Synthesis and properties of cross-conjugated ω,ω′-bis- dimethylamino ketones and dinitriles with N-acetyl- and N-benzylpiperidine cycles

Article abstract of DOI:10.1007/s11172-011-0306-5

Reactions of N-acetyl- and N-benzyl-4-piperidones with aminal of β-dimethylaminoac-rolein yielded ketocyanines bearing piperidine cycle. Reaction of 3-dimethylamino-1,1,3-tri-methoxypropane with 1-acetylpiperidin-4- ylidenemalononitrile in the presence of ionic liquid, 1-butyl-3- methylimidazolium tetrafluoroborate ([bmim]BF₄), resulted in cross-conjugated ω,ω′-dimethylamino dinitrile. Protonation of ketocyanines bearing N-acetyl- and N-benzyl-piperidine cycles with Et ₂O · HBF₄ (1 equiv.) furnished piperidinium salts, while protonation of the latter with Et₂O·HBF₄ (2 equiv.) afforded doubly charged 4-hydroxypolymethine salts. Unlike protonation, reaction of 3,5-bis(3-dimethylaminoprop-2-enylidene)-1-acetylpiperidin-4-one with Me₂SO₄ involved only the oxygen atom and led to a singly charged 4-methoxypoly-methine salt. Methylation of 3,5-bis(3- dimethylaminoprop-2-enylidene)-1-benzylpiperidin-4-one with Me ₂SO₄ (1 equiv.) involved cyclic nitrogen atom and resulted in piperidinium salt; heating of the latter with the excess of Me ₂SO₄ afforded doubly charged bis-methoxysulfonate. Starting from 4-methoxytetrahydropyridinium salts, meso- methoxythiapentacarbocyanine dyes were synthesized.

Full text of DOI:10.1007/s11172-011-0306-5

Russian Chemical Bulletin, International Edition, Vol. 60, No. 10, pp. 2014—2020, October, 2011
2014
Synthesis and properties of crossꢀconjugated ω,ω´ꢀbisꢀdimethylamino ketones
and dinitriles with Nꢀacetylꢀ and Nꢀbenzylpiperidine cycles
Zh. A. Krasnaya, E. O. Tret´yakova, V. V. Kachala, and S. G. Zlotin
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5328. Eꢀmail: kra@ioc.ac.ru
Reactions of Nꢀacetylꢀ and Nꢀbenzylꢀ4ꢀpiperidones with aminal of βꢀdimethylaminoacꢀ
rolein yielded ketocyanines bearing piperidine cycle. Reaction of 3ꢀdimethylaminoꢀ1,1,3ꢀtriꢀ
methoxypropane with 1ꢀacetylpiperidinꢀ4ꢀylidenemalononitrile in the presence of ionic liquid,
1ꢀbutylꢀ3ꢀmethylimidazolium tetrafluoroborate ([bmim]BF4), resulted in crossꢀconjugated
ω,ω´ꢀdimethylamino dinitrile. Protonation of ketocyanines bearing Nꢀacetylꢀ and Nꢀbenzylꢀ
piperidine cycles with Et2O•HBF4 (1 equiv.) furnished piperidinium salts, while protonation of
the latter with Et2O•HBF4 (2 equiv.) afforded doubly charged 4ꢀhydroxypolymethine salts.
Unlike protonation, reaction of 3,5ꢀbis(3ꢀdimethylaminopropꢀ2ꢀenylidene)ꢀ1ꢀacetylpiperidinꢀ
4ꢀone with Me2SO4 involved only the oxygen atom and led to a singly charged 4ꢀmethoxypolyꢀ
methine salt. Methylation of 3,5ꢀbis(3ꢀdimethylaminopropꢀ2ꢀenylidene)ꢀ1ꢀbenzylpiperidinꢀ
4ꢀone with Me2SO4 (1 equiv.) involved cyclic nitrogen atom and resulted in piperidinium salt;
heating of the latter with the excess of Me2SO4 afforded doubly charged bisꢀmethoxysulfonate.
Starting from 4ꢀmethoxytetrahydropyridinium salts, mesoꢀmethoxythiapentacarbocyanine dyes
were synthesized.
Key words: ketocyanines, malononitrile, protonation, methylation, polymethine salts,
cyanines, absorption spectra.
Recently,1 we synthesized the first representatives of
Scheme 1
crossꢀconjugated ω,ω´ꢀbisꢀdimethylamino ketones bearꢀ
ing piperidine cycle in the polyene chain. In contrast to
ketocyanines studied previously,2 these compounds conꢀ
tain two reactive centers, which can be attacked by electroꢀ
philes, e.g., the carbonyl group and the cyclic nitrogen
atom. Spectral study and investigation of chemical propꢀ
erties of these compounds revealed several specific feaꢀ
tures.3 Earlier,1 analog of ketocyanine 3,5ꢀbis(3ꢀdimethylꢀ
aminopropꢀ2ꢀenylidene)ꢀ1ꢀethoxycarbonylpiperidinꢀ4ꢀ
one bearing dicyanomethylidene moiety instead of the carꢀ
bonyl group was also synthesized. This replacement reꢀ
sulted in significant bathochromic shift of the absorption
maximum in the electronic absorption spectra.
The present work was devoted to the synthesis and study
of the properties of hitherto unknown crossꢀconjugated
ω,ω´ꢀbisꢀdimethylamino ketones and the corresponding
dinitriles with Nꢀbenzyl and Nꢀacetylpiperidine cycles.
R = C(O)Me (a), CH2Ph (b)
Condensation of aminal of βꢀdimethylaminoacrolein 1
(see Ref. 4) with Nꢀsubstituted 4ꢀpiperidones 2a,b
(65—70 °C, 40—90 min) afforded ketocyanines 3a,b in
75—85% yields (Scheme 1).
With the aim at synthesizing crossꢀconjugated diniꢀ
triles 4a,b (analogs of ketocyanines 3a,b with dicyanomeꢀ
thylidene fragment instead of the carbonyl group), we studꢀ
ied condensation of aminal 1 and 3ꢀdimethylaminoꢀ1,1,3ꢀ
trimethoxypropane 5 (see Ref. 5) with hitherto unknown
(1ꢀacetylpiperidinꢀ4ꢀylidene)malononitrile 6a and
(1ꢀbenzylpiperidinꢀ4ꢀylidene)malononitrile 6b (see Ref. 6)
(Scheme 2).
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1978—1983, October, 2011.
1066ꢀ5285/11/6010ꢀ2014 © 2011 Springer Science+Business Media, Inc.

ω,ω´ꢀBisdimethylamino ketones and dinitriles
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 10, October, 2011
2015
Scheme 2
R = C(O)Me (a), CH2Ph (b)
The attempts to prepare polyenic dinitriles 4a,b using
aminal 1 failed. Crossꢀconjugated dinitrile 4a was accessꢀ
ed in 20% yield by the condensation of compound 5 with
dinitrile 6a only in the presence of ionic liquid, 1ꢀbutylꢀ3ꢀ
methylimidazolium tetrafluoroborate ([bmim]BF4). The
latter, apparently, contribute in the polarization of the
C—H bonds of compound 6a. All attempts to synthesize
benzylꢀsubstituted analog 4b were unsuccessful.
the latter with Et2O•HBF4 (1 eqiuv.) afforded the doubly
charged 4ꢀhydroxypolymethine salts 8a,b due to protonaꢀ
tion on the oxygen atom. Salts 8a,b can be prepared diꢀ
rectly from ketocyanines 3a,b using 2 equiv. of Et2O•HBF4
(Scheme 3).
Scheme 3
Structures of crossꢀconjugated polyenes 3a,b and 4a
were established based on 1H and 13C NMR spectroscopy,
UV spectroscopy, mass spectrometry and confirmed by
microanalysis.
1
The H and 13C NMR spectra were interpreted using
2D NMR experiments (COSY, HSQC, and HMBC).
3
The values of the vicinal coupling constants Jβ—γ and
3Jγ—δ equal 12.0 and 12.4 Hz, respectively, indicate the
transꢀconfiguration of the protons of the CβH—CγH—CδH
moiety and domination of Sꢀtransꢀconformation for the
diene fragments of the polymethine chains.
Comparison of the UV spectra of ketocyanine 3a and
dinitrile 4a reveals that absorption maximum of dinitrile
4a shifted to longer wavelengths by 80 nm. It is of note
that UV spectra of dinitrile 4a, unlike that of ketocyanines
3a,b, exhibits not only long wavelength band with high
absorption coefficient ε (ε = 70000—90000 L mol–1 cm–1
)
but also short wavelength band with the maximum at
310—320 nm with significantly lower ε value (ε =
= 10000—11000 L mol–1 cm–1). Ketocyanines 3a,b and
dinitrile 4a show bathochromic solvent effect: on going
from nonꢀpolar (CHCl3) to polar (EtOH) solvent the abꢀ
sorption band shifted to longer wavelengths by 20 nm.
Ketocyanines 3a,b possess properties of the Lewis
bases. Thus, treatment of these compounds with
Et2O•HBF4 (1 equiv.) resulted in the protonation on the
cyclic nitrogen atom to give piperidinium salts 7a,b in the
yields of 66 and 75%, respectively. Further treatment of
R = C(O)Me (a), CH2Ph (b)
Reagents and conditions: Et2O•HBF4, 1 equiv. (i), 2 equiv. (ii);
7a (66%), 7b (75%), 8a (86% from 7a, 73% from 3a), 8b (45%
from 7b, 77% from 3b).
In contrast to compounds 3a,b, reaction of dinitrile 4a
with Et2O•HBF4 failed and dinitrile was recovered.
Direction of the alkylation of ketocyanines 3a,b deꢀ
pends on the nature of the substituent at the cyclic nitrogen
atom. Unlike protonation, methylation of ketocyanine 3a

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Krasnaya et al.
Scheme 5
by Me2SO4 in CH2Cl2 involved only the oxygen atom
to give a singly charged 4ꢀmethoxypolymethine salt 9
(Scheme 4).
Scheme 4
On treatment of ketocyanine 3a with methyl sulfate
(1 equiv.), product 9 begins to form even at 20 °C, its
amount increasing during the reaction. When the excess
of Me2SO4 is used and the reaction carried out at elevated
temperature, the reaction rate is higher and the yield of 9
is also higher. In contrast to ketocyanine 3a, treatment of
ketocyanine 3b with Me2SO4 (1 equiv.) resulted in methylaꢀ
tion at cyclic nitrogen atom to give piperidinium methoxyꢀ
sulfonate 10. The latter under the action of large excess of
Me2SO4 at 50—55 °C was converted into tetrahydropyriꢀ
dinium bisꢀmethoxysulfonate sulfate 11 (Scheme 5).
Structures of salts 7a,b, 8a,b, and 9—11 were conꢀ
Reagents: Me2SO4, CH2Cl2, 1 equiv. (i); 6 equiv. (ii).
dilute solutions of salt 7a in CHCl3 and CH2Cl2, proton
migration from the nitrogen to oxygen occurs and salts 7a
and 12 equilibrate (Scheme 6).
Scheme 6
1
firmed by H NMR spectra in DMSOꢀd6 and electronic
absorption spectra.
The UV spectra of salts 7a,b protonated at the nitrogen
atom and quaternary ammonium salt 10 in CHCl3
(λmax = 470—485 nm, yellow colored solution) are almost
identical to that of the starting ketocyanines 3a,b (λmax
=
= 470—475 nm). The absorption band in the spectra of
the salts protonated and methylated at the oxygen atom
significantly shifted in the longer wavelengths. Thus, salts
8a,b have absorption maxima at 600—620 nm, while salts
9 and 11 exhibit maxima at 640 nm (blue colored soꢀ
lutions).
Specific spectral behavior of the salt 7a is of interest;
its absorption spectra are notably solvent dependent. Thus,
the spectra of 7a in DMSO and MeCN exhibit one abꢀ
sorption band with maximum at 475 nm, while in CHCl3
and CH2Cl2 they have two bands with maxima at 470 and
615 nm, whose intensity ratio depends on concentration.
Removal of CHCl3 and CH2Cl2 from the solutions to dryꢀ
ness afforded salt 7a, whose spectra in DMSO and MeCN
have only one maximum at 470 nm. Apparently, in very
In the presence of triethylamine, salts 9 and 11 react
with benzothiazolium salt 13 affording hitherto unknown
mesoꢀmethoxythiapentacarbocyanine dyes 14 and 15. The

ω,ω´ꢀBisdimethylamino ketones and dinitriles
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 10, October, 2011
2017
Scheme 7
TsO–
=
Scheme 8
structures of dyes 14 and 15 were established by 1H NMR
spectroscopy and electronic absorption spectroscopy
(Schemes 7 and 8).
Absorption spectra were recorded on Specord UVꢀVis (comꢀ
pounds 6a, 7a,b, 8a,b, and 9—11) and U 1900 (compounds 14
and 15) spectrophotometers. For low soluble compounds, the
extinction coefficient (ε) was not determined. MS spectra (EI,
70 eV) were recorded on a Kratos MSꢀ30 instrument, high resoꢀ
lution MS were performed on a Bruker micrOTOF II instrument
with electrospray ionization (ESI). The reaction course was monꢀ
itored by UV/VIS spectroscopy. All reactions with Et2O•HBF4
were performed under argon. Dry, acidꢀfree CH2Cl2 was used as
a solvent. Due to low stability, microanalysis of the salts protoꢀ
nated by the oxygen atom was not performed.
2ꢀ(1ꢀAcetylpiperidinꢀ4ꢀylidene)malononitrile (6a). A mixture
of 1ꢀacetylꢀ4ꢀpiperidone 2a (4 g, 0.028 mol), malononitrile
(2.8 g, 0.045 mol), ammonium acetate (0.84 g, 0.011 mol), glaꢀ
cial acetic acid (2 g, 0.033 mol), and benzene (15 mL) was reꢀ
fluxed for 2 h with azeotropic removal of water. The reaction
mixture was concentrated in vacuo, diethyl ether (100 mL) was
added to the residue, the precipitate that formed was separated
and suspended in benzene (100 mL). Benzene solution was filꢀ
tered, washed with aqueous NaHCO3 and water, the organic
layer was dried with anhydrous MgSO4, and the solvent was
removed in vacuo. Yield of dinitrile 6a was 1.55 g (27%),
m.p. 101—103 °C. Found (%): C, 63.22; H, 5.61; N, 22.10.
C10H11N3O. Calculated (%): C, 63.48; H, 5.86; N, 22.21. UV
(EtOH), λmax/nm (ε): 225 (5815), 265 (4500). 1H NMR (CDCl3),
δ: 2.17 (s, 3 H, CH3); 2.79 (m, 4 H, CH2); 3.65 (m, 2 H, CH2);
3.79 (m, 2 H, CH2).
Dye 15 is the doubly charged and contains 2 equiv. of
TsO– anions. The absorption spectrum of dye 15 shows
longest wavelength absorption with maximum at 964 nm with
a very high absorption coefficient ε = 237703 L mol–1 cm–1
.
This band is significantly shifted to shortest wavelengths
(by 38—42 nm) as compared with singly charged dyes 14
and mesoꢀalkoxythiapentacarcocyanine dyes synthesized
earlier.2,3
Good solubility in water is the specific feature of dye 15,
which could be used for the study of its complexation
with DNA.
In summary, methylation of ketocyanines bearing pipeꢀ
ridine cycle afforded 4ꢀmethoxytetrahydropyridinium
salts, which were used for the synthesis of hitherto unꢀ
known alkoxythiapentacarbocyanine dyes. The photoꢀ
chemical and photophysical investigation of the latter will
be published elsewhere.
Experimental
1
H NMR spectra of compounds 6a, 7a,b, 8a,b, 9—11,
14, and 15 were recorded on a Bruker Avance 300 instrument
(300.13 MHz) in DMSOꢀd6. 1H and 13C NMR spectra of
compounds 3a,b were measured and 2D NMR experiments
(COSY, HSQC, and HMBC) were performed on
a Bruker Avance 600 instrument (600.13 MHz (1H) and
150.90 MHz (13C)).
1ꢀAcetylꢀ3,5ꢀbis(3ꢀdimethylaminopropenꢀ2ꢀenylidene)ꢀ4ꢀ
piperidone (3a). To 1ꢀacetylꢀ4ꢀpiperidone 2a (0.56 g, 4 mmol),
aminal 1 (1.37 g, 8 mmol) was added dropwise. The reaction
mixture was heated at 65—70 °C for 40 min. To a crystalline
residue, anhydrous diethyl ether (10 mL) was added, the precipꢀ
itate that formed was filtered, washed with diethyl ether, and

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Krasnaya et al.
dried. The yield of compound 3a was 1.02 g (85%), bright orange
crystals, m.p. 205—208 °C. Found (%): C, 66.96; H, 8.47; N, 14.01.
C17H25N3O2. Calculated (%): C, 67.30; H, 8.31; N, 13.85. UV,
tals, m.p. >235 °C. Found (%): C, 52.40; H, 6.52; N, 10.66.
C17H26BF4N3O2. Calculated (%): C, 52.19; H, 6.70; N, 10.74.
UV, λmax/nm: 475 (DMSO), 475 (CH3CN), 470 and 615 (CHCl3),
1
λ
max/nm (ε): 490 (62300) (EtOH), 470 (54540) (CHCl3).
470 and 615 (CH2Cl2). H NMR (DMSOꢀd6), δ: 2.03 (s, 3 H,
1H NMR (DMSOꢀd6), δ: 2.05 (s, 3 H, NCOCH3); 2.90 (s, 12 H,
NMe2); 4.28 (s, 2 H, CH2); 4.31 (s, 2 H, CH2); 4.97 (t, 1 H, γꢀH,
J = 12.4 MHz); 5.12 (t, 1 H, γ´ꢀH, J = 12.4 MHz); 7.03 (d, 1 H,
δꢀH, J = 12.4 MHz); 7.07 (d, 1 H, δ´ꢀH, J = 12.4 MHz); 7.17 (d, 2 H,
β and β´, J = 12.4 MHz). 1H NMR (CDCl3), δ: 2.16 (s, 3 H,
NCOCH3); 2.94 (s, 12 H, NMe2); 4.33 (s, 2 H, CH2); 4.52
(s, 2 H, CH2); 4.96 (t, 1 H, γꢀH, J = 12.4 MHz); 5.12 (t, 1 H,
γ´ꢀH, J = 12.4 MHz); 6.76 (d, 2 H, δꢀH and δ´ꢀH, J = 12.4 MHz);
7.40 (d, 1 H, βꢀH, J = 12.4 MHz); 7.43 (d, 1 H, β´ꢀH,
J = 12.4 MHz). 13C NMR (CDCl3), δ: 21.53 (NCOCH3); 39.5
(NMe2); 41.97 (CH2); 46.15 (CH2); 93.11 (γꢀC); 94.5 (γ´ꢀC);
119.10 (αꢀC); 137.52 (βꢀC); 138.93 (β´ꢀC); 151.77 (δꢀC); 168.91
(NCOCH3); 183.61 (CO). MS (ESI), m/z: [M + H]+, found
304.2021, calculated 304.2031, C17H25N3O2.
1ꢀBenzylꢀ3,5ꢀbis(3ꢀdimethylaminopropꢀ2ꢀenylidene)ꢀ4ꢀpipeꢀ
ridone (3b). Aminal 1 (1.37 g, 8 mmol) was added dropwise to
1ꢀbenzylꢀ4ꢀpiperidone 2b (0.76 g, 4 mmol). The reaction mixꢀ
ture was heated with stirring at 65—70 °C for 1.5 h. The crystalꢀ
line reaction mixture was diluted with anhydrous diethyl ether
(10 mL), the bright orange precipitate was filtered, and washed
with diethyl ether. The yield of compound 3b was 1.05 g (75%),
m.p. 198—201 °C. Found (%): C, 74.68; H, 8.32; N, 11.97.
C22H29N3O. Calculated (%): C, 75.18; H, 8.32; N, 11.96. UV,
NCOCH3); 3.00 (s, 12 H, NMe2); 4.28 (s, 2 H, CH2); 4.31
(s, 2 H, CH2); 5.25 (t, 1 H, γꢀH, J = 12.5 Hz); 5.38 (t, 1 H, γ´ꢀH,
J = 12.5 Hz); 7.23 (d, 2 H, δꢀH and δ´ꢀH, J = 12.5 Hz); 7.32
(d, 2 H, βꢀH and β´ꢀH, J = 12.5 Hz).
1ꢀBenzylꢀ3,5ꢀbis(3ꢀdimethylaminopropꢀ2ꢀenylidene)ꢀ4ꢀoxoꢀ
piperidinium tetrafluoroborate (7b). To a stirred mixture of ketoꢀ
cyanine 3b (0.06 g, 0.17 mmol) in CH2Cl2 (1.5 mL) cooled to
–5—0 °C, a solution of Et2O•HBF4 (0.03 g, 0.17 mmol) in
CH2Cl2 (1 mL) was added dropwise. After 30 min, the solvent
was removed in vacuo, the residue was triturated with diethyl
ether, the precipitate that formed was filtered, and washed with
anhydrous diethyl ether. The yield of tetrafluoroborate 7b was
0.055 g (75%), black crystals, m.p. >240 °C. Found (%): C, 59.80;
H. 6.62; N, 9.35. C22H30BF4N3O. Calculated (%): C, 60.15;
H, 6.88; N, 9.57. UV (CHCl3), λmax/nm (ε): 480 (54468). 1H NMR
(DMSOꢀd6), δ: 2.90 (br.s, 12 H, NMe2); 3.90 (br.s, 4 H, CH2);
4.20 (s, 2 H, CH2Ph); 4.85 (t, 2 H, γꢀH and γ´ꢀH, J = 12.5 Hz);
7.15 (d, 2 H, δꢀH and δ´ꢀH, J = 12.5 Hz); 7.38 (d, 2 H, βꢀH and
β´ꢀH, J = 12.5 Hz); 7.45 (br.s, 5 H, Ph).
1ꢀAcetylꢀ3ꢀ(3ꢀdimethylaminopropꢀ2ꢀenylidene)ꢀ5ꢀ(3ꢀdimethylꢀ
iminiopropꢀ1ꢀenyl)ꢀ4ꢀhydroxyꢀ1,2,3,6ꢀtetrahydropyridimium bisꢀ
tetrafluoroborate (8a). A. To a mixture of compound 7a (0.071 g,
0.18 mmol) in anhydrous CH2Cl2 (1.5 mL) cooled to –5 °C,
a solution of Et2O•HBF4 (0.03 g, 0.17 mmol) in CH2Cl2 (1 mL)
was added dropwise. The reaction mixture was kept for 30 min
and the solvent was removed in vacuo, the residue was washed
several times with anhydrous diethyl ether. The yield of comꢀ
pound 8a was 0.075 g (86%), black crystals, m.p. 168—170 °C.
UV, λmax/nm (ε): 620 (89619) (CH2Cl2); 620 (CHCl3). 1H NMR
(DMSOꢀd6), δ: 2.10 (s, 3 H, NCOMe); 3.15 (br.s, 12 H, NMe2);
4.25 (br.s, 4 H, CH2); 5.61 (t, 1 H, γꢀH, J = 12.5 Hz); 5.75 (t, 1 H,
γ´ꢀH, J = 12.5 Hz); 7.50—7.65 (m, 4 H, βꢀH, β´ꢀH, δꢀH,
and δ´ꢀH).
B. To a mixture of ketocyanine 3a (0.10 g, 0.33 mmol) in
CH2Cl2 (3 mL) cooled to –5—0 °C, a solution of Et2O•HBF4
(0.12 g, 0.68 mmol) in CH2Cl2 (2 mL) was added dropwise. The
reaction mixture was stirred at –5—0 °C for 1 h and the solvent
was removed in vacuo. Anhydrous diethyl ether was added to the
residue, the precipitate that formed was filtered and washed with
anhydrous diethyl ether. The yield of compound 8a was 0.11 g
(73%), the product was identical to the one described above.
1ꢀBenzylꢀ3ꢀ(3ꢀdimethylaminopropꢀ2ꢀenylidene)ꢀ5ꢀ(3ꢀdiꢀ
methyliminiopropꢀ1ꢀenyl)ꢀ4ꢀhydroxyꢀ1,2,3,6ꢀtetrahydropyridiniꢀ
um bisꢀtetrafluoroborate (8b). A. To a mixture of tetrafluoroꢀ
borate 7b (0.028 g, 0.06 mmol) in CH2Cl2 (1 mL) cooled to
–5—0 °C, a solution of Et2O•HBF4 (0.012 g, 0.07 mmol) in
CH2Cl2 (0.5 mL) was added dropwise with stirring. In the reacꢀ
tion mixture, the precipitate immediately formed. The UV specꢀ
trum of the precipitate in CHCl3 showed absorption maximum
at 600 nm, no absorption for the starting tetrafluoroborate 7b
λ
max/nm (ε): 495 (68200) (EtOH), 475 (66200) (CHCl3).
1H NMR (CDCl3), δ: 2.89 (s, 12 H, NMe2); 3.51 (s, 4 H, CH2);
3.71 (s, 2 H, NCH2Ph); 4.86 (t, 2 H, γꢀH, J = 12.4 Hz); 6.69
(d, 2 H, δꢀH, J = 12.6 Hz); 7.24—7.37 (m, 5 H, Ph); 7.43(d, 2 H,
βꢀH, J = 12.4 Hz). 13C NMR (CDCl3), δ: 40.61 (NMe2); 52.97
(CH2); 60.99 (NCH2Ph); 94.32 (γꢀC); 120.88 (αꢀC); 126.81
(pꢀC, Ph); 128.26 (mꢀC, Ph); 129.21 (oꢀC, Ph); 137.64 (βꢀC);
138.94 (NCH2C); 150.81 (δꢀC); 184.41 (CO). MS (EI), m/z:
351 [M]+.
[1ꢀAcetylꢀ3,5ꢀbis(3ꢀdimethylaminopropꢀ2ꢀenylidene)piperꢀ
idinꢀ4ꢀylidene]malononitrile (4a). A mixture of compound 6a
(0.4 g, 2.1 mmol) and ion liquid [bmim]BF4 (1.2 g, 5.3 mmol)
was extensively stirred until fine dispersion was formed. Then
3ꢀdimethylaminoꢀ1,1,3ꢀtrimethoxypropane 5 (0.94 g, 5.3 mmol)
was added and the reaction mixture was kept at 20—22 °C for
24 h, and the solvent was removed in vacuo. Water (30 mL) was
added to the residue, the precipitate that formed was filtered,
washed with water, diethyl ether, and dried. The yield of comꢀ
pound 4a was 0.1 g (20%), brawn crystals, m.p. >260 °C. UV,
λ
max/nm (ε): 570 (89500) (EtOH), 550 (67100) (CHCl3).
1H NMR (DMSOꢀd6), δ: 2.05 (s, 3 H, NCOCH3); 3.05 (s, 12 H,
NMe2); 4.06 (d, 4 H, CH2, J = 12.4 Hz); 5.38 (t, 1 H, γꢀH,
J = 12 Hz); 5.57 (t, 1 H, γ´ꢀH, J = 12 Hz); 7.35 (d, 4 H, βꢀH and
δꢀH, J = 12.4 Hz). MS (ESI), m/z: [M + H]+, found 352.2125,
calculated: 352.2143, C20H25N5O.
1ꢀAcetylꢀ3,5ꢀbis(3ꢀdimethylaminopropꢀ2ꢀenylidene)ꢀ4ꢀoxoꢀ
piperidinium tetrafluoroborate (7a). To a mixture of ketocyanine
3a (0.1 g, 0.33 mmol) in CH2Cl2 (3 mL) cooled to –5 °C,
a solution of Et2O•HBF4 (0.06 g, 0.34 mmol) in CH2Cl2 (1 mL)
was added dropwise. The reaction mixture was stirred at –5 °C
for 1 h and the solvent was removed in vacuo. Anhydrous diethyl
ether was added to the crystalline residue, the precipitate was
filtered and thoroughly washed with anhydrous diethyl ether.
The yield of tetrafluoroborate 7a was 0.085 g (66%), black crysꢀ
(λ
= 470 nm) was detected. After 15 min, the solution was
max
decanted, the precipitate was successfully washed with anhydrous
diethyl ether. The yield of bisꢀtetrafluoroborate 8b was 0.015 g
(45%), black crystals, m.p. 120—124 °C (decomp.) UV (CHCl3),
1
λ
max/nm (ε): 600 (28745). H NMR (DMSOꢀd6), δ: 3.10 (br.s,
6 H, NMe2); 3.20 (br.s, 6 H, Me2N+); 3.90 (br.s, 2 H, CH2);
4.15 (br.s, 2 H, CH2); 4.35 (s, 2 H, CH2Ph); 5.45 (t, 2 H, γꢀH

ω,ω´ꢀBisdimethylamino ketones and dinitriles
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 10, October, 2011
2019
and γ´ꢀH, J = 12.5 Hz); 7.47 (br.s, 5 H, Ph), 7.60—7.80 (m, 4 H,
βꢀH, β´ꢀH, δꢀH, δ´ꢀH); 10.35 (br.s, 1 H, OH).
C24H35N3O5S. Calculated (%): C, 60.35; H, 7.39; N, 8.80. UV
(CHCl3), λmax/nm (ε): 485 (75202). 1H NMR (DMSOꢀd6), δ:
2.95 (br.s, 12 H, NMe2); 3.35 (s, 3 H, MeN+); 3.40 (s, 3 H,
MeSO4); 4.30 (s, 4 H, CH2); 4.45 (s, 2 H, CH2Ph); 5.05 (t, 2 H,
γꢀH and γ´ꢀH, J = 12.5 Hz); 7.25—7.40 (m, 4 H, βꢀH, β´ꢀH,
δꢀH, δ´ꢀH); 7.45—7.60 (m, 5 H, Ph).
B. To a mixture of ketocyanine 3b (0.12 g, 0.34 mmol) in
CH2Cl2 (3 mL) cooled to –5—0 °C, a solution of Et2O•HBF4
(0.12 g, 0.75 mmol) in CH2Cl2 (1 mL) was added dropwise with
stirring. The color of the reaction mixture immediately turned
blue. In the UV spectra of the reaction mixture, new absorption
band with maximum at 600 nm appeared, while absorption band
with maximum at 470 nm disappeared. After 30 min, the soluꢀ
tion was decanted, the precipitate that formed was successfully
washed with anhydrous diethyl ether. The yield of bisꢀtetrafluoꢀ
roborate 8b was 0.14 g (77%), m.p. 124—127 °C (decomp.). The
UV and 1H NMR spectra of the sample are identical to the
described above.
1ꢀBenzylꢀ3ꢀ(3ꢀdimethylaminopropꢀ2ꢀenylidene)ꢀ5ꢀ(3ꢀdiꢀ
methyliminiopropꢀ1ꢀenyl)ꢀ4ꢀmethoxyꢀ1ꢀmethylꢀ1,2,3,6ꢀtetraꢀ
hydropyridinium bisꢀmethoxysulfonate (11). To compound 10
(0.15 g, 0.31 mmol), Me2SO4 (0.24 g, 1.9 mmol) was added and
the reaction mixture was heated at 50—55 °C; the course of the
reaction was monitored with UV spectroscopy. After 1.5 h, no
absorption with maximum at 485 nm attributed to methyl sulfate 10
was detected, the observed band with maximum at 640 nm
was ascribed to compound 11. The reaction mixture was cooled
to ambient temperature and triturated with anhydrous diethyl
ether, the precipitate that formed was filtered, and washed
with anhydrous diethyl ether. The yield of compound 11 was
0.14 g (75%), black crystals, m.p. >240 °C. Found (%): C, 51.32;
H, 6.58; N, 6.65. C26H41N3O9S2. Calculated (%): C, 51.72; H, 6.84;
N, 6.96. UV (CHCl3), λmax/nm (ε): 640 (110550). 1H NMR
(DMSOꢀd6), δ: 3.12 (s, 6 H, NMe2); 3.35 (s, 6 H, Me2N+); 3.4
(s, the signal of the methyl group of anion MeSO4– overlaps with
the signal of the protons of H2O in DMSOꢀd6); 3.90 (s, 3 H,
OMe); 4.32 (s, 4 H, CH2); 4.50 (s, 2 H, CH2Ph); 5.85 (t, 2 H,
γꢀH and γ´ꢀH, J = 12.5 Hz); 7.40—7.50 (m, 5 H, Ph); 7.62 (d, 2 H,
βꢀH and β´ꢀH, J = 12.5 Hz); 8.08 (d, 2 H, δꢀH and δ´ꢀH,
J = 12.5 Hz).
2ꢀ(4ꢀ{3ꢀ[1ꢀAcetylꢀ4ꢀmethoxyꢀ4ꢀ(3ꢀethylbezothiazolinꢀ2ꢀ
ylidene)butꢀ2ꢀenꢀ1ꢀylidene]ꢀ1,2,3,6ꢀtetrahydropyridinꢀ5ꢀyl}ꢀ
butaꢀ1,3ꢀdienꢀ1ꢀyl)ꢀ3ꢀethylbenzothiazolium tosylate (14). Comꢀ
pounds 9 (0.10 g, 0.23 mmol) and 13 (0.32 g, 0.93 mmol) were
carefully grinded and mixed with Ac2O (4 mL). To the obtained
mixture, a solution of 1 M Et3N (1.6 mL) in Ac2O was added
dropwise at room temperature with stirring. Soon the bright blue
color of the reaction mixture turned green brownish. After 2 h,
diethyl ether (20 mL) was added, the reaction mixture was trituꢀ
rated, and after another 30 min the precipitate that formed was
filtered, washed with diethyl ether, small portion of cold water
and again with diethyl ether. The yield of dye 14 was 0.08 g
(49%), black crystals, m.p. 143—145 °C. UV (CH2Cl2), λmax/nm
(ε): 1002 (217500), 894 (81743). 1H NMR (DMSOꢀd6), δ: 1.32
(t, 6 H, CH3CH2N); 2.14 (s, 3 H, NCOMe; 2.26 (s, 3 H, Me,
TsO–); 3.78 (s, 3 H, OCH3); 4.25—4.45 (m, 8 H, CH3CH2N
and NCH2, cycl.); 6.56 (t, 2 H, βꢀH, J = 13 Hz); 6.82 (d, 2 H,
δꢀH, J = 13 Hz); 7.10 (d, 2 H, H(4″), J = 7.5 Hz); 7.16—7.70
(m, 10 H, γꢀH, αꢀH, H(5´), H(6´), H(3″)); 7.89 (d, 2 H, H(7´),
J = 7.7 Hz); 7.98 (d, 2 H, H(4´), J = 7.8 Hz).
Nꢀ{1ꢀAcetylꢀ3ꢀ[3ꢀ(3ꢀdimethylaminopropꢀ2ꢀenylidene)ꢀ4ꢀ
methoxyꢀ1,2,3,6ꢀtetrahydropyridinꢀ5ꢀyl]propꢀ2ꢀenylidene}ꢀN,Nꢀ
dimethylammonium methoxysulfonate (9). A. To a solution of
ketocyanine 3a (0.3 g, 1 mmol) in CH2Cl2 (4.5 mL), a solution
of Me2SO4 (0.36 g, 2.86 mmol) in CH2Cl2 (2.5 mL) was added
dropwise. The reaction mixture was refluxed with stirring for
8 h, then the solvent was removed in vacuo. The residue was
triturated with anhydrous diethyl ether, the precipitate that
formed was filtered, and washed with diethyl ether. The yield of
compound 9 was 26 g (62%), black powder, m.p. 168—170 °C.
Found (%): C, 53.34; H, 7.15; N, 9.52. C19H31N3O6S. Calculatꢀ
ed (%): C, 53.13; H, 7.27; N, 9.78. UV, λmax/nm (ε): 640 (103350)
(EtOH); 640 (70928) (CHCl3). 1H NMR (DMSOꢀd6), δ: 2.05
(s, 3 H, NCOMe); 3.20 (br.s, 12 H, NMe2, Me2N+); 3.78 (s, 3 H,
OMe); 4.30 (br.s, 4 H, CH2); 5.75 (t, 1 H, γꢀH, J = 12.5 Hz);
5.88 (t, 1 H, γ´ꢀH, J = 12.5 Hz); 7.40 (m, 2 H, βꢀH and β´ꢀH);
7.85 (m, 2 H, δꢀH and δ´ꢀH); 3.40 (the signal of the methyl
–
group of anion MeSO4 overlaps with the signal of the protons
of H2O in DMSOꢀd6).
B. To a solution of ketocyanine 3a (0.1 g, 0.33 mmol) in
CH2Cl2 (1.5 mL), a solution of Me2SO4 (0.04 g, 0.33 mmol) in
CH2Cl2 (1 mL) was added dropwise with stirring. The reaction
mixture was stirred at 20—25 °C monitoring the reaction course
with UV spectroscopy. After 3.5 h, the main absorption band was
the band with maximum at 470 nm, but the bans of low intensiꢀ
ty at 640 nm was also observed. The aliquot of the reaction
mixture was taken, the solvent was removed in vacuo, the preciꢀ
pitate that formed was washed with anhydrous diethyl ether, and
1
dried. The H NMR spectrum of this precipitate was similar to
that of the starting ketocyanine 3a and contained signals of low
intensity attributed to methyl sulfate 9. The reaction mixture was
then stirred for 3 days until the band with the maximum at 470 nm
disappeared in the UV spectra; the intensity of the band with
maximum at 640 nm increased. Methyl sulfate 9 was separated
as described above.
1ꢀBenzylꢀ3,5ꢀbis(3ꢀdimethylaminopropꢀ2ꢀenylidene)ꢀ1ꢀmeꢀ
thylꢀ4ꢀoxopiperidinium methoxysulfonate (10). To a mixture of ketoꢀ
cyanine 3b (0.15 g, 0.44 mmol) in CH2Cl2 (1 mL), a solution of
Me2SO4 (0.056 g, 0.44 mmol) in CH2Cl2 (0.5 mL) was added
dropwise at 20 °C. The reaction mixture turned dark, the absorpꢀ
tion band shifted to longer wavelengths by 10 nm as compared
with that of starting ketocyanine 3b. (The UV spectra became
symmetrical in contrast to the spectra of starting ketocyanine 3b
with the shoulder). After 20 min, the solvent was removed
in vacuo, the residue was triturated with anhydrous diethyl ether.
The yield of compound 10 was 0.16 g (77%), dark violet crystals,
m.p. 120—122 °C. Found (%): C, 60.05; H, 7.21; N, 8.52.
2ꢀ(4ꢀ{1ꢀBenzylꢀ4ꢀmethoxyꢀ1ꢀmethylꢀ3ꢀ[4ꢀ(3ꢀethylbenzoꢀ
thiazolinꢀ2ꢀylidene)butꢀ2ꢀenꢀ1ꢀylidene]ꢀ1,2,3,6ꢀtetrahydropyriꢀ
dinꢀ1ꢀiumꢀ5ꢀyl}butaꢀ1,3ꢀdienꢀ1ꢀyl)ꢀ3ꢀethylbenzothiazolium bisꢀ
tosylate (15). Compounds 11 (0.10 g, 0.17 mmol) and 13 (0.24 g,
0.68 mmol) were carefully grinded and mixed with Ac2O (4 mL).
To the obtained mixture, a solution of 1 M Et3N (1.2 mL) in
Ac2O was added dropwise with stirring. The color of the reaction
mixture immediately changed, in the UV spectra, the absorption
band with maximum at 640 nm disappeared. After 1 h, diethyl
ether (15 mL) was added, the reaction mixture was triturated,
the precipitate that formed was filtered, and successfully washed
with diethyl ether. The yield of dye 15 was 0.06 g (41%), black
crystals, m.p. 224—226 °C. Found (%): C, 65.21; H, 5.56;

2020
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 10, October, 2011
Krasnaya et al.
N, 3.95. C54H57N3O7S4. Calculated (%): C, 65.63; H, 5.81;
N, 4.25. UV (CH2Cl2), λmax/nm (ε): 964 (237703), 856 (124869).
1H NMR (DMSOꢀd6), δ: 1.32 (t, 6 H, CH3CH2N); 2.25 (s, 6 H,
CH3, TsO–); 3.10 (s, 3 H, MeN+); 3.90 (s, 3 H, OCH3); 4.40
(m, 8 H, CH3CH2N and NCH2, cycl.); 4.65 (s, 2 H, CH2Ph);
6.40 (t, 2 H, βꢀH, J = 13.5 Hz); 6.65 (d, 2 H, δꢀH, J = 13.5 Hz);
7.10 (d, 4 H, H(4″), J = 7.5 Hz); 7.40—7.60 (m, 17 H, Ph, γꢀH,
αꢀH, H(5´), H(6´), H(3″)); 7.75 (d, 2 H, H(7´), J = 8.1 Hz);
8.00 (d, 2 H, H(4´), J = 7.8 Hz).
3. Zh. A. Krasnaya, E. O. Tret´yakova, V. V. Kachala, S. G.
Zlotin, Izv. Akad. Nauk, Ser. Khim., 2010, 796 [Russ. Chem.
Bull., Int. Ed., 2010, 59, 812].
4. (a) Zh. A. Krasnaya, T. S. Stytsenko, Izv. Akad. Nauk SSSR,
Ser. Khim., 1983, 850 [Bull. Acad. Sci. USSR, Div. Chem. Sci.
(Engl. Transl.), 1983, 32, 776]; (b) Zh. A. Krasnaya, T. S.
Stytsenko, Izv. Akad. Nauk SSSR, Ser. Khim., 1983, 855
[Bull. Acad. Sci. USSR, Div. Chem. Sci. (Engl. Transl.), 1983,
32, 780].
5. Zh. A. Krasnaya, T. S. Stytsenko, E. P. Prokof´ev, V. F.
Kucherov, Izv. Akad. Nauk SSSR, Ser. Khim., 1973, 2008 [Bull.
Acad. Sci. USSR, Div. Chem. Sci. (Engl. Transl.), 1973,
22, 1959].
This work was financially supported by the Russian
Foundation for Basic Research (project No. 10ꢀ03ꢀ00647ꢀa).
6. G. Dörnyei, M. Incze, I. Moldvai, C. Szántay, Synth. Comꢀ
mun., 2003, 33, 2329.
References
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Tret´yakova, V. V. Kachala, S. G. Zlotin, Izv. Akad. Nauk,
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2. Zh. A. Krasnaya, A. S. Tatikolov, Izv. Akad. Nauk, Ser. Khim.,
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Received November 11, 2010;
in revised form March 3, 2011