Synthesis, characterization, and reactions of pyridine-3-carbonitrile derivatives

Article abstract of DOI:10.1080/10426500701693552

2-Thioxopyridine-3-carbonitrile derivatives 6a-c reacted with several halogen containing reagents 7a-d to afford the corresponding thieno[2,3-b]pyridine derivatives 9a-l, respectively. Thieno[2,3-b]pyridines 9c, g,k used for the preparation of their corresponding carbohydrazide derivatives 10a-c which in turn, used as good synthons for the synthesis of N-phenylmethylenethieno[2,3-b]pyridine-2-carbohydrazides 13a-c, pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidinones 15a-c, 16a-c and 17 and 1,3,4-oxadiazole-2-thiols 20a-c and 21a-c via their reactions with benzaldehyde or benzylidenemalononitrile, triethylorthoformate and carbon disulfide followed by hydrazine hydrate respectively. Considering the data of IR, 1H NMR, mass spectra, and elemental analyses elucidated the chemical structures of the newly synthesized heterocyclic compounds. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426500701693552

Phosphorus, Sulfur, and Silicon and the Related Elements
ISSN: 1042-6507 (Print) 1563-5325 (Online) Journal homepage: http://www.tandfonline.com/loi/gpss20
Synthesis, Characterization, and Reactions of
Pyridine-3-Carbonitrile Derivatives
A. M. Abdel-Fattah , M. A. A. Elneairy , M. N. Gouda & F. A. Attaby
To cite this article: A. M. Abdel-Fattah , M. A. A. Elneairy , M. N. Gouda & F. A. Attaby
(2008) Synthesis, Characterization, and Reactions of Pyridine-3-Carbonitrile Derivatives,
Phosphorus, Sulfur, and Silicon and the Related Elements, 183:7, 1592-1614, DOI:
10.1080/10426500701693552
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Phosphorus, Sulfur, and Silicon, 183:1592–1614, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500701693552
Synthesis, Characterization, and Reactions
of Pyridine-3-Carbonitrile Derivatives
A. M. Abdel-Fattah, M. A. A. Elneairy, M. N. Gouda,
and F. A. Attaby
Chemistry Department, Faculty of Science, Cairo University, Giza,
Egypt
2-Thioxopyridine-3-carbonitrile derivatives 6a-c reacted with several halogen con-
taining reagents 7a-d to afford the corresponding thieno[2,3-b]pyridine deriva-
tives 9a-l, respectively. Thieno[2,3-b]pyridines 9c, g,k used for the preparation
of their corresponding carbohydrazide derivatives 10a-c which in turn, used
as good synthons for the synthesis of N-phenylmethylenethieno[2,3-b]pyridine-2-
carbohydrazides 13a–c, pyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-d]pyrimidinones 15a-c, 16a-c
and 17 and 1,3,4-oxadiazole-2-thiols 20a-c and 21a-c via their reactions with ben-
zaldehyde or benzylidenemalononitrile, triethylorthoformate and carbon disulfide
followed by hydrazine hydrate respectively. Considering the data of IR, 1H NMR,
mass spectra, and elemental analyses elucidated the chemical structures of the
newly synthesized heterocyclic compounds.
Keywords 1,3,4-oxadiazole-2-thiols; 2-Cyanoethanethioamide; 2-thioxopyridine-3-
carbonitrile; carbohydrazides; pyridothienopyrimidinones; thieno[2,3-b]pyridine; thiopy-
ranopyridines triethyl orthoformate
INTRODUCTION
Synthetic potentiality, as well as the reported biological activ-
ity of 2-thioxopyridine,1−3 thieno[2,3-b]pyridine,4,5 and pyridothieno-
pyrimidines6,7 stimulated our interest to synthesize and characterize
several derivatives of these ring systems required for several chemical
transformation as well as medicinal chemistry programs and this tar-
get represents a continuation of our previous work.8−31 In this article,
we are interested in the synthesis of 2-thioxo-1,2-dihydropyridine-3-
carbonitrile derivatives 6a–c, as well as to investigate their synthetic
potentiality with several reagents to achieve our target.
Received 20 August 2007; accepted 27 August 2007.
Address correspondence to Fawzy A. Attaby, Chemistry Department, Faculty of Sci-
ence, Cairo University, Giza, 12613, Egypt. E-mail: Fattaby@hotmail.com
1592

Pyridine-3-Carbonitrile Derivatives
1593
RESULTS AND DISCUSSION
4-(4-bromophenyl)-6-phenyl-2-thioxo-1,2-dihydropyridine-3-carboni-
trile(6a) synthesized either by the reaction 3-(4-bromophenyl)-1-
phenylprop-2-en-1-one (2a) with malononitrile/H2S32−34 or by the
reaction of pyridinium bromide 4 with 2-cyanoethanethioamide (1)
followed by ammonium acetate.35 On carrying out such reactions, com-
pound 6a was obtained in a very low yield and in an impure state, and
this stimulate our interest to synthesize 6a via another pathway. Thus,
it has been found that 1 reacted with 3-(4-bromophenyl)-1-phenylprop-
2-en-1-one (2a) in ethanol containing the catalytic amount of triethyl
amine gave 4-(4-bromophenyl)-6-phenyl-2-thioxo-1,2-dihydropyridine-
3-carbonitrile 6a. The formation of 6a seemed to be proceeded via the
addition of –CH2- in 1 on the –CH=CH- in 2a followed by spontaneous
cyclization to 3a which auto-oxidizes under the reaction conditions to
afford 6a in good yield and in very pure state.
Similarly, 1 reacted with each of 3-[4-(dimethylamino)phenyl]-
1-phenylprop-2-en-1-one (2b) and 3-[4-(dimethylamino)phenyl]-1-(4-
methylphenyl)prop-2-en-1-one (2c) under the same experimental condi-
tions to afford the corresponding 6b,c respectively. The chemical struc-
ture of 6a-c was elucidated based on its IR, 1H NMR, and its elemental
analyses (cf. Experimental section). Moreover, the mass spectrum of 6b
as a typical example gave m/z = 331, which corresponds to the molecular
weight of the molecular formula C20H17N3S of the assigned structure.
Also, such mass spectrum gave several peaks with their fragments and
this confirms the given structure (cf. Chart 1 and Experimental section).
Synthons 6a–c used as good starting materials for the present study,
thus, it has been found that 6a reacted with 1-chloroacetone (7a) 1:1
in methanolic sodium methoxide solution via the dehydrochlorination
followed by addition of -CH2- on the CN group to afford the imino
derivative (I), which spontaneously rearranged to give a reaction prod-
uct 9a. Similarly, compounds 9e,i obtained via the reaction of 6b,c
with 7a under the same above mentioned experimental conditions. The
IR (cm−1) spectra of these reaction products showed no bands of the
CN function, and instead, the newly formed NH2 group was detected;
thus, we can conclude that both CN and –SCH2- were involved in cy-
clization step to afford directly 9a,e,i. Also, compounds 6a-c reacted
with each of 2-chloroacetamide, ethyl chloroacetate and 2-bromo-1-(4-
chlorophenyl)-ethanone 7b–d under the same above mentioned exper-
imental conditions to afford the corresponding thieno[2,3-b]pyridine
derivatives 9b–d, g,h,l and 8f,j,k whose structures established by con-
1
sidering the data of IR, H NMR and elemental analyses (cf. Experi-
mental section and Chart 2). Further confirmation of 8f,j,k structures

1594
A. M. Abdel-Fattah et al.
CHART 1
was given through their cyclization in methanolic sodium methox-
ide to afford the corresponding thieno[2,3-b]pyridine derivatives 9f,j,k
respectively.
On the other hand, compound 6a reacted with chloroacetyl
chloride 7e under the same above-mentioned experimental con-
ditions to afford the corresponding S-4-(4-bromophenyl)-3-cyano-
6-phenyl-pyridin-2-yl-2-chloroethanethioate 8m, which converted
to its enol form 2-(2-chloro-1-hydroxyvinylthio)-4-(4-bromophenyl)-
6-phenyl-pyridine-3-nitrile (8ꢀm). The reaction seemed to proceed
via the dehydrochlorination between 6a and 7e selectively along

Pyridine-3-Carbonitrile Derivatives
1595
CHART 2
the more electrophilic C-atom (ClCO- not ClCH2-). Compound 8m
cyclized in methanolic sodium methoxide to give the corresponding
4-amino-3-chloro-5-(4-bromo-phenyl)-7-phenyl-2H-thiopyrano[2,3-
b]pyridin-2-one 9m. Other analogues 6b,c reacted with 7e to give
the corresponding 8ꢀn,o, which converted to 8ꢀn,om which cyclized

1596
A. M. Abdel-Fattah et al.
CHART 3
to give the corresponding 9n,o, respectively. Structures 8m-o, and
9m-o elucidated by considering the data of IR, 1H NMR and elemental
analyses (cf. Experimental section and Chart 3).
The work was extended to shed more light on the chemical reac-
tivity of the –COOC2H5 group in compounds 9c,g,k through their re-
actions with hydrazine hydrate to afford the corresponding carbohy-
drazide derivatives 10a–c, respectively. Chemical elucidation of the
-CONHNH2 group in each of 10a–c performed through their reactions
with benzaldehyde or benzylidenemalononitrile (11) in a separated two
reactions (cf. Experimental section). The IR (cm−1) of these reaction
products showed no bands for -NHNH2. It is important to report here
that the reaction products of 10a–c with benzaldehyde or benzyliden-
emalononitrile (11) have the same physical and chemical properties
(m.p., mixed m.p.., and IR), and this confirms that the compounds 10a–
c reacted with 11 to give 13a–c via the formation of 1:1 adduct 12a–c
followed by the loss of malononitrile. Considering the data of IR and that
of elemental analyses the structure of 13a–c was established. Moreover,
the mass spectrum of 13a as a selective example gave m/z = 527 (M+,
11.21%) which corresponding to the molecular weight of the molecular

Pyridine-3-Carbonitrile Derivatives
1597
CHART 4
formula C27H19BrN4OS of the assigned structure, in addition to several
peaks which confirm the assigned structure (cf. Chart 4 and Exp. Part).
The position and chemical reactivity of NH2 and –NHN=CH-Ph in
compounds 13a–c confirmed through their cyclization with triethy-
lorthoformate. The reaction seemed to be proceeded through the non-
isolable products 14a–c, which underwent cyclization through the elim-
ination of ethanol molecule to give compounds 15a–c. The NH and NH2
1
detected in 13a–c neither detected in IR nor H NMR for compounds
15a–c. Moreover, the mass spectrum of 15a as a typical example gave
m/z = 537 (M+, 2.43%) which corresponding to the molecular weight of
the molecular formula C28H17BrN4OS of the assigned structure. Con-
sidering the above mentioned data as well as that of elemental analyses

1598
A. M. Abdel-Fattah et al.
these reaction products 15a–c formulated as pyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-
d]pyrimidinone derivatives (cf. Experimental section and Chart 4).
Further extension of this study aimed to investigate the synthetic
potentiality of synthons 10a–c via their reactions with triethyl ortho-
formate. Thus, it has been found 10b reacted with triethyl orthoformate
in acetic acid to afford compound 16b. Compound 16b is most probably
formed via the reaction of 10b with triethyl orthoformate in ratio 1 : 1
along NH2 at thiophene 3-position to afford the non-isolable interme-
diate (I), which cyclized spontaneously via the elimination of ethanol
molecule to give the final isolated product 16b. In a similar reaction,
10c reacted with triethylorthoformate to afford the final isolable prod-
uct 16c whose structure was established by considering the data of
1
IR, H NMR, and elemental analyses (cf. Experimental section). On
the other hand, 10a reacted with triethylorthoformate under the same
above-mentioned experimental conditions to afford compound 17. The
formation of compound 17 explained via the reaction of 10a with tri-
ethylorthoformate in ratio 1 : 2 along both NH2at thiophene 3-position
and that of -NHNH2to afford the non-isolable intermediate (II), which
cyclized spontaneously via the elimination of ethanol molecule to give
the final isolated product 17. Further confirmation of structure 17 was
given through its reaction with hydrazine hydrate to afford the corre-
1
sponding 16a. Considering the data of elemental analyses, IR and H
NMR the structures of 16a–c and 17 were elucidated (cf. Experimental
section and Chart 5). Moreover, the mass spectra of 17, 16a and 16b
gave m/z = 505 (M+, 26.3%), 449 (M+, 51.11%) and 413 (M+, 100%)
respectively and these corresponding to the molecular weights of the
molecular formulas C24H17BrN4O2S, C21H13BrN4OS and C23H19N5OS
of the assigned structures, in addition to several peaks that confirm
the structures of 17, 16a, and 16b, respectively (cf. Chart 5 and Exper-
imental section).
Further confirmation of the carbohydrazide group in each of 10a–
c obtained through their reactions with carbon disulfide in potassium
hydroxide mixture to afford the corresponding 1,3,4-oxadiazole-2-thiol
derivatives 20a–c via the non-isolable products 18a–c and 19a–c. The
IR of these reaction products showed no bands of CO amidic and in-
stead the newly formed band of SH group was detected. The mass
spectrum of 20c as a typical example gave m/z = 459 (M+, 0.65%),
which corresponded to the molecular weight of the molecular formula
C24H21N5OS2 of the assigned structure. Also, several peaks for the cor-
responding fragments were detected, e.g., 431, 415, 400, and 384, and
this represents further elucidation of 20a–c structures (cf. Chart 6 and
Experimental section).Compounds 20a–c reacted with hydrazine hy-
drate to give the corresponding 21a–c whose structures established by

Pyridine-3-Carbonitrile Derivatives
1599
CHART 5
considering the data of IR, 1H NMR and elemental analyses (cf. Exper-
imental section). Moreover, the mass spectra of 21a,c gave m/z = 495
and 457 which corresponding to the molecular weights of the molecular
formulas C21H15BrN6S2and C24H23N7OS respectively of the assigned
structures (cf. Chart 6 and Exp. Part).
EXPERIMENTAL
All melting points are uncorrected. IR spectra were recorded as KBr
discs on Shimadzu FTIR-8201PC Spectrophotometer. 1H-NMR spectra

1600
A. M. Abdel-Fattah et al.
CHART 6
were recorded on Varian Mercury 300 MHz. and Varian Gemini 200
MHz. Spectrometers using TMS as an internal standard and CDCl3 and
DMSO-d6 as solvents and chemical shifts are expressed as δ ppm units.
Mass spectra were recorded on Shimadzu GCMS-QP1000EX using inlet
type at 70 eV. The Microanalytical Center of Cairo University performed
microanalyses.

Pyridine-3-Carbonitrile Derivatives
1601
Synthesis of 2-Thioxo-1,2-dihydropyridine-3-carbonitrile
derivatives 6a-c—General Procedure
A solution of each of 1 (1g, 1 mmol) and 2a–c (2.87g, 2.51g, 2.65g; 1
mmol of each respectively) in absolute ethanol (30 mL) containing a
catalytic amount of piperidine (0.4 mL) was heated under reflux for
5 h. The reaction mixture was then evaporated till dryness and then
cooled. The products so formed were collected by filtration, washed with
cold ethanol, and then crystallized from the proper solvent to give the
corresponding 6a–c, respectively.
4-(4-Bromophenyl)-6-phenyl-2-thioxo-1,2-dihydropyridine-3-
carbo-nitrile (6a)
Crystallized from acetic acid as orange crystals (69%); m.p.. 256–
258◦C; IR (ν cm−1): 3151 (NH), 3059 (aromatic-CH) and 2219(CN);
Anal. for C18H11BrN2S (367.26): Calcd./Found (%): C,58.87/58.70,
H,3.02/3.0, Br,21.76/21.90, N,7.63/7.50, S,8.73/8.70.
4-[4-(Dimethylamino)phenyl]-6-phenyl-2-thioxo-1,2-
dihydropyridine-3-carbonitrile (6b)
Crystallized from ethanol-dioxane as yellow crystals (69%); m.p..
300–302◦C; IR (ν cm−1): 3291 (NH), 3059 (aromatic-CH), 2893 (sat.
CH) and 2211(CN); 1H-NMR (δppm): 2.77 (s. 6H, two CH3), 6.45–7.56
(m, 10H, aromatic and pyridine H-5 protons) and 12.9 (s, br., 1H, NH);
MS: 331 (M+, 68.1%) which corresponding to the molecular weight of
the molecular formula C20H17N3S of the assigned structure, 330 (M+-H,
100%), 316 (M+-CH3, 5.8%), 301 (316-CH3, 1.7%), 298 (M+-SH, 1.8%)
287 (M+-NMe2, 7.3%), 254 (287-SH, 2.7%), 228 (M+-PhCN, 2.8%) and
103 (PhCN, 4.6%); Anal. for C20H17N3S (331.43): Calcd./Found (%):
C,72.48/72.20, H,5.17/5.20, N,12.68/12.70, S,9.67/9.70.
4-[4-(Dimethylamino)phenyl]-6-(4-methylphenyl)-2-thioxo-1,2-
dihydro-pyridine-3-carbonitrile (6c)
Crystallized from ethanol-dioxane as reddish-orange crystals (79%);
m.p.. 290–202◦C; IR (ν cm−1): 3423 (NH), 3043 (aromatic-CH)
and 2211(CN); Anal. for C21H19N3S (345.46): Calcd./Found (%):
C,73.01/73.20, H,5.54/5.40, N,12.16/12.0, S,9.28/9.30.
Synthesis of 8f, g,k,m-o—General Method
A solution of each of the reactants A (1.65 g, 1.72 g, 1.72 g, 1.83 g,
1.65 g, 1.73 g; 0.5 mmol of each) in sodium methoxide (prepared from
0.12 g of sodium metal in 10 mL methanol)) and reactants B (0.47 g,

1602
A. M. Abdel-Fattah et al.
TABLE I
Reactant A
Reactants B
Products
6b
6c
6c
6a
6b
6c
7b
7b
7c
7e
7e
7e
8f
8j
8k
8m
8n
8o
0.47 g, 0.66 g, 0.56 g, 0.56 g, 0.56 g; 0.5 mmol of each ) was stirred for
2–3 h. The products so formed were collected by filtration, washed with
cold ethanol and then crystallized from the proper solvent to give the
products see Table I.
2-({3-Cyano-4-[4-(dimethylamino)phenyl]-6-phenylpyridin-2-
yl}thio)-acetamide (8f)
Crystallized from ethanol as pale yellow crystals (77%); m.p.. 260–
262◦C; IR (ν cm−1): 3277, 3379(NH2), 3071 (aromatic-CH), 2966
(sat. CH), 2210 (CN) and 1649 (amidic-CO); Anal. for C22H20N4OS
(388.48): Calcd./Found (%): C,68.02/68.10, H,5.19/5.20, N,14.42/14.30,
S,8.25/8.40.
2-({6-(4-methylphenyl)-3-cyano-4-[4-
(dimethylamino)phenyl]pyridin-2-yl}thio)acetamide 8j
Crystallized from ethanol-dioxane as yellow crystals (72%); m.p..
282-284◦C; IR (ν cm−1): 3202, 3382(NH2), 3028 (aromatic-CH), 2916
(sat. CH), 2209 (CN) and 1628 (amidic-CO); Anal. for C23H22N4OS
(402.51): Calcd./Found (%): C,68.63/68.50, H,5.51/5.30, N,13.92/14.10,
S,7.97/8.10.
Ethyl
({6-(4-methylphenyl)-3-cyano-4-[4-(dimethylamino)
phenyl]-pyridin-2-yl}thio)acetate 8k: Crystallized from ethanol-
dioxane as pale yellow crystals (70%); m.p. 236–238◦C; IR (ν cm−1):
3071 (aromatic-CH), 2945 (sat. CH), 2210 (CN) and 1742 (ester-CO);
Anal. for C25H25N3O2S (431.54): Calcd./Found (%): C,69.58/69.70,
H,5.84/5.90, N,9.74/9.80, S,7.43/7.40.
4-(4-Bromophenyl)-2-[(2-chloro-1-hydroxyvinyl)thio]-6-
phenylnicotino-nitrile (8m)
Crystallized from ethanol as orange crystals (73%); m.p. 254–256◦C;
IR (ν cm−1): 3446–3544(br. OH), 3099 (aromatic-CH) and 2220 (CN);
Anal. for C20H12BrClN2OS (443.74): Calcd./Found (%): C,54.13/54.20,
H,2.73/2.80, Br,18.01/18.10, Cl, 7.99/8.10, N,6.31/6.40, S,7.23/7.30.

Pyridine-3-Carbonitrile Derivatives
1603
TABLE II
Reactants A
Reactants B
Products
6a(1.83 g, 0.5 mmol)
6a(1.83 g, 0.5 mmol)
6a(1.83 g, 0.5 mmol)
6a(1.83 g, 0.5 mmol)
6b(1.65 g, 0.5 mmol)
6b(1.65 g, 0.5 mmol)
6b(1.65g g, 0.5 mmol)
6c(1.72 g, 0.5 mmol)
6c(1.72 g, 0.5 mmol)
7a(0.46 g, 0.5 mmol)
7b(0.47 g, 0.5 mmol)
7c(0.66 g, 0.5 mmol)
7d(1.16 g, 0.5 mmol)
7a(0.46 g, 0.5 mmol)
7c(066 g, 0.5 mmol)
7d(1.16 g, 0.5 mmol)
7a(0.46 g, 0.5 mmol)
7d(1.16 g, 0.5 mmol)
9a
9b
9c
9d
9e
9g
9h
9i
9l
2-[(2-Chloro-1-hydroxyvinyl)thio]-4-[4-
(dimethylamino)phenyl]-6-phenylnicotinonitrile (8n)
Crystallized from ethanol-dioxane as orange crystals (77%); m.p.
290–292◦C; IR (ν cm−1): 3420–3540(br., OH), 3043 (aromatic-CH), 2910
(sat. CH) and 2214 (CN); 1H-NMR (δppm): 3.08 (s, 6H, two CH3,
NMe2), 3.71 (s, 1H, =CH-), 6.80–7.9 (m, 10H, aromatic and pyridineH-
5 protons, and 13.9 (s, br. 1H, enolic OH).; Anal. for C22H18ClN3OS
(407.91): Calcd./Found (%): C,64.78/64.90, H,4.45/4.40, Cl,8.69/8.80,
N,10.30/10.40, S,7.86/7.90.
2-[(2-Chloro-1-hydroxyvinyl)thio]-4-[4-
(dimethylamino)phenyl]-6-(4-methylphenyl)nicotinonitrile (8o)
Crystallized from ethanol-dioxane as orange crystals (77%); m.p.
244–246◦C; IR (ν cm−1): 3399–3465 (br., OH), 3176 (aromatic-CH),
2915 (sat. CH) and 2211 (CN); Anal. for C23H20ClN3OS (421.94):
Calcd./Found (%): C,65.47/65.60, H,4.78/4.70, Cl,8.40/8.50, N,9.98/10.0,
S,7.60/7.50.
Synthesis of 9a-e, g-i,l—General Method
A solution of each of the reactants A in ethanol and potassium hydrox-
ide solution (10 mL of 10% KOH) was heated with each of reactantsB
under reflux for 2–3 h. The reaction mixture was cooled, poured into ice-
cold water, acidified with hydrochloric acid. The products formed were
collected by filtration, washed with water followed by cold ethanol and
crystallized from the proper solvent to give the corresponding products
see Table II.
Synthesis of 9f,j,k,m-o—General Procedure)
A mixture of each of 8f,j,k,m–o (1.94 g, 2.01 g, 2.15 g, 2.21 g, 2.03 g, 2.10
g; 0.5 mmol of each) and methanolic sodium methoxide (0.11 g of sodium

1604
A. M. Abdel-Fattah et al.
with about 50 mL methanol) was heated under reflux for 5 hs. It was
poured onto ice-cold water and acidified with concentrated hydrochlo-
ric acid. Collect the formed solid by filtration, wash with water and
crystallize from the proper solvent to afford 9f,j,k,m–o, respectively.
1-[3-Amino-4-(4-bromophenyl)-6-phenylthieno[2,3-b]pyridin-
2-yl]-ethanone (9a)
Crystallized from ethanol as orange crystals, , m.p. 230–232◦C; IR (ν
cm−1): 3481, 3296 (NH2), 3050(CH-aromatic); Anal. for C21H15BrN2OS
(423.32): Calcd./Found (%): C,59.58/60.10, H,3.57/3.70, Br,18.88/19.0,
N,6.62/6.70, S,7.57/7.60.
3-Amino-4-(4-bromophenyl)-6-phenylthieno[2,3-b]pyridine-2-
carbox-amide (9b)
Crystallized from ethanol as pale green crystals, m.p. 236–238◦C; IR
(ν cm−1): 3482, 3312, 3166 (two NH2), and 1668 (CO amidic); Anal. for
C20H14BrN3OS (424.31): Calcd./Found (%): C,56.61/56.50, H,3.33/3.50,
Br,18.83/18.60, N,9.90/10.0, S,7.56/7.60.
Ethyl 3-amino-4-(4-bromophenyl)-6-phenylthieno[2,3-
b]pyridine-2-carboxylate 9c
Crystallized from ethanol as yellow crystals, m.p. 260-2◦C; crystal-
lize from acetic acid; IR (ν cm−1): 3495, 3359, 3342 (NH2), 3083(CH
aromatic, 2981-2898 (CH-aliphatic) and 1666 (C=O ester); Anal. for
C22H17BrN2O2S (453.35): Calcd./Found (%): C,58.28/58.40, H,3.78/3.70,
Br,17.63/17.80, N,6.18/6.50, S,7.07/7.10.
[3-Amino-4-(4-bromophenyl)-6-phenylthieno[2,3-b]pyridin-2-
yl](4-chlorophenyl)methanone 9d
Crystallized from ethanol as orange crystals, m.p. 250–252◦C;
IR (ν cm−1): 3488, 3296 (NH2) and 3055 (CH aromatic); Anal. for
C26H16BrClN2OS (519.84): Calcd./Found (%): C,60.07/60.10, H,3.10/3.0,
Br,15.37/15.40, Cl,6.82/6.90, N,5.39/5.50, S,6.17/6.20.
1-3-Amino-4-[4-(dimethylamino)phenyl]-6-phenylthieno[2,3-
b]pyridin-2-ylethanone 9e
Crystallized from ethanol as yellow crystals, m.p. 237–239◦C; IR
(ν cm−1): 3459, 3303 (NH2), and 2994–2809 (aliphatic CH); MS: 387
(M+, 67.1%), which corresponds to the molecular weight of the molecu-
lar formula C23H21N3OS of the assigned structure, 386 (M+-H, 100%),
385 (386-H, 38.0%), 371 (M+-NH2, 17.5%), 356 (371-CH3, 1.8%), 343
(M+-NMe2, 15.5%), 344 (M+-COCH3, 9.7%), 300 (344- NMe2, 14.4%),

Pyridine-3-Carbonitrile Derivatives
1605
284 (M+-PhCN, 1.9%), 240 (284-NMe2, 3.0%), 103 (PhCN, 4.0%); Anal.
for C23H21N3OS (387.49): Calcd./Found (%): C,71.29/71.10, H,5.46/5.50,
N,10.84/11.0, S,8.27/8.20.
Ethyl 3-Amino-4-[4-(dimethylamino)phenyl]-6-phenylthieno
[2,3-b]-pyridine-2-carboxylate 9g
Crystallized from ethanol-dioxane as yellow crystals, m.p. 230–
232◦C; cIR (ν cm−1): 3495, 3381 (NH2), 2989–2889 (CH-aliphatic) and
1
1672 (C=O ester); H-NMR (δppm): 1.5 (t, 3H, CH3CH2-), 3.09 (s, 6H,
NMe2), 3.87 (q, 2H, CH3CH2-), 5.93 (s, br., 2H, NH2) and 6.81-8.12
(m, 10H, aromatic and pyridineH-5 protons); Anal. for C24H23N3O2S
(417.52): Calcd./Found (%): C,69.04/70.0, H,5.55/5.70, N,10.06/10.10,
S,7.68/7.70.
[3-Amino-4-[4-(dimethylamino)phenyl]-6-phenylthieno[2,3-
b]pyridin-2-yl](4-chlorophenyl)methanone 9h
Crystallized from ethanol as yellow crystals, m.p. 212–214◦C; IR (ν
cm−1): 3456, 3278 (NH2), 3061 (CH aromatic) and 2886–2807(aliphatic
CH); MS: 484 (M+, 88.8%), which corresponds to the molecular weight
of the molecular formula C28H22ClN3OS of the assigned structure,
483 (M+-H, 100%), 482 (483-H, 64.9%), 469 (M+-CH3, 6.3%), 468
(483-CH3, 6.5%), 467 (482-CH3, 8.3%), 373 (M+-C6H4-p-Cl, 1.2%),
345 (M+-COC6H4-p-Cl, 1.0%), 329 (345-C6H4-p-Cl, 2.7%), 301 (345-
NMe2, 4.5%), 139 (COC6H4-p-Cl, 41.2%), 111 (C6H4-p-Cl, 47.3%), 103
(PhCN, 4.5%); Anal. for C28H22ClN3OS (484.01): Calcd./Found (%):
C,69.48/70.0, H,4.58/4.60, Cl,7.32/7.40, N,8.68/8.80, S,6.62/6.70.
1-[3-Amino-4-[(4-dimethylaminophenyl)]-6-(4-
methylphenyl)thieno-[2,3-b]pyridin-2-yl]ethanone 9i
Crystallized from ethanol as yellow crystals, m.p. 202–204◦C; IR
(ν cm−1): 3469, 3322 (NH2), and 2887–2807 (aliphatic CH); Anal. for
C24H23N3OS (401.52): Calcd./Found (%): C,71.79/71.70, H,5.77/5.80,
N,10.47/10.60, S,7.99/8.10.
[3-Amino-4-[4-(dimethylaminophenyl)]-6-(4-
methylphenyl)thieno[2,3-b]pyridin-2-yl](4-
chlorophenyl)methanone (9l)
Crystallized from ethanol as yellow crystals, m.p. 234–236◦C; IR (ν
cm−1): 3466, 3295 (NH2), 3027 (CH aromatic), and 2911–2805 (aliphatic
CH); Anal. for C29H24ClN3OS (498.03): Calcd./Found (%): C,69.94/70.10,
H,4.86/4.90, Cl,7.12/7.30, N,8.44/8.60, S,6.44/6.60.

1606
A. M. Abdel-Fattah et al.
3-Amino-4-[4-(dimethylamino)phenyl]-6-phenylthieno[2,3-
b]pyridine-2-carboxamide (9f)
Crystallized from ethanol as yellow crystals, m.p. 260◦C; IR (ν
cm−1): 3466, 3428, 3358 ( two NH2), 2966–2806 (aliphatic CH) and
1654 (CO amide); Anal. for C22H20N4OS (388.48): Calcd./Found (%):
C,68.02/68.10, H,5.19/5.20, N,14.42/14.40, S,8.25/8.40.
3-Amino-4-[4-(dimethylamino)phenyl]-6-(4-
methylphenyl)thieno[2,3-b]pyridine-2-carboxamide 9j
Crystallized from ethanol-dioxane as orange crystals, m.p. 280◦C; IR
(ν cm−1): 3454, 3379, 3330 ( two NH2), 2965–2800 (aliphatic CH) and
1650 (CO amide); Anal. for C23H22N4OS (402.51): Calcd./Found (%):
C,68.63/68.70, H,5.51/5.60, N,13.92/14.10, S,7.97/8.10.
Ethyl 3-Amino-4-(dimethylaminophenyl)-6-(4-
methylphenyl)thieno-[2,3-b]pyridine-2-carboxylate (9k)
Crystallized from ethanol-dioxane as yellow crystals, m.p. 268◦C;
IR (ν cm−1): 3481, 3357 (NH2), 3026 (aromatic CH0, 2976–2803 (CH-
aliphatic) and 1681 (C=O ester); Anal. for C25H25N3O2S (431.54):
Calcd./Found (%): C,69.58/69.60, H,5.84/5.70, N,9.74/9.80, S,7.43/7.50.
4-Amino-5-(4-bromophenyl)-3-chloro-7-phenyl-2H-
thiopyrano[2,3-b]-pyridin-2-one (9m)
Crystallized from ethanol-dioxane as yellow crystals, m.p. >
300◦C; IR (ν cm−1): 3484, 3383 (NH2), and 1671 (CO); Anal.
for C20H12BrClN2OS (443.74): Calcd./Found (%): C,54.13/54.20,
H,2.73/2.80, Br,18.01/18.10, Cl,7.99/8.10, N,6.31/6.40, S,7.23/7.40.
4-Amino-3-chloro-5-[4-(dimethylamino)phenyl]-7-phenyl-2H-
thiopyrano-[2,3-b]pyridin-2-one (9n)
Crystallized from ethanol as yellow crystals, m.p. 230◦C; IR (ν cm−1):
3485, 3363 (NH2), 3039 (aromatic CH), 2977–2807 (aliphatic CH), and
1
1666 (CO); H NMR (δppm): 3.06 (s, 6H, two CH3, NMe2), 5.92 (s, br.,
2H, NH2) and 6.81-8.12 (m, 10H, aromatic and pyridineH-5 protons);
Anal. for C22H18ClN3OS (407.91): Calcd./Found (%): C,64.78/64.80,
H,4.45/4.50, Cl,8.69/8.70, N,10.30/10.40, S,7.86/7.90.
4-Amino-3-chloro-5-[4-(dimethylamino)phenyl]-7-(4-
methylphenyl)-2H-thiopyrano[2,3-b]pyridin-2-one (9o)
Crystallized from ethanol as yellow crystals, m.p. 272◦C; IR (ν cm−1):
3485, 3363 (NH2), 3029 (aromatic CH), 2982–2805 (aliphatic CH),

Pyridine-3-Carbonitrile Derivatives
1607
and 1666 (CO); Anal. for C23H20ClN3OS (421.94): Calcd./Found (%):
C,65.47/65.50, H,4.78/4.80, Cl,8.40/8.50, N,9.96/10.10, S,7.60/7.60.
Synthesis of Thieno[2,3-b]pyridine-2-carbohydrazide
Derivatives 10a-c—General Procedure
compounds 9c, g g,k (1.13 g, 1.04 g, 1.07 g; 0.25 mmol of each) and
hydrazine hydrate 95% (5 mL) were heated under reflux for 5h. The
reaction mixture evaporated to half of its volume and allowed to cool.
The solid products formed collected by filtration and recrystallized from
the proper solvent.
3-Amino-4-(4-bromophenyl)-6-phenylthieno[2,3-b]pyridine-2-
carbo-hydrazide (10a)
Crystallized from ethanol as yellow crystals (62%); m.p. 242–244◦C;
IR (ν cm−1): 3484, 3460, 3424, 3328 (NH2 and NH), and 3037
(CH aromatic); Anal. for C20H15BrN4OS (439.3): Calcd./Found (%):
C,54.68/54.50, H,3.44/3.50, Br,18.19/18.30, N,12.75/12.60, S,7.30/7.40.
3-Amino-4-[4-(dimethylamino)phenyl]-6-phenylthieno[2,3-
b]pyridine-2-carbohydrazide (10b)
Crystallized from ethanol as orange crystals (69%); m.p. 220◦C;
IR (ν cm−1): 3475, 3397, 3346, 3348 (NH2and NH), and 3038
(CH aromatic); 1H-NMR (δppm): 2.97 (s, 6H, NMe2), 3.14 (s, br.,
3H, NH-NH2), 6.05 (s, br. 2H, NH2 at position-3), 6.81–8.10 (m,
10H, aromatic and pyridineH-5 protons); Anal. for C22H21N5OS
(403.5): Calcd./Found (%): C,65.49/65.50, H,5.25/5.10, N,17.36/17.50,
S,7.95/8.0.
3-Amino-4-[4-(dimethylamino)phenyl]-6-(4-
methylphenyl)thieno[2,3-b]pyridine-2-carbohydrazide (10c)
Crystallized from ethanol as orange crystals (59%); m.p. 220◦C; IR
(ν cm−1): 3471, 3316, (NH2and NH), and 3037 (CH aromatic); Anal.
for C23H23N5OS (417.5): Calcd./Found (%): C,66.16/66.2, H,5.55/5.6,
N,16.77/16.5, S,7.68/7.8.
Synthesis of N ꢀ-(phenylmethylene)thieno[2,3-b]pyridine-
2-carbohydr-azide derivatives 13a-c—General Procedure)
A solution of each 10a–c (2.19 g, 2.01 g, 2.08 g; 0.5 mmol of each) in acetic
acid (50 mL) with benzaldehyde (0.54 g) or benzyldenemalononitrile 11
(0.77 g); 0.5 mmol of each. The reaction mixture heated under reflux

1608
A. M. Abdel-Fattah et al.
for 3 hrs. The solid products so formed were collected by filtration and
crystallized from proper solvent to afford 13a-c, respectively.
3-Amino-4-(4-bromophenyl)-6-phenyl-Nꢀ-
(phenylmethylene)thieno-[2,3-b]pyridine-2-
carbohydrazide (13a)
Crystallized from DMF-ethanol mixture as orange crystals (54%);
m.p. 300◦C; IR (ν cm−1): 3479, 3325 (NH2, and NH), and 1624 (CO hy-
drazidic); MS: 527 (M+, 11.21%) which corresponding to the molecular
weight of the molecular formula C27H19BrN4OS of the assigned struc-
ture, 528 (M+1, 34.96%), 529 (M+2, 10.23%), 408 (M+-Ph-CH=N-NH,
94.11%), 407 (408-H, 27.95%), 406 (407-H, 100%), and 379 (407-CO,
39.99%), 119 (Ph-CH=N-NH, 22.59%), 103 (PhCN, 13.88%); Anal. for
C27H19BrN4OS (527.4): Calcd./Found(%): C,61.48/61.50, H,3.63/3.60,
N,10.62/10.50 S,10.62/10.50, Br,15.15/15.20.
3-Amino-4-[4-(dimethylamino)phenyl-6-phenyl-Nꢀ-
(phenylmethylene)-thieno[2,3-b]pyridine-2-
carbohydrazide (13b)
Crystallized from dioxane-ethanol as orange crystals (59%); m.p.
290–292◦C; IR (ν cm−1): 3468, 3315, 3150 (NH2 and NH), and
3041 (CH aromatic); Anal. for C29H25N5OS (491.6): Calcd./Found (%):
C,70.85/71.0, H,5.13/5.20, N,14.29/14.40, S,6.52/6.60.
3-Amino-4-[4-(dimethylamino)phenyl-6-(4-methylphenyl)-Nꢀ-
(phenylmethylene)thieno[2,3-b]pyridine-2-
carbohydrazide (13c)
Crystallized from dioxane as yellow crystals (59%); m.p. 290–292◦C;
IR (ν cm−1): 3468, 3308, 3149 (NH2and NH), and 3029 (CH aro-
matic); Anal. for C30H27N5OS (505.6): Calcd./Found (%): C,71.26/71.10,
H,5.38/5.40, N,13.85/13.90, S,6.34/6.40.
Synthesis of 15a–c 16b,c, and 17—General Procedure
A solution of each of 13a-c (1.31 g, 1.25 g, 1.26 g), 10b,c (1.01 g, 1.04 g),
and10a (1.09 g); 0.25 mmol of each; in glacial acetic acid (30–50 mL)
and triethyl orthoformate (1.48 g, 1 mmol) was heated under reflux
5 hs. The reaction mixture evaporated to its half volume then cooled
with ice-cold water. The solid product isolated in each case collected by
filtration, washed with ethanol and crystallized from the proper solvent
to yield 15a-c, 16b,c, and 17, respectively.

Pyridine-3-Carbonitrile Derivatives
1609
Synthesis of 16a
A mixture of 17 (1.26g, 0.25 mmol) and hydrazine hydrate (15-20 mL)
was heated under reflux for 5-7 hs. The product so formed after cooling
was filtered off, washed with cold ethanol, and crystallized from the
acetic acid to give 16a.
9-(4-Bromophenyl)-7-phenyl-3-
[(phenylmethylene)amino]pyrido[3ꢀ,2ꢀ-
:4,5]thieno[3,2-d]pyrimidin-4(3H)-one (15a)
Crystallized from acetic acid as colorless crystals (59%); m.p.
320◦C; IR (ν cm−1): 3061 (CH aromatic) and 1667 (CO); 1H-NMR
(δppm): 7.27–7.87 (m, 15H, aromatic and pyridineH-5 protons), 8.31
(s, 1H, Pyrimidine-CH) and 9.72 (s, 1H, -CH=N); MS: 537 (M+,
2.43%) which corresponding to the molecular weight of the molec-
ular formula C28H17BrN4OS of the assigned structure, 538 (M+1,
5%), 539 (M+2, 1.99%), 433 (M+-Ph-CH=N, 95.34%), 435 (539-Ph-
CH=N, 51.09%), and 378 (433-CHNCO, 11.51%); 104 (Ph-CH=N,
25.69%), 103 (PhCN, 83.20%), 77 (Ph, 100%), Anal. for C28H17BrN4OS
(537.4): Calcd./Found (%): C,62.58/62.60, H,3.19/3.20, Br,14.87/15.0,
N,10.42/10.40, S,5.97/6.10.
9-(4-Dimethylaminophenyl)-7-phenyl-3-
[(phenylmethylene)amino]-pyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-
d]pyrimidin-4(3H)-one (15b)
Crystallized from dioxane as yellow crystals (59%); m.p. 310–312◦C;
IR (ν cm−1): 3052 (CH aromatic) and 1671 (CO); Anal. for C30H23N5OS
(501.6): Calcd./Found (%): C,71.83/72.0, H,4.62/4.70, N,13.96/14.0,
S,6.39/6.40.
9-(4-Dimethylaminophenyl)-7-(4-methylphenyl)-3-
[(phenylmethylene)-amino]pyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-
d]pyrimidin-4(3H)-one (15c)
Crystallized from dioxane as orange crystals (59%); m.p. 307–309◦C;
IR (ν cm−1): 3023 (CH aromatic), 2916–2855 (aliphatic CH) and 1663
(CO); Anal. for C31H25N5OS (515.6): Calcd./Found (%): C,72.21/72.20,
H,4.89/4.80, N,13.58/13.60, S,6.22/6.20.
Ethyl [9-(4-Bromophenyl)-4-oxo-7-phenylpyrido
[3ꢀ,2ꢀ:4,5]thieno[3,2-d]pyrimidin-3(4H)-yl]imidoformate 17
Crystallized from acetic acid as yellowish-white crystals (55%);
m.p. > 300◦C; IR (ν cm−1): 3060 (CH aromatic), 2990 (aliphatic CH)

1610
A. M. Abdel-Fattah et al.
and 1668 (CO); 1H-NMR (δppm): 1.44 (t, 3H, COOCH2CH3, J =
7.2), 4.43 (q, 2H, COOCH2CH3, J =7 .2), 7.26–8.17 (m, 10H, aro-
matic and pyridineH-5 protons), 8.18 (s, 1H, Pyrimidine-CH) and
8.73 (s, 1H, -CH=N); MS: 505 (M+, 26.3%) which corresponds to
the molecular weight of the molecular formula of the assigned struc-
ture, 506 (M+1,23.7%), 507 (M+2, 25.7%), 460 (M+-OC2H5, 6.8%),
461 (506-OC2H5, 7.0%), 462 (507-OC2H5, 4.4%), 447 (505-CHOC2H5,
0.9%), 448 (506-CHOC2H5, 1.1%), (433 (M+-N=CH-OC2H5, 100%),
434 (506-N=CH-OC2H5, 94.3%), 435 (507-N=CH-OC2H5, 34.2%), 380
(435- CON-CH=, 5.0%), 379 (434- CON-CH=, 11.7%), 378 (433-CON-
CH=, 12.3%), 103 (PhCN, 3.7%), 72 (-N=CH-OC2H5, 7.4%); Anal. for
C24H17BrN4O2S (505.38): Calcd./Found (%): C,57.04/57.12, H,3.39/3.40,
Br,15.81/15.90, N,11.09/11.10, S,6.34/6.40.
3-Amino-9-(4-bromophenyl)-7-
phenylpyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-d]-pyrimidin-4(3H)-one 16a
Crystallized from dioxane as pale yellow crystals (50%); m.p. >300◦C;
IR (ν cm−1): 3315, 3261, 3208 (NH2), 3039 (CH aromatic), 2852
(aliphatic CH), and 1668 (CO); 1H-NMR (δppm): 6.08 (s, br., 2H, NH2),
7.53-8.28 (m, 10H, aromatic and pyridineH-5 protons) and 8.39 (s,
1H, Pyrimidine-CH); MS: 449 (M+, 51.11%), which corresponds to the
molecular weight of the molecular formula C21H13BrN4OS of the as-
signed structure, 450 (M+1, 100%), 451 (M+2, 24.01%), 448 (M+-H,
93.40%), 419 (448-NNH, 33.63%), 85 [-N=CH-N(NH2)CO, 29.41%], 72
(COCS, 38.31%), 57 (-N-CH=N-NH2, 60.43%); Anal. for C21H13BrN4OS
(449.32): Calcd./Found (%): C,56.13/56.20, H,2.92/3.0, Br,17.78/17.90,
N,12.47/12.50, S,7.14/7.20.
3-Amino-9-[4-(dimethylamino)phenyl]-7-
phenylpyrido[3ꢀ,2ꢀ:4,5]thieno-[3,2-d]pyrimidin-4(3H)-one 16b
Crystallized from alcohol-dioxane as yellow crystals (58%); m.p.
310◦C; IR (ν cm−1): 3326, 3278, 3212 (NH2), 3054 (CH aromatic), 2890
1
(aliphatic CH), and 1674 (CO); H-NMR (δppm): 3.07 (s, 6H, -NMe2),
6.11(s, br., 2H, NH2), 6.84–8.05 (m, 10H, aromatic and pyridineH-5 pro-
tons) and 8.44 (s, 1H, Pyrimidine-CH); MS: 413 (M+, 100%), which cor-
responds to the molecular weight of the molecular formula C23H19N5OS
of the assigned structure, 412 (M+-H, 20.50%), 397 (M+-NH2, 6.45%),
370 (M+-NH2-N-CH=, 27.11%), and 328 (370-CON-, 11.29%); Anal.
for C23H19N5OS (413.49): Calcd./Found (%): C,66.81/66.90, H,4.63/4.70,
N,16.94/17.0, S,7.75/7.80.

Pyridine-3-Carbonitrile Derivatives
1611
3-Amino-9-[4-(dimethylamino)phenyl]-7-(4-
methylphenyl)pyrido-[3’,2’:4,5]thieno[3,2-d]pyrimidin-4(3H)-
one 16c
Crystallized from dioxane as yellow crystals (52%); m.p. 280◦C; IR
(ν cm−1): 3447, 3314, 3202 (NH2), 3032 (CH aromatic), 2917 (aliphatic
CH), and 1667 (CO); Anal. for C24H21N5OS (427.52): Calcd./Found (%):
C,67.43/67.50, H,4.95/5.0, N,16.38/16.40 S,7.50/7.6.
Synthesis of 1,3,4-Oxadiazol-2-thiols 20a-c—General
Procedure
Carbon disulfide (0.76 g, 1 mmol) was added to a solution of potassium
hydroxide (0.56 g, 1 mmol), absolute ethanol (50 mL) and each 10a-
c (2.19 g, 2.01 g, 2.08 g; 0.5 mmol). Dilute this mixture with about
50 mL absolute ethanol, stir at room temperature for 5-7 hs. Leave
overnight, collect the products formed by filtration, wash with ethanol,
and crystallize with the proper solvent.
5-[3-Amino-4-(4-bromophenyl)-6-phenylthieno[2,3-b]pyridin-
2-yl]-1,3,4-oxadiazole-2-thiol 20a
Crystallized from dioxane as orange crystals (53%); m.p. 280◦C;
IR (ν cm−1): 3250–3550 (broad band NH2, SH), 1653 (C=N) and
1613 (C=C); MS: 422 (M+-HS-C=N, 10%), 406 (422-O, 86.9%), 404
[M+-O(HS)C=N-N=, 86.1%], 380 (M+-oxadiazolyl-2-thiol, 8.6%), 103
(PhCN, 12.5%) and 73 (=N-N=C-SH, 17%); Anal. for C21H13BrN4OS2
(481.38): Calcd./Found (%): C,52.40/52.50, H,2.72/2.80, Br,16.60/16.50,
N,11.64/11.40, S,13.32/13.40.
5-{3-Amino-4-[4-(dimethylamino)phenyl]-6-phenylthieno[2,3-
b]pyrid-in-2-yl}-1,3,4-oxadiazole-2-thiol 20b
Crystallized from dioxane as orange crystals (51%); m.p. 280◦C; IR
(ν cm−1): 3150–3471 (broad band NH2, SH) and 1607 (C=C); Anal. for
C23H19N5OS2 (445.55): Calcd./Found (%): C,62.00/62.10, H,4.30/4.20,
N,15.72/15.80 S,14.39/14.40.
5-{3-Amino-4-[4-(dimethylamino)phenyl]-6-(4-
methylphenyl)thieno-[2,3-b]pyridin-2-yl}-1,3,4-oxadiazole-2-
thiol 20c
Crystallized from dioxane as brown crystals (62%); m.p. 260◦C; IR (ν
cm−1): 3179–3464 (broad band NH2, SH) and 1608 (C=C); MS: 459 (M+,
0.65%), which corresponds to the molecular weight of the molecular
formula C24H21N5OS2of the assigned structure, 457 (M+-2H, 0.56%),
431 (M-N2,1.02%), 415 (M+- NMe2, 1.69%), 400 (415-CH3, 5.43%), 384

1612
A. M. Abdel-Fattah et al.
(457-N2, =CSH, 100%), 368 (384-O, 6.67%), 324 (368-NMe2, 1.86%);
Anal. for C24H21N5OS2 (459.58): Calcd./Found (%): C,62.72/62.80,
H,4.61/4.50, N,15.24/15.30 S,13.95/14.00.
Synthesis of 21a–c
A mixture of each of 20a-c (1.20 g, 1.11 g, 1.15 g; 0.25 mmol of each)
and hydrazine hydrate (15–20 mL) was heated under reflux for 5–
7 hs. The products so formed after cooling were filtered off, washed
with cold ethanol, and crystallized from the proper solvent to give
21a–c.
4-Amino-5-[3-amino-4-(4-bromophenyl)-6-phenylthieno[2,3-
b]pyrid-in-2-yl]-4H-1,2,4-triazole-3-thiol 21a
Crystallized from dioxane as orange crystals (57%); m.p. 324◦C; IR
(ν cm−1): 2761–3452 (broad band NH2, SH) and 1604 (C=C); MS: 494
(M+-1, 18.84%), which corresponds to the loosing of H from the parent
peak, 462 (M+-SH,4.91%), 405 (M+-HNCS, N-NH2, 7.55%), 380 (M+- tri-
azole ring, 11.32%), 59 (HNCS, 34.34%), 60 (HS-N=CH2, 100%); Anal.
for C21H15BrN6S2 (495.41): Calcd./Found (%): C,50.91/51.0, H,3.05/3.10,
Br,16.13/16.20, N,16.96/17.10, S,12.94/13.0.
4-(4-Dimethylaminophenyl)-2-(5-hydrazino-1,3,4-oxadiazol-2-
yl)-6-phenylthieno[2,3-b]pyridin-3-amine 21b
Crystallized from ethanol as orange crystals (52%); m.p. 200◦C; IR (ν
cm−1): 3387, 3261 (NH2, NH) and 1608 (C=C); Anal. for C23H21N7OS
(443.52): Calcd./Found (%): C,62.28/62.40, H,4.77/4.50, N,22.11/22.10,
S,7.23/7.40.
4-(4-Dimethylaminophenyl)-2-(5-hydrazino-1,3,4-oxadiazol-2-
yl)-6-(4-methylphenyl)thieno[2,3-b]pyridin-3-amine 21c
Crystallized from ethanol as orange crystals (58%); m.p. 210◦C; IR (ν
1
cm−1): 3466, 3300 (NH2, NH), and 1610 (C=C); H NMR (δppm): 0.95
(s, 3H, CH3), 2.84 (s, 6H, NMe2), 4.90 (s, br., 2H, NH2 at thiophene), 5.44
(s, br., 2H, NH2NH), 5.73 (s, br., 1H, NHNH2), and 6.51–7.70 (m, 9h,
aromatic and Pyridine H-5); MS: 457 (M+, 1.88%), which corresponds
to the molecular weight of the molecular weight C24H23N7OS of the as-
signed structure, 441 (M+-NH2), 426 (M+-NH2NH, 8.85%), 429 (M+-N2,
5.50%), 413 (M+-NMe2), 359 (M+-oxadiazole residue, 100%), 315 (359-
NMe2, 36%); 314 (359-oxadiazole, CS, 34%), 143 (M+-314, 2.73%); Anal.
for C24H23N7OS (457.55): Calcd./Found (%): C,63.00/63.10, H,5.07/5.10,
N,21.43/21.30, S,7.01/7.10.

Pyridine-3-Carbonitrile Derivatives
1613
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