The reaction of cyclohexan-1,3-dione with cyanomethylenes: Synthesis of thiophenes and their fused derivatives with antifungal activities

Article abstract of DOI:10.1080/10426500802421127

2-Amino-7-oxotetrahydrobenzo[b]thiophenes 3a,b were prepared according to the Gewald procedure. Their reactivity toward a variety of chemical reagents was studied to give annulated heterocycles with potential bio-responses.

Full text of DOI:10.1080/10426500802421127

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The Reaction of
Cyclohexan-1,3-dione with
Cyanomethylenes: Synthesis
of Thiophenes and Their Fused
Derivatives with Antifungal
Activities
Rafat M. Mohareb a b , Sherif M. Sherif b & Hosam El-
Dean Moustafa b
a Department of Organic Chemistry, Faculty of
Pharmacy, October University for Modern Sciences
and Arts (MSA), October, A. R., Egypt
b Department of Chemistry, Faculty of Science, Cairo
University, Giza, A. R., Egypt
Published online: 22 Jul 2009.
To cite this article: Rafat M. Mohareb , Sherif M. Sherif & Hosam El-Dean Moustafa
(2009): The Reaction of Cyclohexan-1,3-dione with Cyanomethylenes: Synthesis of
Thiophenes and Their Fused Derivatives with Antifungal Activities, Phosphorus, Sulfur,
and Silicon and the Related Elements, 184:8, 2078-2096
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Phosphorus, Sulfur, and Silicon, 184:2078–2096, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802421127
The Reaction of Cyclohexan-1,3-dione with
Cyanomethylenes: Synthesis of Thiophenes
and Their Fused Derivatives with Antifungal Activities
Rafat M. Mohareb,1,2 Sherif M. Sherif,2 and Hosam
El-Dean Moustafa2
1Department of Organic Chemistry, Faculty of Pharmacy, October
University for Modern Sciences and Arts (MSA), October, A. R. Egypt
2Department of Chemistry, Faculty of Science, Cairo University, Giza,
A. R. Egypt
2-Amino-7-oxotetrahydrobenzo[b]thiophenes 3a,b were prepared according to the
Gewald procedure. Their reactivity toward a variety of chemical reagents was stud-
ied to give annulated heterocycles with potential bio-responses.
Keywords Annulated derivatives; pyridine; thiazole; thiophene
INTRODUCTION
Benzothiophenes are one of the most common and consequently the
most studied classes of aromatic heterocycles.1 The occurrence of these
heterocycles in a significant number of medicinal agents,2 active in a
variety of disease areas, has led to an enduring interest in the develop-
ment of new methods for their synthesis.3–5 Methods that utilize new
classes of precursors are particularly valuable. Among the many syn-
theses available, transition metal catalyzed processes6 and palladium-
mediated methods in particular7 feature heavily. Syntheses based on
palladium-catalyzed cyclizations of appropriately substituted alkenyl
or alkynyl phenols, or thiophenols, are versatile and have been used on
many occasions.8–10 Related tandem processes involving catalyzed C–C
bond formation, usually employing Sonogashira-type reactions, before
construction of the key C–S bond have also been developed.11–14 The
crucial bond-forming event in these processes is intramolecular attack
Received 27 May 2008; accepted 20 August 2008.
Address correspondence to Rafat M. Mohareb, Department of Organic Chemistry,
Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), El-Wahaat
Road, October, A. R. Egypt. E-mail: raafat mohareb@yahoo.com
2078

Synthesis of Thiophenes
2079
of a nucleophilic oxygen or sulfur atom onto a palladium-activated C–C
multiple bond, resulting in formation of the X–C2 bond of the hetero-
cycle. We aim to develop an alternative method for the synthesis of
2-amino-7-oxotetrahydrobenzo[b]thiophenes starting from cyclohexan-
1,3-dione and cyanomethylene reagents.
RESULTS AND DISCUSSION
Chemistry
In continuation of our previous work,15−17 we report herein on the scope
and applicability of the 2-amino-7-oxotetrahydrobenzo[b]thiophenes
3a,b, which were synthesized according to procedures in the
literature18,19 through the reaction of cyclohexan-1,3-dione (1) with ei-
ther malononitrile (2a) or ethyl cyanoacetate (2b) and sulfur for the
synthesis of annulated thiophene derivatives with potential pharma-
ceutical interest. The reaction of 3a,b with benzaldehyde (4) in the
presence of piperidine results in the formation of Schiff’s bases 5a,b.
(Scheme 1)
The reactivity of 3a,b with cyanomethylene reagents was stud-
ied. Thus, the reaction of 3a,b with either malononitrile (2a) or
ethyl cyanoacetate (2b) gave the cyclohexeno[b]thieno[5,4:2,3]pyridine
derivatives 6a–d. Structures of 6a–d were based on analytical and
spectral data, thus the 1H NMR spectrum of 6a showed two multiplets
at δ 2.70, 3.08 for two CH2 groups and two singlets at δ 4.23, 5.94
(D2O-exchangeable) corresponding to two NH2 groups.
The reaction of either 3a or 3b with ethyl acetoacetate (7) in 1,4-
dioxan containing piperidine gave the amide derivatives 8a,b. The
structures of the latter products were confirmed on the basis of an-
alytical and spectral data. The downfield chemical shift of CH3 groups
in compounds 8a,b are δ 3.14 and 3.20, respectively, is due to the ex-
istence of the COCH2CO moiety directly attached to the CH3 group.
The 13CNMR data of 8a showed signals at δ 34.1 (CH3), 54.9, 64.3, 77.9
(3 CH2), 90.0 (C), 120.9 (CN), 121.4, 123.8, 138.1, 140.7 (thiophene C),
176.5, 177.5, 183.0 (3 C O).
Compounds 8a,b underwent ready cyclization when heated in
sodium ethoxide solution to give the 7-oxocyclohexeno[b]thieno[5,4:2,3]
pyridino[b]thieno[5,4-b]pyridine derivatives 9a,b respectively. Struc-
tures of compounds 9a–b were based on analytical and spectral data.
The 13C NMR spectrum of 9a showed signals at δ 30.3 (CH3), 50.6, 64.7
(2 CH2), 88.2 (C), 120.6, 122.0, 122.8, 132.6, 142.7, 144.5 (thiophene
and pyridine-C), 169.1, 176.9 (2C O).

2080
R. M. Mohareb et al.
SCHEME 1
The reaction of either 8a or 8b with either 2a or 2b in ethanol
containing piperidine gave the Knoevenagel condensation products
10a–d respectively. The structures of the latter products were con-
firmed on the basis of analytical and spectral data (see the Experi-
mental section). On the other hand, conducting the same reaction in
sodium ethoxide solution alone gave the pyridine derivatives 11a–d
(Scheme 2).
Recently our research group was interested in a series of re-
actions involving the reaction of phenyl isothiocyanate with active

Synthesis of Thiophenes
2081
SCHEME 2
methylene reagents followed by heterocyclization with α-haloketones.
These reactions led to the formation of thiophene as well as thiazole
derivatives.20,21 In continuation of this program, we studied here the
reactivity of either 8a,b towards phenyl isothiocyanate (12) in basic

2082
R. M. Mohareb et al.
dimethylformamide to give the intermediate potassium sulfide salts
13a,b. Reaction of either 13a or 13b with ethyl chloroacetate (14) gave
the thiazole derivatives 15a,b. The structures of the latter products
were based on analytical and spectral data (see the Experimental sec-
tion). Moreover, the reaction of 13a,b with phenacyl bromide (16) gave
the thiazolidene derivatives 17a,b.
The reaction of either 17a or 17b with hydrazine hydrate gave
the pyrazole derivatives 18a,b respectively. Compounds 18a,b un-
derwent ready cyclization when heated in sodium ethoxide solu-
tion to give the corresponding cyclohexeno[b]thieno[5,4:2:3]pyrimidino
[5,1:1,2]pyrazole derivatives 19a,b, respectively. On the other hand,
the reaction of 17a,b with cyanomethylene reagents was studied, and
thus the reaction of 17a,b with either malononitrile (2a) or ethyl
cyanoacetate (2b) gave the pyridine derivatives 20a–d. The struc-
tures of the latter products were based on analytical and spectral data
(Scheme 3).
BIOLOGICAL/FUNGICIDAL ACTIVITY
Sclerotium cepivorum Berk is a soilborne fungus that causes the white
rot disease of onion. Primary inoculum of the pathogen results from
spherical small black sclerotia. Sclerotia, which are formed by many
other fungi, play a vital role in life cycle because they are the structures
by which these fungi survive for long periods in unfavorable conditions
in the soil. Although several heterocyclic compounds were tried against
the sclerotium-forming fungi, however, the antifungal activity of these
compounds depends on their chemical structure. Attempts have been
made to increase the toxicity of biologically active compounds through
introducing efficient functional groups. In this work, we succeeded in
synthesizing fused thiophene derivatives and evaluated their bioactiv-
ity against the mycelial growth, sclerotial formation, and cellulolytic
activity of Sclerotium cepivorum.
MATERIAL AND METHODS
Sclerotium cepivorum Berk was isolated from an infected onion bulb
(Allium cepa). The sclerotia were surface sterilized in 0.5% sodium
hypochlorite for 20 min then transferred to plates containing fresh
potato-dextrose agar (PDA) medium. The plates were incubated at 20◦C
for 30 days, after which the sclerotia were individually transferred
to the experimental media. Twenty-seven thiophene derivatives were
used, each in four concentrations (namely 4, 12, 30, and 75 µg cm−3).

Synthesis of Thiophenes
2083
SCHEME 3
For each treatment, three Erlenmeyer flasks (250 cm3), each containing
90 mL of the previously prepared PDA medium, were melted and cooled
to about 50◦C. Each of the three flasks received 10 cm3 of prepared stock
solutions of thiophene derivatives. A suitable aliquot of each mixture
was then poured into each of the six sterile plates (9 cm diameter)

2084
R. M. Mohareb et al.
TABLE I Effect of Different Concentrations of Thiophene
Derivatives After 44 h on Percentage Inhibition of Germination of
Slerotium cepivorum
Compound
No.
Conc.
Conc.
Conc.
Conc.
[µg cm−3] 4
[µg cm−3] 12
[µg cm−3] 30
[µg cm−3] 75
5a
5b
6a
88.7
27.5
7.5
100.0
47.8
8.8
100.0
72.7
32.3
100.0
87.4
—
6b
6c
6d
8a
22.3
69.9
25.2
67.6
1.5
33.4
100.0
39.8
77.5
4.7
37.9
100.0
44.7
100.0
7.8
44.1
100.0
88.5
100.0
12.6
8b
9a
9b
22.1
80.0
44.6
33.1
55.2
2.3
11.4
1.8
74.1
69.4
28.8
5.2
43.7
2.5
75.4
21.3
88.7
32.4
100.0
59.6
48.1
78.4
4.5
18.6
4.4
100.0
78.5
35.6
7.6
77.2
4.7
100.0
33.8
100.0
53.8
100.0
80.4
62.6
100.0
14.7
34.8
22.7
100.0
100.0
47.9
29.5
100.0
16.8
100.0
46.1
100.0
66.9
100.0
100.0
74.2
100.0
19.4
44.6
36.4
100.0
100.0
40.3
30.3
100.0
31.7
100.0
88.3
100.0
10a
10b
10c
10d
11a
11b
11d
15a
15b
17a
17b
18a
18b
20a
20d
to form upon solidification, a thin layer at the bottom. Thirty-day-old
sclerotia were then individually transferred under aseptic conditions to
each of three plates for estimation of percentage germination. The other
three plates of each treatment were used for estimation of mycelial
growth, sclerotial formation, and sclerotial germination.
As can be seen from Table I, the effectiveness of the synthesized
thiophene derivatives depends on the concentration and whether the
structure contains either ethyl carboxylate or hydroxyl group. In most
cases, the presence of the ethyl carboxylate group induced higher toxic-
ity than the hydroxyl group. Compounds 9b and 20d showed the high-
est toxicity, as both of them bear the ethyl carboxylate and hydroxyl
group.

Synthesis of Thiophenes
2085
EXPERIMENTAL
Chemistry
All melting points are uncorrected. IR spectra were recorded for (KBr)
1
discs on a Pye Unicam SP-1000 spectrophotometer. H NMR and 13C
NMR spectra were measured on a Varian EM 390-200 MHz in DMSO-
d6 as solvent and using TMS as internal standard, and chemical shifts
are expressed as δ ppm. Analytical data were recorded at the Microan-
alytical Data Unit at Cairo University, Giza, Egypt.
Reaction of Compound 1 with Cyanomethylene Reagents:
General Procedure for the Synthesis of 3a,b
To a solution of cyclohexan-1,3-dione (1) (1.12 g, 0.01 mol) in 1,4-
dioxan (40 mL) containing triethylamine (1.0 mL) and sulfur (0.32 g,
0.01 mol), either malononitrile (2a) (0.66 g, 0.01 mol ) or ethyl cyanoac-
etate (2b) (1.13 g, 0.01 mol) was added. The reaction mixture was heated
under reflux for 3 h, then poured onto ice water containing few drops of
hydrochloric acid. The formed solid product was collected by filtration
and crystallized from the proper solvent.
2-Amino-3-cyano-7-oxocyclohexeno[b]thiophene (3a)
Pale yellow crystals from ethanol, 70% yield (1.35 g), mp 145◦C. IR
(ν, cm−1): 3058 (CH aromatic), 2985, 2893 (CH3, CH2), 2232 (CN), 1684
(C O), 1650 (C N), 1640 (C C). 1H NMR (δ, ppm): 2.72, 2.88 (2m,
4H, 2CH2), 2.92 (m, 2H, CH2), 4.77 (s, 2H, NH2). Calc. for C9H8N2OS
(192.24): C, 56.23; H, 4.19; N, 14.57; S, 16.68. Found: C, 56.27; H, 4.21;
N, 14.49; S, 16.70.
Ethyl 2-Amino-7-oxocyclohexeno[b]thiophene-3-carboxylate
(3b)
Pale brown crystals from ethanol, 82.4% yield (1.97 g), mp 270◦C.
IR (ν, cm−1): 3060 (CH aromatic), 2973, 2895 (CH3, CH2), 1698, 1680
(2C O), 1645 (C N), 1638 (C C). 1H NMR (δ, ppm): 1.13(t, 3H, J = 7.22
Hz, CH3), 2.73, 2.79 (2m, 4H, 2CH2), 2.92 (m, 2H, CH2), 4.24 (q, 2H,
J = 7.22 Hz, CH2), 4.79 (s, 2H, NH2). Calc. For C11H13NO3S (239.29):
C, 55.21; H, 5.48; N, 5.85; S, 13.40. Found: C, 55.26; H, 5.42; N, 6.04; S,
13.47.
Reaction of Benzaldhyde with 3a,b: General Procedure for the
Synthesis of 5a,b
To a solution of either 3a (1.92 g, 0.01 mol) or 3b (2.39 g, 0.01 mol) in
1,4-dioxan (30 mL) containing piperidine (0.50 mL), benzaldehyde (4)

2086
R. M. Mohareb et al.
(1.10 g, 0.01 mol) was added. The reaction mixture was heated under
reflux for 5 h then evaporated in vacuum, and the remaining semisolid
product was triturated with ethanol. The formed solid product was
collected by filtration and crystallized from the proper solvent.
3-Cyano-2-benzalamino-7-oxocyclohexeno[b] thiophene (5a)
Pale yellow crystals from ethanol, 80.3% yield (2.25 g), mp 220◦C.
IR (ν, cm−1): 3058 (CH aromatic), 2988, 2893 (CH3, CH2), 2235 (CN),
1
1688 (C O), 1650 (C N), 1640 (C C). H NMR (δ, ppm) = 2.75, 2.96
(2m, 4H, 2CH2), 2.99 (m, 2H, CH2), 6.86 (s, 1H, CH N), 7.03–7.29 (m,
5H, C6H5). Calc. For C16H12N2OS (280.34): C, 68.55; H, 4.31; N, 9.99;
S, 11.44. Found: C, 68.71; H, 3.99; N, 9.96; S, 11.50.
Ethyl 2-benzalamino-7-oxocyclohexeno[b]thiophene-
3-carboxylate (5b)
Pale brown crystals from ethanol, 77% yield (2.52 g), mp 190◦C. IR (ν
cm−1): 3060 (CH aromatic), 2973, 2895 (CH3, CH2), 1698, 1680 (2C O),
1
1645 (C N), 1638 (C C). H NMR (δ, ppm): 1.14 (t, 3H, J = 6.21 Hz,
CH3), 2.71–3.02 (2m, 6H, 3CH2), 4.26 (q, 2H, J = 6.21 Hz, CH2), 6.93 (s,
1H, CH N), 7.32, 7.38 (m, 5H, C6H5). Calc. for C18H17NO3S (327.40):
C, 66.03; H, 5.23; N, 4.28; S, 9.79. Found: C, 65.92; H, 5.05; N, 4.37; S,
10.01%.
Reaction of 3a,b with Cyanomethylene Reagents: General
Procedure for the Synthesis of 6a–d
Equimolar amounts of either 3a (1.92 g, 0.01 mol) or 3b (2.39 g,
0.01 mol) in ethanol (40 mL) containing piperidine (0.50 mL), either
malnonitrile (2a) (0.66 g, 0.01 mol) or ethyl cyanoacetate (2b) (1.13 g,
0.01 mol) was added. The reaction mixture was heated under reflux for
8 h then evaporated in vacuum. The remaining product was triturated
with ethanol, and the formed solid product was collected by filtration
and crystallized from the proper solvent.
3-Cyano-2,4-diamino-8-oxo-cyclohexeno[b]thieno[5,4:2,3]
pyridine (6a)
Pale brown crystals from acetic acid, 66.2% yield (1.71 g), mp 165◦C.
IR (ν, cm−1): 3485, 3340 (2NH2), 2990, 2875( CH3, CH2), 2225 (CN),
1
1680 (C O), 1645 (C N), 1630 (C C). H NMR (δ, ppm) = 2.70, 3.08
(2m, 4H, 2CH2), 3.17 (m, 2H, CH2), 4.23, 5.94 (2s, 4H, 2NH2, D2O
exchangeable). Calc. for C12H10N4OS (258.30): C, 55.80; H, 3.90; N,
21.69; S, 12.41. Found: C, 55.97; H, 4.04; N, 21.89; S, 12.54%.

Synthesis of Thiophenes
2087
Ethyl 2,4-Diamino-8-oxo-cyclohexeno[b]thieno[5,4:2,3]pyridine
-3-carboxylate (6b)
Orange crystals from 1,4-dioxan, 78.6% yield (2.40 g), mp 221◦C.
IR (ν, cm−1) 3493–3360 (2NH2), 2978, 2870 (CH3, CH2), 1690, 1680
1
(2C O), 1660 (C N), 1645 (C C). H NMR (δ, ppm): 1.13 (t, 3H, J =
6.68 Hz, CH3), 2.66, 3.09 (2m, 4H, 2CH2), 3.17 (m, 2H, CH2), 4.26 (q,
2H, J = 6.68 Hz, CH2), 5.31, 5.85 (2s, 4H, 2NH2). Calc. for C14H15N3O3S
(305.35): C, 55.07; H, 4.95; N, 13.76; S, 10.50. Found : C, 55.13; H, 5.08;
N, 14.01; S, 10.54%.
2-Amino-3-cyano-4-hydroxy-8-oxo-
cyclohexeno[b]thieno[5,4:2,3]-pyridine (6c)
Buff crystals from 1,4-dioxan, 66.4% yield (1.72 g), mp 190◦C. IR (ν,
cm−1): 3580, 3353 (OH, NH2) 2975, 2880 (CH3, CH2), 2223 (CN), 1698
(C O), 1655 (C N), 1630 (C C). 1H NMR (δ, ppm): 2.69, 3.12 (2m, 4H,
2CH2), 3.17 (m, 2H, CH2), 5.63 (s, 2H, NH2), 10.39 (s, 1H, OH). Calc.
for C12H9N3O2S ( 259.28): C, 55.59; H, 3.50; N, 16.21; S, 12.37. Found:
C, 55.71; H, 3.67; N, 15.98; S, 12.45%.
Ethyl 2-amino-4-hydroxy-8-oxocyclohexeno[b]thieno[5,4:2,3]-
pyridine-3-carboxylate (6d)
Pale yellow crystals from acetic acid, 82.6% yield (2.53 g). mp 150◦C.
IR (ν, cm−1): 3590–3373 (NH2,OH), 2960, 2882 (CH3, CH2), 1690–1680
1
(2 C O), 1650 (C N), 1640 (C C). H NMR (δ, ppm): 1.13 (t, 3H, J =
5.68 Hz, CH3), 2.62, 3.09 (2m, 4H, 2CH2), 3.12 (m, 2H, CH2), 4.22 (q,
2H, J = 5.68 Hz , CH2), 4.88 (s, 2H, NH2), 10.01 (s, 1H, OH). Calc. for
C14H14N2O4S (306.34): C, 54.89; H, 4.61; N, 9.14; S, 10.47. Found: C,
54.73; H, 4.66; N, 9.30; S, 10.68%.
Reaction of 3a,b with Ethyl Acetoacetate: General Procedure
for the Synthesis of 8a,b
To a solution of either 3a (1.92 g, 0.01 mol) or 3b (2.39 g, 0.01 mol) in
1,4-dioxan (60 mL) containing piperdine (1.0 mL), ethyl acetoacetate
(7) (1.30 g, 0.01 mol) was added. The reaction mixture was heated
under reflux for 4 h then poured onto ice water containing few drops of
hydrochloric acid. The formed solid product was collected by filtration
and crystallized from the proper solvent.
3-Cyano-2-(α-oxo-butyramido-N-yl)-7-
oxocyclohexen[b]thiophene (8a)
Orange crystals from acetic acid, 60.5% yield (1.67 g), mp 147◦C.
IR (ν, cm−1): 3460-3320 (NH), 2960, 2875 (CH3, CH2), 2222 (CN),

2088
R. M. Mohareb et al.
1
1696–1683 (C O), 1640 (C C). H NMR (δ, ppm): 2.68, 2.84 (2m, 4H,
2CH2), 2.99 (m, 2H, CH2), 3.14 (s, 3H, CH3), 5.21 (s, 2H, CH2), 8.83 (s,
1H, NH). 13C NMR (DMSO-d6): δ 34.1 (CH3), 54.9, 64.3, 77.9 (3 CH2),
90.0 (C), 120.9 (CN), 121.4, 123.8, 138.1, 140.7 (thiophene C), 176.5,
177.5, 183.0 (3C O). Calc. for C13H12N2O3S (276.31): C, 56.51; H, 4.38;
N, 10.14; S, 11.60. Found: C, 56.70; H, 4.57; N, 9.92; S, 11.53%.
Ethyl 2-(β-oxo-butyramido-N-yl)-7-
oxocyclohexeno[b]thiophene-3-carboxylate (8b)
Reddish brown crystals (from acetic acid), 62.8% yield (2.03 g), mp
200◦C. IR (ν, cm−1): 3490–3330 (NH), 2973, 2890 (CH3, CH2), 1705–
1680 (4C O), 1630 (C C). 1H-NMR (δ, ppm): 1.14 (t, 3H, J = 7.02 Hz,
CH3), 2.73, 2.88 (2m, 4H, 2CH2), 2.98 (m, 2H, CH2), 3.20 (s, 3H, CH3),
4.24 (q, 2H, J = 7.02 Hz, CH2), 4.53 (s, 2H, CH2), 9.01 (s, 1H, NH). Calc.
for C15H17NO5S (323.36): C, 55.71; H, 5.30; N, 4.33; S, 9.92. Found: C,
55.70; H, 5.62; N, 4.56; S, 10.03%.
General Procedure for the Synthesis of 9a,b
A solution of either 8a (1.38 g, 0.005 mol) or 8b (1.61 g, 0.005 mol) in
sodium ethoxide (0.005 mol) [prepared by adding sodium metal (0.11 g,
0.005 mol) to absolute ethanol (20 mL)] was heated under reflux in a
boiling water bath for 6 h. The reaction mixture was poured in to ice
water containing few drops of hydrochloric acid (until pH = 6), and the
formed solid product was collected by filtration and crystallized from
the proper solvent.
3-Acetyl-4-amino-2-hydroxy-8-
cyclohexeno[b]thieno[5,4:2,3]pyridine (9a)
Orange crystals from 1,4-dioxan, 66.6% yield (0.92 g), mp 233◦C. IR
(ν, cm−1): 3560–3320 (OH, NH2), 2960, 2873 (CH3, 2CH2), 1696, 1685
1
(2C O), 1655 (C N), 1630 (C C). H NMR (δ, ppm): 2.65, 2.80 (2m,
4H, 2CH2), 2.93 (m, 2H, CH2), 3.09 (s, 3H, CH3), 4.53 (s, 2H, NH2),
10.21 (s, 1H, OH). 13C-NMR (DMSO-d6): δ 30.3 (CH3), 50.6, 64.7 (2
CH2), 88.2 (C), 120.6, 122.0, 122.8, 132.6, 142.7, 144.5 (thiophene and
pyridine-C), 169.1, 176.9 (2C O). Calc. for C13H12N2O3S (276.31): C,
56.51; H, 4.38; N, 10.14; S, 11.60. Found: C, 56.51; H, 4.70; N, 10.18; S,
11.54%.
3-Acetyl-2,4-dihydroxy-8-oxocyclohexeno-
[b]thieno[5,4:2,3]pyridine (9b)
Yellow crystals from DMF, 60% yield (0.83 g), mp 182◦C. IR (ν, cm−1):
3575–3340 (2OH), 2890 (CH2), 1695, 1683(2C O), 1666 (C N), 1640

Synthesis of Thiophenes
2089
(C C). 1H NMR (δ, ppm): 2.68, 2.76 (2m, 4H, 2CH2), 2.89 (m, 2H, CH2),
3.09 (s, 3H, CH3), 9.38, 10.02 (2s, 2H, 2OH). Calc. for C13H11NO4S
(277.30): C, 56.31; H, 4.00; N, 5.05; S, 11.56. Found: C, 56.60; H, 4.16;
N, 5.32; S, 11.38%.
Reaction of 8a,b with Cyanomethylene Reagents: General
Procedure for the Synthesis of 10a–d
To a solution of either 8a (1.38 g, 0.005 mol) or 8b (1.61 g, 0.005 mol)
in dimethylformamide (40 mL) containing piperidine (0.50 mL), either
malononitrile (2a) (0.33 g, 0.005 mol) or ethyl cyanoacetate (2b) (0.56 g,
0.005 mol) was added. The reaction mixture was heated under reflux
for 6 h then evaporated under vacuum, and the remaining product was
triturated with ethanol. The formed solid product, in each case, was
collected by filtration and crystallized from the proper solvent.
3-Cyano-2-(α-dicyanomethino-β-ylidino-butyramido-N-yl)-7-
oxo-cyclohexeno[b]thiophene (10a)
Pale brown crystals from 1,4-dioxan, 60% yield (0.97 g), mp 244◦C.
IR (ν, cm−1): 3475–3365 (NH), 2973, 2885 (CH3,CH2), 2225, 2222–2218
1
(3CN) 1685, 1680 (2C O), 1643 (C C). H NMR (δ ppm): 2.22, 2.67
(2m, 4H, 2CH2), 2.85 (m, 2H, CH2), 3.25 (s, 3H, CH3), 5.03 (s, 2H, CH2),
8.73 (s, 1H, NH). 13C NMR (DMSO-d6): δ 29.5 (CH3), 53.1, 66.4, 82.3
(3CH2), 117.4, 118.0, 120.1 (3CN), 123.9, 124.0, 134.8, 140.0 (thiophene-
C), 78.36, 180.4 (2C O). Calc. for C16H12N4O2S (324.36): C, 59.25; H,
3.73; N, 17.27; S, 9.89. Found: C, 59.40; H, 3.96; N, 17.45; S, 10.15%.
3-Cyano-2-(α-cyanoethoxycarbonylmethino-β-
ylidinobutyramido-N-yl)-7-oxocyclohexeno[b]thiophene (10b)
Orange crystals from 1,4-dioxan, 66% yield (1.25 g), mp 222◦C. IR
(ν, cm−1): 3460–3345 (NH), 2975, 2883 (CH3, CH2), 2225-2218(3CN),
1
1703, 1690–1680 (3C O),1645 (C C). H NMR (δ, ppm): 1.13 (t, 3H,
J = 5.49 Hz, CH3), 2.65, 2.78 (2m, 4H, 2CH2), 2.91 (m, 2H, CH2), 3.21
(s, 3H, CH3), 4.22 (q, 2H, J = 5.49 Hz, CH2), 4.83 (s, 2H, CH2), 8.89
(s,1H, NH). Calc. for C18H17N3O4S (371.20): C, 58.21; H, 4.61; N, 11.31;
S, 8.63. Found: C, 58.34; H, 4.79; N, 11.57; S, 8.94%.
Ethyl 2-(α-Dicyano-methino-β-ylidino-butyramido-N-yl)-7-oxo-
cyclohexeno[b]thiophene-3-carboxylate (10c)
Yellow crystals from 1,4-dioxan, 76% yield (1.41 g), mp 236◦C. IR
(ν, cm−1): 3460–3345 (NH), 2975, 2883 (CH3, CH2), 2225-2218 (2CN),

2090
R. M. Mohareb et al.
1
1703, 1690–1680 (3C O), 1645 (C C). H NMR (δ, ppm): 1.13(t, 3H,
J = 6.92 Hz CH3), 2.65, 2.78 (2m, 4H, 2CH2), 2.88 (m, 2H, CH2), 3.21
(s, 3H, CH3), 4.22 (q, 2H, J = 6.92 Hz, CH2), 4.83 (s, 2H, CH2), 8.89 (s,
1H, NH). Calc. for C18H17N3O4S (371.20): C, 58.21; H, 4.61; N, 11.31;
S, 8.63. Found: C, 58.54; H, 4.56; N, 11.42; S, 8.90%.
Ethyl 2-(α-Cyanoethoxycarbonylmethino-β-ylidino-butyr-
amido-N-yl)-7-oxocyclohexeno[b]thiophene-3-carboxylate
(10d)
Pale yellow crystals from acetic acid, 70% yield (1.47 g), mp 130◦C.
IR (ν, cm−1): 3475–3365 (NH), 2220 (CN), 1708–1685 (4C O), 2970,
1
2843 (CH3, CH2), 1645 (C C). H NMR (δ, ppm): 1.12, 1.14 (2t, 6H,
J = 7.04 Hz, 6.44 Hz, 2CH3), 2.66, 2.73 (2m, 4H, 2CH2), 2.77 (m, 2H,
CH2), 2.82 (s, 3H, CH3), 4.20, 4.27 (2q, 4H, J = 7.04 Hz, 6.44 Hz, 2CH2),
4.91 (s, 2H, CH2), 8.30 (s, 1H, NH). Calc. for C20H22N2O6S (418.46): C,
57.40; H, 5.30; N, 6.69; S, 7.66. Found: C, 57.23; H, 4.99; N, 7.00; S,
7.52%.
Cyclization of 8a,b with Cyanomethylene Reagents: General
Procedure for Synthesis of 11a–d
To a suspension of either 8a (1.38 g, 0.005 mol) or 8b (1.61 g,
0.005 mol) in sodium ethoxide [prepared by dissolving sodium metal
(0.11 g, 0.005 mol) in absolute ethanol (50 mL)], either malononitrile
(2a) (0.33 g, 0.005 mol) or ethyl cyanoacetate (2b) (0.56 g, 0.005 mol)
was added. The reaction mixture, in each case, was heated in a boil-
ing water bath for 6 h. The solid product that formed upon dilution
with water containing hydrochloric acid (until pH = 6) was collected by
filtration and crystallized from the proper solvent.
3-Cyano-2-(2-amino-3-cyano-4-methyl-6-oxopyridin-1-yl)-7-
oxocyclohexeno[b]thiophene (11a)
Orange crystals from ethanol, 80% yield (2.3 g), mp 180◦C. IR (ν,
cm−1): 3463–3340 (NH2), 2978, 2883 (CH3, CH2), 2225-2220 (2CN),
1695, 1680 (2C O), 1640 (C O).1H NMR (δ, ppm): 2.60, 2.78 (2m, 4H,
2CH2), 2.84 (m, 2H, CH2), 3.22 (s, 3H, CH3), 4.90 (s, 2H, NH2), 6.63 (s,
1H, Pyridine H-5). 13C NMR (DMSO) δ: 53.8, 66.2, 83.2 (3 CH2), 118.9,
120.1 (2 CN), 122.0, 123.3, 124.9, 132.2, 142.0, 144.4 (thiophene and
pyridine-C), 178.2, 180.5 (2C O). Calc. for C16H12N4O2S (324.36): C,
59.25; H, 3.73; N, 17.27; S, 9.89. Found: C, 59.28; H, 3.86; N, 16.98; S,
10.03%.

Synthesis of Thiophenes
2091
3-Cyano-2-(3-cyano-2-hydroxy-4-methyl-6-oxopyridin-1-yl)-7-
oxocyclohexeno[b]thiophene (11b)
Reddish brown crystals from ethanol, 67% yield (1.19 g), mp > 300◦C.
IR (ν, cm−1): 3460–3340 (OH), 2977, 2880 (CH3, CH2), 2222-2220 (2CN),
1692, 1685 (2C O), 1645 (C C). 1H NMR (δ, ppm): 2.60, 2.77 (2m, 4H,
2CH2), 2.82 (m, 2H, CH2), 3.26 (s, 3H, CH3), 6.60 (s, 1H, pyridine-H-5),
8.90 (s, 1H, OH). Calc. for C16H11N3O3S (325.34): C, 59.07; H, 3.41; N,
12.92; S, 9.86. Found: C, 59.02; H, 3.68; N, 16.91; S, 10.37%.
Ethyl 2-(2-Amino-3-cyano-4-methyl-6-oxopyridin-1-yl)-7-
oxocyclo-hexeno[b]thiophene-3-carboxylate (11c)
Yellow crystals from ethanol, 70% yield (2.3 g), mp 182◦C. IR (ν,
cm−1): 3465–3340 (NH2), 2978, 2883 (CH3, CH2), 2222 (CN), 1695,
1
1690, 1680 (3C O), 1640 (C C). H NMR (δ, ppm): 1.12 (t, 3H, CH3),
2.60, 2.70 (2m, 4H, 2CH2), 2.84 (m, 2H, CH2), 3.21 (s, 3H, CH3), 4.22
(q, 2H, CH2), 4.90 (s, 2H, NH2), 6.66 (s, 1H, pyridine H-5). Calc. for
C18H17N3O4S ( 371.41): C, 58.21; H, 4.61; N, 11.31; S, 8.63. Found: C,
58.31; H, 4.74; N, 11.29; S, 8.75%.
Ethyl 2-(3-Cyano-2-hydroxy-4-methyl-6-oxopyridin-1-yl)-7-
oxocyclohexeno[b]thiophene-3-carboxylate (11d)
Yellowish brown crystals from ethanol, 56% yield (1.0 g), mp 220◦C.
IR (ν, cm−1): 3463-3343 (OH), 2975, 2880 (CH3, CH2), 2222 (CN), 1692,
1690, 1680 (3C O), 1640 (C O). 1H-NMR (δ, ppm): 1.16 (t, 3H, J = 6.48
Hz, CH3), 2.61, 2.75 (2m, 4H, 2CH2), 2.86 (m, 2H, CH2), 3.24 (s, 3H,
CH3), 4.26 (q, 2H, J = 6.48 Hz, CH2), 6.66 (s, 1H, pyridine-H-5), 10.20
(s, 1H, OH). Calc. for C18H16N2O5S (372.40): C, 58.05; H, 4.33; N, 7.52;
S, 8.61 Found: C, 58.14; H, 4.18; N, 7.82; S, 8.81%.
Reaction of 10a,b with Phenyl Isothiocyanate and
α-Haloketones: General Procedure for Synthesis of
15a,b and 17a,b
To a solution of either 10a (1.62 g, 0.005 mol) or 10b (1.85 g, 0.005 mol)
in DMF (20 mL), phenyl isothiocyanate (12) (0.67 g, 0.005 mol) and
potassium hydroxide (0.28 g, 0.005 mol) were added. The reaction mix-
ture was heated under reflux in a water bath for 3 h. To the reaction
mixture, either ethyl chloroacetate (14) (0.60 g, 0.005 mol) or phenacyl
bromide (16) (1.00 g, 0.005 mol) was added and left overnight. The
solid product that formed upon pouring into an ice water mixture con-
taining a few drops of hydrochloric acid was collected by filtration and
crystallized from the proper solvent.

2092
R. M. Mohareb et al.
3-Cyano-2-[α-oxo-β-(3-phenyl-4-oxo-thiazolideno-2-ylideno)-
butyramido-N-yl]-7-oxocyclohexeno[b]thiophene (15a)
Yellow crystals from ethanol, 64% yield (1.45 g), mp 190◦C. IR (ν,
cm−1): 3480–3375 (NH), 3060 (CH aromatic), 2970, 2884 (CH3, CH2),
1
2225 (CN), 1707, 1690–1680 (4C O), 1640 (C C). H NMR (δ, ppm):
2.23–2.26 (m, 4H, 2CH2), 2.30–2.36 (m, 2H, CH2), 3.28 (s, 3H, CH3),
6.86 (s, 1H, thiazole H-5), 7.32–7.43 (m, 5H, C6H5), 8.81 (s, 1H, NH),
10.23 (s, 1H, OH). Calc. for C22H17N3O4S2(451.52): C, 58.52; H, 3.79;
N, 9.31; S, 14.20. Found: C, 58.47; H, 3.58; N, 9.34; S, 14.16%.
Ethyl 2-[α-Oxo-β-(3-phenyl-4-oxo-thiazolideno-2-ylideno)-
butyramido-N-yl]-7-oxocyclohexen[b]thiophene-3-carboxylate
(15b)
Pale yellow crystals (from 1,4-dioxan), 67% yield (1.67 g), mp 200◦C.
IR (ν, cm−1): 3480–3375 (NH), 3060 (CH aromatic), 2983, 2879 (CH3,
1
CH2) 1710, 1690-1675 (4C O), 1640 (C C). H-NMR (δ, ppm): 1.14 (t,
3H, J = 6.40 Hz, CH3), 2.30–2.36 (m, 2H, CH2), 2.64, 2.80 (2m, 4H,
2CH2), 3.24 (s, 3H, CH3), 4.21 (q, 2H, J = 6.40 Hz, CH2), 5.69 (s, 2H,
CH2), 6.81 (s, 1H, thiazole H-5), 7.30, 7.40 (m, 5H, C6H5), 8.76 (s, 1H,
NH), 10.04 (s, 1H, OH). Calc. for C24H22N2O6S2(498.57): C, 57.82; H,
4.45; N, 5.62; S, 12.86. Found: C, 57.90; H, 4.42; N, 5.78; S, 12.73%.
3-Cyano-2-[α-oxo-β-(3,4-dipheno-thiazolo-2-ylidino)-
butyramido-N-yl-7-oxocyclohexeno[b]thiophene (17a)
Orange crystals from 1,4-dioxan, 71% yield (1.82 g), mp 168◦C. IR
(ν,cm−1): 3480–3364 (NH), 3050 (CH aromatic), 2990, 2870 (CH3, CH2),
1
2227 (CN), 1704–1680 (3C O), 1640 (C C). H-NMR (δ, ppm): 2.24–
2.26 (m, 4H, 2CH2), 2.34–2.38 (m, 2H, CH2), 3.20 (s, 3H, CH3), 6.99 (s,
1H, thiazole H-5), 7.32–7.40 (m, 10H, 2C6H5), 8.94 (s, 1H, NH). 13C-
NMR (DMSO-d6): δ 35.0 (CH3), 50.5, 68.9 (2 CH2), 120.1 (CN), 120.9,
126.4, 125.3, 133.8, 136.1, 145.8 (thiophene and thiazole-C), 177.2,
179.6, 180.3 (3C O). Calc. for C28H21N3O3S2(511.37): C, 65.80; H, 4.10;
N, 8.21; S, 12.53. Found: C, 65.64; H, 3.86; N, 8.45; S, 12.84%.
Ethyl 2-[α-Oxo-β-(3,4-dipheno-thiazolo-2-ylidino)butyramido-
N-yl]-7-oxocyclohexeno[b]thiophene-3-carboxylate (17b)
Pale yellow crystals from ethanol, 60.75% yield (1.69 g), mp 170◦C.
IR (ν, cm−1): 3483–3368 (NH), 3050 (CH aromatic), 2990, 2870 (CH3,
1
CH2), 2227 (CN), 1704–1680 (3C O), 1640 (C C). H-NMR (δ, ppm):
1.13 (t, 3H, J = 5.68 Hz, CH3), 2.64, 2.80 (2m, 4H, 2CH2), 3.01 (m, 2H,
CH2), 3.22 (s, 3H, CH3), 4.26 (q, 2H, J = 5.68 Hz, CH2), 6.99 (s, 1H,
thiazole H-5), 7.31–7.37 (m, 10H, 2 C6H5), 8.77 (s, 1H, NH). Calc. for

Synthesis of Thiophenes
2093
C30H26N2O5S2(558.37): C, 64.52; H, 4.65; N, 5.01; S, 11.48. Found: C,
64.44; H, 4.87; N, 5.24; S, 11.25%.
Reaction of Hydrazine Hydrate with 17a,b: General Procedure
for the Synthesis of 18a,b
To a solution of either 17a (2.55 g, 0.005 mol) or 17b (2.79 g, 0.005 mol)
in ethanol (50 mL), hydrazine hydrate (0.25 g, 0.005 mol) was added.
The reaction mixture was heated under reflux for 4 h, then it was
poured in to ice water containing a few drops of hydrochloric acid. The
formed solid product was collected by filtration and crystallized from
the proper solvent.
3-Cyano-2-[5-methyl-4-ylideno-(4-oxo-3-phenyl-thiazolideno-
2-yl)pyrazolo-3-yl]-7-oxocyclohexeno[b]thiophene (18a)
Orange crystals from acetic acid, 76% yield (1.70 g), mp 264–266◦C.
IR (ν, cm−1): 3466–3380 (NH), 3060 (CH aromatic), 2988, 2884 (CH3,
CH2), 2225 (CN), 1706, 1685 (2C O), 1663 (C N), 1640 (C C). 1H NMR
(δ, ppm): 2.66, 2.81 (2m, 4H, 2CH2), 3.21 (s, 3H, CH3), 2.89 (s, 2H, CH2),
6.97 (s, 1H, thiazole H-5), 7.31–7.39 (m, 5H, C6H5), 8.33 (s, 1H, NH),
10.23 (s, 1H, OH). Calc. for C22H17N5O2S2(447.32): C, 59.06; H, 3.80;
N, 15.64; S, 14.33. Found: C, 60.15; H, 4.06; N, 15.99; S, 14.68%.
Ethyl 2-[5-methyl-4-ylideno-(4-oxo-3-phenyl-thiazolideno-2-yl)-
pyrazolo-3-yl]-7-oxocyclohexeno[b]thiophene-3-carboxylate
(18b)
Yellow crystals from acetic acid, 70.8% yield (1.75 g), mp 235◦C. IR
(ν, cm−1): 3460–3385 (NH), 3068 (CH aromatic), 2973, 2898 (CH3, CH2),
1
1703, 1690–1680 (3C O), 1655 (C N), 1640 (C C). H NMR (δ, ppm):
1.16 (t, 3H, CH3), 2.61, 2.77 (2m, 4H, 2CH2), 3.11 (s, 3H, CH3), 4.24 (q,
2H, CH2), 2.32 (s, 2H, CH2), 6.96 (s, 1H, thiazole H-5), 7.30–7.37 (m,
5H, C6H5), 8.36 (s, 1H, NH), 10.03 (s, 1H, OH). Calc. for C24H22N4O4S2
(494.32): C, 58.31; H, 4.45; N, 11.32; S, 12.97. Found: C, 58.29; H, 4.36;
N, 11.49; S, 13.01%.
Synthesis of the Cyclohexeno[b]thieno[5,4:2:3]pyrimidino-
[5,1:1,2]-pyrazole Derivatives 19a,b
A suspension of either 18a (2.23 g, 0.005 mol) or 18b (2.47 g, 0.005 mol)
in sodium ethoxide solution (0.005 mol) was heated in a boiling water
bath for 2 h. The reaction mixture was poured in to ice water containing
few drops of hydrochloric acid (until pH = 7) and the formed solid

2094
R. M. Mohareb et al.
product was collected by filtration and crystallized from the proper
solvent.
1-(4-Hydroxy-3phenyl-3H-thiazol-2-ylidene)-4-imino-2-methyl-
1,4,6,7-tetrahydro-5H-9-thia-3,3a,10-triaza-cyclopenta[b]-
fluoren-8-one (19a)
White crystals from ethanol, 60% yield (1.35 g), mp 180◦C. IR (ν,
cm−1): 3475–3360 (NH), 3063 (CH aromatic), 2970, 2882 (CH3, CH2),
1720, 1691 (2C O), 1670 (exocyclic C N), 1635 (C C). 1H NMR (δ,
ppm): 2.22–2.25 (m, 4H, 2CH2), 2.36 (s, 2H, CH2), 3.22 (s, 3H, CH3),
6.20 (s, 1H, thiazole H-5), 7.30–7.42 (m, 5H, C6H5), 8.92 (s, 1H, NH),
10.05 (s, 1H, OH). Calc. for C22H17N5O2S2(447.08): C, 59.04; H, 3.83;
N, 15.65; S, 14.33. Found: C, 59.01; H, 3.65; N, 15.78; S, 14.44%.
1-(4-Hydroxy-3phenyl-3H-thiazol-2-ylidene)-2-methyl-6,7-
dihydro-1H,5H-9-thia-3,3a,10-triaza-cyclopenta[b]fluoren-4,8-
dione (19b)
Yellow crystals from 1,4-dioxan, 68% yield (1.52 g), mp 170◦C. IR (ν,
cm−1): 3056 (CH aromatic), 2972, 2878 (CH3 , CH2), 1710, 1706, 1688
(3C O), 1663 (C N), 1643 (C C). 1H-NMR (δ, ppm): 2.65–2.80 (2m, 6H,
3CH2), 3.07 (s, 3H, CH3), 6.22 (s, 1H, thiazole H-5), 7.30–7.32 (m, 5H,
C6H5), 10.10 (s, 1H, OH). Calc. for C22H16N4O3S2(448.07): C, 58.91; H,
3.60; N, 12.49; S, 14.30. Found : C, 58.71; H, 3.80; N, 12.59; S, 14.28%.
Reaction of 17a,b with Cyanomethylenes: General Procedure
for the Synthesis of 20a–d
To a solution of either 17a (2.55 g, 0.005 mol) or 17b (2.79 g, 0.005
mol) in ethanol (40 mL) containing piperidine (0.50 mL), either mal-
ononitrile (2a) (0.33 g, 0.005 mol) or ethyl cyanoacetate (2b) (0.56 g,
0.005 mol) was added. The reaction mixture, in each case, was heated
under reflux for 6 h, then evaporated in vacuum. The remaining product
was triturated with ethanol, and the formed solid product was collected
by filtration and crystallized from the proper solvent.
3-Cyano-2-[3-cyano-4-methyl-2-imino-6-oxo-5-(3-phenyl-4-
oxo-thia-zolideno-2-ylideno)pyridin-1-yl]-7-oxocylohexeno[b]-
thiophene (20a)
Brown crystals from acetic acid, 67% yield (1.68g), mp 176◦C. IR (ν,
cm−1): 3463–3384 (OH, NH) , 3053 (CH aromatic), 2983, 2890 (CH3,
CH2), 2227–2220 (2CN), 1702–1685 (3C O), 1650 (C N), 1630 (C C).
1H-NMR (δ, ppm): 2.66–2.79 (2m, 6H, 3CH2), 3.43 (s, 3H, CH3), 6.26 (s,

Synthesis of Thiophenes
2095
1H, thiazole H-5), 7.34–7.80 (m, 5H, C6H5), 8.93(s, 1H, NH), 10.38 (s,
1H, OH). Calc. for C25H17N5O3S2(499.34): C, 60.12; H, 3.40; N, 14.01;
S, 12.84. Found: C, 59.98; H, 3.26; N, 13.87; S, 13.02%.
3-Cyano-2-[3-cyano-4-methyl-2,6-dioxo-5-(3-phenyl-4-oxo-thia-
zolideno-2-ylideno)pyridin-1-yl]-7-oxocylohexeno[b]thiophene
(20b)
Orange crystals from 1,4-dioxan, 59% yield (1.47 g), mp 180◦C. IR (ν,
cm−1): 3520–3330 (OH), 3056 (CH aromatic), 2934, 2866 (CH3, CH2),
1
2225, 2220 (2CN), 1720, 1685–1682 (4C O), 1643 (C C). HNMR (δ,
ppm): 2.64, 2.80 (2m, 4H, 2CH2), 3.32 (s, 3H, CH3), 6.28 (s, 1H, thiazole
H-5), 6.45 (s, 2H, CH2), 7.32–7.36 (m, 5H, C6H5), 10.32 (s, 1H, OH).
Calc. for C25H16N4O4S2(500.33): C, 60.01; H, 3.19; N, 11.19; S, 12.81.
Found: C, 59.77; H, 3.35; N, 11.16; S, 12.72%.
Ethyl 2-[3-Cyano-4-methyl-2-imino-6-oxo- 5-(3-phenyl-4-oxo-
thiazolideno-2-ylideno)pyridin-1-yl]-7-oxocylohexeno[b]-
thiophene-3-carboxylate (20c)
Yellow crystals from 1,4-dioxan, 65% yield (1.77 g), mp 190◦C. IR (ν,
cm−1): 3455–3365 (NH), 3053 (CH aromatic), 2968, 2875 (CH3, CH2),
1
2223 (CN), 1695–1680 (3C O), 1648 (C N), 1640 (C C). H-NMR (δ,
ppm): 1.13 (t, 3H, J = 7.30 Hz, CH3), 2.64–2.82 (2m, 6H, 3CH2), 3.25
(s, 3H, CH3), 4.26 (q, 2H, J =7.30 Hz, CH2), 6.34 (s, 1H, thiazole H-5),
7.30–7.35 (m, 5H, C6H5), 8.55 (s, 1H, NH), 10.28 (s, 1H, OH). Calc. for
C27H22N4O5S2(546.34): C, 59.35; H, 4.02; N, 10.25; S, 11.73. Found: C,
59.44; H, 4.10; N, 10.19; S, 12.00%.
Ethyl 2-[3-Cyano-4-methyl-2,6-dioxo-5-(3-phenyl-4-oxo-
thiazolideno-2-ylideno)pyridin-1-yl]-7-oxocylohexeno[b]-
thiophene-3-carboxylate (20d)
Reddish brown crystals from 1,4-dioxan, 65% yield (1.82 g), mp
155◦C. IR (ν, cm−1): 3053 (CH aromatic), 2968, 2875 (CH3, CH2), 2223
1
(CN), 1695–1680 (4C O), 1648 (C N), 1640 (C C). H NMR (δ, ppm):
1.13 (t, 3H, J = 7.22 Hz, CH3), 2.64, 2.82 (2m, 6H, 3CH2), 3.23 (s, 3H,
CH3), 4.22 (q, 2H, J =7.22 Hz, CH2), 6.34 (s, 1H, thiazole H-5) 7.30–
7.33 (m, 5H, C6H5), 10.34 (s, 1H, OH). Calc. for C27H21N3O6S2(547.09):
C, 59.22; H, 3.87; N, 7.67; S, 11.71. Found: C, 59.54; H, 3.58; N, 8.00; S,
11.73%.

2096
R. M. Mohareb et al.
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