DBU-catalyzed three-component one-pot synthesis of highly functionalized pyridines in aqueous ethanol

Article abstract of DOI:10.1002/jhet.32

1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) efficiently catalyzes three-component one-pot condensations of aldehyde, malononitrile, and thiophenol to produce highly functionalized pyridines in excellent yield in aqueous ethanol.

Full text of DOI:10.1002/jhet.32

January 2009
DBU-Catalyzed Three-Component One-Pot Synthesis of Highly
Functionalized Pyridines in Aqueous Ethanol
69
Ritu Mamgain, Ram Singh, and Diwan S. Rawat*
Department of Chemistry, University of Delhi, Delhi 110007, India
*E-mail: dsrawat@chemistry.du.ac.in
Received March 6, 2008
DOI 10.1002/jhet.32
Published online 11 February 2009 in Wiley InterScience (www.interscience.wiley.com).
1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) efficiently catalyzes three-component one-pot condensa-
tions of aldehyde, malononitrile, and thiophenol to produce highly functionalized pyridines in excellent
yield in aqueous ethanol.
J. Heterocyclic Chem., 46, 69 (2009).
INTRODUCTION
as the risk of air pollution is significantly reduced due to
their nonvolatile nature [29,30] but their toxicity, espe-
cially, immidazolium-based ionic liquids and cost has been
a matter of concerns [31,32]. So, development of an
improved synthetic protocol for the generation of pyridine-
3,5-dicarbonitriles for lead optimization is of considerable
interest. As a part of our ongoing effort towards the synthesis
of biologically active compounds [33–35] and keeping the
medicinal values of pyridine-3,5-dicarbonitriles in mind, we
considered it necessary to develop an efficient high yielding
synthetic protocol for the synthesis of this class of
compounds.
The pyridine scaffold is a key constituent of a wide
range of naturally occurring and synthetic bioactive com-
pounds, pharmaceuticals, and functional materials [1–3].
Penta-substituted pyridines are known as medicinally priv-
ileged scaffold, inhibit MAPK-activated PK-2 [4] and
modulate androgen receptor functions [5]. These com-
pounds are also useful in the treatment of urinary inconti-
nence [6], HBF infections [7], Creutzfeldt-Jacob disease
[8], and Parkinson’s disease, hypoxia/ischemia, asthma,
kidney disease, epilepsy, cancer [9–11] and also exhibit
antibacterial, anti-biofilm and anti-infective activities [12].
The importance of this class of compounds can be real-
ized by the number of patents filed in the recent years [4–
7,12]. Thus, synthesis of highly functionalized pyridine
derivatives, with the aim to develop new drug molecules
has been an active area of research [13–15]. Various syn-
thetic protocols have been developed for the synthesis of
pyridine-3,5-dicarbonitriles [16–25]. The most interesting
synthetic methodology has been three-component conden-
sation of aldehydes, malononitrile, and thiolphenols
[17,26,27]. Various bases such as Et3N, DABCO
[17,26,27], and piperidine, morpholine, thiomorpholine,
pyrrolidine, N,N-DIPEA, pyridine, 2,4,6-collidine, DMAP,
aniline, N-methyl-aniline, N,N-dimethylaniline, and N,N-
diethylaniline [27] have been used. However, the major
drawback of these procedures is the formation of various
side products [26], thus reducing the yield of the desired
product to 20–48% [26,27]. It is important to mention
here that Ranu et al. [28] have reported a better synthetic
protocol for this reaction and immidazolium-based ionic
liquid and ethanol have been used as reaction media.
Although ionic liquids are considered to be green solvents
RESULTS AND DISCUSSION
Careful literature analyses revealed that a variety of
bases with pKa ranges from 4 to 11 have been used for
this multicomponent reaction. We speculated that use of
neutral organic base that have high basicity, and can
form a stable protonated species, may suppress the for-
mation of enaminonitrile and other side products. 1,8-
Diazabicyclo-[5.4.0]undec-7-ene (DBU) fulfills these
requirements, and it has been used in many organic
transformations in recent years. DBU is commercially
available, cheap homogenous catalyst. It is a sterically
hindered amidine base and especially useful where side
reactions due to the inherent nucleophilicity of a basic
nitrogen are a problem [36–40]. DBU is one of the
strongest organic neutral base (pKa ¼ 12) and the þM
effect of the adjacent nitrogen stabilizes the protonated
species. Inspired with the catalytic potential of DBU, we
examined the catalytic role of DBU in the synthesis of
pyridine-3,5-dicarbonitriles via three component reaction
of aldehydes, malononitriles, and thiols. The reaction of
C
V
2009 HeteroCorporation

70
R. Mamgain, R. Singh, and D. S. Rawat
Vol 46
of 4a at 35ꢀC in 15 min in 80% yield, while the same
reaction takes 1.5 h to complete at reflux temperature in
ethanol, and yield of the product was reported to be 35%
when other bases were used [26]. Encouraged by this ob-
servation, a series of reactions were carried out under
identical reaction conditions, and in all of the cases the
product was isolated in very good yield (Table 1). How-
ever, reaction temperature was increased up to 65ꢀC in
some cases. A library of compounds was synthesized
using 5 mol % DBU as base. The same reactions were
also carried out in ethanol, but it was observed that the
addition of 10% water in the reaction lead to increase in
the yield to 8–10%. However, when ethanol-water (1:1)
and water was used as a reaction media, no or very low
yield was observed even at elevated temperature, due to
the insolubility of the starting materials. We have also
explored the possibility of using polyethylene glycol
(PEG) as a reaction media, but no product formation was
observed in PEG. This multicomponent reaction works
well for unsubstituted (entry 4a, 4q, 4w), electron poor
(entry 4g, 4h), electron rich (entry 4b–4e, 4i–4v), and
Scheme 1
an aldehyde (1), malononitrile (2), and thiol (3) was car-
ried out in the presence of catalytic amount of DBU
(Scheme 1). We were pleased to observe that use of
5 mol % DBU as a catalyst in 10% aqueous ethanol sig-
nificantly increases the rate of reaction and yield of the
product at lower temperatures (Table 1). A wide range
of substituted aromatic as well as heteroaromatic alde-
hydes underwent this three-component condensation
with malononitrile and thiols to produce pyridine-3,5-
dicarbonitriles (4) in high yield. The results are summar-
ized in Table 1. All the utilized functionalities were
found to be compatible under the reaction conditions.
For example, three-component reaction of benzalde-
hyde, malononitrile, and thiophenol lead to the formation
Table 1
DBU catalyzed three-component synthesis of substituted pyridine-3,5-dicarbonitriles via Scheme 1.
MP (ꢀC)
Reported
Compd. No.
R
R0
Temp (ꢀC)
Time (min)
Yield (%)
Found
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
4r
4s
Ph
4-Cl-Ph
Ph
Ph
Ph
Ph
35
35
50
55
50
65
55
50
50
50
50
50
55
35
55
55
50
55
55
60
60
55
15
15
15
15
25
15
15
20
15
10
20
15
20
20
20
15
15
30
35
30
40
25
80
87
90
89
85
87
85
83
85
89
88
88
89
90
91
89
86
80
85
80
75
88
220–221
223
241–244
313
<300
258–260
219–220
290–291
230–231
236
218 [26]
222 [26]
240 [27]
315 [17]
4-OMe-Ph
4-OH-Ph
3-Pyridinyl
1-Naphthyl
3-NO2-Ph
2-NO2-Ph
4-Cl-Ph
Ph
Ph
305–306 [26]
–
Ph
–
4-Me-Ph
Ph
Ph
–
228–230 [28]
–
250 [10]
2-Naphthyl
4-F-Ph
Ph
Ph
Ph
Ph
248–249
265–266
278–280
255–257
236
2-OH-Ph
3-Me-Ph
4-Br-Ph
3-Me-Ph
4-Cl-Ph
Ph
–
280 [10]
–
–
4-Me-Ph
4-Me-Ph
4-Me-Ph
2-NH2-Ph
2-NH2-Ph
2-NH2-Ph
2-NH2-Ph
2-NH2-Ph
245–246
238
–
–
207–208 [41]
4-Me-Ph
4-OMe-Ph
4-Cl-Ph
208–210
232
233
235–236 [41]
239–240 [26]
4t
4u
4v
4-OH-Ph
1-Naphthyl
175
220–222
–
–
4w
4x
Ph
60
60
55
60
60
60
55
40
35
30
25
25
40
30
85
80
79
83
85
85
85
189
–
–
–
–
–
–
–
4-Me-Ph
4-Br-Ph
180–181
180–182
220–222
248
4y
4z
1-Naphthyl
2-Naphthyl
4-OMe-Ph
4-Cl-Ph
4aa
4ab
4ac
198
193–195
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2009
DBU-Catalyzed Three-Component One-Pot Synthesis of Highly Functionalized
Pyridines in Aqueous Ethanol
71
a waters micromass LCT Mass Spectrometer/Data system. The
1H NMR and 13C NMR spectra were recorded on Bruker
Spectrospin spectrometer at 300 MHz and 75.5 MHz, respec-
tively using TMS as an internal standard. The chemical shift
values are recorded on d scale and the coupling constants (J)
are in Hz. Elemental analysis were performed on a Carlo Erba
Model EA-1108 elemental analyzer and data of C, H, and N is
within ꢂ0.4% of calculated values.
heteroaromatic aldehydes (entry 4e). However, aliphatic
aldehydes either gave very poor yield or did not react.
According to the proposed mechanisms, the first step
of this reaction is the formation of Knoevenagel product
by the condensation of an aldehyde with malononitrile
[26,27,41,42]. During this base-catalyzed three-compo-
nent reaction, formation of many side products such as
enaminonitrile, higher adducts, reduced products, and
malononitrile self addition products have been noticed
[26,41]. We believe that low reaction temperature,
higher basicity, and stability of DBU-Hþ species gener-
ated in this reaction suppress the formation of these side
products and, hence, yield of the product increases. It is
important to mention here that use of DABCO has been
shown to promote the reaction of hindered aldehydes,
with marginal increase of yield of the product [26].
To assess the feasibility of the methodology on higher
scale under identical reaction conditions, we carried out
the reaction on a 50 gm scale (entry 4b, 4g) and it was
observed that the reaction proceeded smoothly and the
desired product was isolated in 87% and 85% yields,
respectively. It is important to mention here that the
reaction media can be reused for further reactions. For
example, after completion of the reaction, the reaction
mixture was cooled, and solid product was collected by
filtration (entry 4b). To the filtrate, p-chlorobenzaldehyde,
malononitrile, and thiophenol were added in the same
molar ratio without additional load of DBU. The reaction
mixture was stirred for specified time, marginal loss of the
yield was observed in first three run (87%, 86%, and
83%), while in fourth and fifth run the yield dropped to
75% and 65%, respectively. Structures of all of the com-
pounds were identified by their mp and spectral data.
General procedure for the synthesis of substituted
pyridines. To a stirred solution of substituted benzaldehyde
(4.71 mmol) in 10% aqueous ethanol (5 mL), DBU (5 mol %)
was added followed by dropwise addition of malononitrile
(9.43 mmol) at room temperature. To this stirred mixture sub-
stituted thiols (4.71 mmol) was added dropwise. The reaction
mixture was stirred at 35–65ꢀC as specified in Table 1; reac-
tion progress was monitored by TLC. The crude product was
collected by filtration and was purified by crystallization or by
SiO2 column chromatography. Spectral data of all unknown
compounds is given later.
2-Amino-4-(1-naphthyl)-6-phenylsulphanylpyridine-3,5-
dicarbonitrile (4f). IR: 3437, 3327, 3217, 2219, 1626, 1552,
;
1462, 1377, 1270, 798, 776, 750, 721 cmꢁ1 1H NMR (300
MHz, DMSO-d6): d 7.53–7.62 (m, 5H), 7.66–7.68 (m, 5H),
7.91 (brs, 2H), 8.07–8.15 (m, 2H); HRMS calc. for
C23H14N4S: 378.0939, found: 378.0929; Anal. calc. for
C23H14N4S: C, 72.99; H, 3.73; N, 14.80; S, 8.47; found: C,
72.89; H, 3.66; N, 14.88; S, 8.42.
2-Amino-4-(3-nitrophenyl)-6-phenylsulphanylpyridine-3,5-
dicarbonitrile (4g). IR: 3400, 3323, 3230, 2213, 1647, 1550,
1
1526, 1426, 1377, 1260, 1037, 805, 754 cmꢁ1; H NMR (300
MHz, DMSO-d6): d 7.52–7.61 (m, 5H), 7.89–7.94 (m, 2H),
8.07 (d, J ¼ 6 Hz, 1H), 8.45 (d, J ¼ 6 Hz, 1H), 8.52 (brs,
2H); HRMS calc. for C19H11N5O2S: 373.0633, found:
373.0631; Anal. calc. for C19H11N5O2S: C, 61.12; H, 2.97; N,
18.76; S, 8.59; found: C, 61.18; H, 3.01; N, 18.69; S, 8.51.
2-Amino-4-(2-nitrophenyl)-6-(4-tolyl)sulphanylpyridine-3,5-
dicarbonitrile (4h). IR: 3395, 3323, 3231, 2211, 1645, 1551,
1
1523, 1463, 1354, 1258, 1036, 813, 736 cmꢁ1; H NMR (300
MHz, DMSO-d6): d 2.37 (s, 3H), 7.30 (d, J ¼ 8 Hz, 2H), 7.50
(d, J ¼ 8 Hz, 2H), 7.91–7.94 (m, 2H), 8.05 (d, J ¼ 6 Hz,
1H), 8.43 (d, J ¼ 6Hz, 1H), 8.52 (brs, 2H); 13C NMR
(75.5 MHz, DMSO-d6): d 87.15, 93.22, 114.78, 115.09,
123.36, 123.59, 125.13, 130.18, 130.65, 134.92, 135.21,
135.42, 139.66, 147.66, 156.26, 159.52, 166.64; HRMS calc.
for C20H13N5O2S: 378.0790, found: 378.0799; Anal. calc. for
C20H13N5O2S: C, 62.00; H, 3.38; N, 18.08; S, 8.28; found: C,
61.96; H, 3.42; N, 18.13; S, 8.20.
CONCLUSION
In conclusion, we have developed a novel synthetic
methodology for the synthesis of pyridine-3,5-dicarbo-
nitriles using 5 mol % DBU as a catalyst and 10% aqueous
ethanol as the reaction media through a three component
condensation of aldehydes, malononitrile and thiols. The
short reaction times, high yields, use of commercially inex-
pensive DBU as a catalyst, and reusability of the reaction
media are the main advantages of this process.
2-Amino-4-(2-naphthyl)-6-phenylsulphanylpyridine-3,5-
dicarbonitrile (4j). IR: 3371, 2209, 1615, 1545, 1458, 1377,
1246, 815, 736 cmꢁ1 1H NMR (300 MHz, DMSO-d6): d
;
7.50–7.53 (m, 5H), 7.63–7.65 (m, 5H), 7.89 (brs, 2H), 8.06–
8.18 (m, 2H); 13C NMR (75.5 MHz, DMSO-d6): d 87.34,
93.63, 115.06, 115.38, 125.38, 127.03, 127.75, 128.41, 129.46,
129.67, 131.41, 132.25, 133.33, 134.82, 158.66, 159.68,
166.18; HRMS calc. for C23H14N4S: 378.0939, found:
378.0935; Anal. calc. for C23H14N4S: C, 72.99; H, 3.73; N,
14.80; S, 8.47; found: C, 72.93; H, 3.64; N, 14.85; S, 8.42.
2-Amino-4-(2-hydroxyphenyl)-6-phenylsulphanylpyridine-
3,5-dicarbonitrile (4l). IR: 3422, 3338, 3208, 2183, 1639,
1614, 1579, 1545, 1460, 1404, 1377, 1263, 1193, 1046, 763,
EXPERIMENTAL
All of the chemicals used in the synthesis were purchased
from Sigma-Aldrich and used as received. Thin-layer chroma-
tography was used to monitor reaction progress. Compounds
were purified either by crystallization or over silica gel col-
umn. Melting points were determined on a melting point appa-
ratus and are uncorrected. IR (KBr) spectra were recorded
using Perkin-Elmer FTIR spectrophotometer and the values are
expressed as mmax cmꢁ1. Mass spectral data were recorded on
749 cmꢁ1 1H NMR (300 MHz, DMSO-d6): d 6.95–7.15 (m,
;
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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R. Mamgain, R. Singh, and D. S. Rawat
Vol 46
6H), 7.33 (brs, 1H), 7.50–7.61 (m, 5H); HRMS calc. for
C19H12N4OS: 344.0732, found: 344.0738; Anal. calc. for
C19H12N4OS: C, 66.26; H, 3.51; N, 16.27; S, 9.31; found: C,
66.30; H, 3.55; N, 16.33; S, 9.40.
2-((Furan-2-yl)methylthio)-6-amino-4-(4-tolyl)pyridine-3,5-
dicaronitrile (4x). IR: 3458, 3331, 3225, 2208, 1634, 1543,
1
1263, 1007, 769, 732 cmꢁ1; H NMR (300 MHz, DMSO-d6):
d 2.38 (s, 3H), 4.58 (s, 2H), 6.39–6.54 (m, 2H), 7.34–7.59 (m,
5H), 8.16 (brs, 2H); HRMS calc. for C19H14N4OS: 346.4068;
found: 346.4159; Anal. calc. for C19H14N4OS: C, 65.88; H,
4.07; N, 16.17; S, 9.26; found: C, 65.82; H, 4.17; N, 16.21; S,
9.30.
2-Amino-4-(4-bromophenyl)-6-phenylsulphanylpyridine-
3,5-dicarbonitrile (4n). IR: 3441, 3336, 3220, 2219, 1629,
1
1555, 1529, 1459, 1378, 1312, 1257, 1022, 784, 758 cmꢁ1; H
NMR (300 MHz, DMSO-d6): d 7.52–7.60 (m, 5H), 7.80–7.82
(m, 4H), 7.88 (brs, 2H); Anal. calc. for C19H11BrN4S: C,
56.03; H, 2.72; N, 13.76; S, 7.87; HRMS calc. for
C19H11BrN4S: 405.9888, found: 405.9885; found: C, 56.09; H,
2.78; N, 13.69; S, 7.81.
2-((Furan-2-yl)methylthio)-6-amino-4-(4-bromophenyl)pyri-
dine-3,5-dicaronitrile (4y). IR: 3407, 3337, 3245, 2216., 1629,
1573, 1527, 1487, 1373, 1294, 1133, 1090, 1016, 806, 743
1
cmꢁ1; H NMR (300 MHz, DMSO-d6): d 4.11 (s, 2H), 7.29–
7.33 (m, 3H), 7.50–7.65 (m, 4H), 7.99 (brs, 2H); HRMS calc.
for C18H11BrN4OS: 411.2763; found: 411.2753; Anal. calc. for
C18H11BrN4OS: C, 52.57; H, 2.70; N, 13.62; S, 7.80; found:
C, 52.61; H, 2.71; N, 13.61; S, 7.89.
2-((Furan-2-yl)methylthio)-6-amino-4-(1-naphthyl)pyrid-
ine-3,5-dicaronitrile (4z). IR: 3475, 3328, 3220, 3053, 2993,
2214, 1630, 1547, 1503, 1419, 1269, 1245, 1211, 1155, 1040,
1010, 933, 825, 780, 733, 685 cmꢁ1 1H NMR (300 MHz,
;
2-Amino-4-(3-tolyl)-6-(4-tolyl)sulphanylpyridine-3,5-dicar-
bonitrile (4o). IR: 3487, 3324, 3219, 2215, 1631, 1548, 1460,
1
1377, 1264, 1243, 1016, 801, 716 cmꢁ1; H NMR (300 MHz,
DMSO-d6): d 2.40 (s, 3H), 2.44 (s, 3H), 6.89 (brs, 2H), 7.25–
7.30 (m, 4H), 7.33–7.36 (m, 1H), 7.40–7.45 (m, 3H); HRMS
calc. for C21H16N4S: 356.1096; found: 356.1099; Anal. calc.
for C21H16N4S: C, 70.76; H, 4.52; N, 15.72; S, 9.00; found: C,
70.80; H, 4.48; N, 15.77; S, 9.05.
DMSO-d6): d 4.64 (s, 2H), 6.43–6.61 (m, 2H), 7.57–7.63 (m,
4H), 8.05–8.10 (m, 4H), 8.13 (brs, 2H); HRMS calc. for
C22H14N4OS: 382.4389; found: 382.4487; Anal. calc. for
C22H14N4OS: C, 69.09; H, 3.69; N, 14.65; S, 8.38; found: C,
69.10; H, 3.73; N, 14.61; S, 8.39.
2-Amino-4-(4-chlorophenyl)-6-(4-tolyl)sulphanylpyridine-
3,5-dicarbonitrile (4p). IR: 3477, 3346, 3222, 2214, 1635,
1
1574, 1495, 1457, 1377, 1258, 1092, 836, 805, 795 cmꢁ1; H
NMR (300 MHz, DMSO-d6): d 2.37 (s, 3H), 7.30 (d, J ¼
8Hz, 2H), 7.48 (d, J ¼ 8Hz, 2H), 7.58–7.68 (m, 4H), 7.83
(brs, 2H); HRMS calc. for C20H13ClN4S: 376.0549, found:
376.0546; Anal. calc. for C20H13ClN4S: C, 63.74; H, 3.48; N,
14.87; S, 8.51; found: C, 63.77; H, 3.51; N, 14.81; S, 8.4.
2-Amino-4-phenyl-6-(4-tolyl)sulphanylpyridine-3,5-dicarb-
onitrile (4q). IR: 3451, 3323, 3208, 2215, 1618, 1547, 1523,
2-((Furan-2-yl)methylthio)-6-amino-4-(2-naphthyl)pyrid-
ine-3,5-dicaronitrile (4aa). IR: 3475, 3328, 3220, 2214,
1630, 1547, 1461, 1419, 1269, 1245, 1211, 1155, 1040, 1010,
1
933, 860, 780, 733 cmꢁ1; H NMR (300 MHz, DMSO-d6): d
4.60 (s, 2H), 6.40–6.56 (m, 2H), 7.61–7.63 (m, 4H), 8.00–8.09
(m, 4H), 8.12 (brs, 2H); Anal. calc. for C22H14N4OS: C, 69.09;
H, 3.69; N, 14.65; S, 8.38; found: C, 69.13; H, 3.79; N, 14.66;
S, 8.32.
2-((Furan-2-yl)methylthio)-6-amino-4-(4-methoxyphenyl)-
pyridine-3,5-dicaronitrile (4ab). IR: 3469, 3326, 3211, 2218,
1616, 1574, 1542, 1455, 1294, 1255, 1177, 1019, 839, 816,
749 cmꢁ1 1H NMR (300 MHz, DMSO-d6): d 3.83 (s, 3H),
;
4.58 (s, 2H), 6.40–6.55 (m, 2H), 7.09–7.11 (m, 2H), 7.48–7.60
(m, 3H), 8.12 (brs, 2H); HRMS calc. for C19H14N4O2S:
362.4062; found: 362.4162; Anal. calc. for C19H14N4O2S: C,
62.97; H, 3.89; N, 15.46; S, 8.85; found: C, 62.92; H, 3.93; N,
15.40; S, 8.79.
1458, 1377, 1266, 1015, 897, 810, 755 cmꢁ1 1H NMR (300
;
MHz, DMSO-d6): d 2.37 (s, 3H), 7.30 (d, J ¼ 8Hz, 2H), 7.47
(d, J ¼ 8Hz, 2H), 7.54–7.56 (m, 5H), 7.80 (brs, 2H); HRMS
calc. for C20H14N4S: 342.0939; found: 342.0949; Anal. calc.
for C20H14N4S: C, 70.15; H, 4.12; N, 16.36; S, 9.36; found: C,
70.20; H, 4.08; N, 16.30; S, 9.30.
2-Amino-4-(4-hydroxyphenyl)-6-(2-aminophenyl)sulphan-
ylpyridine-3,5-dicarbonitrile (4u). IR: 3317, 2197, 1638, 1610,
1
1542, 1508, 1456, 1410, 1247, 1170, 1023, 845, 760 cmꢁ1; H
NMR (300 MHz, DMSO-d6): d 5.50 (brs, 2H), 5.88 (brs, 1H),
6.40–6.46 (m, 2H), 6.79–6.86 (m, 4H), 7.28–7.31 (m, 2H), 7.69
(brs, 2H); HRMS calc. for C19H13N5OS: 359.4056; found:
359.4146; Anal. calc. for C19H13N5OS: C, 63.49; H, 3.65; N,
19.49; S, 8.92; found C, 63.51; H, 3.70; N, 19.41; S, 8.96.
2-((Furan-2-yl)methylthio)-6-amino-4-(4-chlorophenyl)pyri-
dine-3,5-dicaronitrile (4ac). IR: 3455, 3336, 3229, 2211,
1
1634, 1573, 1544, 1494, 1264, 1092, 929, 805, 742 cmꢁ1; H
2-Amino-4-(1-naphthyl)-6-(2-aminophenyl)sulphanylpy-rid-
ine-3,5-dicarbonitrile (4v). IR: 3429, 3333, 3219, 2217, 1632,
NMR (300 MHz, DMSO-d6): d 4.58 (s, 2H), 6.39–6.55 (m,
2H), 7.56–7.66 (m, 5H), 8.20 (brs, 2H); HRMS calc. for
C18H11ClN4OS: 366.8250; found: 366.8151; Anal. calc. for
C18H11ClN4OS: C, 58.94; H, 3.02; N, 15.27; S, 8.74; found:
C, 58.99; H, 3.03; N, 15.29; S, 8.78.
1
1611, 1548, 1468, 1310, 1271, 1162, 1022, 996, 797 cmꢁ1; H
NMR (300 MHz, DMSO-d6): d 5.50 (brs, 2H), 6.58 (t, 1H),
6.81 (d, J ¼ 8 Hz, 1H), 7.20 (t, 1H), 7.29 (d, J ¼ 8 Hz, 1H),
7.55–7.69 (m, 4H), 7.77 (brs, 3H), 8.05–8.13 (m, 2H); HRMS
calc. for C23H15N5S: 393.4649; found: 393.4556; Anal. calc.
for C23H15N5S: C, 70.21; H, 3.84; N, 17.80; S, 8.15; found: C,
70.25; H, 3.88; N, 17.88; S, 8.11.
Acknowledgments. DSR is thankful to Department of Science
and Technology (DST), New Delhi, University Grant Commis-
sions, New Delhi, and University of Delhi, India for financial sup-
port. RS is grateful to DST for the DST-Young Scientist award.
2-((Furan-2-yl)methylthio)-6-amino-4-phenylpyridine-3,5-
dicaronitrile (4w). IR: 3470, 3325, 3215, 2210, 1625, 1540,
1
1419, 1243, 1150, 1010, 930, 780 cmꢁ1; H NMR (300 MHz,
REFERENCES AND NOTES
DMSO-d6): d 4.59 (s, 2H), 6.40–6.56 (m, 2H), 7.54–7.60 (m,
6H), 8.16 (brs, 2H); HRMS calc. for C18H12N4OS: 332.3802;
found: 332.3781; Anal. calc. for C18H12N4OS: C, 65.04; H,
3.64; N, 16.86; S, 9.65; found: C, 65.09; H, 3.57; N, 16.90; S,
9.69.
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