711 (CO) and 1677 (CO); H NMR (DMSO) δ 3.85–3.91

Thioxo-Thiazolidinones and Fused Thiazole Derivatives
2081
(dd, 1H, J = 5.6 Hz, 8.6 Hz, H-6), 4.42 (d, 1H, J = 5.6 Hz, H-5), 5.22
(d, 1H, J = 8.6 Hz, H-7), 5.60 (s, 2H, CH2), 6.50 (d, 2Hb, J = 8.8 Hz,
ꢀ
ꢀ
ArH’s), 6.88 (m, 3Ha,c , ArH’s), 7.18 (t, 2Hb , J = 8.4 Hz, ArH’s), 7.32
ꢀ
(m, 2Ha , ArH’s), 7.35 (t, 2Hd, J = 7.6 Hz, Ar’s), 7.57 (t, 1He, J = 7.0
Hz, Ar’s), 8.01 (d, 2Hc, J = 7.2 Hz, ArH’s), and 11.80 (s, 1H, NH). Anal.
for C28H20N2O5S2 (528.60) calcd.: C, 63.62; H, 3.81; N, 5.30; S, 12.13.
Found: C, 63.45; H, 3.65; N, 5.48; S, 12.28.
7-[4-(Benzoylmethoxy)phenyl]-N-(4-methoxyphenyl)-5,6-
dihydrothiopyrano[2,3-d]thiazolidin-2-oxo-5,6-
dicarboximide (7b)
Pale brown crystals (EtOH/dioxane); yield (63%); m.p. 225◦C; IR
1
(cm−1) υ 3165 (NH), 1716 (CO) and 1677 (CO); H NMR (DMSO) δ
3.75 (s, 3H, OCH3), 3.88–3.95 (dd, 1H, J = 5.6, 8.6 Hz, H-6), 4.45 (d,
1H, J = 5.6 Hz, H-5), 5.24 (d, 1H, J = 8.6 Hz, H-7), 5.62 (s, 2H, CH2),
ꢀ
6.53 (d, 2Hb, J = 9.0 Hz, ArH’s), 6.91–7.0 (m, 2Ha, 2Hb , ArH’s), 7.22 (d,
ꢀ
2Ha , J = 8.6 Hz, ArH’s), 7.55 (t, 2Hd, J = 7.8 Hz, ArH’s), 7.65 (t, 1He,
J = 7.4 Hz, ArH’s), 8.03 (d, 2Hc, J = 6.8 Hz, ArH’s), and 11.82 (s, 1H,
NH). Anal. for C29H22N2O6S2 (558.62) calcd.: C, 62.35; H, 3.97; N, 5.01;
S, 11.48. Found: C, 62.20; H, 3.80; N, 5.18; S, 11.65.
7-[4-(Benzoylmethoxy)phenyl]-N-(4-chlorophenyl)-5,6-
dihydrothiopyrano[2,3-d]thiazolidin-2-oxo-5,6-
dicarboximide (7c)
Pale brown crystals (EtOH/dioxane); yield (65%); m.p. 235◦C; IR
(cm−1) υ 3176 (NH), 1710 (CO) and 1680 (CO); 1H NMR (DMSO) δ 3.98–
4.11 (dd, 1H, J = 6.0, 8.8 Hz, H-6), 4.71 (d, 1H, J = 6.0 Hz, H-5), 5.10
(d, 1H, J = 8.8 Hz, H-7), 5.70 (s, 2H, CH2), 6.62 (d, 2Hb, J = 8.8, ArH’s),
ꢀ
ꢀ
6.93–7.10 (m, 2Ha, 2Hb , ArH’s), 7.25 (d, 2Ha , J = 8.6 Hz, ArH’s), 7.58
(t, 2Hd, J = 7.6 Hz, ArH’s), 7.67 (t, 1He, J = 7.2 Hz, ArH’s), 8.04 (d, 2Hc,
J = 6.8 Hz, ArH’s), and 11.78 (s, 1H, NH). Anal. for C28H19ClN2O5S2
(563.04) calcd: C, 59.73; H, 3.40; Cl, 6.30; N, 4.98; S, 11.39. Found: C,
59.56; H, 3.24; Cl, 6.20; N, 4.80; S, 11.57.
7-[4-(Benzoylmethoxy)pheny]-N-phenyl-5,6-
dihydrothiopyrano[2,3-d]thiazolidin-2-thioxo-5,6-
dicarboximide (7d)
White crystals (EtOH); yield (57%); m.p. 228◦C; IR (cm−1) υ 3173
1
(NH) and 1717 (CO); H NMR (DMSO) δ 3.90–3.98 (dd, 1H, J = 6.2,
9.0 Hz, H-6), 4.63 (d, 1H, J = 6.2 Hz, H-5), 5.30 (d, 1H, J = 9.0 Hz,
ꢀ
H-7), 5.59 (s, 2H, CH2), 6.62 (d, 2Hb, J = 8.0 Hz, ArH’s), 6.91 (d, 3Ha,c ,
ꢀ
ꢀ
ArH’s), 7.21 (t, 1Hb , J = 8.6 Hz, ArH’s) 7.42 (t, 2Ha , J = 7.0 Hz, ArH’s),
7.57 (t, 2Hd, J = 7.2 Hz, Ar’s), 7.69 (t, 1He, J = 7.6 Hz, Ar’s), 8.05 (d,

2082
N. H. Metwally
2Hc, J = 7.0 Hz, ArH’s), and13.77 (s, 1H, NH). Anal. for C28H20N2O4S3
(544.66) calcd.: C, 61.74; H, 3.70; N, 5.14; S, 17.66. Found: C, 61.86; H,
3.58; N, 5.26; S, 17.73.
7-[4-(Benzoylmethoxy)phenyl]-N-(4-methoxyphenyl)-5,6-
dihydrothiopyrano[2,3-d]thiazolidin-2-thioxo-5,6-
dicarboximide (7e)
White crystals (acetic acid); yield (61%); m.p. 195◦C; IR (cm−1) υ 3165
1
1
(NH), 1710 (CO) and 1680 (CO); H NMR (DMSO) H NMR (DMSO)
δ 3.75 (s, 3H, OCH3), 3.91–3.96 (dd, 1H, J = 6.0, 8.8 Hz, H-6), 4.65 (d,
1H, J = 6.0 Hz, H-5), 5.33 (d, 1H, J = 8.8 Hz, H-7), 5.60 (s, 2H, CH2),
ꢀ
6.63 (d, 2Hb, J = 6.0 Hz, ArH’s), 6.91–7.22 (m, 2Ha, 2Hb , ArH’s), 7.28
ꢀ
(d, 2Ha , J = 8.6 Hz, ArH’s), 7.57 (t, 2Hd, J = 7.0 Hz, ArH’s), 7.68 (t,
1He, J = 7.2 Hz, ArH’s), 8.05 (d, 2Hc, J = 6.8Hz, ArH’s), and 13.75 (s,
1H, NH). Anal. for C29H22N2O5S3 (574.69) calcd.: C, 60.61; H, 3.86; N,
4.87; S, 16.74. Found: C, 60.51; H, 3.97; N, 4.71; S, 16.86.
7-[4-(Benzoylmethoxy)phenyl]-N-(4-chlorophenyl)-5,6-
dihydrothiopyrano[2,3-d]thiazolidin-2-thioxo-5,6-
dicarboximide (7f)
White crystals (acetic acid), yield (63%); m.p. 242◦C; IR (cm−1) υ 3187
(NH) and 1718 (CO); 1H NMR (DMSO) δ 3.97–4.06 (dd, 1H, J = 6.0, 9.0
Hz, H-6), 4.71 (d, 1H, J = 6.0 Hz, H-5), 5.43 (d, 1H, J = 9.0 Hz, H-7),
5.65 (s, 2H, CH2), 6.68 (d, 2Hb, J = 6.0 Hz, ArH’s), 6.93 (d, 2Ha, J = 8.8,
ꢀ
ArH’s), 7.30 (d, 2Hb , J = 8.8 Hz, ArH’s), 7.60 (t, 2Hd, J = 7.4 Hz, ArH’s),
7.71 (t, 1He, J = 7.2 Hz, ArH’s), 8.06 (d, 2Hc, J = 7.2 Hz, ArH’s), and
13.76 (s, 1H, NH). Anal. for C28H19ClN2O4S3 (579.11) calcd.: C, 58.07;
H, 3.31; Cl, 6.12; N, 4.84; S, 16.61. Found: C, 58.16; H, 3.44; Cl, 6.0; N,
4.95; S, 16.48.
10-[4-(Benzoylmethoxy)phenyl]-7-phenyl-thiazolo[5,4-
e]thiadiazino[2‘,3‘-a]triazole-2,6,8-trione (9a)
White crystals (DMF); yield (45%); m.p. 297◦C; IR (cm−1) υ 3170 (NH)
and 1711 (CO); 1H NMR (DMSO6)δ 5.30 (s, 1H, H-7), 5.73 (s, 2H, CH2),
ꢀ
ꢀ
6.47 (d, 2Hb, J = 8.6 Hz, ArH’s), 6.85 (m, 3Ha,c , ArH’s), 7.18 (t, 2Hb ,
ꢀ
J = 8.6 Hz, ArH’s), 7.44 (d, 2Ha , J = 7.4 Hz, ArH’s), 7.55 (t, 2Hd, J =
7.6 Hz, Ar’s), 7.68 (t, 1He, J = 7.2 Hz, Ar’s), 8.0 (d, 2Hc, J = 7.4 Hz,
ArH’s), and 11.76 (s, 1H, NH). Anal. for C26H18N4O5S2 (530.57) . calcd.:
C, 58.86; H, 3.42; N, 10.56; S, 12.09. Found: C 58.98; H, 3.53; N, 10.41;
S, 12.28.

Thioxo-Thiazolidinones and Fused Thiazole Derivatives
2083
10-[4-(Benzoylmethoxy)pheny]-7-phenyl-2-thioxo-
thiazolo[5,4-e]thiadiazino[2‘,3‘-a]triazole-6,8-dione (9b)
Pale brown crystals (DMF); yield (47%); m.p. 325◦C; IR (cm−1) υ 3174
(NH) and 1712 (CO); 1H NMR (DMSO) δ 5.40 (s, 1H, H-7), 5.66 (s, 2H,
ꢀ
CH2), 6.45 (d, 2Hb, J = 6.8 Hz, ArH’s), 6.90 (m, 3Ha,c , ArH’s), 7.23 (t,
ꢀ
ꢀ
2Hb , J = 8.6 Hz, ArH’s), 7.46 (d, 2Ha , J = 7.6 Hz, ArH’s), 7.58 (t, 3Hd,
J = 7.6Hz, Ar’s), 7.70 (t, 1He, J = 7.4 Hz, Ar’s), 8.02 (d, 2Hc, J = 7.4 Hz,
ArH’s), and 13.73 (s, 1H, NH). Anal. for C26H18N4O4S3 (546.64) calcd.:
C, 57.13; H, 3.32; N, 10.25; S, 17.60. Found: C 57.25; H, 3.43; N, 10.41;
S, 17.45.
7-[4-(Benzoylmethoxy)phenyl]-2-oxo-3,5,6,7-tetrahydro-2H-
thiopyrano[2,3-d]thiazole-6-carboxylate (11a)
Pale brown crystals (acetic acid); yield (55%); m.p. 167◦C; IR (cm−1) υ
1
3177 (NH), 1735 (CO) and 1684 (CO); H NMR (DMSO) δ 1.13 (t, 3H,
J = 7.2 Hz, CH3), 3.04–3.15 (m, 1H, H-6), 3.28–3.37 (dd, 1H, J = 4.6,
8.2 Hz, H-5), 3.99 (q, 2H, CH2), 4.45 (d, 1H, J = 5.1 Hz, H-7), 5.53 (s, 2H,
CH2), 6.88 (d, 2Hb, J = 8.7 Hz, ArH’s), 7.0 (d, 2Ha, J = 9.0 Hz, ArH’s),
7.56 (t, 2Hd, J = 7.8 Hz, ArH’s), 7.67 (t, 1He, J = 7.5 Hz, ArH’s), 8.0 (d,
2Hc, J = 7.0 Hz, ArH’s), and 11.37 (s, 1H, NH). Anal. for C23H21NO5S2
(455.55) calcd.: C, 60.64; H, 4.65; N, 3.07; S, 18.04. Found: C, 60.50; H,
4.77; N, 3.22; S, 18.19.
7-[4-(Benzoylmethoxy)phenyl]-2-thioxo-3,5,6,7-tetrahydro-2H-
thiopyrano-[2,3-d]thiazole-6-carboxylate (11b)
Pale brown crystals (acetic acid); yield (58%); m.p. 188◦C; IR (cm−1) υ
1
3165 (NH) 1733 (CO) and 1686 (CO); H NMR (DMSO) δ 1.14 (t, 3H,
J = 7.2 Hz, CH3), 3.08–3.17 (m, 1H, H-6), 3.30–3.41 (dd, 1H, J = 4.1,
8.4 Hz, H-5), 4.09 (q, 2H, CH2), 4.46 (d, 1H, J = 5.2 Hz, H-7), 5.57 (s, 2H,
CH2), 6.91 (d, 2Hb, J = 8.8 Hz, ArH’s), 7.11 (d, 2Ha, J = 9.0 Hz, ArH’s),
7.55 (t, 2Hd, J = 7.8 Hz, ArH’s), 7.68 (t, 1He, J = 7.6 Hz, ArH’s), 8.03 (d,
2Hc, J = 7.2 Hz, ArH’s), and 13.67 (s, 1H, NH). Anal. for C23H21NO4S3
(471.61) calcd.: C, 58.57; H, 4.49; N, 2.97; S, 20.40. Found: C, 58.40; H,
4.62; N, 2.80; S, 20.52.
7-[4-(Benzoylmethoxy)phenyl]-6-nitro-5-phenyl-5,6-
dihydrothiopyrano[2,3-d]thiazolidin-2-one (11c)
Pale yellow crystals (acetic acid); yield (60%); m.p. 188◦C; IR (cm−1) υ
3178 (NH), 1680 (CO); 1H NMR (DMSO) δ 3.76 (d, 1H, J = 15.3 Hz, H-5),
3.85 (d, 1H, J = 14.4 Hz, H-7) 4.71–4.93 (dd, 1H, J = 5.7, 11.4 Hz, H-6),
5.58 (s, 2H, CH2), 6.92 (d, 2Hb, J = 8.7 Hz, ArH’s), 7.03 (d, 2Ha, J = 8.6
Hz, ArH’s), 7.31 (m, 5H, ArH’s), 7.68 (t, 2Hd, J = 7.2 Hz, Ar’s), 8.02 (d,

2084
N. H. Metwally
2Hc, J = 8.4 Hz, ArH’s), and 11.63 (s, 1H, NH). Anal. for C26H20N2O5S2
(504.58) calcd.: C, 61.89; H, 4.0; N, 5.55; S, 12.71. Found: C, 61.76; H,
4.12; N, 5.72; S, 12.53.
7-[4-(Benzoylmethoxy)phenyl]-6-nitro-5-phenyl-5,6-
dihydrothiopyrano[2,3-d]thiazolidin-2-thione (11d)
Pale violet crystals (acetic acid); yield (63%); m.p. 165◦C; IR (cm−1) υ
3175 (NH) and 1702 (CO); 1H NMR (DMSO) δ 3.78 (d, 1H, J = 15.4 Hz,
H-5), 3.86 (d, 1H, J = 14.6 Hz, H-7) 4.70–4.94 (dd, 1H, J = 5.6, 11.2 Hz,
H-6), 5.56 (s, 2H, CH2), 6.93 (d, 2Hb, J = 8.8 Hz, ArH’s), 7.0 (d, 2Ha, J =
8.6 Hz, ArH’s), 7.33 (m, 5H, ArH’s), 7.70 (t, 2Hd, J = 7.2 Hz, Ar’s), 8.0 (d,
2Hc, J = 8.8 Hz, ArH’s), and 13.73 (s, 1H, NH). Anal. for C26H20N2O4S3
(520.64) calcd.: C, 59.98; H, 3.87; N, 5.38; S, 18.48. Found: C, 59.84; H,
4.0; N, 5.55; S, 18.34.
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