Stepwise fusion of porphyrin β,β′-pyrrolic positions to imidazole rings

Article abstract of DOI:10.1021/ol2010215

A strategy for the stepwise annulation of pyrrolic rings of a porphyrin to imidazole rings is presented. Mono(imidazole), Janus and corner bis(imidazole), T-shaped tris(imidazole), and tetrakis(imidazole) porphyrins have been synthesized and characterized

Full text of DOI:10.1021/ol2010215

ORGANIC
LETTERS
2011
Vol. 13, No. 12
3110–3113
Stepwise Fusion of Porphyrin
β,β0-Pyrrolic Positions to Imidazole
Rings
Mamadou Lo,† Jean-Franc-ois Lefebvre,† Dominique Leclercq,† Arie van der Lee,‡ and
,†
ꢀ
Sebastien Richeter*
ꢀ
Institut Charles Gerhardt Montpellier, UMR 5253 CNRS-UM2-ENSCM-UM1 equipe
Chimie Moleculaire et Organisation du Solide, Universite Montpellier 2, batiment 17,
ꢀ
ꢀ
^
ꢀ
and Institut Europeen des Membranes, UM2, CNRS, ENSCM, CC 045, Universite
Montpellier 2, Place Eugene Bataillon, 34095 Montpellier Cedex 05, France
ꢀ
ꢁ
sebastien.richeter@univ-montp2.fr
Received April 17, 2011
ABSTRACT
A strategy for the stepwise annulation of pyrrolic rings of a porphyrin to imidazole rings is presented. Mono(imidazole), Janus and corner
bis(imidazole), T-shaped tris(imidazole), and tetrakis(imidazole) porphyrins have been synthesized and characterized.
Among π-conjugated molecules, porphyrins are of
great interest because they are photo- and electroactive
molecules which have wide applications in catalysis,1
medicine,2 and materials science.3 The introduction
of π conjugated systems fused to the aromatic core of
a porphyrin can deeply modify their electronic prop-
erties, as illustrated for exocyclic fused rings such
as pyridine,4 quinoxaline,5 quinoline,6 isoquinoline,6a
† Institut Charles Gerhardt Montpellier.
‡
ꢀ
Institut Europeen des Membranes.
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r
10.1021/ol2010215
Published on Web 05/23/2011
2011 American Chemical Society

azulene,7 naphthalene,8 pyrene,9 or anthracene.10 Several
porphyrins fused to five-membered N-heterocycles such as
pyrrole,11 pyrrazole,12 triazole,13 and imidazole14ꢀ17
groups have also been synthesized.
Scheme 1. Fusion of Porphyrin β,β0-Pyrrolic Positions to One
Imidazole Ring17
Porphyrins containing imidazole rings fused across β,
β0-pyrrolic positions and conjugated to the macrocycle
have notably been reported by Crossley and colleagues,
who prepared fused porphyrinꢀimidazole systems by
condensation of porphyrin-2,3-diones with an aryl alde-
hyde in the presence of NH4OAc.14 Following this proce-
dure, the compounds obtained have C(20)-aryl groups, and
these molecules were shown to be interesting subunits in
donorꢀacceptor linked dyads15a or triads15b for the study
of photoinduced electron-transfer processes. Following a
different synthetic strategy, we synthesized porphyrins
fused to an imidazole ring with C(20)-H. We have shown
that the corresponding N,N0-dialkylimidazolium salts are
N-heterocyclic carbene (NHC) precursors and that metal
complexes such as palladium(II)16a or rhodium(I)16b com-
plexes can be anchored at the peripheral NHC ligand.
These studies led us to develop an efficient synthetic strategy
to prepare metalloporphyrins annulated to one exocyclic
imidazole ring with a C(20)-H instead of a C(20)-aryl group,
according to the following four steps:17 (i) nitration of one
β-pyrrolic position, (ii) amination of the adjacent β-pyrrolic
position, (iii) reduction of the nitro group to obtain the 2,
3-diaminoporphyrin, and (iv) cyclization, in order to obtain
compound 1 which contains one pyrrole annulated to one
imidazole ring (Scheme 1). Herein, we show that up to
four imidazole rings can be fused to the porphyrin macro-
cycle by repeating this sequence of reactions. This stepwise
ring annelation of each of the four β,β0-pyrrolic positions
using successive porphyrin-R-diamines complements that of
Crossley and colleagues who elaborated mono-, bis-, tris-,
and tetrakis(quinoxalino)porphyrins by their porphyrin-R-
dione methodology.5b,c,18
nitroporphyrin isomers 2ꢀ4 in 92% yield (Scheme 2).
The nitration reaction did not occur at the C(20) of the
imidazole ring. Crossley and colleagues studied the
nitration of porphyrin-2,3-diones and also obtained a
mixture of three β-pyrrolic functionalized nitroporphyr-
in isomers. They used an elegant metalation/demetala-
tion procedure to separate the three isomers.19 Here, the
β-nitroporphyrin isomers 2ꢀ4 could not be separated by
column chromatography at this stage, and the mixture
was thus used as such in the following amination step.
The β-pyrrolic carbons next to the β-NO2 groups were
regioselectively aminated with 4-amino-4H-1,2,4-tria-
zole under basic conditions. Then, column chromato-
graphic separation on silica gel allowed the separation of
isomer 5 (nitro and amino groups on the pyrrole op-
posed to the one fused to the imidazole ring) with 29%
yield from the two other isomers 6 and 7 (nitro and
amino groups on the pyrrole next to the one fused to the
imidazole ring) obtained as a mixture with 60% yield.
The reduction of the nitro group of the porphyrin 5 led to
the corresponding diaminoporphyrin, which was not
isolated but used directly for the cyclization reaction
with HC(OMe)3 under acidic conditions. The Janus
bis(imidazole) 8 was thus obtained in 81% yield. The
same reduction and cyclization reactions were per-
formed on the mixture of isomers 6 and 7, leading to
the corner bis(imidazole) 9 in 85% yield (Scheme 2).
Right mass peaks corresponding to the mono- and
diprotonated species were observed for both isomers
by ESI-TOF mass spectrometry (m/z = 975.4 [M þ H]þ
and 488.2 [M þ 2H]2þ, respectively). The signals ob-
The mononitration reaction performed on porphyrin 1
leads to a mixture of three β-pyrrolic functionalized
(11) (a) Jaquinod, L.; Gros, C.; Olmstead, M. M.; Antolovich, M.;
Smith, K. M. Chem. Commun. 1996, 1475–1476. (b) Gros, C. P.;
Jaquinod, L.; Khoury, R. G.; Olmstead, M. M.; Smith, K. M.
J. Porphyrins Phthalocyanines 1997, 1, 201–212. (c) Silva, A. M. G.;
Faustino, M. A. F.; Tome, A. C.; Neves, M. G. P. M. S.; Silva, A. M. S.;
Cavaleiro, J. A. S. J. Chem. Soc. Perkin Trans. 1 1999, 2752–2753.
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A. M. S.; Cavaleiro, J. A. S. Tetrahedron 2005, 61, 11866–11872.
(12) Silva, A. M. G.; Tome, A. C.; Neves, G. P. M. S.; Cavaleiro,
J. A. S. Synlett 2002, 7, 1155–1157.
(13) Lacerda, P. S. S.; Silva, A. M. G.; Tome, A. C.; Neves, M. G. P.
M. S.; Silva, A. M. S.; Cavaleiro, J. A. S.; Llamas-Saiz, A. L. Angew.
Chem., Int. Ed. 2006, 45, 5487–5491.
(14) Crossley, M. J.; McDonald, J. A. J. Chem. Soc., Perkin Trans. 1
1999, 2429–2431.
1
served on the H NMR spectra of bis(imidazole) por-
phyrins 8 and 9 recorded in CDCl3 at room temperature
are globally broad due the slow imidazole tautomerism
on the 1H NMR time scale.20 The 1H NMR spectrum of
Janus bis(imidazole) 8 displayed one singlet at δ = 1.59
ppm corresponding to the tert-butyl groups and one
broad singlet at δ = 8.82 ppm corresponding to the four
Cβ-H. In the 1H NMR spectrum of the corner bis-
(imidazole) 9, the three singlets observed at δ = 1.61,
1.58, and 1.55 ppm corresponding to tert-butyl groups
(15) (a) Kashiwagi, Y.; Ohkubo, K.; McDonald, J. A.; Blake, I. M.;
Crossley, M. J.; Araki, Y.; Ito, O.; Imahori, H.; Fukuzumi, S. Org. Lett.
2003, 5, 2719–2721. (b) Curiel, D.; Ohkubo, K.; Reimers, J. R.;
Fukuzumi, S.; Crossley, M. Phys. Chem. Chem. Phys. 2007, 9,
5260–5266.
(16) (a) Richeter, S.; Hadj-Aıssa, A.; Taffin, C.; van der Lee, A.;
Leclercq, D. Chem. Commun. 2007, 2148–2150. (b) Lefebvre, J. -F.; Lo,
M.; Leclercq, D.; Richeter, S. Chem. Commun. 2011, 47, 2976–2978.
(17) Lefebvre, J. -F.; Leclercq, D.; Gisselbrecht, J. -P.; Richeter, S.
Eur. J. Org. Chem. 2010, 1912–1920.
(19) Crossley, M. J.; Sheehan, C. S.; Khoury, T.; Reimers, J. R.;
Sintic, P. J. New J. Chem. 2008, 32, 340–352.
(20) Although bis-, tris-, and tetrakis(imidazole) porphyrin deriva-
tives described here exist as a mixture of tautomers, only one tautomeric
structure is represented for each compound in Schemes 2ꢀ4 and in the
Supporting Information. See also refs 14ꢀ17.
(18) Crossley, M. J.; Govenlock, L. G.; Prashar, J. K. Chem. Com-
mun. 1995, 2379–2380.
Org. Lett., Vol. 13, No. 12, 2011
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are well resolved, whereas the signals corresponding to
the pyrrolic protons are not. However, sharper signals
were observed after the addition of an excess of trifluor-
oacetic acid (TFA) to sample 9: in this case, two signals
are observed for the pyrrolic protons (two doublets at
δ = 8.97 and 8.92 ppm) due to the lower symmetry of
this molecule compared to bis(imidazole) 8.
mean plane (based on a least-squares plane calculated for
the 24 core atoms of the porphyrin). The additional
imidazole rings and their corresponding fused pyrroles
are coplanar. Thus, because of the saddle-shape conforma-
tion of the porphyrin, one imidazole ring is above the mean
plane of the porphyrin, while the other is underneath. The
nickel(II) metal ion is in a slightly distorted square planar
geometry: the four NiꢀN distances are almost equivalent
(1.945(3)ꢀ1.960(3) A), the four NꢀNiꢀN cis-angles are
close to 90° (89.67(9)ꢀ90.91(9)°), and the two NꢀNiꢀN
trans-angles are 172.60(9) and 172.02(10)°. Interestingly,
because both imidazole rings are protonated, porphyrins
are self-assembled in the solid state thanks to a network of
hydrogen bonds between 9-2H2þ dications, trifluoroace-
tate anions, and TFA molecules (Figure S1, Supporting
Information).
Scheme 2. Fusion of Porphyrin β,β0-Pyrrolic Positions to Two
Imidazole Rings
Figure 1. ORTEP view of the X-ray structure of the diproto-
nated bis(imidazole) 9-2H2þ with displacement ellipsoids drawn
at the 50% probability level (CF3CO2H and CF3CO2
ꢀ
molecules have been omitted for clarity).21
In the case of bis(imidazole) 9, we were able to grow
single crystals suitable for X-ray study by adding TFA to
the solvent system used for crystallization (CHCl3/
n-heptane).21 Single-crystal X-ray analysis unambiguously
establishes the structure of bis(imidazole) 9, showing that
two neighboring pyrroles are fused to imidazole rings and
that nickel(II) coordination distorts the porphyrin from
planarity (Figure 1). The porphyrin macrocycle is saddle-
shaped, asshownbythemaximum displacementof 0.566A
for one of the Cβ carbons and the average displacement of
0.283 A for the core atoms with respect to the porphyrin
The construction of the third imidazole ring was
achieved by performing the same four synthetic steps on
the Janus-type bis(imidazole) 8 or on the corner bis-
(imidazole) 9. Knowing that the four Cβ-H are equivalent,
nitration of Janus-type bis-imidazole 8 with LiNO3 af-
forded compound 10 as a single compound in 74% yield.
Again, the β-pyrrolic carbon next to the β-NO2 group was
regioselectively aminated, and compound 11 was obtained
in 83% yield. The reduction of the nitro group of 11 and
the cyclization reaction afforded the T-shape tris-
(imidazole) 16 in 69% yield (Scheme 3). This compound
was also obtained starting from corner bis(imidazole) 9.
Nitration of bis(imidazole) 9 afforded an inseparable
mixture of nitro isomers 12 and 13 which were subse-
quently aminated to obtain 14 and 15 as an inseparable
mixture. The reduction and cyclization reactions with the
mixture of the isomers 14 and 15 afforded the same
(21) Crystal data for 9-2H2þ
:
C62H62N8Ni 3(CF3CO2H) 3-
3
3
(CF3CO2), MW = 1546.01, triclinic, space group P-1, a = 12.1781(3)
A, b = 18.0930(4) A, c = 18.6755(4) A, R = 94.0274(17)°, β =
108.2505(19)°, γ = 99.0435(17)°, V = 3827.91(15) A3, Z = 2,
Dcalcd=1.365 g cmꢀ3, T = 173 K, λ (Mo KR) = 0.71073 A, μ
(Mo KR) = 0.35 mmꢀ1, 17527 reflections collected, 12985 unique reflns
I > 2σ(I), Rint = 0.053, RF = 0.066 and wRF = 0.075. See the
Supporting Information for experimental details.
3112
Org. Lett., Vol. 13, No. 12, 2011

T-shape tris(imidazole) 16 in 70% yield (Scheme 3). As
expected, right mass peaks corresponding to the mono-,
di- and triprotonated species were observed for 16 by ESI-
TOF mass spectrometry (at m/z = 1015.4 [M þ H]þ, 508.2
[M þ 2H]2þ, and 339.1 [M þ 3H]3þ, respectively). The 1H
NMR spectrum of 16 displayed one singlet at δ = 8.80
ppm corresponding to the two remaining Cβ-H.
Scheme 4. Fusion of Porphyrin β,β0-Pyrrolic Positions to Four
Imidazole Rings
Scheme 3. Fusion of Porphyrin β,β0-Pyrrolic Positions to Three
Imidazole Rings
mass spectrometry (at m/z = 1055.4 [M þ H]þ, 528.2 [M þ
2H]2þ, and 352.5 [M þ 3H]3þ, respectively).
In conclusion, a strategy for the stepwise annulation of
the pyrrolic rings of a porphyrin to imidazole rings has
been presented. Interestingly, all the possible isomers
resulting from the fusion of one to four imidazole rings
to the porphyrin were obtained by repeating a sequence of
four reactions. Using this established synthetic protocol,
further complex molecules may then be obtained, such as
bis-, tris-, or tetrakis(imidazol-2-ylidene) ligands and their
metal complexes, for the formation of 1D-polymeric ma-
terials or square grid networks of porphyrins. This re-
search is in progress in our group.
Acknowledgment. We are grateful to the French Min-
istry of Research, the CNRS, and the Agence Nationale de
la Recherche for financial support of the research project
ANR-09-JCJC-0089-01.
Further functionalization of these two remaining
β-pyrrolic positions of the T-shaped tris(imidazole) 16
was achieved, and compounds 17 and 18 were obtained
in 60 and 65% yields, respectively. The cyclization reaction
then afforded tetrakis(imidazole) 19 in 52% yield (Scheme 4).
Supporting Information Available. Detailed experimen-
tal procedures, spectroscopic characterizations of all
compounds, crystallographic data, and a CIF file for
compound 9. This material is available free of charge
via the Internet at http://pubs.acs.org.
1
The H NMR spectrum of tetrakis(imidazole) 19 is very
simple because of its C4 symmetry. As expected, no signal
corresponding to pyrrolic protons was observed. Mono-,
di-, and triprotonated species were detected by ESI-TOF
Org. Lett., Vol. 13, No. 12, 2011
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