An efficient and direct synthesis of 2-thiopyridines via microwave-assisted three-component reaction

Article abstract of DOI:10.1002/jhet.161

(Chemical Equation Presented) A series of 2-p-tolylthiopyridine derivatives was directly synthesized via three-component reactions of chalcones, malononitrile, and 4-methylbenzenethiol catalyzed by Et₃N in DMF under microwave irradiation. It is

Full text of DOI:10.1002/jhet.161

886
An Efficient and Direct Synthesis of 2-Thiopyridines via
Microwave-Assisted Three-Component Reaction
Vol 46
Xing-Han Wang, Xu-Dong Cao, Shu-Jiang Tu,* Xiao-Hong Zhang,
Wen-Juan Hao, Shu Yan, Shan-Shan Wu, Zheng-Guo Han, and Feng Shi
Key Laboratory of Biotechnology for Medicinal Plant, School of Chemistry and Chemical
Engineering, Xuzhou Normal University, Xuzhou, Jiangsu 221116, People’s Republic of China
*E-mail: laotu2001@263.net
Received August 2, 2008
DOI 10.1002/jhet.161
Published online 2 September 2009 in Wiley InterScience (www.interscience.wiley.com).
A series of 2-p-tolylthiopyridine derivatives was directly synthesized via three-component reactions
of chalcones, malononitrile, and 4-methylbenzenethiol catalyzed by Et3N in DMF under microwave irra-
diation. It is an efficient and promising synthetic strategy to construct 2-thiopyridine skeleton with the
advantage of short time, excellent yield, and convenient operation.
J. Heterocyclic Chem., 46, 886 (2009).
INTRODUCTION
dine-3-carbonitrile derivatives using a,b-unsaturated
ketones as starting materials (Scheme 1).
The pyridine nucleus, as the key constituent in a
range of bioactive compounds, is one of the most well-
known systems among the naturally occurring hetero-
cycles [1]. Polysubstituted pyridines including the
related 2-thiopyridines are prominent building blocks,
exhibit antibacterial [2,3], pesticidal [4], antifungal
[4,5], and acaricidal properties [5] and may have poten-
tial ability to form complexes with transition metals.
Thus, the synthesis of pyridines and their analogs has
attracted much attention. The majority of synthetic
methods to the target compounds start from the conden-
sation of a,b-unsaturated ketones or b-diketones with
cyanothioacetamide, and then formed 2-alkylthio-pyri-
dines by the reaction of the iodoalkane [6]. However,
even these methods are still not satisfactory because of
the narrow scope of substituted alkylthiopyridines pro-
duced and the multistep synthesis. Therefore, the devel-
opment of a simple, one-pot, and directed synthetic
route, which provides diverse of 2-thiopyridine com-
pounds, is strongly desired for this important class of
heterocycles.
RESULTS AND DISCUSSION
To choose the most appropriate medium in this heter-
ocyclization reaction, the MW-assisted reaction of 3-(4-
bromophenyl)-1-p-tolylprop-2-en-1-one (1a), malononi-
trile (2), and 4-methylbenzenethiol (3) was examined
using the solvent of HOAc, glycol, THF, DMF, and
EtOH as solvent at 100ꢀC, respectively. The results are
summarized in Table 1, the reaction in DMF gave the
best yield. Therefore, DMF was chosen as the solvent of
this reaction. Moreover, to further improve the reaction
yields, different bases were examined for their ability to
promote this reaction at 100ꢀC. As shown in Table 2,
the Et3N afforded the target product 4a in an 85% yield.
Finally, to further optimize the reaction temperature, the
synthesis of 4a was performed in the presence of Et3N
at the temperatures ranging from 100 to 130ꢀC. As illus-
trated in Table 3, the yield of product 4a was increased
and the reaction time was shortened as the temperature
was increased from 100 to 120ꢀC. The yield decreased
slightly when the temperature was further increased
from 120 to 130ꢀC. So, the temperature of 120ꢀC was
chosen for all further microwave-assisted reactions.
As a part of our ongoing development of efficient
protocols for the preparation of polysubstituted hetero-
cycles [7] from common intermediates, we recently dis-
covered technically simple microwave (MW) conditions
for the synthesis of new 2-(p-tolylthio)-4,6-diarylpyri-
C
V
2009 HeteroCorporation

September 2009
An Efficient and Direct Synthesis of 2-Thiopyridines via
Microwave-Assisted Three-Component Reaction
887
Scheme 1
Table 2
Catalyst optimization for the synthesis of 4a.
Entry
Base
Time (min)
Yield (%)
1
2
3
4
5
NaOH
K2CO3
DMAP
Piperidine
Et3N
12
12
12
12
12
70
72
75
78
85
ured on a DPX 400 MHz spectrometer using TMS as an inter-
nal standard and DMSO-d6 as solvent. Elemental analyses
were determined with a Perkin-Elmer 240c elemental analysis
instrument.
Under these optimized reaction conditions, we synthe-
sized a series of products 4 using this simple procedure.
The results are summarized in Table 4 (Entries 1–14).
This methodology is applicable to aromatic and hetero-
aromatic chalcones. Furthermore, the electronic effect
with various substituents on the chalcones was studied
and had no significant effect on this reaction.
General procedure for 2-(p-Tolylthio)-4,6-diphenylpyri-
dine-3-carbonitrile derivatives (4). The reactions were per-
formed in a 10 mL EmrysTM reaction vial. Chalcones 1
(1 mmol), malononitrile 2 (1 mmol), and 4-methylbenzenethiol
3 (1 mmol) in DMF in the presence of Et3N were mixed and
then capped. The mixture was heated for a given time at
120ꢀC under microwave irradiation (initial power 200 W and
maximum power 250 W). Upon complete consumption of
starting materials, as monitored by TLC, the reaction mixture
was cooled to room temperature, and then filtered to give the
crude product, which was further purified by recrystallization
from EtOH (95%) to give pure target products 4.
A mechanism for the formation of the products 4 is
outlined in Scheme 2. The reaction occurs via initial for-
mation of compounds 5 afforded by Michael addition
reaction of chalcones and malononitrile followed by the
thiolate nucleophilic attack in the presence of Et3N. The
intermediate 5 cyclizes to dihydropyridine 6 and subse-
quent afford the fully aromatized compound 4 with the
loss of hydrogen. This type of oxidation is well prece-
dented [8b,9]. In this study, all the products were char-
2-(p-Tolylthio)-4-(4-bromophenyl)-6-p-tolylpyridine-3-car-
bonitrile 4a. This compound was obtained according to the
above general procedure; IR (potassium bromide): 3017, 2917,
1
2210, 1572, 1522, 1491, 1368, 1008, 820, 803, 761 cmꢁ1; H
1
acterized by mp, IR, and H NMR spectral data and ele-
mental analysis.
NMR (DMSO-d6): d 7.92 (s, 1H, PyH),7.79 (t, J ¼ 7.6 Hz,
4H, ArH), 7.68 (d, J ¼ 8.4 Hz, 2H, ArH), 7.56 (d, J ¼ 8.4
Hz, 2H, ArH), 7.38 (d, J ¼ 8.0 Hz, 2H, ArH), 7.20 (d, J ¼
8.0 Hz, 2H, ArH), 2.44 (s, 3H, CH3), 2.32 (s, 3H, CH3); Anal.
Calcd. for C26H19BrN2S: C, 66.24; H, 4.06; N, 5.94; Found:
C, 66.45; H, 4.10; N, 5.90.
2-(p-Tolylthio)-4-(4-chlorophenyl)-6-p-tolylpyridine-3-car-
bonitrile 4b. This compound was obtained according to above
general procedure; IR (potassium bromide): 3063, 2918, 2210,
1595, 1523, 1367, 1093, 821, 801, 760 cmꢁ1 1H NMR
;
In summary, we demonstrated a rapid and direct
method that offers a simple and efficient route for the
one-pot, three-component synthesis of highly functional-
ized 2-thiopyridine derivatives in excellent yields. Par-
ticularly valuable features of this method include opera-
tional simplicity and increased safety for small-scale
high-speed synthesis.
(DMSO-d6): d 7.92 (s, 1H, PyH),7.79 (t, J ¼ 7.6 Hz, 4H,
ArH), 7.68 (d, J ¼ 8.4 Hz, 2H, ArH), 7.56 (d, J ¼ 8.4 Hz,
2H, ArH), 7.38 (d, J ¼ 8.0 Hz, 2H, ArH), 7.20 (d, J ¼ 8.0
Hz, 2H, ArH), 2.44 (s, 3H, CH3), 2.32 (s, 3H, CH3). Anal.
Calcd. For C26H19ClN2S: C, 73.14; H, 4.49; N, 6.56; Found:
C, 73.29; H, 4.52; N, 6.63.
EXPERIMENTAL
Microwave irradiation was carried out with an EmrysTM
Creator microwave oven from Personal Chemistry, Uppsala,
Sweden. Melting points were determined in open capillaries
and were uncorrected. IR spectra were recorded on a FT-IR-
Tensor 27 spectrometer in KBr. 1H NMR spectra were meas-
Table 3
Temperature optimization for the synthesis 4a.
Table 1
Temp (ꢀC)
Time (min)
Yield (%)
Solvent optimization for the synthesis of 4a.
Entry
1
2
3
4
5
6
7
100
105
110
115
120
125
130
12
11
10
10
9
85
86
88
89
95
94
94
Entry
Solvent
Time (min)
Yield (%)
1
2
3
4
5
THF
Glycol
EtOH
HOAc
DMF
12
12
12
12
12
25
28
24
40
55
9
9
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

888
X.-H. Wang, X.-D. Cao, S.-J. Tu, X.-H. Zhang, W.-J. Hao, S. Yan, S.-S. Wu,
Z.-G. Han, and F. Shi
Vol 46
Table 4
Physical data of products 4.
Entry
Product
Chalcones
Time (min)
Yield (%)
Mp (ꢀC)
1
2
4a
4b
4c
4d
4f
4e
4g
4h
4i
4j
4k
4l
4m
4n
3-(4-Bromophenyl)-1-p-tolylprop-2-en-1-one
3-(4-Chlorophenyl)-1-p-tolylprop-2-en-1-one
3-(4-Nitrophenyl)-1-p-tolylprop-2-en-1-one
9
8
95
93
92
90
93
94
89
90
91
94
94
93
90
90
254–255
195–196
266–268
174–175
212–215
221–223
195–196
182–184
245–248
183–184
201–202
195
3
4
9
10
9
3-(3,4-Dimethoxyphenyl)-1-p-tolylprop-2-en-1-one
3-(Benzo[d][1,3]dioxol-6-yl)-1-p-tolylprop-2-en-1-one
3-(4-Bromophenyl)-1-(4-methoxyphenyl)prop-2-en-1-one
1-(4-Methoxyphenyl)-3-phenylprop-2-en-1-one
5
6
7
8
9
8
9
3-(4-(Dimethylamino)phenyl)-1-(4-methoxyphenyl)prop-2-en-1-one
3-(3,4-Dimethoxyphenyl)-1-phenylprop-2-en-1-one
1-(4-Fluorophenyl)-3-(3,4-dimethoxyphenyl)prop-2-en-1-one
1-(4-Fluorophenyl)-3-(4-methoxyphenyl)prop-2-en-1-one
1-(4-Chlorophenyl)-3-(4-methoxyphenyl)prop-2-en-1-one
3-(3,4-Dimethoxyphenyl)-1-(pyridin-2-yl)prop-2-en-1-one
3-(4-Bromophenyl)-1-(pyridin-2-yl)prop-2-en-1-one
9
10
7
10
11
12
13
14
7
8
7
7
189–190
191–192
2-(p-Tolylthio)-4-(4-nitrophenyl)-6-p-tolylpyridine-3-car-
bonitrile 4c. This compound was obtained according to the
above general procedure; IR (potassium bromide): 3071, 2207,
2-(p-Tolylthio)-6-(4-methoxyphenyl)-4-phenylpyridine-3-
carbonitrile 4g. This compound was obtained according to the
above general procedure; IR (potassium bromide): 3015, 2976,
2214, 1608, 1568, 1525, 1491, 1406, 1368, 1310, 1168, 1022,
1
1604, 1567, 1526, 1353, 1018, 859, 820, 808 cmꢁ1; H NMR
1
(DMSO-d6): d 8.44 (d, J ¼ 8.4 Hz, 2H, ArH), 8.05 (d, J ¼ 8.0
Hz, 2H, ArH), 8.00 (s, 1H, PyH), 7.79 (d, J ¼ 8.0 Hz, 2H,
ArH), 7.57 (d, J ¼ 8.0 Hz, 2H, ArH), 7.39 (d, J ¼ 8.0 Hz,
2H, ArH ), 7.22 (d, J ¼ 8.0 Hz, 2H, ArH), 2.44 (s, 3H, CH3),
2.33 (s, 3H, CH3). Anal. Calcd. for C26H19N3O2S: C, 71.38;
H, 4.38; N, 9.60; Found: C, 71.54; H, 4.40; N, 9.65.
834, 808, 773, 757, 698 cmꢁ1; H NMR (DMSO-d6): d 7.88–
7.86 (m, 3H, ArH, PyH), 7.77–7.75 (m, 2H, ArH), 7.61–7.57
(m, 5H, ArH), 7.39 (d, J ¼ 8.0 Hz, 2H, ArH), 6.93 (d, J ¼ 8.8
Hz, 2H, ArH), 3.81 (s, 3H, OCH3), 2.45 (s, 3H, CH3). Anal.
Calcd. for C26H20N2OS: C, 76.44; H, 4.93; N, 6.86; Found: C,
76. 04; H, 4.96; N, 6.88.
2-(p-Tolylthio)-4-(3,4-dimethoxyphenyl)-6-p-tolylpyridine-
3-carbonitrile 4d. This compound was obtained according to
the above general procedure; IR (potassium bromide): 3003,
2935, 2214, 1604, 1569, 1523, 1506, 1270, 1140, 1022, 800,
2-(p-Tolylthio)-4-(4-(dimethylamino)phenyl)-6-(4-methox-
yphenyl)pyridine-3-carbonitrile 4h. This compound was
obtained according to the above general procedure; IR (potas-
sium bromide): 3070, 3014, 2889, 2208, 1610, 1567, 1506,
1406, 1365, 1310, 1246, 1202, 1167, 1060, 836, 808, 735
1
662 cmꢁ1; H NMR (DMSO-d6): d 7.84 (s, 1H, PyH), 7.73 (d,
1
J ¼ 8.0 Hz, 2H, ArH), 7.51 (d, J ¼ 8.0 Hz, 2H, ArH), 7.35–
7.29 (m, 4H, ArH), 7.17–7.11 (m, 3H, ArH), 3.83 (s, 3H,
OCH3), 3.81 (s, 3H, OCH3), 2.39 (s, 3H, CH3), 2.28 (s, 3H,
CH3). Anal. Calcd. for C28H24N2O2S: C, 74.31; H, 5.35; N,
6.19; Found: C, 74.11; H,5.51; N, 6.32.
cmꢁ1; H NMR (DMSO-d6): d 7.84 (d, J ¼ 9.2 Hz, 2H, ArH),
7.77 (s, 1H, PyH), 7.65(d, J ¼ 8.8 Hz, 2H, ArH), 7.55 (d, J ¼
8.0 Hz, 2H, ArH), 7.37 (d, J ¼ 8.0 Hz, 2H, ArH), 6.92 (d,
J ¼ 9.2 Hz, 2H, ArH), 6.86 (d, J ¼ 9.2 Hz, 2H, ArH), 3.80 (s,
3H, OCH3), 3.02 (s, 6H, N(CH3)2), 2.43 (s, 3H, CH3). Anal.
Calcd. for C28H25N3OS: C, 74.47; H, 5.58; N, 9.31; Found: C,
74.27; H, 5.65; N, 9.57.
2-(p-Tolylthio)-4-(3,4-dimethoxyphenyl)-6-phenylpyridine-
3-carbonitrile 4i. This compound was obtained according to
the above general procedure; IR (potassium bromide): 3034,
2998, 2210, 1606, 1570, 1551, 1491, 1368, 1266, 1252, 1172,
2-(p-Tolylthio)-4-(benzo[d][1,3]dioxol-6-yl)-6-p-tolylpyri-
dine-3-carbonitrile 4e. This compound was obtained accord-
ing to the above general procedure; IR (potassium bromide):
2918, 2214, 1566, 1525, 1502, 1376, 1251, 1042, 816 cmꢁ1
;
1H NMR (DMSO-d6): d 7.85 (s, 1H, PyH), 7.77 (d, J ¼ 8.0
Hz, 2H, ArH), 7.55 (d, J ¼ 8.0 Hz, 2H, ArH), 7.39–7.37 (m,
3H, ArH), 7.30–7.27 (m, 1H, ArH), 7.19 (d, J ¼ 8.0 Hz, 2H,
ArH), 7.14 (d, J ¼ 7.6 Hz, 2H, ArH), 6.16 (s, 2H, OCH2O),
2.43 (s, 3H, CH3), 2.32 (s, 3H, CH3). Anal. Calcd. for
C27H20N2O2S: C, 74.29; H, 4.62; N, 6.42; Found: C, 74.31; H,
4.76; N, 6.53.
Scheme 2
2-(p-Tolylthio)-4-(4-bromophenyl)-6-(4-methoxyphenyl)-
pyridine-3-carbonitrile 4f. This compound was obtained
according to the above general procedure; IR (potassium bro-
mide): 3065, 2961, 2212, 1600, 1574, 1519, 1489, 1421, 1256,
1176, 1024, 1009, 983, 839, 820, 810 cmꢁ1
;
1H NMR
(DMSO-d6): d 7.87 (s, 1H, PyH), 7.84–7.81 (m, 4H, ArH),
7.71 (d, J ¼ 8.4 Hz, 2H, ArH), 7.56 (d, J ¼ 8.0 Hz, 2H,
ArH), 7.39 (d, J ¼ 7.6 Hz, 2H, ArH), 6.93 (d, J ¼ 9.2 Hz,
2H, ArH), 3.81 (s, 3H, OCH3), 2.44 (s, 3H, CH3). Anal. Calcd.
for C26H19BrN2OS: C, 64.07; H, 3.93; N, 5.75; Found: C,
64.26; H, 3.85; N, 5.89.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

September 2009
An Efficient and Direct Synthesis of 2-Thiopyridines via
Microwave-Assisted Three-Component Reaction
889
1024, 828, 813, 781, 758, 691 cmꢁ1; H NMR (DMSO-d6): d
7.96–7.93 (m, 3H, ArH, PyH), 7.56 (d, J ¼ 8.0 Hz, 2H, ArH),
7.40–7.35 (m, 4H, ArH), 7.25 (t, J ¼ 8.8 Hz, 2H, ArH), 7.17
(d, J ¼ 8.0 Hz, 1H, ArH), 3.87 (s, 3H, OCH3), 3.86 (s, 3H,
OCH3), 2.45 (s, 3H, CH3). Anal. Calcd. for C27H22N2O2S: C,
73.95; H, 5.06; N, 6.39; Found: C, 73.86; H, 5.16; N, 6.59.
2-(p-Tolylthio)-6-(4-fluorophenyl)-4-(3,4-dimethoxyphenyl)
pyridine-3-carbonitrile 4j. This compound was obtained
according to the above general procedure; IR (potassium bro-
mide): 3004, 2955, 2207, 1600, 1573, 1524, 1506, 1263, 1219,
1151, 1029, 824, 808; 1H NMR (DMSO-d6): d 7.96–7.93 (m,
3H, ArH, PyH), 7.56 (d, J ¼ 8.0 Hz, 2H, ArH), 7.40–7.35 (m,
4H, ArH), 7.25 (d, J ¼ 8.8 Hz, 2H, ArH), 7.17 (d, J ¼ 8.4
Hz, 2H, ArH), 3.87 (s, 3H, OCH3), 3.81 (s, 3H, OCH3), 2.44
(s, 3H, CH3). Anal. Calcd. for C27H21FN2O2S: C, 71.03; H,
4.64; N, 6.14; Found: C, 71.15; H, 4.67; N, 6.20.
2217, 1592, 1574, 1523, 1490, 1372, 1294, 1278, 1059,
1010, 806 cmꢁ1 1H NMR (DMSO-d6): d 8.70–8.69 (m,
;
1
1H, PyH), 8.20 (s, 1H, PyH), 7.89–7.86 (m, 1H, PyH),7.83
(d, J ¼ 8.4 Hz, 2H, ArH), 7.71 (d, J ¼ 8.4 Hz, 2H,
ArH), 7.67 (d, J ¼ 8.0 Hz, 2H, ArH), 7.59 (d, J ¼ 8.0
Hz, 2H, ArH), 7.51–7.59 (m, 1H, PyH), 7.41 (d, J ¼ 8.0
Hz, 2H, ArH), 2.45 (s, 3H, CH3). Anal. Calcd. for
C24H16BrN3S: C, 62.89; H, 3.52; N, 9.17; Found: C, 63.01;
H, 3.65; N, 9.29.
Acknowledgments. The authors are grateful to financial support
from the National Science Foundation of China (No. 20672090),
Natural Science Foundation of the Jiangsu Province (No.
BK2006033), the Qing Lan Project (No. 08QLT001), and Six
Kinds of Professional Elite Foundation of the Jiangsu Province
(No. 06-A-039).
2-(p-Tolylthio)-6-(4-fluorophenyl)-4-(4-methoxyphenyl)-
pyridine-3-carbonitrile 4k. This compound was obtained
according to the above general procedure; IR (potassium bro-
mide): 2918, 2214, 1600, 1571, 1524, 1515, 1373, 1255, 1154,
1034, 827, 799 cmꢁ1 1H NMR (DMSO-d6): d 7.96–7.92 (m,
;
REFERENCES AND NOTES
3H, ArH, PyH), 7.75 (d, J ¼ 8.8 Hz, 2H, ArH), 7.56 (d, J ¼
8.4 Hz, 2H, ArH), 7.38 (d, J ¼ 8.0 Hz, 2H, ArH), 7.24 (t, J ¼
8.8 Hz, 2H, ArH), 7.15 (d, J ¼ 8.8 Hz, 2H, ArH), 3.86 (s, 3H,
OCH3), 2.44 (s, 3H, CH3). Anal. Calcd. for C26H19FN2OS: C,
73.22; H, 4.49; N, 6.57; Found: C, 73.21; H, 4.48; N, 6.80.
2-(p-Tolylthio)-6-(4-chlorophenyl)-4-(4-methoxyphenyl)-
pyridine-3-carbonitrile 4l. This compound was obtained
according to the above general procedure; IR (potassium bro-
mide): 3061, 2934, 2211, 1609, 1577, 1524, 1491, 1369, 1255,
[1] Yates, F.; Courts, R. T.; Casy, A. F. In Pyridine and Its
Derivatives: Supplement IV; Abramovitch, R. A., Ed.; Wiley, New
York, 1975; p 445.
[2] (a) Kuwada, Y.; Meguro, K.; Sato, Y.; Fugono, T. Ger
Offen 1975, 2,435,025; (b) Kuwada, Y.; Meguro, K.; Sato, Y.;
Fugono, T. Chem Abstr 1975, 82, 156252.
[3] (a) Freeman, P. F. H. U.S. Pat. 1972, 3,674,877; (b) Free-
man, P. F. H. Chem Abstr 1972, 77, 88314.
[4] Guerrera, F.; Salerno, L.; Sarva, M. C.; Siracusa, M. A.
Farmacoi Ed Sci 1993, 48, 1725.
1182, 1090, 1034, 1010, 829, 803 cmꢁ1 1H NMR (DMSO-
;
[5] (a) Tahara, T.; Hamasaki, T. Japan Kokai 1975, 75, 140;
(b) Tahara, T.; Hamasaki, T. Chem Abstr 1976, 85, 21428.
[6] (a) Zubarev, A. A.; Zav’yalova, V. K.; Litvinov, V. P. Russ
Chem Bull 2005, 54, 2578; (b) Zubarev, A. A.; Zavyalova, V. K.; Lit-
vinov, V. P. Russ Chem Bull 2003, 5, 978; (c) Victory, P.; Borrell,
J. I.; Cirujeda, J.; Vidal-Ferran, A. Heterocycles 1993, 36, 777;
(d) Krauze, A.; Pelcher, Yu. E.; Kalme, Z.; Duburs, G. Khimiya Geter-
otsiklicheskikh Soedinenii 1984, 8, 1140; (e) Aivars, K.; Skaidrite, G.
Eur J Med Chem 1999, 34, 301.
d6): d 7.94 (s, 1H, PyH),7.89 (d, J ¼ 8.8 Hz, 2H, ArH), 7.75
(d, J ¼ 8.8 Hz, 2H, ArH), 7.55 (d, J ¼ 8.0 Hz, 2H, ArH),
7.46 (d, J ¼ 8.4 Hz, 2H, ArH), 7.38 (d, J ¼ 8.0 Hz, 2H,
ArH), 7.16 (d, J ¼ 8.8 Hz, 2H, ArH), 3.86 (s, 3H, OCH3),
2.44 (s, 3H, CH3). Anal. Calcd. for C26H19ClN2OS: C, 70.50;
H, 4.32; N, 6.32; Found: C, 70.29; H, 4.50; N, 6.20.
2-(p-Tolylthio)-4-(3,4-dimethoxyphenyl)-6-(pyridin-2-yl)
pyridine-3-carbonitrile 4m. This compound was obtained
according to the above general procedure; IR (potassium bro-
mide): 2932, 2834, 2213, 1560, 1511, 1269, 1142, 1025, 866,
[7] (a) Tu, S. J.; Jiang, B.; Zhang, Y.; Zhang, J. Y.; Jia, R. H.;
Yao, C. S. Chem Lett 2006, 35, 1338; (b) Tu, S. J.; Jia, R. H.; Jiang,
B.; Zhang, J. Y.; Zhang, Y.; Yao, C. S.; Ji, S. J. Tetrahedron 2007, 63,
381; (c) Tu, S. J.; Jiang, B.; Zhang, Y.; Jia, R. H.; Zhang, J. Y.; Yao,
C. S.; Shi, F. Org Biomol Chem 2007, 5, 355.
800 cmꢁ1
;
1H NMR (DMSO-d6): d 8.70 (d, 1H, J ¼ 4.4 Hz,
PyH), 8.22 (s, 1H, PyH), 7.86 (t, J ¼ 8.0 Hz, 1H, PyH), 7.68
(d, J ¼ 8.0 Hz, 1H, PyH), 7.59 (d, J ¼ 8.0 Hz, 2H, ArH),
7.48 (t, J ¼ 8.0 Hz, 1H, PyH), 7.42–7.36 (m, 3H, ArH), 3.87
(s, 3H, OCH3), 3.86 (s, 3H, OCH3), 2.45 (s, 3H, CH3). Anal.
Calcd. for C26H21N3O2S: C, 71.05; H, 4.82; N, 9.56; Found:
C, 71.20; H, 4.85; N, 9.57.
[8] (a) Evdokimov, N. M.; Kireev, A. S.; Yakovenko, A. A.;
Antipin, M. Y.; Magedov, I. V.; Kornienko, A. J Org Chem 2007, 72,
3443; (b) Evdokimov, N. M.; Magedov, I. V.; Kireev, A. S.; Kor-
nienko, A. Org Lett 2006, 8, 899.
2-(p-Tolylthio)-4-(4-bromophenyl)-6-(pyridin-2-yl)pyridine-
3-carbonitrile 4n. This compound was obtained according to
the above general procedure; IR (potassium bromide): 3053,
[9] (a) Yoneda, F.; Yano, T.; Higuchi, M.; Koshiro, A. Chem
Lett 1979, 155; (b) Devi, I.; Kumarb, B. S. D.; Bhuyana, P. J. Tetrahe-
dron Lett 2003, 44, 8307.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet