β-Functionalized zinc(II)aminoporphyrins by direct catalytic hydrogenation

Article abstract of DOI:10.1016/j.tetlet.2012.10.117

We report on a novel synthetic procedure to obtain β-aminoporphyrins with zinc(II) as the metal center by using the catalytic reduction of the parent Zn(II)β-nitroporphyrins with hydrogen in the presence of Pd/C using dimethylformamide as the solvent. This simple method allows the preparation of β-aminoporphyrins with substituents with diverse electronic properties: meso-tetraphenylporphyrin (TPP), meso-tetrakis(2,6-dichlorophenyl)porphyrin (TDCPP), and meso-tetrakis(2,3,4,5,6-pentafluorophenyl)porphyrin (TPFPP).

Full text of DOI:10.1016/j.tetlet.2012.10.117

Tetrahedron Letters 54 (2013) 110–113
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Tetrahedron Letters
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b-Functionalized zinc(II)aminoporphyrins by direct catalytic hydrogenation
a
a
b
a
a,
⇑
´
Monika E. Lipinska , Dalila M. D. Teixeira , Cesar A. T. Laia , Ana M. G. Silva , Susana L. H. Rebelo
,
Cristina Freire a
a REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre s/n, 4169-007 Porto, Portugal
b REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 18 July 2012
Revised 25 October 2012
Accepted 29 October 2012
Available online 3 November 2012
We report on a novel synthetic procedure to obtain b-aminoporphyrins with zinc(II) as the metal center
by using the catalytic reduction of the parent Zn(II)b-nitroporphyrins with hydrogen in the presence of
Pd/C using dimethylformamide as the solvent. This simple method allows the preparation of b-aminopor-
phyrins with substituents with diverse electronic properties: meso-tetraphenylporphyrin (TPP), meso-tet-
rakis(2,6-dichlorophenyl)porphyrin (TDCPP), and meso-tetrakis(2,3,4,5,6-pentafluorophenyl)porphyrin
(TPFPP).
Keywords:
Ó 2012 Elsevier Ltd. All rights reserved.
Zinc(II)porphyrin
b-Functionalization
Aminoporphyrin
Catalytic hydrogenation
Porphyrinoid macrocycles are important naturally occurring
compounds. They play an essential role in a variety of biological pro-
cesses, suchas photosynthesis, oxygentransport/storage, and oxida-
tive metabolism.1 Synthetic (metallo)porphyrins have been
extensively investigated in biomimetic processes, namely in artifi-
cial photosynthesis, photoinduced electron transfer,2 and as models
of monooxygenase and peroxidase enzymes for catalytic oxidation3
and pollutant degradation.4 They also find relevant applications in
medicine for diagnosis and in photodynamic therapy (PDT)5 or bor-
on neutron capture therapy (BNCT).6 The amino-functionalized por-
phyrins are key precursors for the preparation of dimers,7
supramolecular systems,8 and hybrids, in particular, porphyrin
structures covalently bonded to fullerenes or carbon nanotubes,
affording photoactive nanocomposites for electronic and photonic
devices9,10 and heterogeneous photocatalysis.11
The preparation of aminoporphyrins has been mainly achieved
through the synthesis of macrocycles with nitrophenyl groups in
one or several meso-positions, followed by their reduction to ami-
nophenyl derivatives using excess of tin(II) chloride in concen-
trated hydrochloric acid (Fig. 1a, R1 = NH2 or Ph-NH2; R2–
4 = Ph).12,13 Alternatively, palladium catalyzed coupling reactions
on meso-halo(metallo)porphyrins were described to afford the cor-
responding meso-aminoporphyrins.14,15 However, the preparation
of asymmetric porphyrin core structures requires more complex
procedures and thus, the introduction of an amino group in the
b-positions of a more easily obtainable symmetric porphyrin is
preferable. Furthermore, (metallo)porphyrin structures covalently
bonded through b-position were shown to have anhanced perfor-
mance for electron transfer processes relatively to structures
bonded through meso-phenyl groups.16
The preparation of b-amino substituted porphyrins was also re-
ported for Ni(II) and Cu(II) derivatives of TPP (Fig. 1a) using the
reduction with tin powder under acidic conditions17,18 or multi-
step reactions based on palladium catalyzed couplings.19 However,
these methodologies were not suitable to directly synthesize
aminoporphyrins carrying a labile central metal such as zinc or
to avoid the conversion of the reactive b-NH2 group during the
multi-step procedures.
The preparation of aminoporphyrin derivatives carrying elec-
tron withdrawing substituents can also be significant for a vast
range of applications: halogen substituted (metallo)porphyrins
are important for photochemical processes based on the genera-
tion of triplet states, such as the photosensitized production of sin-
glet oxygen20 or for the preparation of photonic devices.21
Furthermore, metalloporphyrins with electron withdrawing
groups have been reported as efficient catalysts for several oxida-
tion reactions, and currently their anchoring onto solid supports
is of primary importance to allow easy catalyst removal at reaction
end and reuse, or to obtain stereo-control during the catalytic reac-
tion.22 In this context, the synthesis of amino derivatives is very
appropriate to establish strong covalent binding to catalyst sup-
ports. To the best of our knowledge, b-amino derivatives of TDCPP
and TPFPP have not been reported previously in the literature.
Reduction reaction using hydrogen in the presence of heteroge-
neous Pd/C catalyst is a simple method that proceeds under mild
⇑
Corresponding author. Fax: +351 220402695.
E-mail address: susana.rebelo@fc.up.pt (S.L.H. Rebelo).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.10.117

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M. E. Lipinska et al. / Tetrahedron Letters 54 (2013) 110–113
Figure 1. (a) Metalloporphyrin structures. (b) Preparation of the Zn(II)b-aminoporphyrins through catalytic reduction of the corresponding nitro derivatives.
conditions and requires small amount of solvent. This methodol-
ogy has been previously used for the reduction of porphyrins,
namely TPP and uroporphyrin I, to chorins and porphyrinogen
derivatives.23,24 In this Letter, it is described the synthesis of
Zn(II)b-aminoporphyrins: zinc(II)b-amino(meso-tetraphenyl)por-
phyrin (Znb-NH2TPP) I, zinc(II)b-amino(meso-tetrakis(2,6-dichlo-
rophenyl))porphyrin (Znb-NH2TDCPP) II, and zinc(II)b-amino-
elemental analysis (Fig. 1 and Table 1), which confirmed the struc-
tures of Zn(II)b-aminoporphyrins I,28 II29 and III.30 Isolated yields
were 30%, 23%, and 20%, respectively. The mass spectra (MALDI)
for compounds I–III showed a signal at m/z corresponding to the
[M+H]+ ion and the elemental composition of all compounds was
in accordance with theoretical values.28–30 The 1H NMR spectra
of I, II, and III exhibited a broad singlet peak from the –NH2 group
at 4.53, 4.58, and 4.69 ppm, respectively, showing an increase in
the chemical shift as the electron withdrawing properties of the
porphyrin ring increase. Protons in the aromatic region confirmed
the porphyrinic structures in Figure 1b. Moreover, the absence of
signals of the internal ring NH protons confirmed that the ami-
no-porphyrin fractions were only present as the Zn(II) complex.
The electronic absorption and fluorescence emission spectra of
Zn(II)b-amino compounds are shown in Figure 2. The electronic
spectra showed the characteristic Soret band at kmax 423, 426,
and 416 nm, respectively, for compounds I, II, III and three Q-
bands. The presence of an amino group in one of the b-positions
of the metalloporphyrin ring changes the D4h symmetry of the Zn
meso-tetraphenylporphyrins, (normally showing two Q-bands), to
Cs symmetry and consequently, the number of Q bands increased.
As can be seen in Table 1, the fluorescence quantum yields of Znb-
NH2TPP (UF 0.056) decreased relatively to the ZnTPP precursor (UF
0.110), indicating the occurrence of quenching of the excited state
in some extend by the amino group through charge transfer com-
plex in the excited-state. The same can be seen with Znb-NH2TPFPP
(UF 0.018 vs 0.045 for ZnTPFPP). However, an increase of fluores-
cence quantum yield is observed for Znb-NH2TDCPP (UF 0.022) rel-
atively to its ZnTDCPP precursor (UF 0.010). The low ZnTDCPP
fluorescence quantum yield is due to the heavy atom effect. By
the introduction of an amino group, the balance of excited-state
processes (including intersystem crossing) is affected rendering a
higher fluorescence.
(meso-tetrakis(2,3,4,5,6-pentafluorophenyl))porphyrin
(Znb-
NH2TPFPP) III, through reduction of zinc(II)b-nitroderivatives
using hydrogen as the reductive agent and Pd/C as heterogeneous
catalyst. Preparation of the porphyrin free bases and subsequent
one-step metallation/nitration affording zinc(II)b-nitroporphyrins
were performed following the literature procedures.25,26 The
hydrogenation reaction was tested using several solvents and dif-
ferent reaction times in order to optimize the reaction conditions.
The reaction was performed in methanol, anhydrous tetrahydrofu-
ran (THF), anhydrous toluene, 1-methyl-2-pyrrolidone, and in both
anhydrous and non-anhydrous dimethylformamide (DMF). Only in
the case of the last two solvents, the reaction led to the desired
aminoporphyrins. In consequence DMF was chosen as the reaction
solvent since no advantage was observed by performing the reac-
tion in the anhydrous solvent. Furthermore, the reaction was also
carried out at different reaction times: 30, 60 min, 2, 4, and 16 h.
The substrate conversion was complete after 4 h; longer reaction
times, for example 16 h, did not change the yields of the aminopor-
phyrin, originating the amino-product in the same yield. Finally,
the reduction reaction in DMF was carried out at room tempera-
ture, keeping the reaction mixture protected from light and using
Pd/C (10%) catalyst and hydrogen pressure of 4 bar. The reaction
was monitored by TLC and at its end the catalyst was filtrated
and the metalloporphyrin products were precipitated with n-hex-
ane/chloroform mixtures; in-some cases (Znb-NH2TPFPP), the DMF
was evaporated at low temperature. The total reaction mixture
was analyzed by 1H NMR or fractionated by preparative TLC or col-
umn chromatography.27 The observed first red products were iso-
lated and characterized using 1D and 2D 1H and 13C NMR
spectroscopies, APT, COSY, HSQC, HMBC; mass spectrometry and
The control of the reactions by TLC indicated the presence of the
other compounds. The isolated green fractions showed characteris-
tic electronic spectra of chlorin compounds, with a relatively in-
tense Q-band at kmax 620 nm and confirmed the occurrence of

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M. E. Lipinska et al. / Tetrahedron Letters 54 (2013) 110–113
112
Table 1
Selected spectroscopic data and isolated yields for the Zn(II)b-aminoporphyrins
1H NMR (ppm) (ÀNH2)
4.53 (s, 2H)
4.58 (s, 2H)
4.69 (s, 2H)
MS m/z [M+H]+
Soret band (nm)
Ufa
Yield (%)
Znb-NH2TPP (I)
Znb-NH2TDCPP (II)
Znb-NH2TPFPP (III)
692.2a
963.8a
423
426
416
0.056 [ZnTPP:0.110]
0.022 [ZnTDCPP:0.010]
0.018 [ZnTPFPP:0.045]
30
23
20
1051.9a
a
k = 562 nm, standard:TPP Uf = 0.11.
Figure 2. Photophysical data for Znb-aminoporphyrins: (a) electronic absorption spectra in CH2Cl2. (b) Fluorescence spectra in CH3CN.
Ar
Ar
Ar
and project ref. PTDC/QUI-QUI/105304/2008. We thank Professor
J.L. Figueiredo from Laboratório de Catálise e Materiais (LCM)
(FEUP, Portugal) for providing the access to the reactor Framo–Ger-
NO2
Ar
NO
Ar
NH2
Ar
N
N
N
Zn
Zn
Zn
´
atetechnik Model M21/1. Monika E. Lipinska also thanks FCT for a
PhD grant SFRH/BD/66297/2009.
Red
Green
Green
References and notes
Scheme 1. Observed stepwise reduction of nitro to nitroso and amino derivatives.
1. The Porphyrin Handbook; Kadish, K. M., Smith, K. M., Guilard, R., Eds.; Academic
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hydrogenation of the b-positions of porphyrin core as a competing
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tives.23 During the reduction of Znb-NO2TPFPP the reductive
dehalogenation reaction of fluorine substituents was also observed
as confirmed by MS analysis of other isolated fractions.31 In addi-
tion, TLC control of the reduction reaction of Znb-NO2TPP showed
the initial formation of green compounds and only after 2 h it was
observed the presence of a red spot, which was assigned to the
amino-porphyrin. The green derivative with the highest Rf was iso-
lated and identified by MS (MALDI) analysis showing a molecular
ion with m/z 706.2, which matches with the [M+H]+ ion of the b-ni-
troso derivative. Accordingly, the stepwise reduction pathway
shown in Scheme 1 can be proposed. More detailed studies will
be presented in a full paper.
The described procedure is an easy and a versatile way to obtain
new zinc(II)b-aminoporphyrins with different electron withdraw-
ing properties through direct hydrogenation reaction of the corre-
sponding Zn(II)-nitro precursors that have potential photochemical
applications and as precursors to catalytic and photo-active
structures.
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Acknowledgments
This work was funded by the Fundação para a Ciência e a Tecn-
ologia (FCT) and FEDER through grant no. PEst-C/EQB/LA0006/2011
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27. Experimental details: 30 mg of zinc(II)b-nitroporphyrin and 30 mg of Pd/C
(10%) were dissolved in 10 mL of DMF (p.a. Fisher Chemicals, used without
further purification). The reaction mixture was kept stirring in hydrogenator
(Framo–Geratetechnik Model M21/1) at the room temperature under
hydrogen pressure of 4 bar for 4 h. After that time, the mixture was filtrated
to remove the catalyst that was washed with chloroform followed by
evaporation of the solvents at a low temperature (<60 °C) or precipitation in
n-hexane/chloroform mixtures. The product was isolated by preparative thin
28. Znb-NH2TPP: Violet solid. Isolated yield 30%. 1H NMR (CDCl3, 400 MHz)
d = 8.84–8.89 (5H, m, H-b), 8.75 (1H, d, J = 4.6 Hz, H-b), 8.63 (1H, d, J = 4.6 Hz,
H-b), 8.18–8.20 (4H, m, H-Phortho); 8.13 (2H, d, J = 6.0 Hz, H-Phortho), 8.06 (2H, d,
J = 6.8 Hz, H-Phortho), 7.66–7.78 (12H, m, H-Phmeta+para), 4.53 (2H, s, NH2) ppm.
13C NMR (CDCl3, 100 MHz) d = 134.5, 134.4, 134.3, 133.7, 133.0, 132.6, 132.4,
131.8, 131.6, 128.1, 127.2, 126.9, 126.7, 126.7, 126.6 ppm. MS (MALDI) m/z
692.2 [MH+]. Vis (CHCl3) kmax 626 (relative absorbance, 0.05), 611 (0.05), 559
(0.07), 423 nm (1.0). Anal. Calcd for C44H29N5ZnÁ4H2O: C, 69.2; N, 9.2; found: C,
69.1; N, 9.1.
29. Znb-NH2TDCPP: Violet solid. Isolated yield 23%. 1H NMR (CDCl3, 400 MHz)
d = 8.66–8.72 (4H, m, H-b), 8.63 (1H, d, J = 4.8 Hz, H-b), 8.52 (1H, d, J = 4.8 Hz,
H-b), 7.88 (1H, s, H-b), 7.66-7.79 (12H, m, H-Phmeta+para), 4.58 (2H, s, NH2) ppm.
13C NMR (CDCl3, 100 MHz) d = 131.5, 131.3, 131.0, 130.9, 130.7, 130.4, 130.0,
129.0, 128.9, 127.8, 127.7. MS (MALDI) m/z 963.8 [MH+]. Vis (CHCl3) kmax 634
(relative absorbance, 0.05), 610 (0.06), 562 (0.06), 426 nm (1.0). Anal. Calcd for
C
44H21N5Cl8Zn 2H2OÁCH3OH: C, 52.4; N, 6.8; found C, 52.3; N, 6.4.
30. Znb-NH2TPFPP: Violet solid. Isolated yield 20%. 1H NMR (CDCl3, 400 MHz)
d = 8.82–8.90 (6H, m, H-b), 8.70 (1H, d, J = 4.8 Hz, H-b), 4.69 (2H, s, NH2) ppm.
13C NMR (CDCl3, 100 MHz) d = 132.1, 131.8, 131.6, 131.4, 131.0, 130.8, 130.7.
MS (MALDI) m/z 1051.9 [MH+]. Vis (CHCl3) kmax 631 (relative absorbance, 0.02),
603 (0.03), 558 (0.07), 416 nm (1.0). Anal. Calcd for
4H2OÁCH3OH: C, 46.7; N, 6.0; found C, 46.8; N, 5.8.
C44H9N5F20Zn
layer chromatography on silica plates using as the eluent
chloroform:methanol (99.5:0.5).
a
mixture of
31. Ramanathan, A.; Jimenez, L. S. Synthesis 2010, 2, 217–220.