Synthesis of an octa-tert-butylphthalocyanine: A low-aggregating and photochemically stable photosensitizer

Article abstract of DOI:10.1002/ejoc.201300415

The synthesis of a new octa-tert-butylphthalocyanine is described. First, the 4,5-di-tert-butylphthalonitrile building block was synthesized in a six-step approach, in which the last step is a three reaction domino sequence. Then, this phthalonitrile was cyclotetramerized to furnish a new phthalocyanine dye, which presented no aggregation in solution and good photophysical properties. The synthesis of a new octa-tert-butylphthalocyanine is described. First, the 4,5-di-tert-butylphthalonitrile building block was synthesized in a six-step approach, in which the last step is a three reaction domino sequence. Then, this phthalonitrile was cyclotetramerized to furnish a new phthalocyanine dye, which presented no aggregation in solution and good photophysical properties. Copyright

Full text of DOI:10.1002/ejoc.201300415

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Date: 11-06-13 09:48:31
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SHORT COMMUNICATION
Phthalocyanines
The synthesis of a new octa-tert-butyl-
phthalocyanine is described. First, the 4,5-
di-tert-butylphthalonitrile building block
was synthesized in a six-step approach, in
which the last step is a three reaction dom-
ino sequence. Then, this phthalonitrile was
cyclotetramerized to furnish a new phthalo-
cyanine dye, which presented no aggre-
gation in solution and good photophysical
properties.
N. R. S. Gobo, T. J. Brocksom,
J. Zukerman-Schpector,
K. T. de Oliveira* .............................. 1–5
Synthesis of an Octa-tert-butylphthalo-
cyanine: A Low-Aggregating and Photo-
chemically Stable Photosensitizer
Keywords: Dyes / Chromophores / Macro-
cycles / Photodynamic therapy / Diels–
Alder / Domino reactions
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Job/Unit: O30415
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Date: 11-06-13 09:48:31
Pages: 5
N. R. S. Gobo, T. J. Brocksom, J. Zukerman-Schpector, K. T. de Oliveira
SHORT COMMUNICATION
DOI: 10.1002/ejoc.201300415
Synthesis of an Octa-tert-butylphthalocyanine: A Low-Aggregating and
Photochemically Stable Photosensitizer
Nicholas R. S. Gobo,[a] Timothy J. Brocksom,[a] Julio Zukerman-Schpector,[a] and
Kleber T. de Oliveira*[a]
Keywords: Dyes / Chromophores / Macrocycles / Photodynamic therapy / Diels–Alder / Domino reactions
The synthesis of a new octa-tert-butylphthalocyanine is de-
scribed. First, the 4,5-di-tert-butylphthalonitrile building
block was synthesized in a six-step approach, in which the
last step is a three reaction domino sequence. Then, this
phthalonitrile was cyclotetramerized to furnish a new
phthalocyanine dye, which presented no aggregation in
solution and good photophysical properties.
containing 5-aminolevulinic acid (ALA) and menthyl frag-
ments showed low aggregation, water solubility, and very
good properties for PDT.[11]
The peripheral positions of unsubstituted PCs can be di-
rectly functionalized, but this leads to very complex mix-
tures of isomers and many byproducts, because of the harsh
conditions used for these transformations.[12] However, aim-
ing at solving this problem, cross-coupling reactions have
been described with success.[13]
Generally, functionalization of phthalonitriles with bulky
groups[14,15] has been considered as a versatile solution for
the synthesis of non-aggregating PCs. Nevertheless, to the
best of our knowledge, phthalonitriles with vicinal bulky
groups, such as tert-butyl at the 4,5-positions, have not been
reported,[16] and they thus represent an important synthetic
challenge.
Herein, we describe the synthesis of 4,5-di-tert-butyl-
phthalonitrile (8) by using a three-step domino sequence
that includes a Diels–Alder reaction as the key step in trans-
ferring two vicinal tert-butyl groups of a thiophene ring to
a benzenoid system. In addition, we describe the synthesis
of octa-tert-butylphthalocyanines 9 and 10 by using this
new phthalonitrile as the building block. Thus, we demon-
strate the potential of 8 to synthesize a range of new and
useful phthalocyanine derivatives (Scheme 1).
Introduction
Phthalocyanines (PCs) are aromatic macrocycles con-
taining 18π electrons that were accidentally discovered at
the beginning of the 1900s. However, they were only well-
characterized by Linstead and Robertson in the 1930s.[1] As
owing to their high thermal stability and low solubility, they
were first applied in the dye and textile industries.[1]
During the last century, several research groups discov-
ered that such systems have a strong absorption in the 600–
750 nm range and that they can be applied in many high-
technology areas such as transistors,[2] liquid crystals,[3]
semiconductors,[4] gas sensors,[5] solar cells,[6] catalysts,[7]
photodynamic therapy (PDT) agents,[8] and others.[9,10]
However, unsubstituted PCs present limitations for use in
some areas because of their tendency to undergo aggrega-
tion (π-stacking interactions), which leads to low solubility
in most known organic solvents and a reduction in their
optical and redox properties.[1] Known approaches to
counter this problem include the functionalization of PCs
at the peripheral positions, changing the coordinating metal
in the central core, building block functionalization, chang-
ing the meso atoms or the synthesis of nonsymmetric core
structures. However, some of these proposals are quite dis-
pendious.[1]
We have already shown that nonsymmetric phthalocyan-
ines synthesized from functionalized phthalonitriles present
low aggregation and good solubility in both hydrophobic
and hydrophilic media.[11] For example, a nonsymmetric PC
Results and Discussion
For the synthesis of 8, pinacolone (1) was brominated at
the α position to furnish 2 in 83% yield.[17] Compound 2
was subsequently treated with Na2S·9H2O by using a modi-
fied literature procedure[18] to afford 3 in 95% yield. Tetra-
hydrothiophene 4 was obtained by treating 3 with TiCl4/
Zn0 under McMurry reductive coupling conditions.[18] In
our hands, thiophene 5 was obtained by dehydration of 4
in benzene/p-toluenesulfonic acid (PTSA),[18] but only in
[a] Departamento de Química, Universidade Federal de São
Carlos,
Rodovia Washington Luís, km 235 – SP-310, 13565-905, São
Carlos, SP, Brazil
Fax: +55-16-3351-8350
E-mail: kleber.oliveira@ufscar.br
Homepage: www.lqbo.ufscar.br
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201300415.
2
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Synthesis of an Octa-tert-butylphthalocyanine
Scheme 1. Synthesis of PCs 9 and 10.
very low yield (Ͻ10%). When we carried out the dehy-
dration by using anhydrous CuSO4 in anhydrous toluene
(high-pressure glass tube), 3,4-di-tert-butylthiophene (5)
was obtained in 82% yield.[19]
The Diels–Alder reaction between thiophene 5 and fum-
aronitrile was tested, and there was no reaction, as ex-
pected.[20] Thus, we performed the oxidation of thiophene
5 by using m-chloroperbenzoic acid (mCPBA), which gave
much more reactive thiophene dioxide 6 in 76% yield.[18]
We then planned a three-step domino transformation in-
volving a Diels–Alder reaction, cheletropic elimination of
SO2, and elimination of HBr to obtain 4,5-di-tert-butyl-
phthalonitrile (8). The reaction between 6 and bromofum-
aronitrile 7[21] (no solvent) gave 8 successfully in 50% yield.
All of the compounds were fully characterized by standard
spectroscopy techniques, and the structure of new
phthalonitrile 8 was confirmed by X-ray crystallography
(Figure 1).
Compound 8 was then cyclotetramerized in n-pentanol/
Na0 at 140 °C and subsequently quenched with water to
yield non-metalated phthalocyanine 9 in 22% yield after
purification.[22] When crude PC 9 was heated at reflux in
a mixture of Zn(OAc)2 and THF/CHCl3/MeOH (1:1:0.5),
compound 10 was obtained in 21% yield over the last two
steps (8 to 10).[22,23]
Figure 1. Molecular structure of 8 showing the atom labeling and
displacement ellipsoids at the 50% probability level (arbitrary
spheres for the H atoms). The molecule sits on a mirror plane so
that C11 and C11_i are symmetry related.
Fluorescence and singlet-oxygen quantum yields as well
as aggregation studies of new PC derivatives 9 and 10 were
The photobleaching studies (example in Figure 2 for
determined to demonstrate their preliminary photophysical compound 10) were performed in THF, and both com-
properties. These initial studies showed that the introduc- pounds 9 and 10 showed no significant degradation after
tion of two neighboring tert-butyl groups at the periphery irradiation with a red light of intensity 50 mWcm–2 (see the
of these macrocycles results in compounds that present ex- Supporting Information for further details and Fig-
cellent photostability (Figure 2), no aggregation in solution ures S15–S18).
(Figure 3), promote singlet-oxygen production (Figure 4),
Aggregation studies were accomplished by using UV/Vis
and a good fluorescence quantum yield (see also Figure S12 analysis at different concentrations. As observed, PCs 9 and
in the Supporting Information).
10 (see the example for compound 10 in Figure 3) presented
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N. R. S. Gobo, T. J. Brocksom, J. Zukerman-Schpector, K. T. de Oliveira
SHORT COMMUNICATION
ing Information, Figures S12–S14).[27,28] Stokes shift (the
difference in the maxima of the absorption and emission
bands) of PCs 9 and 10 were 5 and 7 nm, respectively.
Figure 2. Photobleaching study of phthalocyanine10 in THF.
no maximum distortion of the Q bands and no blueshift,
which indicates that there is aggregation at the limit of the
Lambert–Beer law. Very similar behavior was found for
compound 9. Additional experiments accomplished with
polar and nonpolar solvents for both compounds 9 and 10,
and the results are provided in the Supporting Information
(Figures S19–S26).
Figure 4. 1,3-Diphenylisobenzofuran (DBPF) decay under singlet-
oxygen quantum yield experiments for phthalocyanine 10 in THF.
Conclusions
In conclusion, phthalonitrile 8 was synthesized and fully
characterized including by X-ray diffraction. Phthalocyan-
ines 9 and 10 were synthesized by cyclotetramerization of 8
and showed good preliminary photophysical proprieties
and non-aggregating behavior.
Above all, the main purpose of this work was to present
the synthesis of compound 8 and its transformation into
simple and symmetrical phthalocyanines 9 and 10. As far
as we can determine, this is the first synthesis of a vicinal di-
tert-butylphthalonitrile.[16b] This work certainly opens the
possibility to prepare more sophisticated PC derivatives, as
well as nonsymmetric compounds.
CCDC-924160 (for 8) contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre via www.ccdc.cam.
ac.uk/data_request/cif.
Supporting Information (see footnote on the first page of this arti-
Figure 3. Aggregation study of compound 10 in ethyl acetate.
cle): Experimental procedures and characterization data along with
1
copies of the H NMR and 13C NMR spectra and high-resolution
mass spectra for new compounds.
Singlet-oxygen quantum yields (ΦΔ) were measured for
compounds 9 and 10 and were 0.10 and 0.13, respectively
(see the example in Figure 4; for further details, calcula-
tions, and measurements see also the Supporting Infor-
mation, Figures S1–S9; for comparison with standard
ZnPC, see Figures S10 and S11).[24,25] These results are con-
sistent with values for alkylphthalocyanines, as described in
the literature.[26,27] The fluorescence quantum yields (ΦF) of
PCs 9 and 10 were also measured, and the values obtained
were typical for alkyl-substituted PCs, being ΦF = 0.15 and
Acknowledgments
The authors thank Fundação de Amparo à Pesquisa do Estado
de São Paulo (FAPESP), Conselho Nacional de Desenvolvimento
Científico e Tecnológico (CNPq), and Coordenação de Aper-
feiçoamento de Pessoal de Nível Superior (CAPES) for financial
support and fellowships. Thanks are also due to Prof. E. Rodrig-
ues Filho, M. A. Trapp, Prof. N. P. Lopes, and J. C. Tomaz for
HRMS-TOF analysis and to Prof. M. Aparicio of IQ-UNICAMP
ΦF = 0.42, respectively (for further details see the Support- for the X-ray data collection.
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Synthesis of an Octa-tert-butylphthalocyanine
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Received: March 20, 2013
Published Online: ᭿
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