Studies on the synthesis of some new cyanopyridine-thione and thieno[2,3-b]pyridine derivatives

Article abstract of DOI:10.1080/10426500601096369

The work included in this article involves the synthesis of new cyanopyridinethiones as good synthons for new thieno[2,3-b]pyridines with anticipated biological activities. Thus, the reaction of -aryl - thiocarbamoylacrylonitrile (1a-c) with (2-thenoyl)-,-trifluoroacetone led to an unexpected formation of 4-aryl-3-cyano-6-(2-thienyl)pyridine-2(1H)-thiones (4a-c). In contrast, the reaction of 1a,b with ethyl acetoacetate produced 4-aryl-3-cyano-5-ethoxycarbonyl-6-methylpyridine-2(1H)-thiones (12a,b). The reaction of compound 4a with methyl iodide gave 2-methylthio derivative 6, which upon treatment with hydrazine hydrate furnished pyrazolopyridine 7. Treatment of 4a-c with chloroacetaimde, in the presence of sodium ethoxide, led to the formation of 3-amino-4-aryl-6-(2-thienyl)thieno[2,3-b]pyridine-2-carboxamides (8a-c). The reactions of 8a with some aromatic aldehydes and/or cycloalkanones were carried out and their products were identified. Compounds 12a,b were reacted with chloro-N-arylacetamides to give ethyl 4-aryl-2-(N-aryl) carbamoylmethylthio-3-cyano-6-methylpyridine-5-carboxylates (13a-j). Upon treatment of compounds 13a-j with sodium alkoxide in alcohol, they underwent an intramolecular Thorpe-Ziegler cyclization to furnish ethyl 3-amino-4-aryl-2-(N- aryl)carbamoyl-6-methylthieno[2,3-b]pyridine-5-carboxylates (14a-j). Compounds 14a-j, in turn, were reacted with triethyl orthoformate and/or carbon disulfide to give corresponding pyridothienopyrimidinone derivatives 15a-j and 18. Pyridothienotriazinone analogs 17a-j were synthesized via diazotisation of compounds 14a-j.

Full text of DOI:10.1080/10426500601096369

Phosphorus, Sulfur, and Silicon, 182:1061–1082, 2007
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500601096369
Studies on the Synthesis of Some New
Cyanopyridine-Thione and Thieno[2,3-b]pyridine
Derivatives
Omima S. Mohamed
Chemistry Department, Assiut University, Assiut, Egypt
Elham A. Al-Taifi
Chemistry Department, Sana’a University, Yemen
Talaat I. El-Emary
Etify Abdel-Ghafar Bakhite
Chemistry Department, Assiut University, Assiut, Egypt
The work included in this article involves the synthesis of new cyanopy-
ridinethiones as good synthons for new thieno[2,3-b]pyridines with anticipated
biological activities. Thus, the reaction of β–aryl-α-thiocarbamoylacrylonitrile
(1a–c) with (2-thenoyl)-ω,ω,ω-trifluoroacetone led to an unexpected formation of
4-aryl-3-cyano-6-(2-thienyl)pyridine-2(1H)-thiones (4a–c). In contrast, the reac-
tion of 1a,b with ethyl acetoacetate produced 4-aryl-3-cyano-5-ethoxycarbonyl-6-
methylpyridine-2(1H)-thiones (12a,b). The reaction of compound 4a with methyl
iodide gave 2-methylthio derivative 6, which upon treatment with hydrazine hy-
drate furnished pyrazolopyridine 7. Treatment of 4a–c with chloroacetaimde,
in the presence of sodium ethoxide, led to the formation of 3-amino-4-aryl-6-
(2-thienyl)thieno[2,3-b]pyridine-2-carboxamides (8a–c). The reactions of 8a with
some aromatic aldehydes and/or cycloalkanones were carried out and their prod-
ucts were identified. Compounds 12a,b were reacted with chloro-N-arylacetamides
to give ethyl 4-aryl-2-(N-aryl)carbamoylmethylthio-3-cyano-6-methylpyridine-5-
carboxylates (13a–j). Upon treatment of compounds 13a–j with sodium alkox-
ide in alcohol, they underwent an intramolecular Thorpe-Ziegler cyclization to
furnish ethyl 3-amino-4-aryl-2-(N-aryl)carbamoyl-6-methylthieno[2,3-b]pyridine-
5-carboxylates (14a–j). Compounds 14a–j, in turn, were reacted with triethyl ortho-
formate and/or carbon disulfide to give corresponding pyridothienopyrimidinone
derivatives 15a–j and 18. Pyridothienotriazinone analogs 17a–j were synthesized
via diazotisation of compounds 14a–j.
Keywords Cyanopyridinethiones; pyridothienopyrimidines; pyridothienotriazines;
thienopyridines
Received July 27, 2006; accepted October 12, 2006.
Address correspondence to Etify A. Bakhite, Chemistry Department, Faculty of Sci-
ence, Assiut, University, Assiut 71516, Egypt. E-mail: ebakhite@yahoo.com
1061

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O. S. Mohamed et al.
INTRODUCTION
The biological activities of condensed pyrimidines as sedatives,
antibacterials, and antimalarials are well documented.1,2 Numer-
ous thieno[2,3-b]pyridines have been investigated in relation with
their biological and pharmacological activities. Some of them
proved to possess antibacterial,3,4 antiviral,5 antihypertensive,6 and
immunostimulating7 activities. Others are useful as gonadtropin-
releasing hormone antagonists8−13 and as lipoxygenases inhibitors.14
Recently, certain thieno[2,3-b] pyridine derivatives were prepared
as antinflammatory agents, particularly for treating arthritis and
bone–resorption inhibiting agents.15 Pyridothienopyrimidine deriva-
tives have found applications as analgesics,16 antipyretics,17 and
anti-inflammatories.18 In view of all these facts and as a con-
tinuation of work on the synthesis of new condensed thieno[2,3-
b]pyridines,19−22 we undertook the synthesis and reactions of the ti-
tle compounds, which might have shown good biological and medicinal
applications.
RESULTS AND DISCUSSION
Our approach to the synthesis of the target compounds started from
the reaction of β–aryl-α-thiocarbamoylacrylonitriles (1a–c) with (2-
thenoyl)-ω,ω,ω-trifluoro-acetone in boiling ethanol containing a cat-
alytic amount of piperidine, which gave orange crystalline products. The
structure of them was assigned as 4-aryl-3-cyano-6-(2-thienyl)pyridine-
2(1H)-thiones (4a–c) rather than the others, 2a–c and 3a–c. The
latter assignment was based on elemental and spectral analyses
(Scheme 1).
The pathway of the latter reaction may have involved a Michael ad-
dition of cyanothioacetamide on the activated double bond of 1a–c to
give intermediate A, which, in turn, underwent enolization, deacyla-
tion, cyclodehydration, and spontaneous dehydrogenation to afford tar-
get compounds 4a–c 23,24 (Scheme 2).
The structural formulas of compounds 4a–c were confirmed by
comparison with authentic samples prepared according to our re-
ported method22 by reaction of chalcones 5a–c with cyanothioacetamide
(Scheme 2).
The reaction of 3-cyano-4-phenyl-6-(2-thienyl)pyridine-2(1H)-thione
(4a) with methyl iodide, in the presence of sodium acetate, gave the
corresponding 2-methylthio derivative 6. Heating compound 6 with hy-
drazine hydrate under a neat condition furnished pyrazolopyridine 7
(Scheme 3).

Cyanopyridinethione Pyridine Derivatives
1063
SCHEME 1
The reactivity of compounds 4a–c as bifunctions was test through
a reaction with chloroacetamide in the presence of sodium ethoxide
wherein 3-aminothieno[2,3-b]pyridines 8a–c were obtained (Scheme 3).
The characterization data of compounds 8a–c were in agreement
with those reported before by us.21
Heating o-aminoamide 8a with some aromatic aldehydes in ethanol
containing a few drops of acetic acid afforded the corresponding

1064
O. S. Mohamed et al.
SCHEME 2
tetrahdyropyridothienopyrimidinones 9a–c. Upon treatment of 8a with
cyclopentanone or cyclohexanone under the same conditions, the prod-
ucts were identified as spiro compounds 10a,b rather than Schiff’s
bases 11a,b25(Scheme 4).

Cyanopyridinethione Pyridine Derivatives
1065
SCHEME 3
SCHEME 4

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O. S. Mohamed et al.
In contrast, the reaction of β–aryl-α-thiocarbamoylacrylonitriles
(1a,b) with ethyl acetoacetate, by refluxing in ethanol containing a
catalytic amount of piperidine, gave a good yield of 4-aryl-3-cyano-5-
ethoxycarbonyl-6-methylpyridine-2(1H)-thiones (12a,b)25 (Scheme 5).
SCHEME 5
The reaction of 12a,b with chloro-N-arylacetamides in ethanol,
in the presence of sodium acetate, as a basic catalyst, gave ethyl
4-aryl-2-(N-aryl)carbamoylmethylthio-3-cyano-6-methyl-pyridine-5-
carboxylates (13a–j). Upon treatment of products 13a–i with sodium
ethoxide in ethanol, they underwent intramolecular Thorpe-Ziegler
cyclization to furnish ethyl 3-amino-4-aryl-2-(N-aryl)carbamoyl-6-
methylthieno[2,3-b]pyridine-5-carboxylates (14a–j). Similarly, cycliza-
tion of compound 13j to the corresponding thienopyridine 14j was
achieved by using sodium methoxide in boiling methanol. The latter
thienopyridines 14a–j were also prepared via direct reaction of 12a,b
with the respective chloroacetamide derivative in the presence of the
appropriate sodium alkoxide as a basic catalyst (Scheme 6).
Compounds 14a–j seem to be good synthons for other new con-
densed thienopyridines. Thus, the cyclocondensation of 14a–j with
triethyl orthoformate in the presence of acetic anhydride afforded
pyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-d]pyrimidine-4(3H)-ones (15a–j). The reac-
tivity of the acetyl group of compound 15g was tested via its
condensation with phenylhydrazine or thiosemicarbazide where the
corresponding condensation products 16a,b were obtained in a nearly
quantitative yield. Triazinone derivatives 17a–j were prepared by
diazotisation of 14a–j using sodium nitrite and an acetic acid–sulfuric
acid mixture at a low temperature. The interaction of 14a with carbon

Cyanopyridinethione Pyridine Derivatives
1067
SCHEME 6
disulfide in hot pyridine resulted in the formation of thioxopyrimidi-
none derivative 18. Methylthiopyrimidine derivative 19 was synthe-
sized through the reaction of 18 with methyl iodide in the presence of
sodium hydroxide (Scheme 7).
In conclusion, 3-cyanopyridine-2(1H)-thiones 4a–c and 12a–c that
were investigated are good starting materials to synthesize 1,3-diamino
compounds 8a–c and 3-aminoimine derivatives 14a–j. Compounds 8a
and 14a–j, in turn, were used as precursors to construct pyridothienopy-
rimidine and pyridothienotriazine systems.
The structures of all newly synthesized compounds were confirmed
by elemental analyses, IR, 1H NMR, and mass spectral data.
EXPERIMENTAL
All melting points are uncorrected and were measured on a Gallan-
Kamp apparatus. IR spectra: Shmiadzu 470 IR-spectrophotometer

1068
O. S. Mohamed et al.
SCHEME 7
(KBr; υmax in cm−1). 1H NMR spectra: Varian EM-390, 90 MHz 1H NMR
spectrometer using TMS as an internal standard (δ in ppm); MS: Jeol
JMS-600; elemental analyses: Elementar Analysensystem GmbH VAR-
IOEL V2.3 July 1998 CHNS Mode; their results were in good agreement
with the calculated values.
Reaction of β-aryl-α-thiocarbamoylacrylonitrile (1a–c) with
(2-thenoyl)-ω,ω,ω-trifluoroacetone; General procedure
To a mixture of β–aryl-α-thiocarbamoylacrylonitrile (1a–c) (10 mmol)
and (2-thenoyl)-ω,ω,ω-trifluoroacetone (2.22 g, 10 mmol) in ethanol
(20 mL), a few drops of piperidine were added. The reaction mixture

Cyanopyridinethione Pyridine Derivatives
1069
was refluxed for 3 h and then left to cool. The solid that formed was
collected and recrystallized from acetic acid to give orange crystalline
compounds. The structure of them was assigned as 4-aryl-3-cyano-6-(2-
thienyl)pyridine-2(1H)-thiones (4a–c).
3-Cyano-4-phenyl-6-(2-thienyl)pyridine-2(1H)-thione (4a)
Prepared from 1a. Yield: 63%; m.p. 246◦C, (Lit. m.p. 245◦C). Anal. calcd.
for C16H10N2S2(294.4): C, 65.28; H, 3.42; N, 9.52; S, 21.78%. Found: C,
65.45; H, 3.19; N, 9.30; S, 21.54%.
4-(4-Chlorophenyl)-3-cyano-6-(2-thienyl)pyridine-2(1H)-thione
(4b)
Prepared from 1b. Yield: 72%; m.p. 242◦C, (Lit. m.p. 242◦C). Anal. calcd.
for C16H9ClN2S2(329.9): C, 58.44; H, 2.76; N, 8.52; S, 19.50; Cl, 10.78%.
Found: C, 58.58; H, 3.01; N, 8.26; S, 19.78; Cl, 10.64%.
3-Cyano-4-(4-methoxyphenyl)-6-(2-thienyl)pyridine-2(1H)-
thione (4c)
Prepared from 1c. Yield: 75%; m.p. 253◦C, (Lit. m.p. 250◦C). Anal. calcd.
for C17H12N2OS2(324.4): C, 62.94; H, 3.73; N, 8.63; S, 19.77%. Found:
C, 63.13; H, 3.81; N, 8.26; S, 19.55%.
Synthesis of 4-aryl-3-cyano-6-(2-thienyl)pyridine-2(1H)-thione
(4a–c)
To a solution of chalcone 5a–c (10 mmol) and cyanothioacetamide (1.0
g, 10 mmol) in ethanol (30 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
of 4a–c (yield: 43–62%). These products were identical in all aspects to
those previously described.
Synthesis of 3-cyano-2-methylthio-4-phenyl-6-
(2-thienyl)pyridine (6)
A mixture of 4a (2.94 g, 10 mmol), methyl iodide (10 mmol), and sodium
acetate trihydrate (1.4 g, 10 mmol) in ethanol (20 mL) was heated under
reflux for 1 h. The precipitate that formed on cooling was collected and
recrystallized from ethanol as pale yellow needles of 6, yield: 2.5 g (81%);

1070
O. S. Mohamed et al.
m.p. 140–141◦C. Anal. calcd. for C17H12N2S2 (308.4): C, 66.20; H, 3.92;
N, 9.08; S, 20.79%. Found: C, 66.38; H, 3.87; N, 9.03; S, 20.91%.
Synthesis of 3-amino-4-phenyl-6-(2-thienyl)-
lH-pyrazolo[3,4-b]pyridine (7)
Compound 6 (1.54 g, 5 mmol), in an excess amount of hydrazine hy-
drate (5 mL, 100 mmol), was heated under reflux for 4 h. The reaction
mixture was triturated with ethanol (10 mL) and left to cool. The precip-
itated solid was collected and recrystallized from ethanol to give yellow
fine needles of 7, yield: 1.1 g (75%); m. p: 243–244◦C. Anal. calcd. for
C16H12N4S (292.3): C, 65.73; H, 4.14; N, 19.16; S, 10.97%. Found: C,
65.50; H, 4.11; N, 19.32; S, 11.20%.
Synthesis of 3-amino-4-aryl-6-(2-thienyl)thieno[2,3-b]pyridine-
2-carboxamides (8a–c): General Procedure
To a solution of compound 4a–c (10 mmol) in sodium ethoxide solu-
tion (0.35 g sodium in 40 mL abs. ethanol), chloroacetamide (0.94 g,
10 mmol) was added. The reaction mixture was refluxed for 20 min and
then left to cool. The precipitated product was collected and recrystal-
lized from an ethanol-chloroform mixture to give compounds 8a–c.
3-Amino-4-phenyl-6-(2-thienyl)thieno[2,3-b]pyridine-2-
carboxamide (8a)
Prepared from 4a. Yield: 78%; m.p. 235–238◦C. Anal. calcd. for
C18H13N3OS2(351.4): C, 61.51; H, 3.73; N, 11.96; S, 18.25%. Found: C,
61.68; H, 3.91; N, 11.66; S, 17.98%.
3-Amino-4-(4-chlorophenyl)-6-(2-thienyl)thieno[2,3-b]pyridine-
2-carboxamide (8b)
Prepared from 4b. Yield: 76%; m.p. 240–243◦C. Anal. calcd. for
C18H12ClN3OS2(385.9): C, 56.10, H, 3.11; N, 10.90; S, 16.62; Cl, 9.09%.
Found: C, 55.71; H, 3.26; N, 11.15; S, 16.82; Cl, 9.25%.
3-Amino-4-(4-methoxyphenyl)-6-(2-thienyl)thieno[2,3-b]-
pyridine-2-carboxamide (8c)
Prepared from 4c. Yield: 83%; m.p. 231◦C. Anal. calcd. for
C19H15N3O2S2(381.4): C, 59.82; H, 3.96; N, 11.02; S, 16.81%. Found:
C, 59.74; H, 4.11; N, 11.12; S, 16.79%.

Cyanopyridinethione Pyridine Derivatives
1071
Synthesis of 2-Aryl-9-phenyl-7-(2-thienyl)-4-oxo-1,2,3,4-
tetrahydropyrido[3’,2’: 4,5]thieno[3,2-d]pyrimidines (9a-c).
General Procedure
To a mixture of 8a (0.7 g, 2 mmol) and the respective aldehyde (0.002
mol) in ethanol (20 mL), a few drops of glacial acetic acid was added.
The reaction mixture was heated under reflux for 3 h. The product that
formed was collected and recrystallized from chloroform to give yellow
crystals of 9a–c.
2,9-Diphenyl-7-(2-thienyl)-4-oxo-1,2,3,4-tetrahydropyrido-
[3’,2’:4,5]thieno[3,2-d] pyrimidines (9a)
This compound was prepared by using benzaldehyde, yield 80%; m.p.
292–293◦C. Anal. calcd. for C25H17N3OS2(439.55): C, 68.31; H, 3.90; N,
9.56; S, 14.59%. Found: C, 68.12; H, 3.77; N, 9.53; S, 14.70%.
2-(4-Chlorophenyl)-9-phenyl-7-(2-thienyl)-4-oxo-1,2,3,4-
tetrahydropyrido[3’,2’: 4,5]thieno[3,2-d]pyrimidines
(9b)
This compound was prepared by using 4-chlorobenzaldehyde, yield:
90%; m.p. 295–296◦C. Anal. calcd. for C25H16ClN3OS2(473.99): C, 63.53;
H, 3.40; N, 8.68; S, 13.53%. Found: C, 63.35; H, 3.36; N, 8.42; S,
13.78%.
2-(4-Methoxyphenyl)-9-phenyl-7-(2-thienyl)-4-oxo-1,2,3,4-
tetrahydropyrido [3’,2’: 4,5]thieno[3,2-d]pyrimidines (9c)
This compound was prepared by using 4-methoxybenzaldehyde, yield
88%; m.p. 287–288◦C. Anal. calcd. for C26H19N3O2S2(469.58): C, 66.50;
H, 4.08; N, 8.95; S, 13.66%. Found: C, 66.38; H, 4.18; N, 9.18; S,
13.37%.
Reaction of 8a with Cyclopentanone or Cyclohexanone, the
Formation of Spiro Compounds 10a,b: General Procedure
A mixture of 8a (0.7 g, 2 mmol) and cyclopentanone or cyclohexanone
(0.002 mol) in ethanol (20 mL) containing a few drops of glacial acetic
acid was heated under reflux for 3 h. The product that formed was
collected and recrystallized from ethanol to give yellow needles of
10a,b.

1072
O. S. Mohamed et al.
9-Phenyl-7-(2-thienyl)-4-oxo-1,2,3,4-tetrahydro-2,2-
tetramethylene-pyrido[3’,2’: 4,5]thieno[3,2-d]pyrimidine (10a)
This compound was prepared using cyclopentanone, yield: 83%; m.p.
261–262◦C. Anal. calcd. for C23H19N3OS2 (417.55): C, 66.16; H,
4.59; N, 10.06; S, 15.36%. Found: C, 66.00; H, 4.69; N, 10.23; S,
15.11%.
9-Phenyl-7-(2-thienyl)-4-oxo-2,2-pentamethylene-1,2,3,4-
tetrahydropyrido[3’,2’: 4,5]thieno[3,2-d]pyrimidine (10b)
This compound was prepared using cyclohexanone, yield: 80%; m.p.
287–288◦C. Anal. calcd. for C24H21N3OS2(431.57): C, 66.79; H, 4.90; N,
9.74; S, 14.86%. Found: C, 66.54; H, 4.97; N, 9.55; S, 14.67%.
4-Aryl-3-cyano-5-ethoxycarbonyl-6-methylpyridine-2(1 H)-
thiones (12a,b)
These compounds were prepared according to the reported method.25
Synthesis of ethyl 4-aryl-2-(N-aryl)carbamoylmethylthio-3-
cyano-6-methyl-pyridine-5-carboxylates (13a–j)
To a suspension of compound 12b (5 mmol) and sodium acetate tri-
hydrate (3.0 g, 22 mmol) in ethanol (50 mL), the respective chloro-N-
arylacetamide (20 mmol) was added. The resulting mixture was heated
under reflux for 2 h. The precipitate that formed on cooling was col-
lected and recrystallized from ethanol as white needles of 13a–j. Melt-
ing points, yields, and analytical data of these compounds are given in
Table I.
Synthesis of Ethyl 3-amino-4-aryl-2-(N-aryl)carbamoyl–6-
methylthieno[2,3-b] pyridine-5-carboxylates (14a–i)
Method A
Compounds 13a–i (10 mmol) were suspended in sodium ethoxide
solution (0.12 g sodium in 30 mL abs. ethanol) and heated under re-
flux for 5 mins. The solid that formed after cooling was collected and
recrystallized from ethanol as canary yellow crystals of 14a–i. Melt-
ing points, yields, and analytical data of these compounds are given in
Table I.
Method B
To a suspension of compound 12a,b (10 mmol) in sodium ethox-
ide solution (0.35 g sodium in 40 mL abs. ethanol), the respective

Cyanopyridinethione Pyridine Derivatives
1073
TABLE I Melting Points, Yields, and Analytical Data of Compounds
13a–j, 14a–j, 15a–j, 16a,b, 17a–j, 18, and 19
Calculated/Found (%)
M.P., ◦C,
Yield, %
Formula
(M.W.)
Compound
C
H
N
S
Cl
13a
139–140
88
157–158
85
171–172
90
125–126
86
C24H20ClN3O3S
(465.96)
61.87
61.93
60.54
60.24
61.47
61.32
65.06
65.19
4.33
4.15
4.47
4.45
4.36
4.24
5.02
4.91
9.02
9.34
8.47
8.52
8.27
8.19
9.10
9.00
6.88
6.58
6.46
6.39
6.31
6.48
6.95
6.88
7.61
7.70
7.15
6.80
6.98
6.77
13b
13c
13d
C25H22ClN3O4S
(495.98)
C26H22ClN3O4S
(507.99)
C25H23N3O4S
(461.54)
+
13e
150–151
91
155–156
87
168–169
90
125–126
92
148–149
85
153–154
85
175–176.
94
184–185
95
239–240
90
158–159
92
175–176
94
172–173
95
204–204
93
194–195
96
189–190
95
210–211
90
C
C
C
C
C
26H25N3O4S
(475.56)
26H25N3O5S
(491.56)
27H25N3O5S
(503.57)
25H22ClN3O4S
(495.98)
28H27N3O6S
(533.60)
65.67
65.77
63.53
63.56
64.40
64.14
60.54
60.29
63.03
62.78
62.42
62.31
61.87
62.13
60.54
60.45
61.47
61.55
65.06
65.08
65.67
65.40
63.53
63.70
64.40
64.37
60.54
60.29
63.03
62.78
62.42
62.40
63.09
63.16
5.30
5.14
5.13
5.34
5.00
5.19
4.47
4.30
5.10
5.15
4.85
4.96
4.33
4.35
4.47
4.37
4.36
4.34
5.02
5.21
5.30
5.18
5.13
5.33
5.00
5.23
4.47
4.58
5.10
5.15
4.85
506
8.84
8.52
8.55
8.71
8.34
8.22
8.47
8.41
7.87
8.11
8.09
8.22
9.02
8.91
8.47
8.28
8.27
8.44
9.10
8.93
8.84
9.02
8.55
8.34
8.34
8.60
8.47
8.60
7.87
8.11
8.09
8.01
8.83
8.75
6.74
6.59
6.52
6.35
6.37
6.36
7.15
7.33
6.01
6.90
6.17
6.19
6.88
6.97
6.46
6.31
6.31
6.19
6.95
7.06
6.74
6.89
6.52
6.71
6.37
6.57
7.15
7.12
6.01
6.90
6.17
6.00
6.74
6.78
13f
13g
13h
13i
13j
C27H25N3O6S
(519.57)
14a
14b
14c
14d
14e
14f
14g
14h
14i
C
C
C
24H20ClN3O3S
7.61
7.92
7.15
7.22
6.98
7.12
(465.96)
25H22ClN3O4S
(495.98)
26H22ClN3O4S
(507.99)
C25H23N3O4S
(461.54)
C
C
C
C
26H25N3O4S
(475.56)
26H25N3O5S
(491.56)
27H25N3O5S
(503.57)
25H22ClN3O4S
(495.98)
C28H27N3O6S
(533.60)
C27H25N3O6S
(519.57)
C25H18ClN3O3S
(475.95)
14j
15a
215–216
87
3.81
3.94
7.54
7.20
(Continued on next page)

1074
O. S. Mohamed et al.
TABLE I Melting Points, Yields and Analytical Data of Compounds
13a–j, 14a–j, 15a–j, 16a,b, 17a–j, 18, and 19 (Continued)
Calculated/Found (%)
M.P., ◦C,
Compound Yield, %
Formula
(M.W.)
C
H
N
S
Cl
15b
15c
15d
15e
15f
15g
15h
15i
15j
231–232
84
208–209
84
230–232
85
242–243
86
236–237
85
185–186
80
186–187
84
195–196
89
180–181
86
265–266
80
281–282
84
180–181
81
188-189
83
197–198
80
228–229
82
197–198
80
198–199
86
164–165
82
174–175
80
170–171
85
173–174
86
267–268
C26H20ClN3O4S
(505.98)
61.72
61.75
62.61
62.35
66.23
66.00
66.79
66.89
64.66
64.42
65.48
65.63
61.72
61.66
64.08
64.32
63.51
63.66
67.66
67.51
59.38
59.13
60.44
60.19
59.23
59.01
60.17
60.36
63.55
63.20
64.18
64.09
62.14
62.41
63.02
62.74
59.23
59.27
61.76
61.46
61.12
61.33
59.17
59.08
59.88
59.60
3.98
4.11
3.89
3.80
4.49
4.51
4.77
4.34
4.62
4.91
4.51
4.24
3.98
4.91
4.64
4.30
4.38
4.40
4.81
4.85
4.44
4.36
3.59
3.50
3.78
3.73
3.69
3.71
4.27
4.21
4.56
4.59
4.41
4.55
4.31
4.38
3.78
3.52
4.44
4.67
4.18
4.02
3.55
3.68
3.84
3.91
8.30
8.16
8.11
8.16
8.91
8.53
8.65
8.90
8.38
8.49
8.18
8.50
8.30
8.12
7.73
7.59
6.34
6.70
6.19
6.09
6.80
6.92
6.60
6.79
6.39
6.22
6.24
6.40
6.34
6.63
5.90
5.78
6.05
5.82
5.31
5.00
10.92
10.71
6.72
6.56
6.32
6.25
6.18
6.00
6.79
6.56
6.59
6.44
6.38
6.30
6.23
6.00
6.32
6.49
5.89
5.70
6.04
5.80
12.62
12.73
12.28
12.19
7.01
7.13
6.84
6.95
C
27H20ClN3O4S
(517.99)
26H21N3O4S
(471.53)
C
C27H23N3O4S
(485.56)
27H23N3O5S
(501.56)
28H23N3O5S
(513.57)
26H20ClN3O4S
(505.98)
29H25N3O6S
(543.59)
28H23N3O6S
(529.57)
34H29N5O4S
(603.00)
29H26N6O4S2
(586.00)
24H17ClN4O3S
(476.94)
25H19ClN4O4S
(506.96)
26H19ClN4O4S
(518.98)
25H20N4O4S
(472.52)
26H22N4O4S
(486.55)
26H22N4O5S
(502.54)
27H22N4O5S
(514.56)
25H19ClN4O4S
(506.96)
28H24N4O6S
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
7.01
6.82
7.93
7.81
16a
16b
17a
17b
17c
17d
17e
17f
17g
17h
17i
17j
11.61
11.78
14.33
14.24
11.75
11.84
11.05
10.79
10.80
10.58
11.86
11.97
11.52
11.61
11.15
11.30
10.89
10.78
11.05
11.00
10.29
11.00
10.56
10.41
8.28
7.43
7.34
6.99
6.80
6.83
6.55
6.99
6.92
(544.58)
27H22N4O6S
(530.56)
18
22H18ClN3O3S2
6.90
6.79
6.72
6.78
78
204–205
85
(507.00)
C23H20ClN3O3S2
(521.00)
8.00
8.06
8.11
19

Cyanopyridinethione Pyridine Derivatives
1075
TABLE II IR, 1H NMR, and MS Spectral Data of All Newly
Synthesized Compounds
Compound
Spectral Data
4a
IR: ν = 3190 (NH), 2210 (C N) cm−1
.
1H NMR (DMSO-d6): δ = 8.3 (d, 1H,
CH thienyl), 7.6–8.2 (m, 6H: 5ArH’s and CH pyridine), 7.3 (d, 1H, CH
thienyl) and 7.1 (t, 1H, CH thienyl) ppm. MS: 294 (M+, 100%).
4b
4c
6
IR: ν = 3190 (NH), 2210 (C N) cm−1
.
1H NMR (DMSO-d6): δ = 8.2 (d, 1H,
CH thienyl), 7.5–7.8 (m, 6H: 4ArH’s, CH thienyl and CH pyridine) and 7.2
(t, 1H, CH thienyl) ppm.
IR: ν = 3190 (NH), 2210 (C N) cm−1
.
1H NMR (TFA): δ = 7.8–8.2 (m, 5H:
2ArH’s, 2CH thienyl and CH pyridine), 7.2–7.5 (m, 3H: 2ArH’s and CH
thienyl) and 4.0 (s, 3H, OCH3) ppm.
IR: ν = 2200 (C N) cm−1
.
1H NMR (CDCl3): δ = 8.1 (d, 1H, CH thienyl),
7.5–8.0 (m, 6H: 5ArH’s and CH pyridine), 7.3 (d, 1H, CH thienyl), 7.1 (t,
1H, CH thienyl) and 2.7 (s, 3H, SCH3) ppm.
7
IR: ν = 3480, 3320, 3200 (NH2, NH) cm−1
.
1H NMR (CDCl3): δ = 12.5 (1H,
NH), 8.1 (d, 1H, CH thienyl), 7.4–7.9 (m, 6H: 5ArH’s and CH pyridine),
7.2 (d, 1H, CH thienyl), 6.9 (t, 1H, CH thienyl) and 4.5 (s, 2H, NH2) ppm.
IR: ν = 3480, 3300, 3150 (2NH2), 1640 (C O) cm.−11H NMR (DMSO-d6):
δ = 8.3 (d, 1H, CH thienyl), 7.6–8.2 (m, 6H: 5ArH’s and CH pyridine), 7.3
(d, 1H, CH thienyl), 7.1 (m, 3H:CH thienyl and CONH2) and 6.0 (s, 2H,
NH2) ppm.
8a
8b
IR: ν = 3480, 3300, 3150 (2NH2), 1640 (C O) cm.−1 1H NMR (DMSO-d6):
δ = 8.0 (d, 1H, CH thienyl), 7.5–7.8 (m, 6H: 4ArH’s, CH thienyl and CH
pyridine), 7.3 (m, 3H:CH thienyl and CONH2) and 5.9 (s, 2H, NH2) ppm
ms.
8c
9a
9b
9c
IR: ν = 3480, 3300, 3150 (2NH2), 1640 (C O) cm.−1 1H NMR (DMSO-d6):
δ = 7.1–8.1 (m, 10H: 4ArH’s, 3CH thienyl, CH pyridine and CONH2), 5.9
(s, 2H, NH2) and 3.5 (s, 3H, OCH3) ppm.
IR: ν = 3400, 3200 (2NH), 1650 (C O) cm−1
.
1H NMR (TFA): δ = 8.3 (d, 1H,
CH thienyl), 7.4–8.2 (m, 11H: 10ArH’s and CH pyridine), 7.3 (d, 1H, CH
thienyl) and 7.1 (t, 1H, CH thienyl) and 6.0 (s, 1H, CH at C-2) ppm.
IR: ν = 3400, 3200 (2NH), 1650 (C O) cm−1
.
1H NMR (TFA): δ = 8.4 (d, 1H,
CH thienyl), 7.5–8.2 (m, 10H: 9ArH’s and CH pyridine), 7.3 (d, 1H, CH
thienyl) and 7.0 (t, 1H, CH thienyl) and 6.0 (s, 1H, CH at C-2) ppm.
IR: ν = 3400, 3200 (2NH), 1650 (C O) cm−1
.
1H NMR (TFA): δ = 8.2 (d, 1H,
CH thienyl), 7.2–8.2 (m, 10H: 9ArH’s and CH pyridine), 7.2 (d, 1H, CH
thienyl) and 6.9 (t, 1H, CH thienyl), 6.0 (s, 1H, CH at C-2) and 3.9 (s, 3H,
OCH3) ppm.
10a
10b
IR: ν = 3400, 3200 (2NH), 1650 (C O) cm−1
.
1H NMR (CDCl3): δ = 8.1 (d,
1H, CH thienyl), 7.3–7.8 (m, 6H: 5ArH’s and CH pyridine), 7.1 (d, 1H, CH
thienyl), 6.9 (t, 1H, CH thienyl), 6.6 (s, 1H, CONH), 3.7 (s, 1H, NH),
1.7–2.0 (br s, 6H, (CH2)3 of cyclopentane ring) and 1.2–1.5 (br s, 2H, CH2
of cyclopentane ring) ppm.
IR: ν = 3400, 3200 (2NH), 1650 (C O) cm−1
.
1H NMR (CDCl3): δ = 8.2 (d,
1H, CH thienyl), 7.4–7.9 (m, 6H: 5ArH’s and CH pyridine), 7.2 (d, 1H, CH
thienyl), 7.0 (t, 1H, CH thienyl), 6.8 (s, 1H, CONH), 3.6 (s, 1H, NH),
1.9–2.2 (m, 4H, (CH2)2 of cyclohexane ring) and 1.3–1.6 (m, 4H, (CH2)2 of
cyclohexane ring), 0.6–0.9 (m, 2H, CH2 of cyclohexane ring) ppm.
(Continued on next page)

1076
O. S. Mohamed et al.
TABLE II IR, 1H NMR, and MS Spectral Data of All Newly
Synthesized Compounds (Continued)
Compound
Spectral Data
13a
IR: ν = 3200 (NH), 2200 (C N), 1720 (C O, ester), 1670 (C O, amide),
cm−1
.
1H NMR (CDCl3): δ = 8.6 (s, 1H, NH), 7.0–7.5 (m, 9H, ArH’s),
3.9–4.2 (m, 4H: SCH2 and OCH2), 2.7 (s, 3H, CH3 at C-6), 0.9–1.2 (t, 3H,
CH3 of ester) ppm. MS: 466 (M+, 79%).
13b
IR: ν = 3200 (NH), 2200 (C N), 1720 (C O, ester), 1670 (C O, amide)
cm−1
.
1H NMR (CDCl3): δ = 8.8 (s, 1H, NH), 7.3–7.7 (m, 6H, ArH’s),
6.8–7.0 (d, 2H, ArH’s), 4.0–4.3 (m, 4H: SCH2and OCH2), 3.8 (s, 3H,
OCH3), 2.7 (s, 3H, CH3 at C-6), 0.9–1.2 (t, 3H, CH3 of ester) ppm. MS: 496
(M+, 100%). .
13c
13d
13e
13f
IR: ν = 3200 (NH), 2200(C N), 1720 (C O, ester), 1680 (2C O, amide and
acety) cm−1
.
1H NMR (CDCl3): δ = 8.7 (s, 1H, NH), 7.3–7.8 (m, 6H, ArH’s),
6.8–7.0 (d, 2H, ArH’s), 4.0–4.3 (m, 4H: SCH2and OCH2), 2.7 (s, 3H, CH3 at
C-6), 2.6 (s, 3H, COCH3), 1.0–1.3 (t, 3H, CH3 of ester) ppm.
IR: ν = 3200 (NH), 2200 (C N), 1720 (C O, ester), 1670 (C O, amide)
cm−1
.
1H NMR (CDCl3): δ = 8.9 (s, 1H, NH), 6.9–7.5 (m, 9H, ArH’s),
3.9–4.3 (m, 4H: SCH2and OCH2), 3.8 (s, 3H, OCH3), 2.7 (s, 3H, CH3 at
C-6), 0.9–1.2 (t, 3H, CH3 of ester) ppm.
IR: ν = 3200 (NH), 2200 (C N), 1720 (C O, ester), 1670 (C O, amide)
cm−1
.
1H NMR (CDCl3): δ = 8.9 (s, 1H, NH), 7.0–7.5 (m, 8H, ArH’s),
3.9–4.3 (m, 4H: SCH2and OCH2), 3.8 (s, 3H, OCH3), 2.7 (s, 3H, CH3 at
C-6), 2.4 (s, 3H, CH3), 0.9–1.2 (t, 3H, CH3 of ester) ppm.
IR: ν = 3200 (NH), 2200 (C N), 1720 (C O, ester), 1670 (C O, amide)
cm−1
.
1H NMR (CDCl3): δ = 8.8 (s, 1H, NH), 7.0–7.7 (m, 8H, ArH’s),
4.0–4.4 (m, 4H: SCH2and OCH2), 3.9 (s, 3H, OCH3), 3.8 (s, 3H, OCH3), 2.7
(s, 3H, CH3 at C-6), 0.9–1.2 (t, 3H, CH3 of ester) ppm.
13g
IR: ν = 3200 (NH), 2200 (C N), 1720 (C O, ester), 1670 (2 C O, amide
and acetyl) cm−1
.
1H NMR (CDCl3): δ = 9.3 (s, 1H, NH), 7.5–8.0 (dd, 4H,
ArH’s), 6.9–7.4 (dd, 4H, ArH’s), 3.9–4.3 (m, 4H: SCH2and OCH2), 3.8 (s,
3H, OCH3), 2.6 (s, 3H, COCH3), 2.5 (s, 3H, CH3 at C-6), 0.8–1.1 (t, 3H,
CH3 of ester) ppm.
13h
13i
IR: ν = 3200 (NH), 2200 (C N), 1720 (C O, ester), 1670 (C O, amide)
cm−1
.
1H NMR (CDCl3): δ = 9.0 (s, 1H, NH), 6.8–7.6 (m, 8H, ArH’s),
4.0–4.3 (m, 4H: SCH2and OCH2), 3.8 (s, 3H, OCH3), 2.7 (s, 3H, CH3 at
C-6), 0.9–1.2 (t, 3H, CH3 of ester) ppm.
IR: ν = 3200 (NH), 2200 (C N), 1720 (C O, ester), 1700 (C O, ester), 1680
(C O, amide) cm−1
4H, ArH’s), 6.9–7.5 (dd, 4H, ArH’s), 4.0–4.3 (m, 6H: SCH2and 2OCH2), 3.8
(s, 3H, OCH3), 2.7 (s, 3H, CH3 at C-6), 1.2–1.5 (t, 3H, CH3 of ester),
0.8–1.1 (t, 3H, CH3 of ester) ppm.
.
1H NMR (CDCl3): δ = 9.3 (s, 1H, NH), 7.5–8.1 (dd,
13j
IR: ν = 3200 (NH), 2200 (C N), 1720 (C O, ester), 1700 (C O, ester), 1680
(C O, amide) cm−1
.
1H NMR (CDCl3): δ = 9.3 (s, 1H, NH), 7.5–8.1 (dd,
4H, ArH’s), 6.9–7.5 (dd, 4H, ArH’s), 4.0–4.3 (m, 4H: SCH2and OCH2), 3.9
(s, 3H, CO2CH3), 3.8 (s, 3H, OCH3), 2.7 (s, 3H, CH3 at C-6), 0.9–1.2 (t, 3H,
CH3 of ester) ppm.
14a
IR: ν = 3500, 3300 (NH2), 3200 (NH), 1720 (C O, ester), 1660 (C O, amide)
cm−1
.
1H NMR (CDCl3): δ = 8.7 (s, 1H, NH), 7.0–7.7 (m, 9H, ArH’s), 5.7 (s,
2H, NH2), 3.8–4.2 (q, 2H, OCH2), 2.6 (s, 3H, CH3 at C-6), 0.7–1.0 (t, 3H,
CH3 of ester) ppm.

Cyanopyridinethione Pyridine Derivatives
1077
TABLE II IR, 1H NMR, and MS Spectral Data of All Newly
Synthesized Compounds (Continued)
Compound
Spectral Data
14b
IR: ν = 3500, 3300 (NH2), 3200 (NH), 1720 (C O, ester), 1660 (C O, amide)
cm.−1 1H NMR (CDCl3): δ = 8.8 (s, 1H, NH), 7.0–7.8 (m, 8H, ArH’s), 5.7(s,
2H, NH2), 3.8–4.1 (q, 2H, OCH2), 3.8 (s, 3H, OCH3), 2.7 (s, 3H, CH3 at
C-6), 0.9–1.2 (t, 3H, CH3 of ester) ppm.
14c
IR: ν = 3500, 3300 (NH2), 3200 (NH), 1720 (C O, ester), 1680 (C O,
acetyl), 1660 (C O, amide) cm.−1 1H NMR (DMSO-d6): δ = 8.9 (s, 1H,
NH), 7.3–8.0 (m, 8H, ArH’s), 5.6 (s, 2H, NH2), 3.9–4.2 (q, 2H, OCH2), 2.7
(s, 3H, COCH3), 2.6 (s, 3H, CH3 at C-6), 0.8–1.1 (t, 3H, CH3 of ester) ppm.
MS: 508 (M+, 100%).
14d
14e
14f
IR: ν = 3500, 3300 (NH2), 3200 (NH), 1720 (C O, ester), 1660 (C O, amide)
cm−1
.
1H NMR (CDCl3): δ = 8.7 (s, 1H, NH), 6.9–7.7 (m, 9H, ArH’s), 5.8 (s,
2H, NH2), 3.9–4.2(q, 2H, OCH2), 3.8 (s, 3H, OCH3), 2.6 (s, 3H, CH3 at
C-6), 0.8–1.1 (t, 3H, CH3 of ester) ppm.
IR: ν = 3500, 3300 (NH2), 3200 (NH), 1720 (C O, ester), 1660 (C O, amide)
cm−1
.
1H NMR (CDCl3): δ = 8.7 (s, 1H, NH), 6.8–7.7 (m, 8H, ArH’s), 5.8 (s,
2H, NH2), 4.0–4.3 (q, 2H, OCH2), 3.8 (s, 3H, OCH3), 2.6 (s, 3H, CH3 at
C-6), 2.4 (s, 3H, CH3), 0.9–1.1 (t, 3H, CH3 of ester) ppm.
IR: ν = 3500, 3300 (NH2), 3200 (NH), 1720 (C O, ester), 1660 (C O, amide)
cm−1
.
1H NMR ((DMSO-d6): δ = 8.7 (s, 1H, NH), 6.8–7.7 (m, 8H, ArH’s),
5.8 (s, 2H, NH2), 4.0–4.3 (q, 2H, OCH2), 3.9 (s, 3H, OCH3), 3.8 (s, 3H,
OCH3), 2.6 (s, 3H, CH3 at C-6), 0.9–1.1 (t, 3H, CH3 of ester) ppm.
IR: ν = 3500, 3300 (NH2), 3200 (NH), 1720 (C O, ester), 1680 (C O,
14g
acetyl), 1660 (C O, amide) cm−1
.
1H NMR (CDCl3): δ = 9.0 (s, 1H, NH),
7.7–8.2 (dd, 4H, ArH’s), 7.1–7.6 (dd, 4H, ArH’s), 6.0 (s, 2H, NH2), 4.1–4.4
(q, 2H, OCH2), 4.0 (s, 3H, OCH3), 2.8 (s, 3H, COCH3), 2.6 (s, 3H, CH3 at
C-6), 1.0–1.3 (t, 3H, CH3 of ester) ppm.
14h
14i
IR: ν = 3500, 3300 (NH2), 3200 (NH), 1720 (C O, ester), 1660 (C O, amide)
cm−1
.
1H NMR (CDCl3): δ = 9.1 (s, 1H, NH), 6.9–7.6 (m, 8H, ArH’s), 5.8 (s,
2H, NH2), 3.9–4.2 (q, 2H, OCH2), 3.8 (s, 3H, OCH3), 2.6 (s, 3H, CH3 at
C-6), 0.8–1.1 (t, 3H, CH3 of ester) ppm.
IR: ν = 3500, 3300 (NH2), 3200 (NH), 1720 (C O, ester), 1700 (C O, ester),
1660 (C O, amide) cm−1
(dd, 4H, ArH’s), 6.9–7.4 (dd, 4H, ArH’s), 5.9 (s, 2H, NH2), 4.3–4.6 (q, 2H,
OCH2), 3.9–4.2 (q, 2H, OCH2), 3.8 (s, 3H, OCH3), 2.7 (s, 3H, CH3 at C-6),
1.3–1.6 (t, 3H, CH3 of ester), 0.9–1.2 (t, 3H, CH3 of ester) ppm.
.
1H NMR (CDCl3): δ = 9.1 (s, 1H, NH), 7.5–8.1
14j
IR: ν = 3500, 3300(NH2), 3200 (NH), 1720 (C O, ester), 1700 (C O, ester),
1660 (C O, amide) cm−1
.
1H NMR (CDCl3): δ = 9.2 (s, 1H, NH), 7.5–8.1
(dd, 4H, ArH’s), 6.9–7.5 (dd, 4H, ArH’s), 5.9 (s, 2H, NH2), 4.3–4.6 (q, 2H,
OCH2), 3.9 (s, 6H: OCH3 and CO2CH3), 2.6 (s, 3H, CH3 at C-6), 0.9–1.2 (t,
3H, CH3 of ester) ppm.
15a
15b
IR: ν = 1720 (C O, ester), 1660 (C O, pyrimidinone) cm−1
.
1NMR (CDCl3):
δ = 8.0 (s, 1H, CH pyrimidinone), 7.2–7.6 (m, 9H, ArH’s), 4.0–4.3(q, 2H,
OCH2), 2.8 (s, 3H, CH3 at C-7), 1.0–1.3 (t, 3H, CH3 of ester)
IR: ν = 1720 (C O, ester), 1660 (C O, pyrimidinone) cm−1
.
1NMR (CDCl3):
δ = 8.0 (s, 1H, CH pyrimidinone), 7.0–7.5 (m, 8H, ArH’s), 4.0–4.3 (q, 2H,
OCH2), 3.8 (s, 3H, OCH3), 2.8 (s, 3H, CH3 at C-7), 1.0–1.3 (t, 3H, CH3 of
ester) ppm.
(Continued on next page)

1078
O. S. Mohamed et al.
TABLE II IR, 1H NMR, and MS Spectral Data of All Newly
Synthesized Compounds (Continued)
Compound
Spectral Data
15c
IR: ν = 1720 (C O, ester), 1680 (C O, acetyl), 1660 (C O, pyrimidinone)
cm−1
.
1NMR (CDCl3): δ = 8.2 (d, 2H, ArH’s), 8.0 (s, 1H, CH pyrimidinone),
7.2–7.6 (m, 6H, ArH’s), 4.0–4.3 (q, 2H, OCH2), 2.8 (s, 3H, COCH3), 2.6 (s,
3H, CH3 at C-7), 1.0–1.3 (t, 3H, CH3 of ester) ppm.
15d
15e
15f
IR: ν = 1720 (C O, ester), 1660 (C O, pyrimidinone) cm−1
.
1H NMR
(CDCl3): δ = 7.9 (s, 1H, CH pyrimidinone), 6.8–7.6 (m, 9H, ArH’s), 4.0–4.3
(q, 2H, OCH2), 3.8 (s, 3H, OCH3), 2.8(s, 3H, CH3 at C-7), 0.9–1.2 (t, 3H,
CH3 of ester) ppm.
IR: ν = 1720 (C O, ester), 1660 (C O, pyrimidinone) cm−1
.
1H NMR
(CDCl3): δ = 8.0 (s, 1H, CH pyrimidinone), 6.8–7.4 (m, 8H, ArH’s), 4.0–4.3
(q, 2H, OCH2), 3.9 (s, 3H, OCH3), 2.8 (s, 3H, CH3 at C-7), 2.4 (s, 3H, CH3),
0.9–1.2 (t, 3H, CH3 of ester) ppm.
IR: ν = 1720 (C O, ester), 1660 (C O, pyrimidinone) cm−1
.
1H NMR
(CDCl3): δ = 8.0 (s, 1H, CH pyrimidinone), 6.9–7.4 (m, 8H, ArH’s), 4.0–4.3
(q, 2H, OCH2), 3.8 (s, 6H, two OCH3), 2.8 (s, 3H, CH3 at C-7), 0.9–1.2 (t,
3H, CH3 of ester) ppm. MS: 501 (M+, 56%).
15g
IR: ν = 1720 (C O, ester), 1680 (C O, acetyl), 1660 (C O, pyrimidinone)
cm−1
.
1H NMR (CDCl3): δ = 8.2 (s, 1H, CH pyrimidinone), 7.5–8.0 (dd,
4H, ArH’s), 6.9–7.4 (dd, 4H, ArH’s),), 4.0–4.3 (q, 2H, OCH2), 3.8 (s, 3H,
OCH3), 2.8 (s, 3H, COCH3), 2.7 (s, 3H, CH3 at C-7), 0.9–1.2 (t, 3H, CH3 of
ester) ppm.
15h
15i
IR: ν = 1720 (C O, ester), 1660 (C O, pyrimidinone) cm−1
.
1H NMR
(CDCl3): δ = 8.1 (s, 1H, CH pyrimidinone), 6.9–7.5 (m, 8H, ArH’s), 4.0-4.3
(q, 2H, OCH2), 3.8 (s, 3H, OCH3), 2.7 (s, 3H, CH3 at C-7), 0.9–1.2 (t, 3H,
CH3 of ester) ppm.
IR: ν = 1720 (C O, ester), 1700 (C O, esterl), 1660 (C O, pyrimidinone)
cm−1
.
1H NMR (CDCl3): δ = 6.9–8.3 (m, 9H: 8ArH’s and CH
pyrimidinone), 4.3–4.6 (q, 2H, OCH2), 3.9–4.2 (q, 2H, OCH2), 3.8 (s, 3H,
OCH3), 2.8 (s, 3H, CH3 at C-7), 1.3–1.6 (t, 3H, CH3 of ester), 0.9–1.2 (t,
3H, CH3 of ester) ppm.
15j
IR: ν = 1720 (C O, ester), 1700 (C O, ester), 1660 (C O, pyrimidinone)
cm−1
.
1H NMR (CDCl3): δ = 8.2 (s, 1H, CH pyrimidinone), 7.4–8.0 (dd,
4H, ArH’s), 6.9–7.5 (dd, 4H, ArH’s), 4.3–4.6 (q, 2H, OCH2), 3.9 (s, 6H:
OCH3 and CO2CH3), 2.7 (s, 3H, CH3 at C-7), 0.9–1.2 (t, 3H, CH3 of ester)
IR: ν = 3400 (NH), 1720 (C O, ester), 1660 (C O, pyrimidinone), 1600
16a
16b
(C=N) cm−1
.
1NMR (TFA): δ = 8.2 (s, 1H, CH pyrimidinone), 6.8–8.0 (m,
15H, ArH’s), 4.0–4.3 (q, 2H, OCH2), 3.8 (s, 3H, OCH3), 2.8 (s, 3H, CH3 at
C-7), 2.4 (s, 3H, CH3C=N), 1.0–1.3 (t, 3H, CH3 of ester) ppm.
IR: ν = 3500–3400 (NH2, NH), 1720 (C O, ester), 1660 (C O,
pyrimidinone), 1600 (C=N) cm−1
.
1H NMR (DMSO-d6):: δ = 8.2 (s, 1H, CH
pyrimidinone), 6.8–8.0 (m, 8H, ArH’s), 5.5 (s, 2H, NH2), 4.0–4.3 (q, 2H,
OCH2), 3.9 (s, 3H, OCH3), 2.7(s, 3H, CH3C=N), 2.5 (s, 3H, CH3 at C-6),
1.0–1.3 (t, 3H, CH3 of ester) ppm.
17a
IR: ν = 1720 (C O, ester), 1660 (C O, triazinone) cm−1
.
1H NMR (CDCl3):
δ = 7.1–7.6 (m, 9H, ArH’s), 3.9–4.2 (q, 2H, OCH2), 2.8 (s, 3H, CH3 at C-7),
1.0–1.3 (t, 3H, CH3 of ester) ppm.

Cyanopyridinethione Pyridine Derivatives
1079
TABLE II IR, 1H NMR, and MS Spectral Data of All Newly
Synthesized Compounds (Continued)
Compound
Spectral Data
17b
IR: ν = 1720 (C O, ester), 1660 (C O, triazinone) cm−1
.
1NMR (CDCl3):
δ = 7.0–7.6 (m, 8H, ArH’s), 4.0–4.3 (q, 2H, OCH2), 3.8 (s, 3H, OCH3), 2.7
(s, 3H, CH3 at C-7), 1.0–1.3 (t, 3H, CH3 of ester) ppm.
17c
17d
IR: ν = 1720 (C O, ester), 1680 (C O, acetyl), 1660 (C O, triazinone)
cm−1
.
1NMR (CDCl3): δ = 8.1 (d, 2H, ArH’s), 7.2–7.5 (m, 6H, ArH’s),
4.0–4.3 (q, 2H, OCH2), 2.8 (s, 3H, COCH3), 2.6 (s, 3H, CH3 at C-7),
0.9–1.2 (t, 3H, CH3 of ester) ppm.
IR: ν = 1720 (C O, ester), 1660 (C O, triazinone) cm−1
.
1NMR (CDCl3):
δ = 6.9–7.7 (m, 9H, ArH’s), 4.1–4.4 (q, 2H, OCH2), 3.9 (s, 3H, OCH3), 2.8
(s, 3H, CH3 at C-6), 0.9–1.2 (t, 3H, CH3 of ester) ppm. MS: 472 (M+,
100%).
17e
17f
17g
IR: ν = 1720 (C O, ester), 1660 (C O, triazinone) cm−1
.
1NMR (CDCl3):
δ = 6.8–7.5 (m, 8H, ArH’s), 4.0–4.3 (q, 2H, OCH2), 3.8 (s, 3H, OCH3), 2.7
(s, 3H, CH3 at C-7), 2.4 (s, 3H, CH3), 0.9–1.2 (t, 3H, CH3 of ester) ppm.
IR: ν = 1720 (C O, ester), 1660 (C O, triazinone) cm−1
.
1NMR (CDCl3):
δ = 6.9–7.6 (m, 8H, ArH’s), 4.0–4.3 (q, 2H, OCH2), 3.8 (s, 6H, two OCH3),
2.8 (s, 3H, CH3 at C-7), 0.9–1.2 (t, 3H, CH3 of ester) ppm. .
IR: ν = 1720 (C O, ester), 1680 (C O, acetyl),1660 (C O, triazinone)
cm−1
.
1NMR (CDCl3): δ = 7.7–8.2 (dd, 4H, ArH’s), 6.9–7.4 (dd, 4H,
ArH’s),), 4.0–4.3 (q, 2H, OCH2), 3.8 (s, 3H, OCH3), 2.8 (s, 3H, COCH3), 2.7
(s, 3H, CH3 at C-7), 0.9–1.2 (t, 3H, CH3 of ester) ppm.
17h
17i
IR: ν = 1720 (C O, ester), 1660 (C O, triazinone) cm−1
.
1NMR (CDCl3):
δ = 7.1–7.6 (m, 8H, ArH’s), 4.0–4.3 (q, 2H, OCH2), 3.9 (s, 3H, OCH3), 2.8
(s, 3H, CH3 at C-7), 1.0–1.3 (t, 3H, CH3 of ester) ppm.
IR: ν = 1720 (C O, ester), 1700 (C O, ester),1660 (C O, triazinone) cm.−1
1H NMR (CDCl3): δ = 7.0–8.4 (m, 8H, ArH’s), 4.3–4.6 (q, 2H, OCH2),
3.9–4.2 (q, 2H, OCH2), 3.8 (s, 3H, OCH3), 2.7 (s, 3H, CH3 at C-7), 1.3–1.6
(t, 3H, CH3 of ester), 0.9–1.2 (t, 3H, CH3 of ester) ppm.
.
17j
IR: ν = 1720 (C O, ester), 1700 (C O, ester), 1660 (C O, triazinone)
cm.−1
.
1H NMR (CDCl3): δ = 7.4–8.0 (dd, 4H, ArH’s), 6.9–7.5 (dd, 4H,
ArH’s), 4.3–4.6 (q, 2H, OCH2), 3.9 (s, 6H: OCH3 and CO2CH3), 2.8 (s, 3H,
CH3 at C-7), 1.0–1.3 (t, 3H, CH3 of ester) ppm.
18
19
IR: ν = 3300 (NH), 1720 (C O, ester), 1660 (C O, triazinone) cm−1
.
1NMR
(TFA): δ = 7.2–7.7 (m, 9H, ArH’s), 3.9–4.2 (q, 2H, OCH2), 2.8 (s, 3H, CH3
at C-7), 0.9–1.2 (t, 3H, CH3 of ester) ppm.
IR: ν = 1720 (C O, ester), 1660 (C O, triazinone) cm−1
.
1NMR (TFA):
δ = 7.2–7.7 (m, 9H, ArH’s), 3.9–4.2 (q, 2H, OCH2), 2.9 (s, 3H, CH3 at C-7),
1.8 (s, 3H, SCH3), 1.0–1.3 (t, 3H, CH3 of ester) ppm.
chloro-N-arylacetamide (10 mmol) was added. The resulting mixture
was refluxed for 20 min. The yellow precipitate that formed on cooling
was collected and recrystallized from ethanol to give compounds 14a–
i. These products were identical in all aspects to those described in
Method A.

1080
O. S. Mohamed et al.
Synthesis of Ethyl 3-amino-4-aryl-2-[N-(4-methoxy-
carbonylphenyl)]carbamoyl–6-methylthieno[2,3-b]pyridine-5-
carboxylate (14j)
Method A
Compound 13j (2.6 g, 5 mmol) was suspended in sodium methox-
ide solution (0.11 g sodium in 30 mL abs. methanol) and heated under
reflux for 5 min. The solid that formed on cooling was collected and re-
crystallized from ethanol to give canary yellow crystals of 14j (Table I).
Method B
To a suspension of compound 12a,b (5 mmol) in sodium methoxide
solution (0.23 g sodium in 30 mL abs. methanol), the respective chloro-
N-(4-methoxycarbonylpheny) acetamide (10 mmol) was added. The re-
sulting mixture was refluxed for 20 min. The yellow precipitate that
formed on cooling was collected and recrystallized from ethanol to give
compound 14j (yield: 76%). This product was identical in all aspects to
that described in Method A
Synthesis of 3,9-diaryl-8-ethoxycarbonyl-7-methylpyrido
[3’,2’:4,5]thieno[3,2-d]pyrimidine-4(3H)-ones (15a–j)
A mixture of 14a–j (2 mmol) and triethyl orthoformate (1 mL) in acetic
anhydride (5 mL) was refluxed for 4 h. The solid that formed while hot
was collected and recrystallized from an ethanol-chloroform mixture to
give white needles of 15a–j. Melting points, yields, and analytical data
of these compounds are given in Table I.
Condensation of Compound 15g with Aniline or
Thiosemicarbazide; General Procedure
To a mixture of 15 g (1.03 g, 2 mmol) and aniline or thiosemicar-
bazide (2 mmol) in ethanol (20 mL), a few drops of acetic acid were
added. The reaction mixture was refluxed for 2 h. and then left to cool.
The precipitated solid was collected and recrystalized from an ethanol-
chloroform mixture to give white crystals of 16a or 16b, respectively.
Melting points, yields, and analytical data of these compounds are given
in Table I.
Synthesis of 3,9-Diaryl-8-ethoxycarbonyl-7-methylpyrido
[3’,2’:4,5]thieno[3,2-d][1,2,3] triazine-4(3H)-ones (17a–j)
Sodium nitrite solution 10% (4 mL) was added to a solution of compound
14a–j (2 mmol) in concentrated sulphuric acid (4 mL) and glacial acetic
acid (4 mL) at 0◦C during 5 min. with stirring. The mixture was allowed

Cyanopyridinethione Pyridine Derivatives
1081
to stand at r.t. for 30 min. The solid that precipitated on dilution with
water was collected and recrystallized from ethanol as white needles of
17a–j. Melting points, yields, and analytical data of these compounds
are given in Table I.
Synthesis of 9-(4-Chlorophenyl)-8-ethoxycarbonyl-7-methyl-
4-oxo-3-phenyl-1,2,3,4-tetrahydro-2-thioxopyrido
[3’,2’:4,5]thieno[3,2-d]pyrimidine (18)
A mixture of 14a (1.4 g, 3 mmol) and carbon disulphide (3 mL) in dry
pyridine (20 mL) was refluxed on a water bath for 48 h. During the
reaction time, hydrogen sulphide evolved. The solvent was removed by
distillation under reduced pressure and the residue was crystallized
from acetic acid to give pale yellow crystals of 18 (Table I).
Synthesis of 9-(4-Chlorophenyl)-5-ethoxycarbonyl-2-
methylthio-7-methyl-3-phenylpyrido
[3’,2’:4,5]thieno[3,2-d]pyrimidine-4(3H)-one (19)
Compound 18 (0.5 g, 2 mmol) was dissolved in 4% (5 mL, 5 mmol)
ethanolic sodium hydroxide solution. To this solution methyl iodide
(0.2 mL, 3 mmol) was added. The reaction mixture was refluxed for
2 h. The precipitate on cooling was filtered off and recrsytallized from
ethanol as white needles of 19 (Table I).
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