Synthesis and reactions of some new heterocyclic compounds containing the thienylthieno[2,3-b]pyridine moiety

Article abstract of DOI:10.1080/10426500490467147

(4-Aryl-3-cyano-6-(2-thienyl)pyridin-2-ylthio)acethydrazides (5a-c), 3-amino-4-aryl-6-(2-thienyl)thieno[2,3-b]pyridine-2-carbohydrazides (6a-c) and 3-amino-4-phenyl-6-(2-thienyl)thieno[2,3-b]pyridine-2-carboxylic acid (30) were prepared and employed as key intermediates in the synthesis of the title compounds.

Full text of DOI:10.1080/10426500490467147

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SYNTHESIS AND REACTIONS OF SOME NEW
HETEROCYCLIC COMPOUNDS CONTAINING THE
THIENYLTHIENO[2,3-B]PYRIDINE MOIETY
Etify A. Bakhite a , Abdu E. Abdel-Rahman a , Omima. S. Mohamed a & Eman A. Thabet a
a Chemistry Department, Faculty of Science, Assiut University, Assiut, Egypt
Version of record first published: 16 Aug 2010
To cite this article: Etify A. Bakhite, Abdu E. Abdel-Rahman, Omima. S. Mohamed & Eman A. Thabet (2004): SYNTHESIS AND
REACTIONS OF SOME NEW HETEROCYCLIC COMPOUNDS CONTAINING THE THIENYLTHIENO[2,3-B]PYRIDINE MOIETY, Phosphorus,
Sulfur, and Silicon and the Related Elements, 179:10, 1983-2006
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Phosphorus, Sulfur, and Silicon, 179:1983–2006, 2004
ꢀC
Copyright Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500490467147
SYNTHESIS AND REACTIONS OF SOME NEW
HETEROCYCLIC COMPOUNDS CONTAINING THE
THIENYLTHIENO[2,3-b]PYRIDINE MOIETY
Etify A. Bakhite, Abdu E. Abdel-Rahman, Omima. S. Mohamed,
and Eman A. Thabet
Chemistry Department, Faculty of Science, Assiut University,
Assiut, Egypt
(Received October 10, 2003; accepted February 20, 2004)
(4-Aryl-3-cyano-6-(2-thienyl)pyridin-2-ylthio)acethydrazides (5a–c),
3-amino-4-aryl-6-(2-thienyl)thieno[2,3-b]pyridine-2-carbohydrazides
(6a–c) and 3-amino-4-phenyl-6-(2-thienyl)thieno[2,3-b]pyridine-2-
carboxylic acid (30) were prepared and employed as key intermediates
in the synthesis of the title compounds.
Keywords: Cyanopyridinethiones; imidazolothienopyridines; pyrano-
thienopyridines; pyrazolinothienopyridines; pyridothienopyrimidines;
thienopyridines
INTRODUCTION
Pyridine derivatives have occupied a unique position in medicinal
chemistry. The naturally occurring B6 vitamins pyridoxine, pyridoxal,
pyridoxamine, and codecarboxylase1 contain a pyridine nucleus. In
addition, many pyridines are reported to be useful as herbicides,2,3
bactericides,4,5 fungicides,6 inseticides,7,8 and pharmaceuticals.9−16
In particular, several thieno[2,3-b]pyridine derivatives are known
to possess antibacterial,17−19 antihypertensive,20 and gonadotropin-
releasing hormone-antagonizing21,22 activity. Pyridothienopyrimidine
derivatives have found applications as analgesics,23 antipyretics24 and
anti-inflammatories.25 Encouraged by these facts, and as a continua-
tion of our previous work 26−33 on thieno[2,3-b]pyridines, we undertook
the synthesis of the title compounds, which might exhibit enhanced
Address correspondence to Etify A. Bakhite, Chemistry Department, Faculty of Sci-
ence, Assiut University, Assiut 71516, Egypt. E-mail: etiafy@acc.aun.edu.eg
1983

1984
E. A. Bakhite et al.
activities owing to the incorporation of different pharmacophores into
their structures.
RESULTS AND DISCUSSION
4-Aryl-3-cyano-6-(2-thienyl)pyridine-2(1H)-thiones (2a–c) were used
as starting materials in this investigation. They were prepared in
analogy to the method described before by the reaction of 3-aryl-1-(2-
thienyl)prop-2-en-1-ones (1a–c) with cyanothioacetamide in the pres-
ence of piperidine as a basic catalyst.31 The reaction of 2a–c with ethyl
chloroacetate in the presence of sodium acetate gave ethyl (4-aryl-
3-cyano-6-(2-thienyl)-2-pyridinylthio)acetates (3a–c). The latter com-
pounds underwent intramolecular Thorpe-Ziegler cyclization to afford
thieno[2,3-b]pyridines 4a–c upon treatment with a catalytic amount of
sodium ethoxide in refluxing ethanol. Heating the esters 3a–c with
hydrazine hydrate in refluxing ethanol produced the corresponding
acethydrazide derivatives 5a–c. When this reaction was performed un-
der neat conditions, the products were assigned as 3-amino-4-aryl-6-(2-
thienyl)thieno[2,3-b] pyridine-2-carbohydrazides (6a–c). Compounds
6a–c were also obtained by the reaction of o-aminoesters 4a–c with
hydrazine hydrate in boiling ethanol (Scheme 1).
On treatment of acethydrazide 5a in glacial acetic acid with sodium
nitrite solution at room temperature, the carboazide derivative 7
was obtained. When the acid azide 7 was heated in ethanol Cur-
tius rearrangement occurred, whereby the isocyanate intermediate 8
was formed. The latter intermediate reacted concomitantly with the
ethanol, which was used as a solvent, to give the corresponding ethyl
carbamate 9. It is worthy of note that when the acid azide 7 was heated
in an excess of aniline, Curtius rearrangement did not occur and the
product proved to be the anilide 10 rather than the expected urea
derivative 11. The latter reaction may proceed via nucleophilic substi-
tution mechanism. The compound 10 was also prepared by the direct
reaction of 2a with chloro-N-phenylacetamide in the presence of sodium
acetate (Scheme 2).
The condensation of acethydrazide 5a with aromatic aldehydes
yielded the corresponding hydrazones 12a–c which underwent in-
tramolecular Thorpe-Ziegler cyclization upon heating with catalytic
amounts of sodium ethoxide in ethanol to furnish N1-arylmethylene-3-
amino-4-phenyl-6-(2-thienyl)thieno[2,3-b]pyridine-2-carbohydrazides
(13a–c).33 The compounds 13a–c were also synthesized through direct
condensation of 6a with the respective aldehydes in boiling ethanol.
Treatment of 13a–c with triethyl orthoformate in refluxing acetic

Synthesis and Reactions of Some New Heterocyclic Compounds
1985
R
R
CN
CH2
CN
S
CH
piperidine
CH
C
+
C
O
S
N
H2N
S
S
H
2a–c
1a–c
ClCH2CO2Et /
AcONa
R
R
CN
CN
N2H4.H2O /
EtOH
N
SCH2CONHNH2
N
SCH2CO2Et
EtONa
S
S
5a–c
3a–c
R
R
N2H4.H2O /
neat
NH2
NH2
N2H4.H2O/
EtOH
N
6a–c
S
CONHNH2
N
S
CO2Et
S
S
4a–c
1–6
R
a
b
c
H
OCH3
Cl
SCHEME 1
anhydride led to the fomation of the corresponding pyridothienopyrim-
idinones 14a–c. Also, heating of 13a–c with acetic anhydride at ref-
lux temperature afforded 3-arylmethyleneamino-2-methyl-9-phenyl-7-
(2-thienyl)pyrido[3ꢁ,2ꢁ:4,5]thieno[3,2-d]pyrimidine-4(3H)-ones (15a–c)
(Scheme 3).

1986
E. A. Bakhite et al.
Ph
Ph
CN
CN
EtOH
N
SCH2NCO
N
SCH2NHCO2Et
S
S
8
9
EtOH / heat
-N2
Ph
CN
NaNO2/AcOH
r.t.
5a
N
SCH2CON3
S
7
PhNH2 / heat
Ph
Ph
CN
CN
N
SCH2NHCONHPh
N
SCH2CONHPh
S
S
10
11
ClCH2CONHPh
AcONa
2a
SCHEME 2
On heating of 6a with urea in decalin for 4 hours, the product was
identified as 3-amino-9-phenyl-7-(2-thienyl)pyrido[3ꢁ,2ꢁ:4,5]thieno[3,2-
d]pyrimidine-2,4(1H,3H)-dione (16). Heating of compound 6a with
formic acid led to the formation of N-formylaminopyrimidinone
derivative 17. In contrast, heating of 6a–c with acetic acid at reflux
temperature for 8 h furnished the corresponding pyrazolinothieno-
pyridines 18a–c.34 The latter reaction may proceed via acetylation
followed by elimination of an acetamide molecule. The interaction
of 6a–c with acetic anhydride at reflux temperature afforded 9-
aryl-3-diacetylamino-2-methyl-7-(2-thienyl)pyrido[3ꢁ,2ꢁ:4,5]thieno[3,2-
d]pyrimidine-4(3H)-ones (19a–c). When compounds 6a–c were allowed
to react with acetylacetone, the dimethylpyrazolyl derivatives 20a–c
were obtained in high yields (Scheme 4).
The cyclocondensation of carbohydrazide derivatives 6a–c with tri-
ethyl orthoformate by heating in DMF produced 3-ethoxymethylene-
aminopyrimidine-4(3H)-ones 21a–c. Treatment of compound 21a with

Synthesis and Reactions of Some New Heterocyclic Compounds
1987
5a
6a
ArCHO/ EtOH
ArCHO/ EtOH
CN
Ph
Ph
N
NH2
EtONa
CONHN
N
SCH2CONHN=CHAr
S
S
S
13a–c
12a–c
CHAr
Ac2O
HC(OEt)3/Ac2O
Ph
N
Ph
N
N
CH3
N
O
N
S
N
N
S
N
S
S
O
CHAr
CHAr
14a–c
15a–c
12–15
Ar
C6H5
C6H4-OCH3(p)
C6H4-Cl(p)
a
b
c
SCHEME 3
hydrazine hydrate under neat conditions resulted in the formation
of N-aminopyrimidinone derivative 22, while the interaction of 21a
with hydrazine hydrate in dioxane at room temperature furnished 3-
hydrazinomethyleneaminopyrimidinone derivative 23. When the lat-
ter compound (23) was fused with hydrazine hydrate, it gave com-
pound 22. The reactivity of the amino group of 22 was tested via
condensation with benzaldehyde to give the Schiff’s base 14a or
treating with acetic anhydride to produce the diacetyl derivative 24
(Scheme 5).
The compound 6a was also reacted with carbon disulfide in hot pyri-
dine to produce 1,3,4-oxadiazole-5(4H)-thione derivative 25.26 Upon
treatment of 25 with ethyl chloroacetate in the presence of sodium
acetate, the S-alkylated compound 26 was isolated. Diazotization of
6a–c in acetic acid with sodium nitrite solution at room tempera-
ture resulted in the formation of the acid azides 27a–c. On heating
of 27a–c in isopropyl alcohol at reflux temperature, they underwent
Curtius rearrangement, forming the isocyanate intermediates 28a–c

1988
E. A. Bakhite et al.
Ph
N
N
NHCHO
N
S
S
17
R
O
Ph
N
H
N
HCO2H
(6a)
O
CH3
N
N
NH2
S
N
S
O
16
N
19a–c
S
N(COCH3)2
S
O
(NH2)2CO
(6a)
Ac2O
6a–c
R
R
AcOH
NH2
Ac2CH2
NH2
N
S
CO N
N
N
R
S
CONHNHCOCH3
S
S
20a–c
H3C
CH3
-CH3CONH2
H
N
16, 18, 19
R
NH
a
b
c
H
OCH3
Cl
N
S
O
S
18a–c
SCHEME 4
followed by intramolecular cycloaddition reaction to afford the imida-
zolone derivatives 29a–c26 (Scheme 6).
Saponification of 4a with an ethanolic sodium hydroxide solution
followed by acidification with acetic acid gave 3-amino-4-phenyl-
6-(2-thienyl)thieno[2,3-b] pyridine-2-carboxylic acid (30), which
underwent ring closure reaction upon treatment with acetic anhydride
to furnish 2-methyl-9-phenyl-7-(2-thienyl)-pyrido[3ꢁ,2ꢁ:4,5]thieno[3,2-
d]oxazin-4-one (31). The oxazinone derivative 31 was recyclized

Synthesis and Reactions of Some New Heterocyclic Compounds
6a–c
HC(OEt)3/
1989
14a
R
PhCHO
DMF
Ph
N
N
O
N
N2H4.H2O/neat
(21a)
N
N
NH2
N
CHOEt
S
N
S
S
22
S
O
21a–c
(21a)
N2H4.H2O/
Dioxane
N2H4.H2O /
neat
Ac2O
Ph
Ph
N
N
N
N
N
N
CH-NHNH2
N(COCH3)2
N
S
23
S
S
O
S
O
24
21
R
a
b
c
H
OCH3
Cl
SCHEME 5
into some pyrimidinone derivatives upon treatment with certain
reagents. Thus, the reaction of 31 with aniline or with ethyl gly-
cinate hydrochloride gave the pyrimidinone derivatives 32 and 33,
respectively. Also, the reaction of 31 with hydrazine hydrate gave
3-amino-2-methyl-9-phenyl-7-(2-thienyl)pyrido[3ꢁ,2ꢁ:4,5]thieno[3,2-d]-
pyrimidine-4(3H)-one (34). The latter compound (34) was reacted,
in turn, with aromatic aldehydes or acetic anhydride to give the
corresponding pyrimidinone derivatives 15a–c and 19a, which were
prepared from the hydrazones 13a–c or o-aminocarbohydrazide 6a,
respectively (Scheme 7).
In contrast, heating of o-aminocarboxylic acid 30 with orthophos-
phoric acid at 100˚C resulted in decarboxylation followed by hy-
drolysis of the imino group to give 4-phenyl-6-(2-thienyl)thieno[2,3-
b]pyridine-3(2H)-one (35).33 On treatment of the ketone 35 with
arylmethylenemalononitriles in ethanol containing catalytic amounts
of piperidine, a cycloaddition reaction occurred and 2-amino-4,9-diaryl-
7-(2-thienyl)-4H-pyrano[2ꢁ,3ꢁ:4,5]thieno[2,3-b]pyridine-3-carbonitriles

1990
E. A. Bakhite et al.
CS2
NaNO2 /
AcOH
6a–c
R
(6a)
Ph
N
NH2
NH2
O
S
S
N
S
CON3
S
25
N
NH
S
27a–c
isopropyl
RCl
alcohol / ∆
Ph
N
NH2
R
O
SR
S
S
N
N
26, R= CH2CO2Et
NH2
R
N
S
N=C=O
S
28a–c
NH
27–29
R
a
b
c
H
OCH3
Cl
O
N
S
N
H
S
29a–c
SCHEME 6
(37a,b) were obtained in high yield (Scheme 8). The structures of com-
pounds 37a,b were further confirmed by another route of preparation
via condensation of compound 35 with aromatic aldehydes followed
by the treating of the formed chalcones 36a,b with malononitrile
(Scheme 8).33
The structural formulas of all newly synthesized compounds were
established and confirmed on the basis of their elemental analyses and
spectral data (see Table I and the Experimental sectin below).
EXPERIMENTAL
All melting points are uncorrected and measured on a Gallenkamp
apparatus. IR spectra were recorded on a Shimadzu 470 IR

Synthesis and Reactions of Some New Heterocyclic Compounds
1991
Ph
NH2
(i) NaOH
(ii) AcOH
4a
N
S
CO2H
S
30
Ph
Ph
N
N
O
Me
N-Ph
N
O
Me
N-CH2CO2Et
Ac2O
N
S
S
S
S
33
32
Ph
N
N
O
Me
HCl.H2NCH2CO2Et
PhNH2
O
S
S
31
NH2NH2.H2O /
EtOH
Ph
N
N
Me
NH2
PhCHO
15a–c
Ac2O
19a
N
S
S
O
34
SCHEME 7
spectrophotometer (KBr; ν max in cm−1); 1H NMR spectra on a
Varian EM-390, 90 MHz spectrometer with TMS as internal standard
(δ in ppm); MS on a Jeol JMS-600 mass spectrometer and elemental
analyses on an Elementar Analysensystem GmbH VARIOEL V2.3 July
1998 CHNS Mode. Melting points, yields, and analytical data of all
newly synthesized compounds are listed in Table I.
4-Aryl-3-cyano-6-(2-thienyl)pyridine-2(1H)-thiones (2a–c)
To a solution of chalcone 1a–c (20 mmol) and cyanothioacetamide (2.0 g,
20 mmol) in ethanol (50 ml), a few drops of piperidine were added.
The reaction mixture was refluxed for 4 h. The solid that formed while
hot was collected and recrystallized from acetic acid as orange needles
1
of 2a–c. IR: ν = 3190–3180 (NH), 2210 (C N) cm−1. H NMR of 2a
(DMSO-d6): δ = 8.3 (m, 1H, CH thienyl), 7.6–8.2 (m, 6H: 5ArH’s and
CH pyridine), 7.3 (m, 1H, CH thienyl), 7.1 (m, 1H, CH thienyl) ppm.
1H NMR of 2b (TFA): δ = 7.8–8.2 (m, 5H: 2ArH’s, 2CH thienyl and CH

1992
E. A. Bakhite et al.
Ph
Ph
NH
NH2
H3PO4
100ºC
30
N
S
S
N
S
S
S
Ph
Ph
O
ArCHO / piperidine
O
CH Ar
N
S
S
N
36a,b
S
35
CH2(CN)2/
piperidine
Ar-CH=C(CN)2
Ph
36, 37 Ar
O
NH2
a
b
C6H5
C6H4Cl(4)
CN
N
S
37a,b
S
Ar
SCHEME 8
pyridine), 7.2–7.5 (m, 3H: 2ArH’s and CH thienyl), 4.0 (s, 3H, OCH3)
ppm. 1H NMR of 2c (DMSO-d6): δ = 8.2 (d, 1H, CH thienyl), 7.5–7.8 (m,
6H: 4ArH’s, CH thienyl and CH pyridine), 7.2 (m, 1H, CH thienyl) ppm.
MS of 2a: 295 (M+ + 1, 100%); 294 (M+, 100%); 261 (M+-SH, 30%); 250
(M+-CS, 37%); 190 (14%);147 (21%); 77 (C6H+5 , 7%); 44 (CS+, 3%).
Ethyl (4-Aryl-3-cyano-6-(2-thienyl)pyridin-2-ylthio)-
acetates (3a–c)
A mixture of 2a–c (20 mmol), ethyl chloroacetate (2.2 ml, 20 mmol)
and sodium acetate trihydrate (3.0 g, 22 mmol) in ethanol (60 ml) was
heated under reflux for 2 h. The precipitate that formed on cooling was
collected and recrystallized from ethanol to give pale yellow crystals of
1
3a–c. IR: ν = 2210 (C N), 1730 (C O) cm−1. H NMR of 3a (CDCl3):
δ = 7.6–8.2 (m, 8H: 5ArH’s, 2CH thienyl and CH pyridine), 7.3 (m, 1H,
CH thienyl), 4.1–4.4 (m, 4H, SCH2 and OCH2), 1.2–1.4 (t, 3H, CH3 of
1
ester) ppm. H NMR of 3b (CDCl3): δ = 7.0–7.8 (m, 8H: 4ArH’s, 3CH
thienyl and CH pyridine), 4.2–4.5 (m, 4H, SCH2 and OCH2), 3.9 (s, 3H,

Synthesis and Reactions of Some New Heterocyclic Compounds
1993
% Cl
TABLE I Melting Points, Yields, and Analytical Data of all Newly
Synthesized Compounds
Calculated/found
m.p. (◦C)/
yield (%)
Formula
(M.W.)
Compound
% C
% H
% N
% S
2a
245/43
250/62
242/47
162/95
180/97
145–150/95
182/90
185/90
205/89
215/86
190/82
193/80
260/84
220/85
160/80
115/80
180/82
200/90
235/95
238/98
237/90
C16H10N2S2
(294.40)
C17H12N2OS2
(324.42)
C16H9ClN2S2
(329.86)
C20H16N2O2S2
(380.49)
65.28 3.42
65.02 3.26
62.94 3.73
62.65 3.95
58.44 2.76
58.19 2.98
63.13 4.24
63.02 4.14
61.44 4.42
61.73 4.12
57.89 3.64
57.58 3.50
63.13 4.24
63.34 4.11
61.44 4.42
61.71 4.67
57.89 3.64
57.99 3.36
58.10 3.85 15.29 17.50
58.30 3.99 15.62 17.42
57.56 4.07 14.13 16.18
57.96 4.21 14.46 16.58
53.93 3.27 13.98 15.99
53.40 3.24 13.70 16.12
58.99 3.85 15.29 17.50
59.13 3.66 15.11 17.77
57.56 4.07 14.13 16.18
57.85 4.00 14.45 16.19
53.93 3.27 13.98 15.99
53.96 3.12 13.60 16.08
57.28 2.94 18.55 16.99
57.51 2.75 18.70 16.81
9.52 21.78
9.25 21.82
8.63 19.77
8.54 19.85
8.52 19.50 10.78
8.36 19.81 10.90
7.36 16.86
7.76 16.94
6.82 15.62
6.55 15.86
6.75 15.46
6.85 15.22
7.36 16.86
7.77 16.89
6.82 15.62
6.80 15.30
6.75 15.46
6.54 15.70
2b
2c
3a
3b
3c
4a
4b
4c
5a
5b
5c
6a
6b
6c
7
C21H18N2O3S2
(410.51)
20H15ClN2O2S2
(414.94)
C
8.54
8.39
C20H16N2O2S2
(380.49)
C21H18N2O3S2
(410.51)
20H15ClN2O2S2
(414.94)
C
8.54
8.90
C
18H14N4OS2
(366.47)
C19H16N4O2S2
(396.49)
C18H13ClN4OS2
(400.91)
8.84
9.00
C
18H14N4OS2
(366.47)
C19H16N4O2S2
(396.49)
18H13ClN4OS2
(400.91)
C
8.84
8.98
C
18H11N5OS2
(377.45)
9
C21H17N3O3S2
(423.52)
59.56 4.05
59.70 4.19
67.42 4.01
67.70 4.22
66.06 3.99 12.33 14.11
65.81 4.18 12.65 14.25
64.44 4.15 11.56 13.23
64.66 4.37 11.91 13.00
61.40 3.50 11.46 13.11
61.58 3.28 11.70 13.22
9.92
9.99
9.83
9.90
15.14
15.35
14.10
14.00
10
12a
12b
12c
C
24H17N3OS2
(427.55)
C
25H18N4OS2
(454.58)
C26H20N4O2S2
(484.60)
C25H17ClN4OS2
(489.03)
7.25
7.17
(Continued on next page)

1994
E. A. Bakhite et al.
TABLE I Melting Points, Yields, and Analytical Data of all Newly
Synthesized Compounds (Continued)
Calculated/found
m.p. (◦C)/
yield (%)
Formula
(M.W.)
Compound
% C
% H
% N
% S
% Cl
13a
295/99
297/98
290/95
275/92
310/90
305/90
260/90
300/91
>300/65
320/89
>320/60
300/80
290/90
250/71
250/80
265/70
195–198/82
180/78
198/80
300/88
220/75
215/80
C25H18N4OS2
(454.58)
C26H20N4O2S2
(484.60)
C25H17ClN4OS2
(489.03)
C26H16N4OS2
(464.57)
66.06 3.99
66.25 4.18
64.44 4.16
64.42 4.35
61.40 3.50
61.68 3.71
67.22 3.47
67.41 3.12
65.57 3.67
65.23 3.80
62.58 3.03
62.25 3.01
67.76 3.79
67.82 3.39
63.21 3.34
63.12 3.48
58.15 3.08
58.11 3.25
59.39 2.99
59.65 3.11
61.87 3.17
61.85 3.22
60.14 3.45
60.50 3.71
56.32 2.63
56.18 2.86
60.74 3.82
60.62 3.90
59.51 3.99
59.62 3.75
56.63 3.37
56.43 3.40
64.16 4.21
64.34 4.11
62.59 4.38
62.22 4.43
59.41 3.69
59.62 3.85
65.97 4.03
65.95 4.06
59.72 3.92
59.87 3.92
56.59 3.24
56.23 3.54
12.33 14.11
12.59 14.36
11.56 13.23
11.80 13.02
11.46 13.11
11.31 13.27
12.06 13.80
12.22 13.60
11.33 12.97
11.03 13.01
11.25 12.85
11.07 12.76
11.71 13.40
11.40 13.11
10.92 12.50
10.95 12.21
14.28 16.34
14.38 16.42
15.85 13.85
16.07 13.66
12.03 18.35
12.25 18.19
11.07 16.90
11.08 17.21
10.95 16.71
11.04 16.91
11.81 13.51
11.99 13.41
11.10 12.71
11.11 12.65
11.07 12.60
11.00 12.37
13.01 14.90
13.29 15.20
12.16 13.92
12.02 13.80
12.05 13.79
11.98 13.65
13b
13c
14a
14b
14c
15a
15b
16
7.25
7.06
C
27H18N4O2S2
(494.59)
C
26H15ClN4OS2
(499.02)
7.11
7.30
C
27H18N4OS2
(478.59)
C27H17ClN4OS2
(513.05)
6.91
6.54
C
19H12N4O2S2
(392.46)
17
C
20H12N4O2S2
(404.47)
18a
18b
18c
19a
19b
19c
20a
20b
20c
21a
21b
21c
C
18H11N3OS2
(349.44)
C19H13N3O2S2
(379.46)
C
18H10ClN3OS2
(383.88)
9.24
9.06
C
24H18N4O3S2
(474.56)
C
25H20N4O4S2
(504.58)
C
24H17ClN4O3S2
6.97
7.10
(509.00)
C23H18N4OS2
(430.55)
C
24H20N4O2S2
(460.57)
C
23H17ClN4OS2
(464.99)
7.62
7.85
C
22H16N4O2S2
(400.53)
13.99
14.15
8.02
8.06
C23H18N4O3S2
(462.55)
22H15ClN4O2S2
12.11 13.86
12.03 13.60
11.99 13.73
12.25 13.80
C
7.59
7.70
(466.96)

Synthesis and Reactions of Some New Heterocyclic Compounds
1995
% Cl
TABLE I Melting Points, Yields, and Analytical Data of all Newly
Synthesized Compounds (Continued)
Calculated/found
m.p. (◦C)
yield (%)
Formula
(M.W.)
Compound
% C
% H
% N
% S
22
320/80
195/90
243/71
248/71
186/87
150/95
190/90
110/90
220/50
230/60
260/65
214/86
279/84
312/93
179/76
288/86
211/80
215/78
212/83
301/80
327/85
C19H12N4OS2
(376.46)
C20H14N6OS2
(402.50)
C23H16N4O3S2
(460.56)
C19H12N4OS3
(408.53)
60.62
60.28
57.40
57.11
59.99
60.21
55.86
55.93
55.85
55.43
57.28
57.21
56.00
56.12
52.49
52.55
61.87
61.83
60.14
60.14
56.32
56.12
61.34
61.12
63.81
63.66
69.15
69.00
62.45
62.73
61.52
61.31
65.97
65.93
72.50
72.45
66.61
66.74
69.95
70.22
65.11
65.30
3.21
3.41
3.37
3.62
3.50
3.38
2.96
2.88
3.67
3.80
2.99
2.59
3.22
3.11
2.45
2.66
8.17
3.12
3.45
3.25
2.63
2.25
3.43
3.65
3.21
3.11
3.79
3.97
4.15
4.56
3.61
3.39
3.59
3.57
3.81
3.88
3.27
3.33
3.96
3.87
3.24
2.99
14.88
14.84
20.08
20.08
12.17
11.89
23.55
23.75
11.33
11.40
18.55
18.35
17.19
17.09
17.00
17.11
12.03
12.09
11.07
11.14
10.95
11.16
7.95
8.01
7.44
7.23
9.31
9.14
9.10
9.23
14.35
14.56
4.53
4.52
3.52
3.91
3.24
3.40
9.06
17.03
17.16
15.32
15.14
13.92
13.66
31.71
31.12
19.45
19.43
16.99
17.11
15.74
15.84
15.57
15.35
18.35
18.40
16.90
17.10
16.70
16.90
18.20
18.38
17.04
17.00
14.20
13.93
13.89
13.78
16.42
16.60
20.74
20.77
16.14
16.31
14.85
14.91
13.83
13.93
12.88
12.85
23
24
25
26
C23H18N4O3S3
(494.62)
27a
27b
27c
29a
29b
29c
30
C
18H11N5OS2
(377.45)
C19H13N5O2S2
(407.47)
C18H10ClN5OS2
(411.90)
8.61
8.43
C
18H11N3OS2
(349.43)
C19H13N3O2S2
(377.46)
C
18H10ClN3OS2
(383.89)
9.24
9.12
C18H12N2O2S2
(352.44)
31
C20H12N2O2S2
(376.45)
32
C
26H17N3OS2
(451.56)
33
C24H19N3O3S2
(461.57)
34
C
20H14N4OS2
(390.48)
35
C17H11NOS2
(309.21)
36a
36b
37a
37b
C
24H15NOS2
(397.25)
C24H14ClNOS2
8.22
8.35
(431.74)
C
27H17N3OS2
(463.58)
9.01
8.44
8.60
C27H16ClN3OS2
(498.08)
7.13
7.09

1996
E. A. Bakhite et al.
1
OCH3), 1.2–1.4 (t, 3H, CH3 of ester) ppm. H NMR of 3c (CDCl3): δ =
7.0–7.5 (m, 8H: 4ArH’s, 3CH thienyl and CH pyridine), 3.9–4.2 (m, 4H,
SCH2 and OCH2), 1.0–1.2 (t, 3H, CH3 of ester) ppm.
Ethyl 3-Amino-4-aryl-6-(2-thienyl)thieno[2,3-b]pyridine-
2-carboxylates (4a–c)
Compounds 3a–c (20 mmol) were suspended in sodium ethoxide solu-
tion (0.05 g sodium in 30 ml abs. ethanol) and heated under reflux for
5 min. The solid that formed after cooling was collected and recrystal-
lized from ethanol-chloroform mixture to give yellow crystals of 4a–c.
1
IR: ν = 3490, 3390 (NH2), 1660 (C O) cm−1. H NMR of 4a (CDCl3):
δ = 7.67–6.68 (d, 1H, CH thienyl), 7.45–7.56 (m, 6H, 5ArH’s and CH
thienyl), 7.41 (s, 1H, CH pyridine), 7.11–7.13 (d, 1H, CH thienyl), 5.63
(br, 2H, NH2), 4.29–4.35 (q, 2H, OCH2), 1.35–13.39 (t, 3H, CH3 of ester)
ppm. 1H NMR of 4b (CDCl3): δ = 7.1–7.8 (m, 8H: 4ArH’s, 3CH thienyl
and CH pryidine), 5.8 (s, 2H, NH2), 4.2–4.5 (q, 2H, OCH2), 4.0 (s, 3H,
OCH3), 1.3–1.5 (t, 3H, CH3 of ester) ppm.
(4-Aryl-3-cyano-6-(2-thienyl)pyridin-2-ylthio)-
acethydrazides (5a–c)
A mixture of ester 3a–c (20 mmol) and hydrazine hydrate 99% (1.0 ml,
20 mmol) in ethanol (50 ml) was heated under reflux for 4 h. The pre-
cipitate thus formed while hot was collected and recrystallized from
chloroform-ethanol mixture as pale yellow crystals of 5a–c. IR: ν =
1
3420–3300, 3200–3100 (NHNH2), 2200 (C N), 1650 (C O) cm−1. H
NMR of 5a (DMSO-d6): δ = 9.4 (s, 1H, NH), 8.2 (d, 1H, CH thienyl),
7.4–8.0 (m, 7H: 5ArH’s, CH thienyl and CH pyridine), 7.2–7.3 (t, 1H,
CH thienyl), 4.3 (s, 2H, NH2), 4.0 (s, 2H, SCH2) ppm.
3-Amino-4-aryl-6-(2-thienyl)thieno[2,3-b]pyridine-
2-carbohydrazides (6a–c)
Method A
Compound 3a–c (20 mmol) and hydrazine hydrate 99% (5.0 ml,
100 mmol) were heated under reflux for 2 h. The reaction mixture was
triturated with ethanol (10 ml) and allowed to cool. The solid product
was collected and recrystallized from dioxane as canary yellow needles
of 6a–c. IR: ν = 3420, 3300 (NH2), 3250, 3150 (NHNH2), 1620 (C O)
1
cm−1. H NMR of 6a (DMSO-d6): δ = 9.2 (br, 1H, NH), 8.0 (d, 1H, CH
thienyl), 7.1–7.8 (m, 7 H, 4ArHs, 2 CH thienyl and CH pyridine), 6.0
(s, 2H, NH2 at C-3), 4.6 (br, 2H, NH2 of hydrazide), 3.9 (s, 3H, OCH3)

Synthesis and Reactions of Some New Heterocyclic Compounds
1997
ppm. MS of 6a: 366 (M+, 90%); 351 (M+-NH, 100%); 355 (M+-NHNH2,
100%); 333 (M+-NHNH2-H2, 100%); 306 (86%); 261(21%); 153 (16%);
44 (CS+, 16%).
Method B
To a solution of ester 4a–c (20 mmol) in absolute ethanol (50 ml),
hydrazine hydrate 99% (2 ml, 40 mmol) was added. The mixture was
refluxed for 2 h and then left to cool. The compounds which obtained
upon recrystallization were identical to those described in method A.
(3-Cyano-4-phenyl-6-(2-thienyl)pyridin-2-ylthio)acetic
Acid Azide (7)
To a cold solution of 5a (3.66 g, 10 mmol) in glacial acetic acid (25 ml),
sodium nitrite solution 10% (7.7 ml, 11 mmol) was added dropwise
with stirring during 5 mins at room temperature. The precipitate that
formed was collected, dried in air, and utilized in the next reaction with-
out purification. IR: ν = 2210 (C N), 2160 (N3), 1660 (C O) cm−1
.
Ethyl N-(3-cyano-4-pheny-6-(2-thienyl)pyridin-
2-ylthio)methylcarbamate (9)
Compound 7 (1.1 g, 3 mmol) was heated under reflux in abs. ethanol
(20 ml) for 2 h. The reaction mixture was then concentrated and left to
cool. The solid crystals were collected and recrystallized from ethanol
as pale yellow needles of 9. IR: ν = 3400 (NH), 2200 (C N), 1710 (C O)
1
cm−1. H NMR (CDCl3): δ = 7.2–8.3 (m, 9H: 5ArHs, 3 CH thienyl and
CH pyridine), 6.0 (br, 1H, NH), 5.2 (s, 2H, SCH2), 4.0–4.3 (q, 2H, OCH2),
1.1–1.4 (t, 3H, CH3) ppm.
Reaction of the Acid Azide 7 with Aniline
Compound 7 (0.75 g, 2 mmol) in aniline (5 ml) was gently refluxed
for 3 h. The reaction mixture was triturated with ethanol (10 ml) and
left to cool. The white precipitate which obtained upon recrystallization
from ethanol was identified as 3-cyano-4-phenyl-2-(N-phenyl)carbamo-
ylmethylthio-6-(2-thienyl)pyridine (10). IR: ν = 3300 (NH), 2210 (C N),
1660 (C O) cm−1. 1H NMR (DMSO-d6): δ = 10.7 (s, 1H, NH), 8.2 (d, 1H,
CH thienyl), 7.0–7.8 (m, 13H, 10ArHs, 2CH thienyl and CH pyridine),
4.3 (s, 2H, SCH2) ppm.
This compound was also prepared by refluxing a mixture of 2a (0.59 g,
2 mmol) and chloro-N-phenylacetamide (0.34 g, 2 mmol) in ethanol

1998
E. A. Bakhite et al.
(10 ml) containing sodium acetate trihydrate (0.41 g, 3 mmol) for 2 h;
yield: 0.74 g (86%).
N1-Arylmethylene-(3-cyano-4-phenyl-(2-thienyl)pyridin-
2-ylthio)acethydrazides (12a–c)
To a solution of acethydrazide 5a (3.66 g, 10 mmol) in ethanol (50 ml),
an ethanolic solution of aromatic aldehyde (10 mmol) was added. The
resulting mixture was heated under reflux for 4 h. The solid that formed
while hot was collected and recrystallized from dioxane to give yellow
crystals of 12a–c. IR: ν = 3390–3300 (NH), 2210 (C N), 1670 (C O)
cm−1. 1H NMR of 12b (DMSO-d6): δ = 9.2 (s, 1H, NH), 8.2–8.3 (m, 2H,
CH thienyl and N CH), 7.0–8.0 (m, 12H: 9ArHs, 2 CH thienyl and CH
pyridine), 4.8 (s, 2H, SCH2), 3.8 (s, 3H, OCH3) ppm.
3-Amino-N1-arylmethylene-4-aryl-6-(2-thienyl)thieno-
[2,3-b]pyridine-2-carbo-hydrazides (13a–c)
Method A
Compound 12a–c (10 mmol) in ethanol (30 ml) containing dissolved
sodium (0.05 g) was heated under reflux for 15 min. The solid that
formed was collected by filtration and recrystallized from ethanol-
chloroform mixture to give yellow needles of 13a–c. IR: ν =
3490, 3300 (NH2), 3150 (NH), 1620 (C O) cm−1. MS of com-
pound 13b: 485 (M+, 50%); 454 (M+-OCH3, 4%); 380 (M+-
C6H4OCH3, 10%); 351 (M+-N CHC6H4OCH3, 15%); 336 (M+-
NHN CHC6H4OCH3, 15%); 335 (M+-1-NHN CHC6H4OCH3, 100%);
308 (M+-CONHN CHC6H4OCH3, 42%); 77 (C6H5+, 5%); 44 (CS+, 15%).
Method B
A mixture of 6a (3.66 g, 10 mmol) and the respective aldehyde
(10 mmol) in ethanol (30 ml) was refluxed for 3 h and then left to cool.
The solid obtained upon recrystallization was identical in all aspects
with those described in method A (Yield, 78–83%).
3-Arylmethyleneamino-9-phenyl-7-(2-thienyl)pyrido-
[3ꢀ,2ꢀ:4,5]thieno[3,2-d]pyrimidine-4(3H)-ones (14a–c)
Method A
A mixture of 13a–c (2 mmol) and triethyl orthoformate (5 ml) in acetic
anhydride (10 ml) was heated under reflux for 5 h. and then allowed to
cool. The solid product was collected and recrystallized from ethanol as
pale yellow crystals of 14a–c. IR: ν = 1670 (C O) cm−1. 1H NMR of 14a

Synthesis and Reactions of Some New Heterocyclic Compounds
1999
(TFA) δ = 9.0 (s, 1H, CH N), 8.9 (s, 1H, CH pyrimidine), 7.4–8.4 (m,
14H, 10 ArHs: 3CH thienyl and CH pyridine) ppm. MS of compound
14a: 464 (M+, 36%); 360 ((M+-N CHC6H5, 100%); 305 (M+-CO-HCN,
33%); 106 (46%); 103 (C6H5CN+, 35%); 77 (C6H5+, 42%).
Method B
To a suspension of 22 (1.8 g, 5 mmol) and benzaldehyde (0.5 ml,
5 mmol) in ethanol (20 ml), few drops of piperidine were added. The
resulting mixture was refluxed for 6 h. The solid that formed while hot
was collected and recrystallized from ethanol to give 14a (Yield, 87%).
The products obtained by the two synthetic routes are identical in all
aspects.
3-Arylmethyleneamino-2-methyl-9-phenyl-7-
(2-thienyl)-pyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-d]pyrimidine-
4(3H)-ones (15a–c)
Compound 13a–c (2 mmol) in acetic anhydride (15 ml) were heated
under reflux for 4 h and left to cool. The precipitated solid was collected
and recrystallized from dioxane as pale yellow crystals of 15a–c. IR: ν =
1670 (C O) cm−1. 1H NMR of 15c (TFA): δ = 9.0 (s, 1H, N CH), 7.5–8.4
(m, 13H, 9ArHs, 3CH thienyl and CH pyridine), 2.9 (s, 3H, CH3) ppm.
MS of compound 15a: 478 (M+, 15%); 374 (M+-N CHC6H5, 100%); 103
(M+- C6H5CN, 12%).
3-Amino-9-phenyl-7-(2-thienyl)pyrido[3ꢀ,2ꢀ:4,5]thieno-
[3,2-d]pyrimidine-2,4(1H,3H)dione (16)
A mixture of 6a (0.72 g, 2 mmol) and urea (0.18 g, 3 mmol) in decalin
(15 ml) was heated under reflux for 4 h. The precipitate that formed
while hot was collected and recrystallized from ethanol-chloroform mix-
ture as buff crystals of 16. IR: ν = 3480, 3300 (NH2), 3200–2900 (NH),
1720–1660 (2C O) cm−1. MS: 392 (M+, 6%), 376 (M+-NH2, 23%), 361
(M+-NH2-NH, 9%), 333 (M+-NH2-NH-CO, 11%), 305 (M+-NH2-NH-
2CO, 11%), 129 (100%), 44 (CS+, 85%).
3-Formylamino-9-phenyl-7-(2-theinyl)pyrido[3ꢀ,2ꢀ:4,5]-
thieno[3,2-d]pyrimidin-4(3H)-one (17)
Compound 6a (0.72 g, 2 mmol) in formic acid 85% (20 ml) was refluxed
for 4 h. The cooled reaction mixture was diluted with water whereupon
a white solid precipitated. It was collected and crystallized from ethanol
to give 17. IR: ν = 3250 (NH), 1720 (C O), 1680 (C O) cm−1. 1H NMR

2000
E. A. Bakhite et al.
(DMSO-d6): δ = 8.6 (s, 1H, CH pyrimidine), 8.4 (s, 1H, NH), 8.1–8.2 (d,
1H, CH thienyl), 8.0 (s, 1H, CH pyridine), 7.8–7.9 (d, 1H, CH thienyl),
7.6–8.0 (m, 6H: ArHs and CHO), 7.3–7.5 (t, 1H, CH thienyl) ppm.
8-Aryl-6-(2-thienyl)-∆3-pyrazolino[3ꢀ,4ꢀ:4,5]thieno-
[2,3-b]pyridine-3-ones (18a–c)
Compound 6a–c (2 mmol) in glacial acetic acid (15 ml) was heated under
reflux for 8 h. The solid product thus formed while hot was collected and
recrystallized from ethanol to give pale yellow crystals of 18a–c. IR: ν =
3300, 3200 (2NH), 1620 (C O) cm−1. MS of compound 18a: 350 (M+ + 1,
26%); 349 (M+, 42%), 44 (CS+, 15%).
9-Aryl-3-diacetylamino-2-methyl-7-(2-thienyl)pyrido-
[3ꢀ,2ꢀ:4,5]thieno[3,2-d]pyrimidine-4(3H)-ones (19a–c)
A suspension of compound 6a–c (3 mmol) in acetic anhydride (20 ml)
was refluxed for 3 h. The reaction mixture was diluted with water
(20 ml) and allowed to stand at room temperature for 2 h. The pre-
cipitated solid was collected and recrystallized from ethanol as white
fine crystals of 19a–c. IR: ν = 1730 (2C O), 1700–1680 (C O) cm−1
.
1H NMR of 19a (CDCl3): δ = 7.4–7.9 (m, 8H: 5ArHs and 2CH thienyl
and CH pyridine), 7.2 (t, 1H, CH thienyl), 2.4 (s, 6H, 2XCOCH3), 2.1
(s, 3H, CH3) ppm. MS of 335a:475 (M+ + 1, 7%), 474 (M+, 88%), 389
(M+ − 1-2COCH3, 100%), 432 (M+ + 1-COCH3, 83%).
1-(3-Amino-4-aryl-6-(2-thienyl)thieno[2,3-b]pyridin-2-yl)-
carbonyl-3,5-dimethyl-1H-pyrazoles (20a–c)
A mixture of 6a–c (2 mmol) in acetylacetone (5 ml) was heated under
reflux for 6 h. The reaction mixture was triturated with ethanol (5 ml)
and then left to cool. The precipitated solid was collected by filtration
and recrystallized from ethanol to give yellow crystals of 16a–c. IR:
ν = 3490, 3330 (NH2), 1630 (C O) cm−1. 1H NMR of 20a (CDCl3): δ =
7.5–7.8 (m, 8H, 5ArHs, 2CH thienyl and CH pyridine), 7.1–7.3 (t, 1H,
CH thienyl), 6.7 (br, 2H, NH2), 6.0 (s, 1H, CH pyrazole), 2.7 (s, 3H, CH3
pyrazole), 2.4 (s, 3H, CH3 pyrazole) ppm. MS of compound 20a: 430 (M+,
70%), 431 (M+ + 1, 20%), 415 (M+-CH3, 1%), 333 (M+-dimethypyrazolyl
radical, 100%); 305 (M+-dimethylpyrazolylcarbonyl radical, 21%).
9-Aryl-3-ethoxymethyleneamino-7-(2-thienyl)pyrido-
[3ꢀ,2ꢀ:4,5]thieno[3,2-d]pyrimidine-4(3H)-ones (21a–c)
A mixture of 6a–c (2 mmol) and triethyl orthoformate (3 ml) in DMF
(10 ml) was refluxed for 6 h. The solid that formed on cooling was

Synthesis and Reactions of Some New Heterocyclic Compounds
2001
collected and recrystallized from DMF as orange crystals of 21a–c. IR:
1
ν = 1660 (C O) cm−1. H NMR of 21a (TFA): δ = 9.1 (s, 1H, N CH),
8.7 (s, 1H, CH pyrimidine), 7.3–8.2 (m, 9H: 5ArHs, 3CH thienyl and CH
pyridine), 7.4–7.5 (d, 1H, CH thienyl), 4.3–4.5 (q, 2H, OCH2), 1.2–1.5
(t, 3H, CH3) ppm. 1H NMR of 21c (TFA): δ = 9.0 (s, 1H, N CH), 8.7 (s,
1H, CH pyrimidine and CH pyridine), 8.1–8.5 (m, 3H, 2CH thienyl and
CH pyridine), 7.5–7.9 (m, 5H: 4ArHs and CH thienyl), 4.4–4.7 (m, 2H,
OCH2), 1.4–1.7 (t, 3H, CH3) ppm.
3-Amino-9-phenyl-7-(2-thienyl)pyrido[3ꢀ,2ꢀ:4,5]thieno-
[3,2-d]pyrimidine-4(3H)-one (22)
A mixture of 21a or 23 (3 mmol) and hydrazine hydrate (10 ml) was
heated under reflux for 4 h. The reaction mixture was triturated with
ethanol (5 ml) and then left to cool. The precipitated solid was collected
by filtration and recrystallized from ethanol-chloroform mixture as yel-
low crystals of 22. IR: ν = 3450, 3290 (NH2), 1660 (C O) cm−1. 1H NMR
(DMSO-d6): δ = 8.3 (s, 1H, CH pyrimidine), 7.1–8.2 (m, 9H: 5ArHs, 3CH
thienyl and CH pyridine), 6.0 (s, 2H, NH2) ppm.
3-Hydrazinomethyleneamino-9-phenyl-7-(2-thienyl)
pyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-d]pyrimidine-4(3H)-one (23)
To a suspension of compound 21a (0.4 g, 1 mmol) in dioxane (5 ml), hy-
drazine hydrate (1 ml) was added. The reaction mixture was stirred at
room temperature for 1 h. The formed precipitated was filtered, washed
with water, dried in air and recrysallized from dioxane as white needles
of 23. IR: ν = 3320, 3250 (NHNH2), 1650 (C O) cm−1
.
3-Diacetylamino-9-phenyl-7-(2-thienyl)-
pyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-d]pyrimidine-4(3H)-one (24)
A suspension of compound 22 (1.1 g, 3 mmol) in acetic anhydride (20 ml)
was refluxed for 3 h. The reaction mixture was diluted with water (20
ml) and allowed to stand at room temperature for 2 h. The precipi-
tated solid was collected and recrystallized from ethanol as white fine
1
crystals of 24. IR: ν = 1730 (2C=O), 1700–1680 (C O) cm−1. H NMR
(CDCl3): δ = 8.2 (s, 1H, CH pyrimidine), 7.8 (d, 1H, CH thienyl), 7.7 (s,
1H, CH pyridine), 7.2–7.6 (m, 7H: 5ArHs and 2CH thienyl), 2.4 (s, 6H,
2XCOCH3) ppm.

2002
E. A. Bakhite et al.
2-(3-Amino-4-phenyl-6-(2-thienyl)thieno[2,3-b]pyridin-
2-yl)-1,3,4-oxadiazole-5(4H)-thione (25)
A mixture of 6a (0.72 g, 2 mmol) and carbon disulphide (3 ml) in pyridine
(10 ml) was heated on a water bath for 8 h. The precipitate that formed
after cooling was collected and recrystallized from dioxane as yellow
crystals of 25. IR: ν = 3490–3390 (NH2), 3100 (NH) cm−1. MS: 410
(M+ + 2, 15%), 409 (M+ + 1, 23%), 408 (M+, 100%), 392 (M+-NH2, 16%).
2-(3-Amino-4-phenyl-6-(2-thienyl)thieno[2,3-b]pyridin-
2-yl)-5-ethoxycarbonyl methylthio-1,3,4-oxadiazole (26)
A mixture of 25 (0.81 g, 2 mmol), ethyl chloroacetate (0.22 ml, 2 mmol)
and sodium acetate trihydrate (0.41 g, 3 mmol) in ethanol (40 ml) was
heated under reflux for 2 h. The precipitate that formed was collected,
washed with water, dried in air, and recrsytallized from ethanol as
pale yellow crystals of 26. IR: ν = 3490–3300 (NH2), 1720 (C O) cm−1
.
1H NMR (CDCl3): δ = 7.4–7.8 (m, 9H: 5ArHs, 3CH thienyl and CH
pyridine), 5.5 (s, 2H, NH2), 4.2–4.4 (q, 2H, OCH2), 4.1 (s, 2H, SCH2),
1.2–1.5 (t, 3H, CH3) ppm.
3-Amino-4-aryl-6-(2-thienyl)thieno[2,3-b]pyridine-
2-carbonylazides (27a–c)
To a cold solution of 6a–c (5 mmol) in glacial acetic acid (25 ml), sodium
nitrite solution 100% (7.7 ml, 11 mmol) was added dropwise with stir-
ring during 5 min at room temperature. The formed precipitate was
collected, dried in air, and utilized in the next reaction without purifi-
cation. IR: ν = 3480, 3320 (NH2), 2120 (N3), 1680(CO) cm−1
.
4-Aryl-6-(2-thienyl)-1H-imidazolo[4ꢀ,5ꢀ:4,5]thieno[2,3-b]-
pyridine-2(3H)-ones (29a–c)
The acid azide 27a–c (3 mmol) was heated under reflux for 3 h in iso-
propyl alcohol (30 ml). The reaction mixture was cooled whereupon a
precipitate formed. It was collected and recrystallized from isopropyl al-
cohol as brown crystals of 29a–c. IR: ν = 3500, 2500 (NH), 1680 (C O)
cm−1. MS of 27a: 349 (M+,8%), 45 (HCS+, 100%).
3-Amino-4-phenyl-6-(2-thienyl)-thieno[2,3-b]pyridine-2-
carboxylic acid (30)
A suspension of 4a (3.8 g, 9 mmol) in ethanolic sodium hydroxide solu-
tion 10% (50 ml) was heated under reflux for 4 h and then allowed to
cool. The reaction mixture was diluted with 50 ml water, filtered, and

Synthesis and Reactions of Some New Heterocyclic Compounds
2003
then the clear filtrate was acidified with dilute acetic acid. The precipi-
tate was collected and crystallized from ethanol–chloroform mixture to
give yellow crystals of 30. IR: ν = 3490, 3350 (NH2), at 3200–3000 (OH),
1640 (C O) cm−1. 1H NMR (TFA): δ = 10.2 (s, 1H, CO2H); 7.1–8.2 (m,
9H: 5ArHs, 3CH thienyl and CH pyridine) ppm.
2-Methyl-9-phenyl-7-(2-thienyl)pyrido[3ꢀ,2ꢀ:4,5]-
thieno[3,2-d]oxazine-4-one (31)
Compound 30 (1.76 g, 5 mmol) in redistilled acetic anhydride (25 ml)
was heated under reflux for 4 h and then left to cool. The solid product
was collected by filtration and dried in air to give white needles of 31.
IR: ν = 1740 (C O) cm−1. 1H NMR (TFA): δ 7.3–8.5 (m, 9H: 5ArHs, 3CH
thienyl and CH pyridine); 2.4 (s, 3H, CH3) ppm.
3,9-Diphenyl-2-methyl-7-(2-thienyl)pyrido[3’,2’:4,5]-
thieno[3,2-d]pyrimidine-4(3H)-one (32)
A mixture of 31 (0.37 g, 1 mmol) and aniline (0.4 ml) in glacial acetic acid
(10 ml) was heated under reflux for 3 h. The reaction mixture was cooled
and diluted with water, whereupon a solid precipitated. It was collected
and crystallized from ethanol–chloroform mixture to give white needles
1
of 32. IR: ν = 1660 (C O) cm−1. H NMR (TFA): δ = 7.3–8.3 (m, 14H:
10ArHs, 3CH thienyl and CH pyridine); 2.4 (s, 3H, CH3) ppm.
3-Ethoxycarbonylmethyl-2-methyl-9-phenyl-7-
(2-thienyl)pyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-d]pyrimidine-
4(3H)-one (33)
Ethyl glycinate hydrochloride (0.69 g, 4 mmol) and sodium acetate
(0.5 g) were refluxed in acetic acid (20 ml) for 1 h, the precipitated
sodium chloride was filtered off, compound 31 (0.75 g, 2 mmol) was
added to the filtrate, and it was further refluxed for 3 h. The cooled
reaction mixture was diluted with water and the precipitated solid was
collected to give 33. IR: ν = 1730 (C O, ester), 1660 (C O, pyrimidi-
none) cm−1. 1H NMR spectrum (TFA): δ = 7.1–8.2 (m, 9H; 5 ArHs, 3 CH
thienyl and CH pyridine), 4.9 (s, 2H, NCH2), 4.2–4.4 (q, 2H, OCH−2),
2.4 (s, 3H, CH3 at C-2), 1.2–1.4 (t, 3H, CH3 of ester) ppm.
3-Amino-2-methyl-9-phenyl-7-(2-thienyl)pyrido-
[3ꢀ,2ꢀ:4,5]thieno[3,2-d]pyrimidine-4(3H)-one (34)
A mixture of oxazinone 31 (0.75 g, 2 mmol) and hydrazine hydrate 99%
(0.5 ml, 10 mmol) in ethanol (20 ml) was refluxed for 2 h. The product
that formed was collected and recrystallized from ethanol to give white

2004
E. A. Bakhite et al.
needles of 34. IR: ν = 3300–3200 (NH2); 1660(C O, pyrimidinone) cm−1
.
1H NMR (DMSO-d6): δ = 7.0–7.5 (m, 9H: 5 ArHs, 3CH thienyl and CH
pyridine), 6.0 (s, 2H, NH2), 2.3 (s, 3H, CH3 at C-2) ppm. MS: m/z = 390.4
(M+, 100%), 361 (M+-NH2 CH3, 100%), 77 (C6H5+, 6%).
Reaction of Compound 30 with Orthophosphoric Acid:
Formation of 4-Phenyl-6-(2-thienyl)thieno-
[2,3-b]pyridine-3(2H)-one (35)
A solution of 30 (1.41 g, 4 mmol) in orthophosphoric acid 85% (30 ml)
was heated on a water bath for 8 h. The reaction mixture was poured
onto ice-water (60 ml), whereupon a solid product precipitated. It was
collected by filtration, dried in air, and crystallized from benzene to give
1
35 as pale yellow crystals. IR: ν = 1680 (C O) cm−1. H NMR (TFA):
δ = 8.1–8.2 (d, 1H, CH thienyl), 7.9 (s, 1H, CH pyridine), 7.5–7.7 (m,
6H: 5 ArHs and CH thienyl), 6.9–7.1(t, 1H, CH thienyl), 4.4 (s, 2H,
SCH2) ppm.
Reaction of Compound 35 with Aromatic Aldehydes:
Formation of Chalcones 36a,b
To a mixture of 35 (0.62 g, 2 mmol) and the respective aromatic alde-
hyde (2 mmol) in ethanol (15 ml) a few drops of piperidine were added.
The resulting mixture was heated under reflux for 1 h. The precipitate
was collected and recrystallized from chloroform to give yellow crystals
of 36a,b. IR: ν = 1680 (C O) cm−1. MS of 36a: m/z = 397 (M+, 41%);
396 (M+-1, 24%), 28 (CO+, 100%).
2-Amino-4-aryl-9-phenyl-7-(2-thienyl)-4H-pyrano-
[2ꢀ,3ꢀ:4,5]thieno[2,3-b] pyridine-3-carbonitriles (37a,b)
Method A
To a mixture of 35 (1.24 g, 4 mmol) and the respective arylmethylen-
emalononitrile (4 mmol) in ethanol (25 ml) a few drops of piperidine
were added. The reaction mixture was heated under reflux for 2 h. The
precipitate that formed was collected by filtration while hot and recrys-
tallized from dioxane as yellow crystals of 37a,b. IR: ν = 3400, 3300,
3200 (NH2), 2200 (C N), 1640 (C N) cm−1. MS of 37b: m/z = 497.08
(M+, 4%), 431 (M+-CN-C CNH2, 100%).
Method B
To a mixutre of 36a,b (3 mmol) and malononitrile (3 mmol) in ethanol
(20 ml), few drops of piperidine were added. The mixture was refluxed
for 1 h. The solid that formed was collected and recrystallized to give

Synthesis and Reactions of Some New Heterocyclic Compounds
2005
37a,b in 67–71% yield. These compounds were identical in all aspects
to those described in method A.
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