A novel synthesis of 1,4-bis(thiopyrano[2,3-d] thiazolyl) benzene derivatives

Article abstract of DOI:10.3987/COM-07-11208

The novel 5-(4-formylphenyl)methylene-thiazolidine-2,4-dithione 3 and 1,4-bis[(4-thioxo-thiazolidinyl)methylene]benzene derivatives 4a,b were synthesized by condensation of each of 4-thioxo-thiazolidin-2-one (1a) and thiazolidine-2,4-dithione (1b) with terephthalaldehyde (2), in good yields depending on the molar ratio of 1 to 2. The cycloaddition of the newly synthesized compounds to N-arylmaleimides, ethyl acrylate, ω-nitrostyrene and malononitrile was studied. The structures of the synthesized compounds were established by elemental analyses and spectral data.

Full text of DOI:10.3987/COM-07-11208

HETEROCYCLES, Vol. 75, No. 2, 2008
319
HETEROCYCLES, Vol 75, No. 2, 2008, pp. 319 - 329. © The Japan Institute of Heterocyclic Chemistry
Received, 23rd August, 2007, Accepted, 29th October, 2007, Published online, 30th October, 2007. COM-07-11208
A NOVEL SYNTHESIS OF 1,4-Bis(THIOPYRANO[2,3-d] THIAZOLYL)
BENZENE DERIVATIVES
Nadia Hanafy Metwally
Department of Chemistry, Faculty of Science, University of Cairo, Giza, Egypt
E-mail: nhmmohamed@yahoo.com
Abstract - The novel 5-(4-formylphenyl)methylene-thiazolidine-2,4-dithione 3
and 1,4-bis[(4-thioxo-thiazolidinyl)methylene]benzene derivatives 4a,b were
synthesized by condensation of each of 4-thioxo-thiazolidin-2-one (1a) and
thiazolidine-2,4-dithione (1b) with terephthalaldehyde (2), in good yields
depending on the molar ratio of 1 to 2. The cycloaddition of the newly
synthesized compounds to N-arylmaleimides, ethyl acrylate, ω-nitrostyrene and
malononitrile was studied. The structures of the synthesized compounds were
established by elemental analyses and spectral data.
INTRODUCTION
4-Thiazolidinone derivatives are known to possess various biological activity such as hypnotic,1
anesthetic,2 antifungal,3 anathelmintic4 and antiviral agents5 as well as CNS6 stimulants. Moreover, the
heterocyclic systems having both thiazolidine and thiopyrano moieties were found to be important in the
field of medicinal chemistry.7-9 Recently, it was reported that the bis-heterocyclic compounds exhibit
much higher antibacterial activity than heterocyclic compounds10,11 as well as various biological
activities12-16 including antibacterial, fungicidal and tuberculostatic, in addition, much higher antibacterial
activity than heterocyclic compounds.15,16 In view of this and in the course of our studies on the chemistry
of 4-thiazolidinones,17-24 I found the synthetic routs of the novel 5-arylmethylene-thiazolidine-2,4-
dithione 3 and 1,4-bis(4-thioxo-thiazolidinylmethylene)benzene derivati-ves 4a,b which can be used as
active heterodiene components in hetero-Diels-Alder reactions. The latter reaction led to formation of the
hitherto unknown compounds which containing two thiopyrano-thiazole units, starting from 4-thioxo-
thiazolidinones and terephthalaldehyde.
RESULTS AND DISCUSSION
The condensation of equimolar amounts of thiazolidine-2,4-dithione (1b) and terephthalaldehyde (2) in
glacial acetic acid and in the presence of sodium acetate at room temperature yielded a brown solid of
o
mp 226 C, in good yield. The structure of the isolated product was established based on elemental

320
HETEROCYCLES, Vol. 75, No. 2, 2008
analyses and spectral data. The IR spectrum of this product showed a characteristic absorption band
at 3028 cm-1 assignable to NH. In addition, the characteristic absorption bands at 2855, 2738 and 1686
1
cm-1 due to the aldehydic group appeared in the IR spectrum. Its H NMR spectrum revealed a singlet
signal at δ 8.11 due to olefinic proton, a singlet signal at δ 10.03 exhibited by the aldehydic CH proton
and a D2O-exchangeable singlet signal at δ 13.73 attributed to NH proton, beside the other expected
signals due to the aromatic protons. In addition, the mass spectrum of the product gave the molecular ion
peak at m/z 265 which is exactly consistent with the molecular weight of structure 3. Based on the
elemental analysis and spectral data, structure 3 was assigned to the product 3 (see EXPERIMENTAL
and Scheme 1).
S
NH
OHC
CHO
+
X
S
2
1a, X = O
b, X = S
AcOH / AcONa
rt
AcOH / AcONa
CHO
S
S
S
S
NH
NH
NH
S
S
S
X
X
3
4a, X= O
b, X = S
1b
AcOH/AcONa/
Scheme 1
On the other hand, condensation of terephthalaldehyde with two equivalents of each of 4-thioxo-
thiazolidin-2-one (1a) and thiazolidine-2,4-dithione (1b) in refluxing glacial acetic acid and in the
presence of sodium acetate afforded the highly coloured products, bis-arylidenes 4a,b, respectively, in
good yields. The structures of the bis-products 4a,b were confirmed based on elemental analyses and
spectral data. For example, the IR spectrum of 4a showed characteristic absorption bands at 3071 and
1724 cm-1 assignable to NH and C=O groups. Its 1H NMR spectrum revealed a singlet signal at δ 8.07 due
to olefinic proton and a D2O-exchangeable singlet signal at δ 13.75 attributed to NH proton, beside the
other expected signals. In addition, the mass spectrum of 4a gave the expected molecular ion peak at m/z
1
364. Configurational assignments of compounds 3 and 4 were based exclusively on H NMR

HETEROCYCLES, Vol. 75, No. 2, 2008
321
spectroscopy by comparing the observed chemical shifts value;25 and according to literature data for
analogous 4-thiazolidinone.26-29 The olefinic protons of the Z-isomers are relatively deshielded by the
thioxo groups of the thiazole moiety compared with the E-isomers (see EXPERIMENTAL and Scheme 1).
The compound 4b can be also obtained by refluxing equimolar amounts of 3 with 1b in glacial acetic acid
and in the presence of fused sodium acetate.
In the course of study of cycloaddition reactions of α,β-unsaturated thiocarbonyl heterocycles with
electron-poor dienophiles, new 1:1 adducts, thiopyrano[2,3-d]thiazoles 6a-c via the reaction of 3 with N-
arylmaleimides 5a-c in refluxing acetic acid were obtained. The IR spectrum of the isolated product 6b
showed absorption bands at 3023, 2745, 2859, 1719 and 1702 cm-1, corresponding to NH, aldehydic CH
1
and CO groups, respectively. Furthermore, the H NMR spectrum of this adduct showed signals
reasonably assignable to the structures proposed (see EXPERIMENTAL and Scheme 2). Based on the
elemental analyses and spectral data, structures 6a-c were proposed to these adducts.
CHO
Ar
N
O
O
S
O
O
6
5
AcOH
4
OHC
S
7
N Ar
NH
+
S
S
3
1
S
NH
2
5a-c
3
S
6a, Ar = C6H5
b, Ar = 4-MeOC6H4
c, Ar = 4-ClC6H4
Scheme 2
Reaction of 3 with two equivalents of malononitrile in refluxing absolute ethanol in the presence of
triethylamine, afforded coloured product 7 (Scheme 3). Structure of 7 was deduced from its elemental
analysis and spectral data. Thus the IR spectrum of this isolated product showed absorption bands at 3310,
3128 and 3101 cm-1 corresponding to NH2 and NH groups, and characteristic absorption bands at 2214
1
and 2184 cm-1 corresponding to CN groups and the absence of CHO band. Its H NMR data showed
signals assignable reasonably to the proposed structure (see EXPERIMENTAL). From these results, the
structure 7 was assigned to this adduct. (see EXPERIMENTAL and Scheme 3).

322
HETEROCYCLES, Vol. 75, No. 2, 2008
NC
NH2
S
5
6
7
4
EtOH/TEA
NC
CH (CN)
+
2
2
3
3NH
S1
CN
2
S
7
Scheme 3
It is interesting to explore the utility of the novel 1,4-bis[(2-oxo-4-thioxo-thiazolidinyl)methylene]benzene
(4a) as heterodienes in Diels-Alder reaction with various dienophiles. Thus, refluxing compound 4a with
1
two equivalents of N-arylmaleimides 5a-c in glacial acetic acid gave colorless adducts. The H NMR
spectrum of the adduct 8b showed double doublets at δ 3.39-3.45 (J = 6.0 and 9.0 Hz) attributed to H-6,
in addition to two doublets at δ 4.64 and 5.24 (J = 5.7 and 9.3 Hz), respectively, corresponding to H-5 and
H-7, beside the other expected signals due to the aromatic protons (see EXPERIMENTAL). IR spectrum
of product 8b also showed the absorptions consistent with the proposed structure (see EXPERIMENTAL).
Based on the elemental analyses and spectral data, structures 8a-c were assigned to these adducts (see
EXPERIMENTAL and Scheme 4).
Ar
N
Ar
N
O
O
O
O
O
5
6
AcOH
4a
N Ar
+
7
S
4
S
O
1
3
HN
S
S
NH
5a-c
2
8a-c
8a, Ar = C6H5
O
O
b, Ar = 4-MeOC6H4
c, Ar = 4-ClC6H4
Scheme 4
Similarly, refluxing 4a with ethyl acrylate (9a) and/or ω-nitrostyrene (9b) in molar ratio 1:2 in glacial
acetic acid gave the symmetric N-aryl-1,4-bis(thiazolothiopyranyl)benzenes 10a,b (Scheme 5). The
structures of 10a,b were also assigned on the basis of their elemental analyses and spectral data (see

HETEROCYCLES, Vol. 75, No. 2, 2008
323
1
EXPERIMENTAL). The H NMR spectrum of compounds 10a revealed a doublet at δ 4.45
corresponding to H-7 and double doublets at δ 3.28-3.37 corresponding to H-5ax and H-5eq in addition to
multiplet at δ 3.04-3.15 corresponding to H-6. The formation pathway of compound 10a from 4a and
9a,b is similar to these of compounds 9a,b (Scheme 5 and see EXPERIMENTAL).
Y
R
Y
R
R
6
5
AcOH
4a
+
4
S
S
7
Y
9a,b
1
3
NH
HN
S
S
2
O
O
10a, R = H, Y = CO2Et
b, R =C6H5, Y = NO2
Scheme 5
1
All the new adducts 6a-c, 8a-c and 10a,b showed only one isomer in the H NMR spectra (see
EXPERIMENTAL) and this seems logic, since the endo-adduct is obtained as a kinetically controlled
product at room temperature, but under thermal conditions it is transformed into the exo-adduct which is
thermally stable controlled product.
The reaction of 4a,b toward malononitrile was also investigated. Thus, the reaction of 4 and two
equivalents of malononitrile in refluxing absolute ethanol in the presence of triethylamine, afforded
highly coloured products 12ab (Scheme 6). Structures of 12a,b were proposed from their analytical and
spectral data. Absorption bands of the IR spectrum of 12b of at 3428, 3320 and 3085 cm-1 corresponding
to NH2 and NH groups and a strong absorption band at 2188 cm-1 due to CN group were observed. In the
1H NMR spectrum of this adduct, a singlet signal at δ 4.43 attributed to H-7 and two D2O-exchangeable
signals at δ 9.93 and 8.63 attributed to NH2 and NH protons appeared. Further more, the adducts 12a,b
were synthesised separately by another reaction between 1,4-bis(2,2`-dicyanovinyl)benzene and two
equivalents of each of 1a and 1b. The formation of the adducts 12 is assumed to proceed via initial
Michael addition to yield acyclic adducts 11, followed by the cyclization via the attack of the mercapto
group on the cyano group.

324
HETEROCYCLES, Vol. 75, No. 2, 2008
NC
CN
CN
H
H
H
H
C
N
N C
HS
CN
SH
EtOH / TEA
4a,b CH (CN)
+
EtOH/TEA
2
2
1a,b
+
S
S
NH
HN
CN
11a,b
X
X
CN
NC
CN
NH2
H2N
6
H
H
5
4
S
S
7
1
S
3
S
NH
HN
2
12a, X = O
b, X = S
X
X
Scheme 6
EXPERIMENTAL
All melting points were determined on an electrothermal (9100) apparatus and are uncorrected. The IR
spectra were recorded as KBr pellets on a Perkin Elmer 1430 spectrophotometer. 1H NMR and 13C NMR
spectra were recorded on a Varian Gemini 300 MHz spectrometer (TMS as internal standard, DMSO-d6
as solvent, δ values in ppm). Mass spectra were taken on a Shimadzu GCMS-QP-1000 EX (Japan) with
ionization potential 70 eV. Elemental analyses were carried out by the Microanalysis Center at Cairo
University, Giza, Egypt.
5-(4-Formylphenyl)methylenethiazolidine-2,4-dithione (3).
To a solution of 1b (10 mmol) in glacial acetic acid (25 mL) and sodium acetate (1.64 g, 20 mmol) was
added terephthalaldehyde (2) (10 mmol). The reaction mixture was stirred at rt for 15 min. The solid
which separated from the reaction mixture, was collected and recrystallized from acetic acid.
Brown crystals; yield (85%); mp 226 °C; IR (KBr) υ 3028 (NH) and 2855, 2738, 1686 (aldehydic CHO)
cm-1; 1H NMR (DMSO-d6): δ 7.80 (m, 4H, ArH’s), 8.11 (s, 1H, CH), 10.03 (s, 1H, aldehydic CH), 13.73
(brs, NH, exchangeable). MS, m/z 265 (M+, 100%), 236 (46.7%), 177 (65.1%), 161 (37.5%), 133 (21.7%),
89 (38.2%), 64 (50.7%). Anal. Calcd for C11H7NOS3 (265.37): C, 49.79; H, 2.66; N, 5.28; S, 36.25%.
Found: C, 49.67; H, 2.53; N, 5.44; S, 36.37%.

HETEROCYCLES, Vol. 75, No. 2, 2008
325
Condensation of terephthaldehyde with 4-thioxothiazolidin-2-one (1a) and thiazolidine-2,4-dithione
(1b).
General procedure.
To a solution of each of 1a and 1b (20 mmol) in glacial acetic acid (25 mL) and sodium acetate (3.82 g,
40 mmol) was added terephthalaldehyde (2) (10 mmol). The reaction mixture was refluxed for 1 h on
water bath, cooled and then poured into cold water. The solid, which separated, was collected and
recrystallized from DMF/EtOH.
(Z)-1,4-Bis(2-oxo-4-thioxothiazolidinylmethylene)benzene (4a).
Red crystals; yield (75%); mp >300 °C; IR (KBr) υ 3071 (NH) and 1724 (C=O) cm-1; 1H NMR (DMSO-
d6): δ 7.80 (s, 4H, ArH’s), 8.07 (s, 2H, 2CH), 13.75 (br, 2NH, exchangeable). 13C NMR: δ = 117.21,
121.10, 127.30, 134.18, 169.32 (C=O) and 198.80 (C=S); MS, m/z 364 (M+, 100%), 276 (27.5%), 233
(75%), 190 (29.9%), 145 (20%), 95 (43.4%). Anal. Calcd for C14H8N2O2S4 (364.49): C, 46.13; H, 2.21; N,
7.69; S, 35.19%. Found: C, 46.25; H, 2.34; N, 7.83; S, 35.32%.
(Z)-1,4-Bis(2,4-dithioxothiazolidinylmethylene)benzene (4b).
1
Brown crystals; yield (82%), mp >300 °C; IR (KBr) υ 3028 (NH) cm-1; H NMR (DMSO-d6): δ 7.85 (s,
4H, ArH’s), 8.11 (s, 2H, CH), 13.73 (brs, 2NH, exchangeable). Anal. Calcd for C14H8N2S6 (396.62): C,
42.40; H, 2.03; N, 7.07; S, 48.51%. Found: C, 42.55; H, 2.16; N, 7.23; S, 48.37%.
Reaction of 3 with N-arylmaleimides
A mixture of 3 (10 mmol) and N-arylmaleimides 5a-c (10 mmol) in glacial acetic acid (30 mL) was
refluxed for 30 min. The separated solid, was collected and recrystallized from the appropriate solvent.
7-(4-Formylphenyl)-N-phenyl-5,6-dihydrothiopyrano[2,3-d]thiazolidine-2-thioxo-5,6-dicarboximide-
(6a).
o
White crystals (EtOH/dioxane); yield (60%); mp 268 C; IR (KBr) υ 3017 (NH), 2743, 2855 (aldehydic
1
CH), 1720 (CO), 1695 (CO) cm-1; H NMR (DMSO-d6): δ 3.40-3.46 (dd, H, J = 6.8 Hz, 8.8 Hz, H-6),
4.80 (d, 1H, J = 7.0 Hz, H-5), 5.24 (d, 1H, J = 9.0 Hz, H-7), 6.60-7.34 (m, 5H, ArH’s), 7.57 (d, 2H, J =
8.4 Hz, ArH’s), 7.88 (d, 2H, J = 8.4 Hz, ArH’s), 10.0 (s, 1H, aldehydic CH), 13.78 (s, 1H, NH). Anal.
Calcd for C21H14N2O3S3 (438.54): C, 57.52; H, 3.22; N, 6.38; S, 21.94%. Found: C, 57.65; H, 3.36; N,
6.55; S, 22.08%.

326
HETEROCYCLES, Vol. 75, No. 2, 2008
7-(4-Formylphenyl)-N-(4-methoxyphenyl)-5,6-dihydrothiopyrano[2,3-d]thiazolidin-2-thioxo-5,6-
dicarboximide (6b).
White crystals (EtOH/dioxane); yield (63%); mp 255 oC; IR (KBr) υ 3023 (NH), 2745, 2859 (aldehydic
CH), 1719 (CO), 1702 (CO) cm-1; 1H NMR (DMSO-d6): δ 3.72 (s, 3H, OMe), 3.42-3.48 (dd, 1H, J = 6.9,
9.1 Hz, H-6), 4.81 (d, 1H, J = 7.2 Hz, H-5), 5.26 (d, 1H, J = 9.0 Hz, H-7), 6.51 (d, 1H, J = 8.7 Hz,
ArH’s), 6.88 (d, 1H, J = 9.3 Hz, ArH’s), 7.56 (d, 1H, J = 7.8 Hz, ArH’s), 7.87 (d, 1H, J = 8.1 Hz, ArH’s),
9.99 (s, 1H, aldehydic CH), 13.80 (s, 1H, NH). Anal. Calcd for C22H16N2O4S3 (468.57): C, 56.39; H,
3.44; N, 5.97; S, 20.53%. Found: C, 56.52; H, 3.58; N, 6.14; S, 20.67%.
7-(4-Formylphenyl)-N-(4-chlorophenyl)-5,6-dihydrothiopyrano[2,3-d]thiazolidin-2-thioxo-5,6-
dicarboximide (6c).
o
White crystals (AcOH); yield (65%); mp 285 C; IR (KBr) υ 3025 (NH), 2744, 2861 (aldehydic CH),
1723 (CO), 1700 (CO) cm-1; 1H NMR (DMSO-d6): δ 3.42-3.51 (dd, 1H, J = 6.9, 9.1 Hz, H-6), 4.82 (d, 1H,
J = 7.2 Hz, H-5), 5.28 (d, 1H, J = 9.2 Hz, H-7), 6.54 (d, 1H, J = 8.8 Hz, ArH’s), 6.90 (d, 1H, J = 9.2 Hz,
ArH’s), 7.60 (d, 1H, J = 7.6 Hz, ArH’s), 7.89 (d, 1H, J = 8.1 Hz, ArH’s), 10.01 (s, 1H, aldehydic CH),
13.80 (s, 1H, NH). Anal. Calcd for C21H13ClN2O3S3 (472.99): C, 53.33; H, 2.77; Cl, 7.50; N, 5.92; S,
20.33%. Found: C, 53.46; H, 2.91; Cl, 7.64; N, 6.10; S 20.49%.
5-Amino-7-[4-(2,2-dicyanovinyl)phenyl]-3,7-dihydro-2-thioxothiopyrano[2,3-d]thiazole-6-carbonitr-ile
(7).
A mixture of compound 3 (10 mmol) and malononitrile (20 mmol) in ethanol (100 mL), containing
several drops of triethylamine, was refluxed for 2 h. The solid product was collected by filtration and
recrystallized from EtOH/DMF to afford violet crystals.
o
1
Yield (62%); mp >300 C; IR (KBr) υ 3310, 3128, 3101 (NH2 and NH) and 2214, 2184 (CN) cm-1; H
NMR (DMSO-d6): δ 4.41 (s, 1H, H-7), 7.81 (s, 1H, CH), 7.88 (d, 2H, J = 8.4 Hz, ArH’s), 8.02 (d, 2H, J =
8.4 Hz, ArH’s), 8.10 (br., 1H, NH), 11.0 (s, 2H, NH2). Anal. Calcd for C17H9N5S3 (379.48): C, 53.80; H,
2.39; N, 18.40; S, 25.35%. Found: C, 53.92; H, 2.52; N, 18.52; S, 25.22%.
Reaction of 4a with N-arylmaleimides, ethyl acrylate and ω-nitrostyrene.
General Procedure.
A mixture of 4a (10 mmol) and the appropriate dienophile (20 mmol) in glacial acetic acid (30 mL) was
refluxed for 2 h. The solid product was collected and recrystallized from appropriate solvent.

HETEROCYCLES, Vol. 75, No. 2, 2008
327
1,4-Bis(N-phenyl-3,5,6,7-tetrahydrothiopyrano[2,3-d]thiazolidin-2-oxo-5,6-dicarboximidyl)benzene
(8a).
Pale brown crystals (AcOH); yield (45%); mp 277 oC; IR (KBr) υ 3095 (NH), 1716 (CO) and 1675 (CO)
cm-1; 1H NMR (DMSO-d6): δ 3.38-3.44 (dd, 2H, J = 5.7 Hz, 8.9 Hz, 2H-6), 4.63 (d, 2H, J = 5.8 Hz, 2H-
5), 5.24 (d, 2H, J = 9.0 Hz, 2H-7), 6.62 (m, 10H, 2ArH), 7.33 (s, 4H, ArH’s), 11.82 (s, 2H, 2NH). Anal.
Calcd for C34H22N4O6S4 (710.82): C, 57.45; H, 3.12; N, 7.88; S, 18.04%. Found: C, 57.57; H, 3.26; N,
7.72; S, 18.18%.
1,4-Bis(N-(4-methoxyphenyl)-3,5,6,7-tetrahydrothiopyrano[2,3-d]thiazolidin-2-oxo-5,6-dicarbox-
imidyl)benzene (8b).
o
Pale brown crystals (EtOH/dioxane); yield (48%); mp 295 C; IR (KBr) υ 3100 (NH), 1717 (CO) and
1677 (CO) cm-1; 1H NMR (DMSO-d6): δ 3.73 (s, 6H, 2OMe), 3.39-3.45 (dd, 2H, J = 6.0, 9.0 Hz, 2H-6),
4.64 (d, 2H, J = 5.7 Hz, 2H-5), 5.24 (d, 2H, J = 9.3 Hz, 2H-7), 7.26 (s, 4H, ArH’s), 7.56 (d, 2H, J = 8.1
Hz, 2ArH’s), 7.87 (d, 2H, J = 8.1 Hz, 2ArH’s), 11.84 (s, 2H, 2NH). Anal. Calcd for C36H26N4O8S4
(770.87): C, 56.09; H, 3.40; N, 7.27; S, 16.64%. Found: C, 56.22; H, 3.52; N, 7.44; S, 16.50%.
1,4-Bis(N-(4-chlorophenyl)-3,5,6,7-tetrahydrothiopyrano[2,3-d]thiazolidin-2-oxo-5,6-dicarbox-
imidyl)benzene (8c).
o
Brownish yellow crystals (EtOH/DMF); yield (52%); mp >300 C; IR (KBr) υ 3098 (NH), 1717 (CO)
and 1678 (CO) cm-1; 1H NMR (DMSO-d6): δ 3.37-3.46 (dd, 2H, J = 6.0, 8.8 Hz, 2H-6), 4.65 (d, 2H, J =
6.0 Hz, 2H-5), 5.23 (d, 2H, J = 9.0 Hz, 2H-7), 7.30 (s, 4H, ArH’s), 7.60 (d, 2H, J = 8.4 Hz, 2ArH’s),
7.90 (d, 2H, J = 8.4 Hz, 2ArH’s), 11.80 (s, 2H, 2NH). Anal. Calcd for C34H20Cl2N4O6S4 (779.71): C,
52.37; H, 2.59; Cl, 9.09; N, 7.19; S, 16.45%. Found: C, 52.24; H, 2.72; Cl, 9.22; N, 7.36; S 16.33%.
1,4-Bis[6-ethoxycarbonyl-2-oxo-3,5,6,7-tetrahydro-2H-thiopyrano[2,3-d]thiazolyl]benzene (10a).
o
Pale brown crystals (acetic acid); yield (44%); mp 265 C; IR (KBr) υ 3132 (NH), 1732 (CO) and 1686
(CO) cm-1; 1H NMR (DMSO-d6): δ 1.13 (t, 6H, J = 7.2 Hz, 2Me), 3.04-3.15 (m, 2H, 2H-6), 3.28-3.37 (dd,
2H, J = 4.6, 8.2 Hz, 2H-5), 3.99 (q, 4H, 2CH2), 4.45 (d, 2H, J = 5.1 Hz, 2H-7), 7.35 (s, 4H, ArH’s), 11.37
(s, 2H, 2NH). MS, m/z 564 (M+, 11%), 346 (25.3%), 320 (6.8%), 233 (16%), 190 (4.3%), 177 (4.1%),
152 (5%), 129 (6.7%), 95 (8.0%), 55 (100%). Anal. Calcd for C24H24N2O6S4 (564.72): C, 51.04; H, 4.28;
N, 4.96; S, 22.71%. Found: C, 51.16; H, 4.44; N, 4.80; S, 22.88%.

328
HETEROCYCLES, Vol. 75, No. 2, 2008
1,4-Bis(6-nitro-5-phenyl-2-oxo-3,5,6,7-tetrahydrothiopyrano[2,3-d]thiazolyl)benzene (10b).
o
1
Pale yellow crystals (acetic acid); yield (49%); mp 288 C; IR (KBr) υ 3138 (NH), 1685 (CO) cm-1; H
NMR (DMSO-d6): δ 3.76 (d, 2H, J = 15.3 Hz, 2H-5), 3.85 (d, 2H, J = 14.4 Hz, 2H-7) 4.71-4.93 (dd, 1H,
J = 5.7, 11.4 Hz, 2H-6), 6.70 (s, 10H, 2ArH’s), 7.42 (s, 4H, ArH’s), 11.85 (s, 2H, 2NH). Anal. Calcd for
C30H22N4O6S4 (662.78): C, 54.37; H, 3.35; N, 8.45; S, 19.35%. Found: C, 54.50; H, 3.48; N, 8.30; S,
19.47%.
1,4-Bis [thiopyrano[2,3-d]thiazolyl]benzene derivatives 12a,b
A mixture of 4a,b (10 mmol) and malononitrile (20 mmol) in EtOH (100 mL), containing a few drops of
triethylamine, was refluxed for 2 h then left at rt overnight. The solid product so obtained was filtered off
and recrystallized from EtOH/DMF.
1,4-Bis (5-amino-6-cyano-2-oxo-thiopyrano[2,3-d]thiazolyl)benzene (12a).
o
Orange crystals; yield (60%); mp >300 C; IR (KBr) υ 3425, 3318, 3081 (NH2 and NH), 2190 (CN)
and1680 (CO) cm-1; 1H NMR (DMSO-d6): δ 4.40 (s, 2H, 2H-7), 7.31 (s, 4H, ArH’s), 8.60 (br., 4H, 2NH2),
9.90 (s, 2H, 2NH). Anal. Calcd for C20H12N6O2S4 (496.61): C, 48.37; H, 2.44; N, 16.92; S, 25.83%.
Found: C, 48.50; H, 2.56; N, 16.75; S, 25.96%.
1,4-Bis(5-amino-6-cyano-2- thioxothiopyrano[2,3-d]thiazolyl)benzene (12b).
o
Violet crystals; yield (62%); mp >300 C; IR (KBr) υ 3428, 3320, 3085 (NH2 and NH) and 2188 (CN)
1
cm-1; H NMR (DMSO-d6): δ 4.43 (s, 2H, 2H-7), 7.26 (s, 4H, ArH’s), 8.63 (s, 2H, 2NH), 9.93 (s, 4H,
2NH). Anal. Calcd for C20H12N6S6 (528.74): C, 45.43; H, 2.29; N, 15.89; S, 36.39%. Found: C, 45.58; H,
2.46; N, 15.72; S, 36.53%.
REFERENCES
1. N. Guru and S. D. Srivastava, J. Scient. Ind. Res., 2001, 60, 601.
2. M. S. Chande and K. S. Jathar, Indian J. Chem., 1995, 34B, 654.
3. S. N. Sawhney, P. K. Sharama, and A. Gupta, Indian J. Chem., 1993, 32B, 1125.
4. S. K. Srivastava and S. D. Srivastava, Indian J. Chem., 1997, 36B, 826.
5. R. S. Lodhi and S. D. Srivastava, Indian J. Chem., 1997, 36B, 947.
6. L. Saish and S. K. Srivastava, J. Scient. Ind. Res., 2001, 60, 33.
7. E. Elslager, Prog. Drug. Res., 1974, 18, 99.

HETEROCYCLES, Vol. 75, No. 2, 2008
329
8. R. K. Razdan, R. J. Bruni, A. C. Mehta, K. K. Weinhardt, and Z. B. Papanastassiou, J. Med. Chem.,
1978, 21, 643.
9. R. Lesyk, B. Zimenkovsky, D. Atamanyuk, F. Jensen, K. K. Kononowicz, and A. Gzella, Bioorg. and
Med. Chem., 2006, 14, 5230.
10. L. E. N. Quadri, T. A. Keating, H. M. Patel, and C. T. Walsh, Biochemistry, 1999, 38, 14941.
11. H. Liming, L. Xuesh, C. Zhiyuan, and L. Zhaojie, Chin. J. Org. Chem., 2003, 23, 1125.
12. C. Kirilmis, M. Koca, A. Cukurovali, M. Ahmedzade, and C. Kazaz, Molecules, 2005, 10, 1399.
13. M. E. Hensler, G. Bernstein, V. Nizet, and A. Nefzi, Bioorg. Med. Chem. Lett., 2006, 16, 5073.
14. M. S. Chande, P. A. Barve, R. R. Khanwelkar, S. S. Athalye, and D. S. Venkataraman, Can. J. Chem.,
2007, 85, 21.
15. Z. Y. Zhang, X. Chen, L. L. Wei, and Z. L. Ma, Chem., Res. Chin. Univ., 1991, 7, 129.
16. R. S. Roy, N. L. Kelleher, J. C. Milne, and C. T. Walsh, Chem. Biol., 1999, 6, 305.
17. S. O. Abd Allh, H. A. Ead, N. A. Kassab, and N. H. Metwally, Heterocycles, 1983, 20, 637.
18. H. A. Ead, S. O. Abd Allh, N. A. Kassab, N. H. Metwally, and Y. E. Saleh, Arch. Pharm. (Weinheim),
1987, 320, 1227.
19. H. A. Ead, S. O. Abd Allh, N. A. Kassab, and N. H. Metwally, Sulfur Letters, 1989, 9, 23.
20. H. A. Ead and N. H. Metwally, Egypt. J. Chem., 1989, 32, 691.
21. H. A. Ead, N. H. Metwally, and N. Morsy, Arch. Pharm. (Weinheim), 1990, 13, 5.
22. N. H. Metwally, Indian J. Chem., 2000, 39B, 757.
23. N. H. Metwally, Sulfur Chemistry, 2007, 33, 234.
24. N. H. Metwally, Phosphorus, Sulfur, Silicon and Related Elements, in press, 2007.
25. C. Pascual, J. Meier, and W. Simon, Helv. Chim. Acta, 1966, 49, 164.
26. V. L. M. Guarda, M. A. Pereir, C. A. De Simone, J. F. C. Albuquerque, S. L. Galdino, J. Chantegrel,
M. Perrissin, C. Beney, F. Thomasson, I. R. Pitta, and C. Luu-Duc, Sulfur Letters, 2003, 26, 17.
27. V. L. M. Guarda, C. Bosso, S. L. Galdino, J. F. C. Albuqerque, M. C. A. Lima, J. B. P. Silva, L. F. C.
Leite, and I. R. Pitta, Spectroscopy, 2004, 18, 613.
28. P. Delgado, J. Quiroga, J. Cobo, J. N. Low, and C. Glidewell, Acta Cryst. Section C, 2005, 61, 477.
29. R. Markovic, M. M. Pergal, M. Baranac, D. Stanisavljev, and M. Stojanovic, ARKIVOC, 2006, 2, 83.