Full text of DOI:10.1134/S1070428018080079

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2018, Vol. 54, No. 8, pp. 1161–1165. © Pleiades Publishing, Ltd., 2018.
Original Russian Text © I.N. Bardasov, А.Yu. Alekseeva, S.S. Chunikhin, О.V. Ershov, 2018, published in Zhurnal Organicheskoi Khimii, 2018, Vol. 54,
No. 8, pp. 1152–1155.
Three-Component Synthesis and Optical Properties
of Nicotinic Acid Esters Containing
Buta-1,3-dien-1,1,3-tricarbonitrile Fragment
a
a
a
a
I. N. Bardasov ,* А. Yu. Alekseeva , S. S. Chunikhin , and О. V. Ershov
a
I.N. Ul’yanov Chuvash State University, Moskovskii pr. 15, Cheboksary, 428015 Russia
*
e-mail: bardasov.chem@mail.ru
Received February 12, 2018
Abstract—Three-component synthesis of ethyl 4-aryl-2-methyl-5-cyano-6-(dicyanomethylidene)-1,6-
dihydropyridine-3-carboxylates was developed consisting in the reaction of acetoacetic ester, aromatic
aldehydes, and malononitrile dimer in the presence of sodium nitrite. Optical properties of synthesized
compounds were investigated and it was demonstrated that they possessed intensive fluorescence in solution
and in solid state with emission maxima in the yellow and green region of the visible light.
DOI: 10.1134/S1070428018080079
Derivatives of nicotinic acid play a significant role
in biological processes and find application in different
areas of medicine, science, and technology [1, 2].
These compounds are interesting not only because of a
broad spectrum of biological activity, but also by
properties discovered in the latest years. Applications
were described of nitriles of nicotinic acids as special
fluorescent markers [3], new promising compounds for
WOLED-technologies [4], as fluorescent chemo-
sensors for biologically important ions of Fe(III) and
Hg(II) [5].
The fragment BDTC is a promising component of
organic donor-acceptor chromophores that find
application in molecular electronics [11] and non-
linear optics [12–17].
The synthesis of target ethyl 4-aryl-2-methyl-5-
cyano-6-(dicyanomethylidene)-1,6-dihydropyridine-3-
carboxylates 1a–1g is underlain by a polycomponent
reaction between acetoacetic ester, aromatic aldehydes,
and malononitrile dimer in the presence of sodium
nitrite that functions as a base catalyzing the addition
and as an oxidizer (Scheme 2). Yields of compounds
1
a–1g reached 65–76%.
In this study we present a three-component
synthesis of nicotinic acid esters 1, containing buta-1,3
The reaction apparently starts by tandem occurring
-
dien-1,1,3-tricarbonitrile (BDTC) fragment [6–10].
Knoevenagel and Michael reactions and the
intermediate А formation. Further intermolecular
cyclization of the amino group with the carbonyl
results in the forming of a piperidine cycle B. After
that the dehydration leads to derivatives of
tetrahydropyridine 2 that may be isolated in low yields
The most known compounds possessing such structural
element are 3-cyano-2-(dicyanomethylidene)-2,5-
dihydrofuranes (TCF) [11] and 2-oxo-4-cyano-5-
(
(
dicyanomethylidene)-3-pyrrolines (TCP) [12, 13]
Scheme 1).
Scheme 1.
R
Ar
R
R
CN
CN
CN
CN
CN
EtOOC
CN
CN
R
R
O
CN
CN
CN
CN
O
N
X
N
H
H
CN
BDTC
TCF
TCP
1
1
161

1
162
BARDASOV et al.
Scheme 2.
OEt
NC
CN
O
Ar
O
NH2
O
O
O
NaNO2
CN
+
+
EtO
EtOH
Ar
H
NH2
CN
CN
CN
A
O
Ar
O
Ar
O
Ar
CN
CN
CN
CN
EtO
HO
EtO
[O]
EtO
_
H O
2
CN
CN
CN
N
H
N
H
N
H
CN
CN
_
B
2
1a 1g
Ar = Ph (a), 4-MeC
6
H
4
6
(b), 4-FC H
4
(c), 2-ClC
6
H
4
(d), 4-Me
2 6
NC H
4
(e), 4-MeOC
6
H
4
(f), 2-MeOC
6
H
4
(g).
Table 1. Effect of a solvent on optical properties of ethyl 2-methyl-4-phenyl-5-cyano-6-(dicyanomethylidene)-1,6-
dihydropyridine-3-carboxylate 1а
Solvent
Ethyl acetate
Ethanol
λ
abs, nm
338
335
336
335
329
333
340
344
А
max
ε
max
λ
fl, nm
520
520
521
514
456
516
520
519
I
max
0.5187
1.0839
1.1650
0.3390
0.9515
0.6762
1.0708
0.9171
47587
94250
92458
31387
93280
61476
101984
90802
1.2769
1.2894
2.6862
0.4056
0.0478
0.3183
3.3929
3.4421
Acetonitrile
Benzene
Acetic acid
Dioxane
DMSO
Pyridine
Table 2. Optical properties of compounds 1a–1g
а
b
c
d
Compound no.
λ
abs, nm
334
332
346
334
339
334
339
А
max
ε
max
λ
fl, nm
I
max
λ
fl, nm
526
533
524
529
561
528
521
RI
1
1
a
1.0708
0.6730
0.7520
0.7914
0.4491
0.4417
0.4381
10708
67298
75200
79141
44910
44170
43810
521
518
518
512
506
512
508
3.4211
6.2761
4.7947
16.1677
12.2428
8.0319
11.8309
1.00
0.70
1.57
1.82
0.64
1.24
1.27
b
1
c
1
d
1
e
1
f
1
g
а
b
c
d
Maximum fluorescence emission in DMSO.
Intensity of fluorescence in DMSO.
Maximum fluorescence emission in solid phase.
Intensity of solid phase fluorescence relatively to compound 1а.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 8 2018

THREE-COMPONENT SYNTHESIS AND OPTICAL PROPERTIES OF NICOTINIC ACID ESTERS
1163
1
1
1
1
6
4
2
1
d
2
3
1e
g
3
1
1
0
8
6
4
2
1
f
1
b
2
1
0
1
c
4
5
1
a
0
4
30 450 470 490 510 530 550 570 590 610
λ, nm
Fig. 2. Fluorescence spectra of compounds 1a–1g in DMSO.
6
7
0.6
.5
4
50
475
500
525
λ, nm
550
575
600
1d
1
c
0
1
g
Fig. 1. Fluorescence spectra of ethyl 2-methyl-4-phenyl-5-
cyano-6-(dicyanomethylidene)-1,6-dihydropyridine-3-
carboxylate 1а in different solvents: 1, pyridine; 2, DMSO;
1f
0.4
0.3
3
, acetonitrile; 4, ethyl acetate; 5, benzene; 6, dioxane; 7,
1a
acetic acid.
1
b
0
0
.2
.1
1
e
at acidifying the reaction mass. Their oxidation with
sodium nitrite completes the process.
0
4
80
500
520
540
λ, nm
560
580
600
Structure of synthesized compounds 1a–1g is
1
confirmed by IR, Н NMR, and mass spectra.
Fig. 3. Fluorescence spectra of compounds 1a–1g in solid
state.
The obtained derivatives of the nicotinic acid 1a–1g
exhibit fluorescence both in solution and solid state,
therefore we have investigated their optical properties.
As a first step the effect of a solvent on absorption and
fluorescence properties of compound 1а was
investigated (Table 1).
density and strongly affects the fluorescence intensity,
while the wavelengths of maxima remain almost
unchanged. From the spectral data it can be seen that the
intensity of fluorescence increases in the presence of a
substituent in the position 2 of the benzene ring (Fig 2).
In polar solvents the optical density is higher than in
low-polar and non-polar solvents. In going from a
solution in acetic acid to solutions in basic solvents, like
pyridine and DMSO, a red shift is observed. The intensity
of fluorescence is also affected by the polarity and acid-
base properties of solvents. The maximal fluorescence is
observed for solutions in pyridine and DMSO, a little
lower in acetonitrile, low in dioxane and benzene and
practically no fluorescence in acetic acid (Fig. 1).
Further we investigated the solid phase
fluorescence of compounds 1a–1g. The most intensive
fluorescence was observed in 2-chlorosubstituted
compound 1d. In general an intensive fluorescence in
solid state is observed in halogen- and methoxy-
substituted compounds. The fluorescence maximum
appears in the range 520–530 nm, except for
compound with 4-dimethylamine substituent, whose
maximum of is shifted to 561 nm (Table 2, Fig. 3).
Further we investigated optical properties of all
synthesized compounds 1a–1g in DMSO (Table 2). As
it is evident from the table data, a change in the nature
of substituent in the aromatic ring affects the optical
Hence we synthesized a series of nicotinic acid
derivatives containing BDTC fragment and investigated
their optical properties.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 8 2018

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164
BARDASOV et al.
EXPERIMENTAL
Ethyl 2-methyl-4-(2-chlorophenyl)-5-cyano-6-
dicyanomethylidene)-1,6-dihydropyridine-3-
(
IR spectra were registered on Fourier spectrometer
FSM-1202 in thin layer (suspension in mineral oil). Н
carboxylate (1d). Yield 76%, mp 238–239°С
(decomp.) {218–219°С (decomp.) [6]}.
1
NMR spectra were registered on a spectrometer Bruker
Ethyl 2-methyl-4-(4-dimethylaminophenyl)-5-
cyano-6-(dicyanomethylidene)-1,6-dihydropyridine-
DRX-500 in DMSO-d , internal reference TMS. Mass
6
spectra were recorded on an instrument Finnigan МАТ
INCOS-50 (EI, 70 eV). Elemental analysis was carried
out on a CHN-analyzer vario Micro cube. Melting
points were determined on automatic apparatus
OptiMelt MPA100. Monitoring of the reactions
progress and purity of synthesized compounds was
performed by TLC method on Sorbfil PTLC-AF-А-
UV plates (eluent EtOAc, development under UV
irradiation, by iodine vapor and thermal
decomposition).
3
-carboxylate (1e). Yield 65%, mp 231–232°С
(
decomp.) {209–210°С (decomp.) [6]}.
Ethyl 2-methyl-4-(4-methoxyphenyl)-5-cyano-6-
(dicyanomethylidene)-1,6-dihydropyridine-3-
carboxylate (1f). Yield 68%, mp 211–212°С
(decomp.). IR spectrum, ν, cm : 3260–3110 (NH),
2227, 2200 (C≡N), 1729 (С=О), 1607 (C=C). Н NMR
spectrum, δ, ppm: 0.82 t (3Н, СН СН , J 7.1 Hz), 2.38
s (3Н, СН ), 3.80 s (3Н, ОСН ), 3.88 q (2Н, СН СН ,
–
1
1
2
3
3
3
2
3
J 7.1 Hz), 7.02 d (2Н, С Н , J 8.7 Hz), 7.21 d (2Н,
6
4
Ethyl 2-methyl-4-phenyl-5-cyano-6-(dicyano-
methylidene)-1,6-dihydropyridine-3-carboxylate
+
С Н , J 8.7 Hz). Mass spectrum, m/z (I , %): 360 [M]
6
4
rel
+
(
13), 315 [M – 45] (100). Found, %: С 66.54; H 4.59;
(
1a). A mixture of 0.264 g (2 mmol) of 2-aminoprop-1
N 15.68. C H N О . Calculated, %: C 66.66; H 4.48;
2
0
16
4
3
-
en-1,1,3-tricarbonitrile and 0.212 g (2 mmol) of
N 15.55. M 360.37.
benzaldehyde was stirred in 10 ml of ethanol in the
presence of catalytic amount of piperidine acetate at
Ethyl 2-methyl-4-(2-methoxyphenyl)-5-cyano-6-
(dicyanomethylidene)-1,6-dihydropyridine-3-
carboxylate (1g). Yield 70%, mp 215–216°С
6
0°С till components dissolved, then into the reaction
mixture was added 0.260 g (2 mmol) of acetoacetic
ester and 0.152 g (2.1 mmol) of sodium nitrite. After
the end of reaction (TLC) the reaction mixture was
cooled, conc. HCl was added dropwise till рН 3–4, the
precipitate was filtered off, washed with a small
amount of 2-propanol and with distilled water. The
product was recrystallized from a mixture 2-propanol–
dioxane. Yield 0.462 g (70%), mp 224–225°С
–
1
(decomp.). IR spectrum, ν, cm : 3268–3100 (NH);
1
2223, 2202 (C≡N), 1725 (С=О), 1604 (C=C). Н NMR
spectrum, δ, ppm: 0.74 t (3Н, СН СН , J 7.1 Hz), 2.41
2
3
s (3Н, СН ), 3.72 s (3Н, OСН ), 3.81 q (2Н, СН СН ,
3
3
2
3
J 7.1 Hz), 6.99 t (1Н, С Н , J 7.2 Hz), 7.04 d.d (1Н,
6
4
С Н , J 7.5, 1.8 Hz), 7.15 d (1Н, С Н , J 8.3 Hz), 7.39–
6
4
6
4
7.43 m (1Н, С Н ). Mass spectrum, m/z (I , %): 360
6
4
rel
+
+
(
decomp.) {224–225°С (decomp.) [6]}.
[M] (32), 315 [M – 45] (100). Found, %: С 66.51; H
4
4
.57; N 15.68. C H N О . Calculated, %: C 66.66; H
.48; N 15.55. M 360.37.
20 16 4 3
Compounds 1b–1g were obtained similarly.
Ethyl 2-methyl-4-(4-tolyl)-5-cyano-6-(dicyano-
methylidene)-1,6-dihydropyridine-3-carboxylate
1b). Yield 68%, mp 238–239°С (decomp.). IR
AKNOWLEDGMENTS
(
–
1
spectrum, ν, cm : 3250–3100 (NH), 2220, 2196
The investigation was performed under a financial
support of the Russian Science Foundation (project no.
17-13-01237).
1
(
C≡N), 1725 (С=О), 1625 (C=C). Н NMR spectrum, δ,
ppm: 0.78 t (3Н, СН СН , J 7.1 Hz), 2.36 s (3Н, СН ),
2
3
3
2
.39 s (3Н, СН ), 3.85 q (2Н, СН СН , J 7.1 Hz), 7.15
3 2 3
d (2Н, С Н , J 8.1 Hz), 7.26 d (2Н, С Н , J 8.0 Hz).
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6
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