Synthesis and properties of aza analogs of merocyanine dyes based on N-substituted 2- and 4-aminopyridinium salts

Article abstract of DOI:10.1007/s11172-018-2054-2

A series of aza analogs of the merocyanine dyes based on 1-N-alkyl-2- and 1-N-alkyl-4-aminopyridinium salts and ethoxymethylidenemalononitrile was synthesized. Their physico-chemical properties were studied.

Full text of DOI:10.1007/s11172-018-2054-2

1
68
Russian Chemical Bulletin, International Edition, Vol. 67, No. 1, pp. 168—171, January, 2018
Synthesis and properties of aza analogs of merocyanine dyes
based on Nꢀsubstituted 2ꢀ and 4ꢀaminopyridinium salts
I. A. Borisova, A. A. Zubarev, L. A. Rodinovskaya, and A. M. Shestopalov
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
4
7 Leninsky prosp., 119991 Moscow, Russian Federation.
Eꢀmail: irdbor@gmail.com
A series of aza analogs of the merocyanine dyes based on 1ꢀNꢀalkylꢀ2ꢀ and 1ꢀNꢀalkylꢀ4ꢀ
aminopyridinium salts and ethoxymethylidenemalononitrile was synthesized. Their physicoꢀ
chemical properties were studied.
Key words: aminopyridinium salts, ethoxymethylidenemalononitrile, azomerocyanine
dyes, spectral characteristics, protonation.
Merocyanine dyes are classified as polymethine dyes, the
Scheme 1
structure of which contains a donor and an acceptor linked by
a polyene chain.1 Increasing interest in these compounds
is related to the fact that merocyanines find wide use in
various areas: optoelectronics, biology, and medicine.3—8
Presently, attention of researchers is focused on the
dyes containing the dihydropyridine fragment as a donor
component, since merocyanines of this structure, proꢀ
bably, will be appropriate as materials in nonlinear optics
,2
9
,10
and anticancer agents.
These dyes can be obtained
rather easily using simple modifications of the dihydroꢀ
pyridine fragment itself and variation of the acceptor
group.1
1—13
It is known that the modification of the doꢀ
nor or acceptor moiety of merocyanine by the introducꢀ
tion of heteroatoms into the dye structure makes it possiꢀ
1
4
ble to change their optical properties. Therefore, the
study of the merocyanine dyes containing the heteroatom
in the polyene chain is interesting, because single examꢀ
ples of the synthesis of merocyanine dyes of similar strucꢀ
1
5—17
ture are met in the literature.
This work is devoted to the simple and convenient
method for the synthesis of the merocyanine dyes from
the 1ꢀNꢀsubstituted aminopyridine salts and malononitrile
derivative. The study of the physicochemical characterisꢀ
tics will make it possible to establish the structure—propꢀ
erty relationship of the obtained substances.
This study was carried out in the framework of the
complex program of investigation of molecular and hybrid
systems.18
1ꢀNꢀAlkylꢀsubstituted 2ꢀ and 4ꢀaminopyridine salts
1а—с and 2а—с were obtained by quaternization. The
further condensation of salts 1а—с and 2а—с with ethoxyꢀ
20
methylidenemalononitrile afforded a series of the corꢀ
responding azamerocyanine dyes 3а—с and 4а—с
(Scheme 2) in high yields (63—78%) (Table 1).
As in the case of the Cꢀanalogs, spectral analysis
was carried out for the obtained azamerocyanine dyes,
and some specific features in the IR and UV spectra
were found.
Results and Discussion
In this work, the azamerocyanine dyes were syntheꢀ
sized according to the procedure developed by us previꢀ
ously19 for the Cꢀanalogs (Scheme 1).
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 0168—0171, January, 2018.
066ꢀ5285/18/6701ꢀ0168 © 2018 Springer Science+Business Media, Inc.
1

Azamerocyanine dyes: synthesis and properties
Russ.Chem.Bull., Int.Ed., Vol. 67, No. 1, January, 2018
A
169
Scheme 2
3.0
2.5
2.0
1.5
1.0
0.5
3a
4a
3
00
350
400
450
500
550 λ/nm
Fig. 1. UV spectra of dyes 3а and 4а (solvent CH Cl , C =
M
2
2
–
5
–1
=
10 mol L ).
The intensity of the absorption maximum of the
Nꢀanalogs of merocyanines is lower by 70—80 nm than
that of the Cꢀanalogs.1
9
As in the case of the Cꢀanalogs, the protonation of
azamerocyanines (dye 4а was chosen as model) with triꢀ
fluoroacetic acid proceeds at the nitrogen atom in the
γꢀposition of the polyene chain (Scheme 3), which is
indicated by the appearance of two doublets at 8 and
1
1
0 ppm in the Н NMR spectrum (Fig. 2).
In the UV spectra of protonated dye 4а, the absorpꢀ
tion maximum is shifted to the shortꢀwavelength range to
95 nm (lower by 114 nm), which probably indicates that
2
the partial conjugation between the pyridine ring and side
chain is retained (Fig. 3).
X = I (a), Br (b, c)
This phenomenon can also be confirmed by the fact
that the absorption maximum in the UV spectrum disꢀ
appears upon the protonation of the Cꢀanalogs of the
merocyanine dyes at the carbon atom in the γꢀposition of
The IR spectra of the synthesized compounds contain
two absorption bands corresponding to vibrations of the
nitrile groups in ranges of 2197 and 2212 cm– . This indiꢀ
cates, most likely, that one of the nitrile groups is more
conjugated with the polyene chain than another. This
specific feature can be explained by the fact that in the
aza analogs, as in the Cꢀanalogs of the merocyanine dyes,
the electron density is distributed between the donor and
acceptor groups along the conjugated bonds of the polyꢀ
ene chain.1
1
a
1
2.0
10.0
8.0
6.0
4.0
2.0
δ
The introduction of the nitrogen atom into the polyꢀ
ene chain results in the shift of the absorption maximum
in the UV spectrum to the shortꢀwavelength range to
b
3
85—410 nm (Fig. 1).
H2O
Table 1. Yields of compounds 3а—с and 4а—с
1
2.0
10.0
8.0
6.0
4.0
2.0
δ
Compound
R
Yield (%)
Fig. 2. 1Н NMR spectra of protonated* (a) and nonꢀprotoꢀ
nated** (b) compound 4а.
3a
3b
3c
4a
4b
4c
Me
Bu
75
69
63
78
70
67
1
*
The Н NMR spectrum was detected in CF СООН, boundꢀ
3
aries of the spectrum are 1.5—13 ppm (broadened singlet at
C H
6
13
1
1.5 ppm is assigned to the proton in CF СООН).
3
Me
Bu
1
*
* The Н NMR spectrum was detected in DMSOꢀd , boundꢀ
6
aries of the spectrum are 1.5—13 ppm (broadened singlet at
.4 ppm is assigned to H O of the deuterated solvent).
C H
6
13
3
2

1
70
Russ.Chem.Bull., Int.Ed., Vol. 67, No. 1, January, 2018
Borisova et al.
Scheme 3
into the polyene chain of the merocyanine dye changes
the optical properties of the substance, and the absorpꢀ
tion maximum shifts to the shortꢀwavelength range. Solꢀ
vatochromism was found for model dye 4а and showed
that the absorption spectra of the aza analogs of the meroꢀ
cyanine dyes demonstrated an insignificant hypsochroꢀ
mic shift.
Experimental
1Н and 13С NMR spectra were recorded on a Bruker AM 300
instrument (DMSOꢀd as the solvent). IR spectra were detected
6
the polyene chain, indicating, most likely, the cleavage of
the conjugation.21
in KBr pellets on a Bruker ALPHAꢀT instrument. UV spectra
were recorded on an Agilent 8453 instrument in quartz cells
with a path length of 1 cm using the substance concentration
As in the case of the Cꢀanalogs, solvatochromism of
the azamerocyanine dyes was detected for the earlier unꢀ
studied compound 4а as an example (Fig. 4).
This type of dyes demonstrates negative solvatoꢀ
chromism unlike the Cꢀanalogs of merocyanine dyes,
CM = 10– mol L (solvent СН2Cl2). Mass spectra were meaꢀ
sured on a micrOTOF instrument. All solvents were purified
prior to use according to known procedures. The course of the
reactions was monitored by TLC on the Merck plates (chroꢀ
matograms were visualized by iodine vapors or UV irradiation
at 254 nm). Salts 1а—с and 2а—с were obtained using a known
5
–1
1
9
which manifest positive solvatochromism.
To conclude, new azamerocyanine dyes 3а—c and
a—c were synthesized in high yields. It is shown that the
21
procedure.
4
Synthesis of azamerocyanine dyes 3а—с and 4а—с (general
procedure). The starting salt 1а—с or 2а—с (1.0 mmol) was
dissolved in DMF (3 mL), and triethylamine (2.0 mmol) was
added dropwise. Ethoxymethylidenemalononitrile (2.0 mmol)
was introduced into the reaction mixture, and the latter was
stirred for 2—4 h at 70 °C. After cooling, the reaction mixture
was diluted with water, and the formed precipitate was filtered
off, washed with a solution of hydrochloric acid (рН = 4) and
water, and dried in air.
protonation of the Nꢀanalogs of the merocyanine dyes at
the nitrogen atom in the γꢀposition of the polyene chain
does not cleave the conjugation between the heterocyclic
ring and side chain. The introduction of the heteroatom
A
3.0
2.5
2.0
1.5
1.0
0.5
2
ꢀ([{1ꢀMethylpyridinꢀ2(1Н)ꢀylidene}amino]methylene)malꢀ
ononitrile (3а). The yield was 293 mg (75%), yellow powder,
m.p. 201—203 °C. IR, ν/cm–1: 2185 (=С=N), 2202 (—CN).
1
2
1
UV (CH Cl ), λ /nm (logε): 340 (3.07), 387 (3.07). Н NMR,
2
2
max
δ: 3.87 (s, 3 H, NCH ); 7.06 (t, 1 H, Н(4), J = 6.7 Hz); 7.58
3
(d, 1 Н, Н(6), J = 8.8 Hz); 7.96 (t, 1 Н, Н(5), J = 8.8 Hz); 8.31
3
(
d, 1 H, Н(3), J = 6.7 Hz); 8.45 (s, 1 Н, СН). 1 С NMR, δ:
4
1
1.79; 56.95; 115.57; 115.61; 116.83; 119.31; 142.70; 143.02;
64.40. Highꢀresolution mass spectrum (HRMS), calculated (М):
3
50
450
550
λ/nm
[
M + H], 185.0822; C H N ; found: m/z 185.0826. Found (%):
10 8 4
Fig. 3. UV spectra of protonated (1) and nonꢀprotonated (2)
С, 64.97; Н, 4.40; N, 30.52. C H N . Calculated (%): С, 65.21;
1
0
8
4
–
5
–1
compound 4а (solvent CH Cl , C = 10 mol L ).
Н, 4.38; N, 30.42.
ꢀ([{1ꢀButylpyridinꢀ2(1Н)ꢀylidene}amino]methylene)malꢀ
2
2
M
2
ononitrile (3b). The yield was 455 mg (69%), yellow powder,
m.p. 83—85 °C. IR, ν/cm–1: 2202 (=С=N), 2213 (—CN). UV
D
1
(
CH Cl ), λ
/nm(logε): 339 (0.84), 391 (2.04). Н NMR, δ:
2
2
max
3.5
2.5
1.5
0.5
2
0.91 (t, 3 H, NCH CH CH CH , J = 7.3 Hz); 1.06—1.50 (m, 2 H,
2 2 2 3
3
NCH CH CH CH ); 1.72 (dd, 2 Н, NCH CH CH CH ,
2 2 2 3 2 2 2 3
4
J = 14.6 Hz, J = 7.3 Hz); 4.36 (t, 2 Н, NCH CH CH CH ,
2
2
2
3
1
5
J = 7.3 Hz); 7.06 (t, 1 H, Н(4), J = 6.7 Hz); 7.59 (d, 1 Н, Н(6),
J = 8.9 Hz); 7.95 (t, 1 Н, Н(5), J = 8.9 Hz); 8.32 (d, 1 H, Н(3),
J = 6.7 Hz); 8.47 (s, 1 Н, СН). 1 С NMR, δ: 13.85; 19.58; 31.24;
3
5
1
3.38; 57.01; 115.75; 115.81; 116.70; 119.29; 141.91; 142.95; 157.63;
64.39. HRMS, calculated (М): [M + H], 227.1291; C13H N ;
14
4
found: m/z 227.1297. Found (%): С, 68.70; Н, 6.26; N, 24.77.
3
50
Fig. 4. Solvatochromism for compound 4а detected in acetone
1), ethanol (2), acetonitrile (3), DMSO (4), and dichloroꢀ
400
450
500 λ/nm
C13H14N . Calculated (%): С, 69.00; Н, 6.24; N, 24.76.
4
2ꢀ([{1ꢀHexylpyridinꢀ2(1Н)ꢀylidene}amino]methylene)malꢀ
ononitrile (3с). The yield was 310 mg (63%), yellow powder,
(
–
5
–1
–1
methane (5) (CM = 10 mol L ).
m.p. 89—91 °C. IR, ν/cm : 2196 (=С=N), 2211 (—CN).

Azamerocyanine dyes: synthesis and properties
Russ.Chem.Bull., Int.Ed., Vol. 67, No. 1, January, 2018
171
1
UV (CH Cl ), λ /nm (logε): 340 (0.86), 389 (1.91). Н NMR,
2. V. Z. Shirinian, I. V. Zavarzin, E. S. Leonova, A. I. Markoꢀ
syan, Mendeleev Commun., 2015, 25, 262.
2
2
max
δ: 0.85 (t, 3 H, NCH CH CH CH CH CH , J = 7.5 Hz);
2
2
2
2
2
3
1
2
4
.13—1.47 (m, 6 H, NCH CH CH CH CH CH ); 1.74 (dd,
3. F. Wurthner, J. Schmidt, M. Stolte, R. Wortmann, Angew.
Chem., Int. Ed., 2006, 45, 3842.
2
2
2
2
2
3
Н, NCH CH CH CH CH CH , J = 14.6 Hz, J = 7.5 Hz);
2
2
2
2
2
3
.35 (t, 2 Н, NCH CH CH CH CH CH , J = 7.5 Hz); 7.06
4. J.ꢀF. Xiang, Y.ꢀX. Liu, D. Sun, S.ꢀJ. Zhang, Y.ꢀL. Fu, X.ꢀH.
Zhang, L.ꢀY. Wang, Dyes Pigm., 2012, 93, 1481.
5. C. J. MacNevin, D. Gremyachinskiy, C.ꢀW. Hsu, L. Li,
M. Rougie, T. T. Davis, K. M. Hahn, Bioconjug. Chem.,
2013, 24, 215.
6. A. S. Brown, L.ꢀM. Bernal, T. L. Micotto, E. L. Smith,
J. N. Wilson, Org. Biomol. Chem., 2011, 9, 2142.
7. H. A. Shindy, Dyes Pigm., 2017, 145, 505.
2
2
2
2
2
3
(
(
(
t, 1 H, Н(4), J = 6.7 Hz); 7.60 (d, 1 Н, Н(6), J = 8.8 Hz); 7.95
t, 1 Н, Н(5), J = 8.8 Hz); 8.32 (d, 1 H, Н(3), J = 6.7 Hz); 8.47
s, 1 Н, СН). С NMR, δ: 14.23; 22.41; 25.90; 29.17; 31.03;
1
3
5
1
3.59; 57.00; 115.77; 116.66; 119.30; 141.91; 142.96; 157.64;
64.36. HRMS, calculated (М): [M + H], 255.1604; C15H N ;
18
4
found: m/z 255.1612. Found (%): С, 66.19; Н, 7.14; N, 20.88.
C15H18N •H O. Calculated (%): С, 66.15; Н, 7.40; N, 20.57.
4
2
2
ꢀ([{1ꢀMethylpyridinꢀ4(1Н)ꢀylidene}amino]methylene)ꢀ
8. A. Haque, Md. S. H. Faizi, J. A. Rather, M. S. Khan,
Bioorg. Med. Chem., 2017, 25, 2017.
9. W. H. Hao, P. Yan, G. Li, Z. Y. Wang, Dyes Pigm., 2014,
111, 145.
malononitrile (4а). The yield was 304 mg (78%), yellow powꢀ
der, m.p. 221—223 °C. IR, ν/cm : 2185 (=С=N), 2202 (—CN).
UV (CH Cl ), λ /nm (logε): 405 (2.75). 1Н NMR, δ: 3.96
–
1
2
2
max
(
(
s, 3 Н, NCH ); 7.24 (d, 2 H, Н(2), Н(6), J = 6.9 Hz); 8.26
d, 2 H, Н(3), Н(5), J = 6.9 Hz); 8.37 (s, 1 Н, СН). С NMR,
10. C. G. Fortuna, V. Barresi, C. Bonaccorso, G. Consiglio,
S. Failla, A. TrovatoꢀSalinaro, G. Musumarra, Eur. J. Med.
Chem., 2012, 74, 221.
11. A. A. Vasilev, S. Baluschev, D. Cheshmedzhieva, S. Ilieva,
O. D. Castano, J. J. Vaquero, S. E. Angelova, K. Landꢀ
fester, Aust. J. Chem., 2015, 68, 1399.
12. J. R. Carreon, K. M. Stewart, K. P. Mahon, Jr., S. Shin,
S. O. Kelley, Bioorg. Med. Chem. Lett., 2007, 17, 5182.
13. A. Kurutos, O. Ryzhova, V. Trusova, U. Tarabara, G. Gorꢀ
benko, N. Gadjev, T. Deligeorgiev, Dyes Pigm., 2016,
130, 122.
3
1
3
δ: 45.19; 109.68; 116.78; 117.65; 120.09; 144.20; 164.15; 165.06.
HRMS, calculated (М): [M + H], 185.0822; C10H N ; found:
m/z 185.0826. Found (%): С, 62.36; Н, 4.84; N, 29.33. C H N .
Calculated (%): С, 65.21; Н, 4.38; N, 30.42.
ꢀ([{1ꢀButylpyridinꢀ4(1Н)ꢀylidene}amino]methylene)malꢀ
ononitrile (4b). The yield was 462 mg (70%), yellow powder,
m.p. 154—156 °C. IR, ν/cm : 2189 (=С=N), 2209 (—CN).
UV (CH Cl ), λ /nm (logε): 406 (2.27). Н NMR (300 MHz),
δ: 0.90 (t, 3 H, NCH CH CH CH , J = 7.3 Hz); 1.16—1.51
8
4
1
0
8
4
2
–
1
1
2
2
max
2
2
2
3
(
m, 2 H, NCH CH CH CH ); 1.67—1.99 (m, 2 Н, NCH CH ꢀ
14. C. Reichardt, W. Mormann, Chem. Ber., 1972, 105, 1815.
15. A. Kakehi, S. Ito, T. Funahashi, N. Ogasawara, Bull. Chem.
Soc. Jpn, 1976, 49, 8, 2250.
16. J. Lokaj, V. Kettmann, V. Milata, R. Kada, J. Ulrich, Acta
Crystallogr., Sect. C: Cryst. Struct. Commun., 1998, 54, 6, 785.
17. K. Mizuyama, Y. Tominaga, Y. Matsuda, G. Kobayashi,
Chem. Pharm. Bull., 1979, 27, 12, 2879.
2
2
2
3
2
2
CH CH ); 4.19 (t, 2 Н, NCH CH CH CH , J = 7.2 Hz); 7.25
(
2
3
2
2
2
3
d, 2 H, Н(2), Н(6), J = 6.9 Hz); 8.34 (d, 2 H, Н(3), Н(5),
1
3
J = 6.9 Hz); 8.39 (s, 1 Н, СН). С NMR, δ: 13.80, 19.23,
2.81, 57.67, 116.94, 117.56, 120.02, 143.31, 164.35, 165.13. HRMS,
calculated (М): [M + H], 227.1291; C H N ; found: m/z
3
1
3
14
4
2
27.1295. Found (%): С, 68.50; Н, 6.31; N, 24.52. C H N .
13 14 4
Calculated (%): С, 69.00; Н, 6.24; N, 24.76.
18. V. P. Ananikov, D. B. Eremin, S. A. Yakukhnov, A. D.
Dilman, V. V. Levin, M. P. Egorov, S. S. Karlov, L. M.
Kustov, A. L. Tarasov, A. A. Greish, A. A. Shesterkina,
A. M. Sakharov, Z. N. Nysenko, A. B. Sheremetev, A. Yu.
Stakheev, I. S. Mashkovsky, A. Yu. Sukhorukov, S. L. Ioffe,
A. O. Terent´ev, V. A. Vil´, Yu. V. Tomilov, R. A. Novikov,
S. G. Zlotin, A. S. Kucherenko, N. E. Ustyuzhanina, V. B.
Krylov, Yu. E. Tsvetkov, M. L. Gening, N. E. Nifantiev,
Mendeleev Commun., 2017, 27, 425.
2
ꢀ([{1ꢀHexylpyridinꢀ4(1Н)ꢀylidene}amino]methylene)malꢀ
ononitrile (4с). The yield was 328 mg (67%), yellow powder,
–
1
m.p. 109—111 °C. IR, ν/cm : 2198 (=С=N), 2213 (—CN).
1
UV (CH Cl ), λ /nm (logε): 267 (1.31), 346 (2.23). Н NMR,
2
2
maх
δ: 0.85 (t, 3 H, NCH CH CH CH CH CH , J = 7.6 Hz);
2
2
2
2
2
3
1
.12—1.44 (m, 6 H, NCH CH CH CH CH CH ); 1.73 (dd, 2 Н,
2 2 2 2 2 3
NCH CH CH CH CH CH , J = 14.5 Hz, J = 7.6 Hz); 4.32
2
2
2
2
2
3
(
t, 2 Н, NCH CH CH CH CH CH , J = 7.5 Hz); 7.26 (d, 2 H,
2 2 2 2 2 3
Н(2), Н(6), J = 6.7 Hz); 8.35 (d, 2 H, Н(3), Н(5), J = 6.7 Hz);
19. I. A. Borisova, A. A. Zubarev, L. A. Rodinovskaya, A. M.
Shestopalov, Arkivoc, 2017, 3, 73.
20. L. Nicholl, P. J. Tarsio, H. Blohm, US Pat. 2824121; Chem.
Abstr., 1958, 52, 11909.
1
3
8
3
1
.41 (s, 1 Н, СН). С NMR, δ: 14.26; 22.39; 25.85; 29.13;
1.01; 53.67; 57.05; 115.70; 116.61; 119.28; 141.97; 142.99;
57.61; 164.29. HRMS, calculated (М): [M + H], 255.1604;
C15H18N ; found: m/z 255.1605. Found (%): С, 66.75; Н, 6.12;
21. A. Ilagnovan, P. Venkatesan, M. Sundararaman, R. R.
Kumar, Med. Chem. Res., 2012, 21, 694.
4
N, 23.31. C15H18N •0.5H O. Calculated (%): С, 68.41;
4
2
Н, 7.27; N, 21.28.
This work was financially supported by the Russian
Science Foundation (Project No. 14ꢀ50ꢀ00126).
References
Received August 18, 2017;
in revised form November 7, 2017;
accepted November 20, 2017
1
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7