Synthesis of new highly organosoluble metallophthalocyanines with 1,8-dioxo-octahydroxanthene substituents

Article abstract of DOI:10.1016/j.tetlet.2011.10.122

New highly organosoluble metallophthalocyanines (M = Zn, Co, Ni and Cu) bearing four [4-(3,3,6,6-tetramethyl-1,8-dioxo-2,3,4,5,6,7,8,9-octahydro-1H- xanthen-9-yl)phenoxy] substituents at peripheral positions have been prepared by tetramerization of 4-[4-(

Full text of DOI:10.1016/j.tetlet.2011.10.122

Tetrahedron Letters 53 (2012) 123–126
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Tetrahedron Letters
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Synthesis of new highly organosoluble metallophthalocyanines
with 1,8-dioxo-octahydroxanthene substituents
⇑
Ali Reza Karimi , Fahimeh Bayat
Department of Chemistry, Faculty of Science, Arak University, Arak 38156-8-8349, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 24 July 2011
Revised 27 September 2011
Accepted 21 October 2011
Available online 28 October 2011
New highly organosoluble metallophthalocyanines (M = Zn, Co, Ni and Cu) bearing four [4-(3,3,6,
6-tetramethyl-1,8-dioxo-2,3,4,5,6,7,8,9-octahydro-1H-xanthen-9-yl)phenoxy] substituents at peripheral
positions have been prepared by tetramerization of 4-[4-(3,3,6,6-tetramethyl-1,8-dioxo-dodecahydro-
1H-xanthen-9-yl)phenoxy]phthalonitrile in 2-(dimethylamino)ethanol using microwave irradiation or
conventional heating. Ni(II), Co(II) and Cu(I) chloride were employed in order to synthesize the correspond-
ing metal phthalocyanines and Zn(OAc)2 was used for the preparation of the zinc phthalocyanines. 4-[4-
(3,3,6,6-Tetramethyl-1,8-dioxo-2,3,4,5,6,7,8,9-octahydro-1H-xanthen-9-yl)phenoxy]phthalonitrile was
obtained by nucleophilic displacement of the nitro group in 4-nitrophthalonitrile with 9-(4-hydroxy-
phenyl)-3,3,6,6-tetramethyl-3,4,6,7-tetrahydro-2H-xanthene-1,8(5H,9H)-dione. 9-(4-Hydroxyphenyl)-3,
3,6,6-tetramethyl-3,4,6,7-tetrahydro-2H-xanthene-1,8(5H,9H)-dione was synthesized efficiently from
dimedone and 4-hydroxybenzaldehyde. All the phthalocyanines are soluble in DMSO, DMF, CHCl3, THF,
CH2Cl2, and CH3CN. The new compounds were characterized by IR, NMR, and UV–vis spectroscopy, elemen-
tal analysis and thermogravimetric analysis.
Keywords:
Phthalocyanine
1,8-Dioxo-octahydroxanthene
Organosoluble
Microwave synthesis
Ó 2011 Elsevier Ltd. All rights reserved.
Significant interest has been focused on the synthesis of phthal-
ocyanines (Pc) due to their applications as liquid crystals,1,2 solar
cells,3,4 electrochromic displays,5 in photodynamic therapy of can-
cer,6,7 in semiconductor devices,8 gas sensors,9–11 non-linear op-
tics,12 laser dyes,13 Langmuir–Blodgett films14 and various
catalytic processes.15
The solubility of phthalocyanines is very important for the
investigation of their chemical and physical characteristics and is
influenced by the nature of the substituents on the periphery of
the Pc ring. The main limitation in the applications of metallopht-
halocyanine complexes is their low solubility in common organic
solvents.16
Water-soluble phthalocyanines have received great attention
with regard to photodynamic efficacy,17a but the purification of
these compounds can be a problem. Furthermore, aggregation
(especially in aqueous media) is a very common phenomenon in
this family of compounds.17b
Organo-soluble phthalocyanines are, therefore, important and
potentially useful materials. The insolubility of phthalocyanines
in organic solvents can be overcome by the introduction of
organo-solubilizing substituents into the ring system.18
A number of phthalocyanines bearing apolar groups, such as
bulky substituents,19 long-chain groups (e.g., alkyl and alkoxy),20
N-tosyl derivatives21 and crown ethers22 have been reported.
Xanthenes have been of much interest due to the broad spec-
trum of their pharmaceutical and biological properties which in-
clude
anti-inflammatory,23
antibacterial,24
and
antiviral
activities25 as well as their efficiency in photodynamic therapy
(PDT)26 and as antagonists toward the paralyzing action of zoxazo-
lamine.27 Furthermore, xanthenes are employed in laser technol-
ogy.28 Among the xanthenes developed thus far, it is known that
octahydroxanthene derivatives can be applied as fluorescent
fuels29 and as antispasmodics.30
The development of new systems that can target specific cells
for PDT relies on a connection between biological subunits and
the photosensitizer. We expect that the conjugation of phthalocy-
anines with xanthene moieties may improve their organosolubili-
ty, and PDT effects.
This information encouraged us to design highly organosoluble
metal (Zn, Ni, Cu and Co) phthalocyanines 6–9 containing four 9-
(4-hydroxyphenyl)-3,3,6,6-tetramethyl-3,4,6,7-tetrahydro-2H-xan
thene-1,8(5H,9H)-dione moieties (Scheme 1).
A number of methods have been developed for the preparation
of MPcs. Microwave-assisted organic synthesis has attracted con-
siderable attention, due to shorter reaction times, increased yields,
and fewer side reactions.31
The present paper reports both the microwave-assisted and
conventional synthesis of metal (Zn, Ni, Cu and Co) phthalocya-
nines 6–9. These phthalocyanines display good solubility in com-
mon organic solvents such as DMSO, DMF, CHCl3, THF, CH2Cl2
and CH3CN.
⇑
Corresponding author. Tel.: +98 861 4173400; fax: +98 861 4173406.
E-mail address: a-karimi@araku.ac.ir (A.R. Karimi).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.10.122

124
A. R. Karimi, F. Bayat / Tetrahedron Letters 53 (2012) 123–126
OH
O
CHO
O
O
i
O
O
+
2
O
OH
1
2
3
O
N
O
N
i
: DMF, MW 350 W, 2 min.
ii : DMF, K2CO3, N2, 25 oC, 24 h
iii : DMAE, MX, MW 350 W, 10 min
iv: DMAE, MX, reflux, N2, 24 h
O
CN
CN
ii
4
O
O
O
O
N
M
N
NO2
O
O
N
N
O
O
N
N
CN
CN
M
Co
Cu
MX
6-9
6
O
CoCl2
O
O
O
O
7
CuCl
NiCl2
5
O
O
8
9
Ni
Zn
O
Zn(OAc)2
iii or iv
6-9
Scheme 1. Synthesis of metallophthalocyanines 6–9.
The preparation of substituted phthalonitrile derivatives is an
The 1H NMR spectra were also in good agreement with the
structures of the synthesized compounds. The spectrum of 5 exhib-
ited aliphatic (–CH3, –CH3, –CH2, –CH2 and –CH) protons at d 1.03, d
1.14, d 2.25, d 2.51 and d 4.81, as a singlet, singlet, ABq, broad sin-
glet and singlet, respectively, and the aromatic protons in the low
field region around d 6.91–7.70 as doublets and doublet of dou-
blets. 1H NMR measurements 6 and 7 were precluded due to their
paramagnetic nature. On the other hand, the 1H NMR spectra were
in good agreement with the structures of 8 and 9. The aromatic
protons appeared at d 6.90–7.82 for 8 and at d 7.01–9.10 for 9 while
the aliphatic –CH signals were observed in the range d 1.04–4.72
for 8 and at d 0.90–4.67 for 9.
The UV–vis spectral properties of Pcs have been of intrinsic
interest since their inception. The spectra of MPc complexes con-
sist of two strong absorption regions at 600–700 nm (Q band)
and around 300–400 nm (Soret or B band). The UV–vis spectra of
the phthalocyanines in chloroform are shown in Figure 1. The UV
spectra of CoPc, NiPc, ZnPc and CuPc show single intense bands
at 669, 670, 676, and 677 nm, respectively. There is also a shoulder
at slightly higher energy for all the phthalocyanines. The weaker
absorptions appear at 604, 604, 607, and 610 nm for CoPc, NiPc,
ZnPc, and CuPc, respectively. This is typical of metal complexes
of substituted and unsubstituted metallophthalocyanines with
D4h symmetry.34 The B bands for CoPc, NiPc, ZnPc, and CuPc were
observed at 238, 286; 238, 287; 237, 275, 348; 244 and 333 nm,
respectively.
important step in phthalocyanine synthesis. Nucleophilic aromatic
substitution of the nitro group in 4-nitrophthalocyanine is a useful
route to many tetrasubstituted phthalocyanines owing to the rela-
tive ease of this displacement. Using this method, suitable substit-
uents can be introduced into the periphery of the final
phthalocyanine to enhance solubility. The synthetic route to the
compounds presented in this work is shown in Scheme 1.
Compound 3 was prepared via the one-pot pseudo three-com-
ponent condensation of dimedone (1) and p-hydroxybenzaldehyde
(2) using PPA–SiO2 as the catalyst.32 Dicyano compound 5 was ob-
tained by base-catalyzed nucleophilic displacement of 4-nitropht-
halonitrile 4 with 1,8-dioxo-octahydroxanthene 3. The reaction
was carried out at room temperature in anhydrous DMF with
anhydrous K2CO3 as the base. Cyclotetramerization of dinitrile
compound 5 in the presence of anhydrous metal salts [CoCl2, CuCl,
NiCl2 and Zn(OAc)2], gave the desired metallophthalocyanines 6–9
in 2-(dimethylamino)ethanol (DMAE) under microwave irradiation
or via conventional heating. The products were precipitated by
addition of ethanol and filtered. The residues were washed with
ethanol and hot distilled water, respectively. Elemental analysis,
IR, 1H NMR, and UV–vis spectra confirmed the proposed structures
of the synthesized componds.33 Thermogravimetric analysis (TGA)
was used for determining the thermal stability of these complexes.
In the IR spectrum, the formation of compound 3 was confirmed
by the appearance of a new band at 3412 cmÀ1 related to the OH
group. The disappearance of the OH band of 1,8-dioxo-octahydrox-
anthene 3 at 3412 cmÀ1 and the NO2 band of 4-nitrophthalonitrile
4 at 1538 and 1355 cmÀ1, and the appearance of a CN band at
2233 cmÀ1 indicated the formation of compound 5. After conver-
sion of 5 into phthalocyanines 6–9, this sharp CN vibration was
no longer present.
In this study, the aggregation behavior of the phthalocyanines (
8–9) was investigated in different solvents (chloroform, dichloro-
methane, DMF, DMSO, and THF). While complex 9 did not show
aggregation in these solvents, complex 8 showed aggregation in
DMSO and minimal aggregation in DMF, as judged by the broaden-
ing of the Q band (Tables 1 and 2).

A. R. Karimi, F. Bayat / Tetrahedron Letters 53 (2012) 123–126
125
Table 3
Thermal analysis data for 6–9
Pc
Temp of dec. °C Mass loss Probable Nature of fragment lost
(% found) (% calcd)
O
O
3
1
229–506
506–866
36
40.26
13.42
O
CoPc (6)
O
O
13.24
O
O
O
O
CuPc (7) 240–781
70.77
71.87
4
4
O
O
O
NiPc (8)
300–886
51
53.69
5.91
O
ZnPc (9) 200–272
5.2
8CH3
O
O
2
O
O
288–540
33.90
13.81
34.53
13.38
O
O
Figure 1. Absorption spectra of 6–9 in chloroform (c = 2 Â 10À5).
1
O
O
540–869
1
O
Table 1
Absorption data for phthalocyanine 8 in different solvents (c = 3 Â 10À5
)
Solvent
kmax (nm) (loge)
Acknowledgment
DMSO
DMF
CH3Cl
THF
673 (4.61), 622 (4.37), 282 (4.89)
670 (4.81), 606 (4.33), 281 (4.95)
669 (4.90), 604 (4.35), 287 (4.97), 241 (4.91)
668 (4.85), 603 (4.32), 294 (4.89), 251 (4.83)
669 (4.85), 603 (4.31), 285 (4.93), 237 (4.91)
We gratefully acknowledge the financial support from the Re-
search Council of Arak University.
CH2Cl2
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2011.10.122.
Table 2
Absorption data for phthalocyanines 9 in different solvents (c = 3 Â 10À5
)
Solvent
kmax (nm) (log
e)
References and notes
DMSO
DMF
CH3Cl
THF
677 (4.76), 610 (4.17), 353 (4.52), 274 (4.69)
670 (4.81), 606 (4.33), 281 (4.95)
675 (4.96), 608 (4.33), 350 (4.73), 274 (4.81), 237 (4.85)
671 (4.88), 606 (4.28), 374 (4.66), 289 (4.69), 250 (4.81)
679 (4.71), 611 (4.16), 351 (4.57), 237 (4.88)
1. Torre, G.; Bottari, G.; Hahn, U.; Torres, T. Struct. Bond. 2010, 135, 1.
2. Makhseed, S.; Bumajdad, A.; Ghanem, B.; Msayib, K.; McKeown, N. B.
Tetrahedron Lett. 2004, 45, 4865.
3. Yang, F.; Forrest, S. R. J. Am. Chem. Soc. 2008, 2, 1022.
CH2Cl2
4. Fischer, M. K. R.; Lopez-Duarte, I.; Wienk, M. M.; Martinez-Diaz, M. V.; Janssen,
R. A. J.; Bauerle, P.; Torres, T. J. Am. Chem. Soc. 2009, 131, 8669.
5. Somani, P. R.; Radhakrishnan, S. Mater. Chem. Phys. 2002, 77, 117.
6. Clarke, M. J. Coord. Chem. Rev. 2002, 232, 69.
The thermal properties of all the synthesized MPcs were ana-
lyzed by thermal gravimetric analysis (TGA) in the temperature
range 30–900 °C under a nitrogen atmosphere with a heating rate
of 10 °C/min. The initial weight loss up to 200 °C was related to the
residual solvent which was typical of a TGA heating run. The ZnPc,
CoPc and CuPc complexes exhibited some degradation steps whilst
NiPc had one distinct degradation step. For all the complexes ex-
cept CuPc, the xanthene moieties were sensitive to decomposition
up to 900 °C and the aromatic rings were stable. CuPc from 240 up
to 781 °C in two steps lost 70.77% of its mass which was attributed
to the four xanthenes and four C6H4O groups. The groups which
can be attributed to weight loss are listed in Table 3. The initial
decomposition temperatures of the compounds are in the order:
Ni > Cu > Co > Zn. No obvious correlation between the transition
metal ions in the phthalocyanine rings and the initial decomposi-
tion temperature was observed.
In conclusion, the metallophthalocyanines 6–9 showed good
solubility in common organic solvents (0.01 g in 5 mL of DMSO,
DMF, CHCl3, THF and CH2Cl2). Furthermore, for the conversion of
dinitrile 5 into metallophthalocyanines microwave irradiation en-
hanced the yield and reduced the reaction times in comparison
with conventional heating. While complex 9 did not show aggrega-
tion, complex 8 showed aggregation in DMSO and minimal aggre-
gation in DMF. The Pcs reported in this work can be considered as
efficient candidates for solution studies requiring the monomeric
form of these materials as in the case of photosensitizers used in
photodynamic therapy.
7. Hu, Y. Y.; Lai, G. Q.; Shen, Y. J.; Li, Y. F. Dyes Pigments 2005, 66, 49.
8. Cai, X.; Zhang, Y.; Qi, D.; Jiang, J. J. Phys. Chem. A 2009, 113, 2500.
9. Schlettwein, D.; Wöhrle, D.; Jaeger, N. I. J. Electrochem. Soc. 1989, 136, 2882.
10. Ding, X.; Shen, S.; Zhou, Q.; Xu, H. Dyes Pigments 1999, 40, 187.
11. Basova, T.; Kol’tsov, E.; Ray, A. K.; Hassan, A. K.; Gürek, A. G.; Ahsen, V. Sens.
Actuators, B 2006, 113, 127.
12. De La Torre, G.; Vazquez, P.; Agullo-Lopez, F.; Torres, T. J. Mater. Chem. 1998, 8,
1671.
13. Leznoff, C. C.; Lever, A. B. P. In Phthalocyanines, Properties and Applications; VCH:
New York, 1996; Vol. 4,
14. Cook, M. J.; McKeown, N. B.; Simmons, J. M.; Thomson, A. J.; Daniel, M. F.;
Harrison, K. J.; Richardson, R. M.; Roser, S. J. J. Mater. Chem. 1991, 1, 121.
15. Kaliya, O. L.; Lukyanets, E. A.; Vorozhtsov, G. N. J. Porphyrins Phthalocyanines
1999, 3, 592.
16. Beck, A.; Mangold, K. M.; Hanack, M. Chem. Ber. 1991, 124, 2315.
17. (a) Ogunsipe, A.; Nyokong, T. J. Photochem. Photobiol., A: Chem. 2005, 173, 211;
(b) Sylvain, I.; Zerrouki, R.; Granet, R.; Huang, Y. M.; Lagorce, J.-F.; Guilloton,
M.; Blais, J.-C.; Krausz, P. Bioorg. Med. Chem. 2002, 10, 57.
18. Sharon, N.; Lis, H. Science 1989, 246, 227.
19. Hanack, M.; Knecht, S.; Polley, R. Chem. Ber. 1995, 128, 929.
20. Biyikliog˘lu, Z.; Kantekin, H. Polyhedron 2008, 27, 1650.
21. Biyikliog˘lu, Z.; Kantekin, H. J. Organomet. Chem. 2008, 693, 505.
22. Biyikliog˘lu, Z.; Koca, A.; Kantekin, H. Polyhedron 2009, 28, 2171.
23. Poupelin, J. P.; Saint-Rut, G.; Foussard-Blanpin, O.; Narcisse, G.; Uchida-Ernouf,
G.; Lacroix, R. Eur. J. Med. Chem. 1978, 13, 67.
24. Hideo, T. Jpn Tokkyo Koho JP 56005480, 1981; Chem. Abstr. 1981, 95, 80922b.
25. Lambert, R. W.; Martin, J. A.; Merrett, J. H.; Parkes, K. E. B.; Thomas, G. J. PCT Int.
Appl. WO 9706178, 1997; Chem. Abstr. 1997, 126, 212377y.
26. Ion, R. M. Prog. Catal. 1997, 2, 55.
27. Saint-Ruf, G.; De, A.; Hieu, H. T. Bull. Chim. Ther. 1972, 7, 83.
28. Sirkecioglu, O.; Tulinli, N.; Akar, A. J. Chem. Res. (S) 1995, 502.
29. Zhao, T. F.; Zhao, D. F.; Sun, X. S.; Cheng, L. B. Chem. Ind. Eng. 1998, 49, 515.
30. Ji, X. S.; Liu, Y.; Miao, Y.; Jin, T. Chin. J. Pharm. Sci. 1998, 7, 221.
31. Kappe, C. O. Angew. Chem., Int. Ed. 2004, 43, 6250.
32. Kantevari, S.; Bantu, R.; Nagarapu, L. J. Mol. Catal. A: Chem. 2007, 269, 53.

126
A. R. Karimi, F. Bayat / Tetrahedron Letters 53 (2012) 123–126
33. Preparation of 9-(4-hydroxyphenoxy)-3,3,6,6-tetramethyl-3,4,6,7-tetrahydro-2H-
xanthene-1,8(5H,9H)-dione (3): To a mixture of dimedone (1) (0.25 g, 1.7 mmol)
and 4-hydroxybenzaldehyde (2) (0.11 g, 0.89 mmol) in DMF (2 mL), one drop
of H2SO4 was added. The mixture was irradiated at 350 W for 2 min. After
cooling to room temperature, EtOH (5 mL) and H2O (2 mL) were added. The
resulting precipitate was filtered and washed with hot H2O. Yield: 87%. Mp:
2CH3), 2.19–2.32 (4H, ABq, 2CH2), 2.51 (4H, s, 2CH2), 4.81 (1H, s, CH), 6.91 (2H,
d, J = 8.40 Hz, Harom), 7.16 (1H, dd, J = 8.70 and 2.25 Hz, Harom), 7.28 (1H,
masked by the CHCl3 signal), 7.40 (2H, d, J = 8.42 Hz, Harom), 7.70 (1H, d,
J = 8.70 Hz,
Harom). Cobalt(II) phthalocyanine (6): Method A: Compound 5
(0.10 g, 0.2 mmol) and anhydrous CoCl2 (8.8 mg, 0.067 mmol) were added to 2-
(dimethylamino)ethanol (DMAE) (2 mL). The mixture was irradiated at 350 W
for 10 min and then cooled to room temperature. In the next step EtOH was
added and the product was filtered under reduced pressure. Yield: 55%. IR
250–252 °C. IR (KBr) (m
max, cmÀ1): 3412, 3024, 2962, 2931, 2899, 2872, 1662,
1614, 1514, 1450, 1359, 1246, 1201, 1003, 839. Preparation of 4-[4-(3,3,6,6-
tetramethyl-1,8-dioxo-2,3,4,5,6,7,8,9-octahydro-1H-xanthen-9-yl)phenoxy]
phthalonitrile (5): 4-Nitrophthalonitrile (4) (0.11 g, 0.6 mmol) and compound 3
(0.22 g, 0.61 mmol) were dissolved in DMF (2 mL). Anhydrous K2CO3 (0.084 g,
0.61 mmol) was added and the mixture was stirred at room temperature for
24 h. Next, acetone (6 mL) and H2O (2 mL) were added. The product was
(KBr) (
1097, 856. UV/vis (CHCl3): kmax/nm: 669, 604, 285, 238. Anal. Calcd for
124H112CoN8O16: C, 73.40; H, 5.56; N, 5.52. Found: C, 73.00; H; 5.69; N; 5.80.
Method B: A mixture of compound 5 (0.10 g, 0.2 mmol), anhydrous CoCl2
(8.8 mg, 0.067 mmol) and DMAE (10 ml) was refluxed under nitrogen
m
max, cmÀ1): 2957, 2872, 1670, 1601, 1504, 1469, 1359, 1195, 1165,
C
a
filtered and washed with hot H2O. Yield: 80%, mp: 200–202 °C. IR (KBr) (mmax
,
atmosphere for 24 h. The above purification method was applied to this
material. Yield: 45%.
34. Riesen, A.; Zehnder, M.; Kaden, T. A. Helv. Chim. Acta 1986, 69, 2074.
cmÀ1): 3041, 2960, 2872, 2233, 1662, 1595, 1491, 1361, 1257, 1195, 1136,
1001, 841. 1H NMR (DMSO-d6, 300 MHz) dH: 1.03 (6H, s, 2CH3), 1.14 (6H, s,