1,3-Disubstitutedpyrazole-4-caboxaldehyde in heterocyclic synthesis: A novel synthesis of pyridine-2(1H)-thione and fused nitrogen and/or sulfur heterocyclic derivatives

Article abstract of DOI:10.1080/10426500902814049

Pyridine-2(1H)-thione 5 was synthesized from the reaction of 3-[3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-yl]-1-phenylpropenone (3) and cynothioacetamide (4). Compound 5 reacted with halogented compounds 6a-e to give 2-S-alkylpyridine derivatives 7a-e, which could be in turn cyclized into the corresponding thieno[2,3-b]-pyridine derivatives 8a-e. Compound 8a reacted with hydrazine hydrate to give 9. The latter compound reacted with acetic anhydride (10a), formic acid (10b), acetic acid, ethyl acetoacetate, and pentane-2,4-dione to give the corresponding pyrido[3′,2′:4,5]thieno-[3,2-d]pyrimidine 13a,b, pyrazolo[3′,4′:4,5]thieno[3,2-d]pyridine 14 and thieno[2,3-b]-pyridine derivatives 18 and 20, respectively. Alternatively, 8c reacted with 10a,b and nitrous acid to afford the corresponding pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine 24a,b and pyrido[3′,2′:4,5]thieno[3,2-d][1,2,3]triazine 26 derivatives, respectively. Finally compound 5 reacted with methyl iodide to give 2-methylthiopyridine derivative 27, which could be reacted with hydrazine hydrate to yield the corresponding pyrazolo[3,4-b]-pyridine derivative 29.

Full text of DOI:10.1080/10426500902814049

This article was downloaded by: [University of Saskatchewan Library]
On: 22 June 2012, At: 04:00
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Phosphorus, Sulfur, and Silicon and the
Related Elements
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/gpss20
1,3-Disubstitutedpyrazole-4-
caboxaldehyde in Heterocyclic
Synthesis: A Novel Synthesis of
Pyridine-2(1H)-thione and Fused
Nitrogen and/or Sulfur Heterocyclic
Derivatives
Mohamed A. A. Elneairy a
a Cairo University, Faculty of Science, Chemistry Department, Giza,
Egypt
Available online: 03 Feb 2010
To cite this article: Mohamed A. A. Elneairy (2010): 1,3-Disubstitutedpyrazole-4-caboxaldehyde in
Heterocyclic Synthesis: A Novel Synthesis of Pyridine-2(1H)-thione and Fused Nitrogen and/or Sulfur
Heterocyclic Derivatives, Phosphorus, Sulfur, and Silicon and the Related Elements, 185:2, 469-483
To link to this article: http://dx.doi.org/10.1080/10426500902814049
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation
that the contents will be complete or accurate or up to date. The accuracy of any
instructions, formulae, and drug doses should be independently verified with primary
sources. The publisher shall not be liable for any loss, actions, claims, proceedings,
demand, or costs or damages whatsoever or howsoever caused arising directly or
indirectly in connection with or arising out of the use of this material.

Phosphorus, Sulfur, and Silicon, 185:469–483, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500902814049
1,3-DISUBSTITUTEDPYRAZOLE-4-CABOXALDEHYDE IN
HETEROCYCLIC SYNTHESIS: A NOVEL SYNTHESIS OF
PYRIDINE-2(1H)-THIONE AND FUSED NITROGEN
AND/OR SULFUR HETEROCYCLIC DERIVATIVES
Mohamed A. A. Elneairy
Cairo University, Faculty of Science, Chemistry Department, Giza, Egypt
Pyridine-2(1H)-thione 5 was synthesized from the reaction of 3-[3-(4-chlorophenyl)-1-
phenyl-1H-pyrazol-4-yl]-1-phenylpropenone (3) and cynothioacetamide (4). Compound
5 reacted with halogented compounds 6a–e to give 2-S-alkylpyridine derivatives 7a–e,
which could be in turn cyclized into the corresponding thieno[2,3-b]-pyridine derivatives
8a–e. Compound 8a reacted with hydrazine hydrate to give 9. The latter compound re-
acted with acetic anhydride (10a), formic acid (10b), acetic acid, ethyl acetoacetate, and
pentane-2,4-dione to give the corresponding pyrido[3ꢀ,2ꢀ:4,5]thieno-[3,2-d]pyrimidine 13a,b,
pyrazolo[3ꢀ,4ꢀ:4,5]thieno[3,2-d]pyridine 14 and thieno[2,3-b]-pyridine derivatives 18 and
20, respectively. Alternatively, 8c reacted with 10a,b and nitrous acid to afford the cor-
responding pyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-d]pyrimidine 24a,b and pyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-
d][1,2,3]triazine 26 derivatives, respectively. Finally compound 5 reacted with methyl iodide
to give 2-methylthiopyridine derivative 27, which could be reacted with hydrazine hydrate to
yield the corresponding pyrazolo[3,4-b]-pyridine derivative 29.
Keywords Pyrazolo[3ꢁ,4ꢁ:4,5]thieno[3,2-d]pyridine; pyridine-2(1H)-thione; pyrido[3ꢁ,2ꢁ:4,5]
thieno[3,2-d]-pyrimidine; pyrido[3ꢁ,2ꢁ:4,5]thieno[3,2-d]-[1,2,3]triazine; thieno[2,3-b]pyridine
INTRODUCTION
The pyrazole nucleus and its chemistry have found considerable attention due to out-
standing biological activities such as anti-anxiety,1 antibacterial, and antifungal properties.2
These findings prompted this work to introduce several pharmacophores such as pyridine,
pyrimidine, and thieno moieties into a pyrazole system hoping to obtain compounds with
enhanced potency. For the last three decades, synthesis and characterization of heterocyclic
derivatives of expected biological activities has gained considerable attention by this group
of researchers.3–13 A vast number of nitrogen heterocyclic derivatives have been synthesized
from which compounds containing the pyridine nucleus and its azolo, azino, and thieno
derivatives have constituted the main members. The reason is that these derivatives pos-
sess a wide range of biological activities and are commonly used in many pharmaceutical
and medicinal preparations. The pyridine nucleus exhibits antitumor14 and anti-amnsic15
Received 17 December 2008; accepted 11 February 2009.
Address correspondence to Mohamed A. A. Elneairy, Cairo University, Faculty of Science, Chemistry
Department, Giza 12613, Egypt. E-mail: elneairy65@yahoo.com
469

470
M. A. A. ELNEAIRY
activities. Ontheother hand, the S-alkylpyridinethionederivativeshaveshownneurotropic16
activity and are used as adenosine receptor ligands.17,18 They also have also cardiovascu-
lar.19 In addition, thieno[2,3-b]pyridine derivatives were reported to possess a broad range
of biological activities such as antimicrobial,20–24 anti-inflamatory,25 neurotropic,16 and
ganadotropin-releasing hormone-antagonizing activities.26
Furthermore, the pyridothienopyrimidines are reported to possess antiallergic ac-
tivity,27 antiprotozoals active against phelasterides dicentrarchi,28 antianaphylactic,29 and
antimicrobial20,21 activities. In addition, these compounds possess antipyretic,30 analgesic,31
and hypo-holesterolenic32 activities. Furthermore, the pyrazolo[3,4-d]pyridine derivatives
have been used as antimicrobial22,33,34 inhibitors of cyclindependent kinases35,36 and in-
hibitors of phosphodiesterase.37 Pyridine-2(1H)-thione was taken as the starting material
for the present study.
RESULTS AND DISCUSSION
The starting material 4-[3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-yl]-2-thioxo-
1,2-dihydropyridine-3-carbonitrile (5) was prepared in good yield via the reaction of
3-[3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-yl]-1-phenylpropenone (3) with cyanoth-
ioacetamide (4) in absolute ethanol in the presence of a catalytic amount of piperidine.
Thus, the IR spectrum of 5 showed the presence of the bands of the NH group (3280 cm−1
)
1
and the nitrile function at (2219 cm−1). The H NMR spectrum of 5 revealed signals of
the ring NH at δ = 7.0 ppm and 5H-pyrazole at δ = 9.1 ppm, in addition to the aromatic
protons (m, 15H, 7.42–7.99 δ ppm) (see Scheme 1 and the Experimental section).
O
O
N
N
H
N
O
CH3
N
+
H
N
2
Cl
Ph
3
N
1
Cl
NH2
Ar
Ph
NC
CN
S
S
4
N
H
5, Ar = C6H4-Cl-p
Scheme 1
The synthetic potential of 5 was demonstrated via its reaction with a variety of
halogenated active methylene reagents 6a–e. Thus, it has been found that 5 reacted with
ethyl chloroacetate (6a) in boiling ethanol in the presence of sodium acetate to give a
reaction product resulting from equimolecular addition of 6a to 5 and the loss of one
molecule of hydrogen chloride. The IR spectrum of this reaction product showed among

NOVEL SYNTHESIS OF PYRIDINE-2(1H)-THIONE
471
its absorption bands those corresponding to the presence of CN group (2215 cm−1) and
C O (1743 cm−1). Its 1H NMR spectrum revealed signals of CH2CH3 (t, 3H at δ = 1.32–
1.37 ppm), CH2CH3 (q, 2H at δ = 4.32–4.34 δppm), SCH2CO (s, 4.27 ppm). Based on
the above data, in addition to correct elemental analysis, this compound was formulated
as ethyl 2-[(3-cyano-6-phenyl-pyridin-2-yl)thio]acetate derivative 7a (see the Experimen-
tal section). In a similar manner, compound 5 reacted with each of chloroacetone (6b),
chloroacetamide (6c), chloroacetonitrile (6d), and 1-(4-chlorophenyl)-2-bromoethanone
(6e) to give the corresponding 2-S-alkylpyridine derivatives 7b–e, respectively. The struc-
tures of 7b–e were established based on the correct data of elemental analyses and spectra
(see the Experimental section and Scheme 2).
Ph
Ph
N
N
N
N
Ar
Ph
Ar
Ph
CN
S
CN
S
AcONa
reflux
XCH2Y
6a-e
+
N
H
Y
N
6a, x = Cl,Y = CO 2C2H5
b, x = Cl,Y = COCH 3
c, x = Cl,Y = CONH2
7a-e
MeONa
5
d, x = Cl,Y = CN
e, x = Br,Y = COC6H4-Cl-p
Ph
N
N
Ar
Ph
NH2
Y
6a-e/MeONa/hot
stirring
N
S
5,7,8a,Ar = C6H4-Cl-p,Y = CO2C2H5
b, Ar = C6H4-Cl-p,Y = COCH3
c,Ar = C6H4-Cl-p,Y = CONH2
d, Ar = C6H4-Cl-p,Y = CN
8a-e
e,Ar = C6H4-Cl-p,Y = COC6H4-Cl-p
Scheme 2
A further proof for the structures of 7a–e came from their cyclization by boiling
in sodium methoxide solution to give the corresponding thieno[2,3-b]pyridine derivatives
8a–e, respectively. The IR spectra of 8a–e were found to be free from the absorption bands
of the nitrile function, and instead new bands of the NH2 function were detected. Analytical
data of 8a–e were found almost identical to that of 7a–e, respectively, proving that the
nitrile function is involved in the cyclization step via addition of the active methylene group
at position-2 of the pyridine ring to the nitrile function at position-3 of 7a–e. The 1H NMR
spectra of 8a–e were also found to be free from the signals of the active methylene group,
proving also its involvement in the cyclization step leading to the formation of 8a–e.

472
M. A. A. ELNEAIRY
Another piece of solid evidence for the structures of 8a–e came from their inde-
pendent synthesis by performing the reaction between 5 and 6a–e, respectively, in a hot
methanolic/sodium methoxide solution for 2 h. Compounds 8a–e prepared via this route
1
were found to be completely identical in all aspects (analyses, IR and H NMR spectra)
with 8a–e prepared via the first route (see the Experimental section).
An unequivocal support for the structure of compound 8 came from the series of
reactions concerning which compound contains the ester group at position-2 of the thienyl
moiety. Thus, it has been found that 8a reacted with hydrazine hydrate to give 9. The IR
spectrum of this product showed the presence of the absorption bands of NH2, NH, and
C O groups. Its 1H NMR spectrum revealed signals of two NH2 and NH groups in addition
to the aromatic protons and 5H-pyrazole. Based on the above data, this reaction product
could then be formulated as the 3-amino-4-[3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-
yl]-6-phenylthieno[2,3-b]pyridine-2-carbohydrazide (9) (see the Experimental section and
Scheme 3).
Ph
Ph
N
N
N
N
Ar
Ph
Ar
Ph
NH2
NHNH2
NH2
OC2H5
H2N-NH2.H2O
N
S
N
S
O
O
9
8a
8a,9,Ar = C6H4-Cl-p
Scheme 3
The isolation of compound 9 with its adjacent NH2 and CONHNH2 functions stimu-
lated the insertion to utilize them as versatile starting material for the synthesis of several,
otherwise difficult to obtain heterocyclic derivatives through its reactions with a variety of
activated reagents. Thus, it has been found that 9 reacted with acetic anhydride (10a) to give
a reaction product with molecular formula C31H21ClN6OS corresponding to acetylation of
the NH2 group at the thiophene ring followed by cyclization via loss of one molecule of
water 13a. The structure of 13a was established based on the correct data of elemental
analyses and spectra. The IR spectrum of this reaction product showed the presence of
absorption bands of NH2 (3494, 3362 cm−1) and the ring CO group (1673 cm−1). The 1H
NMR spectrum of this reaction product revealed signals of NH2 and methyl at pyrimidine
ring (see the Experimental section and Scheme 4).
Moreover, compound 9 reacted with formic acid (10b), giving rise to the 3-
aminopyrido[3ꢁ,2ꢁ:4,5]thieno[3,2-d]pyrimidinone derivative 13b. The structure of 13b was
elucidated on the basis of elemental analysis and spectral data. The IR spectra of 13b
1
showed the presence of one NH2 and one CO. The H NMR spectrum of 13b revealed
also signals of NH2 group (s, 2H, at δ = 6.02 ppm) in addition to the multiplet of aromatic
protons (at δ = 7.27–8.30 ppm) (see the Experimental section). The formation of 13b in
this reaction is assumed to proceed via initial formylation of the NH2 group at position-3 of
the thienyl moiety of 9 followed by enolization, subsequent loss of the elements of water,
to yield the final isolable 13b (Scheme 4).

NOVEL SYNTHESIS OF PYRIDINE-2(1H)-THIONE
473
On the other hand, compound 9 was boiled in glacial acetic acid to afford the
corresponding pyrazolo[3ꢁ,4ꢁ:4,5]thieno[3,2-d]pyridine derivative 14. The structure of 14
could be confirmed based on the correct elemental analysis and spectral data backgrounds
(see the Experimental section and Scheme 4). Compound 14 was formed according to the
following mechanism38,39
:
Ph
Ph
N
N
N
N
Ar
Ph
Ar
Ph
NH2
NH2
AcOH
N
S
CONHNH2
N
S
CONHNHCOCH3
9
Ph
- CH3CONH2
N
N
Ar
H
N
NH
Ph
N
S
O
14
Compound 9 reacted also, with 3-(4-chlorophenyl)-2-cyanopropenonitrile with the
aim of obtaining the expected pyrazole derivative 15.
Unexpectedly, the 1H NMR spectrum of this reaction product did not agree with the
expected value of 15. Instead, and surprisingly, the 1H NMR spectrum of this product was
found to be in agreement with compound 16. This conclusion could be explained by the
fact that compound 9, instead of reacting of 3-(4-chloro-phenyl)-2-cyanopropenonitrile to
give the expected 15, underwent ylidene exchange with the liberation of the molecule of
malononitrile to give the final isolable 16. The structure of compound 16 could be elucidated
via its preparation via another route by reacting compound 9 with 4-chlorobenzaldehyde to
afford 16. Compound 16 prepared via this route was found to be completely identical with
16 prepared before in all aspects (mp = 320–322◦C, mixed mp = 320–322◦C, IR and 1H
NMR data), (see the Experimental section and Scheme 4).
As a further continuation of exploring the synthetic potential of 9, it was thus of
value to investigate its reaction with a variety of active methylene esters and ketones.
Thus, it has been found that a reaction product of molecular formula C33H23ClN6O2S
was obtained upon reacting 9 with ethyl acetoacetate in boiling glacial acetic acid. This
formula corresponded to an equimolecular addition of 9 to the ester and the loss of one
molecule of water and one molecule of ethanol. The IR spectrum of this reaction product
showed the presence of absorption bands of one NH2 group (3430, 3390 cm−1) and CO
1
group (1670 cm−1). Its H NMR spectrum revealed the presence of signals of one CH3
(s, 3H, at δ = 2.29 ppm) and NH2 (s, 2H, at δ = 5.99 ppm) (see the Experimental
section). No proton signals corresponding to the ethyl ester group were detected. This
means that the ester group was consumed in the reaction to give the final isolable product,
which was formulated as 3-amino-2-[(3-methylpyrazol-5-on-1-yl)carbonyl]-6-phenyl-4-
[3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-yl]thieno[2,3-b]pyridine (18). The formation
of 18 in this reaction is assumed to proceed via initial condensation between the carbonyl
group of ethyl acetoacetate and the amino group of hydrazonyl with the loss of molecule

474
M. A. A. ELNEAIRY
Ph
Ph
N
N
N
N
Ar
H
Ar
Ph
R
R
N
N
OH
NHNH2
O
NHNH2
Ph
N
S
N
S
O
O
11a,b
12a,b
10a, R = CH3, R' =COCH3
b, R = R' = H
Ph
N
-H2O
Ph
N
N
N
RCO2R'
10a,b
Ar
Ph
NH2
NHNH2
Ar
Ph
N
R
N
S
9
NNH2
O
N
S
O
13a, R = CH3
b, R = H
ArCH=C(CN)2
or ArCHO
CH3COOH
Ph
N
N
Ph
N
N
Ar
NH2
Ar
Ph
H
N
H
N
NH
O
Ph
N
N
Ar'
S
O
N
S
Ph
N
16
N
14
Ar
NH2
NH2
N
CN
N
Ph
N
S
9,11-16,Ar = C6H4-Cl-p
Ar
O
15
Scheme 4
of water and cyclization via loss of one molecule of ethanol to yield the final isolable 18
through the intermediate 17.
The reaction between 9 and pentane-2,4-dione was also investigated. Thus, a reaction
product of molecular formula C34H25ClN6OS was obtained upon reacting 9 with pentane-
2,4-dione (see Scheme 5).
This formula corresponded to equimolecular addition followed by the loss of two
molecules of water to give compound 20. Only the bands of NH2 group (3430, 3380 cm−1
)
and one CO group (1680 cm−1) were detected in the IR spectrum of this reaction
product. Also signals of one NH2 group (s, 2H, at δ = 6.22 ppm) and two CH3 groups
(2.28 and 2.53 δ ppm) were detected in the 1H NMR spectrum of this reaction product. By

NOVEL SYNTHESIS OF PYRIDINE-2(1H)-THIONE
475
Ph
N
N
Ar
Ph
NH2
NHNH2
CH3COCH2COCH3
-H2O
CH3COCH2CO2Et
-H2O
N
S
O
Ph
N
Ph
9
N
N
N
Ar
Ph
Ar
Ph
NH2
NH2
CH3
CH3
H
N
H
N
N
N
S
N
N
S
O
O
EtO
O
H3C
O
17
-EtOH
19
-H2O
Ph
Ph
N
N
N
N
Ar
Ph
Ar
CH3
CH3
NH2
NH2
N
N
N
N
N
S
Ph
N
S
O
O
CH3
O
18
20
9,17-20,Ar = C6H4-Cl-p
Scheme 5
collecting the above data in addition to correct elemental analysis, this reaction product
could be formulated as 3-amino-2-[(3,5-dimethylpyrazol-5-on-1-yl)carbonyl]-4-[3-(4-
chlorophenyl)-1-phenyl-1H-pyrazol-4-yl]-6-phenylthieno[2,3-b]pyridine (20) (see the
Experimental section and Scheme 5).
Also, compound 8c reacted with acetic anhydride (10a) to give 2-methyl-9-
[3-(4-chloropheyl)-1-phenyl-1H-pyrazol-4-yl)]-7-phenylpyrido-[3ꢁ,2ꢁ:4,5]thieno[3,2-d]
pyrimidin-4(3H)-one (24a), whose structure was established based on correct elemental
analysis and spectral data studies. The formation of 24a in this reaction is assumed to
proceed first via acetylation of the NH2 group at position-3 of the thiophene moiety in
8c, followed by enolization and subsequent loss of the elements of water to give the final
isolable product 24a (see Scheme 6).
Moreover, compound 8c also reacted with formic acid (10b) to give 24b. The IR
spectrum of the reaction product showed the disappearance of the absorption bands of
the two NH2 groups and instead showed the presence of only one NH, a fact which
1
was confirmed by the H NMR data. Compound 24b is assumed to be formed via initial
formylation of the amino group followed by enolization and subsequent loss of the elements
of water to yield the final isolable product (see the Experimental section and Scheme 6).
Compound 24b could be prepared via another route by reacting 8c with triethylortoformate
to give 24b. Compound 24b prepared via this route was found to be identical in all
backgrounds as 24b previously prepared.

476
M. A. A. ELNEAIRY
Ph
N
N
Ph
N
N
Ar
Ph
Ar
Ph
N
O
N
-HCl
N
N
Cl
NH
N
S
NH2
N
S
26
Ph
O
25
N
N
10a, R = CH3, R' = COCH3
b, R = R' =H
HNO2
Ar
Ph
NH2
RCO2R'
10a,b
CH(OC2H5)3
NH2
N
S
Ph
O
Ph
8c
N
N
N
N
Ar
Ph
H
Ar
Ph
H
R
N
N
OC2H5
NH2
O
NH2
N
S
N
S
O
O
23
21a,b
-EtOH
Ph
Ph
N
N
N
N
Ar
Ph
Ar
R
N
N
O
R
-H2O
OH
NH2
NH
N
S
Ph
N
S
O
24a, R = CH3
b, R = H
22a,b
8, 21-26,Ar = C6H4-Cl-p
Scheme 6
On the other hand, compound 8c reacted with nitrous acid to give 26. The IR spec-
trum of this reaction product showed the absorption band that corresponded to NH and
1
CO groups. Moreover, its H NMR spectrum revealed a signal corresponding to NH.
Based on the above data, compound 26 could be formulated as 9-[(3-(4-chloropheyl)-1-
phenyl-1H-pyrazol-4-yl)]-7-phenyl pyrido[3ꢁ,2ꢁ:4,5]thieno[3,2-d][1,2,3]triazin-4(3H)-one
(26) (see the Experimental section and Scheme 6).
Finally, compound 5 reacted with methyl iodide in sodium methoxide to afford a
reaction product corresponding to equimolecular addition of 5 to the reagent followed by
the loss of one molecule of hydrogen iodide to give 27. The IR spectrum of this reaction
1
product showed the band of the nitrile function at (2221 cm−1). The H NMR of 27
revealed the signal of methyl (s, 3H, 2.76). Based on the above data, this reaction product

NOVEL SYNTHESIS OF PYRIDINE-2(1H)-THIONE
477
could be formulated as the 2-methylthionicotinonitrile derivative 27 (see Scheme 7 and the
Experimental section).
Ph
Ph
Ph
N
N
N
N
N
N
Ar
Ph
Ar
Ph
Ar
Ph
CN
S
CN
H2N-NH2.H2O
CN
CH3I
SCH3
N
H
N
N
NHNH2
27
Ph
28
N
N
5
Ar
Cycl.
NH2
5,27-29,Ar = C6H4-Cl-p
N
Ph
N
N
H
29
Scheme 7
The 2-methylthionicotinonitrile derivative 27 reacted with hydrazine hydrate to give a
sulfur-free reaction product of molecular formula C27H19ClN6. This formula corresponded
to equimolecular addition of the reactant and reagent and the loss of one molecule of methyl
mercaptan. The band of the nitrile function was entirely absent in the IR spectrum of the
reaction product, and instead a band of new amino group was detected (3418, 3383 cm−1
)
and NH (3317 cm−1) in this spectrum. The H NMR spectrum revealed one NH2 (s, 2H,
at δ = 4.59 ppm) and one NH (s, 1H, at δ = 12.29 ppm). Based on the above data, the
reaction product could be formulated as the 3-aminopyrazolo[3,4-b]pyridine derivative 29,
most likely formed via the intermediary of the non-isolable 2-hydrazinopyridine derivative
28 (see the Experimental section and Scheme 7).
1
EXPERIMENTAL
All melting points are uncorrected. IR spectra were recorded as KBr discs on a
Shimadzu FTIR-8201PC spectrophotometer. 1H NMR spectra were recorded on a Varian
Mercury 300 MHz and Varian Gemini 200 MHz. Spectrometers using TMS as an internal
standard and DMSO-d6 as solvents and chemical shifts are expressed as δ ppm units. The
Microanalytical Center of Cairo University performed microanalyses. Compounds 140 and
341 were prepared according to procedures in the literature.
Synthesis of 4-[3-(4-Chlorophenyl)-1-phenyl-1H-pyrazol-4-yl]-6-phenyl-
2-thioxo-1,2-dihydropyridine-3-carbonitrile (5)
A mixture of each of 3 (0.01 mol) and 4 (0.01 mol) in absolute ethanol (30 mL)
containing a catalytic amount of piperidine (0.4 mL) was heated under reflux for 4 h. The
product formed was collected by filtration, washed with cold ethanol, and then crystallized
from ethanol to give 5 as yellow crystals (72%); mp 240–242◦C; IR(υ cm−1): NH (3280),
CN (2219), 1H NMR (δ ppm): 7.00 (br, 1H, NH) and 7.42–7.99 (m, 15H, ArH’s), 9.10 (s,

478
M. A. A. ELNEAIRY
1H, 5H-pyrazole), Anal. for C27H17ClN4S (464.97): calcd./found(%): C (69.74/69.77), H
(3.69/3.71), Cl (7.62/7.65) N (12.05/12.03), S (6.90/6.92).
Synthesis of 7a–e
A mixture of 5 (0.01 mol), each of 6a–e (0.01 mol), and sodium acetate (0.015 mol,
2.04 g) in ethanol (20 mL) was heated under reflux for 2 h. The products thus formed were
collected by filtration, washed with cold ethanol, and then crystallized from the proper
solvent to give 7a–e, respectively.
Ethyl
2-({4-[3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-yl]-3-cyano-6-
phenylpyridin-2-yl}thio)acetate (7a). Crystallized from ethanol as yellow crystals
(73%); mp 180–182◦C; IR (υ cm−1): CN (2215), C O (1743); 1H NMR (δ ppm): 1.32–1.37
(t, 3H, CH2CH3), 4.27 (s, 2H, SCH2), 4.32–4.34 (q, 2H, OCH2CH3), 7.40–7.89
(m, 15H, ArH’s), 9.10 (s, 1H, 5H-pyrazole), Anal. for C31H23ClN4O2S (551.059):
calcd./found(%): C (67.57/67.55), H (4.21/4.23), Cl (6.43/6.45), N (10.17/10.15), S
(5.82/5.85).
4-[3-(4-Chlorophenyl)-1-phenyl-1H-pyrazol-4-yl]6-phenyl-2-[(2-oxo-propyl)
thio]nicotinonitrile (7b). Crystallized from dioxane as buff crystals (67%); mp
1
226–228◦C; IR (υ cm−1): CN (2220), C O (1715), H NMR (δ ppm): 2.30 (s, 3H,
SCH2COCH3), 4.36 (s, 2H, SCH2COCH3), 7.49–7.97 (m, 15H, ArH’s), 9.08 (s, 1H, 5H-
pyrazole), Anal. for C30H21ClN4OS (521.003) calc./found C (69.16/69.19), H (4.06/4.03),
Cl (6.80/6.83), N (10.75/10.72), S (6.15/6.17).
2-({4-[3-(4-Chlorophenyl)-1-phenyl-1H-pyrazol-4-yl]-3-cyano-6-phenyl-
pyridin-2-yl}thio)acetamide (7c). Crystallized from dioxane as white crystals (70%);
1
mp 267–269◦C; IR (υ cm−1): NH2 (3450,3410), CN (2215), C O (1682), H NMR
(δ ppm): 4.08 (s, 2H, SCH2CONH2), 7.23 (s, 2H, SCH2CONH2), 7.42–8.18 (m, 15H,
ArH’s), 9.07 (s, 1H, 5H-pyrazole), Anal. for C29H20ClN5OS (522.02): calcd./found(%): C
(66.72/66.75), H (3.86/3.84), Cl (6.79/6.82), N (13.42/13.44), S (6.14/6.12).
4-[3-(4-Chlorophenyl)-1-phenyl-1H-pyrazol-4-yl]-2-[(cyanomethyl)thio]-
6-phenylnicotinonitrile (7d). Crystallized from dioxane/ethanol as gray crystals
1
(68%); mp 23–25◦C; IR (υ cm−1): CN (2221), CH2CN (2232), H NMR (δ ppm):
4.51 (s, 2H, SCH2CN), 7.40–8.25 (m, 15H, ArH’s), 9.11 (s, 1H, 5H-pyrazole), Anal. for
C29H18ClN5S (504.006): calcd./found(%): C (69.11/69.13), H (3.60/3.63), Cl (7.03/7.00),N
(13.90/13.92), S (6.36/6.34).
4-[3-(4-Chlorophenyl)-1-phenyl-1H-pyrazol-4-yl]-2-[2-(4-chlorophenyl)oxo-
ethyl]thio]-6-phenylnicotinonitrile (7e). Crystallized from ethanol as yellow
1
crystals (71%); mp 135–137◦C; IR (υ cm−1): CN (2222), C O (1697), H NMR (δ
ppm): 5.02 (s, 2H, SCH2CO), 7.41–8.13 (m, 19H, ArH’s), 9.11 (s, 1H, 5H-pyrazole),
Anal. for C35H22Cl2N4OS (617.547): calcd./found(%): C (68.07/68.05), H (3.59/3.61), Cl
(11.48/11.51), N (9.07/9.05), S (5.19/5.21).
Synthesis of Thieno[2,3-b]pyridine Derivatives 8a–e
Method A. A mixture of each of 5 (0.01 mol) and sodium methoxide (0.01 mol,
0.23 g of sodium in 20 mL of CH3OH) was heated before boiling for 2 min, then each of
6a–e (0.01 mol) was added and stirred for 2 h at room temperature. The products formed
were collected by filtration, washed with cold ethanol, and then crystallized from the proper
solvent to give the final products 8a–e, respectively.

NOVEL SYNTHESIS OF PYRIDINE-2(1H)-THIONE
479
Method B. A mixture of each of 7a–e (0.01 mol) in methanolic sodium methoxide
was heated under reflux for 2 h. The products formed were collected by filtration, washed
with cold ethanol, and then crystallized from the proper solvent to give 8a–e, respectively.
Ethyl
3-amino-4-[(3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)]-6-
phenylthieno[2,3-b]pyridine-2-carboxylate (8a). Crystallized from dioxane as
yellow crystals (67%); mp 267–269◦C; IR (υ cm−1): NH2 (3492, 3380), C O (1674),
1H NMR (δ ppm):1.28–1.33 (t, 3H, COCH2CH3), 4.22–4.25 (s, 2H, COCH2CH3),
6.17 (s, 2H, NH2), 7.37–8.18 (m, 15H, ArH’s), 8.96 (s, 1H, 5H-pyrazole), Anal.
for C31H23ClN4O2S (551.059): calcd./found(%): C (67.57/67.55), H (4.21/4.23), Cl
(6.43/6.44), N (10.17/10.19), S (5.82/5.85).
3-Acetyl-3-amino-4-[(3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)-6-
phenylthieno[2,3-b]pyridine (8b). Crystallized from acetic acid as pale yellow
1
crystals (67%); mp 254–256◦C; IR (υ cm−1): NH2 (3449, 3278), C O (1681), H NMR
(δ ppm): 2.37 (s, 3H, COCH3), 6.20 (s, 2H, NH2), 6.98–8.03 (m, 15H, ArH’s), 8.76 (s,
1H, 5H-pyrazole), Anal. for C30H21N4OSCl (521.033): calcd./found(%): C (69.16/69.18),
H (4.06/4.04), Cl (6.80/6.83), N (10.75/10.72), S (6.15/16.12).
3-Amino-4-[(3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)]-6-phenyl-
thieno[2,3-b]pyridine-2-carboxamide (8c). Crystallized from dioxane as yellow
1
crystals (67%); mp 267–269◦C; IR (υ cm−1): NH2 (3458, 3318), C O (1658), H NMR
(δ ppm): 6.19 (s, 2H, NH2), 7.22 (s, 2H, CONH2), 7.37–8.14 (m, 15H, ArH’s), 8.96 (s,
1H, 5H-pyrazole), Anal. for C29H20ClN5OS (522.02): calcd./found(%): C (66.72/66.75),
H (3.86/3.83), Cl (6.79/7.01), N (13.42/10.44) and S (6.14/16.12).
3-Amino-4-[(3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)]-6-phenyl-
thieno[2,3-b]pyridine-2-carbonitrile (8d). Crystallized from acetic acid as yellow
crystals (69%); mp 292–294◦C; IR (υ cm−1): NH2 (3462, 3345), CN (2194), 1H NMR (δ
ppm): 6.00 (s, 2H, NH2), 7.38–8.19 (m, 15H, ArH’s), 8.96 (s, 1H, 5H-pyrazole), Anal. for
C29H18ClN5S (504.006): calcd./found(%): C (69.11/69.13), H (3.60/3.63), Cl (7.03/7.05),
N (13.90/13.93), S (6.36/6.32).
3-Amino-2-(4-chlorobenzoyl)-4-[(3-(4-chloropheyl)-1-phenyl-1H-pyrazol-
4-yl]-6-phenylthieno[2,3-b]pyridine (8e). Crystallized from acetic acid as yellow
crystals (67%); mp 243–245◦C; IR (υ cm−1): NH2 (3475, 3305), C O (1678), Anal.
for C35H22Cl2N4OS (617.547): calcd./found(%): C (68.07/68.05), H (3.59/3.61), Cl
(11.48/11.50), N (9.07/9.10), S (5.19/5.22).
Synthesis of 3-Amino-4-[(3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)-
6-phenylthieno[2,3-b]pyridine-2-carbohydrazide (9)
A solution of 8a (0.01 mol) in hydrazine hydrate (10 mL) and pyridine (30 mL)
was heated under reflux for 10 h. The reaction mixture was evaporated to one-third
of its volume and allowed to cool, then was treated with ethanol. The solid product
was collected by filtration and crystallized from dioxane to give 9 as yellow crystals
1
(72%); mp 198–199◦C; IR (υ cm−1): NHNH2 (3494, 3362, 3318), C O (1669), H
NMR (δ ppm): 3.6 (s, 2H, CONHNH2), 6.15 (s, 2H, NH2 at thiophene ring), 7.35–8.16
(m, 16H, ArH’s and CONHNH2), 8.90 (s, 1H, 5H-pyrazole), Anal. for C29H21ClN6OS
(537.05): calcd./found(%): C (64.86/64.89), H (3.94/3.96), Cl (6.60/6.63), N (15.65/15.67),
S (5.97/6.00).

480
M. A. A. ELNEAIRY
Synthesis of (13a,b)
A solution of 9 (0.01 mol) and each of acetic anhydride (10a) and formic acid (10b)
(20 mL of each) was heated under reflux for 5 h. Excess solvent was evaporated in vacuo and
cooled. The solid formed was collected by filtration, washed with ethanol, and crystallized
from acetic acid to give 13a,b, respectively.
3-Amino-9-[(3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)]-2-methyl-7-
phenylpyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-d]pyrimidin-4(3H)-one
(13a). Crystallized
from acetic acid as buff crystals (69%); mp 286–288◦C; IR (υ cm−1): NH2 (3494, 3362),
1
C O (1673), H NMR (δ ppm): 2.21 (s, 3H, CH3 at pyrimidine ring), 7.29–8.22 (m,
17H, ArH’s and NNH2), 8.97 (s, 1H, 5H-pyrazole), Anal. for C31H21ClN6OS (561.057):
calcd./found(%): C (66.36/66.33), H (3.77/3.75), Cl (6.32/6.35), N (14.98/14.96), S
(5.72/5.74).
3-Amino-9-[(3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)]-7-phenyl-
pyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-d]pyrimidin-4(3H)-one (13b). Crystallized from acetic
acid as yellow crystals (73%); mp 350–352◦C; IR (υ cm−1): NH2 (3450, 3330),
C O (1673), 1H NMR (δ ppm): 6.02 (s, 2H, NNH2), 7.27–8.30 (m, 16H, ArH’s
and 2H-pyrimidine), 8.98 (s, 1H, 5H-pyrazole), Anal. for C30H19ClN6OS (547.03):
calcd./found(%): C (65.87/65.85), H (3.50/3.52), Cl (6.48/6.51), N (5.36/5.34), S
(5.86/5.90).
Synthesis of 8-[(3-(4-Chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)-6-phenyl-
1,2-dihydropyrazolo[3ꢀ,4ꢀ:4,5]thieno[3,2-d]pyridin-3-one (14)
A solution of 9 (0.01 mol) in glacial acetic acid (30 mL) was heated under reflux for 5
h. The excess solvent was evaporated in vacuo and cooled. The solid product was collected
by filtration, washed with ethanol, and crystallized from acetic acid to give 14 as brown
crystals (67%); mp 307–309◦C, IR (υ cm−1): two NH (3435, 3380), C O (1675), 1H NMR
(δ ppm): 3.89 (s, 1H, NH), 5.96 (s, 1H, NH), 7.26–8.25 (m, 15H, ArH’s), 8.99
(s, 1H, 5H-pyrazole), Anal. for C29H18ClN5OS (520.005): calcd./found(%): C
(66.98/67.01), H (3.49/3.47), Cl (6.82/6.85), N (13.47/3.50), S (6.17/6.15).
Synthesis of 3-amino-N-(4-chlorophenylmethylene)4-[(3-(4-chlorophe-
nyl)-1-phenyl-1H-pyrazol-4-yl)]-6-phenylthieno[2,3-b]pyridine-2-carbohyrazide
(16). A solution of each of 9 (0.01 mol) and 4-chlorobenzaldehyde or (4-
chlorobenzylidene)malononitrile (0.01 mol) in pyridine (30 mL) was heated under
reflux for 5 h. The excess solvent was evaporated in vacuo and cooled. The solid product
was collected by filtration, washed with ethanol, and crystallized from dioxane/ethanol
to give 16 as yellow crystals (71%); mp 320–322◦C; IR (υ cm−1): NH2 (3455, 3342),
1
NH (3320), C O (1670), H NMR (δ ppm): 6.77 (s, 2H, NH2 at thiophene ring),
7.37–8.20 (m, 19H, ArH’s), 8.96 (s, 1H, 5H-pyrazole), 11.56 (s, 1H, CONH N ),
Anal. for C36H24ClN6OS (659.587): calcd./found(%): C (65.55/65.58), H (3.67/3.65), Cl
(10.75/10.73), N (12.74/2.77), S (4.86/4.85).
Synthesis of 3-Amino-4-[(3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)]-
2-(3-methyl-1H-pyrazol-5-on-1-yl)carbonyl]-6-phenylthieno[2,3-b]pyridine
(18)
A solution of 9 (0.01 mol) and ethyl acetoacetate (0.01 mol) in acetic acid (30 mL)
was heated under reflux for 4 h. The excess solvent was evaporated in vacuo and cooled.

NOVEL SYNTHESIS OF PYRIDINE-2(1H)-THIONE
481
The solid product was collected by filtration, washed with ethanol, and crystallized from
acetic acid to give 18 as yellow crystals (67%); mp above 360◦C; IR (υ cm−1): NH2 (3430,
3390), CO (1670), 1H NMR (δ ppm): 2.10 (s, 2H, COCH2C(CH3) = N), 2.29 (s, 3H, CH3
at pyrazolone), 5.99 (s, 2H, NH2), 7.31–8.09 (m, 15H, ArH’s), 9.09 (s, 1H, 5H-pyrazole),
Anal. for C33H23ClN6O2S (603.094): calcd./found(%): C (65.72/65.74), H (3.84/3.81), Cl
(5.88/5.91), N (13.93/13.95), S (5.32/5.35).
Synthesis of 3-Amino-4-[(3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)]
2-(3,5-dimethyl-1H-pyrazol-1-yl)carbonyl]-6-phenylthieno[2,3-b]pyridine (20)
A solution of 9 (0.01 mol) and pentane-2,4-dione (30 mL) was heated under reflux
for 5 h. The excess solvent was evaporated in vacuo and cooled. The solid product was
collected by filtration, washed with ethanol, and crystallized from dioxane to give 20 as
yellow crystals (73%); mp 260–262◦C; IR (υ cm−1): NH2 (3430, 3380), C O (1680),
1H NMR (δ ppm): 2.28 (s, 3H, CH3 at pyrazolone-5), 2.53 (s, 3H, CH3 at pyrazolone-
3), 6.22 (s, 2H, NH2), 7.37–8.19 (m, 16H, ArH’s), 8.98 (s, 1H, 5H-pyrazole), Anal. for
C34H25ClN6OS (601.121): calcd./found(%): C (67.93/67.95), H (4.19/4.16), Cl (5.90/5.93),
N (13.98/14.01), S (5.33/5.35).
Synthesis of 2-Methyl-9-[(3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-
yl)]-7-phenylpyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-d]pyrimidin-4(3H)-one (24a)
A mixture of 8c (0.01 mol) and acetic anhydride (10a) (20 mL) was heated under
reflux for 5 h. The excess solvent was evaporated in vacuo and allowed to cool. The solid
product was formed collected by filtration and crystallized from acetic acid to give 24a as
1
brown crystals (69%); mp 357–359◦C; IR (υ cm−1): NH (3420), C O (1673), H NMR
(δ ppm): 2.12 (s, 3H, CH3 at pyrimidine-2), 7.25–8.19 (m, 15H, ArH’s), 8.96 (s, 1H, 5H-
pyrazole), 12.60 (s, 1H, NH), Anal. for C31H20ClN5OS (546.041): calcd./found (%): C
(68.19/68.22), H (3.69/3.66), Cl (6.49/6.51), N (12.83/12.85), S (5.87/5.85).
Synthesis of 9-[(3-(4-Chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)-7-phenyl-
pyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-d]pyrimidin-4(3H)-one (24b)
A solution of 8c (0.01 mol) and formic acid (10b) (20 mL) was heated under reflux
for 3 h. The excess solvent was evaporated in vacuo and allowed to cool. The solid product
formed was collected by filtration and crystallized from acetic acid to give 24b as yellow
1
crystals (66%); mp 364–366◦C; IR (υ cm−1): NH (3455), H NMR (δ ppm): 7.25–8.21
(m, 16H, ArH’s and CH at pyrimidine-2), 8.95 (s, 1H, 5H-pyrazole), 12.75 (s, 1H, NH),
Anal. for C30H18ClN5OS2 (532.016): calcd./found (%): C (67.73/67.71), H (3.41/3.44), Cl
(6.66/6.67), N (13.16/13.13), S (6.03/6.05).
Synthesis of 9-[(3-(4-Chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)-7-phenyl-
pyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-d][1,2,3]triazin-4(3H)-one (26)
A stirred cold solution (0–5◦C) of the 8c (0.01 mol) in acetic acid (5 mL) and
concentrated hydrochloric acid (2 mL) was treated with a cold solution of sodium nitrite
(0.01 mol, 0.23 g in 5 mL of H2O) dropwise with stirring. Stirring was continued for
1 h. The reaction mixture was then allowed to stand at room temperature for 15 min. The

482
M. A. A. ELNEAIRY
solid obtained was collected by filtration and crystallized from dioxane as to give 26 as
1
pale yellow crystals (68%); mp 264–266◦C; IR (υ cm−1): NH (3203), C O (1686), H
NMR (δ ppm): 7.25–8.30 (m, 15H, ArH’s) 9.05 (s, 1H, 5H-pyrazole), 15.47 (s, 1H, NH),
Anal. for C29H17ClN6OS (533.004): calcd./found(%): C (65.35/65.38), H (3.21/3.23), Cl
(6.65/6.63), N (15.77/5.80), S (6.02/6.05).
Synthesis of 4-[(3-(4-Chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)]-6-
phenyl-2-methylthionicotinonitrile (27)
A mixture of 5 (0.01 mol) and iodomethane (0.015 mol) in methanolic sodium
methoxide was heated under reflux for 2 h then cooled. The solid formed was collected
by filtration and washed with water, then crystallized from acetic acid to give 27 as buff
1
crystals (73%); mp 267–269◦C; IR(υ cm−1): CN (2221), H NMR (δ ppm): 2.76 (s, 3H,
CH3 at pyridine), 7.42–8.18 (m, 15H, ArH’s) and 9.08 (s, 1H, 5H-pyrazole), Anal. for
C28H19ClN4S (478.996): calcd./found(%): C (70.21/70.24), H (4.00/4.03), Cl (7.40/7.42),
N (11.70/.73), S (6.69/6.72).
Synthesis of 4-[(3-(4-Chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)]-6-
phenyl-1H-pyrazolo-[3,4-b]pyridine-3-amine (29)
A solution of 27 (0.01 mol), hydrazine hydrate (5 mL), and pyridine (30 mL) was
heated under reflux for 1 week. The excess solvent was evaporated in vacuo and cooled.
The solid formed was collected by filtration, dried, and crystallized from ethanol to give 29
as yellow crystals (67%); mp 180–182◦C; IR (υ cm−1): NH2 (3418, 3383), NH (3317); 1H
NMR (δ ppm): 4.59 (s, 2H, NH2), 7.27–8.13 (m, 15H, ArH’s), 8.96 (s, 1H, 5H-pyrazole),
12.29 (s, 1H, NH) C27H19ClN6 (462.933): calcd./found(%): C (70.05/70.03), H (4.14/4.16),
Cl (7.66/7.68), N (18.15/18.12).
REFERENCES
1. J. Haeufel and E. Breitmaier, Angew. Chem., 13, 604 (1974).
2. V. M. Barot, Asian J. Chem., 8, 565 (1996).
3. A. M. Abdel-Fattah, M. A. A. Elneairy, M. N. Gouda, and F. A. Attaby, Phosphorus, Sulfur, and
Silicon, 183(7), 1592 (2008).
4. A. M. Abdel-Fattah, M. A. A. Elneairy, M. N. Gouda, and F. A. Attaby, Afinidad, 65(534), 163
(2008).
5. M. A. A. Elneairy, M. A. M. Gad-Elkareem, and A. M. Taha, Heteroatom Chem., 18(4), 399
(2007).
6. M. A. M. Gad-Elkareem, M. A. A. Elneairy, and Adel M. Taha, Heteroatom Chem., 18(4), 405
(2007).
7. A. M. Abdel Fattah, M. A. A. Elneairy, and M. A. M. Gad-Elkareem, Phosphorus, Sulfur, and
Silicon, 182(6), 1351 (2007).
8. S. M. Eldin, F. A. Attaby, and M. A. A. Elneairy, Heteroatom Chem., 9, 571 (1998).
9. A. A. Abbas, M. A. A. Elneairy, and Y. N. Mabkhot, J. Chem. Res. (s), 4, 124 (2001).
10. M. A. A. Elneairy, M. A. M. Gad-Elkareem, and A. M. Taha, J. Sulfur Chem., 26(4–5), 381
(2005).
11. S. M. Eldin, M. A. A. Elneairy, F. A. Attaby, and A. K. K. El-Louh, Phosphorus, Sulfur, and
Silicon, 176(1), 49 (2001).

NOVEL SYNTHESIS OF PYRIDINE-2(1H)-THIONE
483
12. M. A. A. Elneairy and A. M. Abdel-Fattah, Phosphorus, Sulfur, and Silicon, 175(1), 15 (2001).
13. F. A. Attaby, S. M. Eldin, and M. A. A. Elneairy, J. Chem. Res., (S), 10, 632 (1998).
14. T. Fujita, K. Wada, M. Oguchi, and S. Kurakata, PCT Int. Appl. WO 01 05, 780 (2001); Chem.
Abstr., 134, 131426b (2001).
15. Y. A. Ammar, M. M. Ghorab, A. M. Sh. El-Sharief, and Sh. I. Mohamed, Heteroatom Chem.,
13, 199 (2002).
16. A. Krauze, S. Germame, O. Eberlins, I. Sturms, V. Klusa, and G. Duburs, Eur. J. Med. Chem.,
34, 301 (1999).
17. U. Rosentreter, R. Henning, M. Bauser, T. Kraemer, A. Vaupel, W. Huebsch, K. Dembowsky,
O. S. Schraufstaetter, P. J. Stasch, T. Krahn, and E. Perzborn, PCT Int. Appl. WO 01 25, 210
(1999); Chem. Abstr., 134, 295744e (2001).
18. U. Rosentreter, T. Kraemer, A. Vaupel, W. Huebsch, N. Diedrichs, T. Krahn, K. Dembowsky,
and P. J. Stasch, PCT Int. Appl. WO 02 70,485 (2002); Chem. Abstr., 137, 216880g (2002).
19. U. Rosentreter, T. Kraemer, A. Vaupel, W. Huebsch, N. Diedrichs, T. Krahn, K. Dembowsky, P.
J. Stasch, and M. Shimada, PCT Int. Appl. WO 02 79,195 (2002); Chem. Abstr., 137, 279099e
(2002).
20. A. M. Hussein, F. A. Abu-Shanab, and E. A. Ishak, Phosphorus, Sulfur, and Silicon, 159, 55
(2000).
21. S. M. Eldin, Z. Naturforsch., 54b, 674 (1999).
22. F. A. Attaby and A. M. Abdel-Fattah, Phosphorus, Sulfur, and Silicon, 155, 253 (1999).
23. F. A. Attaby, M. A. A. Elneairy, and M. S. Elsayed, Arch. Pharm. Res., 22(2), 194 (1999).
24. A. E. Abdel-Rahman, E. A. Bakhite, and E. A. Al-Taifi, J. Chin. Chem. Soc., 49(2), 223 (2002).
25. G. P. Moloney, Molecules, 6, M203 (2001).
26. S. Furuya, N. Choh, N. Suzuki, and T. Imada; PCT Int. Appl. WO 000–000, 493 (2002); Chem.
Abstr., 132, 64179s (2000).
27. J. M. Quintela, C. Peinador, C. Veiga, L. Gonzales, L. M. Botana, A. Alfonso, and R. Riguera,
Bioorg. Med. Chem., 6, 1911 (1998).
28. J. M. Quintela, C. Peinador, L. Gonzales, R. Iglesias, A. Parama, F. Alvares, M. L. Sanmartin,
and R. Riguera, Eur. J. Med. Chem., 38, 265 (2003).
29. G. Wagner, S. Leistner, H. Vieweg, U. Krasselt, and J. Prantz, Pharmazie, 48, 342 (1993).
30. E. Bousquet, F.Guerrera, N. A. Siracusa, A. Caruso, and M. A. Roxas, Farmaco Ed. Sci., 39, 110
(1984).
31. C. G. Dave, P. R. Shah, C. K. Dave, and V. J. Patel, J. Indian Chem. Soc., 66, 48 (1989).
32. C. J. Shishoo, M. B. Daventi and V. S. Bhadti, Indian Patent, 151456 (1983); Chem. Abstr., 100,
209858 (1984).
33. M. A. A. Elneairy, F. A. Attaby, and M. S. Elsayed, Phosphorus, Sulfur, and Silicon, 167(1), 161
(2000).
34. F. E. Goda, A. A. M. Abdel-Aziz, and O. A. Attef, Bioorg. Med. Chem., 12, 1845 (2004).
35. R. N. Misra, D. B. Rawlins, H. Y. Xiao, W. Shan, I. Bwsuker, K. A. Kellar, J. G. Mulheron, J.
S. Sack, J. S. Tokarski, S. D. Kimball, and K. R. Webester, Bioorg. Med. Chem. Lett., 13, 1133
(2003).
36. R. N. Misra, H. Y. Xiao, D. B. Rawlins, W. Shan, K. A. Kellar, J. G. Mulheron, J. S. Sack, J. S.
Tokarski, S. D. Kimball, and K. R. Webster, Bioorg. Med. Chem. Lett., 13, 2405 (2003).
37. H. Ochiai, A. Isida, T. Ohtani, K. Kusumi, K. Kishikawa, S. Yamamoto, H. Takeda, T. Obata, H.
Nakai, and M. Toda, Chem. Pharm. Bull., 52(9), 1098 (2004).
38. E. A. Bakhite, A. E. Abdel-Rahman, O. S. Mohamed, and E. A. Thabet, Phosphorus, Sulfur, and
Silicon, 179, 1983 (2004).
39. M. A. A. Elneairy, M. A. M. Gad-Elkareem, and A. M. Abdel-Fattah, Phosphorus, Sulfur, and
Silicon, 181(6), 1451 (2006).
40. M. A. Kira, M. O Abdl-Rahman, and K. Z. Gadalla, Tetrahedron Lett., 2, 109 (1969).
41. T. J. M. Chary, Ch. V. N. Reddy, and A. K. Murthy, Indian J. Chem., 31B, 495 (1992).