Synthesis and optical characterization of new ketocyanine dyes with extended polymethine chaines

Article abstract of DOI:10.1002/jhet.4027

New symmetrical and unsymmetrical near-infrared absorbing ketocyanine-type dyes are synthesized and their optical characterization is done. The relationships between their structure and optical properties are discussed. The synthesized ketocyanine dyes show a positive solvatochromism and are poorly fluorescent. A new procedure for the preparation of N,N,N′,N′-tetramethylvinamidinium perchlorate, which was a very useful reagent for the synthesis of various heterocyclic compounds as well as for the preparation of cyanine dyes is developed.

Full text of DOI:10.1002/jhet.4027

Received: 2 April 2020
DOI: 10.1002/jhet.4027
Revised: 8 May 2020
Accepted: 9 May 2020
A R T I C L E
Synthesis and optical characterization of new ketocyanine
dyes with extended polymethine chaines
Sergey Miltsov1
| Julian Alonso-Chamarro2 | Mar Puyol2
1Institute of Macromolecular Compounds,
Russian Academy of Sciences, St.
Petersburg, Russia
2Grup de Sensors i Biosensors, Unitat de
Quimica Analítica, Facultat de Ciències,
Universitat Autònoma de Barcelona,
Bellaterra, Spain
Abstract
New symmetrical and unsymmetrical near-infrared absorbing ketocyanine-type
dyes are synthesized and their optical characterization is done. The relationships
between their structure and optical properties are discussed. The synthesized
ketocyanine dyes show a positive solvatochromism and are poorly fluorescent. A
new procedure for the preparation of N,N,N0,N0-tetramethylvinamidinium per-
chlorate, which was a very useful reagent for the synthesis of various heterocy-
clic compounds as well as for the preparation of cyanine dyes is developed.
Correspondence
Sergey Miltsov, Institute of
Macromolecular Compounds, Russian
Academy of Sciences, Bol'shoi pr. 31, St.
Petersburg 199004, Russia.
Email: smiltsov2004@mail.ru
Funding information
Generalitat de Catalunya, Grant/Award
Number: 2014SGR837; Ministerio de
Economía y Competitividad, Grant/Award
Number: CTQ2012-36165; Ministry of
Education and Science of the Russian
Federation, Grant/Award Number:
АААА-А16-116071450048-3
1 | INTRODUCTION
Later on ketocyanines found a wide scope of applica-
tion such as reporters of biochemical reactions involving
Cyanine dyes are excellent candidates for use as signaling
recognition molecules of biological processes in bioassays
or as labels, because of their structural variability and
because their active absorption and emission wavelengths
can be easily shifted depending on their structure. Many
biological processes are accompanied by the pH-changes
thus the long-wave absorbing acidochromic dyes are of
special interest as reporters in analytical devices.
Ketocyanines, first described in the works of Patonay,[1–3]
appeared one of the most promising dyes for these applica-
tions due to high molar absoptivities (>105 L mol−1 cm−1)
of their protonated forms lying in NIR-region of the visible
spectra (700-750 nm). It was also shown that the neutral
forms of ketocyanines are strongly fluorescent.[4] The
acid–base equilibrium of ketocyanine dyes is depicted on
Scheme 1.
a pH variation reaction,[5,6] a change in the matrix polar-
ity[7] or just as labels[8,9] with also proved enhanced prop-
erties when used in combination with nanomaterials.[10]
They also were successively employed as probes or bio-
markers to follow biomedical processes as their cyanine
counterparts by locating some specific molecules or ions
and transduce the biochemical processes into optical
signals.[11–15] Owing to their significant fluorescence
ketocyanines can find promising applications in fluores-
cence microscopy[16] and, especially, in newly developed
MINFLUX nanoscopywhich opens new perspectives for
imaging of biological objects with highly increased reso-
lution and does not require extremally strong fluores-
cence of the labels.[17,18]
In course of our research regarding the preparation of
NIR-absorbing acidochromic cyanine dyes we developed
J Heterocyclic Chem. 2020;1–9.
wileyonlinelibrary.com/journal/jhet
© 2020 Wiley Periodicals LLC.
1

2
MILTSOV ET AL.
SCHEME 1 Acid–base
equilibrium for ketocyanines
R1
R2
Z1
I
Z2
I
N
Et
N
Et
R1
R2
O
Z1
O
Z2
2'
2
Me2N
NMe2
N
N
pyridine
Et
Et
3
1
SCHEME 2 Synthesis of ketocyanines 3.[16] Reagents and conditions: 1 (1 mmol) and 2 (1 mmol) in pyridine (10 mL) 1 hour reflux; 20
(1 mmol) 1 hour reflux
a general method for synthesis of ketocyanines 3,[4,19]
which were further successfully used for the construction
of optical sensors (Scheme 2).[20,21]
This work was aimed on preparation of the vin-
ylogues of ketocyanines 3 in order to obtain the new pH-
sensitive chromophores with strong absorptivities shifted
to the longer-wave region relative to parent dyes.
vinamidinium salt 11 from piperidine and compound 10
in similar conditions (Scheme 5),[34] but the attempt to
prepare the salt 4 following directly the same procedure
failed.
Using dimethylamine as 4M methanolic solution and
acetal 10 we made a series of experiments with different
relations of amine to acid and found that when we
used 1.4 equiv of perchloric acid (57%) the product
4 (X = ClO4−) crystallizes directly from the reaction mix-
ture. After the optimization of procedure we formulated
a very simple protocol yielding 62%-65% of salt 4 of high
purity. Upon controlled heating the product melted at
120ꢀC-122ꢀC and decomposed with flash only above
200ꢀC thus demonstrating sufficient safety for wide use
in organic synthesis. The salt 4 can be converted into the
piperidine and pyrrolidine analogs (11 and 12) in practi-
cally quantitative yield by 4-hour boiling in methanol
with corresponding amines (Scheme 6).
Subsequently the required intermediates 5a,b were
successfully obtained from cyclic ketones, 2 equiv of
vinamidinium salt 4 and 4 equiv of sodium methylate
on boiling in methanol–pyridine mixture for 6 hours in
satisfactory yields (5a—71%, 5b—54%). In the same
way unsymmetrical precursor 7 was prepared from
2-dimethylaminomethylenecyclopentanone 6 and 1 equiv
of vinamidinium salt 4 in 63% yield (Scheme 2). It would
be noted that 5a and 5b were synthesized earlier from
ketones and 1,1,3-trimethoxy-3-dimethylaminopropane
even with greater yields (5a— 85%, 5b—87%[35,36]),
but the latter reagent was prepared again from
dimethylaminoacrolein 8[37] by laborious procedure that
made our protocol more attractive.
2 | RESULTS AND DISCUSSION
2.1 | Synthesis of the dyes
In order to synthesize the target ketocyanines with
extended polymethine chains we planned to prepare the
vinylogues of the bis-enaminoketone 1 (compounds 5a,
5b, and 7) like it is shown on the Scheme 3 and then
involve them in condensation with heterocyclic salts just
similarly for synthesis of the dyes 3[19] (Scheme 2).
N,N,N0,N0-Tetramethylvinamidinium salt 4 proved to
be a versatile reagent in the synthesis of various heterocy-
clic compounds, such as pyridines,[22–24] pyrimidines,[25,26]
and pyrroles.[27,28] The main advantages of 4 over its ana-
logs, substituted with other alkyl or aryl groups, are the
minimal steric hindrance of the reaction site for the nucle-
ophilic addition and the ease of the removal of liberating
dimethylamine, that simplifies the separation of target
product, but the use of this very attractive reagent is
greatly limited by the absence of good procedures for its
preparation. The existing approaches require utilization of
hardly available and expensive dimethylaminoa
crolein[29,30] 8 or reduction of 2-chlorosubstituted precur-
sor 9, which is prepared by laborious Vilsmeier-Haak
formylation of chloroacetic acid[31,32] (Scheme 4).
Finally from precursors 5a,b and 7 and corresponding
indoleninium salts 2а and 2b, following our usual proce-
dure[4,19] we obtained target ketocyanines 13a-d and 14
in moderate yields (Scheme 7). Yields of the products as
well as all the data on their spectral and propolytic prop-
erties are listed in Table 1.
It is well known that N,N0-diarylvinamidinium salts
can be easily produced from 1,1,3,3-tetramethoxypropane
10 and aromatic amines in presence of perchloric acid.[33]
Moreover it appeared possible to obtain perchlorate of

MILTSOV ET AL.
3
X
X
O
Me2N
O
O
NMe2
O
Me2N
NMe2
4
4
Me2N
NMe2
Me2N
NMe2
Me2N
n
n
7
6
a - n = 0
b - n = 1
5a,b
SCHEME 3 Proposed scheme for the synthesis of enaminoketones 5a,b and 7
O
SCHEME 4 Preparation
of N,N,N0,
VH
N0-tetramethylvinamidinium
salt 4[29–32]
Cl
O
X
X
HI
Me2NH HCl
VH
Me2N
Me2N
NMe2
Cl
Me2N
O
NMe2
8
OH
9
4
Me2NH
O
properties. Thus pKa-meanings of the dyes 3a, 14, and
13a bearing two, three, and four vinylene groups are 3.0,
2.9, and 3.0 respectively.
N
H
OMe OMe
ClO4
Fluorescence of dyes in 10−5 M ethanolic solution
was tested for both acidic and basic forms. First, none of
the dyes at the acidic form (solution at pH 2) showed any
fluorescence in this form and in this medium, as well as
the previously examined shorter-chain ketocyanines 3.[20]
In case for the basic forms (solution at pH 7.5) only week
emission bonds (Φ < 0.07) were observed on the contrary
to the behavior of shorter-chain analogs which demon-
strated significant fluorescence (Φ > 0.2).[20] Results are
presented in Table 2.
N
N
MeO
OMe
HClO4
11
10
SCHEME 5 Preparation of N,N,N0,N0-
dipentamethylenevinamidinium salt 11.[34] Reagents and
conditions: 10 (85 mmol), 57% HClO4 (18 mL), and piperidine
(170 mmol), 2 hours, rt
2.2 | Spectral properties and acid-base
behavior of ketocyanines
As it was expected the absorbance maxima of the dyes
13a-d and 14 were shifted to the long-wave region as
compared with the unsubstituted indoketocyanine 3a
(Z = C(CH3)3, R1 = R2 = H) (λmax(base) = 566 nm, λmax
2.3 | Solvent effects on the absorption
spectra of ketocyanine dyes
The absorption maxima of the basic form in toluene,
dichloromethane (CH2Cl2), acetonitrile (CH3CN),
dimethylsulfoxide (DMSO), and ethanol (EtOH) are listed
in Table 3. The absorbance of the maximum wavelength
shifts to the red as the polarity of the solvent increases.
This means that the studied ketocyanine dyes present a
positive solvatochromism, as well as shorter-chain
ones.[4]
A plot of the absorbance for all the ketocyanine dyes
as a function of the Dimroth-Reichart empirical solvent
parameter ET(30)[38] is shown in Figure 2. There is a
wide range of linear correlation for the absorbance in tol-
uene, dichloromethane, dimethylsulfoxide, acetonitrile,
and ethanol. For all dyes, acetonitrile is found to exhibit
negative deviations from the common trend like it
was observed for earlier examined shorter-chained
ketocyanines.[4] This suggests that the nature of the inter-
action of the dyes with acetonitrile is somewhat different
= 717 nm), reported earlier.[1,2] The bathochromic
(acid)
shifts caused by introduction of additional vinylene frag-
ment in the structure of the dye 3a are considerably
greater for the protonated form of ketocyanine 14
(94 nm) than for the neutral form (13 nm). Quite the
same is observed on comparison of dyes 14 and 13a also
differing by additional vinylene group. In this case the
difference in absorbance maxima are 92 nm for proton-
ated forms and 37 nm for neutral ones.
All newly synthesized ketocyanine dyes exhibit a
reproducible response in the pH range, where the absor-
bance changes take place. An illustrative example of the
pH-dependence of absorption spectra for dye 14 in etha-
nol is presented in Figure 1. The clear isosbestic points
have been observed as the solution pH has been changed
forth and back. It is obvious that the introduction of addi-
tional vinylenes does not influence their protolytic

4
MILTSOV ET AL.
n
SCHEME 6 Synthesis of
vinamidinium salt 4 and its analogs 11 and
12. Reagents and conditions: (i) 10
N
H
Me2NH
ClO4
OMe OMe
OMe
ClO4
n
n
(17.6 mmol), 57% HClO4 (3.1 mL), and 4 M
Me2NH in MeOH (10 mL), 2d, rt; (ii) 4
(5 mmol), piperidine or pyrrolidine
Me2N
NMe2
N
N
MeO
HClO4
i
ii
4
10
11 (n = 0) 93%
12 (n = 1) 95%
62-65%
(11 mmol) in MeOH (5 mL), 4 hours reflux
R2
R1
N
R2
R2
O
I
2a,b
Et
R1
R1
O
Me2N
NMe2
pyridine
N
N
n
Et
Et
5a,b
n
13a-d
N
O
O
I
2a
Et
Me2N
NMe2
N
N
pyridine
Et
Et
7
14
SCHEME 7 Synthesis of ketocyanine dyes 13a-d and 14. Reagents and conditions: 2a or 2b (2 mmol) and 5a, 5b, or 7 (1 mmol) in
pyridine (10 mL) 2 hours reflux
TABLE 1
Spectral and protolytic properties and yields of ketocyanines
R2
R2
O
R1
R1
O
Me2N
NMe2
N
Et
N
n
Et
5a,b
n
5a - n=0; 5b - n=1
13a-d
13a - n=0, R1= R2= H; 13b - n=0, R1+ R2= -(CH=CH)2-
13c - n=1, R1= R2= H; 13b - n=1, R1+ R2= -(CH=CH)2-
O
O
Me2N
NMe2
N
N
Et
Et
7
14
Dye
5a
n
R1
—
—
—
H
R2
—
—
—
H
λmax, nm (base)
503.5
ε, L mol−1 cm−1 (base)
3.12ꢁ104
λmax (acid)
604.5
ε (acid)
>7.0ꢁ104
>1.7ꢁ105
>1.0ꢁ105
1.00ꢁ105
7.21ꢁ104
1.14ꢁ105
8.08ꢁ104
7.10ꢁ104
pKa
Yield, %
a
0
—
71
54
63
32
43
36
48
44
a
5b
1
486.0
6.43ꢁ104
595.5
—
a
7
—
0
444.0
4.79ꢁ104
517.0
—
13a
13b
13c
13d
14
616.0
5.49ꢁ104
903.0
3.0
3.1
3.2
3.5
2.9
0
(СH СH)2
H
632.0
3.94ꢁ104
938.5
1
H
585.0
5.42ꢁ104
893.0
1
(СH СH)2
606.0
4.09ꢁ104
930.0
—
—
—
579.0
3.30ꢁ104
811.0
aUnstable in acidic media.

MILTSOV ET AL.
5
from that in the case of the ET(30) scale. It appears that
this solvent goes into a lower interaction with the dyes
than it is predicted by the polarity parameters.
The synthesized dyes present very similar regression
parameters which are reported in Table 4.
3 | CONCLUSIONS
To sum up, we have synthesized a set of ketocyanine dyes
whose protonated forms represented tetra- and pen-
tacarbocyanines, absorbing in IR region and examined
their spectral and acid–base properties. The synthesized
ketocyanines probably can be converted to meso-
chlorinated polymethine dyes capable to nucleophilic
substitution thus resulting a library of new functionalized
cyanines absorbing in infrared. We also developed a new
simple and effective procedure for preparation of vin-
amidinium perchlorate, which was a very useful reagent
in the synthesis of polymethine dyes and various hetero-
cyclic compounds.
4 | EXPERIMENTAL SECTION
All starting materials have been purchased form Aldrich
Chemical Co. MS-ES measurements have been made in a
1
Bruker micrOTOF. H and 13C NMR spectra have been
measured in a Bruker 400 Avance at 400.13 MHz and
100.6 МHz, respectively. Spectrophotometric studies were
performed in a UV-Vis-NIR Scanning Spectrophotometer
Shimadzu UV-3101PC and Shimadzu UV-1800. The
absorption spectra were recorded between 1100 and
400 nm. Fluorescence spectra were obtained using a
Fluorolog-3 Fluorometer (Horiba), recording the spectra
from 10 nm above its excitation wavelength to 800 nm,
and using a concentration in the order of 10−6 M of the
dye in ethanol. Fluorescence quantum yields (Φf) were
calculated relative to Rhodamine 6G (Sigma-Aldrich,
Φf = 0.95 0.01, λexc = 490 nm[39]) as Φf = Φf, st (F/Fst)
(Ast/A);[40] where Φf, st is the fluorescence quantum yield
of the standard, F the integrated area under the corrected
fluorescence emission profile (quanta units), and A the
absorbance intensity (always lower than 0.05). In the
expression, the subscript st is referred to the standard
compound.
FIGURE 1 Absorbance spectra of dye 14 in ethanol at the
indicated pH values
TABLE 2
Excitation wavelengths, emission wavelengths,
Stokes' shifts, and quantum yields of the studied ketocyanine dyes
in a 1·10−5 M ethanolic solution
Dye
5a
λex (nm)
495.0
480.5
433.0
600.0
600.0
584.0
600.0
574.5
λem (nm)
556.0
Δ λ (nm)
61.0
Φ
0.070
0.047
0.010
0.013
0.012
0.013
0.012
0.028
5b
542.5
62.0
7
494.0
61.0
13a
13b
13c
13d
14
752.0
152.0
160.0
159.0
162.0
126.5
760.0
743.0
762.0
Quaternary salts 1a,b were prepared by quater-
nization of corresponding heterocycles by ethyl iodide.
701.0
TABLE 3
Maximum absorbance wavelengths of the ketocyanine dyes in solvents with different polarities and ET(30) values
No.
13a
13b
13c
13d
14
Toluene (ET = 33.9)
CH2Cl2 (ET = 41.1)
DMSO (ET = 45.0)
CH3CN (ET = 46.0)
EtOH (ET = 51.9)
565
589
607
557
577
557
599.5
616
583
607
551
569
554
616
632
585
606
579
583
543
566.5
586
559.5
539.5
566

6
MILTSOV ET AL.
640
620
600
580
560
540
520
FIGURE 2 The maximum
absorbance wavelength of ketocyanine
dyes vs ET(30) solvent polarity values for
toluene, dichloromethane,
DMSO (45.0)
dimethylsulfoxide, acetonitrile, and
ethanol
EtOH (51.9)
13a
13b
13c
13d
14
CH2Cl2 (41.1)
CH3CN (46.0)
Toluene (33.9)
32
34
36
38
40
42
44
46
48
50
52
54
ET(30) (Kcal/mol)
TABLE 4
Parameters resulting of the regression analysis of
diluted with 25 mL of ether and kept at −20ꢀC for
3 hours. The resulting crystals were filtered, washed with
cold methanol and ether, and dried on air. Light-yellow
solid; m.p.: 120ꢀC-122ꢀC. Yield 2.55 g (62%); 1H NMR
(DMSO-d6): δ 3.08 (s, 6H), 3.26 (s, 6H), 5.43 (t,
J = 11.5 Hz, 1H), 7.73 (d, J = 11.5 Hz, 2H). 13C NMR
(DMSO-d6): δ 38.31, 46.11, 90.42, 163.26. The experiment
was repeated twice yielding 65% and 63% of 4. Scaling up
to 100 mmol of 10 furnished 12.4 g of 4 (54%).
λmax and ET(30) of the solvents (λmax = AET(30) + B)
No.
13a
13b
13c
13d
14
A
B
r
2.83
2.83
2.71
2.57
2.20
3.21
470.8
470.8
493.2
471.7
465.8
395.6
0.996
0.996
0.994
0.999
0.998
0.983
3a2
Note: Points for acetonitrile are not included.
5.1.2 | 3-(1-Pyrrolidinyl)-2-propenylidene]
pyrrolidinium perchlorate (11)
2-Dimethylaminomethylenecyclopentanone was obtained
from cyclopentanone and dimethylformamide dime-
thylacetal.[41]
Vinamidinium salt 4 (1.14 g, 5 mmol) and pyrrolidine
(780 mg, 11 mmol) were refluxed together in methanol
(5 mL) for 4 hours. Then the volatiles were removed in
vacuo and the residue was washed with ether. Yield of 11
1
5 | PROCEDURES
1.30 g (93%). H NMR (400 MHz, DMSO-d6): δ 1.86-1.95
(m, 4H), 1.95-2.06 (m, 4H), 3.42 (t, J = 7 Hz, 4H), 3.70 (t,
J = 7 Hz, 4H), 5.18 (t, J = 12 Hz, 1H), 7.91 (d, J = 12 Hz,
2H). 13C NMR (100 MHz, DMSO-d6): δ 24.82, 24.99,
48.49, 53.69, 92.24, 158.60.
5.1 | Preparation of vinamidinium salts
5.1.1 | N,N,N0,N0-
Tetramethylvinamidinium perchlorate (4)
Perchloric acid (0.5 mL, 57%, d = 1.47) was added to
1,1,3,3-tetramethoxypropane 10 (2.9 g, 0.176 mmol) and,
after staying at rt for 1.5 hours, more perchloric acid
(2.6 mL) was added and the resulting solution was added
dropwise to 4M solution of dimethylamine in methanol
(10 mL) at cooling, keeping t < 15ꢀC. The mixture was
kept at rt for 2 days (partial crystallization occurred),
5.1.3 | 3-(1-Piperidinyl)-2-propenylidene]
piperidinium perchlorate (12)
In the same way from 4, piperidine 12 was prepared.
Yield 1.46 g (95%). 1H NMR (400 MHz, DMSO-d6): δ
1.53-1.71 (m, 12H), 3.51-3.63 (m, 8H), 5.79 (t,
J = 11.5 Hz, 1H), 7.69 (d, J = 11.5 Hz, 2H). 13C NMR

MILTSOV ET AL.
7
(100 MHz, DMSO-d6): δ 23.51, 25.51, 26.81, 47.20, 55.99,
89.32, 161.58.
(CDCl3) δ (ppm): 24.20, 24.45, 40.57, 42.16, 95.73, 107.81,
128.30, 131.94, 146.00, 149.47, 193.02. ES-MS+ [M + H]+
221.1639 (cal. 221.1653 [M + H]+ for C13H21N2O). λmax
(EtOH) = 444.0 nm (ε 4.79·104 L mol−1 cm−1). λmax
(EtOH + HCl) = 517.0 nm.
5.2 | Preparation of enaminoketones
5.2.1 | bis-2,5-[3-(Dimethylamino)-2-
propene-1-ylidene]-cyclopentanone (5a)
5.3 | Preparation of ketocyanine dyes
Cyclopentanone (420 mg, 5 mmol), viamidinium salt
4 (2.26 g, 10 mmol), 2М solution of sodium methylate in
methanol (7 mL) and pyridine (3 mL) were kept for
6 hours at reflux. After cooling, the mixture was poured
on ice (50 g). The resulting crystals were filtered, washed
with water and dried on air. Brown solid; m.p.: 210ꢀC-
5.3.1 | bis-2,5-[2-(1-Ethyl-1,3-dihydro-
3,3-dimethyl-2H-indol-2-ylidene)
butadienyl-1,3-idene]-cyclopentanone (13a)
Salt 2a (630 mg, 2 mmol) and bis-2,5-[2-(1-ethyl-
1,3-dihydro-3,3-dimethyl-2H-indol-2-ylidene)butadienyl-
1,3-idene]-cyclopentanone 5a (246 mg, 1 mmol) in pyri-
dine (10 mL) were kept at reflux for 2 hours. After
cooling, the mixture was poured on ice (100 g). The
resulting crystals were filtered, washed with water, rec-
rystallized from methanol, and dried on air. Dark-brown
1
212ꢀC (Lit.[42] m.p.: 215ꢀC); Yield of 5а 873 mg (71%). H
NMR (400 MHz, CDCl3): δ 2.59 (s, 4H), 2.88 (s, 12H),
4.97 (m, 2H), 6.68(d, J = 13 Hz, 2H), 7.11 (d, J = 12 Hz,
2H). 13C NMR (100 MHz, CDCl3): δ 23.96, 40.66, 96.02,
129.58, 133.72, 150.33, 192.88. ES-MS+ [M + H]+
247.1832 (cal. 247.1810 [M + H]+ for C15H23N2O). λmax
(EtOH) = 503.5 nm (ε 3.12·104 L mol−1 cm−1). λmax
(EtOH + HCl) = 604.5 nm.
1
solid; m.p.: 154ꢀC-157ꢀC. Yield 170 mg (32%). H NМR
(CDCl3): δ 1.27 (m, 6H), 1.61 (s, 12 H), 2.77 (s, 4H), 3.70
(m, 4H), 5.56 (d, J = 12 Hz, 2H), 6.17 (dd, J1 = 14 Hz,
J2 = 12 Hz, 2H), 6.67 (d, J = 8 Hz, 2H), 6.91 (t, J = 8 Hz,
2H), 7.14-7.34 (m, 8H). 13C NMR (CDCl3): δ 11.39, 23.96,
28.21, 36.90, 46.22, 96.88, 106.37, 120.28, 120.79, 121.75,
127.78, 133.80, 135.35, 139.10, 139.39, 143.78, 158.99,
193.93. ES-MS+ [M + H]+ 531.3396 (cal. [M
5.2.2 | bis-2,6-[3-(Dimethylamino)-2-
propene-1-ylidene]-cyclohexanone (5b)
In the same way from 4 and cyclohexanone 5b was pre-
+ H]+
=
5 313 375 for C37H43N2O). λmax
(base)
pared. Brown solid; m.p.: 178ꢀC-182ꢀC (Lit.[42] m.p.:
(EtOH) = 616.0 nm (ε 5.49·104 L mol−1 cm−1). λmax (acid)
(EtOH + HCl) = 903.0 nm (ε 1.00·105 L mol−1 cm−1).
Ketocyanines 13b-d and 14 were synthesized follow-
ing the same procedure from salts 2а and 2b and bis-
enaminoketones 5a, 5b, and 7.
1
185ꢀC); Yield 702 mg (54%). H NMR (DMSO-d6): δ 1.63
(m, 2H), 2.39 (m, 4H), 2.89 (s, 12H), 5.01 (m, 2H), 6.92 (d,
J = 13 Hz, 2H), 7.20 (d, J = 12 Hz, 2H). 13C NMR
(CDCl3): δ 26.52, 40.63, 95.25, 124.44, 137.94, 150.21,
186.88. ES-MS+ [M + H]+ 261.1951 (cal. 261.1967 [M
+ H]+ for C16H25N2O). λmax (EtOH) = 486.0 nm (ε
6.43·104 L mol−1 cm−1). λmax (EtOH + HCl) = 595.5 nm.
5.3.2 | bis-2,5-[2-(3-Ethyl-1,3-dihydro-
1,1-dimethyl-2H-benz[e]indol-2-ylidene)
butadienyl-1,3-idene]-cyclopentanone (13b)
5.2.3 | 2-[3-(Dimethylamino)-2-propene-
1-ylidene]-5-(dimethylaminomethylene)-
cyclopentanone (7)
Dark-brown solid; m.p.: 172ꢀC-174ꢀC. From 2b and 5a
yield 271 mg (43%). 1H NMR (CDCl3): δ 1.32 (m, 6H), 1.95
(s, 12 H), 2.81 (s, 4H), 3.81 (m, 4H), 5.60 (d, J = 12.0 Hz,
2H), 6.21 (m, 2H), 7.06 (d, J = 8.5 Hz, 2H), 7.25-7.53 (m,
8H), 7.77 (d, J = 8.5 Hz, 2H), 7.82 (d, J = 8.5 Hz, 2H), 8.05
(d, J = 8.5 Hz, 2H). 13C NMR (CDCl3): δ 11.79, 24.02, 27.39,
37.03, 48.22, 96.56, 109.01, 120.67, 121.72, 122.44, 126.84,
129.05, 129.40, 129.54, 129.80, 129.87, 133.88, 135.33,
139.09, 141.18, 160.97, 193.87. ES-MS+ [M + H]+ 6 313 706
2-(Dimethylaminomethylene)-cyclopentanone 6 (700 mg,
5 mmol), 4 (1.13 g, 5 mmol) 2М sodium methylate in
methanol (5 mL) were kept for 6 hours at reflux. After
cooling, the mixture was poured on ice (100 g). The
resulting crystals were filtered, washed with water, and
dried on air. Dark-red solid; m.p.: 149ꢀC-151ꢀC. Yield of
1
7690 mg (63%); H NMR (CDCl3): δ 2.52 (m, 2H), 2.84
(cal. [M + H]+ = 6 313 688 for C45H47N2O). λmax
(base)
(br.s, 8H), 3.01 (s, 6H), 4.91 (m, 1H), 6.57 (d, J = 13 Hz,
1H), 7.09 (d, J = 12 Hz, 1H), 7.23 (br.s, 1H). 13C NMR
(EtOH) = 632 nm (ε 3.94·104 L mol−1 cm−1). λmax (acid)
(EtOH) = 938.5 nm (ε 7.21·104 L mol−1 cm−1).

8
MILTSOV ET AL.
5.3.3 | bis-2,5-[2-(1-Ethyl-1,3-dihydro-
3,3-dimethyl-2H-indol-2-ylidene)
butadienyl-1,3-idene]-cyclohexanone (13c)
132.01, 132.53, 136.13, 137.94, 139.36, 139.83, 143.55,
143.91, 158.35, 162.57, 192.97. ES-MS+ [M + H]+ 505.3210
(cal. [M + H]+ = 5 053 219 for C35H41N2O). λmax
(base)
(EtOH) = 579.0 nm (ε 3.30·104 L mol−1 cm−1). λmax (acid)
Dark-brown solid; m.p.: 127ꢀC-131ꢀC. From 2а and 5b
(EtOH) = 811.0 nm (ε 7.10·104 L mol−1 cm−1).
1
yield 195 mg (36%). H NMR (CDCl3): δ 1.26 (m, 6H),
1.62 (s, 12 H), 1.83 (m, 2H), 2.68 (m, 4H), 3.69 (m, 4H),
5.54 (d, J = 12.0 Hz, 2H), 6.27 (m, 2H), 6.66 (d, J = 8 Hz,
2H), 6.90 (m, 2H), 7.13-7.24 (m, 4H), 7.31 (m, 2H), 7.55
(d, J = 12.0 Hz, 2H). 13C NMR (CDCl3): δ 11.38, 22.54,
26.56, 28.24, 36.86, 46.14, 96.86, 106.25, 120.00, 120.11,
121.74, 127.76, 130.32, 137.84, 138.74, 139.39, 143.87,
158.68, 188.00. ES-MS+ [M + H]+ 5 453 519 (cal. [M
ACKNOWLEDGMENTS
We acknowledge the Center for Magnetic Resonance
and the Center for Chemical Analysis and Materials
Research of Saint Petersburg State University for per-
forming the NMR and ES-MS studies. The work is
carried out according to the State Assignment from
the Ministry of Education and Science of the Russian
Federation (Reg. no. АААА-А16-116071450048-3) and
funded by Ministerio de Economía y Competitividad
(Project CTQ2012-36165) and Generalitat de Catalu-
nya (2014SGR837).
+ H]+ = 5 453 532 for C38H45N2O). λmax
(base)
(EtOH) = 585.0 nm (ε 5.42·104 L mol−1 cm−1). λmax (acid)
(EtOH) = 893 nm (ε 1.14·105 L mol−1 cm−1).
ORCID
5.3.4 | bis-2,5-[2-(3-Ethyl-1,3-dihydro-
1,1-dimethyl-2H-benz[e]indol-2-ylidene)
butadienyl-1,3-idene]-cyclohexanone (13d)
Sergey Miltsov https://orcid.org/0000-0003-1781-3932
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Dark-brown solid; m.p.: 160ꢀC-164ꢀC. From 2b and 5b
yield 309 mg (48%). 1H NMR (CDCl3): δ 1.31 (m, 6H), 1.86
(m, 2H), 1.95 (s, 12 H), 2.71 (m, 4H), 3.80 (m, 4H), 5.58 (d,
J = 12.0 Hz, 2H), 6.30 (m, 2H), 7.06 (d, J = 8.5 Hz, 2H),
7.28 (m, 2H), 7.3-7.53 (m, 4H), 7.62 (d, J = 12.0 Hz, 2H),
7.77 (d, J = 8.5 Hz, 2H), 7.82 (d, J = 8 Hz, 2H), 8.04 (d,
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27.40, 36.98, 48.13, 96.54, 108.98, 119.90, 121.72, 122.34,
126.79, 129.08, 129.32, 129.49, 129.80, 130.28, 137.92,
138.71, 141.27, 160.64, 187.92. ES-MS+ [M + H]+ 6 453 837
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SUPPORTING INFORMATION
Additional supporting information may be found online
in the Supporting Information section at the end of this
article.
How to cite this article: Miltsov S, Alonso-
Chamarro J, Puyol M. Synthesis and optical
characterization of new ketocyanine dyes with
extended polymethine chaines. J Heterocyclic
Chem. 2020;1–9. https://doi.org/10.1002/jhet.4027
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Е. Е. Bol'bat, I. V. Abalov, А. V. Yakimanskii, Russ. J. Appl.
Chem 2010, 83, 1862.