2-Mercapto-4,6-disubstituted nicotinonitriles: versatile precursors for novel mono- and bis[thienopyridines]

Article abstract of DOI:10.1080/17415993.2018.1471143

A series of novel thieno[2,3-b]pyridines were prepared from the reaction of the appropriate bromoacetylbenzofurans or bromoacetylbenzothiazole with the corresponding pyridinethione derivatives in ethanolic sodium ethoxide at reflux. Moreover, new bis(thieno[2,3-b]pyridine) derivatives have also been synthesized by the reaction of the appropriate bis-bromoacetyl derivatives with the corresponding pyridinethiones in the presence of sodium ethoxide. Attempts to synthesize the target bis(thieno[2,3-b]pyridine) derivatives by bis-alkylation of the corresponding (thieno[2,3-b]pyridin-2-yl)(hydroxyphenyl)methanone with the appropriate dihaloalkanes using a mild base were unsuccessful.

Full text of DOI:10.1080/17415993.2018.1471143

Journal of Sulfur Chemistry
ISSN: 1741-5993 (Print) 1741-6000 (Online) Journal homepage: http://www.tandfonline.com/loi/gsrp20
2-Mercapto-4,6-disubstituted nicotinonitriles:
versatile precursors for novel mono- and
bis[thienopyridines]
Mostafa E. Salem, Ahmed F. Darweesh & Ahmed H. M. Elwahy
To cite this article: Mostafa E. Salem, Ahmed F. Darweesh & Ahmed H. M. Elwahy (2018):
2-Mercapto-4,6-disubstituted nicotinonitriles: versatile precursors for novel mono- and
bis[thienopyridines], Journal of Sulfur Chemistry, DOI: 10.1080/17415993.2018.1471143
To link to this article: https://doi.org/10.1080/17415993.2018.1471143
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JOURNAL OF SULFUR CHEMISTRY
https://doi.org/10.1080/17415993.2018.1471143
2
-Mercapto-4,6-disubstituted nicotinonitriles: versatile
precursors for novel mono- and bis[thienopyridines]
Mostafa E. Salem, Ahmed F. Darweesh and Ahmed H. M. Elwahy
Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt
ABSTRACT
ARTICLE HISTORY
A series of novel thieno[2,3-b]pyridines were prepared from the reac-
tion of the appropriate bromoacetylbenzofurans or bromoacetyl-
benzothiazole with the corresponding pyridinethione derivatives in
ethanolic sodium ethoxide at reflux. Moreover, new bis(thieno[2,3-
b]pyridine) derivatives have also been synthesized by the reac-
tion of the appropriate bis-bromoacetyl derivatives with the cor-
responding pyridinethiones in the presence of sodium ethoxide.
Attempts to synthesize the target bis(thieno[2,3-b]pyridine) deriva-
tives by bis-alkylation of the corresponding (thieno[2,3-b]pyridin-
Received 21 April 2018
Accepted 26 April 2018
KEYWORDS
Pyridinethiones;
thieno[2,3-b]pyridines;
alkylation; cyclization;
bis(thieno[2,3-b]pyridines)
2
-yl)(hydroxyphenyl)methanone with the appropriate dihaloalkanes
using a mild base were unsuccessful.
CONTACT Ahmed H. M. Elwahy
aelwahy@hotmail.com
Department of Chemistry, Faculty of Science, Cairo
University, Giza 12613, Egypt
©
2018 Informa UK Limited, trading as Taylor & Francis Group

2
M. E. SALEM ET AL.
1. Introduction
The synthesis of thienopyridines has been the subject of several reviews because of the
potential therapeutic applications of this class of compounds [1,2]. Many publications
have reported the usefulness of these scaffold as anticancer [3–7], antiviral [8,9], anti-
inflammatory [10–12], antimicrobial [13,14], antidiabetic [15,16], antihypertensive [17,18]
and osteogenic [19,20] agents. Moreover, benzofuran, benzothiazole and coumarin sys-
tems are considered to be among the most interesting benzo-fused heterocyclic derivatives
that have attracted much attention in the last decades due to their pronounced pharmaco-
logical activities [21–50]. In addition, the synthesis of bis-heterocyclic compounds with
two bioactive heterocycles tethered via a flexible spacer was recently investigated for their
promising potent anticancer, antimicrobial, antialzheimer and antiprion activity [51–60].
Motivated by these findings and in conjunction with the new concept in drug design which
suggests that a combination of pharmacophoric moieties of different bioactive substances
produce a new hybrid compound with improved affinity and efficacy [61], we report herein
on the synthesis of novel thienopyridines linked to benzofuran or benzothiazole moieties
as well as novel bis-thieno[2,3-b]pyridine derivatives.
Previously, impressive endeavors have been made in the synthesis of thieno[2,3-
b]pyridine 5 as an important class of compounds. Among the several methods that have
been investigated for the synthesis of such compounds, the reaction of pyridinethione 3,
with the appropriate bromoketone 4 in the presence of a basic catalyst is still the most
interesting approach. Pyridinethione 3 can be obtained from the reaction of cyanothioac-
etamide (1) with the appropriate diketone 2 in ethanol in the presence of catalytic amounts
of piperidine (Scheme 1).
Scheme 1. Synthesis of thieno[2,3-b]pyridine 5a,b.
2. Results and discussion
Our study aimed at improving the structure of 5 via replacement of the aromatic ring
with bioactive heterocycles. For this purpose, we studied the synthesis of bromoacetyl-
benzofurans 7a, and 7b, bromoacetylbenzothiazole 7c and bromoacetylcoumarin 7d. The
bromoacetyl derivatives were prepared in good yields by the reaction of the corresponding
acetyl derivatives 6 with bromine in acetic acid (Scheme 2).

JOURNAL OF SULFUR CHEMISTRY
3
Scheme 2. Synthesis
of
bromoacetylbenzofurans,
bromoacetylbenzothiazole
and
bromoacetylcoumarin.
Scheme 3. Synthesis of thienopyridine with benzofuryl moiety.
Thus, reaction of pyridinethione 3a with 2-bromoacetylbenzofuran 7a in refluxing
ethanol containing sodium ethoxide afforded the corresponding thienopyridine derivative
8
a in good yield (Scheme 3).
Similarly, the thienopyridines 8b–f were prepared by the reaction of the appropriate
bromoacetyl derivatives 7a–c with the corresponding pyridinethione derivatives 3a and
3
b (Figure 1).
The reaction pathway is assumed to involve S-alkylation to give 2-((2-oxo-2-
ethyl)thio)nicotinonitrile intermediates 9, followed by intramolecular cyclocondensation
to give 8. The corresponding 2-((2-oxo-2-ethyl)thio)nicotinonitriles 9 could be isolated
thereby providing a strong evidence for the proposed pathway (Scheme 4).
The constitutions of compounds 8a–f were established based on their elemental analy-
sis and spectral data. The IR spectra of compound 8a as a representative example indicated
−
1
−1
the presence of amino group at 3500 and 3296 cm and a carbonyl band at 1590 cm
.
The absence of a characteristic band for cyano group in compound 8a together with the
presence of this band in compound 9a clearly indicates a successful ring closure of 9a.
1
Moreover, the H NMR spectrum of 9a indicated the presence of SCH protons that res-
2
onated at δ 4.75 ppm as a singlet signal, which disappeared on cyclization to compound
8a. All other protons were seen at the expected chemical shifts and integral values (See
Experimental section).
It is noteworthy to mention that attempts to cyclize the appropriate 2-((2-oxo-2-(2-oxo-
H-chromen-3-yl)ethyl)thio)nicotinonitriles 9g and 9h to the corresponding thienopy-
2
ridines 8g and 8h, respectively, under similar conditions were unsuccessful. The reaction

4
M. E. SALEM ET AL.
Figure 1. Thienopyridines with benzofuryl or benzothiazolyl moieties.
Scheme 4. Reaction pathway for the synthesis of thienopyridines.
gave instead a mixture of non-isolable products. Compounds 9g and 9h were prepared
in good yields by the reaction of 3a and 3b, respectively, with 3-(2-bromoacetyl)-2H-
chromen-2-one (7d) in the presence of piperidine as a basic catalyst (Scheme 5).
The study was extended to include the synthesis of novel bis(thieno[2,3-b]pyridines)
12. We investigated here two possible synthetic approaches, path A and path B. In path-
way A, the desired thieno[2,3-b]pyridines 10a and 10b have initially been synthesized, and
allowed to react with the appropriate dihaloalkanes 11 in the presence of mild base aiming
at giving the desired bipodals 12. Unfortunately, the reaction did not lead to the formation

JOURNAL OF SULFUR CHEMISTRY
5
Scheme 5. Attempted synthesis of thienopyridine with chromenyl moiety.
Scheme 6. Attempted synthesis of bis(thieno[2,3-b]pyridines) (Pathway A).
of the corresponding bis(thieno[2,3-b]pyridines) 12 and gave instead a mixture of products
that were not easily separated and have not been characterized (Scheme 6).
Thus, we turn to pathway B, in which bis-bromoacetyl derivatives 13 have been
synthesized in a first step and then allowed to react with pyridinethiones 3a and 3b
in ethanolic sodium ethoxide at reflux to give the desired bipodals 12. The reaction
pathway is also assumed to involve S-alkylation to give the corresponding bis(2-((2-
oxo-2-ethyl)thio)nicotinonitrile intermediates 14. The latter compounds could be iso-
lated under mild basic conditions and then they could be cyclized to the corresponding
bis(thienopyridines) 12 in ethanolic sodium ethoxide (Scheme 7).
The constitutions of compounds 12a–l were established based on their elemental analy-
sis and spectral data. The IR spectra of compound 12a as a representative example indicated
−
1
−1
the presence of amino group at 3465 and 3280 cm and a carbonyl band at 1593 cm
.
The absence of characteristic band for the cyano group in compound 12a together with the
presence of this band in compound 14a clearly indicates a successful ring closure of 14a.
1
Moreover, the H NMR spectrum of 14a indicated the presence of SCH protons, resonat-
2
ing at δ 4.79 ppm as a four proton singlet, which disappeared on cyclization to compound
12a. Moreover, compounds 12a and 14a also featured the methylene ether linkage OCH2

6
M. E. SALEM ET AL.
Scheme 7. Synthesis of bis(thieno[2,3-b]pyridines) (Pathway B).
as a singlet signal at δ 4.46 ppm. All other protons were seen at the expected chemical shifts
and integral values (See Experimental section).
3. Conclusion
We developed a simple method for the synthesis of novel mono- and bis(thienopyridines).
The thienopyridine moiety in the novel bis compounds is linked to alkyl spacer via
phenoxy group. Attempts to synthesize these compounds directly from the corre-
sponding thieno[2,3-b]pyridin-2-yl)(4-hydroxyphenyl)methanone by alkylation with the
appropriate dihalo compound were unsuccessful. We have also synthesized a series of
novel monopodal thienopyridines which are linked to benzofuran and benzothiazole or
coumarin pharmacophores. The new synthesized compounds are interesting for their
promising pharmacological and biological activities resulted from combination of two or
more pharmacophores into a single molecular skeleton.
4. Experimental
4.1. General
Melting points were determined in open glass capillaries with a Gallenkamp apparatus
and were not corrected. Infrared spectra were recorded in potassium bromide disks on a
1
PyeUnicam SP3-300 and Shimadzu FTIR 8101 PC infrared spectrophotometer. H and
1
3
C NMR spectra were determined on a Varian Mercury VX 300NMR spectrometer using
TMS as an internal standard and DMSO-d6 as a solvent. Mass spectra were measured on

JOURNAL OF SULFUR CHEMISTRY
7
a GC MS-QP1000 EX spectrometer at 70 eV. Elemental analyses were carried out at the
Microanalytical Center of Cairo University, Giza, Egypt. The starting 3a,b [62,63], 6a,b
[
64], 6c [65], 6d [66,67], 7a,b [68], 7c [65], 7d [69] and 13a–f [70] were prepared following
literature procedures.
4
.2. Synthesis of (3-amino-4,6-disubstitutedthieno[2,3-b]
pyridin-2-yl)(aryl)methanone (8a–f)
Method A: To a solution of the appropriate bromoacetyl derivatives 7a–c (10 mmol) in
ethanol (25 mL) containing sodium ethoxide (10 mmol), the appropriate 2-mercapto-4,6-
disubstituted nicotinonitriles 3a or 3b (10 mmol) was added. The reaction mixture was
heated at reflux for 5 h. The solid products obtained upon cooling were filtered off and
recrystallized from DMF to afford the title compounds 8a–f.
Method B: A solution of the appropriate 2-((2-oxo-2-ethyl)thio)nicotinonitrile inter-
mediates 9a–f (5 mmol) in ethanol (25 mL) containing sodium ethoxide (10 mmol) was
heated at reflux for 2 h. The reaction mixture was then cooled and the solvent was evap-
orated in vacuo. The solid residue was collected and recrystallized from DMF to afford
8a–f.
4.2.1. (3-amino-4,6-dimethylthieno[2,3-b]pyridin-2-yl)(benzofuran-2-yl)methanone
(8a)
Yellow powder, m.p.: 283–285°C; yield (A) 74%; (B) 69%, IR (KBr disc) ν = 3500, 3296,
−
1 1
3
3
7
2
1
057, 1590, 1548, 1466 cm . H NMR (300 MHz, DMSO) δ 2.52 (s, 3H, CH ), 2.75 (s,
3
H, CH ), 7.06 (s, 1H, pyridine-5-H), 7.37 (t, 1H, J = 7.5 Hz), 7.52 (t, 1H, J = 7.8 Hz),
3
.74 (s, 1H, benzofuran-3-H), 7.76 (d, 1H, J = 7.8 Hz), 7.84 (d, 1H, J = 7.5 Hz), 8.35 (br. s,
1
3
H, NH ). C NMR (75 MHz, DMSO): 20.1, 24.0, 101.0, 111.8, 112.0, 120.7, 122.0, 123.2,
2
+
24.0, 126.9, 127.6, 146.0, 153.0, 154.5, 154.8, 161.4, 162.4, 175.0. MS (m/z) 322 (M ). Anal.
Calcd. For C H N O S: C, 67.06; H, 4.38; N, 8.69; S, 9.95. Found: C, 66.97; H, 4.23; N,
1
8
14
2
2
8
.53; S, 9.78.
4.2.2. (3-amino-4,6-diphenylthieno[2,3-b]pyridin-2-yl)(benzofuran-2-yl)methanone
(8b)
Orange powder, m.p.: 238–240°C; yield (A) 81%; (B) 78%, IR (KBr disc) ν = 3477, 3292,
−
1 1
3
050, 1590, 1540, 1430 cm . H NMR (300 MHz, DMSO) δ 7.27 (br. s, 2H, NH ), 7.41
2
(
t, 1H, J = 8.1 Hz), 7.54–7.60 (m, 4H, ArH), 7.64–7.69 (m, 5H, ArH), 7.83–7.89 (m, 4H,
13
ArH & pyridine-5-H), 8.28–8.30 (m, 2H, ArH). C NMR (75 MHz, DMSO): 102.0, 112.1,
1
1
18.5, 119.0, 123.2, 124.1, 126.9, 127.3, 127.8, 128.4, 128.9, 129.1, 129.5, 130.3, 136.1,
37.1, 148.9, 152.2, 152.9, 154.6, 157.8, 163.0, 175.1. MS (m/z) 446 (M ). Anal. Calcd.
+
For C H N O S: C, 75.32; H, 4.06; N, 6.27; S, 7.18. Found: C, 75.26; H, 4.02; N, 6.20; S,
2
8
18
2
2
7
.16.
4.2.3. (3-amino-4,6-dimethylthieno[2,3-b]pyridin-2-yl)(5-bromobenzofuran-2-
yl)methanone (8c)
Yellow powder, m.p.: 271–274°C; yield (A) 76%; (B) 70%, IR (KBr disc) ν = 3437, 3281,
−1 1
3
075, 1590, 1549, 1461 cm . H NMR (300 MHz, DMSO) δ 2.53 (s, 3H, CH ), 2.76 (s, 3H,
3
CH ), 7.09 (s, 1H, pyridine-5-H), 7.64 (d, 1H, J = 8.7 Hz), 7.70 (s, 1H, benzofuran-3-H),
3

8
M. E. SALEM ET AL.
7
2
1
.75 (d, 1H, J = 9.3 Hz), 8.05 (s, 1H), 8.39 (br. s, 2H, NH ). 13C NMR (75 MHz, DMSO):
2
0.2, 24.1, 101.0, 111.1, 114.2, 116.2, 120.7, 122.1, 125.6, 129.2, 130.1, 146.2, 153.4, 154.1,
+
55.2, 161.6, 162.5, 174.5. MS (m/z) 401 (M ). Anal. Calcd. For C H BrN O S: C, 53.88;
1
8
13
2
2
H, 3.27; Br, 19.91; N, 6.98; S, 7.99. Found: C, 53.69; H, 3.18; Br, 19.83; N, 6.78; S, 7.85.
4.2.4. (3-amino-4,6-diphenylthieno[2,3-b]pyridin-2-yl)(5-bromobenzofuran-2-
yl)methanone (8d)
Orange powder, m.p.: 252–255°C; yield (A) 79%; (B) 75%, IR (KBr disc) ν = 3461, 2912,
−
1 1
1
(
586, 1541, 1425 cm . H NMR (300 MHz, DMSO) δ 7.31 (br. s, 2H, NH ), 7.56–7.59
2
1
3
m, 3H), 7.67–7.72 (m, 6H), 7.79–7.87 (m, 3H), 8.09–8.10 (m, 1H), 8.28–8.31 (m, 2H). C
NMR (75 MHz, DMSO): 93.0, 93.8, 102.0, 104.8, 111.3, 114.3, 116.3, 118.9, 125.6, 127.4,
1
28.4, 129.0, 129.1, 130.3, 136.0, 137.1, 149.0, 152.5, 153.4, 153.9, 163.0, 174.7, 186.1. MS
+
(m/z) 525 (M ). Anal. Calcd. For C H BrN O S: C, 64.01; H, 3.26; Br, 15.21; N, 5.33; S,
2
8
17
2
2
6.10. Found: C, 63.89; H, 3.17; Br, 15.15; N, 5.23; S, 6.05.
4.2.5. (3-amino-4,6-dimethylthieno[2,3-b]pyridin-2-yl)(benzo[d]thiazol-2-
yl)methanone (8e)
Orange powder, m.p.: 292–295°C; yield (A) 76%; (B) 75%, IR (KBr disc) ν = 3495, 2916,
−
1 1
1
590, 1556, 1494 cm . H NMR (300 MHz, DMSO) δ 2.51 (s, 3H, CH ), 2.74 (s, 3H, CH ),
3 3
7
.03 (s, 1H, pyridine-5-H), 7.40–7.47 (m, 1H, ArH), 7.56–7.67 (m, 1H, ArH), 8.00 (d, 1H,
1
3
J = 7.5 Hz), 8.22 (d, 1H, J = 7.5 Hz), 8.62 (br, 2H, NH ). C NMR (75 MHz, DMSO):
2
2
1
0.2, 24.2, 121.9, 122.2, 123.0, 123.6, 124.7, 125.2, 125.6, 127.2, 127.4, 136.0, 136.6, 153.0,
+
53.6, 161.4, 161.9. MS (m/z) 339 (M ). Anal. Calcd. For C H N OS : C, 60.15; H, 3.86;
1
7
13
3
2
N, 12.38; S, 18.89. Found: C, 59.98; H, 3.79; N, 12.31; S, 18.77.
4.2.6. (3-amino-4,6-diphenylthieno[2,3-b]pyridin-2-yl)(benzo[d]thiazol-2-
yl)methanone (8f)
Red powder, m.p.: 254–256°C; yield (A) 79%; (B) 76%, IR (KBr disc) ν = 3459, 3269, 3049,
−
1 1
1
582, 1535, 1490 cm . H NMR (300 MHz, DMSO) δ 4.39 (br. s, 2H, NH ), 7.56–7.59 (m,
2
3
H, ArH), 7.62–7.70 (m, 7H, ArH), 7.83 (s, 1H, pyridine-5-H), 8.25–8.34 (m, 4H, ArH).
C NMR (75 MHz, DMSO): 101.0, 118.2, 118.4, 123.0, 124.8, 127.3, 127.5, 128.5, 129.0,
1
3
1
29.3, 129.6, 130.4, 136.0, 136.1, 137.2, 149.1, 153.0, 154.0, 158.2, 165.4, 168.9, 175.9. MS
+
(m/z) 463 (M ). Anal. Calcd. For C H N OS : C, 69.95; H, 3.70; N, 9.06; S, 13.83. Found:
2
7
17
3
2
C, 69.90; H, 3.53; N, 8.94; S, 13.67.
4.3. Synthesis of 4,6-disubestituted-2-((2-oxo-2-arylethyl)thio)nicotinonitrile
(9a–h)
To a solution of the appropriate bromoacetyl derivatives 7a–d (10 mmol) in ethanol
25 mL) containing few drops piperidine, the appropriate 2-mercapto-4,6-disubstituted
(
nicotinonitriles 3a or 3b (10 mmol) was added. The reaction mixture was heated at reflux
for 3–4 h. The solid obtained upon cooling was filtered off and recrystallized from ethanol/
DMF to afford the title compounds 9a–h.

JOURNAL OF SULFUR CHEMISTRY
9
4.3.1. 2-((2-(benzofuran-2-yl)-2-oxoethyl)thio)-4,6-dimethylnicotinonitrile (9a)
Creamy powder, m.p.: 133–135°C; yield 84%, IR (KBr disc) ν = 3089, 2961, 2214, 1677,
−1 1
1
548, 1439 cm . H NMR (300 MHz, DMSO) δ 2.09 (s, 3H, CH ), 2.39 (s, 3H, CH ), 4.75
3 3
(
s, 2H, SCH ), 7.03 (s, 1H, pyridine-5-H), 7.39 (t, 1H, J = 7.2 Hz), 7.56 (t, 1H, J = 7.2 Hz),
2
1
3
7
.74 (d, 1H, J = 8.4 Hz), 7.87 (d, 1H, J = 7.8 Hz), 8.08 (s, 1H, benzofuran-3-H).
C
NMR (75 MHz, DMSO): 19.5, 23.6, 36.2, 103.4, 112.1, 114.2, 114.8, 120.4, 123.6, 124.0,
+
1
26.7, 128.5, 151.6, 152.5, 154.9, 159.4, 161.0, 184.1. MS (m/z) 322 (M ). Anal. Calcd. For
C H N O S: C, 67.06; H, 4.38; N, 8.69; S, 9.95. Found: C, 66.99; H, 4.46; N, 8.58; S, 9.90.
1
8
14
2
2
4.3.2. 2-((2-(benzofuran-2-yl)-2-oxoethyl)thio)-4,6-diphenylnicotinonitrile (9b)
Yellow powder, m.p.: 220–223°C; yield 87%, IR (KBr disc) ν = 3044, 2917, 2210, 1681,
−
1
1
1
524, 1447 cm . H NMR (300 MHz, DMSO) δ 4.99 (s, 2H, SCH ), 6.91 (t, 2H,
2
J = 7.8 Hz), 7.21 (t, 1H, J = 7.8 Hz), 7.45 (t, 1H, J = 7.8 Hz), 7.58–7.62 (m, 4H), 7.74–7.86
1
3
(
m, 7H), 8.20 (s, 1H, benzofuran-3-H). C NMR (75 MHz, DMSO): 36.8, 102.5, 112.1,
1
1
14.8, 115.4, 116.4, 123.7, 124.1, 126.7, 127.2, 128.2, 128.5, 128.7, 128.8, 130.0, 130.3,
35.4, 136.2, 151.3, 154.2, 155.0, 158.1, 161.4, 183.6. MS (m/z) 446 (M ). Anal. Calcd.
+
For C H N O S: C, 75.32; H, 4.06; N, 6.27; S, 7.18. Found: C, 75.35; H, 4.10; N, 6.21; S,
2
8
18
2
2
7
.12.
4.3.3. 2-((2-(5-bromobenzofuran-2-yl)-2-oxoethyl)thio)-4,6-dimethylnicotinonitrile
(9c)
Creamy powder, m.p.: 130–132°C; yield 86%, IR (KBr disc) ν = 3085, 2916, 2211, 1684,
−1 1
1
549, 1435 cm . H NMR (300 MHz, DMSO) δ 2.03 (s, 3H, CH ), 2.36 (s, 3H, CH ), 4.72
3 3
(
s, 2H, SCH ), 6.99 (s, 1H, pyridine-5-H), 7.65–7.75 (m, 2H, ArH), 8.02 (s, 1H, benzofuran-
-H), 8.07 (s, 1H, ArH). C NMR (75 MHz, DMSO): 19.6, 23.7, 36.3, 103.4, 113.3, 114.4,
2
1
3
3
1
4
14.9, 116.4, 120.5, 126.0, 128.9, 131.1, 152.6, 152.7, 153.7, 159.4, 161.1, 184.3. MS (m/z)
+
01 (M ). Anal. Calcd. For C H BrN O S: C, 53.88; H, 3.27; Br, 19.91; N, 6.98; S, 7.99.
1
8
13
2
2
Found: C, 53.73; H, 3.19; Br, 19.87; N, 6.85; S, 7.83.
4
(
.3.4. 2-((2-(5-bromobenzofuran-2-yl)-2-oxoethyl)thio)-4,6-diphenylnicotinonitrile
9d)
Yellow powder, m.p.: 230–232°C; yield 85%, IR (KBr disc) ν = 3054, 2904, 2210, 1681,
−
1
1
1524, 1440 cm . H NMR (300 MHz, DMSO) δ 4.97 (s, 2H, SCH ), 6.97 (t, 2H,
2
J = 7.8 Hz), 7.26 (t, 1H, J = 7.5 Hz), 7.58–7.60 (m, 4H, ArH), 7.72–7.79 (m, 4H, ArH),
.84–7.86 (m, 1H, ArH), 7.87 (s, 1H, benzofuran-3-H), 8.12 (s, 2H, ArH). 13C NMR
75 MHz, DMSO): 36.7, 102.6, 114.2, 114.5, 115.1, 116.4, 116.7, 126.1, 127.4, 128.4, 128.7,
7
(
1
28.9, 129.0, 130.1, 130.5, 131.1, 135.5, 136.4, 152.4, 153.9, 154.2, 158.2, 161.4, 183.8. MS
+
(
m/z) 525 (M ). Anal. Calcd. For C H BrN O S: C, 64.01; H, 3.26; Br, 15.21; N, 5.33; S,
2
8
17
2
2
6.10. Found: C, 63.94; H, 3.29; Br, 15.15; N, 5.28; S, 6.01.
4.3.5. 2-((2-(benzo[d]thiazol-2-yl)-2-oxoethyl)thio)-4,6-dimethylnicotinonitrile (9e)
Creamy powder, m.p.: 168–171°C; yield 86%, IR (KBr disc) ν = 3061, 2965, 2215, 1689,
−1 1
1
543, 1488 cm . H NMR (300 MHz, DMSO) δ 2.04 (s, 3H, CH ), 2.45 (s, 3H, CH ),
3 3
4
.85 (s, 2H, SCH ), 6.72 (s, 1H, pyridine-5-H), 7.56–7.62 (m, 2H, ArH), 8.01 (d, 1H,
2
1
3
J = 7.5 Hz), 8.23 (d, 1H, J = 8.1 Hz). C NMR (75 MHz, DMSO): 19.6, 23.4, 36.0, 103.3,
1
14.9, 120.5, 123.2, 125.1, 127.5, 128.1, 136.4, 152.6, 152.8, 159.2, 160.9, 165.8, 188.8. MS

10
M. E. SALEM ET AL.
+
(
m/z) 339 (M ). Anal. Calcd. For C H N OS : C, 60.15; H, 3.86; N, 12.38; S, 18.89.
1
7
13
3
2
Found: C, 60.11; H, 3.87; N, 12.29; S, 18.79.
4.3.6. 2-((2-(benzo[d]thiazol-2-yl)-2-oxoethyl)thio)-4,6-diphenylnicotinonitrile (9f)
Creamy powder, m.p.: 224–225°C; yield 87%, IR (KBr disc) ν = 3052, 2977, 2210,
−
1 1
1
691, 1523, 1478 cm . H NMR (300 MHz, DMSO) δ 5.24 (s, 2H, SCH ), 6.77 (t, 2H,
2
J = 7.8 Hz), 7.11–7.17 (m, 1H, ArH), 7.54–7.84 (m, 10H, pyridine-5-H & ArH), 8.27
+
(
d, 1H, J = 8.7 Hz), 8.40 (d, 1H, J = 8.7 Hz). MS (m/z) 463 (M ). Anal. Calcd. For
C H N OS : C, 69.95; H, 3.70; N, 9.06; S, 13.83. Found: C, 69.89; H, 3.77; N, 9.04; S,
2
7
17
3
2
13.78.
4.3.7. 2-((2-oxo-2-(2-oxo-2H-chromen-3-yl)ethyl)thio)-4,6-dimethylnicotinonitrile
(9g)
Colorless powder, m.p.: 226–228°C; yield 76%, IR (KBr disc) ν = 3050, 2924, 2214, 1720,
−1 1
1
550, 1445 cm . H NMR (300 MHz, DMSO) δ 2.26 (s, 3H, CH ), 2.39 (s, 3H, CH ), 4.76
3 3
(
7
2
1
s, 2H, SCH ), 7.06 (s, 1H, pyridine-5-H), 7.44–7.52 (m, 2H, ArH), 7.77 (t, 1H, J = 7.5 Hz),
2
1
3
.97 (d, 1H, J = 7.8 Hz), 8.73 (s, 1H, chromen-4-H). C NMR (75 MHz, DMSO): 19.6,
4.0, 36.1, 103.6, 116.3, 118.1, 120.5, 124.2, 125.2, 130.8, 134.8, 135.5, 147.8, 152.6, 154.6,
+
59.8, 161.3, 191.4, 200.2. MS (m/z) 350 (M ). Anal. Calcd. For C H N O S: C, 65.13;
1
9
14
2
3
H, 4.03; N, 7.99; S, 9.15. Found: C, 65.07; H, 3.93; N, 7.86; S, 9.01.
4.3.8. 2-((2-oxo-2-(2-oxo-2H-chromen-3-yl)ethyl)thio)-4,6-diphenylnicotinonitrile
(9h)
Creamy powder, m.p.: 241–243°C; yield 73%, IR (KBr disc) ν = 3043, 2922, 2213, 1729,
−
1 1
1
4
2
557, 1446 cm . H NMR (300 MHz, DMSO) δ 5.02 (s, 2H, SCH ), 7.25–7.55 (m,
2
H, ArH), 7.58–7.60 (m, 4H, ArH), 7.74–7.88 (m, 5H, ArH & pyridine-5-H), 8.08 (d,
+
H, J = 8.7 Hz), 8.68 (s, 1H, chromen-4-H). MS (m/z) 474 (M ). Anal. Calcd. For
C H N O S: C, 73.40; H, 3.82; N, 5.90; S, 6.76. Found: C, 73.37; H, 3.76; N, 5.79; S, 6.81.
2
9
18
2
3
4.4. Synthesis of bis((3-amino-4,6-disubestitutedthieno[2,3-b]pyridin-2-yl)
methanone) (12a–l)
Method A: To a solution of the appropriate bis-bromoacetyls 13a–f (5 mmol) in
ethanol (25 mL) containing sodium ethoxide (10 mmol), the appropriate 2-mercapto-4,6-
disubstituted nicotinonitriles 3a or 3b (10 mmol) was added. The reaction mixture was
heated at reflux for 5 h. The reaction mixture was then left to cool and the solid product
was filtered off and recrystallized from DMF to afford the title compounds 12a–l.
Method B: A solution of the appropriate bis(2-((2-oxo-2-ethyl)thio)nicotinonitrile
intermediates 14a–l (2 mmol) in ethanol (25 mL) containing sodium ethoxide (4 mmol)
was heated at reflux for 2 h. The reaction mixture was then cooled and the solvent was
evaporated in vacuo. The solid residue was collected and recrystallized from DMF to afford
12a–l.

JOURNAL OF SULFUR CHEMISTRY
11
4
[
.4.1. ((ethane-1,2-diylbis(oxy))bis(4,1-phenylene))bis((3-amino-4,6-dimethylthieno
2,3-b]pyridin-2-yl)methanone) (12a)
Yellow powder, m.p.: 302–305°C; yield (A) 68%; (B) 60%, IR (KBr disc) ν = 3487, 3437,
−1 1
2
911, 1592, 1552, 1428 cm . H NMR (300 MHz, DMSO) δ 2.48 (s, 6H, CH ), 2.77 (s, 6H,
3
CH ), 4.47 (s, 4H, OCH ), 7.10 (s, 2H, pyridine-5-H), 7.15 (d, 4H, J = 8.7 Hz), 7.79 (d, 4H,
3
2
+
J = 8.4 Hz), 7.96 (br. s, 4H, NH ). MS (m/z) 622 (M ). Anal. Calcd. For C H N O S :
2
34 30
4
4 2
C, 65.57; H, 4.86; N, 9.00; S, 10.30. Found: C, 65.49; H, 4.81; N, 8.87; S, 10.22.
4
[
.4.2. ((ethane-1,2-diylbis(oxy))bis(4,1-phenylene))bis((3-amino-4,6-diphenylthieno
2,3-b]pyridin-2-yl)methanone) (12b)
Yellow powder, m.p.: 225–227°C; yield (A) 63%; (B) 55%, IR (KBr disc) ν = 3465, 3052,
−
1 1
2
922, 1590, 1531, 1447 cm . H NMR (300 MHz, DMSO) δ 4.49 (s, 4H, OCH ), 6.85 (br.
2
s, 4H, NH ), 7.17 (d, 4H, J = 8.7 Hz), 7.51–7.86 (m, 22H, pyridine-5-H & ArH), 8.23–8.25
2
+
(
6
m, 4H, ArH). MS (m/z) 871 (M ). Anal. Calcd. For C H N O S : C, 74.46; H, 4.40; N,
5
4
38
4
4 2
.43; S, 7.36. Found: C, 74.39; H, 4.30; N, 6.48; S, 7.29.
4.4.3. ((propane-1,3-diylbis(oxy))bis(4,1-phenylene))bis((3-amino-4,6-dimethyl-
thieno[2,3-b]pyridin-2-yl)methanone) (12c).
Yellow powder, m.p.: 235–238°C; yield (A) 68%; (B) 63%, IR (KBr disc) ν = 3443, 2927,
−
1 1
1
593, 1552, 1425 cm . H NMR (300 MHz, DMSO) δ 2.23 (m, 2H, CH ), 2.50 (s, 6H,
2
CH ), 2.75 (s, 6H, CH ), 4.25 (m, 4H, OCH ), 7.06 (s, 2H, pyridine-5-H), 7.09 (d, 4H,
3
3
2
1
3
J = 8.7 Hz), 7.78 (d, 4H, J = 9.0 Hz), 7.94 (br. s, 4H, NH ). C NMR (75 MHz, DMSO):
2
1
1
8
9.9, 23.8, 28.4, 64.5, 102.4, 114.1, 121.6, 121.8, 129.5, 133.3, 145.7, 152.2, 160.4, 160.7,
+
61.3, 187.9. MS (m/z) 636 (M ). Anal. Calcd. For C H N O S : C, 66.02; H, 5.07; N,
.80; S, 10.07. Found: C, 65.96; H, 5.03; N, 8.71; S, 10.03.
3
5
32
4
4 2
4.4.4. ((propane-1,3-diylbis(oxy))bis(4,1-phenylene))bis((3-amino-4,6-diphenylthieno
[2,3-b]pyridin-2-yl)methanone) (12d)
Orange powder, m.p.: 210–213°C; yield (A) 67%; (B) 58%, IR (KBr disc) ν = 3463, 3054,
−
1 1
2
4
916, 1593, 1528, 1432 cm . H NMR (300 MHz, DMSO) δ 2.49 (m, 2H, CH ), 4.29 (m,
2
1
3
H, OCH ), 6.83 (br. s, 4H, NH ), 7.12–8.25 (m, 30H, pyridine-5-H & ArH). C NMR
2
2
(
1
(
75 MHz, DMSO): 28.4, 64.4, 103.5, 114.1, 118.2, 119.7, 127.1, 128.3, 128.7, 128.9, 129.2,
29.5, 129.9, 133.0, 136.1, 137.1, 148.5, 149.6, 157.0, 160.8, 161.8, 187.8. MS (m/z) 885
+
M ). Anal. Calcd. For C H N O S : C, 74.64; H, 4.56; N, 6.33; S, 7.25. Found: C, 74.57;
5
5
40
4
4 2
H, 4.63; N, 6.29; S, 7.21.
4
[
.4.5. ((butane-1,4-diylbis(oxy))bis(4,1-phenylene))bis((3-amino-4,6-dimethylthieno
2,3-b]pyridin-2-yl)methanone) (12e)
Yellow powder, m.p.: 250–252°C; yield (A) 66%; (B) 64%, IR (KBr disc) ν = 3487, 2928,
−1 1
1593, 1562, 1439 cm . H NMR (300 MHz, DMSO) δ 1.94 (br. s, 4H, CH ), 2.50 (s, 6H,
2
CH ), 2.76 (s, 6H, CH ), 4.16 (br. s, 4H, OCH ), 7.06–7.09 (m, 6H, pyridine-5-H & ArH),
3
3
2
+
7
.77 (d, 4H, J = 9.0 Hz), 7.94 (br. s, 4H, NH ). MS (m/z) 650 (M ). Anal. Calcd. For
2
C H N O S : C, 66.44; H, 5.27; N, 8.61; S, 9.85. Found: C, 66.37; H, 5.19; N, 8.55; S,
3
6
34
4
4 2
9
.81.

12
M. E. SALEM ET AL.
4.4.6. ((butane-1,4-diylbis(oxy))bis(4,1-phenylene))bis((3-amino-4,6-diphenylthieno
[2,3-b]pyridin-2-yl)methanone) (12f)
Yellow powder, m.p.: 230–232°C; yield (A) 67%; (B) 60%, IR (KBr disc) ν = 3468, 3049,
−1 1
2
922, 1588, 1533, 1434 cm . H NMR (300 MHz, DMSO) δ 1.96 (br. s, 4H, CH ), 4.19
2
(
br. s, 4H, OCH ), 6.83 (br. s, 4H, NH ), 7.11 (d, 4H, J = 8.4 Hz), 7.50–7.84 (m, 22H,
2
2
+
pyridine-5-H & ArH), 8.22–8.23 (m, 4H, ArH). MS (m/z) 899 (M ). Anal. Calcd. For
C H N O S : C, 74.81; H, 4.71; N, 6.23; S, 7.13. Found: C, 74.75; H, 4.67; N, 6.20; S,
5
6
42
4
4 2
7
.04.
4.4.7. ((ethane-1,2-diylbis(oxy))bis(2,1-phenylene))bis((3-amino-4,6-dimethylthieno
[2,3-b]pyridin-2-yl)methanone) (12g)
Yellow powder, m.p.: 300–302°C; yield (A) 68%; (B) 56%, IR (KBr disc) ν = 3480, 3281,
−
1 1
2
6
4
6
925, 1596, 1552, 1439 cm . H NMR (300 MHz, DMSO) δ 2.47 (s, 6H, CH ), 2.73 (s,
3
H, CH ), 4.22 (s, 4H, OCH ), 6.99–7.06 (m, 6H, pyridine-5-H & ArH), 7.25–7.33 (m,
H, ArH), 7.81 (br. s, 4H, NH ). MS (m/z) 622 (M ). Anal. Calcd. For C H N O S : C,
5.57; H, 4.86; N, 9.00; S, 10.30. Found: C, 65.53; H, 4.93; N, 8.91; S, 10.28.
3
2
+
2
34 30
4
4 2
4.4.8. ((ethane-1,2-diylbis(oxy))bis(2,1-phenylene))bis((3-amino-4,6-diphenylthieno
[2,3-b]pyridin-2-yl)methanone) (12h)
Yellow powder, m.p.: 230–233°C; yield (A) 61%; (B) 52%, IR (KBr disc) ν = 3460, 3287,
−
1 1
2
951, 1589, 1533, 1442 cm . H NMR (300 MHz, DMSO) δ 4.28 (s, 4H, OCH ), 6.68 (br.
2
+
s, 4H, NH ), 6.98–8.17 (m, 30H, pyridine-5-H & ArH). MS (m/z) 871 (M ). Anal. Calcd.
2
For C H N O S : C, 74.46; H, 4.40; N, 6.43; S, 7.36. Found: C, 74.31; H, 4.35; N, 6.33; S,
5
4
38
4
4 2
7
.21.
4.4.9. ((propane-1,3-diylbis(oxy))bis(2,1-phenylene))bis((3-amino-4,6-dimethyl
thieno[2,3-b]pyridin-2-yl)methanone) (12i)
Yellow powder, m.p.: 275–277°C; yield (A) 63%; (B) 65%, IR (KBr disc) ν = 3434, 2924,
−
1 1
1
598, 1553, 1444 cm . H NMR (300 MHz, DMSO) δ 1.87 (m, 2H, CH ), 2.49 (s, 6H,
2
CH ), 2.73 (s, 6H, CH ), 3.95 (m, 4H, OCH ), 6.76 (d, 2H, J = 8.7 Hz), 6.98 (t, 2H,
3
3
2
J = 7.5 Hz), 7.05 (s, 2H, pyridine-5-H), 7.22–7.27 (m, 4H, ArH), 7.79 (br. s, 4H, NH ).
2
1
3
C NMR (75 MHz, DMSO): 19.8, 23.9, 28.3, 64.6, 105.6, 112.2, 120.3, 121.7, 127.5, 130.8,
31.0, 145.8, 150.9, 154.4, 160.4, 161.6, 188.9. MS (m/z) 636 (M ). Anal. Calcd. For
+
1
C H N O S : C, 66.02; H, 5.07; N, 8.80; S, 10.07. Found: C, 65.91; H, 4.99; N, 8.83; S,
3
5
32
4
4 2
1
0.01.
4.4.10. ((propane-1,3-diylbis(oxy))bis(2,1-phenylene))bis((3-amino-4,6-diphenyl
thieno[2,3-b]pyridin-2-yl)methanone) (12j).
Yellow powder, m.p.: 193–195°C; yield (A) 61%; (B) 55%, IR (KBr disc) ν = 3457, 3057,
−
1 1
2
4
2
1
918, 1598, 1533, 1446 cm . H NMR (300 MHz, DMSO) δ 1.93 (m, 2H, CH ), 3.97 (m,
2
1
3
H, OCH ), 6.75–8.20 (m, 34H, pyridine-5-H, ArH & NH ). C NMR (75 MHz, DMSO):
8.3, 64.5, 106.8, 111.9, 118.0, 119.8, 120.1, 127.1, 128.3, 128.7, 128.8, 129.2, 129.9, 130.7,
30.8, 136.1, 137.1, 148.1, 148.6, 154.3, 156.9, 162.1, 188.9. MS (m/z) 885 (M ). Anal.
2
2
+
Calcd. For C H N O S : C, 74.64; H, 4.56; N, 6.33; S, 7.25. Found: C, 74.59; H, 4.45;
5
5
40
4
4 2
N, 6.26; S, 7.10.

JOURNAL OF SULFUR CHEMISTRY
13
4
[
.4.11. ((butane-1,4-diylbis(oxy))bis(2,1-phenylene))bis((3-amino-4,6-dimethylthieno
2,3-b]pyridin-2-yl)methanone) (12k)
Yellow powder, m.p.: 281–283°C; yield (A) 66%; (B) 68%, IR (KBr disc) ν = 3470, 3284,
−1 1
2
939, 1596, 1544, 1445 cm . H NMR (300 MHz, DMSO) δ 1.52 (br. s, 4H, CH ), 2.47
2
(
&
s, 6H, CH ), 2.72 (s, 6H, CH ), 3.84 (br. s, 4H, OCH ), 7.00–7.37 (m, 10H, pyridine-5-H
ArH), 7.75 (br. s, 4H, NH ). MS (m/z) 650 (M ). Anal. Calcd. For C H N O S : C,
2 36 34 4 4 2
3 3 2
+
66.44; H, 5.27; N, 8.61; S, 9.85. Found: C, 66.33; H, 5.17; N, 8.57; S, 9.72.
4.4.12. ((butane-1,4-diylbis(oxy))bis(2,1-phenylene))bis((3-amino-4,6-diphenylthieno
[2,3-b]pyridin-2-yl)methanone) (12l)
Yellow powder, m.p.: 225–227°C; yield (A) 63%; (B) 69%, IR (KBr disc) ν = 3465, 3053,
−1 1
2
924, 1593, 1534, 1443 cm . H NMR (300 MHz, DMSO) δ 1.53 (br. s, 4H, CH ), 3.84
2
(
7
br. s, 4H, OCH ), 6.73 (br. s, 4H, NH ), 6.96 (t, 4H, J = 7.5 Hz), 7.26 (d, 4H, J = 7.5 Hz),
2
2
1
3
.49–7.59 (m, 16H, ArH), 7.78 (s, 2H, pyridine-5-H), 8.18–8.21 (m, 4H, ArH). C NMR
(
75 MHz, DMSO): 24.8, 67.3, 106.9, 112.8, 118.1, 119.9, 120.2, 127.2, 127.4, 128.4, 128.8,
1
8
7
28.9, 129.3, 130.0, 131.0, 136.2, 137.2, 148.2, 148.7, 154.8, 157.0, 162.1, 189.0. MS (m/z)
+
99 (M ). Anal. Calcd. For C H N O S : C, 74.81; H, 4.71; N, 6.23; S, 7.13. Found: C,
5
6
42
4
4 2
4.85; H, 4.77; N, 6.29; S, 7.09.
4.5. Synthesis of bis(2-((2-oxo-2-ethyl)thio)nicotinonitrile 14a–l
To a solution of the appropriate bis-bromoacetyls 13a–f (5 mmol) in ethanol (25 mL)
containing few drops piperidine, the appropriate 2-mercapto-4,6-disubstituted nicotinon-
itriles 3a or 3b (10 mmol) was added. The reaction mixture was heated at reflux for 3–4 h.
The solid product obtained upon cooling was filtered off and recrystallized from ethanol/
DMF to afford the title compounds 14a–l.
4.5.1. 2,2’-((((ethane-1,2-diylbis(oxy))bis(4,1-phenylene))bis(2-oxoethane-2,1-diyl))
bis(sulfanediyl))bis(4,6-dimethylnicotinonitrile) (14a).
Creamy powder, m.p.: 205–207°C; yield 68%, IR (KBr disc) ν = 3060, 2920, 2213, 1675,
−1 1
1
509, 1432 cm . H NMR (300 MHz, DMSO) δ 2.22 (s, 6H, CH ), 2.40 (s, 6H, CH ), 4.48
3 3
(
8
1
s, 4H, OCH ), 4.78 (s, 4H, SCH ), 7.05 (s, 2H, pyridine-5-H), 7.14 (d, 4H, J = 7.8 Hz),
2
2
1
3
.06 (d, 4H, J = 7.5 Hz). C NMR (75 MHz, DMSO): 19.4, 23.8, 36.5, 66.5, 114.3, 120.2,
+
20.3, 120.3, 120.4, 129.3, 130.5, 152.3, 161.0, 162.2, 191.8. MS (m/z) 622 (M ). Anal.
Calcd. For C H N O S : C, 65.57; H, 4.86; N, 9.00; S, 10.30. Found: C, 65.48; H, 4.79; N,
3
4
30
4
4 2
8
.89; S, 10.24.
4.5.2. 2,2’-((((ethane-1,2-diylbis(oxy))bis(4,1-phenylene))bis(2-oxoethane-2,1-diyl))
bis(sulfanediyl))bis(4,6-diphenylnicotinonitrile) (14b)
Yellow powder, m.p.: 230–232°C; yield 62%, IR (KBr disc) ν = 3058, 2917, 2213, 1680,
−
1 1
1
522, 1445 cm . H NMR (300 MHz, DMSO) δ 4.55 (s, 4H, OCH ), 5.02 (s, 4H, SCH ),
2 2
7
.19–7.36 (m, 10H, ArH), 7.58–7.60 (m, 6H, ArH), 7.74–7.77 (m, 4H, ArH), 7.86 (s, 2H,
1
3
pyridine-5-H), 7.94 (d, 4H, J = 7.5 Hz), 8.15 (d, 4H, J = 8.7 Hz). C NMR (75 MHz,
DMSO): 37.4, 66.6, 102.5, 114.5, 115.5, 116.1, 127.3, 128.4, 128.5, 128.7, 129.1, 130.0, 130.4,
+
1
30.7, 135.5, 136.2, 154.1, 157.8, 161.8, 162.4, 191.2. MS (m/z) 871 (M ). Anal. Calcd. For
C H N O S : C, 74.46; H, 4.40; N, 6.43; S, 7.36. Found: C, 74.34; H, 4.33; N, 6.39; S, 7.24.
5
4
38
4
4 2

14
M. E. SALEM ET AL.
4.5.3. 2,2’-((((propane-1,3-diylbis(oxy))bis(4,1-phenylene))bis(2-oxoethane-2,1-diyl))
bis(sulfanediyl))bis(4,6-dimethylnicotinonitrile) (14c)
Creamy powder, m.p.: 170–172°C; yield 70%, IR (KBr disc) ν = 3063, 2919, 2213, 1686,
−
1 1
1
2
7
2
592, 1469 cm . H NMR (300 MHz, DMSO) δ 2.21 (m, 2H, CH ), 2.39 (s, 6H, CH ),
2 3
.49 (s, 6H, CH ), 4.27 (m, 4H, OCH ), 4.77 (s, 4H, SCH ), 7.03 (s, 2H, pyridine-5-H),
3
2
2
1
3
.10 (d, 4H, J = 8.4 Hz), 8.03 (d, 4H, J = 8.7 Hz). C NMR (75 MHz, DMSO): 19.5, 23.9,
8.3, 36.7, 64.6, 103.5, 114.3, 115.0, 120.3, 129.1, 130.6, 152.4, 159.9, 161.1, 162.5, 191.9.
+
MS (m/z) 636 (M ). Anal. Calcd. For C H N O S : C, 66.02; H, 5.07; N, 8.80; S, 10.07.
3
5
32
4
4 2
Found: C, 65.98; H, 5.05; N, 8.73; S, 10.00.
4.5.4. 2,2’-((((propane-1,3-diylbis(oxy))bis(4,1-phenylene))bis(2-oxoethane-2,1-diyl))
bis(sulfanediyl))bis(4,6-diphenylnicotinonitrile) (14d)
White powder, m.p.: 233–235°C; yield 67%, IR (KBr disc) ν = 3056, 2915, 2210, 1683,
−1 1
1
568, 1518 cm . H NMR (300 MHz, DMSO) δ 2.30 (m, 2H, CH ), 4.34 (m, 4H, OCH ),
2 2
4
.99 (s, 4H, SCH ), 7.14–7.23 (m, 8H, ArH), 7.33 (t, 2H, J = 7.2 Hz), 7.58–7.60 (m, 6H,
2
ArH), 7.73–7.76 (m, 4H, ArH), 7.84 (s, 2H, pyridine-5-H), 7.92 (d, 4H, J = 7.5 Hz), 8.12
1
3
(
d, 4H, J = 8.7 Hz). C NMR (75 MHz, DMSO): 28.2, 37.4, 64.6, 102.5, 114.4, 115.5, 116.1,
1
1
7
27.3, 128.4, 128.5, 128.7, 128.9, 129.9, 130.3, 130.7, 135.5, 136.2, 154.1, 157.8, 161.8, 162.6,
+
91.1. MS (m/z) 885 (M ). Anal. Calcd. For C H N O S : C, 74.64; H, 4.56; N, 6.33; S,
5
5
40
4
4 2
.25. Found: C, 74.53; H, 4.51; N, 6.28; S, 7.19.
4.5.5. 2,2’-((((butane-1,4-diylbis(oxy))bis(4,1-phenylene))bis(2-oxoethane-2,1-diyl))
bis(sulfanediyl))bis(4,6-dimethylnicotinonitrile) (14e).
Creamy powder, m.p.: 238–241°C; yield 71%, IR (KBr disc) ν = 2921, 2213, 1683, 1594,
−1 1
1
509 cm . H NMR (300 MHz, DMSO) δ 1.92 (br. s, 4H, CH ), 2.22 (s, 6H, CH ), 2.39
2 3
(
(
3
(
s, 6H, CH ), 4.16 (br. s, 4H, OCH ), 4.76 (s, 4H, SCH ), 7.03 (s, 2H, pyridine-5-H), 7.07
3 2 2
1
3
d, 4H, J = 8.1 Hz), 8.02 (d, 4H, J = 8.4 Hz). C NMR (75 MHz, DMSO): 19.5, 23.8, 25.1,
6.6, 67.5, 114.3, 120.3, 129.0, 130.5, 140.6, 146.7, 152.3, 156.8, 162.6, 191.8. MS (m/z) 650
+
M ). Anal. Calcd. For C H N O S : C, 66.44; H, 5.27; N, 8.61; S, 9.85. Found: C, 66.32;
3
6
34
4
4 2
H, 5.34; N, 8.53; S, 9.77.
4.5.6. 2,2’-((((butane-1,4-diylbis(oxy))bis(4,1-phenylene))bis(2-oxoethane-2,1-diyl))
bis(sulfanediyl))bis(4,6-diphenylnicotinonitrile) (14f)
Creamy powder, m.p.: 246–248°C; yield 69%, IR (KBr disc) ν = 3058, 2925, 2213, 1682,
−1 1
1
568, 1522 cm . H NMR (300 MHz, DMSO) δ 1.98 (br. s, 4H, CH ), 4.23 (br. s, 4H,
2
OCH ), 4.99 (s, 4H, SCH ), 7.12–7.24 (m, 8H, ArH), 7.36 (t, 2H, J = 7.8 Hz), 7.58–7.60 (m,
2
2
6
H, ArH), 7.73–7.75 (m, 4H, ArH), 7.85 (s, 2H, pyridine-5-H), 7.93 (d, 4H, J = 7.8 Hz),
+
8
.11 (d, 4H, J = 7.8 Hz). MS (m/z) 899 (M ). Anal. Calcd. For C H N O S : C, 74.81;
5
6
42
4
4 2
H, 4.71; N, 6.23; S, 7.13. Found: C, 74.73; H, 4.65; N, 6.11; S, 7.08.
4
.5.7. 2,2’-((((ethane-1,2-diylbis(oxy))bis(2,1-phenylene))bis(2-oxoethane-2,1-diyl))
bis(sulfanediyl))bis(4,6-dimethylnicotinonitrile) (14g).
Creamy powder, m.p.: 207–209°C; yield 66%, IR (KBr disc) ν = 3068, 2930, 2209, 1673,
−1 1
1585, 1444 cm . H NMR (300 MHz, DMSO) δ 2.06 (s, 6H, CH ), 2.29 (s, 6H, CH ), 4.61
3 3
(
7
s, 4H, OCH ), 4.65 (s, 4H, SCH ), 6.88 (s, 2H, pyridine-5-H), 7.06 (t, 2H, J = 7.5 Hz),
2
2
1
3
.29 (d, 2H, J = 8.4 Hz), 7.52–7.61 (m, 4H, ArH). C NMR (75 MHz, DMSO): 19.3, 23.7,

JOURNAL OF SULFUR CHEMISTRY
15
4
1
1
1.2, 67.1, 103.0, 113.1, 114.6, 119.8, 120.4, 120.7, 130.0, 133.9, 151.7, 157.2, 159.9, 160.8,
+
94.4. MS (m/z) 622 (M ). Anal. Calcd. For C H N O S : C, 65.57; H, 4.86; N, 9.00; S,
3
4
30
4
4 2
0.30. Found: C, 65.51; H, 4.77; N, 8.93; S, 10.22.
4.5.8. 2,2’-((((ethane-1,2-diylbis(oxy))bis(2,1-phenylene))bis(2-oxoethane-2,1-diyl))
bis(sulfanediyl))bis(4,6-diphenylnicotinonitrile) (14h)
Yellow powder, m.p.: 203–205°C; yield 64%, IR (KBr disc) ν = 3058, 2924, 2209, 1666,
−
1 1
1
6
1
525, 1482 cm . H NMR (300 MHz, DMSO) δ 4.69 (s, 4H, OCH ), 6.85 (s, 4H, SCH ),
2 2
.97 (t, 2H, J = 7.5 Hz), 7.11 (t, 4H, J = 7.5 Hz), 7.28–7.31 (m, 4H, ArH), 7.47–7.61 (m,
1
3
4H, ArH), 7.62 (s, 2H, pyridine-5-H), 7.75 (d, 4H, J = 7.5 Hz). C NMR (75 MHz,
DMSO): 41.7, 67.2, 102.1, 113.2, 115.3, 115.5, 120.8, 126.4, 126.9, 128.2, 128.4, 128.6, 129.8,
+
1
30.1, 130.3, 134.3, 135.4, 135.9, 153.6, 157.4, 157.6, 161.7, 193.5. MS (m/z) 871 (M ). Anal.
Calcd. For C H N O S : C, 74.46; H, 4.40; N, 6.43; S, 7.36. Found: C, 74.39; H, 4.48; N,
5
4
38
4
4 2
6
.56; S, 7.43.
4.5.9. 2,2’-((((propane-1,3-diylbis(oxy))bis(2,1-phenylene))bis(2-oxoethane-2,1-diyl))
bis(sulfanediyl))bis(4,6-dimethylnicotinonitrile) (14i)
Creamy powder, m.p.: 185–187°C; yield 73%, IR (KBr disc) ν = 3067, 2932, 2212, 1663,
−1 1
1
587, 1448 cm . H NMR (300 MHz, DMSO) δ 2.18 (s, 6H, CH ), 2.35 (s, 6H, CH ), 2.44
3 3
(
2
m, 2H, CH ), 4.38 (m, 4H, OCH ), 4.70 (s, 4H, SCH ), 6.96 (s, 2H, pyridine-5-H), 7.02 (t,
2 2 2
+
H, J = 7.2 Hz), 7.18 (d, 2H, J = 8.1 Hz), 7.48–7.58 (m, 4H, ArH). MS (m/z) 636 (M ).
Anal. Calcd. For C H N O S : C, 66.02; H, 5.07; N, 8.80; S, 10.07. Found: C, 65.89; H,
3
5
32
4
4 2
4
.96; N, 8.71; S, 9.93.
4.5.10. 2,2’-((((propane-1,3-diylbis(oxy))bis(2,1-phenylene))bis(2-oxoethane-2,1-
diyl))bis(sulfanediyl))bis(4,6-diphenylnicotinonitrile) (14j)
Yellow powder, m.p.: 186–188°C; yield 61%, IR (KBr disc) ν = 3056, 2924, 2212, 1661,
−1 1
1
567, 1522 cm . H NMR (300 MHz, DMSO) δ 2.33 (m, 2H, CH ), 4.35 (m, 4H,
2
OCH ), 4.83 (s, 4H, SCH ), 6.94 (t, 2H, J = 7.5 Hz), 7.20 (t, 6H, J = 7.2 Hz), 7.33 (t, 2H,
2
2
J = 7.2 Hz), 7.50–7.68 (m, 14H, ArH), 7.72 (s, 2H, pyridine-5-H), 7.86 (d, 4H, J = 7.5 Hz).
+
MS (m/z) 885 (M ). Anal. Calcd. For C H N O S : C, 74.64; H, 4.56; N, 6.33; S, 7.25.
5
5
40
4
4 2
Found: C, 74.54; H, 4.49; N, 6.27; S, 7.28.
4.5.11. 2,2’-((((butane-1,4-diylbis(oxy))bis(2,1-phenylene))bis(2-oxoethane-2,1-diyl))
bis(sulfanediyl))bis(4,6-dimethylnicotinonitrile) (14k)
White powder, m.p.: 215–217°C; yield 74%, IR (KBr disc) ν = 3075, 2930, 2211, 1651,
−
1 1
1
2
7
586, 1447 cm . H NMR (300 MHz, DMSO) δ 2.08 (br. s, 4H, CH ), 2.18 (s, 6H, CH ),
2 3
.32 (s, 6H, CH ), 4.24 (br. s, 4H, OCH ), 4.66 (s, 4H, SCH ), 6.94 (s, 2H, pyridine-5-H),
3
2
2
.02 (t, 2H, J = 7.5 Hz), 7.19 (d, 2H, J = 8.1 Hz), 7.56 (d, 4H, J = 7.5 Hz). MS (m/z) 650
+
(
M ). Anal. Calcd. For C H N O S : C, 66.44; H, 5.27; N, 8.61; S, 9.85. Found: C, 66.33;
3
6
34
4
4 2
H, 5.20; N, 8.55; S, 9.76.
4.5.12. 2,2’-((((butane-1,4-diylbis(oxy))bis(2,1-phenylene))bis(2-oxoethane-2,1-diyl))
bis(sulfanediyl))bis(4,6-diphenylnicotinonitrile) (14l)
Yellow powder, m.p.: 208–210°C; yield 76%, IR (KBr disc) ν = 3052, 2924, 2212, 1651,
−1 1
1
565, 1525 cm . H NMR (300 MHz, DMSO) δ 1.94 (br. s, 4H, CH ), 4.12 (br. s, 4H,
2

16
M. E. SALEM ET AL.
OCH ), 4.80 (s, 4H, SCH ),), 6.98 (t, 2H, J = 7.5 Hz), 7.00–7.28 (m, 6H, ArH), 7.36 (t, 2H,
2
2
J = 7.5 Hz), 7.54–7.67 (m, 14H, ArH), 7.75 (s, 2H, pyridine-5-H), 7.93 (d, 4H, J = 8.1 Hz).
+
MS (m/z) 899 (M ). Anal. Calcd. For C H N O S : C, 74.81; H, 4.71; N, 6.23; S, 7.13.
5
6
42
4
4 2
Found: C, 74.71; H, 4.64; N, 6.17; S, 7.05.
Acknowledgment
The authors gratefully acknowledge Alexander von Humboldt foundation for a research fellowship.
Disclosure statement
No potential conflict of interest was reported by the authors.
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