Synthesis of sulfonamide-substituted phthalocyanines

Article abstract of DOI:10.1016/j.tetlet.2009.09.128

The synthesis and characterization of new phthalocyanines bearing eight N-alkyl or N-aryl sulfonamide groups is described. The synthetic route involves the chorosulfonation of 4,5-diphenoxyphthalonitrile with chlorosulfonic acid and reaction of the resulting 4,5-bis(p-chlorosulfonylphenoxy)phthalonitrile with amines. The sulfonamide-substituted phthalonitriles are then cyclotetramerized to yield the title compounds in good yields (50-83%).

Full text of DOI:10.1016/j.tetlet.2009.09.128

Tetrahedron Letters 50 (2009) 6882–6885
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Tetrahedron Letters
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Synthesis of sulfonamide-substituted phthalocyanines
*
Eliana F. A. Carvalho, Mário J. F. Calvete, Augusto C. Tomé , José A. S. Cavaleiro
Department of Chemistry/QOPNA, University of Aveiro, 3810-193 Aveiro, Portugal
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 30 June 2009
Revised 21 September 2009
Accepted 22 September 2009
Available online 25 September 2009
The synthesis and characterization of new phthalocyanines bearing eight N-alkyl or N-aryl sulfonamide
groups is described. The synthetic route involves the chorosulfonation of 4,5-diphenoxyphthalonitrile
with chlorosulfonic acid and reaction of the resulting 4,5-bis(p-chlorosulfonylphenoxy)phthalonitrile
with amines. The sulfonamide-substituted phthalonitriles are then cyclotetramerized to yield the title
compounds in good yields (50–83%).
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Phthalocyanines
Phthalonitriles
Chlorosulfonation
Sulfonamides
1. Introduction
rile, followed by the reaction of the chlorosulfonyl groups with
alkyl or aryl amines and then the macrocyclization of the resulting
The pursuit of new materials for novel applications is a continuous
purpose for organic and material chemists. Peripheral modulation of
known aromatic core compounds is still an attractive and challenging
pathway for materials with new, or improved, properties. In this con-
text, phthalocyanines, the longknown bluish pigments, appear to still
have some niches of novelty that should continue to be explored.
Due to their properties, phthalocyanines have a vast area of
applications,1 namely as dyes,2 catalysts,3,4 chemical sensors,5,6
as sensitizers in photodynamic therapy,7–10 and in nonlinear optics
(NLO),11–13 optical data storage or light-harvesting.14–16
Considering applications that require soluble compounds, such
as the pharmacological ones, for instance, the extreme insolubility
of phthalocyanines in water and in most organic solvents is a clear
disadvantage. Functionalization of the periphery of a phthalocya-
nine with appropriate polar groups can afford phthalocyanine
derivatives with increased solubility in polar organic solvents or
in aqueous media. Typical examples are the phthalocyanines bear-
ing cationic groups,17 sugar moieties,18 or cyclodextrin units.19 Sul-
fonated phthalocyanines, both in the sulfonato and sulfonamide
forms, are another group of such compounds.20,21 Some sulfonated
phthalocyanines show potential application as catalysts,4,22 sen-
sors,20,23 while others are being studied as photosensitizers for
photodynamic therapy.24,25
sulfonamide-substituted phthalonitriles.
SO2NR1R2
SO2NR1R2
R1R2NO2S
R1R2NO2S
O
3'
2 '
1 '
O
2
1
O
O
3
N
Zn
N
4
N
N
N
N
N
N
O
O
O
O
SO2NR1R2
SO2NR1R2
R1R2NO2S
R1R2NO2S
2'' 3''
1''
9: R1 = H, R2 =
10: R1 = R2
2. Results and discussion
OCH3
=
(CH2)11CH3
In this Letter we describe a new method to synthesize symmet-
rically substituted phthalocyanines bearing eight sulfonamide
groups. It involves the chlorosulfonation of a diphenoxyphthalonit-
Sulfonation of phthalocyanines usually produces a mixture of
positional isomers or compounds with a varying number of
sulfonic acid groups. In order to circumvent these two problems,
we decided to use a symmetrical phthalonitrile and to introduce
* Corresponding author. Tel.: +351 234 370 712; fax: +351 234 370 084.
E-mail address: actome@ua.pt (A.C. Tomé).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.09.128

E. F. A. Carvalho et al. / Tetrahedron Letters 50 (2009) 6882–6885
6883
the sulfonamide groups in the phthalocyanine precursors. Nucleo-
philic substitution of the two chlorine atoms by phenoxy groups at
the commercially available 4,5-dichlorophthalonitrile (1) afforded
4,5-diphenoxyphthalonitrile (2) in 85% yield (Scheme 1).26
Treatment of 4,5-diphenoxyphthalonitrile with chlorosulfonic acid
produced 4,5-bis(p-chlorosulfonylphenoxy)phthalonitrile (3).27
Reaction of 3 with various amines, namely diethylamine, p-anisi-
dine, and didodecylamine, gave the desired sulfonamide-substi-
tuted phthalonitriles 4–6, respectively, in moderate to good
yields.28 The 4,5-bis(p-chlorosulfonylphenoxy)phthalonitrile (3)
was isolated simply by filtration after precipitation from cold
water, without any further purification.
Cyclotetramerization of phthalonitrile 4, in a solution of magne-
sium bis(pentan-1-olate) in octan-1-ol,12 afforded the expected
phthalocyanine 7 in 50% yield (Scheme 2).29 Treatment of phthalo-
cyanine 7 with CF3COOH in THF gave phthalocyanine free-base 8 in
72% yield.30
Phthalocyanines 9 and 10 were synthesized in high yields (69%
and 83%, respectively) by a slightly different method (Zn(OAc)2 in
N,N-dimethylaminoethanol at reflux).31,32
The electronic absorption spectra of the sulfonamide-substi-
tuted phthalocyanines 7–10 are exemplified in Figure 1 and sum-
marized in Table 1. Figure 1 shows the UV–vis spectra of the
magnesium complex 7 and the metal-free phthalocyanine 8. Both
compounds display UV–vis spectra typical for metallo- and free-
base phthalocyanines: a Soret band (B band) at 359 nm and a Q
band at 677 nm for 7, while compound 8 shows a Soret band at
348 nm and typical split Q bands at 662 and 697 nm.
As expected, the 1H NMR spectra of compounds 7–10 display
common features corresponding to the signals of the phthalocya-
nine
a
protons and phenoxy groups. For instance, the 1H NMR
spectrum of compound 7 shows a singlet at d = 9.21 ppm corre-
sponding to the eight phthalocyanine H-1 protons and two dou-
blets at d = 7.20 ppm (J = 8.8 Hz) and at d = 7.82 ppm (J = 8.8 Hz)
K2CO3, DMF
90 ºC
NC
NC
Cl
NC
NC
O
O
+
HO
85%
Cl
1
2
diethylamine
CH3CN, rt
NC
NC
O
O
SO2NEt2
SO2NEt2
HSO3Cl
5-10 ºC
67%
4
p-anisidine,
CH3CN, rt
NC
NC
O
O
SO2Cl
NC
NC
O
O
SO2 NH
OCH3
OCH3
42%
NH
SO2Cl
SO2
5
3
didodecylamine
K2CO3
CH2Cl2, rt
(CH2)11CH3
NC
NC
O
O
SO2
SO2
N
N
(CH2)11CH3
(CH2)11CH3
28%
(CH2)11CH3
6
Scheme 1.
SO2NEt2
SO2NEt2
Et2NO2S
Et2NO2S
O
O
O
O
N
M
N
Mg,
pentan-1- ol
160 ºC
N
N
N
N
NC
NC
O
O
SO2NEt2
SO2NEt2
N
N
50%
4
O
O
O
O
SO2NEt2
SO2NEt2
Et2NO2S
Et2NO2S
7: M = Mg
8: M = 2H
CF3COOH
THF, 70 ºC
72%
Scheme 2.

6884
E. F. A. Carvalho et al. / Tetrahedron Letters 50 (2009) 6882–6885
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
1
(a)
(b)
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
A
b
s
A
b
s
o
o
r
b
a
n
c
r
b
a
n
c
e
e
-0.1
-0.1
Wavelength (nm)
Wavelength (nm)
Figure 1. UV–vis spectra of phthalocyanines 7 (a) and 8 (b) recorded in CH2Cl2.
11. De la Torre, G.; Vázquez, P.; Agulló-López, F.; Torres, T. Chem. Rev. 2004, 104,
Table 1
3723–3750.
UV–vis data for compounds 7–10 (recorded in CH2Cl2)
12. Calvete, M. J. F.; Dini, D.; Flom, S. R.; Hanack, M.; Pong, R. G. S.; Shirk, J. S. Eur. J.
Org. Chem. 2005, 3499–3509.
13. Saydam, S.; Yılmaz, E.; Bag˘ci, F.; Yag˘hog˘lu, H. G.; Elmalı, A.; Salih, B.; Bekarog˘lu,
O. Eur. J. Inorg. Chem. 2009, 2096–2103.
14. Li, X.; Sinks, L. E.; Rybtchinski, B.; Wasielewski, M. R. J. Am. Chem. Soc. 2004,
126, 10810–10811.
15. Cid, J.-J.; García-Iglesias, M.; Yum, J.-H.; Forneli, A.; Albero, J.; Martínez-Ferrero,
E.; Vázquez, P.; Grätzel, M.; Nazeeruddin, M. K.; Palomares, E.; Torres, T. Chem.
Eur. J. 2009, 15, 5130–5137.
Phthalocyanine
B band (nm)
Q band(s) (nm)
7
8
9
359
348
355
356
677
662 and 697
674
10
677
16. El-Khouly, M. E.; Kim, J. H.; Kay, K.-Y.; Choi, C. S.; Ito, O.; Fukuzumi, S. Chem.
Eur. J. 2009, 15, 5301–5310.
due to the resonances of the protons H-20 and H-30, respectively.
The signals corresponding to the protons of the ethyl groups ap-
pear as a triplet at d = 1.16 ppm and a quartet at d = 3.26 ppm.
The 1H NMR spectrum of phthalocyanine 9 shows, in the aliphatic
region, a diagnostic singlet at d = 3.64 ppm corresponding to the
OCH3 group. The 1H NMR spectrum of phthalocyanine 10 shows,
in the aliphatic region, signals at d = 0.86, 1.24, and 3.10 ppm cor-
responding to the resonances of the CH3, CH2, and NCH2 protons,
respectively.
In conclusion, the method reported here allows the synthesis, in
high yields, of phthalocyanines bearing eight sulfonamide groups
as single compounds. Since many types of amines can be used (pri-
mary or secondary amines, alkyl amines with short or long alkyl
groups, aryl or hetaryl amines), this method is useful for the prep-
aration of a range of new sulfonamide-substituted phthalocyanines
specifically designed for a given application.
17. (a) Idowu, M.; Nyokong, T. Polyhedron 2009, 28, 416–424; (b) Makarov, D. A.;
Yuzhakova, O. A.; Slivka, L. K.; Kuznetsova, N. A.; Negrimovsky, V. M.; Kaliya, O.
L.; Lukyanets, E. A. J. Porphyrins Phthalocyanines 2007, 11, 586–595; (c)
Sharman, W. M.; van Lier, J. E. J. Porphyrins Phthalocyanines 2005, 9, 651–658;
(d) Chiti, G.; Dei, D.; Fantetti, L.; Roncucci, G. J. Porphyrins Phthalocyanines 2005,
9, 463–469.
18. (a) Ana, R. M.; Soares; Tomé, J. P. C.; Neves, M. G. P. M. S.; Tomé, A. C.; Cavaleiro,
J. A. S.; Torres, T. Carbohydr. Res. 2009, 344, 507–510; (b) Liu, J.-Y.; Lo, P.-C.;
Fong, W.-P.; Ng, D. K. P. Org. Biomol. Chem. 2009, 7, 1583–1591; (c) Zorlu, Y.;
Ermeydan, M. A.; Dumoulin, F.; Ahsen, V.; Savoie, H.; Boyle, R. W. Photochem.
Photobiol. Sci. 2009, 8, 312–318; (d) Iqbal, Z.; Hanack, M.; Ziegler, T. Tetrahedron
Lett. 2009, 50, 873–875; (e) Choi, C.-F.; Huang, J.-D.; Lo, P.-C.; Fong, W.-P.; Ng,
D. K. P. Org. Biomol. Chem. 2008, 6, 2173–2181; (f) Ribeiro, A. O.; Tomé, J. P. C.;
Neves, M. G. P. M. S.; Tomé, A. C.; Cavaleiro, J. A. S.; Iamamoto, Y.; Torres, T.
Tetrahedron Lett. 2006, 47, 9177–9180; (g) Alvarez-Mico, X.; Calvete, M. J. F.;
Hanack, M.; Ziegler, T. Tetrahedron Lett. 2006, 47, 3283–3286.
19. Ribeiro, A. O.; Tomé, J. P. C.; Neves, M. G. P. M. S.; Tomé, A. C.; Cavaleiro, J. A. S.;
Serra, O. A.; Torres, T. Tetrahedron Lett. 2006, 47, 6129–6132.
20. (a) Pochekaylov, S.; Nešpu˚ rek, S.; Rakušan, J.; Karásková, M. Mol. Cryst. Liq.
Cryst. 2007, 468, 23–31; (b) Sanchez, M.; Fache, E.; Bonnet, D.; Meunier, B. J.
Porphyrins Phthalocyanines 2001, 5, 867–872.
21. Ali, H.; Cauchon, N.; van Lier, J. E. Photochem. Photobiol. Sci. 2009, 8, 868–874.
22. Das, G.; Sain, B.; Kumar, S.; Garg, M. O.; Dhar, G. M. Catal. Today 2009, 141, 152–
156.
Acknowledgments
23. Basova, T.; Tsargorodskaya, A.; Nabok, A.; Hassan, A. K.; Gürek, A. G.; Gümüs,
G.; Ahsen, V. Mater. Sci. Eng., C 2009, 29, 814–818.
24. Derkacheva, V. M.; Mikhalenko, S. A.; Solov’eva, L. I.; Alekseeva, V. I.; Marinina,
L. E.; Savina, L. P.; Butenin, A. V.; Lukyanets, E. A. Russ. J. Gen. Chem. 2007, 77,
1117–1125.
The authors thank Fundação para a Ciência e a Tecnologia (FCT)
and FEDER for funding the Organic Chemistry Research Unit and
the Project PTDC/QUI/74150/2006. M. Calvete also thanks FCT for
his post-doc grant (SFRH/BPD/26775/2006).
´
´
25. Palewska, K.; Sujka, M.; Urasinska-Wójcik, B.; Sworakowski, J.; Lipinski, J.;
Nešpu˚ rek, S.; Rakušan, J.; Karásková, M. J. Photochem. Photobiol. A: Chem. 2008,
197, 1–12.
References and notes
26. Wöhrle, D.; Eskes, M.; Shigehara, K.; Yamada, A. Synthesis 1993, 194–196.
27. 4,5-Bis(4-chlorosulfonylphenoxy)phthalonitrile, 3. 4,5-Diphenoxyphthalonit-
rile (1.65 g, 5.29 mmol) was slowly added to ice cooled chlorosulfonic acid
(3.5 mL, 52 mmol). The reaction mixture was stirred for 45 min at 0 °C and
then it was poured onto ice (200 g). The resulting solid was filtered, washed
with cold water, and dried under vacuum. Compound 3 was used in the
subsequent reactions without any further purification.
28. Typical procedure: Synthesis of 4,5-bis[4-(diethylaminosulfonyl)phenoxy]pht-
halonitrile, 4. Phthalonitrile 3 (1.00 g, 1.96 mmol) was dissolved in acetonitrile
(5 mL) and the solution was cooled to 0 °C. Diethylamine (1.24 mL, 12 mmol) was
added slowly. The reaction mixture was then stirred at room temperature for 3 h.
The reaction mixture was poured into water (100 mL) with ice (200 g) and the
resulting solid was filtered off. The product was crystallized from methanol. Yield:
0.77 g (67%), mp 164–165 °C. 1H NMR (300 MHz, CDCl3): d = 1.15 (t, 12H,
J = 7.1 Hz, CH3), 3.25 (q, 8H, J = 7.1 Hz, CH2), 7.05 (dd, J = 6.8 and 2.1 Hz, 4H, H-20,
H-60), 7.42 (s, 2H, H-3, H-6), 7.85 (dd, J = 6.8 and 2.1 Hz, 4H, H-30, H-50); 13C NMR
(75 MHz, CDCl3): d = 14.2, 42.1, 112.5, 114.3, 118.7, 124.9, 129.7, 137.6, 150.5,
157.4; HRMS (MALDI-TOF): m/z calcd for C28H31N4O6S2 [M+H]+ 583.1685, found
583.1697.
1. For a recent review, see: De la Torre, G.; Claessens, C. G.; Torres, T. Chem.
Commun. 2007, 2000–2015.
2. McKeown, N. B.. In The Porphyrin Handbook; Kadish, K. M., Smith, K. M., Guilard,
R., Eds.; Academic Press: New York, 2003; Vol. 15, pp 61–124.
3. Shinohara, H.; Tsaryova, O.; Schnurpfeil, G.; Wöhrle, D. J. Photochem. Photobiol.
A: Chem. 2006, 184, 50–57.
4. Nicastro, M.; Tonucci, L.; d’Alessandro, N.; Bressan, M.; Dragani, L. K.; Morvillo,
A. Inorg. Chem. Commun. 2007, 10, 1304–1306.
5. Ding, X.; Shen, S.; Zhou, Q.; Xu, H. Dyes Pigments 1999, 40, 187–191.
6. Bohrer, F. I.; Colesniuc, C. N.; Park, J.; Ruidiaz, M. E.; Schuller, I. K.; Kummel, A.
C.; Trogler, W. C. J. Am. Chem. Soc. 2009, 131, 478–485.
7. Vittar, N. B. R.; Prucca, C. G.; Strassert, C.; Awruch, J.; Rivarola, V. A. Int. J.
Biochem. Cell Biol. 2008, 40, 2192–2205.
8. Lo, P.-C.; Zhao, B.; Duan, W.; Fong, W.-P.; Ko, W.-H.; Ng, D. K. P. Bioorg. Med.
Chem. Lett. 2007, 17, 1073–1077.
9. Mao, J.; Zhang, Y.; Zhu, J.; Zhang, C.; Guo, Z. Chem. Commun. 2009, 908–910.
10. Nishiyama, N.; Nakagishi, Y.; Morimoto, Y.; Lai, P.-S.; Miyazaki, K.; Urano, K.;
Horie, S.; Kumagai, M.; Fukushima, S.; Cheng, Y.; Jang, W.-D.; Kikuchi, M.;
Kataoka, K. J. Controlled Release 2009, 133, 245–251.
29. {2,3,9,10,16,17,23,24-Octakis[4-(diethylaminosulfonyl)phenoxy]phthalo
cyaninato}magnesium(II), 7. Magnesium turnings (9.27 mg) were added to

E. F. A. Carvalho et al. / Tetrahedron Letters 50 (2009) 6882–6885
6885
pentan-1-ol (0.5 mL) and the suspension was heated to 150 °C (reflux) and
maintained at that temperature until the complete formation of the alkoxide
(ꢀ1 h). Octan-1-ol (1 mL) was added to the suspension, followed by
phthalonitrile 4 (100 mg, 0.172 mmol). The reaction mixture was stirred at
160 °C for 3 h and, after cooling to rt, it was poured onto a 5/1 methanol/water
mixture (20 mL). The resulting precipitate was isolated by filtration and washed
several times with methanol. Yield: 50.5 mg (50%). Mp >300 °C, 1H NMR
(300 MHz, CDCl3): d = 1.16 (t, 48H, J = 7.1 Hz, CH3), 3.26 (q, 32H, J = 7.1 Hz,
CH2), 7.20 (d, 16H, J = 8.8 Hz, H-20), 7.82 (d, 16H, J = 8.8 Hz, H-30), 9.21 (s, 8H, Pc-
H); 13C NMR (75 MHz, CDCl3): d = 13.6, 41.5, 116.1, 116.6, 128.6, 134.2, 135.9,
d = 13.6, 41.5, 116.1, 116.6, 128.6, 134.2–135.9, 147.7, 152.8, 160.1; UV–vis
(CH2Cl2): kmax (log e) = 348 (5.15), 607 (5.54), 662 (5.38), 697 (5.55) nm; MS
(MALDI-TOF): m/z 2331.7 [M+H]+.
31. Spectroscopic data for 9: 1H NMR (300 MHz, CDCl3): d = 3.64 (s, 24H, OCH3),
6.79–7.09 (m, 48H, H-20, H-200, H-300); 7.54–7.71 (m, 16H, H-30); 9.28 (s, 8H, Pc-
H); 9.87 (s, 8H, NH); 13C NMR (75 MHz, CDCl3): d = 55.7, 115.1, 117.3, 117.6,
124.9, 130.3, 131.1, 134.6, 148.6–149.2, 151.6, 158.2, 161.1; UV–vis (THF): kmax
(log
e
.
) = 355 (5.03), 608 (4.65), 673 (5.53) nm; MS (MALDI-TOF): m/z 2792.4
[M]+Å
32. Spectroscopic data for 10: 1H NMR (300 MHz, CDCl3): d = 0.86 (t, 48H, J = 7.1 Hz,
CH3), 1.22–1.25 (m, 320H, CH2), 3.10 (q, 32H, J = 8.1 Hz, NCH2), 7.19 (d, 16H,
J = 8.8 Hz, H-20, H-60), 7.82 (d, 16H, J = 8.8 Hz, H-30, H-50), 9.22 (s, 8H, Pc-H); 13C
NMR (75 MHz, CDCl3): d = 13.5, 22.1–31.3, 47.9, 115.3, 116.6, 128.9, 134.0,
147.7, 152.8, 160.1; UV–vis (CH2Cl2): kmax (log e) = 359 (5.39), 610 (4.87), 677
(5.76) nm; MS (MALDI-TOF): m/z 2353.6 [M+H]+.
30. Spectroscopic data for 8: 1H NMR (300 MHz, CDCl3): d = ꢁ2.1 (s, 2H, NH), 1.16 (t,
48H, J = 7.1 Hz, CH3), 3.26 (q, 32H, J = 7.1 Hz, CH2), 7.20 (d, 16H, J = 8.8 Hz, H-
20), 7.82 (d, 16H, J = 8.8 Hz, H-30), 9.21 (s, 8H, Pc-H); 13C NMR (75 MHz, CDCl3):
135.7, 147.9, 152.9, 160.2; UV–vis (CH2Cl2): kmax (log
e) = 356 (5.16), 610
(4.69), 677 (5.63) nm; MS (MALDI-TOF): m/z 4636.3 [M+H]+.