New synthetic approach to aminosquarylium cyanine dyes

Article abstract of DOI:10.1055/s-2002-34226

A novel synthesis of aminosquarylium cyanine dyes, based on the methylation of readily available squarylium dyes with methyl triflate, followed by nucleophilic substitution with appropriate aliphatic amines, was disclosed. By this procedure several new aminosquarylium cyanine dyes bearing benzothiazole, benzoselenazole and quinoline nuclei were prepared.

Full text of DOI:10.1055/s-2002-34226

LETTER
1617
New Synthetic Approach to Aminosquarylium Cyanine Dyes
a
a
b
a
N
L
ew
S
ynthetic
A
.
pproach to
V
A
minosquarylium
.
C
yanine
Dy
R
es eis, J. P. C. Serrano, P. Almeida, P. F. Santos*
a
Departamento de Química, Universidade de Trás-os-Montes e Alto Douro, Apartado 1013, 5001-911 Vila Real, Portugal
Fax +351(259)350480; E-mail: psantos@utad.pt
b
Departamento de Química e Unidade de Materiais Têxteis e Papeleiros, Universidade da Beira Interior, Rua Marquês d’Ávila e Bolama,
201-001 Covilhã, Portugal
6
Received 29 July 2002
may increase its solubility in or its compatibility with cer-
tain media, and provides a potential means for chemically
bonding the dye to other materials.
Abstract: A novel synthesis of aminosquarylium cyanine dyes,
based on the methylation of readily available squarylium dyes with
methyl triflate, followed by nucleophilic substitution with appropri-
ate aliphatic amines, was disclosed. By this procedure several new
aminosquarylium cyanine dyes bearing benzothiazole, benzoselen-
azole and quinoline nuclei were prepared.
To the best of our knowledge, the few hitherto reported
examples of aminosquarylium cyanine dyes were synthe-
sised by condensation of monoalkylaminosquarates 2 and
Key words: aminosquarylium dyes, squaraines, pentamethine-
cyanines, dicarbocyanines, heterocycles
1
-ethyl-2,3,3-trimethylindolenium iodide (1) (Scheme 2)
6
in very low yield (9–15%).
Squarylium cyanine dyes are 1,3-disubstituted com-
pounds synthesised by condensation of one equivalent of
squaric acid (3,4-dihydroxy-1,2-dioxocyclobut-3-ene)
with two molar equivalents of heterocyclic methylenic
1
bases (Scheme 1).
Scheme 2
Scheme 1
Some halogenated aminosquarylium dyes of the hemicy-
In recent years, the family of squarylium dyes has re- anine type have recently been referred as promissing sen-
ceived considerable attention due to their special proper- sitizers for Photodynamic Therapy (PDT).7
ties such as high photochemical stability, outstanding
photoconductivity and sharp and intense absorption in the
8
Following our interest in the search for new potential cy-
anine sensitizers for PDT we developed a novel, expedi-
tious and versatile methodology for the synthesis of
aminosquarylium cyanine dyes and have applied it to the
preparation of several new dyes of this type derived
from benzothiazole, benzoselenazole and quinoline
2
visible and near infrared region, which rend them poten-
3
tial substrates for optical recording media, xerographic
4
5
photoreceptors and organic solar cells. For that reason,
structural modification of squarylium dyes has became an
active area of research.
(
Scheme 3).
It has recently been found that providing an amino group
in place of one of the oxygen atoms of the four-member
ring present in the polymethine chain of a squarylium dye
allows the corresponding absorption peak to be shifted
somewhat, enabling it to be tuneable by changes in the na-
ture of the amino substituent and increasing consequently
the utility of the compound as functional near infrared
The key step is the methylation, under mild conditions,9
of squarylium dyes 6, itself easily prepared via base-cata-
10
lysed condensation between a suitable 2-methylbenzo-
azolium iodide (4) and squaric acid (5), with methyl
triflate. Nucleophilic substitution of the newly formed
methoxy group in the four-member ring by methylamine
11
or N,N-diethylamine proceeded smoothly to give the
6
dye. Furthermore, this substitution allows various func-
tional groups to be incorporated conveniently into the dye,
corresponding aminosquarylium cyanine dyes 8 and 9, re-
spectively, in moderate to good yields (Table 1). When
the secondary amine was used the isolation of the methy-
lated derivative was unnecessary, provided that an excess
of amine was employed, and the reaction could be con-
veniently carried out as a one-pot process.
Synlett 2002, No. 10, Print: 01 10 2002.
Art Id.1437-2096,E;2002,0,10,1617,1620,ftx,en;D12302ST.pdf.
©
Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

1
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L. V. Reis et al.
LETTER
Finally, the counter-ion triflate accompanying dyes 8 and In conclusion, a simple and efficient preparative proce-
1
2
9
was replaced by iodide in order to facilitate crystalli- dure for the production of aminosquarylium cyanine dyes,
sation and to take advantage of the inherent heavy atom based on the methylation of readily available squarylium
effect. The later potentially enhances the efficiency with cyanine dyes, has been developed. This methodology is
which the dye converts triplet oxygen to cytotoxic singlet expected to be easily extended to other nucleophiles such
oxygen, a process that is generally accepted to be involved as hydrazines, hydroxylamines, thiols, etc. Such investi-
in the photosensitizing property of the dye and in the basis gation, as well as the photochemical evaluation of the
1
3
of cellular photodamage.
dyes synthesised, with prominence for the singlet oxygen
generation ability, is currently the subject of a separate
study, the results of which shall be published elsewhere.
Acknowledgement
The authors are grateful to FCT, Lisbon, POCTI and FEDER for fi-
nancial support (Project POCTI/32915/QUI/00).
References and Notes
(1) Sprenger, H. E.; Ziegenbein, W. Angew. Chem., Int. Ed.
Engl. 1967, 6, 553.
(
2) (a) Fabian, J.; Nakazumi, H.; Matsuoka, M. Chem. Rev.
1
992, 92, 1197. (b) Emmelius, M.; Pawlowski, G.;
Vollmann, H. W. Angew. Chem., Int. Ed. Engl. 1989, 28,
445.
1
(
3) (a) Ikuo, S.; Hiroshi, T.; Yukiyoshi, I.; Tsutomu, S. Eur.
Patent 568877, 1993; Chem Abstr. 1993, 121, 46725.
(b) Tsutomu, S.; Keiko, I. US Patent 5260165, 1993; Chem.
Abstr. 1993, 121, 22657. (c) Jipson, V. B.; Jones, C. R. J.
Vac. Sci. Technol. 1981, 18, 105.
(4) (a) Law, K.-Y. Chem. Rev. 1993, 93, 449. (b) Kamat, P. V.;
Das, S.; Thomas, K. G.; George, M. V. Chem. Phys. Lett.
1991, 178, 75. (c) Law, K.-Y. J. Phys. Chem. 1988, 92,
4226.
(
5) (a) Piechowski, A. P.; Bird, G, R.; Morel, D. L.; Stogryn, E.
L. Phys. Chem. 1984, 88, 934. (b) Morel, D. L.; Ghosh, A.
K.; Feng, T.; Stogryn, E. L.; Purwin, P. E.; Shaw, R. F.;
Fishman, C. Appl. Phys. Lett. 1978, 32, 495. (c) Merritt, V.
Y.; Hovel, H. J. Appl. Phys. Lett. 1976, 29, 414.
(
6) (a) Kim, S. H.; Hwang, S. H.; Kim, J. J.; Yoon, C. M.; Keum,
S. R. Dyes Pigm. 1998, 37, 145. (b) Kim, S. H.; Han, S. K.
Color. Technol. 2001, 117, 61.
Scheme 3
(
(
(
7) Morgan, A. R.; Menes, M. E.; Wang, R. W. Patent 44742,
2000; Chem. Abstr. 2000, 133, 151988.
All new compounds showed spectral data, including high-
resolution mass spectra, fully consistent with the assigned
8) Ramos, S. S.; Santos, P. F.; Reis, L. V.; Almeida, P. Dyes
Pigm. 2002, 53, 143.
1
4
structures.
The squarylium dyes exhibited sharp absorption bands in
the visible region ( 632–722 nm) with high extinction
9) General procedure for the preparation of O-methylated
squarylium dyes 7: To a solution of 6 (ca. 0.4 mmol) in
anhyd CH Cl (50 mL), vigorously stirred under N
2
2
2
max
5
–1
–1
atmosphere at r.t., was added a 4-fold excess of CF
3
SO CH .
3 3
coefficients ( >10 cm M ). In general, aminosquaryli-
um cyanine dyes 8 and 9 display absorption at longer
wavelength than the corresponding non-substituted dyes
After 3–5 h, the reaction mixture was quenched with cold
% aq NaHCO . The organic layer, after separation by
5
3
decantation, was dried over anhyd Na SO and the solvent
2
4
6
. The observed bathochromic shifts go up to 21 nm, be-
removed under reduced pressure. The resulting residue was
recrystallized from CH Cl –MeOH–Et O.
ing more pronounced for the dialkylamino dyes 9, pre-
sumably due to the greater electron donating character of
the corresponding auxochrome. The auxochromic effect
of the methoxy residue in dyes 7, on the contrary, shifts
the absorption towards the blue.
2
2
2
(
(
10) Bixian, P.; Tong, L. Dyes Pigm. 1998, 39, 201.
11) (a) General procedure for the preparation of
aminosquarylium dyes 8: Crude 7, prepared as described
above, was re-dissolved in anhyd CH Cl (40 mL), under N
2
2
2
atmosphere, and a 4-fold excess of methylamine was added.
After being stirred at r.t. for 30 min, the reaction mixture was
washed with cold water and the organic layer was separated
by decantation and dried over anhyd Na SO . The solvent
As previously observed for symmetric squarylium cya-
nine dyes bearing N-alkyl-3,3-dimethylindole nuclei, the
length of the N-alkyl group in dyes 8 and 9 has a negligi-
ble effect on the absorption spectrum of the dye.
9
2
4
was removed under reduced pressure and the resulting
residue was recrystallized from CH Cl –MeOH–Et O.
2
2
2
(
b) General procedure for the preparation of amino-
Synlett 2002, No. 10, 1617–1620 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
New Synthetic Approach to Aminosquarylium Cyanine Dyes
1619
Table 1 The Yield, Melting Point, and UV Spectral Data of Squarylium Cyanine Dyes 6–9
c
Dye
X
R
Yield (%)
50
Mp (ºC)
>300
270b
(nm)
Log
5.24
5.41
5.49
5.41
5.39
5.37
5.27
5.23
5.28
5.32
5.62
5.47
5.23
5.22
5.26
5.23
5.43
5.36
5.27
5.33
max
6
6
6
6
6
6
7
7
7
7
7
7
8
8
8
8
8
8
9
9
a
b
c
d
e
f
S
Et
650
S
Hex
Et
76
650
665
668
707
710
632
632
647
650
671
674
659
659
674
677
707
710
668
671
Se
72
300b
Se
Hex
Et
74
262b
CH=CH
45
>300
287b
CH=CH
Hex
Et
42
a
b
c
d
e
f
S
81
274b
S
Hex
Et
87
234b
Se
76
274b
Se
Hex
Et
76
249b
CH=CH
95
289b
CH=CH
Hex
Et
86
259b
a
b
c
d
e
f
S
56a
75 a
44a
69a
76a
82a
62a
75a
291–292
251–252
297b
S
Hex
Et
Se
Se
Hex
Et
240b
CH=CH
>300
260b
CH=CH
Hex
Et
a
b
S
S
283b
Hex
236–238
9
9
9
9
c
d
e
f
Se
Et
56a
88a
89a
84a
284b
287b
282b
242b
686
689
719
722
5.22
5.26
5.55
5.38
Se
Hex
Et
CH=CH
CH=CH
Hex
a
b
c
From the corresponding squarylium dye 6.
With decomposition.
Measured in MeOH/CH Cl (99:1).
2
2
squarylium dyes 9: To a untreated solution of 7 in dry
(14) Selected data. Compound 7a: IR (KBr): 1648, 1506, 1427,
–
1
CH Cl , prepared as described above, vigorously stirred
1396, 1361, 1311, 1247, 1218, 1157, 1118, 750 cm ;
2
2
1
under N atmosphere at r.t., was added a 5-fold excess of
H NMR (400.13 MHz, DMSO–CDCl3): 1.36 (6 H, t, J =
2
N,N-diethylamine. After 3–5 h the reaction mixture was
worked-up as described for the preparation of O-
methylsquarylium dyes 7 and the resulting residue was
recrystallized from CH Cl –MeOH–Et O (Table 1).
7.2 Hz, CH ), 4.44 (4 H, q, J = 7.2 Hz, CH ), 4.51 (3 H, s,
3
2
OCH ), 5.99 (2 H, s, CH=), 7.36 (2 H, t, J = 8.0 Hz, ArH),
3
7.52 (2 H, t, J = 8.0 Hz, ArH), 7.64 (2 H, d, J = 8.0 Hz, ArH),
1
3
7.91 (2 H, d, J = 8.0 Hz, ArH); C NMR (100.62 MHz,
2
2
2
(
(
12) General procedure for the replacement of counter-ion in
dyes 8 and 9: To a solution of the dye, prepared as described,
in MeOH, at r.t., was added an approximately equal volume
of 14% aq KI. After 2 h, the precipitated dye was collected
by filtration, washed with water and recrystallized from
CH Cl –MeOH–Et O.
DMSO–CDCl3): 12.3 (CH ), 41.4 (CH ), 60.3 (OCH ),
3
2
3
84.6, 113.1, 122.5, 125.0, 127.4, 127.7, 139.8, 157.9, 161.5,
173.5, 176.7; HRMS (FAB): calcd for C H N O S
2
5
23
2
2 2
447.120097, found 447.122165. Compound 8a: IR (KBr):
3438, 1633, 1560, 1455, 1428, 1353, 1309, 1251, 1228,
–
1 1
1110, 746 cm ; H NMR (250.13 MHz, DMSO–CDCl ):
2
2
2
3
13) Bonett, R. Chemical Aspects of Photodynamic Therapy;
Gordon and Breach: Amsterdam, 2000.
1.42–1.49 (6 H, m, CH ), 3.36 (3 H, d, J = 5.0 Hz, NCH ,
3
3
collapses to s with D O), 4.31–4.41 (4 H, m, CH ), 5.95 (1
2
2
H, s, CH=), 6.35 (1 H, s, CH=), 7.28–7.51 (6 H, m, ArH),
Synlett 2002, No. 10, 1617–1620 ISSN 0936-5214 © Thieme Stuttgart · New York

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620
L. V. Reis et al.
LETTER
7
.65–7.74 (2 H, m, ArH), 8.63 (1 H, br, NH, exchangeable
3.28 (4 H, q, J = 7.2 Hz, CH ), 3.92 (4 H, q, J = 7.3 Hz, CH ),
2
2
1
3
with D O); C NMR (100.62 MHz, DMSO–CDCl ): 10.7
5.40 (2 H, s, CH=), 6.92 (2 H, t, J = 7.2 Hz, ArH), 7.03–7.10
2
3
1
3
(CH ), 10.9 (CH ), 28.8 (NCH ), 39.5 (CH ), 40.0 (CH ),
(4 H, m, ArH), 7.26 (2 H, d, J = 7.6 Hz, ArH); C NMR
3
3
3
2
2
8
1
4.5, 84.6, 110.8, 111.2, 120.7, 121.0, 122.8, 123.3, 125.9,
26.1, 126.3, 138.5, 138.6, 156.0, 159.4, 162.6, 171.9;
(100.62 MHz, DMSO–CDCl ): 11.4 (CH ), 14.4 (CH ),
3
3
3
40.8 (CH ), 45.6 (CH ), 84.9 (CH=), 111.7, 121.3, 124.3,
2
2
HRMS (FAB): calcd for C H N OS 446.136081, found
127.0, 127.2, 139.1, 155.4, 159.6, 160.9, 173.1; HRMS
(FAB): calcd for C H N OS 488,183031, found
488,185052.
2
5
24
3
2
4
46.137251. Compound 9a: IR (KBr): 1621, 1544, 1421,
2
8
30
3
2
–
1 1
1357, 1313, 1214, 1149, 1116, 1008, 775 cm ; H NMR
(
400.13 MHz, DMSO–CDCl3): 1.00–1.04 (12 H, m, CH3),
Synlett 2002, No. 10, 1617–1620 ISSN 0936-5214 © Thieme Stuttgart · New York