Catalyst-free aromatic nucleophilic substitution of meso-bromoporphyrins with azide anion: Efficient synthesis and structural analyses of meso -azidoporphyrins

Article abstract of DOI:10.1021/ol202973z

meso-Mono- or diazidoporphyrins were readily obtained in high yields by the catalyst-free aromatic nucleophilic reaction of the corresponding bromoporphyrins with azide anions under mild conditions. The molecular structures of the obtained azides were una

Full text of DOI:10.1021/ol202973z

ORGANIC
LETTERS
2012
Vol. 14, No. 1
190–193
Catalyst-Free Aromatic Nucleophilic
Substitution of meso-Bromoporphyrins
with Azide Anion: Efficient Synthesis and
Structural Analyses of
meso-Azidoporphyrins
Ken-ichi Yamashita,* Kazuyuki Kataoka, Motoko S. Asano, and Ken-ichi Sugiura*
Department of Chemistry, Graduate School of Science and Engineering, Tokyo
Metropolitan University, 1-1 Minami-Osawa, Hachioji, Tokyo 192-0397, Japan
*yamashita-kenichi@tmu.ac.jp; sugiura@porphyrin.jp
Received November 4, 2011
ABSTRACT
meso-Mono- or diazidoporphyrins were readily obtained in high yields by the catalyst-free aromatic nucleophilic reaction of the corresponding
bromoporphyrins with azide anions under mild conditions. The molecular structures of the obtained azides were unambiguously determined by
X-ray crystallographic analysis.
Functionalization of the porphyrin periphery is one of
the most important approaches to achieve the construc-
tion of novel porphyrin-based materials with unique
chemical, biological, or optical properties derived from
the extended π-electron system.1 To date, a wide variety
of porphyrins with carbon- or heteroatom-based func-
tional groups have been synthesized through electrophilic
substitutions, nucleophilic reactions involving porphyrin
π-cation radicals, nucleophilic reactions with organome-
tallic reagents followed by oxidation, or transition-metal-
catalyzed coupling reactions.1ꢀ7 In particular, a recent
outstanding development of transition metal catalysts
(1) Vicente, M. G. H.; Jaquinod, L. In The Porphyrin Handbook;
Kadish, K. M., Smith, K. M., Guilard, R., Eds.; Academic Press: San Diego,
2003; Vol. 1, pp 149ꢀ199.
(2) For recent examples of nucleophilic reactions which involve
porphyrin π-cation radicals, see: (a) Shen, D.-M.; Liu, C.; Chen, X.-G.;
Chen, Q.-Y. J. Org. Chem. 2009, 74, 206–211. (b) Devillers, C. H.; Dime,
A. K. D.; Cattey, H.; Lucas, D. Chem. Commun. 2011, 1893–1895.
(3) For recent reviews on nucleophilic reactions with organometallic
reagents followed by oxidation, see: (a) Senge, M. O. Acc. Chem. Res.
2005, 35, 733–743. (b) Senge, M. O. Chem. Commun. 2011, 1943–1960.
(4) For recent examples of nucleophilic reactions with organometallic
reagents followed by oxidation, see: (a) Takanami, T.; Wakita, A.;
Sawaizumi, A.; Iso, K.; Onodera, H.; Suda, K. Org. Lett. 2008, 10,
685–687. (b) Takanami, T.; Matsumoto, J.; Kumagai, Y.; Sawaizumi,
A.; Suda, K. Tetrahedron Lett. 2009, 50, 68–70. (c) Takanami, T.;
Hayashi, S.; Iso, K.; Matsumoto, J.; Hino, F. Tetrahedron Lett. 2011,
52, 5345–5348.
(6) For recent examples of transition-metal-catalyzed CꢀN bond
formations of meso-haloporphyrins, see: (a) Takanami, T.; Hayashi, M.;
Hino, F.; Suda, K. Tetrahedron Lett. 2003, 44, 7353–7357. (b) Chen, Y.;
Zhang, X. P. J. Org. Chem. 2003, 68, 4432–4438. (c) Gao, G. Y.; Chen,
Y.; Zhang, X. P. Org. Lett. 2004, 6, 1837–1840. (d) Chen, Y.; Gao, G.-Y.;
Zhang, X. P. Tetrahedron Lett. 2005, 46, 4965–4969. (e) Esdaile, L. J.;
McMurtrie, J. C.; Turner, P.; Arnold, D. P. Tetrahedron Lett. 2005, 46,
6931–6935. (f) Esdaile, L. J.; Senge, M. O.; Arnold, D. P. Chem.
Commun. 2006, 4192–4194. (g) Liu, C.; Shen, D. M.; Chen, Q. Y.
J. Org. Chem. 2007, 72, 2732–2736. (h) Sakamoto, R.; Sasaki, T.;
Honda, N.; Yamamura, T. Chem. Commun. 2009, 5156–5158. (i)
Pereira, A. M. V. M; Neves, M. G. P. M. S.; Cavaleiro, J. A. S.; Jeandon,
C.; Gisselbrecht, J.-P.; Choua, S.; Ruppert, R. Org. Lett. 2011, 13,
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(5) For recent reviews on transition-metal-catalyzed coupling reac-
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Commun. 2009, 1011–1021.
r
10.1021/ol202973z
Published on Web 12/13/2011
2011 American Chemical Society

enabled us to introduce various functional groups in high
yields.6,7 However, several active metal catalysts are
expensive or not commercially available.
meso-aminoporphyrins is quite cumbersome as described
above. Furthermore, it is quite troublesome to synthesize
meso-diazidoporphyrin by the reported procedure be-
cause of the highly air-sensitive nature of the precursors,
i.e., meso-diaminoporphyrins.13 Therefore, there is still
plenty of room for improvement in the synthetic route to
develop the chemistry of azidoporphyrins. Aromatic
nucleophilic substitution (SNAr) reactions of aryl halides
with an azide anion are facile and efficient procedures to
synthesize aromatic azides, especially in the case of
electron-deficient aromatics.10 However, the SNAr reac-
tions of haloporphyrins have not been energetically in-
vestigated as a method for peripheral functionalization of
the porphyrins.1,14 More recently, Balaban et al. reported
the practical SNAr reactions of meso-bromoporphyrins
with alkylamines.14e,f Herein, we have found that meso-
mono- or dibromodiarylporphyrins undergo the SNAr-
type reaction with an azide anion under mild conditions
without any additive to give the corresponding azidopor-
phyrins in high yields. In addition, we have revealed the
first molecular and crystal structures of mono- and
diazidoporphyrins, which are, to the best of our knowl-
edge, one of the largest aromatic azides confirmed by
X-ray analysis.15
meso-Nitrogen-substituted porphyrins are relatively
well-investigated heteroatom-substituted porphyrins be-
cause the introduced substituents strongly affect a π-electron
system of the porphyrin. There have been two typical
synthetic routes to meso-nitrogen-substituted porphyrins.
One is a transformation of an amino group (ꢀNH2),8 which
is introduced by a nitration and a subsequent reduction of
the introduced nitro group.9 The other is a transition-metal-
catalyzed CꢀN(amine or amide) bond formation from
meso-haloporphyrins described above.6
Azido groups also play important roles in synthetic
chemistry due to their versatile conversion to other func-
tional groups such as amine (by reduction), 1,2,3-triazole
(by cycloaddition with alkyne), and highly reactive nitrene
(by thermal decomposition or photodecomposition).10 De-
spite the synthetic usefulness of the azide groups, there have
been few reports directly concerning azido-substituted
porphyrins.11,12 In a previous report, meso-azidoporphyrin
(Ni complex) was synthesized by treatment of sodium
azide with a diazonium salt prepared from meso-amino-
porphyrin (85% yield).11b However, the synthesis of the
First, we investigated a reaction of a Ni(II) complex of
meso-bromodiarylporphyrin 1a(Ni) with sodium azide.
Typically, 1a(Ni) was treated with 10 equiv of sodium
azide in DMF under a N2 atmosphere with protection
from light. When the reaction was performed at 40 °C for
7 h, the desired meso-azidoporphyrin 2a(Ni) was obtained
in 93% yield (Table 1, entry 1). The reaction time was re-
duced by elevating the reaction temperature to 60 °C
(entry 2), although a longer reaction time led to the
thermal decomposition of 2a(Ni) into meso-aminopor-
phyrin 3a(Ni) and undefined brown byproducts (entry 3).
At 90 °C, 2a(Ni) was completely decomposed with the
formation of 3a(Ni) in 25% yield (entry 4). When the
amount of sodium azide was reduced to 5 equiv (entry 5),
a longer reaction time was required to complete the reac-
tion. Therefore, the yield of 2a(Ni) was reduced compared
to entry 3 (the same condition except for the amount of
sodium azide). The reaction proceeded smoothly in DMF
while no reaction proceeded in THF (entry 6). Reaction
of meso-bromodiphenylporphyrin 1b(Ni) also gave azi-
doporphyrin 2b(Ni) in 68% yield (entry 7). Because of the
poor solubility of 1b(Ni) in DMF, a longer reaction time
was required.
(7) For recent examples of transition-metal-catalyzed other Cꢀ
heteroatom or CꢀC bond formations of meso-haloporphyrins, see: (a)
Hyslop, A. G.; Kellett, M. A.; Iovine, P. M.; Therien, M. J. J. Am. Chem.
Soc. 1998, 120, 12676–12677. (b) Gao, G.-Y.; Colvin, A. J.; Chen, Y.;
Zhang, X. P. Org. Lett. 2003, 5, 3261–3264. (c) Gao, G.-Y.; Colvin, A. J.;
Chen, Y.; Zhang, X. P. J. Org. Chem. 2004, 69, 8886–8892. (d)
Takanami, T.; Hayashi, M.; Chijimatsu, H.; Inoue, W.; Suda, K. Org.
Lett. 2005, 7, 3937–3940. (e) Atefi, F.; McMurtrie, J. C.; Turner, P.;
Duriska, M.; Arnold, D. P. Inorg. Chem. 2006, 25, 6479–6489. (f)
Matano, Y.; Shinokura, T.; Matsumoto, K.; Imahori, H.; Nakano, H.
Chem.;Asian J. 2007, 2, 1417–1429. (g) Gao, G. Y.; Ruppel, J. V.;
Fields, K. B.; Xu, X.; Chen, Y.; Zhang, X. P. J. Org. Chem. 2008, 73,
4855–4858. (h) Matano, Y.; Matsumoto, K.; Nakao, Y.; Uno, H.;
Sakaki, S.; Imahori, H. J. Am. Chem. Soc. 2008, 130, 4588–4589. (i)
Enakieva, Y. Y.; Bessmertnykh, A. G.; Gorbunova, Y. G.; Stern, C.;
Rousselin, Y.; Tsivadze, A. Y.; Guilard, R. Org. Lett. 2009, 11, 3842–
3845.
(8) (a) Screen, T. E. O.; Blake, I. M.; Rees, L. H.; Clegg, W.; Borwick,
S. J.; Anderson, H. L. J. Chem. Soc., Perkin Trans. 1 2002, 320–329. (b)
Redmore, N. P.; Rubtsov, I. V.; Therien, M. J. Inorg. Chem. 2002, 41,
566–570. (c) Yoshida, N.; Ishizuka, T.; Yofu, K.; Murakami, M.;
Miyasaka, H.; Okada, T.; Nagata, Y.; Itaya, A.; Cho, H. S.; Kim, D.;
Osuka, A. Chem.;Eur. J. 2003, 9, 2854–2866. (d) Kamada, T.; Aratani,
N.; Ikeda, T.; Shibata, N.; Higuchi, Y.; Wakamiya, A.; Yamaguchi, S.;
Kim, K. S.; Yoon, Z. S.; Kim, D.; Osuka, A. J. Am. Chem. Soc. 2006,
128, 7670–7678. (e) Esdaile, L. J.; Jensen, P.; McMurtrie, J. C.; Arnold,
D. P. Angew. Chem., Int. Ed. 2007, 46, 2090–2093. (f) Shen, D.-M.; Liu,
C.; Chen, X.-G.; Chen, Q.-Y. Synlett 2009, 6, 945–948. (g) Wallin, S.;
Monnereau, C.; Blart, E.; Gankou, J.-R.; Odobel, F.; Hammarstrom, L.
J. Phys. Chem. A 2010, 114, 1709–1721.
(9) Arnold, D. P.; Bott, R. C.; Eldridge, H.; Elms, F.; Smith, G.;
Zojaji, M. Aust. J. Chem. 1997, 50, 495–503.
€
(10) (a) Brase, S.; Gil, C.; Knepper, K.; Zimmermann, V. Angew.
Chem., Int. Ed. 2005, 44, 5188–5240. (b) Chapyshev, S. V. Synlett 2009,
1–8. (c) Minozzi, M.; Nanni, D.; Spagnolo, P. Chem.;Eur. J 2009, 15,
7830–7840. (d) Organic Azides: Syntheses and Applications; Brase, S.,
(13) To the best of our knowledge, meso-diaminodiarylporphyrins
and their metal complexes have not been reported.
€
Banert, K., Eds.; John Wiley & Sons: Chichester, 2010.
(11) For meso-azidoporphyrins, see: (a) Smith, K. M.; Barnett, G. H.;
(14) (a) Baldwin, J. E.; Crossley, M. J.; DeBernardis, J. Tetrahedron
1982, 38, 685. (b) Gong, L. C.; Dolphin, D. Can. J. Chem. 1985, 63, 3793–
3799. (c) Crossley, M. J.; King, L. G.; Simpson, J. L. J. Chem. Soc.,
Perkin Trans. 1 1997, 3087–3096. (d) Crossley, M. J.; King, L. G.; Pyke,
S. M.; Tansey, C. W. J. Porphyrins Phthalocyanines 2002, 6, 685–694. (e)
Balaban, M. C.; Chappaz-Gillot, C.; Canard, G.; Fuhr, O.; Roussel, C.;
Balaban, T. S. Tetrahedron 2009, 65, 3733–6522. (f) Balaban, M. C.;
Evans, B.; Martynenko, Z. J. Am. Chem. Soc. 1979, 101, 5953–5961. (b)
ꢀ
Severac, M.; Pleux, L. L.; Scarpaci, A.; Blart, E.; Odobel, F. Tetrahedron
Lett. 2007, 48, 6518–6522.
(12) For β-azidoporphyrins, see: (a) Shen, D.-M.; Liu, C.; Chen
Q.-Y. Eur. J. Org. Chem. 2007, 1419–1422. (b) Liu, H.; Duclairoir, F.;
Fleury, B.; Dubois, L.; Chenavier, Y.; Marchon, J. C. Dalton Trans.
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Eichhofer, A.; Buth, G.; Hauschild, R.; Szmytkowski, J.; Kalt, H.;
Balaban, T. S. J. Phys. Chem. B 2008, 112, 5512–5521.
(15) Cambridge Structural Database (CSD), version 5.3.2 (updated
May, 2011).
ꢀ
2009, 3793–3799. (c) 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.
Org. Lett., Vol. 14, No. 1, 2012
191

azide in DMF at 60 °C for 20 min gave the desired
meso-diazidoporphyrin 5a(Ni) in 86% yield (Scheme 1).
We also examined the reaction of a Ni complex of β-
bromotetraphenylporphyrin 6(Ni) to evaluate the reac-
tivity of β-positions. However, no substituted products
were formed by treatment of 6(Ni) with sodium azide at
90 °C for 18 h.
Table 1. Catalyst-Free Aromatic Nucleophilic Substitution
Reaction of meso-Bromoporphyrin 1(M) with Sodium Azidea
Scheme 1. Synthesis of meso-Diazidoporphyrin 5(Ni)
yieldb (%)
temp
time
(h)
entry
1(M)
solvent
(°C)
2(M)
3(M)
1
1a(Ni)
1a(Ni)
1a(Ni)
1a(Ni)
1a(Ni)
1a(Ni)
1b(Ni)
1a(Zn)
1a(2H)
1a(2H)
DMF
DMF
DMF
DMF
DMF
THF
DMF
DMF
DMF
DMF
40
60
60
90
60
60
40
90
60
60
7
93
77
59
0
1
2
1
6
3
3
15c
25c
8
4
1.7
16.5
2
5d
6
67
0
Obtained meso-azidoporphyrins 2(Ni) and 5(Ni) are
moderately stable at room temperature in the dark to
perform structural analyses including NMR, MS, and
X-ray analyses. By contrast, the photodecomposition of
the azides proceeds gradually upon standing the dilute
0
7
16.5
18
2.5
0.5
68
0
12
8
tracee
44c
39f
9
0
23f
10
1
a Reaction condition: 1(M) (10 mM), NaN3 (10 equiv) under N2
atmosphere with protection from light. b Isolated yields unless otherwise
noted. c Undefined byproducts were also obtained. d 5 equiv of NaN3.
e Recovery of 1a(Zn). f Yields were determined by the intergral ratio of
1H NMR of the crude products.
solution under room light (Figure S13). The H NMR
spectrum of 2a(Ni) is almost identical to that of the
reported one.11b IR spectra of 2a(Ni) and 5a(Ni) display
intense characteristic stretching vibrations of the azide
group at 2107 and 2105 cmꢀ1, respectively (Figures
S7ꢀS8). The HR ESI-TOF MS spectrum of 2a(Ni) clearly
shows a expected molecular ion peak at 903.3966 for
[2a(Ni)]þ (Figures S3ꢀS6). By contrast, the MALDI- or
APCI-TOF MS spectrum of 2a(Ni) does not show an
expected molecular ion peak, but rather a peak corre-
sponding to the nitrogen-eliminated ion [2a(Ni)ꢀN2]þ.
UVꢀvis absorption spectra of 2a(Ni) and 5a(Ni) display
typical Soret and Q bands of Ni(II) porphyrins (Figures
S11ꢀS12).
This reaction was also dependent on the central metal
ion of the porphyrin. The reaction of zinc(II) complex
1a(Zn) was significantly slower than that of 1a(Ni).
Furthermore, we were not able to observe the formation
of 2a(Zn) at any stage in this reaction because of the harsh
reaction conditions (Table 1, entry 8). This lower reactiv-
ity of 1a(Zn) is attributed to the increase of the electron
density on the porphyrin core induced by the electro-
positive zinc(II) ion.1,6a In the case of free-base porphyrin
1a(2H), the main product was meso-aminoporphyrin 3a-
(2H) after the complete disappearance of 1a(2H) (entry
9). At an early stage in the reaction, free-base azidopor-
phyrin 2a(2H) was detected by 1H NMR and IR analyses
of the crude reaction mixture but was not able to be
isolated (entry 10). These results indicate that the sub-
stitution in 1a(2H) proceeds slower than that in 1a(Ni)
while the thermal decomposition of the azide 2a(2H)
proceeds much faster than that of 2a(Ni). It is also note-
worthy that the free-base meso-aminodiarylporphyrin is
obtained directly from the corresponding meso-bro-
modiarylporphyrin in modest yield because meso-amino-
diarylporphyrin has not been obtained directly by the
reported procedures.9
The crystal and molecular structures of 2b(Ni) and
5b(Ni) (Ar = phenyl) were determined by X-ray crystal-
lographic analysis. The crystal structure of 2b(Ni) is
depicted in Figure 1. The porphyrin moiety is slightly
ruffled with the average NiꢀN(porphyrin) distance of
˚
1.954 A. The azido group is slightly tilted out of the
porphyrin moiety with the C(1)ꢀC(20)ꢀN(5)ꢀN(6) di-
hedral angle of 18.6(5)° because of the steric repulsion
between the azide group and the neighboring β-hydrogen
of the porphyrin. The closest contact distance between
˚
azide-N and β-H (N(6)•••H(2)) is 2.37 A, which is shorter
˚
˚
than the sum of the van der Waals radii (1.55 A þ 1.20 A =
16
˚
˚
2.75 A). The N(5)ꢀN(6) bond length of 1.19 A is
significantly shorter than that of typical aryl azides (1.22ꢀ
15
˚
˚
1.27 A), while the N(6)ꢀN(7) bond length of 1.16 A is
˚
To demonstrate the versatility of our procedure, the
reaction of meso-dibromoporphyrin 4(Ni) was performed
to give meso-diazidoporphyrin 5(Ni). Indeed, treatment
of meso-dibromoporphyrin 4a(Ni) with10equiv of sodium
longer (1.11ꢀ1.14 A). In addition, the N(5)ꢀN(6)ꢀN(7)
angle of 168.8(4)° is also slightly smaller than that of
(16) Bondi, A. J. Phys. Chem. 1964, 68, 441.
Org. Lett., Vol. 14, No. 1, 2012
192

Figure 2. Crystal structure of 5b(Ni) (ORTEP, 50% probability).
Diffraction data were collected at ꢀ50 °C because of the severe
degradation of the diffraction at lower temperature. Selected
˚
bond lengths (A) and angles (deg): C(5)ꢀN(5) 1.427(5), N(5)ꢀ
N(6) 1.181(5), N(6)ꢀN(7) 1.149(5), C(15)ꢀN(8) 1.471(5), N(8)ꢀ
N(9) 1.187(6), N(9)ꢀN(10) 1.131(7), Ni(1)ꢀN(1) 1.926(3),
Ni(1)ꢀN(2) 1.927(3), Ni(1)ꢀN(3) 1.923(3), Ni(1)ꢀN(4) 1.927(3),
C(5)ꢀN(5)ꢀN(6) 121.5(3), N(5)ꢀN(6)ꢀN(7) 169.9(4), C(15)ꢀ
N(8)ꢀN(9) 115.9(4), N(8)ꢀN(9)ꢀN(10) 172.5(6).
Figure 1. Crystal structure of 2b(Ni): (a) ORTEP view (50%
probability), and (b) side view. Diffraction data were collected at
˚
ꢀ180 °C. Selected bond lengths (A) and angles (deg): C(20)ꢀ
N(5) 1.429(4), N(5)ꢀN(6) 1.185(4), N(6)ꢀN(7) 1.162(4), Ni(1)ꢀ
N(1) 1.961(2), Ni(1)ꢀN(2) 1.955(3), Ni(1)ꢀN(3) 1.952(3), Ni-
(1)ꢀN(4) 1.949(2), C(20)ꢀN(5)ꢀN(6) 124.9(3), N(5)ꢀN(6)ꢀ
N(7) 168.8(4).
porphyrin affects the reactivity of the porphyrin and the
stability of the azides. In addition, the structure of the
obtained azides has been determined by X-ray crystallog-
raphic analysis. X-ray analyses of large aromatic azides
have been less reported despite their widespread synthetic
use. Therefore, our unusual results have important sig-
nificance in the chemistry of organic azides. Application
of the azidoporphyrins based on the versatile reactivity of
the azide group will be reported elsewhere. In addition, we
are currently applying our procedure to the practical
syntheses of various meso-heteroatom-substituted por-
phyrins.
the typical aryl azides (169°ꢀ174°).15 Figure 2 displays
the crystal structure of diazidoporphyrin 5b(Ni). The
porphyrin moiety is more ruffled with the average Niꢀ
˚
N(porphyrin) distance of 1.926 A. Two azide groups were
crystallographically independent with different torsion
angles of 36.7(6)° for azide A (N(5)ꢀN(6)ꢀN(7)) and
67.6(5)° for azide B (N(8)ꢀN(9)ꢀN(10)), respectively.
The bond length and angle of azide A are similar to those
of 2a(Ni) while those of the azide B are rather similar to
those of typical aryl azides. This difference might reflect
the degree of the electronic π-conjugation between the
porphyrin moiety and each azide group.
In summary, we have developed the facile synthesis of
meso-mono- and diazidoporphyrins by the catalyst-free
aromatic nucleophilic substitution of the correspond-
ing meso-bromoporphyrins. The central metal ion of the
Supporting Information Available. The experimental
procedures, physical properties of new compounds, cry-
stallographic data, and a CIF file for 2b(Ni) and 5b(Ni).
This material is available free of charge via the Internet at
http://pubs.acs.org.
Org. Lett., Vol. 14, No. 1, 2012
193