Competing processes in condensation of 3,3-bis(methylthio)-2-cyano-N- arylacrylamides with cyanoacetanilides

Article abstract of DOI:10.1134/S1070363211050185

Reaction of cyanoacetanilides with 3,3-bis(methylthio)-2-cyano-N- arylacrylamides proceeds to form isomeric N,1-diaryl-1,6-dihydropyridine-3- carboxamides. A single crystal consisting of 2-amino-4-methylthio-N-(2- methoxyphenyl)-6-oxo-1-phenyl-5-cyano-1,6

Full text of DOI:10.1134/S1070363211050185

ISSN 1070-3632, Russian Journal of General Chemistry, 2011, Vol. 81, No. 5, pp. 944–955. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © V.D. Dyachenko, O.S. Bityukova, A.D. Dyachenko, O.V. Shishkin, 2011, published in Zhurnal Obshchei Khimii, 2011, Vol. 81,
No. 5, pp. 857–868.
Competing Processes in Condensation of 3,3-Bis(methylthio)-
2-cyano-N-arylacrylamides with Cyanoacetanilides
V. D. Dyachenkoa, O. S. Bityukovaa, A. D. Dyachenkoa, and O. V. Shishkinb
a Taras Shevchenko Lugansk National University, ul. Oboronnaya 2, Lugansk, 91011 Ukraine
e-mail: dvd_lug@online.lg.ua
b Institute of Monocrystals of National Academy of Sciences of Ukraine, Khar’kov, Ukraine
Received April 12, 2010
Abstract—Reaction of cyanoacetanilides with 3,3-bis(methylthio)-2-cyano-N-arylacrylamides proceeds to
form isomeric N,1-diaryl-1,6-dihydropyridine-3-carboxamides. A single crystal consisting of 2-amino-4-methyl-
thio-N-(2-methoxyphenyl)-6-oxo-1-phenyl-5-cyano-1,6-dihydropyridine-3-carboxamide and 2-amino-4-methyl-
thio-1-(2-methoxyphenyl)-6-oxo-N-phenyl-5-cyano-1,6-dihydropyridine-3-carboxamide was studied by XRD.
DOI: 10.1134/S1070363211050185
3,3-Bis(methylthio)acrylonitriles are the reagents
widely used in organic synthesis. They easily enter the
reactions of nucleophilic vinyl substitution (SNVin)
[1]. On their basis various heterocyclic compounds are
prepared, among them the functionalized pyridines
which exhibit a broad spectrum of biological activity
[2]. Nicotine amide derivatives are the antagonists of
5-HT3 serotonin and D2 dopamine receptors [3], the
growth inhibitors of different lines of cancer cells [4],
and the antagonists of CB2 receptors [5]. Hence,
development of synthetic methods for preparing new
pyridine-3-carboxamides as the potentially biologically
active compounds is important.
We have found that the reaction of cyanoaceta-
nilides I with 3,3-bis(methylthio)-2-cyano-N-arylacryl-
amides II under the conditions of SNVin process goes
along two competing pathways to form structural
isomers, N,1-diaryl-1,6-dihydropyridine-3-carboxamides
III and IV.
R2
CN
O
MeS
N
NHR2
O
NH
MeS
O
method a
O
CN
+
+
O
R1HN
−MeSH
O
HN
N
CN
IIа−IId
MeS
R1
NC
R2HN
NHR1
SMe
Iа−If
B
А
SMe
SMe
N
O
O
O
NHR1
O
CN
O
CN
O
MeS
R2HN
H2N
R1HN
method b
−MeSH
CN
+
+
R2HN
CN
VIа−VId
MeS
N
H2N
R1
R2
Vа−Vd
IIIа−IIIg
IVа−IVe
І–VI, R1 = Ph, R2 = o-MeOC6H4 (а), R1 = Ph, R2 = m-MeC6H4 (b), R1 = m-MeC6H4, R2 = o-MeC6H4 (c), R1 = o-MeC6H4,
R2 = p-FC6H4 (d), R1 = о-MeОC6H4, R2 = p-FC6H4 (e), R1 = R2 = о-MeC6H4 (f), R1 = R2 = m-MeC6H4 (g).
944

COMPETING PROCESSES IN CONDENSATION
(a)
945
(b)
Fig. 1. Structure of 2-amino-4-methylthio-N-(2-methoxyphenyl)-6-oxo-1-phenyl-5-cyano-1,6-dihydropyrimidin-3-carboxamide
IIIa (a) and 2-amino-1-(2-methoxyphenyl)-4-methylthio-6-oxo-N-phenyl-5-cyano-1,6-dihydropyridine-3-carboxamide IVa (b)
according to the XRD study.
This reaction proceeds probably non-stereospecifi-
cally according to the addition-elimination mechanism
[6] through the formation of two intermediates A and
B which undergo intramolecular cyclization.
Direct (method a) and another (method b) syntheses
of structural isomers III and IV from the compounds I,
II and V, VI lead to the same products forming in the
same ratio.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 81 No. 5 2011

946
DYACHENKO et al.
Table 1. Crystallographic data for the compounds IIIa and IVa
Parameter
ІIIa
ІVa
Monoclinic
Crystal system
a, Å
Rhombic
35.7534(17)
5.4643(4)
9.9372(7)
9.1885(14)
16.664(3)
13.221(3)
98.783(17)
2000.7(6)
P21/c, 4
1.349
b, Å
c, Å
β, deg
V, Å3
1941.4(2)
Pca21, 4
1.391
Space group, Z
D
calc, g cm–3
μ, mm–1
0.198
0.192
F(000)
848
848
2Θmax
30.0
26.0
Number of reflections measured
Number of independent reflections [Rint]
Number of observed reflections with F > 4σ(F)
Number of refined parameters
wR2, by all independent reflections
R1, by all observed reflections
Refinement quality
26512
5644 [0.042]
4201
8459
3921 [0.049]
2012
265
264
0.094
0.133
0.046
0.057
0.99
0.96
Table 2. Interatomic distances (Å) in structures IIIa and IVa
Bond
S1–C3
Bond
IIIa
IVa
IIIa
IVa
1.7775(17)
1.793(2)
1.774(3)
1.799(4)
1.357(4)
С2–C13
С3–C4
С4–C5
С4–C15
С6–C7
С6–C11
С7–C8
С8–C9
С9–C10
С10–C11
С16–C17
С16–C21
С17–C18
С18–C19
С19–C20
С20–C21
1.419(3)
1.390(2)
1.420(2)
1.505(3)
1.366(3)
1.375(3)
1.396(3)
1.359(4)
1.342(4)
1.389(3)
1.380(3)
1.408(2)
1.392(3)
1.367(3)
1.381(3)
1.374(3)
1.436(4)
1.409(4)
1.406(4)
1.513(4)
1.365(4)
1.407(4)
1.383(5)
1.377(5)
1.376(5)
1.379(4)
1.376(4)
1.384(4)
1.385(5)
1.364(5)
1.381(6)
1.370(5)
S1–C14
O1–C11
O1–C21
O1–C12
O2–C1
O3–C15
N1–C5
N1–C1
N1–C6
N2–C13
N3–C15
N3–C16
N4–C5
С1–C2
С2–C3
1.365(2)
1.424(2)
1.227(2)
1.222(2)
1.377(2)
1.409(2)
1.449(2)
1.139(3)
1.351(2)
1.415(2)
1.322(2)
1.441(2)
1.386(2)
1.424(4)
1.238(4)
1.229(3)
1.368(4)
1.421(3)
1.444(4)
1.143(3)
1.348(4)
1.414(4)
1.321(3)
1.415(4)
1.391(4)
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COMPETING PROCESSES IN CONDENSATION
Table 3. Bond angles (deg) in structures IIIa and IVa
947
Angle
C3S1C14
C11O1C12
C21O1C12
C5N1C1
C5N1C6
C1N1C6
C15N3C16
O2C1C2
O2C1N1
C2C1N1
C3C2C1
C3C2C13
C1C2C13
C2C3C4
C2C3S1
Angle
C7C6N1
C11C6N1
C6C7C8
ІIIa
ІVa
ІIIa
ІVa
103.33(9)
102.81(15)
117.1(3)
119.54(18)
118.55(17)
118.1(2)
122.4(3)
117.2(3)
120.7(3)
119.2(3)
120.7(3)
120.7(3)
126.9(3)
114.8(3)
117.76(16)
124.30(13)
119.57(15)
116.13(14)
128.26(16)
125.26(17)
120.07(15)
114.59(15)
121.57(17)
121.60(16)
116.83(17)
121.47(15)
114.78(13)
123.75(12)
118.34(16)
116.06(16)
125.24(14)
117.62(14)
123.12(17)
119.26(16)
121.91(16)
122.9(2)
118.7(2)
118.2(2)
126.4(3)
125.8(3)
118.4(3)
115.7(3)
121.9(2)
120.9(3)
117.1(3)
119.7(3)
116.8(2)
123.4(2)
118.9(3)
116.5(2)
124.4(3)
117.5(3)
122.8(3)
119.8(2)
120.4(3)
C9C8C7
120.3(2)
C10C9C8
C9C10C11
O1C11C10
O1C11C6
O1C21C20
O1C21C16
C10C11C6
N2C13C2
O3C15N3
O3C15C4
N3C15C4
C17C16C21
C17C16N3
C21C16N3
C16C17C18
C19C18C17
C18C19C20
C21C20C19
C20C21C16
120.75(19)
120.9(2)
125.04(16)
114.94(16)
118.0(2)
118.4(3)
177.7(4)
123.2(3)
121.0(3)
115.5(2)
119.7(3)
123.4(3)
116.9(3)
119.5(4)
120.5(4)
120.1(4)
119.7(4)
120.4(4)
178.6(3)
123.48(18)
122.17(17)
114.26(16)
119.28(16)
125.02(15)
115.64(16)
119.90(17)
120.3(2)
C4C3S1
C5C4C3
C5C4C15
C3C4C15
N4C5N1
N4C5C4
N1C5C4
C7C6C11
120.56(19)
119.95(17)
120.02(17)
X-ray studies showed that the pyridin-2-ones
obtained IIIa and IVa crystallize in one crystal. The
crystal under investigation contained a mixture of
isomers of N-(2-methoxyphenyl)-1-phenyl-1,6-dihydro-
pyridine-3-carboxamide IIIa and 1-(2-methoxyphe-
nyl)-N-phenyl-1,6-dihydropyridine-3-carboxamide IVa
in 2.7:1 ratio (Fig. 1, Tables 1–3).
der-Waals radii 3.42 Å [7]) and S1···N3 3.22 Å (IVa),
3.14 Å (IIIa). Due to that these substituents are turned
with respect to the pyridine heteroring [C5–C4–C15–O3
torsion angle –44.0(3)° (IIIa), 41.6(4)° (IVa); and C14–
S1–C3–C4 torsion angle –42.8(2)° (IIIa) and 40.4(3)°
(IVa)].
On the other hand, on the basis of geometric
parameters the existence of intramolecular attraction
N3-H···S1(H···S 2.69Å (IIIa), 2.80 Å (IVa); N–H···S
114° (IIIa), 112° (IVa) can be suggested. But the
analysis of topology of the electronic density distribu-
tion calculated by M06-2X/6-311G** method for the
experimentally obtained geometry of the molecules
IIIa and IVa does not confirm thissuggestion.
Between the phenylamide and thiomethyl substituents
two critical bonding points (3, –1) were found (Table 4).
The pathway of bond passing through one of these
The molecules IIIa and IVa have similar spatial
arrangement. In both structures the pyridine heteroring
has significantly non-planar conformation with the
largest endocyclic torsion angles C5–N1–C1–C2 –5.7(3)°
for the structure IIIa and –9.1(4)° for the structure
IVa, and C2–C3–C4–C5 –6.9(3)° (IIIa) and –10.8(4)
for IVa. This arises obviously from the sterical
repulsion between the phenylamide and thiomethyl
substituents as indicated by the shortened
intramolecular contacts C14···C15 3.14 Å (sum of van-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 81 No. 5 2011

948
DYACHENKO et al.
Table 4. Values of electronic density (au) in critical points
of (3, –1) bonds corresponding to the nonvalent interactions
in molecules IIIa and IVa calculated by M06-2X/6-311G**
method for the experimentally established molecular geometry
elongation of this bond to 1.505(3) Å (IIIa), 1.513(4) Å
(IVa) compared to the average value of ordinary Csp
Csp bonds 1.46 Å [8].
2–
2
For the analysis of intermolecular interactions in
Critical points of bonds
N4–H···O3
ІІІa
ІVa
crystals of compounds IIIa and IVa all the molecules
included in the first coordination sphere of the basic
molecule were evaluated by means of the Voronoi-
Dirichlet polyhedron method [9]. The molecules were
considered to be located quite close if they possessed
common facets of the Voronoi–Dirichlet polyhedrons.
For all the adjacent molecules the energy of interaction
with the basic molecule was calculated by quantum-
chemical method. Analysis of topology of the
electronic density distribution in the dimers formed
permitted to obtain detailed information on the existing
intermolecular interactions.
0.0233
0.0160
0.0146
0.0264
0.0152
0.0122
0.0126
C17–H···O3
S1–H···N3
C14–H···C15
C14–H···N3
0.0130
points connects S1 atom with N3, but not with the amide
hydrogen atom indicating the absence of hydrogen
bond. Second critical point (3, –1) corresponds to the
C14–H···N3 interaction in the structure IIIa and C14–
H···C15 in the structure IVa. These interactions may be
both sterically repulsive and attractive, and they may
have the electrostatic nature as well as arise from the
C–H···π effect.
For the structure IVa the coordination number of
molecule in crystal is 14. Starting from the calculated
interaction energies in dimers (Table 5) it may be
concluded that the strongest interactions take place
only with 8 molecules (Fig. 2). The largest interaction
energy was obtained for the central symmetric dimer
2–1 in which the molecules are bound by N3–H···O2
hydrogen bonds, by stacking interactions between the
pyridine rings and cyano groups, and also by the
attractive C21–H···O2 and C7–H···S1 contacts. Strong
specific intermolecular interactions (N–H···N hydrogen
bond) are also present in the dimer 2–3. With the rest
five molecules the basic molecule is bound by the
relatively weak interactions like C–H···π, C–H···O, and
C–H···S hydrogen bonds (attractive contacts). Despite
this fact the dimers formed by these interactions bring
about 35% into the total energy of interaction of the
basic molecule with its surrounding.
In the structures IIIa and IVa the phenyl
substituent at N3 is to some extent turned with respect
to the amide fragment [C15–N3–C16–C17 torsion angles
are 18.9(3)° for IIIa and 27.2(5)° for IVa] despite the
formation of intramolecular hydrogen bond C17–H···O3
[H···O 2.36 Å (IIIa), 2.40 Å (IVa); C–H···O 118°
(IIIa), 112° (IVa)]. The presence of these interactions
is confirmed also by the presence of critical point (3, –1)
between these atoms in the calculated distribution of
the electronic density. Note that the critical point
corresponding to the possible intramolecular N3–H···O2
(2.22 Å) interaction in the structure IIIa is absent
(Table 4). It arises probably from the too small value
of N3–H···O1 angle 106° preventing the formation of a
hydrogen bond.
In Table 5 the electronic density values in the
critical points of bonds corresponding to the inter-
molecular contacts are presented. These values usually
well correlate with the energies of interaction, in
particular, of hydrogen bonds [10, 11] and stacking
interactions [12]. Results of calculations show that the
strongest interactions taking place in the crystal IVa
are N–H···O and N–H···N hydrogen bonds (electronic
density values are 0.017–0.018 au) Relatively high
values of electronic density were also calculated in
critical points corresponding to the C–H···π bonds (up
to 0.01 au) may be indicatind their sufficiently high
energy. Electronic density in critical points of bonds
corresponding to the stacking interactions (0.005–
0.007 au) is comparable with the density in critical
Also the intramolecular N4–H···O3 hydrogen bond
[H···O 2.11 Å (IIIa), 2.05 Å (IVa); N–H···O 130°
(IIIa), 131° (IVa)] exists In the molecules IIIa and
IVa. In this case no resonance reinforcement of
hydrogen bond is observed demonstrating the absence
of strong conjugation in the N4–C5–C4–C15–O3 frag-
ment. Values of bond lengths C5–N4 1.322(2) Å
(IIIa), 1.321(3) Å (IVa) and C15–O3 1.222(2) Å (IIIa),
1.229(3) Å (IVa) are close to the average values of the
ordinary Csp –NH2 bond 1.34 Å and the C=O double
2
bond 1.21 Å respectively [8]. One of the reasons of
this effect is the some degree of twisting of the C4–C15
bond leading to a decrease in conjugation as seen in
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COMPETING PROCESSES IN CONDENSATION
949
Table 5. Energies of interaction of basic molecules with the adjacent ones in structure IVa (M06-2X/6-311G**), values of
electronic density in critical points (3, –1) corresponding to intermolecular contacts, and geometrical characteristics of
contacts
Dimer
Symmetry
Eint, cal mol–1
Contact
ρ(RCP), au
Distance, Å
Angle, deg
Classification
IV-1 (1 – x, 1 – y, –z)
–29.0
N3–H···O2
C2···C2
C21–H···O2
C7–H···S1
C5···N2
C14–H···C11
C18–H···N2
S1···H–C12
C21···H–C12
C14–H···O2
C19–H···H–C14
N4–H···N2
0.0172
0.0073
0.0062
0.0061
0.0049
0.0102
0.0074
0.0061
0.0041
0.0039
0.0016
0.0179
2.09
3.39
2.64
2.93
3.41
2.57
2.76
3.05
3.10
3.05
3.05
2.12
152
0
HB
stacking
AC
137
150
0
AC
stacking
CH···π
CH... π
AC
IV-2 (1 – x, –0.5 + y, 0.5 – z)
(1 – x, 0.5 + y, 0.5 – z)
–9.6
139
136
152
119
105
CH···π
AC
IV-3 (–1 + x, y, z)
(1 + x, y, z)
–7.4
–6.1
143
HB
IV-4 (–x, 1 – y, –z)
C8–H···C16
C9–H···C21
C8–H···O3
C7–H···N4
N4···N4
C9–H···O3
C10–H···O3
C10···H–C17
C12–H···C18
N4–H···H–C18
0.0073
0.0070
0.0043
0.0024
0.0007
0.0076
0.0043
0.0030
0.0016
0.0004
2.73
2.79
2.93
3.36
4.41
2.54
2.89
3.28
3.52
3.93
134
128
131
CH···π
CH···π
AC
IV-5 (–x, –0.5 + y, 0.5 – z)
(–x, 0.5 + y, 0.5 – z)
–3.6
128
114
99
AC
AC
103
IV-6 (2 – z, 1 – y, 1 – z)
IV-7 (–x, 0.5 – y, 0.5 + z)
(–x, 0.5 – y, 1.5 + z)
–0.7
–0.5
C12–H···C8
C10–H···H–C8
C12–H···O2
0.0040
0.0029
0.0011
3.12
2.62
3.43
119
140
CH···π
AC
IV-8 (–1 + x, 0.5 – y, –0.5 + z)
(1 + x, 0.5 – y, 0.5 + z)
0.2
0.3
IV-9 (1 – x, 1 – y, 1– z)
C12–H···H–C14
0.0047
2.38
points corresponding to the C–H···O and C–H···S
attractive contacts (up to 0.0076 au and 0.0061 au
respectively). From the data presented in the Table 4 it
may be concluded that the contacts corresponding to
the critical points with the electronic density below
0.004 au mostly do not correspond to any attractive
interactions.
In the structure IIIa the coordination number of
molecule is 10. In this case similarly to the structure
IVa the interactions stronger than 4 kcal mol–1 take
place only with 8 molecules (Table 6, Fig. 3). The
strongest interactions are again observed between the
molecules bound with the intermolecular N–H···O
hydrogen bond and stacking interaction. The last ones
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950
DYACHENKO et al.
IV-1
IV-2
IV-3
IV-4
IV-5
Fig. 2. Structures of the strongest interacting dimers of the adjacent molecules IVa in crystal.
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COMPETING PROCESSES IN CONDENSATION
951
Table 6. Energies of interaction of basic molecules with the adjacent ones in structure IIIa (M06-2X/6-311G**), values of elec-
tronic density in critical points (3, –1) corresponding to intermolecular contacts and geometrical characteristics of contacts
Dimer
Symmetry
Eint, cal mol–1
Contact
O2···H–N4
C9–H···C17
N2···C9
N4···C11
O2···C7
C11–H···H–C7
O2···H–C11
N2···H–C14
C12–H···C18
S1···H–C14
C7–H···C11
C12–H···H–C14
C8···H–C10
C7–H···N4
N3–H···O3
C2···C4
ρ(RCP), au
Distance, Å
Angle, deg
Classification
III-1 (1 – x, 1 – y, –0.5 + z)
(1 – x, 1 – y, 0.5 + z)
–14.0
0.0135
0.0074
0.0061
0.0044
0.0039
0.0031
0.0085
0.0070
0.0067
0.0044
0.0038
0.0038
0.0036
0.0033
0.0025
0.0012
0.0009
0.0056
0.0046
0.0041
0.0040
0.0036
0.0024
0.0116
0.0023
0.0033
0.0020
2.19
2.74
3.35
3.61
3.58
2.69
2.45
2.65
2.83
3.17
3.19
2.62
3.39
3.09
3.01
4.46
4.37
2.92
2.58
2.91
3.18
2.89
3.43
2.33
3.06
2.62
4.26
139
135
HB
CH···π
stacking
stacking
stacking
19
18
III-2 (x, –1 + y, z)
(x, 1 + y, z)
–9.4
164
167
153
119
109
AC
AC
CH···π
AC
CH···π
99
CH···π
162
132
AC
C1···N4
III-3 (0.5 +x, –y, –1 + z)
(0.5 + x, –y, z)
–4.4
C14–H···C20
C12–H···H–C19
O1···H–C19
S1···H–C20
C12–H···H–C20
S1···H–C12
N2···H–C8
O2···H–C7
C14–H···H–C18
S1···C18
136
CH···π
131
127
AC
AC
152
171
137
AC
AC
AC
III-4 (1 – x, 2 – y, –0.5 + z)
(1 – x, 2 – y, 0.5 + z)
III-5 (x, y, –1 + z)
(x, y, 1 + z)
–4.0
–0.4
found for the dimer 3–1 can be considered non-classic
because they are realized not between two aromatic
rings, but between the aromatic ring and the cyano, the
amino, or the carbonyl group. In the rest dimers
calculated for the structure IIIa relatively weak C–
H···O, C–H···N, C–H···σ, and C–H···π attractive inter-
actions take place.
energy of interaction of the basic molecule with its
surrounding in the structure IIIa is –64.6 kcal mol–1
which is significantly less as compared to the calculated
overall energy for the structure IVa, –77.1 kcal mol–1.
All the pyridine-2-ones III, IV synthesized flu-
oresce under the UV irradiation.
EXPERIMENTAL
Hence, in the structure IIIa the energy of interac-
tion in the most strongly bound dimer is almost two
times less than in the structure IVa. In the structure
IIIa only one relatively strong intermolecular N–H···O
hydrogen bond is formed. Due to that the summary
Melting points were measured on a Köffler block.
IR spectra were recorded on a Perkin-Elmer FIR
“Spectrum One” device in KBr. 1H NMR spectra were
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952
DYACHENKO et al.
III-1
III-2
III-3
III-4
Fig. 3. Structures of the strongest interacting dimers of the adjacent molecules IIIa in crystal.
taken on a Bruker Avance II 400 (399.9601 MHz)
spectrometer in DMSO-d6 against internal TMS. Mass
spectra were obtained on a MX-1321 apparatus (70 eV)
with the direct injection of substance in the ion source
and a Crommas GC/MS-Hewlett-Packard 5890/5972
instrument equipped with a HP-5MS column (70 eV)
(compounds IIIc.IVc). Reaction progress and indivi-
duality of the compounds obtained were controlled by
TLC on Silufol UV-254 plates, elution with 3:5
acetone-hexane, development with iodine vapor and
UV radiation.
with Uiso = nUeq of the carrying atom (n = 1.5 for
methyl groups and 1.2 for the rest hydrogen atoms).
Crystal of compounds IIIa and IVa was a racemic
twin with the component increments 0.73(7): 0.27(7).
Crystallographic data are listed in Table 1, bond
lengths and bond angles, in Tables 2 and 3 respec-
tively. They were deposited in the Cambridge
Crystallographic Data Center, deposit numbers CCDC
764323, 784324.
Quantum chemistry calculations of molecules of
compounds IIIa and IVa were carried out by the
density functional method M06-2X/6-311G** ac-
cording to the Gaussian 09 program [14]. The inter-
action energies in dimers were calculated with the
consideration of correction of the superposition error
of the basis set. Experimentally established molecular
XRD studies of compounds IIIa IVa were carried
out at 298 K on a four-circle Xcalibur 3 diffractometer
(MoKα, graphite monochromator, CCD detector, ω-
scanning). Structures were solved by the direct method
and refined in the anisotropic approximation for the
nonhydrogen atoms by the SHELX-97 complex of
programs [13]. Location of hydrogen atoms was
calculated geometrically and refined in the rider model
geometry
was
used
for
the
calculations.
Element−hydrogen bond lengths were accepted to be
1.09 Å for CH3 groups, 1.08 Å for Car–H, and 1.01 Å
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COMPETING PROCESSES IN CONDENSATION
953
Table 7. Yields, melting points, and elemental analysis data of the compounds obtained
Found, %
Yield, %,
Calculated, %
H
Comp. no.
mp, °С (solvent)
Formula
method a/b
С
Н
N
C
N
ІІІa and ІVa
IIIb and ІVb
ІІІc and ІVc
IІІd and ІVd
ІІІe and IVe
IIIf
80/78
80/81
74/82
40/54
62/71
82
185–190 (EtOH)
245–247 (BuOH)
233–235 (BuOH)
245–250 (BuOH)
250–253 (BuOH)
223–225 (EtOH)
253–255 (EtOH)
62.14
64.52
65.25
61.64
59.35
65.28
65.21
4.26
4.33
4.86
4.10
3.95
4.84
4.85
13.65
14.28
13.72
13.64
13.11
13.77
13.70
C21H18N4O3S
C21H18N4O2S
C22H20N4O2S
C21H17FN4O2S
C21H17FN4O3S
C22H20N4O2S
C22H20N4O2S
62.05
64.60
65.33
61.75
59.42
65.33
65.33
4.46
4.65
4.98
4.19
4.04
4.90
4.98
13.78
14.35
13.85
13.72
13.20
13.85
13.85
85
IIIg
for N–H ones. Topology of the electronic density dis-
tribution was analyzed with the help of AIM2000
program [15]. Analysis of the crystal packing and
plotting of the Voronoi–Dirichlet polyhedrons was
carried out by the Topos 4.0 program [16].
7.13 d and 7.28 d (1H, Harom, J 8.4 Hz), 7.18 major t
and 7.33 t (1H, Harom, J 8.0 Hz), 7.31 d (1H, Harom
,
J 7.6 Hz), 7.51–7.63 m (2H, Harom), 7.69 major d and
7.99 major d (1H, Harom, J 8.0 Hz), 9.71 major br.s and
10.51 br.s (1H, NH). Mass spectrum (electron impact,
70 eV), m/z (Irel, %): 406 (8.8) [M]+, 314 (8.4), 284
(12.3), 123 (100), 119 (18.4), 108 (20.9), 93 (11.5), 77
(44.8). Ratio of compounds IIIa and IVa according to
NMR data is 3:1, according to XRD data onpacking in
crystal takes place in 2.7:1 ratio.
Synthesis of compounds III–IV. Methods a and
b. To the suspension of 10 mmol of KOH in 10 ml of
DMSO 10 mmol of cyanoacetanilide I (method a) or V
(method b) was added and the mixture obtained was
stirred for 15 min. After that 10 mmol of
corresponding 3,3-bis(methylthio)-2-cyano-N-aryla-
crylamide II (method a) or V (method b) was added,
the reaction mixture was stirred for 1 h and heated for
15 min at 80oC. The resulting mixture was left for 2 h,
poured in cold water, and acidified with equimolar
amount of aqueous 30% HCl. The precipitate formed
was filtered off, washed with water, and then
crystallized from the suitable solvent. Structural
isomers III and IV have very close Rf values com-
plicating their separation (Table 7). Ratio of isomers
for compounds IIIa and IVa is known from the XRD
data. For the rest compounds IIIb–IIIe and IVb–IVe it
was impossible to make a conclusion about the ratio of
signals in the NMR spectra.
2-Amino-4-methylthio-6-oxo-N-m-tolyl-1-phenyl-
5-cyano-1,6-dihydropyridine3-carboxmide IIIb and
2-amino-4-methylthio-6-oxo-1-m-tolyl-N-phenyl-5-
cyano-1.6-dihydropyridine-3-carboxamide (IVb).
IR spectrum, ν, cm–1: 3437, 3321 (N–H); 2209 (C≡N);
1
1644 (NC=O); 1635 [δ(NH2)]. H NMR spectrum, δ,
ppm (J,Hz): 2.29 major s and 2.38 s (3H, CH3), 2.54 s
(3H, SCH3), 6.91 major d (1H, Harom, J 7.6 Hz), 7.02
br.s (2H, NH2), 7.05–7.11 m (2H, Harom), 7.21 major t
and 7.48 t (1H, Harom, J 7.8 Hz), 7.27–7.38 m (2H,
H
arom), 7.42 major d and 7.67 d (1H, Harom, J 8.0 Hz),
7.55–7.62 m (2H, Harom), 10.40 major br.s and 10.47
br.s (1H, NH). Mass spectrum (electron impact,
70 eV), m/z (Irel, %): 390 (17.8) [M]+, 298 (36.9), 284
(22.2), 257 (13.0), 241 (3.0), 181 (2.96), 133 (12.2),
107 (100), 65 (38). Ratio of compounds IIIb and IVb
according to NMR data is 3:2.
2-Amino-4-methylthio-N-(2-methoxyphenyl)-6-
oxo-1-phenyl-5-cyano-1,6-dihydropyridine-5-car-
boxamide IIIa and 2-amino-4-methylthio-1-(2-
methoxyphenyl)-6-oxo-N-phenyl-5-cyano-1,6-dihyd-
ropyridine-3-carboxamide (IVa). IR spectrum, ν,
cm–1: 3368, 3287 (N–H); 2219 (C≡N); 1660 (NC=O);
2-Amino-4-methylthio-6-oxo-1-o-tolyl-N-m-tolyl-
5-cyano-1,6-dihydropyridine-3-carboxamide (IIIc)
and 2-amino-4-methylthio-6-oxo-1-m-tolyl-N-o-tolyl-
5-cyano-1.6-dihydropyridine-3-carboxamide (IVc).
IR spectrum, ν, cm–1: 3403, 3290 (N–H); 2209 (C≡N);
1
1641 [δ(NH2)]. H NMR spectrum, δ, ppm (J, Hz):
2.53 s and 2.57 major s (2H, SCH3), 3.77 s and 3.81
major s (2H, OCH3), 6.95 major t (1H, Harom, J 7.6 Hz),
7.0 major br.s (2H, NH2), 7.06–7.11 m (2H, Harom),
1
1661 (NC=O); 1644 [δ(NH2)]. H NMR spectrum, δ,
ppm (J, Hz): 2.05 s and 2.29 s (3H, CH3), 2.30 s and
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954
DYACHENKO et al.
2.38 s (3H, CH3), 2.55 s and 2.61 s (3H, SCH3), 6.91 d
(1H, Harom, J 7.8 Hz), 7.0 br.s (2H, NH2), 7.07–7.23 m
(2H, Harom), 7.36 d (1H, Harom, J 8.0 Hz), 7.41–7.51 m
%); 404 (10.4) [M]+, 298 (28.1) [M – o-MeC6H4NH]+,
133 (10.5), 107 (100) [o-MeC6H4NH2]+.
2-Amino-4-methylthio-6-oxo-N,1-di(m-tolyl)-5-
cyano-1.6-dihydropyridine-3-carboxamide IIIg. IR
spectrum, ν, cm–1: 3407, 3311 (N–H); 2211 (C≡N),
(2H, Harom), 7.57 s (1H, Harom), 7.73 d (1H, Harom
,
J 8.0 Hz), 9.86 br.s and 10.42 br.s (1H, NH). Mass
spectrum (electron impact, 70 eV). m/z (Irel, %): 405
[M + 1]+ (100). Ratio of compounds IIIc and IVc
according to NMR data is 1:1.
1
1632 (NC–O), 1603 [δ(NH)]. H NMR spectrum, δ,
ppm (J, Hz): 2.29 s (3H, CH3), 2.38 s (3H, CH3), 2.54
s (3H, SCH3), 6.91 d (1H, Harom, J 7.6 Hz), 7.0 br.s
(2H, NH2), 7.07 d (1H, Harom, J 8.0 Hz), 7.1 s (1H,
2-Amino-4-methylthio-6-oxo-1-o-tolyl-N-(p-fluoro-
phenyl)-5-cyano-1,6-dihydropyridine-3-carboxamide
IIId and 2-amino-4-methylthio-6-oxo-N-o-tolyl-1-
(p-fluorophenyl)-5-cyano-1.6-dihydropyridine-3-
carboxamide (IVd). IR spectrum, ν, cm–1: 3343, 3284
(N–H); 2210 (C≡N), 1716 (NC=O), 1669 [δ(NH2)]. 1H
NMR spectrum, δ, ppm (J, Hz): 2.05 s and 2.29 s (3H,
CH3), 2.56 s and 2.62 s (3H, SCH3), 7.06 br.s (2H,
NH2), 7.09 d (1H, Harom, J 7.4 Hz), 7.17–7.22 m (2H,
H
arom), 7.21 t (1H, Harom, J 7.6 Hz), 7.37 d (1H, Harom
J 7.6 Hz), 7.43 d (1H, Harom, J 7.4 Hz), 7.48 t (1H,
arom, J 8.0 Hz), 7.57 s (1H, Harom), 10.40 br.s (1H,
,
H
NH). Mass spectrum (electron impact, 70 eV) m/z (Irel,
%): 404 (12.9) [M]+,, 298 (25.4) [M – m-MeC6H4NH]+,
133 (14.3), 108 (100) [m-MeC6H4NH]+, 77 (13.9), 65
(16.6), 39 (8.1).
H
arom), 7.33–7.46 m (3H, Harom), 7.69–7.71 m (1H,
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p-FC6H4NH]+, 252 (2.0), 133 (12.7). 111 (65.6), 75
(25.1) Ratio of compounds IIId and IVd according to
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(NC=O); 1633 [δ(NH2)]. H NMR spectrum, δ, ppm
(J, Hz): 2.53 s and 2.56 s (3H, SCH3), 3.76 s and 3.81 s
(3H, OCH3), 6.95 t (1H, Harom, J 7.4 Hz), 7.05 br.s
(2H, NH2), 7.12–7.24 m (2H Harom), 7.26 d (1H, Harom
,
J 8.4 Hz), 7.35–7.54 m (2H, Harom), 7.69–7.72 m (2H,
arom), 8.02 d (1H, Harom, J 7.6 Hz), 9.66 br.s and 10.57
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br.s (1H, NH). Mass spectrum (electron impact, 70 eV).
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(2.1), 184 (2.7), 137 (23.8), 123 (100), 75 (33.4). Ratio
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1694 (NC=O), 1613 [δ(NH2)]. H NMR spectrum, δ,
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 81 No. 5 2011

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