One-Pot Synthesis of Squaraine Fluoroionophores

Full text of DOI:10.1021/jo9805145

J . Org. Chem. 1998, 63, 6059-6060
6059
Sch em e 1
On e-P ot Syn th esis of Squ a r a in e
F lu or oion op h or es
Umut Oguz and Engin U. Akkaya*
Department of Chemistry, Middle East Technical University,
TR-06531 Ankara, Turkey
Received March 18, 1998
Squaraines are 1,3-disubstituted squaric acid deriva-
tives with sharp visible absorption peaks in solution and
panchromatic absorption in the solid state. This class
of fluorescent dyes and pigments is well-known for their
applications in electrophotography,1 organic solar cells,2
nonlinear optics,3 and optical data storage.4 Their pho-
tochemistry has been extensively studied,5 and many
derivatives of the parent squaraine skeleton have been
synthesized mostly for improvements in technical ap-
plications. In recent years, squaraines also received
attention as fluorescent labels.6 Their very promising
spectral properties such as long wavelength absorption
and emission, high extinction coefficients, and quantum
yields make them particularly attractive in this area. In
addition, the rational design of fluorescent chemosensors7
is a vibrant field of organic chemistry, and appropriately
derivatized squaraines could lead to novel sensing tech-
nologies as they can be excited with solid-state lasers.
There are already successful examples of squaraine-
based chemosensors in the literature,8 and such modified
squaraines were shown to signal pH, alkaline, and earth-
alkaline metals in various solvent systems. When the
range of selectivities that could be achieved by the
judicious choice of the crown ethers is considered, aza-
crown-appended squaraines (squaraine fluoroionophores)
are targets of prime importance.
removed azeotropically or taken up by molecular sieves.
The synthetic challenge in the preparation of azacrown-
squaraines is essentially the preparation of phenyl- or
((di)hydroxyphenyl)azacrowns, as the rest of the synthe-
sis is straightforward. Phenylazacrowns were synthe-
sized in 1985 by Gokel,10 and the synthesis involves a
multistep synthesis with at least one high-dilution step.
No literature reports of 3-hydroxy- or (3,5-dihydroxyphen-
yl)azacrowns were encountered, and that is unfortunate
because such hydroxy substitutions would not only
increase the yield5 in squaraine synthesis but also result
in higher-quantum yield squaraines with improved solu-
bility characteristics.5 We report here the use of a novel
one-pot reaction that provides an entry to such deriva-
tized squaraines using simple commercially available
synthons.
The general synthetic methodology used in the prepa-
ration of squaraines is rather simple.9 It involves a
reaction of 2 equiv of dialkylanilines with 1 equiv of
squaraic acid, preferably in n-BuOH/toluene (50:50) at
reflux temperatures. Water formed could be either
Syn th esis
Our synthesis makes use of the general reactivity of
phloroglucinol (1,3,5-trihydroxybenzene) with secondary
amines through its keto tautomer. The fact that this
reaction could be made to proceed in the same azeotropic
solvent mixture as that of squaraine synthesis proved to
be very convenient, and our azacrown-appended squaraine
synthesis became a one-pot reaction. Thus, the azacrown
was reacted with equimolar phloroglucinol in n-BuOH/
toluene (50:50) in a Dean-Stark apparatus, where water
that formed was removed continuously. (3,5-Dihydoxy-
phenyl)azacrown formation was complete in 6-8 h
depending on the type of azacrown used. The N-phenyl-
azacrown derivative was not isolated; instead, 0.5 equiv
of squaric acid was added, and heating was continued.
Typically in 15 min, the characteristic intense green color
of the squaraines was observed. The reflux was contin-
ued for 4 h. On cooling, the squaraine-azacrown con-
jugates crystallized out of the solution. The precipitate
was washed with MeOH and dried. Recrystallization
was not necessary as evidenced from the analytical data.
(1) Law, K.-Y. Chem. Rev. 1993, 93, 449, and references therein.
(2) Loutfy, R. O.; Hsiao, C. K.; Kazmaier, P. M. J . Photogr. Sci. 1983,
27, 5.
(3) (a) Chen, C.-T.; Marder, S. R.; Cheng, L. T. J . Chem. Soc. Chem.
Commun. 1994, 259. (b) Andrews, J . H.; Khagdarov, J . D. V.; Singer,
K. D.; Hull, D. L.; Chuang, K. C. Nonlinear Opt. 1995, 10, 227. (c)
Ashwell, G. J .; J efferies, G.; Hamilton, D. G.; Lynch, D. E.; Roberts,
M. P. S.; Bahra, G. S.; Brown, C. R. Nature 1995, 375, 385.
(4) Emmelius, M.; Pawlowski, G.; Vollmann, H. W. Angew. Chem.,
Int. Ed. Engl. 1989, 28, 1445.
(5) Law, K.-Y. J . Phys. Chem. 1987, 91, 5184.
(6) (a) Ghazarossian, V.; Pease, J . S.; Ru, M. W. L.; Laney, M.;
Tarnowski, T. L. Eur. Pat. Appl. EP 356173 A2, 1990. (b) Terpetschnig,
E.; Szmacinski, H.; Ozinskas, A.; Lakowicz, J . R. Anal. Biochem. 1994,
217, 197.
(7) Recent reviews of the field: (a) DeSilva, A. P.; Gunaratne, H. Q.
N.; Gunnlaugsson, T.; Huxley, A. J . M.; Mccoy, C. P.; Rademacher, J .
T.; Rice, T. E. Chem. Rev. 1997, 97, 1515. (b) Desvergne, J .-P., Czarnik,
A. W., Eds. Chemosensors of Ion and Molecule Recognition; Proceedings
of the NATO ASI Series C; Kluwer Academic Press: Dordrecht, The
Netherlands, 1997; Vol. 492.
(8) (a) Oguz, U.; Akkaya, E. U. Tetrahedron Lett. 1997, 38, 4509.
(b) Akkaya, E. U.; Turkyilmaz, S. Tetrahedron Lett. 1997, 38, 4513.
(c) Isgor, Y. G.; Akkaya, E. U. Tetrahedron Lett. 1997, 38, 7417. (d)
Das, S.; Thomas, K. G.; Thomas, K. J .; Kamat, P. V.; George, M. V. J .
Phys. Chem. 1994, 98, 9291. (e) Thomas, K. G.; Thomas, K. J .; Das,
S.; George, M. V. Chem. Commun. 1997, 597.
1
The new compounds were fully characterized by H and
(9) Ziegenbein, W.; Sprenger, H. E. Angew. Chem., Int. Ed. Engl.
1966, 5, 893.
(10) Schultz, R. A.; White, B. D.; Dishong, D. M.; Arnold, K. A.;
Gokel, G. W. J . Am. Chem. Soc. 1985, 107, 6659.
S0022-3263(98)00514-3 CCC: $15.00 © 1998 American Chemical Society
Published on Web 08/01/1998

6060 J . Org. Chem., Vol. 63, No. 17, 1998
Notes
13C NMR, mass spectrometry, and elemental analysis.
NMR spectra reveal the highly symmetrical nature of the
squaraines and the presence of strong internal hydrogen
bonding between the ArOH and the squaryl oxygens.
washed with cold methanol (100 mL). The resulting dark green
solid was dried in vacuo. The yield was 1.0248 g (70%): mp
>250 °C; 1H NMR (CDCl3, 400 MHz) δ 3.82-3.65 (m, 40 H),
5.84 (s, 4 H), 10.99 (s, 4 H); 13C NMR (CDCl3, 50 MHz) δ 53.62,
68.59, 70.08, 70.49, 71.26, 94.11, 103.0, 158.00, 162.00, 163.03,
181.00; MS (EI) m/e 730 [(M - 2H)+], 367 [(azacrown-Ar-CHd
CdO)+]. Anal. Calcd for C36H48N2O14: C, 9.01; H, 5.56; N, 3.83.
Found: C, 59.17; H, 5.66; N, 3.85.
Exp er im en ta l Section
Gen er a l. All reagents were purchased from commercial
suppliers and used without further purification. 1H NMR and
13C NMR spectra were recorded in CDCl3 solution with TMS as
an internal reference at 400 MHz (1H) and 100 MHz (13C). Mass
spectra were recorded by electron impact (70 eV). Melting points
reported are uncorrected. Elemental analyses were performed
by TUBITAK Instrumental Analysis Laboratory (Ankara, Tur-
key).
Bis[4-N-(1-a za -4,7,10,13-tetr a oxa cyclop en ta d ecyl)-3,5-d i-
h yd r oxyp h en yl]squ a r a in e (n ) 0). 1-Aza-15-crown-5 (0.438
g, 2 mmol) and phloroglucinol (0.252 g, 2 mmol) were heated to
reflux in a solvent mixture containing toluene (10 mL) and
n-butanol (10 mL), accompanied by azeotropic distillation of
water, overnight. Without any isolation attempt, the resulting
(3,5-dihydroxyphenyl)azacrown was reacted in the same solvent
system with 3,4-dihydroxy-3-cyclobutene-1,2-dione (squaric acid,
0.114 g, 1 mmol) by refluxing for 6 h in the same Dean-Stark
apparatus. The reaction mixture was cooled to room tempera-
ture. The precipitated product was collected by filtration and
Bis[4-N-(1-a za -4,7,10,13,16-p en ta oxa cycloocta d ecyl)-3,5-
d ih yd r oxyp h en yl]squ a r a in e (n ) 1). The same procedure
applied 1-aza-18-crown-6 yielded dark green crystals with a
metallic luster. The product was collected by filtration washed
with cold methanol (100 mL) and 2-propanol (50 mL), and dried
in vacuo. The yield was 1.23 g (75%): mp >250 °C; 1H NMR
(CDCl3, 400 MHz) δ 3.48-3.73 (m, 48 H), 5.86 (s, 4 H), 10.84 (s,
4 H); 13C NMR (CDCl3, 50 MHz) δ 57.12, 73.88, 75.69, 75.85,
75.96, 99.13, 107.82, 163.87, 166.05, 167.70, 186.63 (one of the
peaks obscured by CDCl3); MS (EI) m/e 818 [(M - 2H)+], 411
[(azacrown-ArCHdCdO)+]. Anal. Calcd for C40H56N2O16‚0.25
H2O: C, 58.21; H, 6.89; N, 3.39. Found: C, 57.86; H, 6.50; N,
3.47.
Ack n ow led gm en t. We gratefully acknowledge sup-
port from TWAS (RGA no. 96-140 RG/CHE/AS).
J O9805145