A new synthetic approach to benzoporphyrins and Kroehnke type porphyrin-2-ylpyridines

Article abstract of DOI:10.1039/c2cc30727h

The reaction of 2-formyl-5,10,15,20-tetraphenylporphyrin with aryl methyl ketones and ammonium acetate, in the presence of La(OTf)₃, affords benzoporphyrins and 2-(2,6-diarylpyridin-4-yl)porphyrins. This methodology was used to prepare, for the

Full text of DOI:10.1039/c2cc30727h

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COMMUNICATION
A new synthetic approach to benzoporphyrins and Krohnke type
¨
porphyrin-2-ylpyridineswz
Nuno M. M. Moura, Maria A. F. Faustino,* Maria G. P. M. S. Neves,*
a
a
a
Filipe A. Almeida Paz, Artur M. S. Silva, Augusto C. Tome and Jose
´ ´
A. S. Cavaleiroa
b
a
a
Received 1st February 2012, Accepted 20th April 2012
DOI: 10.1039/c2cc30727h
The reaction of 2-formyl-5,10,15,20-tetraphenylporphyrin with
aryl methyl ketones and ammonium acetate, in the presence of
3
La(OTf) , affords benzoporphyrins and 2-(2,6-diarylpyridin-4-yl)-
porphyrins. This methodology was used to prepare, for the first
0
0
00
0
time, a 2-(2,2 :6 ,2 -terpyridin-4 -yl)porphyrin. The structures of
two 2-(2,6-diarylpyridin-4-yl)porphyrins were confirmed by single-
crystal X-ray diffraction.
The modification of readily available meso-tetraarylporphyrins,
namely those with b-formyl groups, is recognized as an important
tool to give access to new porphyrin derivatives with adequate
features to be used in medicine, catalysis, electronic devices,
Fig. 1 Structure of some porphyrin derivatives bearing terpyridine
groups.
1
sensors or dyes for solar cells. Synthetic strategies based on
8
specifically for application in the area of organic solar cells.
The photoinduced electron transfer in porphyrin complexes
well-established transformations of the formyl group are being
2
explored to achieve such modifications. In this communication
9
with axial terpyridyloxy groups is also being studied.
we describe a new procedure to transform 2-formyl-5,10,15,20-
tetraphenylporphyrin (1) into a range of new 2-(2,6-diarylpyridin-
Compounds of types B and C are usually prepared in
low yields by acid-catalyzed condensation of pyrrole with
adequate terpyridinecarbaldehydes under the Adler or Lindsay
4
-yl)porphyrins, namely a 2-(terpyridyl)porphyrin of type A
(
Fig. 1), benzoporphyrins and porphyrin–chalcone derivatives.
Transition metal complexes of terpyridines bearing electron
donor and acceptor groups are being extensively used as
5
,6a–c
conditions.
Moreover potentially useful compounds for
the formation of metal complex and supramolecular systems,
2-(terpyridyl)porphyrins (type A compounds), were not
described before. We report here a simple method for the synthesis
of such compounds, where the terpyridine moiety is built
directly in a 2-formylporphyrin by reaction with 2-acetylpyridine
3
,4
models of the photosynthetic system. Especially interesting
are those derivatives that also incorporate a photoactive
group, namely a porphyrin unit. A number of porphyrins
bearing one or more terpyridine groups have been used in such
studies but in all cases the terpyridine units are located at the
meso-positions of the porphyrin macrocycle (compounds of
and ammonium acetate in the presence of La(OTf)
porphyrins are also formed in these reactions.
3
. Benzo-
5
6
7
3
Knowing that La(OTf) is a Lewis acid where the presence
types B, C and D ). A porphyrin bearing an oligothiophene
moiety and a terpyridinethiophene unit in opposite meso-positions
1
0
of water is not a limitation, we envisaged that it could be an
efficient catalyst for the condensation of porphyrin 1 with aryl
methyl ketones and ammonium acetate in order to generate
(
an interesting variation of type C compounds) was designed
1
1
Kro
Kro
asymmetric catalysis, photosensitization and anti-tumour
¨
hnke type porphyrin-2-ylpyridines.
Our interest in
a
b
Department of Chemistry and QOPNA, University of Aveiro,
¨
hnke pyridines is due to their usefulness in fields such as
3
810-193 Aveiro, Portugal. E-mail: gneves@ua.pt, faustino@ua.pt
Department of Chemistry and CICECO, University of Aveiro,
810-193 Aveiro, Portugal
1
2,13
chemotherapeutics.
In fact, we found that porphyrin-2-
3
w This article is part of the ChemComm ‘Porphyrins and phthalocyanines’
web themed issue.
ylpyridines 3a–e can be obtained in good yields under the
experimental conditions indicated in Scheme 1 (Table 1,
entries 1 and 2). Depending on the ketone reactivity, or the
reaction time, porphyrin–chalcone-type derivatives 4, which
are intermediates in the synthesis of 3, can also be isolated.
Because chalcone derivatives find applications in several areas,
z Electronic supplementary information (ESI) available: Experimental
details of the single-crystal X-ray diffraction studies performed for
compounds 3b and 3e; additional structural drawings of the crystal
structures of 3b and 3e emphasising the supramolecular arrangements
of individual units; tables showing details of supramolecular contacts
for compounds 3b and 3e. CCDC 859837 and 859838. For ESI and
crystallographic data in CIF or other electronic format see DOI:
1
4
15
namely in medicine or in optical materials, the properties
10.1039/c2cc30727h
of compounds 4 deserve a careful study. A surprising result of
6
142 Chem. Commun., 2012, 48, 6142–6144
This journal is c The Royal Society of Chemistry 2012

Fig. 2 Structure of 1,5-diketone 5.
Scheme 1
The reaction of diketone 5 with NH
afforded 3d in 82% yield. This result confirmed that diketones
of type 5 are the immediate precursors of the b-pyridylporphyrins
. The formation of compounds 2 probably involves a con-
4
OAc in refluxing toluene
19
Table 1 Products obtained in the reaction of porphyrin 1 with aryl
methyl ketones
a
3
Entry
Ketone
Time (h)
2 (%)
3 (%)
4 (%)
jugate addition of an extra enolate unit to the 3-position of the
porphyrin macrocycle, followed by an intramolecular aldol
condensation and aromatization (see S3 in the ESIz).
1
2
3
4
5
6
7
8
a
b
c
2
4
2.5
2.5
8
8
3
3
14
22
6
26
8
15
19
29
68
61
10
55
19
58
23
45
—
—
46
6
71
9
1
b
The H NMR spectra of compounds 4c–e show characteristic
c
peaks in the aromatic region, namely a singlet at ca. 9 ppm
corresponding to the resonance of the b-pyrrolic proton H-3
and an AB system signal at ca. 7.5 ppm due to the resonance of
the two protons from the a,b-unsaturated ketone moiety; a
coupling constant of B15 Hz confirms the trans configuration
d
d
e
b
40
10
b
e
a
Reaction conditions: aryl methyl ketone (3 equiv.), NH
4
OAc (4 equiv.),
(20 mol%), toluene, reflux. Aryl methyl ketone (5 equiv.),
OAc (8 equiv.), La(OTf) (20 mol%), toluene, reflux.
b
La(OTf)
NH
3
13
of the exocyclic double bond. The C NMR spectra show a
distinctive signal near 190.0 ppm corresponding to the carbonyl
carbon.
4
3
The crystal structures of porphyrins 3b (with a 2,6-di-
p-tolylpyridine unit) or 3e (with a terpyridine unit) were
unequivocally elucidated using single-crystal X-ray diffraction
at 150 K (see experimental details in the ESIz).y Both
these reactions is the formation of benzoporphyrins 2 in all cases.
Compounds of this type, due to their extended p system, are
particularly interesting for application as photosensitizers in
16
photodynamic therapy (PDT) and in electro-optical materials.
In a typical experiment, a toluene solution of porphyrin 1,
acetophenone (3 equiv.), ammonium acetate (4 equiv.) and
%
molecules crystallise in the centrosymmetric triclinic P1 space
group with the asymmetric units being composed of a whole
molecular unit as depicted in Fig. 1 (see also Fig. S41 and S44
in the ESIz for the atomic labelling). The considerable bulky
nature of the 2-substituents, in conjunction with the presence
of four benzene rings attached to the porphyrin cores, leads to
significantly distorted molecules (as depicted in the side views
in Fig. 3). It is noteworthy that in both molecules the central
pyridine ring of the 2-substituent interacts with an adjacent
benzene ring attached to the porphyrin core by way of p–p
stacking interactions (inter-centroid distances ranging from
3
La(OTf) (20 mol%) was heated at reflux for two hours. A TLC
of the reaction mixture revealed the absence of starting porphyrin
and the formation of two new products. After the workup, the
two compounds were separated by column chromatography
(silica gel). The structure of the more polar and major product
(obtained in 68% yield) was established as 3a based on its mass
spectrum, which shows the [M + H] ion at m/z = 843.3, and
+
NMR studies (see ESIz). The spectroscopic data of the minor
product (obtained in 14% yield) are consistent with the structure
+
of benzoporphyrin 2a: its mass spectrum shows the [M + H]
˚
ca. 3.52 to 3.69 A for 3e and 3b, respectively). This leads to a
1
considerable intra-molecular cohesion which is translated into
the way molecules pack in the solid state (see below).
ion at m/z = 741.3 and the H NMR spectrum reveals the
resonances of only six b-pyrrolic protons.
The reaction conditions described above were extended to
0
other aryl methyl ketones, namely 4 -methylacetophenone,
0
0
4
-methoxyacetophenone, 4 -nitroacetophenone and 2-acetyl-
1
7,18
pyridine. In some cases, the porphyrin–chalcone-type
derivatives 4 were the main isolated products (Table 1, entries 3,
and 7). However, when heating was prolonged for 24 h,
5
the chalcone-type derivatives 4c–e were converted into the
corresponding compounds 2c–e and 3c–e. These compounds
are also obtained in higher yields if a larger excess (5 equiv.) of
the aryl methyl ketone is used (Table 1, entries 4, 6 and 8).
It is worth noting that we were also able to isolate a minor
compound (B1% yield) from the reaction of porphyrin 1 with
0
4
-nitroacetophenone.
It was identified as the 1,5-diketone 5 (Fig. 2) after complete
Fig. 3 Top and side views of the molecular units composing the
crystal structures of compounds 3b and 3e. For additional drawings
depicting the atomic labelling and crystal packing features of each
compound see Fig. S41 to S46 in the ESI.z
+
analysis by MS (molecular ion peak at m/z = 955 [M + H] )
1
13
and NMR ( H, C, COSY, HSQC and HMBC) (see ESIz).
This journal is c The Royal Society of Chemistry 2012
Chem. Commun., 2012, 48, 6142–6144 6143

The combination of the steric impediment created by
the presence of the bulky substituent groups, plus the
aforementioned intra-molecular p–p stacking interactions,
leads to crystal packing features which are essentially mediated
by the need to fill the available space in an effective fashion by
employing highly asymmetrical entities. Nevertheless, in both
structures individual molecular units close pack along the [100]
direction forming columnar arrangements (Fig. S42 and S45 in
the ESIz) mediated by weak C–Hꢀ ꢀ ꢀp supramolecular contacts
2007, 9, 5739; (c) E. Baranoff, J.-P. Collin, L. Flamigni and
J.-P. Sauvage, Chem. Soc. Rev., 2004, 33, 147.
P. Jarosz, K. Lotito, J. Schneider, D. Kumaresan, R. Schmehl and
R. Eisenberg, Inorg. Chem, 2009, 48, 2420.
(a) L. Flamigni, F. Barigelletti, N. Armaroli, J.-P. Collin,
J.-P. Sauvage and J. A. G. Williams, Chem.–Eur. J., 1998, 4, 1744;
4
5
(
2
b) I. M. Dixon and J.-P. Collin, J. Porphyrins Phthalocyanines,
001, 5, 600–607.
6
(a) A. Harriman, F. Odobel and J.-P. Sauvage, J. Am. Chem. Soc.,
1995, 117, 9641; (b) T. J. Cho, C. D. Shreiner, S.-H. Hwang,
C. N. Moorefield, B. Courneya, L. A. Godınez, J. Manrıquez,
´ ´
K.-U. Jeong, S. Z. D. Cheng and G. R. Newkome, Chem.
Commun., 2007, 4456; (c) A. C. Benniston, G. M. Chapman,
A. Harriman and M. Mehrabi, J. Phys. Chem. A, 2004,
108, 9026; (d) A. C. Benniston, A. Harriman, C. Pariani and
C. A. Sams, J. Phys. Chem. A, 2007, 111, 8918;
(e) A. C. Benniston, A. Harriman, C. Pariani and C. A. Sams,
Phys. Chem. Chem. Phys., 2006, 8, 2051.
(a) H. T. Uyeda, Y. Zhao, K. Wostyn, I. Asselberghs, K. Clays,
A. Persoons and M. J. Therien, J. Am. Chem. Soc., 2002,
(
Tables S41 and S42 in the ESIz). In 3b the porphyrin cores
˚
of adjacent symmetry-related molecules are at ca. 3.79 A
along [100] which may indicate the presence of weak offset
supramolecular p–p contacts. Neighbouring supramolecular
chains close pack in the solid state to yield the crystal
structures of 3b and 3e (Fig. S43 and S46 in the ESIz) mediated
by additional C–Hꢀ ꢀ ꢀp and p–p stacking interactions. It is worth
noting that in compound 3b one peripheral methylbenzene
moiety is engaged in a weak p–p contact with a symmetry-related
7
1
24, 13806; (b) T. V. Duncan, T. Ishizuka and M. J. Therien,
J. Am. Chem. Soc., 2007, 129, 9691; (c) T. Ishizuka, L. E. Sinks,
K. Song, S.-T. Hung, A. Nayak, K. Clays and M. J. Therien,
J. Am. Chem. Soc., 2011, 133, 2884.
moiety of an adjacent column (inter-centroid distance of about
˚
3
.98 A, see Fig. S43, ESIz).
8 O. Hagemann, M. Jørgensen and F. C. Krebs, J. Org. Chem., 2006,
1, 5546.
7
A new procedure leading to benzoporphyrins, porphyrin-
-ylpyridines and porphyrin–chalcone-type derivatives was
9
(a) P. P. Kumar, G. Premaladha and B. G. Maiya, Chem.
Commun., 2005, 3823; (b) P. K. Poddutoori, P. Poddutoori,
B. G. Maiya, T. K. Prasad, Y. E. Kandrashkin, S. Vasil’ev,
D. Bruce and A. van der Est, Inorg. Chem., 2008, 47, 7512.
2
developed. Each one of these types of compounds is potentially
interesting for a range of applications. By adjusting the reaction
time, the porphyrin–chalcone-type derivatives may be isolated
as the main products or be totally converted into the other two
products.
1
0 (a) C. Alonso, V. I. V. Serra, M. G. P. M. S. Neves, A. C. Tome
A. M. S. Silva, F. A. A. Paz and J. A. S. Cavaleiro, Org. Lett.,
007, 9, 2305; (b) C. Alonso, M. G. P. M. S. Neves, A. C. Tome
A. M. S. Silva and J. A. S. Cavaleiro, Eur. J. Org. Chem., 2004, 3222.
1 Krohnke pyridines is the trivial name for 2,4,6-triarylpyridines.
´
,
2
´
,
1
1
¨
Thanks are due to FCT and FEDER for funding the
QOPNA unit (project PEst-C/QUI/UI0062/2011) and the
Portuguese National NMR Network, also supported by funds
from FCT. We also thank FCT for specific funding towards the
purchase of the single-crystal X-ray diffractometer. N. Moura
thanks FCT for the PhD grant SFRH/BD/44630/2008.
2 (a) S. Tu, R. Jia, B. Jiang, J. Zhang, Y. Zhang, C. Yao and S. Ji,
Tetrahedron, 2007, 63, 381; (b) R.-A. Fallahpour, M. Neuburger
and M. Zehnder, Polyhedron, 1999, 18, 2445.
13 (a) B. Jiang, W.-J. Hao, X. Wang, F. Shi and S.-J. Tu, J. Comb.
Chem., 2009, 11, 846; (b) M. Adib, H. Tahermansouri,
S. A. Koloogani, B. Mohammadi and H. R. Bijanzadeh, Tetrahedron
Lett., 2006, 47, 5957.
1
4 (a) Z. Nowakowska, Eur. J. Med. Chem., 2007, 42, 125 and
references therein; (b) B. P. Bandgar, S. S. Gawande, R. G.
Bodade, J. V. Totre and C. N. Khobragade, Bioorg. Med. Chem.,
Notes and references
45 5
y Crystal data for 3b: C63H N , M = 872.04, triclinic, space group
2
010, 18, 1364.
P 1% , Z = 2, a = 9.4707(7) A, b = 13.9517(11) A, c = 17.6764(11) A,
˚
˚
˚
3
15 (a) K. Rurack, J. L. Bricks, G. Reck, R. Radeglia and U. Resch-
Genger, J. Phys. Chem. A, 2000, 104, 3087; (b) L. Mager,
´
C. Melzer, M. Barzoukas, A. Fort, S. Mery and J.-F. Nicoud,
˚
a = 82.155(3)1, b = 83.403(3)1, g = 78.502(4)1, V = 2258.1(3) A ,
ꢁ1
ꢁ3
m(MoKa) = 0.075 mm , D
c
= 1.283 g cm . Collected reflections
1 489. Independent reflections 8173 (Rint = 0.1052). Crystal size
.11 ꢂ 0.04 ꢂ 0.03 mm . Final R
.1656 (all data). Data completeness to theta = 25.351, 98.8%. CCDC
59837. Crystal data for 3e: C59 , M = 845.97, triclinic, space
3
0
0
8
3
Appl. Phys. Lett., 1997, 71, 2248.
1 2
= 0.0743 [I > 2s(I)] and wR =
1
6 (a) L. Jiang, J. T. Engle, L. Sirk, C. S. Hartley, C. J. Ziegler and
H. Wang, Org. Lett., 2011, 13, 3020; (b) S.-Y. Ku, C. D. Liman,
J. E. Cochran, M. F. Toney, M. L. Chabinyc and C. J. Hawker,
Adv. Mater., 2011, 23, 2289; (c) A. M. G. Silva, K. T. de Oliveira,
39 7
H N
group P 1% , Z = 2, a = 10.6667(14) A, b = 13.6339(17) A, c =
˚
˚
˚
1
2
8.488(3) A, a = 76.355(8)1, b = 78.393(8)1, g = 71.138(7)1, V =
3
ꢁ1
ꢁ3
´
M. A. F. Faustino, M. G. P. M. S. Neves, A. C. Tome, A. M. S.
Silva, J. A. S. Cavaleiro, P. Brandao and V. Felix, Eur. J. Org.
˚
449.6(6) A , m(MoKa) = 0.069 mm , D
c
= 1.147 g cm . Collected
˜
reflections 30 441. Independent reflections 8820 (Rint = 0.1369).
3
Chem., 2008, 704; (d) L. Jiao, E. Hao, F. R. Fronczek, M. G. H.
Vicente and K. M. Smith, Chem. Commun., 2006, 3900; (e) S. Ito,
T. Murashima, H. Uno and N. Ono, Chem. Commun., 1998, 1661.
7 The condensation of porphyrin 1 with ketones, in the presence of
piperidine and piperidine perchlorate, affords porphyrin–chalcone
type derivatives. (a) Y. V. Ishkov, Z. I. Zhilina and L. P. Barday,
J. Porphyrins Phthalocyanines, 2003, 7, 761; (b) Y. V. Ishkov,
Z. I. Zhilina, L. P. Bardai and S. V. Vodzinskii, Russ. J. Org.
Chem., 2004, 40, 434.
Crystal size 0.09 ꢂ 0.07 ꢂ 0.04 mm . Final R
and wR = 0.2542 (all data). Data completeness to theta = 25.341,
8.4%. CCDC 859838.
1
= 0.0919 [I > 2s(I)]
2
9
1
1
Handbook of Porphyrin Science, ed. K. M. Kadish, K. M. Smith
and R. Guilard, World Scientific Publishing Co., Singapore, 2010,
vol. 10–12.
2
(a) A. M. G. Silva, A. C. Tome
and J. A. S. Cavaleiro, J. Org. Chem., 2002, 67, 726; (b) A. M. G.
Silva, P. S. S. Lacerda, A. C. Tome, M. G. P. M. S. Neves, A. M. S.
Silva, J. A. S. Cavaleiro, E. A. Makarova and E. A. Lukyanets, J. Org.
Chem., 2006, 71, 8352; (c) A. C. Tome, M. G. P. M. S. Neves and
´
, M. G. P. M. S. Neves, A. M. S. Silva
´
18 Lindsay described the preparation of hydroporphyrin–chalcones with
extended red or near-infrared absorption from the condensation of
acetylchlorin or diacetylbacteriochlorin with aldehydes. C. Ruzie,
´
´
J. A. S. Cavaleiro, J. Porphyrins Phthalocyanines, 2009, 13, 408.
Reviews: (a) L. Flamigni, J.-P. Collin and J.-P. Sauvage, Acc. Chem.
Res., 2008, 41, 857; (b) A. C. Benniston, Phys. Chem. Chem. Phys.,
M. Krayer and J. S. Lindsay, Org. Lett., 2009, 11, 1761.
19 G. W. V. Cave and C. L. Raston, J. Chem. Soc., Perkin Trans. 1,
2001, 3258.
3
6
144 Chem. Commun., 2012, 48, 6142–6144
This journal is c The Royal Society of Chemistry 2012