2-ethanethioamide in heterocyclic synthesis: Synthesis and characterization of several new pyridine and fused azolo- and azinopyridine derivatives

Article abstract of DOI:10.1080/10426500903051823

Pyridine-2(1H)-thione derivatives 3a,b were synthesized from the reaction of 1-(phenyl-sulfanyl)acetone (1) and cinnnamonitrile derivatives 2a,b. Compounds 3a,b reacted with different halogenated reagents 7a-f to give 2-S-alkylpyridine derivatives 8a-l, which could be, in turn, cyclized into the corresponding thieno[2,3-b]pyridine derivatives 9a-l. Compounds 9d,j reacted with acetic anhydride, formic acid, carbon disulfide, phenyl isothiocyanate, and nitrous acid to yield the corresponding pyrido[3′,2′:4,5]thieno[2, 3-d]pyrimidine 12a,b, 15a,b, 17a,b, 20a,b, and pyrido[3′,2′:4,5] thieno[2,3-d][1,2,3]triazinone derivatives 22a,b, respectively. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426500903051823

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2-Ethanethioamide in Heterocyclic
Synthesis: Synthesis and
Characterization of Several New Pyridine
and Fused Azolo- and Azinopyridine
Derivatives
Mohamed A. A. Elneairy a , Sanaa M. Eldin b & Mohamed F. M. Attia b
a Department of Chemistry, Faculty of Science, Cairo University,
Giza, Egypt
b Department of Pesticidal Chemistry, National Research Centre,
Dokki, Giza, Egypt
Published online: 02 Jul 2010.
To cite this article: Mohamed A. A. Elneairy , Sanaa M. Eldin & Mohamed F. M. Attia (2010) 2-
Ethanethioamide in Heterocyclic Synthesis: Synthesis and Characterization of Several New Pyridine
and Fused Azolo- and Azinopyridine Derivatives, Phosphorus, Sulfur, and Silicon and the Related
Elements, 185:7, 1346-1357, DOI: 10.1080/10426500903051823
To link to this article: http://dx.doi.org/10.1080/10426500903051823
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Phosphorus, Sulfur, and Silicon, 185:1346–1357, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500903051823
2-ETHANETHIOAMIDE IN HETEROCYCLIC SYNTHESIS:
SYNTHESIS AND CHARACTERIZATION OF SEVERAL
NEW PYRIDINE AND FUSED AZOLO- AND
AZINOPYRIDINE DERIVATIVES
Mohamed A. A. Elneairy,1 Sanaa M. Eldin,2
and Mohamed F. M. Attia2
1Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt
2Department of Pesticidal Chemistry, National Research Centre, Dokki, Giza, Egypt
Pyridine-2(1H)-thione derivatives 3a,b were synthesized from the reaction of 1-(phenyl-
sulfanyl)acetone (1) and cinnnamonitrile derivatives 2a,b. Compounds 3a,b reacted with
different halogenated reagents 7a–f to give 2-S-alkylpyridine derivatives 8a–l, which could be,
in turn, cyclized into the corresponding thieno[2,3-b]pyridine derivatives 9a–l. Compounds
9d,j reacted with acetic anhydride, formic acid, carbon disulfide, phenyl isothiocyanate,
and nitrous acid to yield the corresponding pyrido[3ꢀ,2ꢀ:4,5]thieno[2,3-d]pyrimidine 12a,b,
15a,b, 17a,b, 20a,b, and pyrido[3ꢀ,2ꢀ:4,5]thieno[2,3-d][1,2,3]triazinone derivatives 22a,b,
respectively.
Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental
file.
Keywords Pyridine-2(1H)-thione; pyrido[3ꢁ,2ꢁ:4,5]thieno[2,3-d]pyrimidine; pyrido-[3ꢁ,2ꢁ:4,
5]thieno[2,3-d][1,2,3]triazinone
INTRODUCTION
The development of simple synthetic routes for widely used heterocyclic derivatives
from readily available reagents and chemicals is one of the major tasks in organic synthesis.1
For the last three decades, the synthesis and characterization of heterocyclic derivatives of
expected biological activities has gained considerable attention by this group of research.2–12
A vast number of nitrogenous heterocyclic derivatives has been synthesized from which
compounds containing the pyridine nucleus and its azolo, azino, and thieno derivatives
constituted the main members.
The reason is that these derivatives possess a wide range of biological activities
and are commonly used in many pharmaceutical and medicinal preparations. The pyri-
dine nucleus exhibits antitumor13 and anti-aminesic14 activities. On the other hand, the
S-alkylpyridinethione derivatives showed neurotropic15 activity and are used as adenosine
Received 25 October 2008; accepted 19 May 2009.
Address correspondence to Mohamed A. A. Elneairy, Department of Chemistry, Faculty of Science, Cairo
University, Giza 12613, Egypt. E-mail: elneairy65@yahoo.com
1346

2-ETHANETHIOAMIDE IN HETEROCYCLIC SYNTHESIS
1347
receptor ligands.16,17 They have also cardiovascular activity.18 In addition, the thieno[2,3-b]
pyridine derivatives were reported to possess a broad range of biological activities such as
antimicrobial,19–23 anti-inflamatory,24 neurotropic,15 and ganadotropin-releasing hormone
antagonizing activities.25
Furthermore, the pyridothienopyrimidines are reported to possess anti-allergic activ-
ity,26 antiprotozoals active against phelasterides dicentrarchi,27 anti-anaphylictic,28,29 and
antimicrobial19,20 activities. In addition, these compounds possess anti-inflamatory,30–32 an-
tipyretic,33,34 analgesic,35 and hypo-holesterolenic36 activities. The pyridine-2(1H)-thiones
3a,b were taken as the starting materials for the present study.
RESULTS AND DISCUSSION
The starting materials 6-methyl-3-cyano-4-aryl-5-phenylsulfanylpyridine-2(1H)-
thiones 3a,b were prepared in good yields via the reaction of 1-(phenylsulfanyl)acetone,
(compound 1, prepared by the reaction of benzene thiol and chloroacetone in cold methanol
according to the method of Karthikeyan et al.37) with the thiocarboxamidocinnamonitrile
derivatives 2a,b in absolute ethanol in the presence of catalytic amounts of triethylamine.
To our knowledge, compounds 3a,b have been prepared for the first time and are not
previously reported in the literature. Thus, the IR spectrum of 3a showed the presence of
1
the bands of the NH group (3310 cm−1) and the nitrile function at 2221 cm−1. The H
NMR spectrum of 3a revealed signals of ring NH at δ = 6.58 ppm, ring-CH3 at δ = 2.46
ppm in addition to the aromatic protons (m, 10H, at δ = 7.12–7.43 ppm). On the other
hand, the 1H NMR spectrum of 3b revealed signals of ring NH, ring-CH3, phenyl-OCH3
in addition to the aromatic protons (m, 9H, at δ = 7.20–7.51 ppm).
The structure of both 3a,b was further established by their alternative synthesis via
another route by the reaction of 1 with the appropriate aromatic aldehydes 4a,b to give the
corresponding ylidene derivatives 5a,b, respectively.37 Compounds 5a,b then reacted with
cyanothioacetamide (6) in absolute ethanol in the presence of triethylamine to yield the
corresponding 3a,b in good yields. Compounds 3a,b prepared via this route were found to
be identical in all aspects to 3a,b previously prepared (see Scheme 1 and the Experimental
section).
The synthetic potential of 3a,b was demonstrated via their reactions with a variety of
halogenated reagents 7a–f. Thus, it has been found that 3a reacted with chloroacetone (7a)
in hot ethanol in the presence of sodium acetate to give a reaction product resulting from
equimolecular addition of 7a to 3a and loss of one molecule of hydrogen chloride. The IR
spectrum of this reaction product showed among its absorption bands those corresponding
1
to the presence of CN group (2221 cm−1) and chain C O (1715 cm−1). Its H NMR
spectrum revealed signals of two CH3 at δ = 2.55 and 3.58 ppm and CH2 at δ = 4.00 ppm.
Based on the above data, in addition to the correct elemental analysis, this compound was
formulated as the 2-S-acetonylpyridine derivative 8a.
In a similar manner, 3a reacted with each of chloroacetonitrile (7b), ethyl chloroac-
etate (7c), chloroacetamide (7d), 1-(4-chlorophenyl)-2-bromoethanone (7e), and 1-(4-
bromophenyl)-2-bromoethanone (7f) to give the corresponding 2-S-alkylpyridine deriva-
tives 8b–f, respectively. Structures of 8b–f were established based on the correct data of
elemental analyses, IR and 1H NMR spectral data, which were found also to be in a good
agreement with the assigned structures (see the Experimental section).

1348
M. A. A. ELNEAIRY ET AL.
O
Cl
+
PhSH
CH3
Ar
N
O
CN
CN
S
S
S
Ph
Ar
Ph
CH3
+
CSNH2
H3C
2a,b
1
H
3a,b
O
O
NH2
NC
S
Ar
4a,b
H
Ph
CH3
S
6
Ar
H
5a,b
1-5a, Ar = Ph
b,Ar = C6H4-OCH3-p
Scheme 1
A further proof for the structure of 8a–f came from their cyclization by boiling
their ethanolic solutions in the presence of catalytic amounts of piperidine to give the
corresponding thieno[2,3-b]pyridine derivatives 9a-f, respectively. The IR spectra of 9a–f
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 9a–f were found to be almost
identical to that of 8a–f, respectively, proving that the nitrile function is involved in the
cyclization step via addition of the active methylene to the nitrile function in compounds
1
8a–f. The H NMR spectra of 9a–f 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 9a–f.
Another piece of solid evidence for the structure of 9a–f came from their independent
synthesis by performing the reaction between 3a and 7a-f, respectively, in boiling ethanolic
sodium ethoxide. Compounds 9a–f prepared via this route were found to be completely
identical in all aspects (analyses, IR, and 1H- MR spectra) with 9a–f prepared via the first
route (see Scheme 2 and the Experimental section).
The other starting compound 3b was also involved in the same series of reactions as
for 3a described before. Thus, 3b reacted with the halogenated reagents 7a–f in hot ethanolic
sodium acetate to give the corresponding 2-S-alkyl substituted pyridine derivatives 8g–l,
respectively, in good yields. Again the structures 8g–l were established based on correct
elemental analyses and spectral data studies. These data were found to be consistent with the
assigned structure in each case (see Scheme 2 and the Experimental section). Cyclization
of each of 8g–l by boiling their ethanolic solutions in the presence of piperidine afforded
the corresponding thieno[2,3-b]pyridine derivatives 9g–l, respectively.
Again the IR spectra of 9g–l did not show the bands of the nitrile function and showed
the bands of the newly born NH2 group in each case. In addition, no signals of CH2 groups
were detected in the 1H NMR spectra of 9g–l.

2-ETHANETHIOAMIDE IN HETEROCYCLIC SYNTHESIS
1349
Ar
Ar
S
CN
S
S
N
AcONa
Ph
Ph
+
X
Y
C2H5OH
H3C
N
S
Y
H3C
N
7a-f
H
8a-l
Ar
3a,b
NH2
S
EtOH/pip.
/heat
7a-f EtONa/heat
Ph
Y
S
H3C
N
9a-l
7a, X = Cl; Y =COCH3
8-9a,Ar = Ph; Y =COCH 3
b, X = Cl; Y =CN
c, X = Cl; Y = CO2Et
b,Ar = Ph; Y =CN
c,Ar = Ph; Y =CO 2Et
d, X = Cl; Y = CONH2
d,Ar = Ph; Y =CONH 2
e, X = Br; Y =COC6H4-Cl-p
f, X = Br; Y =COC6H4-Br-p
e,Ar = Ph; Y =COC 6H4-Cl-p
f,Ar = Ph; Y =COC 6H4-Br-p
g,Ar = C6H4-OCH3-p; Y =COCH3
h,Ar = C6H4-OCH3-p; Y =CN
i,Ar = C6H4-OCH3-p;Y =CO2Et
j,Ar = C6H4-OCH3-p;Y =CONH2
k,Ar = C6H4-OCH3-p; Y =COC6H4-Cl-p
l,Ar = C6H4-OCH3-p;Y =COC6H4-Br-p
Scheme 2
Another piece of solid evidence for the structure of 9g–l came from their independent
synthesis by performing the reaction between 3b and 7a–f, respectively, in boiling ethanolic
sodium ethoxide. Compounds 9g–l prepared via this route were found to be completely
identical in all aspects (analyses, IR, and 1H NMR spectra) with 9g–l prepared via the first
route (see Scheme 2 and the Experimental section).
The isolation of a large number of compounds of 9a–l with their active polyfunctional
groups stimulated the interest to utilize them as excellent candidates for the synthesis of
other new heterocyclic derivatives via their reactions with a variety of different reagents.
Thus, 9d, as an example of the series, reacted with acetic anhydride to give a reaction
product corresponding to the addition of one molecule of 9d to another molecule of the an-
hydride followed by the loss of one molecule of acetic acid and one molecule of water to af-
ford the corresponding 2,7-dimethyl-9-phenyl-8-phenyl-thiopyrido[3ꢁ,2ꢁ:4,5]thieno[3,2-d]-
pyrimidin-4(3H)-one (12a) through the intermediates 10a and 11a, whose structure was
established based on correct elemental analysis and spectral data studies (see Scheme 3 and
the Experimental section).
In a similar manner, 9j reacted with acetic anhydride also to afford the corresponding
9-(4-methoxyphenyl)-2,7-dimethyl-8-phenylthiopyrido[3ꢁ,2ꢁ:4,5]-thieno[3,2-d]pyrimidin-
4(3H)-one (12b). The IR spectrum of this reaction product showed the presence of an
absorption band of NH group (3413 cm−1) in addition to the band of ring C O (1675 cm−1
)
only. Its 1H NMR spectrum revealed signals of two CH3 groups at δ = 2.10 and 2.66 ppm,
one methoxy group (OCH3) at δ = 3.82 ppm, a signal for NH group (s, 1H, NH, at
δ = 12.80 ppm) in addition to the multiplet of the aromatic protons (m, 9H, at δ = 6.90–7.29
ppm). Based on the above findings, in addition to correct elemental analysis and spectral

1350
M. A. A. ELNEAIRY ET AL.
Ar
NH2
S
(CH3CO)2O
Ph
HCOOH
NH2
H3C
N
S
O
9d,Ar = Ph
j,Ar = C6H4-O-CH3-p
Ar
N
Ar
H
N
H
H
CH3
N
S
S
Ph
Ph
O
NH2
O
NH2
H3C
S
H3C
N
S
O
O
13a,b
10a,b
Ar
N
H
N
Ar
N
H
N
S
H
OH
NH
S
CH3
OH
NH
Ph
Ph
H3C
S
H3C
S
O
O
14a,b
11a,b
-H2O
-H2O
10-15a,Ar = Ph
b,Ar = C6H4-O-CH3-p
Ar
Ar
N
S
N
H
NH
S
N
O
CH3
NH
Ph
Ph
H3C
N
S
H3C
S
O
12a,b
15a,b
Scheme 3
data studies which were found to be in a good agreement with the assigned structure, the
reaction product was formulated as 12b (see Scheme 3 and the Experimental section).
Moreover, compounds 9d,j also reacted with formic acid to afford reaction products
resulting from equimolecular addition of each of 9d,j to the acid followed by the loss of
two molecules of water in each case to yield 15a,b.
The IR spectra of the reaction products showed the disappearance of the absorption
bands of the two NH2 groups and instead showed the presence of only one NH in each
1
case, a fact which was confirmed by the H NMR data. Based on the above findings,
the reaction products could be formulated as the pyrido[3ꢁ,2ꢁ:4,5]thieno[3,2-d]pyrimidin-
4(3H)-one derivatives 15a,b, respectively, which could be formed through the intermediates
13a,b and 14a,b (see Scheme 3 and the Experimental section).
An interesting reaction with carbon disulfide took place with each of 9d,j to give
reaction products formed via the addition of each of 9d,j to carbon disulfide followed
by elimination of one molecule of hydrogen sulfide to give 17a,b. The IR spectra of
these reaction products showed the presence of a NH group, a ring-CO group, and a ring
1
C S group in each case. The H NMR spectrum of compound 17b revealed signals of
one CH3 and one OCH3 groups at δ = 2.58 and 3.79 ppm, respectively, and two NH
groups at δ = 5.60 and 12.38 ppm, in addition to the multiplet of the aromatic protons

2-ETHANETHIOAMIDE IN HETEROCYCLIC SYNTHESIS
1351
Ar
Ar
N
+
N
-
S
N
O
S
N Cl
Ph
N
-HCl
Ph
NH
NH2
H3C
N
S
H3C
S
O
22a,b
21a,b
Ar
N
HNO2
PhNCS
NH2
NH2
S
CS2
Ph
H3C
S
O
9d,Ar = Ph
j,Ar = C6H4-OCH3-p
Ar
N
H
S
H
H
N
Ar
N
N
S
Ph
N
Ph
S
SH
NH2
Ph
S
NH2
H3C
S
H3C
S
O
O
16a,b
-H2S
18a,b
Ar
H
H
N
Ar
N
S
N
S
Ph
Ph
N
S
Ph
NH
SH
NH2
H3C
N
S
H3C
S
O
17a,b
O
19a,b
-H2S
16-22a, Ar = Ph
b,Ar = C6H4-O-CH3-p
Ar
H
N
S
N
O
Ph
Ph
NH
H3C
N
S
20a,b
Scheme 4
at δ = 6.86–7.37 ppm. The reaction products could be formulated as the 2-thioxo-2,3-
dihydropyrido[3ꢁ,2ꢁ:4,5]thieno[3,2-d]pyrimidin-4(1H)-one derivatives 17a,b, respectively,
(see Scheme 4 and the Experimental section).
The synthetic potential of each of 9d,j was further explored via their reactions with
phenyl isothiocyanate. Thus, 9d,j reacted with phenyl isothiocyanate in pyridine to yield
products corresponding to equimolecular addition of the reactants and then cyclization via
loss of hydrogen sulfide in each case. The IR spectra of the reaction products showed the
presence of NH and one ring-CO in each case. The singlet signals of two NH and that of
the ring CH3 in addition to the aromatic protons were revealed in the 1H NMR spectra of
the reaction products. Collecting the above data together with the correct analytical data
led to formulation of the reaction products as the 2-anilinopyrido[3ꢁ,2ꢁ:4,5]thieno[3,2-d]-
pyrimidin-4(3H)-one derivatives 20a,b, respectively (see Scheme 4 and the Experimental
section).

1352
M. A. A. ELNEAIRY ET AL.
Work was also extended to shed more light on the synthetic potential of com-
pounds 9. Thus, each of 9d,j reacted with nitrous acid to give the corresponding
pyrido[3ꢁ,2ꢁ:4,5]thieno[3,2-d][1,2,3]triazin-4(3H)-one derivatives 22a,b, respectively,
whose structures were confirmed based on both elemental analysis and spectral data. In
this respect, the IR spectrum of 22a showed the absorption bands of one NH (3397 cm−1
)
and the ring-CO group (1665 cm−1) only. The IR spectrum of 22b showed the absorption
bands of the NH and ring-CO groups in their proper positions, while its 1H NMR spectrum
revealed the signal of the OCH3 group at δ = 3.73 ppm in addition to those of the NH (s,
1H, 8.00 δppm), pyridine-CH3 at δ = 2.55 ppm, and the aromatic protons (m, 9H, at δ =
6.83–7.37 ppm) (see Scheme 4 and the Experimental section).
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 CDCl3 and DMSO-d6 as solvents; chemical shifts are expressed as δ ppm units.
Mass spectra were recorded on a Shimadzu GCMS-QP1000EX using inlet type at 70 eV.
The Microanalytical Center of Cairo University performed microanalyses. Compounds
2a,b were prepared according to the procedures in the literature.38
Synthesis of 6-Methyl-4-phenyl-5-phenylthio-2-thioxo-1,2-
dihydropyridine-3-carbonitrile (3a)
A mixture of 1 (0.01 mol, 1.66 g) and 2a (0.01 mol, 1.88 g) in absolute ethanol
(30 mL) containing a catalytic amount of triethylamine (0.4 mL) was heated under reflux
for 5 h. The product formed was collected by filtration, washed with cold ethanol, and then
crystallized from ethanol to give 3a as yellow crystals (63%); mp 220–222◦C; IR (υ cm−1):
NH (3310), CN (2221), C S (1541); 1H NMR (δ ppm): 2.46 (s, 3H, CH3 at pyridine), 6.58
(br, 1H, NH), 7.12–7.43 (m, 10H, ArH’s); Anal. for C19H14N2S2 (334.5): calcd./found(%):
C (68.23/68.20), H (4.22/4.25), N (8.38/8.37), S (19.17/19.13).
Synthesis of 4-(4-Methoxyphenyl)-6-methyl-5-phenylthio-2-thioxo-
1,2-dihydropyridine-3-carbonitrile (3b)
A mixture of 1 (0.01 mol, 1.66 g) in sodium methoxide (prepared from 0.01 mol of
sodium metal in methanol 10 mL) and 2b (0.01 mol, 2.18 g) was heated under reflux for 5 h.
The reaction mixture was cooled, poured onto ice-cold water, and then acidified with HCl.
The product formed was collected by filtration, washed with cold ethanol, and crystallized
from ethanol to give 3b as yellow crystals (65%); mp 220–222◦C; IR (υ cm−1): NH (3311),
1
CN (2220), C S (1540); H NMR (δ ppm): 2.56 (s, 3H, CH3 at pyridine), 3.73 (s, 3H,
OCH3), 6.62 (br., 1H, NH), 7.20–7.51 (m, 9H, ArH’s); Anal. for C20H16N2OS2 (364.4):
calcd./found(%): C (65.90/65.93), H (4.42/4.40), N (7.69/7.68), S (17.60/17.64).
Synthesis of 3a,b
A mixture of 5a,b (0.01 mol) and cyanothioacetamide (6, 0.01 mole, 1.0 g) in sodium
methoxide (prepared from 0.01 mol of sodium metal in methanol 10 mL) was heated under

2-ETHANETHIOAMIDE IN HETEROCYCLIC SYNTHESIS
1353
reflux for 5 h. The reaction mixture was cooled, poured onto ice-cold water, and then
acidified with HCl. The product formed was collected by filtration, washed with cold
ethanol, and crystallized from ethanol to give 3a,b, respectively.
Synthesis of 8a–l
A mixture of each of the reactants A (0.01 mol) in ethanol (30 mL), sodium acetate
(0.015 mole, 2.04 g), and reactants B (0.01 mol, of each) was heated under reflux for 2 h.
The products so formed were collected by filtration, washed with cold ethanol, and then
crystallized from the proper solvent. As an example of the characterization provided, 8a is
shown below. Complete data for 8b–8l are found in the Supplemental Materials (available
online).
6-Methyl-2-[(2-oxopropyl)thio]-4-phenyl-5-phenylthionicotinonitrile (8a).
Crystallized from ethanol as yellow crystals (75%); mp 112–4◦C; IR (υ cm−1): CN (2221),
C O (1715); 1H NMR (δ ppm): 2.55 (s, 3H, CH3 at pyridine), 3.58 (s, 3H, COCH3), 4.00 (s,
2H, -SCH2), 6.89–7.42 (m, 10H, ArH’s); Anal. for C22H18N2OS2 (390.5): calcd./found(%):
C (67.66/67.69), H (4.65/4.66), N (7.17/7.14), S (16.42/16.44).
Synthesis of the Thienopyridine Derivatives 9a–l
Method A. A mixture of each of the reactants A (0.01 mol of each) in ethanolic
sodium ethoxide and reactants B (0.01 mol) was heated under reflux for 2 h. The products
so formed were collected by filtration, washed with cold ethanol, and then crystallized
from the proper solvent to give 9a–l, respectively. As an example of the characterization
provided, 9a is shown below. Complete data for 9b–9l are found in the Supplemental
Materials.
Method B. A mixture of each of the reactants C (0.01 mole of each) in ethanolic
sodium ethoxide was heated under reflux for 2 h. The products so formed were collected
by filtration, washed with cold ethanol, and then crystallized from the proper solvent.
2-Acetyl-3-amino-6-methyl-4-phenyl-5-phenylthiothieno [2,3-b]pyridine
(9a). Orange crystals (72%); mp 248–250◦C; crystallized from ethanol/dioxane; IR (υ
cm−1): NH2 (3436, 3484), C O (1680); 1H NMR (δ ppm): 1.61 (s, 2H, NH2), 2.44 (s, 3H,
CH3 at pyridine), 2.76 (s, 3H, COCH3), 7.07–7.50 (m, 10H, ArH’s); Anal. for C22H18N2OS2
(390.5): calcd./found(%): C (67.66/67.62), H (4.65/4.62), N (7.17/7.14), S (16.42/16.44).
Synthesis of the Pyridothienopyrimidinone Derivatives 12a,b
A mixture of 9d,j (0.01 mol of each) and acetic anhydride (20 mL) was heated under
reflux for 3 h. The reaction mixture was then evaporated to half of its volume and allowed
to cool. The solid products formed were collected by filtration and crystallized from the
proper solvent to give 12a,b, respectively.
2,7-Dimethyl-9-phenyl-8-phenylthiopyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-d]pyrimi
din-4(3H)-one (12a). Crystallized from ethanol/dioxane as white crystals (69%); mp
1
350–352◦C; IR(υ cm−1): NH (3410), C O (1673), H NMR (δ ppm): 2.01 (s, 3H, CH3
at pyridine), 2.68 (s, 3H, CH3 at pyrimidine), 6.91–7.39 (m, 10H, ArH’s), 12.66 (1H,
NH at pyrimidine); Anal. for C23H17N3OS2 (415.5): calcd./found(%): C (66.48/66.51), H
(4.12/4.15), N (10.11/10.08), S (15.43/15.47).

1354
M. A. A. ELNEAIRY ET AL.
9-(4-Methoxyphenyl)-2,7-dimethyl-8-phenylthiopyrido[3ꢀ,2ꢀ:4,5]thieno-
[3,2-d]pyrimidin-4(3H)-one (12b). Greenish-white crystals (70%); mp 318–320◦C;
crystallized from ethanol-dioxane mixture; IR (υ cm−1): NH (3413), C O (1675);
1H-NMR (δ ppm): 2.10 (s, 3H, CH3 at pyrimidinone), 2.66 (s, 3H, CH3 at pyridine), 3.82
(s, 3H, OCH3), 6.90–7.29 (m, 9H, ArH’s), 12.80 (s, 1H, NH); Anal. for C24H19N3O2S2
(445.5): calcd./found(%): C (64.70/64.74), H (4.30/4.33), N (9.43/9.42), S (14.39/14.36).
Synthesis of 15a,b
Compounds 9d,j (0.01 mol of each) and formic acid (15 mL) were heated under
reflux for 3 h. The reaction mixture was evaporated to two-thirds of its volume and then
allowed to cool. The solid products formed were collected by filtration and crystallized
from the proper solvent to give 15a,b, respectively.
7-Methyl-9-phenyl-8-phenylthiopyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-d]pyrimidin-
4(3H)-one (15a). Crystallized from ethanol/dioxane as pale yellow crystals (68%); mp
340–341◦C; IR (υ cm−1): NH (3416), C O (1677); 1H NMR (δ ppm): 2.71 (s, 3H, CH3
at pyridine), 6.95–7.41 (m, 10H, ArH’s), 8.04 (s, 1H, pyrimidine-H5), 12.92 (s, 1H, NH
at pyrimidine); Anal. for C22H15N3OS2 (401.5): calcd./found(%): C (65.81/65.83), H
(3.77/3.79), N (10.47/10.50), S (15.97/15.93).
9-(4-Methoxyphenyl)-7-methyl-8-phenylthiopyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-
d]pyrimidin-4(3H)-one (15b). Crystallized from ethanol/dioxane as pale yellow
1
crystals (70%); mp 182–184◦C; IR (υ cm−1): NH (3414), C O (1677); H NMR (δ
ppm): 2.63 (s, 3H, CH3 at pyridine), 3.77 (s, 3H, OCH3), 7.95 (s, 1H, CH), 12.79 (s, 1H,
NH), 6.86–7.22 (m, 9H, ArH’s); Anal. for C23H17N3O2S2 (431.5): calcd. /found(%): C
(64.02/64.05), H (3.97/3.94), N (9.74/9.77), S (14.86/14.83).
Synthesis of 17a,b
A mixture of 9d,j (0.01 mol of each) and carbon disulfide (4 mL) in pyridine (20 mL)
was heated under reflux for 48 h. The reaction mixture was cooled, poured onto ice-cold
water, and then neutralized (pH = 7) with hydrochloric acid. The product formed was
collected by filtration, washed with cold ethanol, and crystallized from the proper solvent
to give 17a,b, respectively.
7-Methyl-9-phenyl-8-phenylthio-2-thioxo-2,3-dihydropyrido[3ꢀ,2ꢀ:4,5]-
thieno[3,2-d]pyrimidin-4(1H)-one (17a). Crystallized from ethanol/dioxane mixture
as brown crystals (70%); mp 266–268◦C; IR (υ cm−1): NH (3400), C S (1540), C O
1
(1668), H NMR (δ ppm): 2.68 (s, 3H, CH3 at pyridine), 6.89–7.83 (m, 11H, ArH’s and
NH pyrimidine-H1), 13.05 (s, 1H, NH pyrimidine-H3); Mass: M+ (100%), 432 (14.9%),
373 (17.8%), 356 (42.5%), 343 (26.8%), 267 (10.2%), 78 (12.1%), 77 (25.5%); Anal. for
C22H15N3OS3 (433.5): calcd./found(%): C (60.94/60.91), H (3.49/3.52), N (9.69/9.66), S
(22.19/22.15).
9-(4-Methoxyphenyl)-7-methyl-8-phenylthio-2-thioxo-2,3-dihydropyrido
[3ꢀ,2ꢀ:4,5]thieno[3,2-d]pyrimidin-4(1H)-one (17b). Crystallized from ethanol/ diox-
ane as brown crystals (69%); mp 148–150◦C; IR(υ cm−1): NH (3402), C S (1543), C O
1
(1666); H NMR (δ ppm): 2.58 (s, 3H, CH3 at pyridine), 3.79 (s, 3H, OCH3), 5.60 (s,
1H, NH), 6.86–7.37 (m, 9H, ArH’s), 12.38 (s, 1H, CO-NH-CS); Mass: M+ (33%), 423
(16.9%), 422 (36%), 421 (100%), 405 (13.9%), 403 (86.8%), 375 (28%), 284 (11.4%), 163

2-ETHANETHIOAMIDE IN HETEROCYCLIC SYNTHESIS
1355
(15.9%), 149 (15.9%), 77 (15.3%); Anal. for C23H17N3O2S3 (463.5): calcd./found(%): C
(59.59/59.57), H (3.70/3.74), N (9.06/9.05), S (20.75/20.77).
Synthesis of 20a,b
A mixture of 9d,j (0.01 mol of each) and phenyl isothiocynate (0.01 mol) in pyridine
(20 mL) was heated under reflux for 5 h. The reaction mixture was cooled, poured onto ice-
cold water, and then acidified with a few drops of hydrochloric acid. The product formed
was collected by filtration, washed with cold ethanol, and crystallized from the proper
solvent to give 20a,b, respectively.
7-Methyl-9-phenyl-8-phenylthio-2-anilinopyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-d]-
pyrimidin-4(3H)-one (20a). Crystallized from dioxane as pale yellow crystals (66%);
1
mp 180–182◦C; IR(υ cm−1): NH (3410), C O (1669); H NMR (δ ppm): 2.59 (s, 3H,
CH3 at pyridine), 5.56 (s, 1H, NH-Ph), 6.90–7.48 (m, 15H, ArH’s), 9.80 (s, 1H, NH in
pyrimidinone); Anal. for C28H20N4OS2 (492.5): calcd./found(%): C (68.27/68.29), H
(4.09/4.11), N (11.37/11.40), S (13.02/13.00).
9-(4-Methoxyphenyl)-7-methyl-8-phenylthio-2-anilinopyrido[3ꢀ,2ꢀ:4,5]
thieno[3,2-d]pyrimidin-4(3H)-one (20b). Crystallized from dioxane as pale yellow
crystals (65%); mp 270–272◦C; IR (υ cm−1): NH (3411), C O (1670); 1H NMR (δ ppm):
2.67 (s, 3H, CH3 at pyridine), 3.84 (s, 3H, OCH3), 6.46–7.37 (m, 14H, ArH’s), 7.64
(s, 1H, -NH-Ph), 9.95 (s, 1H, NH in pyrimidinone); Anal. for C29H22N4O2S2 (522.5):
calcd./found(%): C (66.64/66.65), H (4.24/4.26), N (10.72/10.74), S (12.27/12.31).
Synthesis of 22a,b
A stirred cold solution (0–5◦C) of each of 9d,j (0.01 mol) in acetic acid (10 mL) and
concentrated hydrochloric acid (2 mL) was treated with a cold solution of sodium nitrite
(0.01 mole, 0.23 g in 5 mL) dropwise with stirring. Stirring was continued for 1 h. The
reaction mixture was then allowed to stand at room temperature for 15 min. The solid
obtained was collected by filtration and crystallized from the proper solvent to give 22a,b,
respectively.
7-Methyl-9-phenyl-8-phenylthiopyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-d][1,2,3]-
triazin-4(3H)-one (22a). Crystallized from ethanol/dioxane as pale yellow crystals
1
(68%); mp > 360◦C; IR (υ cm−1): NH (3397), C O (1665); H NMR (δ ppm): 2.85
(s, 3H, CH3 at pyridine), 6.89–7.45 (m, 10H, ArH’s), 12.94 (s, 1H, NH); Anal. for
C21H14N4OS2 (402.5): calcd./found(%): C (62.67/62.64), H (3.51/3.55), N (13.92/13.96),
S (15.93/15.94).
9-(4-Methoxyphenyl)-7-methyl-8-phenylthiopyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-d]
[1,2,3]-triazin-4(3H)-one (22b). Crystallized from ethanol as pale yellow crystals
1
(69%); decompose at 160–162◦C; IR (υ cm−1): NH (3400), C O (1667); H NMR (δ
ppm): 2.55 (s, 3H, CH3 at pyridine), 3.73 (s, 3H, OCH3), 6.83–7.37 (m, 9H, ArH’s),
8.00 (s, 1H, NH); Anal. for C22H16N4O2S2 (432.5): calcd./found(%): C (61.09/61.06), H
(3.73/3.77), N (12.95/12.99), S (14.83/14.81).
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