Synthesis of calixarene-based ketocyanine fluorophores

Article abstract of DOI:10.1016/j.tetlet.2011.05.094

Cup-shaped calix[4]arenes bearing one or two ketocyanine fluorophore fragments at the wide rim of the macrocycle are synthesized by condensation of formyl calix[4]arenes with arylmethylene(hetarylmethylene)cyclopentanones in the presence of the ionic liqu

Full text of DOI:10.1016/j.tetlet.2011.05.094

Tetrahedron Letters 52 (2011) 3922–3925
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis of calixarene-based ketocyanine fluorophores
Yuriy Matvieiev a, Iuliia Karpenko b, Andrii Kulinich a, Aleksey Ryabitskii a, Vasyl Pivovarenko b,
Svitlana Shishkina c, Oleg Shishkin c, Vitaly Kalchenko a,
⇑
a Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Murmanska Str. 5, 02660 Kyiv, Ukraine
b Chemical Faculty, National Taras Shevchenko University of Kyiv, Volodimirska Str. 64, 01601 Kyiv, Ukraine
c Institute for Single Crystals, National Academy of Sciences of Ukraine, Lenin Ave. 60, 61001 Kharkiv, Ukraine
a r t i c l e i n f o
a b s t r a c t
Article history:
Cup-shaped calix[4]arenes bearing one or two ketocyanine fluorophore fragments at the wide rim of the
macrocycle are synthesized by condensation of formyl calix[4]arenes with arylmethylene(hetarylmeth-
ylene)cyclopentanones in the presence of the ionic liquid, dimethylammonium dimethylcarbamate
(DIMCARB) and characterized using UV–vis and fluorescence spectroscopy. Strong positive solvatofluoro-
chromism for the calixarene ketocyanines is observed.
Received 4 April 2011
Revised 6 May 2011
Accepted 20 May 2011
Available online 27 May 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Calix[4]arenes
Ketocyanines
Chemosensors
Solvatofluorochromism
Molecular sensing is a rapidly developing field in science and
technology.1 The key task in construction of efficient chemosensors
is the design of sensor systems capable of producing a high-ampli-
tude physical signal upon selective molecular recognition. Among
a variety of chemosensory devices, fluorescence systems are com-
monly considered superior due to their simple construction and
extremely high sensitivity.2 On the other hand, calixarenes are
phenol-derived macrocycles that possess a unique cup-shaped
molecular cavity and are able to demonstrate high selectivity in
the formation of supramolecular host–guest complexes with metal
cations, anions, and organic and biomolecules.3 This ability makes
calixarenes an attractive framework for construction of optical
sensing systems. A chromo(fluoro)phore electronic system can be
All attempts to react calixarenes 1a–c with cyclopentanones
2a–c7 via typical aldol condensation conditions in basic or acidic
medium failed. However, aldehydes 1a–c reacted smoothly with
cyclopentanones 2a–c in the presence of dimethylammonium dim-
ethylcarbamate (DIMCARB)8 as a co-solvent and catalyst to give
(depending on the reagent ratio) calixarenes 3 and 4 possessing
one or two ketocyanine moieties in moderate to good yields
(Scheme 1). All the reactions were carried out by heating at
45–50 °C in chloroform for 5–11 days. Interestingly, the reaction
proceeds stereoselectively with formation of the E,E-isomer exclu-
sively. In the 1H NMR spectra of compounds 3a–c recorded in CDCl3,
the AB spin system due to the axial and equatorial protons of the
ArCH2Ar methylenes appeared as two doublets at d 4.33 and d
2
conjugated in the sensors with the
p
-system of the calixarene rec-
4.31 (Hax) and a multiplet at d 3.41 (Heq) with JHH 12.8–13.1 Hz.
ognition site.4 Chromophore-functionalized calixarenes were syn-
The chemical shift difference between Hax and Heq of about
0.9 ppm reflects the cone conformation of 3a–c in solution.9 The
protons of the cyclopentanone ring were observed as a broad sin-
glet at d 3.10. The hydroxy protons appeared as two singlets in
the region d 8.30–8.92. 13C NMR resonances for the carbons of the
methylene bridges appeared at d 31.31–31.48, which reflects the
syn orientation of the adjacent phenolic rings in the cone conforma-
tion.10 The presence of long-range couplings between Ha,b and the
cyclopentanone ring protons in the COSY-spectrum gave additional
insight into the structural features of 3a–c. The signals of Ha,b at d
7.48 and d 7.54, which overlap with the doublet due to the aromatic
protons at d 7.52, showed long-range couplings to the cyclopenta-
none methylene protons while couplings to the ortho-protons of
the neighbouring benzene rings were not present. It should be
thesized and studied previously.5
In this Letter, we report the synthesis of calix[4]arenes bearing
ketocyanine chromofluorophore groups, the fluorescence of which
is highly sensitive to the environment and could provide responses
to substrate binding.
To functionalize the macrocyclic backbone with ketocyanine
groups, we employed the condensation reaction between the read-
ily available monoformyl or diformyl propoxycalix[4]arenes 1a,b,6
c and a,b-unsaturated cyclopentanones 2a–c.
⇑
Corresponding author. Tel.: +38 044 499 4616; fax: +38 044 543 2643.
E-mail address: vik@ioch.kiev.ua (V. Kalchenko).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.05.094

Y. Matvieiev et al. / Tetrahedron Letters 52 (2011) 3922–3925
3923
Hb
X
R
O
Ha
1 : 1
YO
O
O
O
HO
3a-e
X
R
OMe
NEt2
X = Y = H;
X = Y = H;
X = Y = H;
X = H; Y =
R =
(3a)
54%
71%
58%
O
DIMCARB
CHCl3
+
R =
R =
(3b)
(3c)
HO
O
OY
O
45-50 oC
O
O
n
-Pr; R =
(3d)
(3e)
52%
85%
1a-c
2a-c
X = CHO; Y = H; R =
OMe
OMe (2a)
X = Y = H
X = CHO; Y = H (1b)
X = H; Y = -Pr (1c)
(1a)
R =
OMe
MeO
O
O
R =
R =
NEt2
(2b)
(2c)
1 : 2
n
X = CHO,
Y = H
O
HO
O
OH
O
90%
4
Scheme 1. Synthesis of calixarene-based ketocyanine fluorophores.
noted that the signal for the hydroxy proton of 3d at d 5.56 was
shifted significantly to a high field compared to 3a–c which is typ-
ical for calixarenes trisubstituted on the narrow rim.11 The alde-
hyde proton of 3e appeared as a sharp singlet at d 9.79.
The 1H NMR spectrum of the disubstituted derivative 4 in CDCl3
contained two well-resolved doublets due to the methylene pro-
tons at d 3.45 (Heq) and d 4.33 (Hax) with coupling constants of
13.1 Hz. This reflects the C2v-symmetry of the cone-shaped macro-
cycle backbone.
Diffraction quality crystals of 3a and 3d were grown from chlo-
roform-methanol and ethyl acetate–hexane mixtures, respectively.
The X-ray diffraction study showed that both the molecules existed
in E,E-form in the solid state.
Macrocycles 3a and 3d adopt a pinched cone conformation (Fig-
ure 1). The angles between the opposite benzene rings of the mac-
rocycles differ considerably (13.6° and 74.9° for 3a, 19.2° and 67.0°
for 3d). Conjugation of the aromatic
p-system with the ketocya-
nine fragment is revealed in both compounds 3a and 3d.
In order to estimate the influence of the calixarene framework
on the absorption and fluorescence properties of 3a–e and 4, model
compound 5 was synthesized (Scheme 2). The structure of 5 can be
considered as that of the isolated fluorophore of 3a.
The reaction between para-hydroxybenzaldehyde and (2E)-2-
(4-methoxybenzylidene)cyclopentanone (2a) was carried out
using conditions similar to those employed for 3a–e and 4 for
5 days and gave (2E,5E)-2-(4-methoxybenzylidene)-5-(4-hydroxb-
enzylidene)cyclopentanone (5) in 76% yield.
Figure 1. X-ray crystal structures of compounds 3a (above) and 3d (below); H-
atoms are omitted for clarity. The E,E-conformations are clearly shown. Thermal
ellipsoids are shown at the 50% probability level.
The UV–vis and steady state fluorescence spectra of compounds
3–5 were studied in solvents of different polarities (toluene, chlo-
roform, acetone, DMSO, and MeOH). Relative fluorescence quan-
tum yields were measured using quinine sulfate in 0.1 M H2SO4
shows a substantial positive solvatochromism. At the same time
all the compounds possess rather strong positive solvatofluoro-
chromism (Table 1 and Figure 2), which for the dye 3b is compara-
ble with that of known analogs13 or Prodan,14 while for other dyes
it is 1.5–2 times lower.
(
Uf = 57.7%) as a reference.12 Selected spectral data are listed in
Table 1.
All the products showing molar extinctions of about
These features provide a regular increase of Stokes’ shifts with
increasing solvent polarity. The fluorescence quantum yields are
relatively low – up to several percent for compound 3b and about
40,000 L molÀ1cmÀ1 absorb on the border of the UV and visible re-
gions, and demonstrate green or yellow fluorescence. Only 3b

3924
Y. Matvieiev et al. / Tetrahedron Letters 52 (2011) 3922–3925
showing the spatial influence of the rigid calixarene skeleton on
the fluorescence properties.
O
O
O
In summary, this preliminary study of calixarene-based ketocy-
anines has demonstrated them to be promising materials as new
fluorescent chemosensors. The estimated solvatofluorochromism
levels and quantum yield values demonstrate clearly the possibil-
ity of control of the fluorescence colour and intensity by varying
the nature of the analyte bound in the proximity of the fluorophore
unit.
+
MeO
OH
2a
DIMCARB
CHCl3; 50 oC
5
HO
OMe
X-ray diffraction study. The colourless crystals of 3a C48H48O6 are
monoclinic. At 100 K: a = 10.0804(7), b = 42.357(2), c = 9.3766(8) Å,
b = 108.380(9), V = 3799.3(5) Å3, Mr = 720.86, Z = 4, space group
O
P21/c, dcalc = 1.260 g/cm3,
l
(MoK) = 0.082 mmÀ1, F(0 0 0) = 1536.
OMe
Intensities of 36345 reflections (11012 independent, Rint = 0.160)
were measured on an Xcalibur-3 diffractometer (graphite mono-
HO
O
chromated Mo
max = 60°).
The colourless crystals of 3d C48H50O6 are triclinic. At 100 K:
a = 9.9903(5), b = 14.195(1), c = 15.524(1) Å, = 65.071(7)°,
b = 74.497(5),
= 86.053(5)°, V = 1921.3(2) Å3, Mr = 722.88, Z = 2,
K
a
radiation, CCD detector,
x-scanning,
O
2H
HO
3a
a
Scheme 2. Synthesis of the model compound 5.
c
space group P1, dcalc = 1.250 g/cm3,
l
(Mo K ) = 0.081 mmÀ1, F (
ꢀ
a
0 0 0) = 772. Intensities of 14310 reflections (6748 independent,
Table 1
UV–vis and fluorescent spectral characteristics of compounds 3–5, measured in CHCl3
and MeOH at 25 °C
Rint = 0.084) were measured on an Xcalibur-3 diffractometer
(graphite monochromated MoKa radiation, CCD detector, x-
Sa
Ufa (%)
SSa (cm–1
)
abs
max
a
fl
max
a
scanning, 2Hmax = 50°).
Compound
Solvent
k
k
The structures were solved by direct methods using the SHEL-
XTL package.15 The positions of the hydrogen atoms were located
from electron density difference maps and refined using the ‘rid-
ing’ model with Uiso = nUeq for the carrier atom (n = 1.5 for methyl
and hydroxy groups and for the water molecule, and n = 1.2 for
other hydrogen atoms). Full-matrix least-squares refinement of
the structures against F2 in anisotropic approximation for non-
hydrogen atoms using 10890 (3a) and 6650 (3d) reflections con-
verged to: wR2 = 0.041 (R1 = 0.047 for 3221 reflections with
(nm)
(nm)
3a
3b
3c
3d
3e
4
CHCl3
MeOH
CHCl3
DMSOb
CHCl3
MeOH
CHCl3
MeOH
CHCl3
MeOH
CHCl3
MeOH
CHCl3
MeOH
403
402
421
462
404
409
401
406
399
402
402
403
384
393
472
498
534
574
484
528
482
529
476
514
474
510
462
497
0.378
1.25
0.8
1.3
3.4
4.6
1.1
1.2
0.7
1.5
0.3
0.6
1.0
1.3
0.03
0.8
3630
4800
5030
4220
4090
5510
4190
5730
4050
5420
3780
5210
4400
5320
0.590
0.560
0.531
0.510
0.521
F > 4r(F), S = 0.589) for structure 3a and wR2 = 0.034 (R1 = 0.043
for 2344 reflections with F > 4r(F), S = 0.573) for structure 3d.
The final atomic coordinates, and crystallographic data for mole-
cules 3a and 3d have been deposited with the Cambridge Crystal-
lographic Data Centre, 12 Union Road, CB2 1EZ, UK (fax: +44 1223
336033; e-mail: deposit@ccdc.cam.ac.uk) and are available on re-
quest quoting the deposition numbers CCDC 793141 for 3a and
CCDC 793142 for 3d.
5
a
abs
max
fl
k
—absorption maximum; k —fluorescence maximum; S—relative solva-
max
tofluorochromism:
tum yield; SS—Stokes’ shift.
D/DProdan for the pair of solvents used; Uf—fluorescence quan-
b
DMSO was used as compound 3b and is almost non-fluorescent in MeOH.
Acknowledgement
1.0
We thank Professor A. A. Ishchenko and Dr. A. V. Solovyov for
helpful discussions.
Supplementary data
Ia (If)
0.5
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2011.05.094.
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