o-(bromomethyl)-substituted tetraarylporphyrin building blocks

Article abstract of DOI:10.1021/ol006028x

matrix presented A series of novel poly-o-(bromomethyl)ated tetraarylporphyrins was synthesized. Their usefulness as building blocks for porphyrinic materials is demonstrated.

Full text of DOI:10.1021/ol006028x

ORGANIC
LETTERS
2000
Vol. 2, No. 14
2129-2132
o-(Bromomethyl)-Substituted
Tetraarylporphyrin Building Blocks
Norbert Jux*
Institut fu¨r Organische Chemie der UniVersita¨t Erlangen-Nu¨rnberg,
Henkestrasse 42, 91054 Erlangen
jux@organik.uni-erlangen.de
Received May 8, 2000
ABSTRACT
A series of novel poly-o-(bromomethyl)ated tetraarylporphyrins was synthesized. Their usefulness as building blocks for porphyrinic materials
is demonstrated.
meso-Tetraphenylporphyrin (TPP) is the most commonly
used porphyrinic system for the construction of photosyn-
thetic model compounds,1 enzyme mimetics, and artificial
receptors.2 Besides biochemical aspects, TPPs are found, for
example, in dendrimers,3 as liquid crystalline materials with
discotic behavior4 and as part of optoelectronic devices.5
Thus, the usefulness of TPPs encompasses chemistry,
medicine, biochemistry, physics, and materials sciences.6
Since the derivatization of TPPs has been well studied, it is
possible to tailor their properties, allowing adaption into the
desired specific environment.
Obviously, novel materials containing porphyrins have
become a major research field in porphyrin chemistry. It
appears to us that by using the inherent geometry of
porphyrins interesting new conjugates would be available.
In this paper we introduce a series of poly-o-(bromomethyl)-
ated tetraphenylporphyrins which are useful building blocks
in this regard.
(1) Osuka, A.; Marumo, S.; Mataga, N.; Taniguchi, S.; Okada, T.;
Yamazaki, I.; Nishimura, Y.; Ohno, T.; Nozaki, K. J. Am. Chem. Soc. 1996,
118, 155-168. Steinberg-Yfrach, G.; Liddell, P. A.; Hung, S.-C.; Moore,
A. L.; Gust, D.; Moore, T. A. Nature, 1997, 385, 239-241. Steinberg-
Yfrach, G.; Rigaud, J.-L.; Durantini, E. N.; Moore, A. L.; Gust, D.; Moore,
T. A. Nature, 1998, 392, 479-432. Liddell, P. A.; Kuciauskas, D.; Sumida,
J. P.; Nash, B.; Nguyen, D.; Moore, A. L.; Moore, T. A.; Gust, D. J. Am.
Chem. Soc. 1997, 119, 1400-1405. Arimura, T.; Brown, C. T.; Springs, S.
L.; Sessler, J. L. Chem. Commun. 1996, 2293-2294. Flamigni, L.;
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(2) Collman, J. Inorg. Chem. 1997, 36, 5145-5155. French, R. R.; Wirz,
J.; Woggon, W.-D.; HelV. Chim. Acta 1998, 81, 1521-1527. Wagenknecht,
H.-A.; Claude; Woggon, W.-D. HelV. Chim. Acta 1998, 81, 1506-1520.
Mizutani, T.; Ema, T.; Tomita, T.; Kuroda, Y.; Ogoshi, H. J. Am. Chem.
Soc. 1994, 116, 4240-4250. Ogoshi, H.; Mizutani, T. Acc. Chem. Res.
1998, 31, 81-89. Rose, E.; Soleilhavoup, M.; Christ-Tommasino, L.;
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1998, 63, 2042-2044. Furusho, Y.; Kimura, T.; Mizuno, Y.; Aida, T. J.
Am. Chem. Soc. 1997, 119, 5267-5268. Takeuchi, M.; Imada, T.; Shinkai,
S. Angew. Chem., Int. Ed. 1998, 37, 2096-2099. Crossley, M. W.; Mackay,
L. G.; Tyr, A. C. Chem. Commun. 1995, 1926-1927.
Because tetraphenylporphyrins are easy to prepare and are
well studied, we decided to use these compounds as
(3) Dandliker, P. J.; Diederich, F.; Gisselbrecht, J.-P.; Louati, A.; Gross,
M. Angew. Chem., Int. Ed. Engl. 1995, 34, 2725-2728. Kimura, M.;
Nakada, K.; Yamaguchi, Y.; Hanabusa, K.; Shirai, H.; Kobayashi, N. Chem.
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(4) Shimizu, Y.; Matsuno, J.; Miya, M.; Nagata, A. Chem. Commun.
1994, 2411-2412.
(5) Prathapan, S.; Johnson, T. E.; Lindsey, J. S. J. Am. Chem. Soc. 1993,
115, 7519-7520. Wagner, R. W.; Lindsey, J. S. J. Am. Chem. Soc. 1994,
116, 9759-9760. Wagner, R. W.; Lindsey, J. S.; Seth, J.; Palaniappan, V.;
Bocian, D. F. J. Am. Chem. Soc. 1996, 118, 3996-3997. Wagner, R. W.;
Seth, J.; Kim, D.; Bocian, D. F.; Holten, D.; Lindsey, J. S. J. Org. Chem.
1998, 63, 5042-5049.
(6) The Porphyrin Handbook; Kadish, K. M.; Smith, K. M.; Guilard,
R., Eds.; Academic Press: San Diego, 2000.
10.1021/ol006028x CCC: $19.00 © 2000 American Chemical Society
Published on Web 06/16/2000

foundation for our research. Our aim was to generate
porphyrins with easily modifiable groups in close proximity
to the core. Therefore, these substituents had to be placed at
the ortho-positions of the phenyl rings. TPPs with o-phenyl
substituents are subject to extensive research7 because ortho-
groups prevent aggregation and protect the core of the
porphyrin from side reactions. The modification of some
derivatives, especially of amino and hydroxy derivatives, was
extensively studied and led to beautiful molecules such as
cyclam-capped porphyrins8 and barrel-shaped systems9 with
a porphyrin center. Molecular modeling suggests that the
geometric situation of substituents in the ortho-positions
should lead to better interactions with the porphyrin core.
Also, due to the size of the porphyrin the rotation of such
groups will be strongly hindered.
about 1% ethanol as solvent and boron trifluoride-diethyl
etherate as catalyst. Porphyrin 3 was obtained after oxidation
with 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) and re-
peated chromatography (silica gel, CH2Cl2/ethyl acetate
19:1) in a yield of 7% (Scheme 2). Identified byproducts
Scheme 2a
These considerations led to the belief that a 2,6-disubsti-
tuted benzaldehyde had to be made and used in the
cyclocondensation reaction with pyrrole to yield porphyrins.
For synthetic reasons and to ensure good solubility the tert-
butyl group was included as the para-substituent. Encouraged
by recently reported improved reaction conditions for the
synthesis of TPPs with sterically encumbered benzalde-
hydes,10 we started by preparing 2,6-bis(methoxymethyl)-
4-tert-butylbenzaldehyde 1 using a modified literature11
procedure for the corresponding acid derivative.12 1 was
obtained by reacting aryl bromide 2 with n-butyllithium at
-78 °C and subsequent addition of dimethylformamide
(Scheme 1). With aldehyde 1, porphyrins 3-5 are available
a (a) i. BF3‚OEt2, CH2Cl2 (+1% EtOH), rt, ii. DDQ, CH2Cl2, rt.
were the oxidized form of dipyrromethane 6, a corrole
derivative, and a linear tetrapyrrole.
The lower symmetries of 4 and 5 required a different
approach. We decided to synthesize the porphyrin under
more or less controlled conditions. Therefore, the dipyrro-
methane 6 was made according to a literature procedure for
mesitaldehyde.13 The formation of 6 proceeded smoothly,
when aldehyde 3 was dissolved in pyrrole and boron
trifluoride-diethyl etherate was used as catalyst.
Scheme 1a
1
The dipyrromethane 6 shows in its H NMR spectrum
broad signals for the methylene and methyl protons of the
ether moiety. This seems to indicate a rotational constriction
of the phenyl group as was expected from a crystal structure
of 5-mesityldipyrromethane.14 Temperature-dependent NMR
spectroscopy will be employed to gain further insight of this
phenomenon. For the synthesis of 4 dipyrromethane 6 and
4-tert-butylbenzaldehyde were dissolved in dry methylene
chloride containing 1% ethanol. Again, boron trifluoride-
diethyl etherate served as Lewis acid. After the oxidation
step with DDQ, porphyrin 4 was obtained in 21% yield. No
scrambling15 of the dipyrromethane unit was observed under
these conditions. Also, when ethanol was not added to the
cyclization reaction the yield of product dropped well below
5%. This result is in contrast to the observations of Lindsey
and co-workers,15 who analyzed reactions of sterically
hindered dipyrromethanes with sterically unhindered alde-
hydes and found that no ethanol was needed in such cases.
The reason for this surprising behavior might be the
formation of a complex of boron trifluoride and the meth-
oxymethyl groups which is destroyed by ethanol. When
a (a) i. n-BuLi, ether, -78 °C, ii. DMF, ether, -78 °C to rt, iii.
NH4Cl, H2O, (b) pyrrole as solvent, BF3‚OEt2, rt.
by employing different strategies for their syntheses. Due
to its symmetry, 3 should be the most easily accessible
porphyrin in the series 3-5. The cyclotetracondensation of
1 with pyrrole was achieved in methylene chloride containing
(7) Wagner, R. W.; Lindsey, J. S.; Turowska-Tyrk, I.; Scheidt, W. R.
Tetrahedron 1994, 50, 11097-11112.
(8) Collman, J. P.; Zhang, X.; Herrmann, P. C.; Uffelman, E. S.; Boitrel,
B.; Straumanis, A.; Brauman, J. I. J. Am. Chem. Soc. 1994, 116, 2681-
2682. Collman, J. P.; Herrmann, P. C.; Fu, L., Eberspacher, T. A.; Eubanks,
M.; Boitrel, B.; Hayoz, P.; Zhang, X.; Brauman, J. I.; Day, V. W. J. Am.
Chem. Soc. 1997, 119, 3481-3489.
(9) Rose, E.; Kossanyi, A.; Quelquejeu, M.; Soleilhavoup, M.; Duwavran,
F.; Bernard, N.; Lecas, A. J. Am. Chem. Soc. 1996, 118, 1567-1568.
(10) Lindsey, J. S.; Hsu, H. C.; Schreiman, I. C. Tetrahedron Lett. 1986,
41, 4969-4970. Lindsey, J. S.; Schreiman, I. C.; Hsu, H. C.; Kearney, P.
C.; Marguerettaz, A. M. J. Org. Chem. 1987, 52, 827-836. Lindsey, J. S.;
Wagner, R. W. J. Org. Chem. 1989, 54, 828-836.
(11) Christenson, B.; Hallnemo, G.; Ullenius, C. Tetrahedron 1991, 47,
4739-4752.
(12) Fuson, R. C.; Freedman, B. J. Org. Chem. 1958, 23, 1161-1166.
(13) Lee, C.-H.; Lindsey, J. S. Tetrahedron 1994, 50, 11427-11440.
(14) Littler, B. J.; Miller, M. A.; Hung, C.-H.; Wagner, R. W.; O’Shea,
D. F.; Boyle, P. D.; Lindsey, J. S. J. Org. Chem. 1999, 64, 1391-1396.
(15) Littler, B. J.; Yangzhen, C.; Lindsey, J. S. J. Org. Chem. 1999, 64,
2864-2872.
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Org. Lett., Vol. 2, No. 14, 2000

dipyrromethane 6 was reacted in a statistical way with 2
equiv of pyrrole and 3 equiv of 4-tert-butylbenzaldehyde
using the above-mentioned conditions, porphyrin 5 was
obtained in 12.5% yield. Tetrakis(4-tert-butylphenyl)por-
phyrin was found to be the major product of this reaction
(24%).
Scheme 4a
The methoxy ethers 3-5 were transformed into their
bromo derivatives by reaction with boron tribromide in dry
methylene chloride or, with even better results, with HBr in
acetic acid to give 7-9. By employing the latter, the yield
of the desired all-bromo compounds was usually around 85%.
Depending on the quality of the BBr3 solution, a certain
amount of monohydroxylated species was always found. The
porphyrins 7-9 were metalated quantitatively by addition
of a solution of zinc acetate in methanol/1% acetic acid to a
solution of the corresponding porphyrin in methylene
chloride.
The new porphyrins 3-5 and 7-12 behave spectroscopi-
cally like other comparable TPPs. The 1H and 13C NMR data
for the metal-free systems as well as for the zinc porphyrins
point out the symmetrical situations of 3/7/10, 4/8/11, and
5/9/12, respectively. The FAB mass spectra of the brominated
materials 7-9 and their zinc complexes 10-12 show the
expected mass distributions for Br2, Br4, and Br8 compounds.
UV/vis spectroscopy reveals no unusual features for all
compounds.
Whereas 3-5 exhibit the typical porphyrin fluorescence
behavior, the fluorescence diminishes on thin-layer chroma-
tography (TLC) sheets the higher the bromine content is (7-
12) and vanishes completely, as expected, when their copper
derivatives (10-12 with M ) Cu in Scheme 4) were
analyzed.
a (a) i. HBr, AcOH, CH2Cl2, rt, ii. NaHCO3, H2O; (b) Zn(OAc)2,
MeOH, AcOH, CH2Cl2, rt.
12 have the typical orbital order for tetraphenyl porphyrins,
i.e., a2u for the HOMO and a1u for the HOMO-1, like the
zinc complexes of the octakis-o-methyl or the octakis-o-
(methoxymethyl) porphyrin 3, the octakis(bromomethyl)ated
compound 10 has an inverse arrangement of these orbitals.
This behavior is known for TPPs with electron-withdrawing
groups in the ortho-positions.17 Obviously, the bromine atoms
have a similar effect on the electronic nature of TPP although
they are not directly attached to the phenyl rings.
At this point the specific geometrical and chemical
properties of the (bromomethyl)ated porphyrins should be
mentioned. Due to their ortho-position on the phenyl rings,
the bromomethyl groups sit atop of the porphyrin and also
very close to the N4 core. Because of the close proximity to
the large porphyrin, the rotation of substituents will be
restricted. The described situation gives rise to novel
porphyrin conjugates with electro/redox-active or ion-bond-
ing substituents that are subject to conformational constraints
and therefore lead to potentially better interactions between
porphyrin and attached groups.
Scheme 3a
The reactive bromomethyl groups, which are in fact benzyl
bromides, allow for reaction with many different nucleophiles
such as azides, primary to tertiary amines, pyridines, thiols,
and also carbon nucleophiles such as cyanide or malonates.
Some examples of interesting materials based on the
aforementioned substances are shown in Scheme 5. Addition
of sodium azide to a solution of 12 in tetrahydrofuran in the
presence of [18]crown-6 gave the interesting bis-azide 13
which shows some potential for inter- and intramolecular
addition reactions. As it turns out not only is it possible to
substitute all of the reactive positions but in case of 12 also
using only half the molar equivalents of reactant gives
a (a) i. 1 equiv of 4-tert-butylbenzaldehyde, BF3‚OEt2, CH2Cl2
(+1% EtOH), rt; ii. DDQ, CH2Cl2, rt, b. 3 equiv of 4-tert-
butylbenzaldehyde, 2 equiv of pyrrole, BF3‚OEt2, CH2Cl2 (+1%
EtOH), rt, ii. DDQ, CH2Cl2, rt.
Calculations16 of the frontier orbitals of the zinc porphyrins
10-12 show some remarkable differences. Whereas 11 and
(17) Strachan, J. P.; Gentemann, S.; Seth, J.; Kalsbeck, W. A.; Lindsey,
J. S.; Holten, D.; Bocian, D. F. J. Am. Chem. Soc. 1997, 119, 11191-
11201. Yang, S. I.; Seth J.; Balasubramanian, T.; Kim, D.; Lindsey, J. S.;
Holten, D.; Bocian, D. F. J. Am. Chem. Soc. 1999, 121, 4008-4018.
(16) Calculations were performed on the PM3 level with PC Spartan
Plus, Wavefunction, Inc.
Org. Lett., Vol. 2, No. 14, 2000
2131

compounds. As an example 12 reacts with potassium cyanide
in THF (presence of [18]crown-6 required) to yield 14.
Azides give access to amino derivatives, cyanides also to
amines but to carboxylates, too. Such materials allow the
syntheses of peptide or carbohydrate conjugates, which create
chiral environments near the metal center of the porphyrin.
Reaction of 10, 11, and 12 with 4-tert-butylpyridine in
refluxing toluene yielded an octa-, a tetra-, and a dipyri-
dinium salt (15, 16, 17), respectively, which showed shifts
in both their NMR and UV spectra, indicating clearly the
influence of the positive charges on the porphyrin chro-
mophore. The shift of the Soret band to longer wavelengths
is (compared to zinc tetrakis[4-tert-butylphenyl]porphyrin;
in methanol) about 5 nm for 17, 12 nm for 16, and 15 nm
for 15. Cyclic voltammetry is currently being performed on
these species, and the results and other data will be presented
elsewhere.
Scheme 5
Acknowledgment. This work was supported by Fonds
der Chemischen Industrie, the BMBF, and the Deutsche
Forschungsgemeinschaft. We thank Prof. Dr. Andreas Hirsch,
Universita¨t Erlangen-Nu¨rnberg, for his generous support.
Supporting Information Available: Descriptions of
experimental procedures, NMR and FAB mass spectral data
for 1, 3-17, and UV/vis data for 3-5, 7-17. This material
is available free of charge via the Internet at http://pubs.acs.org.
differentially substituted molecules. Of course, these can be
modified in a second step to give even more complex
OL006028X
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Org. Lett., Vol. 2, No. 14, 2000