Tetrachlorosilane and zinc chloride as a binary reagent for the preparation of 2-amino-6-chloropyridine-3,5-dicarbonitrile derivatives

Article abstract of DOI:10.1007/s10593-017-2089-6

[Figure not available: see fulltext.] A green one-pot method for efficient synthesis of 2-amino-6-chloropyridine-3,5-dicarbonitrile derivatives was developed, based on stirring of various aldehydes and malononitrile with tetrachlorosilane and zinc chloride under solvent-free conditions at room temperature for 3–10 h. The effects of zinc chloride and the reaction conditions were studied. Compounds were characterized by X-ray analysis and NMR spectroscopy.

Full text of DOI:10.1007/s10593-017-2089-6

DOI 10.1007/s10593-017-2089-6
Chemistry of Heterocyclic Compounds 2017, 53(5), 540–544
Tetrachlorosilane and zinc chloride as a binary reagent
for the preparation of 2-amino-6-chloropyridine-
3,5-dicarbonitrile derivatives
1
2
2
2
Saad S. Elmorsy , Ahmed M. Sheta *, Mohammad M. A. Mashaly , Samy B. Said
1
Department of Chemistry, Faculty of Science, Mansoura University,
El-Gamaa St., Mansoura 35511, Egypt; e-mail: sselmorsy51@yahoo.com
2
Department of Chemistry, Faculty of Science, Damietta University,
El-Kafrawy St., New Damietta 34517, Egypt; e-mail: ahmedsheta@du.edu.eg
Published in Khimiya Geterotsiklicheskikh Soedinenii,
Submitted November 10, 2016
Accepted after revision January 19, 2017
2
017, 53(5), 540–544
A green one-pot method for efficient synthesis of 2-amino-6-chloropyridine-3,5-dicarbonitrile derivatives was developed, based on
stirring of various aldehydes and malononitrile with tetrachlorosilane and zinc chloride under solvent-free conditions at room
temperature for 3–10 h. The effects of zinc chloride and the reaction conditions were studied. Compounds were characterized by X-ray
analysis and NMR spectroscopy.
Keywords: malononitrile, pyridine, tetrachlorosilane, zinc chloride, one-pot synthesis.
The pyridine moiety is present in a wide range of both
naturally occurring and synthetic bioactive compounds,
A few compounds and methods for the synthesis of
2-amino-6-chloropyridine-3,5-dicarbonitrile derivatives have
been reported, such as reaction of benzoyl cyanide with
malononitrile in the presence of piperidine, followed by
treatment with gaseous hydrogen chloride or via sodium
1
which often show considerable complexity. 2-Amino-
6
-chloropyridine-3,5-dicarbonitrile derivatives are used in
the preparation of very important molecules, such as
2
13
2
-chloropyridine-3,5-dicarbonitriles. The evaluation of
1,1,3,3-tetracyanopropenide. Another method was reported
biological properties showed that some of these molecules
were modest inhibitors of acetylcholinesterase and butyryl-
by Schmidt et al.,14 using triethyl orthoesters with malono-
nitrile in the presence of pyridine, followed by treatment
with hydrochloric acid. However, these methods suffer
from certain drawbacks, such as prolonged reaction times,
low yields, toxic and very expensive starting materials, and
complicated procedures.
3
cholinesterase at micromolar concentrations. They also
can be used in the preparation of 5-arylanthyridines and
4
5-methyl-5-deaza analogs of aminopterin, methotrexate,
10 5
folic acid, and N -methylfolic acid.
Thus, the synthesis of highly substituted pyridine
derivatives has attracted much attention, and a number of
methods have been developed to prepare these compounds.
Those include Vilsmeier reactions of tertiary alcohols,6
Diels–Alder reactions of 3-siloxy-1-aza-1,3-butadienes and
With the aim of developing more efficient synthetic
processes, we herein describe a practical and inexpensive
procedure for the preparation of 2-amino-6-chloropyridine-
3,5-dicarbonitrile derivatives 3a–n via reactions of various
aldehydes 1a–n (1 equiv) with malononitrile (2) (2 equiv)
in the presence of tetrachlorosilane (2 equiv) and zinc
chloride (1 equiv) (Scheme 1). The general applicability of
this approach is demonstrated by good yields of products
3a–n (Table 1).
6
-alkyl-3,5-dichloro-2H-1,4-oxazin-2-ones with different
7
types of acetylenic compounds, Ni/Ru-catalyzed cyclo-
8
additions of alkynes and nitriles, (4+2) cycloadditions of
9
oximinosulfonates, reactions of imines with enamines or
1
0
carbonyl compounds, condensation of α,β-unsaturated
The influence of the organic solvent on this reaction was
investigated in detail at room temperature and it was found
that the presence of a small amount of dichloromethane in
1
1
esters or nitriles with thiols, and transformation of ketene
dithioacetals to pyridine derivatives.1
2
0
009-3122/17/53(05)-0540©2017 Springer Science+Business Media New York
5
40

Chemistry of Heterocyclic Compounds 2017, 53(5), 540–544
Scheme 1
Table 1. Reaction time and yields of compounds 3a–n
Com-
pound
Com-
pound
Time, h
Yield, %
Time, h
Yield, %
3
a
6
6
7
8
8
6
8
80
80
82
75
73
76
73
3h
3i
4
3
70
88
74
75
55
80
72
3
b
Figure 1. ORTEP diagram of 2-amino-6-chloro-4-phenylpyridine-
3,5-dicarbonitrile (3a) showing the atom numbering scheme, with
thermal vibration ellipsoids of 50% probability.
3
c
3j
10
6
3
d
3k
3l
3
e
6
3
f
3m
3n
7
3
g
10
the reaction mixture reduced the yield of 2-amino-6-chloro-
pyridine-3,5-dicarbonitrile 3a to 6% and a high yield of
chalcone was obtained instead.
It was determined that the presence of zinc chloride
under solvent-free conditions was essential due to its
–
tendency to form Cl
3
3
Zn species with SiCl
4
, thus producing
+
Cl Si ions in a manner that facilitated the reaction of
Figure 2. A packing diagram of 2-amino-6-chloro-4-phenyl-
pyridine-3,5-dicarbonitrile (3a).
malononitrile with aldehyde. In the course of our
investigations to develop practical regioselective reactions
using this binary reagent, we had to take into consideration
that divalent zinc is able to accept halide ion from
yields. As summarized in Table 1, the reaction with
furfural (1k) or thiophene-2-carboxaldehyde (1l) provided
pyridine derivatives 3k,l in 75 and 55% yields, respecti-
vely. This result was substantially different from the
+
–
16,17
tetrachlorosilane to generate Cl
3
Si and Cl
3
Zn species
from 2 equiv of tetrachlorosilane and 1 equiv of zinc
chloride relative to the starting material.
18
The structure of 2-amino-6-chloro-4-phenylpyridine-
literature report of a reaction between aliphatic aldehydes,
thiols, and malononitrile in the presence of nanocrystalline
magnesium oxide, where unidentified constituents were
isolated instead of the pyridine product.18 In our study, the
reaction of paraldehyde with malononitrile (2) in the
3
,5-dicarbonitrile (3a) was assigned on the basis of IR,
1
13
H and C NMR spectroscopy, mass spectral and elemental
analysis, as well as X-ray crystallographic analysis.
IR spectra taken for KBr pellets showed the characteristic
absorption peaks for C–N, C=C, and C=N groups at 1259,
presence of SiCl
4
–ZnCl gave 2-amino-6-chloro-4-methyl-
2
–
1
1
525, 1562, and 1660 cm , respectively. A nitrile peak
pyridine-3,5-dicarbonitrile (3m) in 80% isolated yield.
When cinnamaldehyde was used in this process, 2-amino-
–
1
was observed at 2225 cm , in addition to the NH
2
–
1 1
stretching bands at 3326 and 3369 cm . H NMR spectra
of this compound in DMSO were in good agreement with
the proposed structure, showing the signals of five aromatic
protons at 7.61 ppm and a singlet of NH
exchanged with D O at 8.36 ppm. These spectra matched
data previously reported in the literature. The molecular
structure of 2-amino-6-chloro-4-phenylpyridine-3,5-dicarbo-
nitrile (3a) was proved conclusively by X-ray crystallo-
graphy. A view of the molecule is shown in Figure 1, along
with packing diagram in Figure 2.
6-chloro-4-styrylpyridine-3,5-dicarbonitrile
(3n)
was
obtained in 72% yield. In the case of product 3l, the yield
was substantially lower (55%), probably due to the side
reactions caused by interaction between thiophene sulfur
2
protons readily
2
atom and SiCl .
4
1
5
We also explored different nitriles with activated
methylene groups, such as ethyl cyanoacetate and 2-phenyl-
acetonitrile for the synthesis of pyridine derivatives. It is
noteworthy that no reaction occurred with ethyl cyano-
acetate or phenylacetonitrile.
In order to investigate the scope of applicability for this
reaction, heterocyclic aldehydes 1k,l were reacted with
malononitrile (2) under similar conditions, easily affording
The mechanism for the formation of product can be
explained as shown in Scheme 2. The reaction pathway is
highly dependent on the electrophilicity of the silicon atom
+
19
+
2-amino-6-chloropyridine-3,5-dicarbonitriles 3k,l in good
in Cl
3
Si species, since aldehyde is activated by Cl Si
3
5
41

Chemistry of Heterocyclic Compounds 2017, 53(5), 540–544
Scheme 2
ion acting as Lewis acid, forming trichlorosilyl enolate
intermediate. The electrophilicity of nitrile carbon atom
was enhanced by the initial transformation of nitriles to
2-Amino-6-chloro-4-phenylpyridine-3,5-dicarbonitrile
(3a). Yield 1.01 g (80%), yellow needles, mp 296°C
1
4
–1
(mp 303–308°C ). IR spectrum, ν, cm : 1259, 1525, 1562,
2
0–22
1
reactive nitrilium salt
intermediates.
1660, 2225, 3178, 3326, 3369. Н NMR spectrum, δ, ppm:
Thus, we have demonstrated that tetrachlorosilane – zinc
chloride is an effective reagent complex for the conden-
sation of structurally diverse aldehydes with malononitrile,
resulting in the formation of 2-amino-6-chloropyridine-
7.60–7.69 (5H, m, H Ph); 8.36 (2H, s, NH , exchanges with
2
13
D
2
O). C NMR spectrum, δ, ppm: 89.7; 96.3; 114.3; 114.9;
128.4; 128.7; 130.6; 133.5; 155.2; 160.3; 160.4. Mass
37
+
37
+
spectrum, m/z (Irel, %): 257 [M( Cl)+H] (5), 256 [M( Cl)]
35
+
35
+
3
,5-dicarbonitrile derivatives in high yields.
(32), 255 [M( Cl)+H] (17), 254 [M( Cl)] (100). Found, %:
C 61.32; H 2.65; N 22.18. C13
C 61.31; H 2.77; N 22.00.
H
7
ClN . Calculated, %:
4
Experimental
IR spectra were obtained for KBr pellets on a Thermo
2-Amino-6-chloro-4-(p-tolyl)pyridine-3,5-dicarbonitrile
(3b). Yield 1.07 g (80%), yellow needles, mp 340°C.
Nicolet Nexus 470 and Mattson 5000 FT-IR spectrometers
1
–1
with only selected absorptions being recorded. H and
IR spectrum, ν, cm : 1261, 1562, 1666, 2221, 3185, 3315,
1
3
1
C NMR spectra were acquired on a Varian Mercury 300
3372. Н NMR spectrum, δ, ppm (J, Hz): 2.40 (3H, s,
instrument (300 and 75 MHz, respectively) using DMSO-d
solvent and TMS as internal standard. Mass spectra were
recorded on a Shimadzu GCMS-QP2010 EX instrument
6
as
CH ); 7.37 (2H, d, J = 8.1, H Ar); 7.45 (2H, d, J = 8.1,
3
H Ar); 8.20 (2H, s, NH
2
, exchanges with D
O). 13C NMR
2
spectrum, δ, ppm: 20.9; 89.6; 96.2; 99.5; 114.4; 115.0;
(
EI at 70 eV). Elemental analysis for carbon, hydrogen, and
128.3; 129.3; 130.6; 140.6; 155.2; 160.3; 160.4. Mass
37
+
37
+
nitrogen was performed on a PerkinElmer 2400 CHN
elemental analyzer. The sulfur content was determined
spectrum, m/z (Irel, %): 271 [M( Cl)+H] (5), 270 [M( Cl)]
35 + 35 +
(32), 269 [M( Cl)+H] (20), 268 [M( Cl)] (100).
Found, %: C 63.22; H 3.39; N 20.67. C14 ClN . Calculated, %:
gravimetrically by oxidation with fuming HNO
precipitation of BaSO
3
and
H
9
4
4
. Melting points were determined
C 62.58; H 3.38; N 20.85.
with a Griffin melting point apparatus in open capillary and
were not corrected. Column chromatography was carried
out by using Merck Kieselgel 60 (230–400 mesh). Analytical
TLC was performed on aluminum-backed Merck Kieselgel
2-Amino-6-chloro-4-(4-methoxyphenyl)pyridine-3,5-
dicarbonitrile (3c). Yield 1.16 g (82%), yellow needles,
–1
mp 320°C. IR spectrum, ν, cm : 1263, 1511, 1567, 1604,
1
1654, 2219, 3191, 3311, 3376. Н NMR spectrum, δ, ppm
6
0 F254 (thickness 0.2 mm) TLC plates.
Tetrachlorosilane was used as obtained from commercial
(J, Hz): 3.84 (3H, s, OCH ); 7.07 (2H, d, J = 8.2, H Ar);
3
7.43 (2H, d, J = 8.2, H Ar); 8.36 (2H, s, NH
with D
O). 13C NMR spectrum, δ, ppm: 55.9; 89.5; 96.2;
113.9; 114.1; 116.3; 129.7; 130.3; 155.3; 160.4; 161.1; 162.1.
2
, exchanges
sources. The solvents were distilled and dried prior to use.
Dichloromethane was dried by refluxing over anhydrous
calcium chloride, followed by distillation. Zinc chloride
was dried by heating at 150°C and stored in a desiccator.
Synthesis of pyridine derivatives 3a–n (General method).
The appropriate aldehyde 1a–n (5 mmol, 1 equiv),
malononitrile (2) (0.66 g, 10 mmol, 2 equiv), zinc chloride
2
37
+
Mass spectrum, m/z (Irel, %): 287 [M( Cl)+H] (4), 286
37
+
35
+
35
+
[M( Cl)] (30), 285 [M( Cl)+H] (16), 284 [M( Cl)]
(100). Found, %: C 59.22; H 3.39; N 19.97. C14
Calculated, %: C 59.06; H 3.19; N 19.68.
H
9
ClN O.
4
2-Amino-6-chloro-4-(4-chlorophenyl)pyridine-3,5-di-
(
0.68 g, 5 mmol, 1 equiv), and SiCl
0 mmol, 2 equiv) were combined in a 50-ml round-bottom
flask, and the mixture was stirred at room temperature for
–10 h. After the completion of reaction (monitored by
4
(1.70 g, 1.15 ml,
carbonitrile (3d). Yield 1.08 g (75 %), white needles,
–1
1
mp 290°C. IR spectrum, ν, cm : 1095, 1255, 1330, 1515,
1
1577, 1654, 2219, 3176, 3313, 3372. Н NMR spectrum,
3
δ, ppm (J, Hz): 7.69 (2H, d, J = 8.7, H Ar); 7.93 (2H, d, J = 8.4,
TLC, ethyl acetate – petroleum ether, 1:5), the mixture was
added to a saturated solution of sodium carbonate and
extracted with dichloromethane. The dichloromethane
H Ar); 8.53 (2H, s, NH
2
, exchanges with D
O). 13C NMR
2
spectrum, δ, ppm: 82.2; 113.0; 114.0; 128.9; 129.7; 130.0;
130.4; 132.1; 139.0; 160.1; 160.2. Mass spectrum, m/z
3
7
+
35 37
+
extract was then dried over anhydrous Na
2
SO
4
and
(Irel, %): 292 [M( Cl
2
)] (10), 291 [M( Cl Cl)+H] (9),
35
37
+
35
+
concentrated by heating to dryness on a boiling water bath.
The residue obtained by complete evaporation of solvent
was collected and recrystallized from ethanol.
290 [M( Cl Cl)] (61), 289 [M( Cl
2
)+H] (15), 288
35
+
[M( Cl
Cl
2
)] (100). Found, %: C 54.22; H 2.39; N 19.67.
C
13
H
6
2
4
N . Calculated, %: C 54.01; H 2.09; N 19.38.
5
42

Chemistry of Heterocyclic Compounds 2017, 53(5), 540–544
2
-Amino-6-chloro-4-(3-chlorophenyl)pyridine-3,5-di-
2-Amino-6-chloro-4-(4-nitrophenyl)pyridine-3,5-di-
carbonitrile (3e). Yield 1.05 g (73%), yellow needles,
carbonitrile (3j). Yield 1.11 g (74%), orange needles,
–
1
–1
mp 254°C. IR spectrum, ν, cm : 1259, 1322, 1552, 1656,
mp 232°C. IR spectrum, ν, cm : 1349, 1521, 1583, 2211,
1
1
2
221, 3176, 3322, 3369. Н NMR spectrum, δ, ppm: 7.53–7.60
3187. Н NMR spectrum, δ, ppm (J, Hz): 7.87 (2H, d, J = 9.0,
(
4H, m, H Ar); 8.46 (2H, s, NH
2
, exchanges with D
2
O).
H Ar); 8.37 (2H, d, J = 9.0, H Ar); 8.69 (2H, s, NH ,
2
1
3
13
C NMR spectrum, δ, ppm: 89.8; 96.3; 114.1; 114.7;
exchanges with D
2
O). C NMR spectrum, δ, ppm: 89.7;
1
1
2
27.2; 128.2; 130.5; 130.7; 133.3; 135.5; 155.1; 158.8;
96.0; 113.9; 114.6; 123.9; 130.2; 139.7; 148.7; 155.2; 158.4;
3
7
+
37
+
60.1. Mass spectrum, m/z (Irel, %): 292 [M( Cl
2
)] (10),
160.1. Mass spectrum, m/z (Irel, %): 302 [M( Cl)+H] (4), 301
37 + 35 + 35 +
35
37
+
35 37
+
91 [M( Cl Cl)+H] (9), 290 [M( Cl Cl)] (61), 289
[M( Cl)] (29), 300 [M( Cl)+H] (15), 299 [M( Cl)]
3
5
)+H]+ (16), 288 [M( Cl
35
+
[
M( Cl
2
2
)] (100). Found, %:
(100). Found, %: C 52.14; H 2.31; N 23.29. C13
Calculated, %: C 52.10; H 2.02; N 23.37.
H
6
ClN
5
2
O .
C 53.92; H 2.18; N 19.37. C13
H
6
Cl
2
N . Calculated, %:
4
C 54.01; H 2.09; N 19.38.
-Amino-4-(2-bromophenyl)-6-chloropyridine-3,5-di-
carbonitrile (3f). Yield 1.30 g (76%), yellow needles,
2-Amino-6-chloro-4-(furan-2-yl)pyridine-3,5-dicarbo-
2
nitrile (3k). Yield 0.91 g (75%), brown needles, mp 310°C.
–
1
IR spectrum, ν, cm : 1268, 1459, 1515, 1575, 1662, 2223,
–
1
1
mp 272°C. IR spectrum, ν, cm : 1263, 1531, 1569, 1658,
3189, 3315, 3355. Н NMR spectrum, δ, ppm (J, Hz): 6.86
1
2
227, 2921, 3180, 3322, 3380. Н NMR spectrum, δ, ppm
(1H, d, J = 2.1, H furan); 7.47 (1H, d, J = 3.6, H furan);
(
J, Hz): 7.56–7.62 (3H, m, H Ar); 7.85 (1H, d, J = 7.8, H Ar);
8.14 (1H, dd, J = 3.6, J = 2.1, H furan); 8.20 (2H, s, NH ,
2
1
3
13
8
.58 (2H, s, NH
2
, exchanges with D
2
O). C NMR
exchanges with D
2
O). C NMR spectrum, δ, ppm: 113.1;
spectrum, δ, ppm: 90.5; 96.7; 113.4; 114.1; 120.7; 128.4;
114.8; 115.5; 117.2; 145.4; 147.0; 160.9. Mass spectrum,
37
+
37
+
1
30.0; 132.3; 132.9; 134.7; 154.9; 159.7; 160.0. Mass
m/z (Irel, %): 247 [M( Cl)+H] (3), 246 [M( Cl)] (31),
35 + 35 +
3
7
81
+
spectrum, m/z (Irel, %): 336 [M( Cl Br)] (24), 335
245 [M( Cl)+H] (12), 244 [M( Cl)] (100). Found, %:
3
5
81
37 79
+
35 81
[
M( Cl Br and Cl Br)+H] (14), 334 [M( Cl Br and
C 54.22; H 2.14; N 22.91. C11
C 54.01; H 2.06; N 22.90.
H
5
ClN O. Calculated, %:
4
3
7
79
+
35 79
+
Cl Br)] (100), 333 [M( Cl Br)+H] (10), 332
3
5
79
+
[
C
M( Cl Br)] (77). Found, %: C 46.43; H 1.89; N 16.82.
BrClN . Calculated, %: C 46.81; H 1.81; N 16.80.
-Amino-4-(3-bromophenyl)-6-chloropyridine-3,5-di-
carbonitrile (3g). Yield 1.22 g (73%), yellow needles,
2-Amino-6-chloro-4-(thiophen-2-yl)pyridine-3,5-di-
H
6
4
carbonitrile (3l). Yield 0.72 g (55%), brown needles, mp
13
2
–
1
304°C. IR spectrum, ν, cm : 1261, 1421, 1519, 1658,
1
2215, 2923, 3178, 3320, 3361. Н NMR spectrum, δ, ppm
–
1
mp 260°C. IR spectrum, ν, cm : 1257, 1317, 1519, 1633,
(J, Hz): 7.25 (1H, dd, J = 2.9, J = 1.7, H thiophene); 7.57
1
2
7
225, 3222, 3324, 3434. Н NMR spectrum, δ, ppm: 7.52–
(1H, d, J = 1.7, H thiophene); 7.91 (1H, d, J = 2.9,
.57 (2H, m, H Ar); 7.78–7.81 (2H, m, H Ar); 8.20 (2H, s,
H thiophene); 8.20 (2H, s, NH
13
2
, exchanges with D O).
2
1
3
NH
2
, exchanges with D
2
O). C NMR spectrum, δ, ppm:
C NMR spectrum, δ, ppm: 113.2; 114.8; 115.6; 118.2;
145.5; 147.9; 160.8. Mass spectrum, m/z (Irel, %): 263
9
0.0; 96.3; 114.0; 114.7; 120.7; 123.6; 125.4; 130.7; 132.1;
37
+
37
+
35
+
1
35.0; 155.1; 158.0; 160.1. Mass spectrum, m/z (Irel, %): 336
[M( Cl)+H] (4), 262 [M( Cl)] (35), 261 [M( Cl)+H]
35 +
3
7
81
+
35 81
37 79
+
[
M( Cl Br)] (25), 335 [M( Cl Br and Cl Br)+H] (14), 334
(15), 260 [M( Cl)] (100). Found, %: C 50.19; H 1.81;
N 21.17; S 12.79. C11 ClN S. Calculated, %: C 50.68;
H 1.93; N 21.49; S 12.30.
3
5
81
37 79
+
35 79
+
[
M( Cl Br and Cl Br)] (100), 333 [M( Cl Br)+H] (12),
H
5
4
35
79
+
3
32 [M( Cl Br)] (80). Found, %: C 46.49; H 1.68; N 16.86.
C
13
2
H
6
BrClN
4
. Calculated, %: C 46.81; H 1.81; N 16.80.
2-Amino-6-chloro-4-methylpyridine-3,5-dicarbonitrile
-Amino-6-chloro-4-(2-nitrophenyl)pyridine-3,5-dicarbo-
(3m). Yield 0.77 g (80%), yellow needles, mp 280°C
14
–1
nitrile (3h). Yield 1.05 g (70%), orange needles, mp 215°C.
(mp 210°C ). IR spectrum, ν, cm : 1272, 1326, 1492, 1577,
–
1
1
IR spectrum, ν, cm : 1268, 1346, 1533, 1573, 1654, 2225,
1662, 2225, 2919, 3176, 3357. Н NMR spectrum, δ, ppm:
1
3
181, 3316, 3376. Н NMR spectrum, δ, ppm: 7.77–8.01
2.49 (3H, s, CH
3
); 8.25 (2H, s, NH
2
, exchanges with D O).
2
13
(
4H, m, H Ar); 8.41 (2H, s, NH
2
, exchanges with D
2
O).
C NMR spectrum, δ, ppm: 19.9; 89.9; 96.7; 114.0; 114.6;
120.6; 154.7; 159.5. Mass spectrum, m/z (Irel, %): 195
1
3
C NMR spectrum, δ, ppm: 89.3; 95.7; 113.4; 114.1;
37
+
37
+
35
+
1
1
3
25.5; 128.3; 131.2; 132.4; 135.2; 146.1; 154.8; 159.9;
[M( Cl)+H] (3), 194 [M( Cl)] (31), 193 [M( Cl)+H]
35 +
3
7
+
61.3. Mass spectrum, m/z (Irel, %): 302 [M( Cl)+H] (5),
(14), 192 [M( Cl)] (100). Found, %: C 50.02; H 2.48;
37
+
35
+
35
+
01 [M( Cl)] (32), 300 [M( Cl)+H] (15), 299 [M( Cl)]
N 29.11. C
N 29.09.
8
H
5
ClN . Calculated, %: C 49.89; H 2.62;
4
(
100). Found, %: C 52.23; H 2.11; N 23.17. C13
H
6
ClN
5
O .
2
Calculated, %: C 52.10; H 2.02; N 23.37.
2-Amino-6-chloro-4-styrylpyridine-3,5-dicarbonitrile
2
-Amino-6-chloro-4-(3-nitrophenyl)pyridine-3,5-di-
(3n). Yield 1.01 g (72%), brown needles, mp 300°C.
–
1
carbonitrile (3i). Yield 1.32 g (88%), orange needles,
IR spectrum, ν, cm : 1276, 1411, 1519, 1563, 1644, 2219,
–
1
1
mp 236°C. IR spectrum, ν, cm : 1261, 1353, 1525, 1633,
3183, 3313, 3361. Н NMR spectrum, δ, ppm: 7.18–7.70
1
2
221, 3226, 3328, 3444. Н NMR spectrum, δ, ppm: 7.58–
.79 (4H, m, H Ar); 8.43 (2H, s, NH , exchanges with
O). C NMR spectrum, δ, ppm: 89.8; 96.3; 114.1; 114.7;
(7H, m, H Ph, CH=CH); 8.30 (2H, s, NH , exchanges with
2
13
7
D
2
D
2
O). C NMR spectrum, δ, ppm: 87.2; 94.0; 114.5; 115.1;
13
2
120.4; 128.2; 128.5; 129.1; 134.6; 141.2; 155.5; 160.5;
37
+
1
1
3
20.6; 121.7; 127.5; 130.9; 133.4; 135.7; 155.1; 158.7;
162.0. Mass spectrum, m/z (Irel, %): 283 [M( Cl)+H] (5),
37 + 35 + 35 +
3
7
+
60.1. Mass spectrum, m/z (Irel, %): 302 [M( Cl)+H] (5),
282 [M( Cl)] (17), 281 [M( Cl)+H] (16), 280 [M( Cl)]
+
37
+
35
+
35
+
01 [M( Cl)] (34), 300 [M( Cl)+H] (15), 299 [M( Cl)]
(52), 279 (23), 90 [C
H 3.08; N 20.38. C15
H 3.23; N 19.96.
6
H
5
CH] (100). Found, %: C 64.50;
ClN . Calculated, %: C 64.18;
(
100). Found, %: C 52.31; H 2.22; N 23.21. C13
H
6
ClN
5
O
2
.
H
9
4
Calculated, %: C 52.10; H 2.02; N 23.37.
5
43

Chemistry of Heterocyclic Compounds 2017, 53(5), 540–544
X-ray crystal structure analysis of compound 3a.
Yellow triclinic crystals of 2-amino-6-chloro-4-phenyl-
pyridine-3,5-dicarbonitrile (3a) having appropriate dimen-
sions 0.44 × 0.21 × 0.17 mm and recrystallized from ethanol were
measured on a Bruker Kappa CCD diffractometer (MoKα
radiation, graphite monochromator (λ 0.71073 Å), the unit
cell dimensions and intensity data were measured at 298 K.
The crystal data were collected up to 2θ 55.70° and the struc-
ture was solved by least squares fit of the angular setting of
8. (a) McCormick, M. M.; Duong, H. A.; Zuo, G.; Louie, J.
J. Am. Chem. Soc. 2005, 127, 5030. (b) Varela, J. A.; Castedo, L.;
Saa, C. J. Org. Chem. 2003, 68, 8595.
9
1
. (a) Renslo, A. R.; Danheiser, R. L. J. Org. Chem. 1998, 63,
7
840. (b) Mashraqui, S. H.; Karnik, M. A. Tetrahedron Lett.
1
998, 39, 4895.
0. (a) Komatsu, M.; Ohgishi, H.; Takamatsu, S.; Ohshiro, Y.;
Agawa, T. Angew. Chem., Int. Ed. Engl. 1982, 21, 213.
(b) Vijin, R. J.; Arts, H. J.; Green, R.; Castelijns, A. M.
Synthesis 1994, 573.
2
strong reflections based on F . The structure was solved
11. (a) Kambe, S.; Saito, K.; Sakurai, A.; Midorikawa, H.
Synthesis 1981, 531. (b) Kambe, S.; Saito, K.; Kishi, H.;
Hayashi, T.; Sakurai, A. Synthesis 1977, 839.
with SIR9223 and refined with maXus software. Integration
24
and scaling of the reflections were performed with the HKL
25
12. (a) Anabha, E. R.; Nirmala, K. N.; Thomas, A.; Asokan, C. V.
Synthesis 2007, 428. (b) Anabha, E. R.; Asokan, C. V.
Synthesis 2006, 151.
Denzo-Scalpack software suite. The non-hydrogen atoms
were refined with anisotropic thermal parameters. Crystallo-
graphic data for the structure of 2-amino-6-chloro-4-phenylpyri-
dine-3,5-dicarbonitrile (3a) have been deposited at the Cambridge
Crystallographic Data Center (deposit CCDC 995091).
1
3. Little, E. L., Jr.; Middleton, W. J.; Coffman, D. D.;
Engelhardt, V. A.; Sausen, G. N. J. Am. Chem. Soc. 1958, 80,
2832.
1
4. Schmidt, H. W.; Junek, H. Monatsh. Chem. 1977, 108, 895.
Supplementary information file containing the results of
X-ray crystallographic analysis is available from the
journal website at http://link.springer.com/journal/10593.
15. Murray, T. J.; Zimmerman, S. C.; Kolotuchin, S. V.
Tetrahedron 1995, 51, 635.
1
1
1
1
6. Lora-Tamayo, M.; Madronero, R.; Leipprand, H. Chem. Ber.
1
964, 97, 2230.
7. Slavinskaya, R. A.; Sumarokova, T. N.; Kovaleva, T. A.;
Nasirdinova, M. K. Zh. Org. Khim. 1982, 18, 2243.
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5
44