Unprecedented degradation of nickel(II) 2,3,12,13-tetrabromo-5,10,15,20- tetraarylporphyrins by the anion of E-benzaldoxime: A novel approach to nickel(II) chlorophins and bacteriophins

Article abstract of DOI:10.1021/ol901052w

A novel and convenient approach to chlorophins and bacteriophins has been developed through a degradation of nickel(ll) 2,3,12,13-tetrabromo5,10,15,20- tetraarylporphyrins by the anion of E-benzaldoxime. The UV-vis spectra of these chlorophins and bacteri

Full text of DOI:10.1021/ol901052w

ORGANIC
LETTERS
2009
Vol. 11, No. 13
2724-2727
Unprecedented Degradation of Nickel(II)
2,3,12,13-Tetrabromo-5,10,15,20-tetra-
arylporphyrins by the Anion of
E-Benzaldoxime: A Novel Approach to
Nickel(II) Chlorophins and Bacteriophins
Ke-Lai Li,† Can-Cheng Guo,*,† and Qing-Yun Chen*,†,‡
College of Chemistry and Chemical Engineering, Hunan UniVersity,
Changsha 410082, China, and Key Laboratory of Organofluorine Chemistry,
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
345 Lingling Road, Shanghai 200032, China
ccguo@hnu.cn; chenqy@mail.sioc.ac.cn
Received February 10, 2009
ABSTRACT
A novel and convenient approach to chlorophins and bacteriophins has been developed through a degradation of nickel(II) 2,3,12,13-tetrabromo-
5,10,15,20-tetraarylporphyrins by the anion of E-benzaldoxime. The UV-vis spectra of these chlorophins and bacteriophins are similar to
those of metalated chlorin and bacteriochlorin systems but with more intense and bathochromically shifted Q-bands.
Porphyrins and related compounds, especially those pos-
sessing intense near-infrared absorption, have received great
attention in the last few decades for their potential applica-
tions in electro-optical materials and photodynamic therapy
(PDT) treatment of cancer.1 Among them, chlorophins and
bacteriophins (porphyrins in which one or two sets of ꢀ,ꢀ′-
carbon atoms have been removed) are of particular interest
due to their chlorin and bacteriochlorin-like photophysical
properties and their close relationship to various structural
models of the porphyrin π-system.2 While secochlorins
(porphyrins in which a ꢀ,ꢀ′-bond is cleaved) can be prepared
by rearrangement of (octadehydrocorrinato)nickel(II) salts3
or oxidative diol cleavage of 2,3-dihydroxy-2,3-chlorins4 and
tetraphenylchlorophin has also been successfully synthesized
by Dolphin et al. via the stepwise decarbonylation of a
nickel(II) secochlorin dialdehyde,2e reports on bacteriophins
are rare. To the best of our knowledge, so far, they can only
be obtained by total synthesis. However, this method
developed by Flitsch and co-workers2c,d was extremely
(2) (a) Flitsch, W. Pure Appl. Chem. 1986, 58, 153. (b) Flitsch, W. AdV.
Heterocycl. Chem. 1988, 43, 73. (c) Flitsch, W.; Schulz, D.; Kneip, H.-G.
Liebigs Ann. Chem. 1985, 1004. (d) Bohusch, M.; Flitsch, W.; Kneip, H.-
G. Liebigs Ann. Chem. 1991, 67. (e) Bru¨ckner, C.; Sternberg, E. D.;
MacAlpine, J. K.; Rettig, S. J.; Dolphin, D. J. Am. Chem. Soc. 1999, 121,
2609. (f) Bru¨ckner, C.; Hyland, M. A.; Sternberg, E. D.; MacAlpine, J. K.;
Rettig, S. J.; Patrick, B. O.; Dolphin, D. Inorg. Chim. Acta 2005, 358, 2943.
(3) Chang, C. K.; Wu, W.; Chern, S.-S.; Peng, S.-M. Angew. Chem.,
Int. Ed. Engl. 1992, 31, 70.
† Hunan University.
‡ Shanghai Institute of Organic Chemistry.
(1) (a) The Porphyrin Handbook; Kadish, K. M., Smith, K. M., Guilard,
R., Eds.; Academic Press: San Diego, CA, 2000-2003; Vols. 1-20. (b)
Jasat, A.; Dolphin, D. Chem. ReV. 1997, 97, 2267.
10.1021/ol901052w CCC: $40.75
Published on Web 05/28/2009
 2009 American Chemical Society

difficult and very low yielding, and even then no full
structural characterization was accomplished. In this com-
munication, we wish to report a novel approach to chlo-
rophins and bacteriophins through a degradation of nickel(II)
2,3,12,13-tetrabromo-5,10,15,20-tetraarylporphyrins by the
anion of E-benzaldoxime.
During our ongoing efforts in the synthesis and application
of perfluoroalkylated porphyrins,5 a novel synthesis of 20
π-electron nonaromatic isophlorin was achieved by reduction
of copper(II) ꢀ-tetrakis(trifluoromethyl)-meso-tetraphenylpor-
phyrin.5f Inspired by this study, we envisioned that a porphyrin
system bearing four strongly electron-donating groups instead
of four strongly electron-withdrawing trifluoromethyl ones
might undergo a two-electron oxidation to afford a 16 π-electron
nonaromatic macrocycle.6
Initially, we attempted to prepare a porphyrin bearing four
hydroxyl groups (which can be converted into alkoxide
anions or ether groups) via nucleophilic substitution of
bromoporphyrin with the anion of E-benzaldoxime by using
the method developed by Crossley et al.7 Thus, 1a was
treated with the sodium salt of E-benzaldoxime in DMSO
at 60 °C for 3 h. Surprisingly, an unexpected dibromochlo-
rophin 2a was obtained in 3% yield with no formation of
the desired product. When a catalyst CuBr8 was added, and
the reaction temperature was elevated to 100 °C, 2a was
formed in 30% yield (Table 1). It should be noted that the
Further elevating the reaction temperature to above 120 °C
led to the formation of bacteriophin 5a. Interestingly, the
best yield of 5a is achieved under the conditions that the
reaction temperature fluctuates regularly between 80 and 160
°C (Table 1). All of the macrocycles, 2a, 3a, 4a, and 5a,
are much more soluble than nickel(II) tetraphenylporphyrin
(NiTPP) in common organic solvents, such as CH2Cl2, acetone,
and petroleum ether, etc., and form green, green, green-blue,
and blue-colored solution in those solvents, respectively.
The structures of these macrocycles are fully characterized
by their spectroscopic and analytical data. Among them, 4a
is a known compound, whose spectral data are identical to
those reported by Dolphin et al.2e The stepwise loss of a
bromine atom from 2a to 3a and then to 4a can be clearly
seen from their mass spectra (MALDI+) (2a: m/z ) 802.0;
3a: m/z ) 724.1; 4a: m/z ) 646.2) and also reflects in the
hypsochromic shift of their Soret band from 2a (λmax [relative
intensity] 436 [1.00]) to 3a (λmax [relative intensity] 430
[1.00]) and to 4a (λmax [relative intensity] 423 [1.00]). The
UV-vis spectra of the three compounds all indicate the
presence of metalated chlorin-like systems (λmax [relative
intensity] for 2a: 436 [1.00], 619 [0.13]; for 3a: 430 [1.00],
613 [0.14]; for 4a: 423 [1.00], 611 [0.16]), showing more
intense and bathochromically shifted Q-bands compared with
NiTPP (λmax [relative intensity] 416 [1.00], 492 [0.01], 521
1
[0.05]) (Figure 1). The H NMR spectra of 2a and 3a also
Table 1. Reaction of 1a with the Sodium Salt of
E-Benzaldoxime in the Presence of CuBra
yieldsb (%)
entry
temp (°C)
time (h)
2a
3a
4a
5a
Figure 1. UV-vis spectra of 2a, 3a, 4a, 5a, 5d, and NiTPP in
1c
2
3
4
5
6
7
8
100
110
120
140
160
180
180
200
4
2
2
1
1
0.5
1
1
2
30
18
7
15
-
33
-
-
-
13
14
11
8
8
6
3
7
-
-
6
-
-
3
CH2Cl2.
d
d
-
-
support their structural alteration from 4a by replacement
of one or two hydrogen atoms with one or two bromine
12
3
3
3
3
16
d
-
22
19
3
(4) (a) McCarthy, J. R.; Hyland, M. A.; Bru¨ckner, C. Org. Biomol. Chem.
2004, 2, 1484. (b) McCarthy, J. R.; Melfi, P. J.; Capetta, S. H.; Bru¨ckner,
C. Tetrahedron 2003, 59, 9137. (c) McCarthy, J. R.; Jenkins, H. A.;
Bru¨ckner, C. Org. Lett. 2003, 5, 19. (d) Bru¨ckner, C.; Rettig, S.; Dolphin,
D. J. Org. Chem. 1998, 63, 2094. (e) Adams, K. R.; Bonnett, R.; Burke,
P. J.; Salgado, A.; Valle´s, M. A. J. Chem. Soc., Perkin Trans. 1 1997, 1769.
(f) Adams, K. R.; Bonnett, R.; Burke, P. J.; Salgado, A.; Valle´s, M. A.
J. Chem. Soc., Chem. Commun. 1993, 1860.
9
80-160
80-160
8
-
10e
2
5
3
26
a Reaction conditions: 1a (49 mg, 0.05 mmol), E-benzaldoxime (30
equiv), NaH (20 equiv), CuBr (20 equiv), in DMSO (10 mL) under nitrogen.
b Isolated yields. c 12% starting material was recovered. d Trace product.
e CuBr was dried by heating at 200 °C under vacuum for 12 h before use.
(5) (a) Jin, L. M.; Zeng, Z.; Guo, C. C.; Chen, Q. Y. J. Org. Chem.
2003, 68, 3912. (b) Liu, C.; Chen, Q. Y. Eur. J. Org. Chem. 2005, 3680.
(c) Chen, L.; Jin, L. M.; Guo, C. C.; Chen, Q. Y. Synlett 2005, 963. (d) Jin,
L. M.; Yin, J. J.; Chen, L.; Zhou, J. M.; Xiao, J. C.; Guo, C. C.; Chen,
Q. Y. Chem.sEur. J. 2006, 12, 7935. (e) Liu, C.; Shen, D. M.; Zeng, Z.;
Guo, C. C.; Chen, Q. Y. J. Org. Chem. 2006, 71, 9772. (f) Liu, C.; Shen,
D. M.; Chen, Q. Y. J. Am. Chem. Soc. 2007, 129, 5814.
copper(II)-catalyzed reaction is sensitive to temperature. If
the reaction temperature is slightly higher than 100 °C,
debrominated products of 2a, namely, 3a and 4a, are also
produced. The higher the temperature and the longer the
reaction time, the more debrominated products there are.
(6) Yamamoto, Y.; Yamamoto, A.; Furuta, S.; Horie, M.; Kodama, M.;
Sato, W.; Akiba, K.; Tsuzuki, S.; Uchimaru, T.; Hashizume, D.; Iwasaki,
F. J. Am. Chem. Soc. 2005, 127, 14540.
Org. Lett., Vol. 11, No. 13, 2009
2725

atoms. The expected overall symmetry of the dibromochlo-
rophin 2a (2-fold symmetry) and monobromochlorophin 3a
(no symmetry) can be seen from the coupling patterns of
the ꢀ-protons locating between 8.0 ppm and 8.5 ppm (2a:
two doublets J ) 4.5 Hz, each integrating for 2H; 3a: four
doublets J ) 4.5 Hz and one singlet, each integrating for
1H). One singlet with an integration corresponding to 2H at
9.53 ppm for 2a and 9.74 ppm for 3a is considered in accord
with the one at 9.83 ppm (lit.,2e 9.80 ppm) for 4a, which
are attributed to the R-protons on the broken pyrrolic unit.
The elemental analysis of 2a and 3a also corroborates the
proposed composition.
C18N4Ni mean plane for 2a, 0.463 Å; for 3a, 0.443 Å).
Compared with 4a (rms of the C18N4Ni mean plane, 0.368
Å),2e the degree of ruffling of 3a and 2a increase with the
gradual introduction of the bromo substituent. In the mean-
while, the average Ni-N bond distance is lengthened, from
1.903 Å measured in 2a to 1.904 Å in 3a and 1.912 Å
reported in 4a.2e The pronounced influence of the bromine
atoms on the degree of the ruffling observed here is
comparable to those of the formyl substituents in secochlorin
aldehydes.2f However, the longest bond length found in 2a
and 3a is not the one between the metal and the nitrogen of
the broken pyrrolic unit (Ni-N3) as observed in 4a, but the
one between the metal and the nitrogen of the dibromo
pyrrole ring (Ni-N1) for 2a and the one between the metal
and the nitrogen of the pyrrole ring which is furthest away
from the bromine atom (Ni-N2) for 3a. We attribute this
to be induced by the presence and position of the bromine
atoms.
A single-crystal X-ray diffraction study was performed on
2a9 and 3a.10 This provided the ultimate proof of the
proposed structure (Figure 2) and allowed us to examine the
The 1H NMR spectrum of 5a indicates that the molecule have
a high degree of symmetry. There are only two singlets
representing the nonphenylic protons, one at 8.20 ppm and
another at 9.55 ppm, the integrals of which both correspond to
four protons. While the signal at 8.20 ppm is comparable to
those measured for ꢀ-protons of the other 18 π-electron
porphyrinic systems, the one at 9.55 ppm is in accordance with
the R-protons measured in chlorophins (for instance, 2a, 3a,
and 4a). Analysis of the mass spectrum of 5a (m/z ) 622.2)
reveals that two carbon atoms are also lost compared with 4a.
The UV-vis spectrum of 5a (λmax [relative intensity] 392 [1.00],
600 [0.31], 755 [0.87]) is similar to those of metalated
bacteriochlorin-like systems but with more intense and batho-
chromically shifted Q-bands (Figure 1). The elemental analysis
of 5a also corroborates with the assigned structure.
Figure 2. Top view (solvated molecules and hydrogen atoms are
omitted for clarity) and side view (solvated molecules, hydrogen
atoms, and the meso-phenyl substituents have been omitted for
clarity) of the X-ray crystal structures of 2a and 3a. Thermal
ellipsoids are shown at the 70% probability level for 3a.
To determine the scope of this novel reaction, some other
easily available nickel(II) 2,3,12,13-tetrabromo-5,10,15,20-
tetraarylporphyrins were investigated (Scheme 1). Under
influence of the bromine atom on the conformation of the
chlorophin core. In a manner similar to that of 4a,2e the plane
of the metallochlorophin 2a and 3a, while retaining a square
planar coordination sphere around the central metal, is
severely twisted along a N-Ni-N axis resulting in a
ruffled11 conformation of the chlorophin core (rms of the
Scheme 1.
Degradation of Other Nickel(II) Tetrabromoporphyrinsa
(7) (a) Crossley, M. J.; King, L. G.; Pyke, S. M. Tetrahedron 1987, 43,
4569. (b) Crossley, M. J.; Burn, P. L.; Langford, S. J.; Pyke, S. M.; Stark,
A. G. J. Chem. Soc., Chem. Commun. 1991, 1567.
a For detailed reaction conditions and yields, see Supporting Information.
(8) (a) Bacon, R. G. R.; Rennison, S. C. J. Chem. Soc. (C) 1969, 312.
(b) Capdevielle, P.; Maumy, M. Tetrahedron Lett. 1993, 34, 1007.
(9) C42H26Br2N4Ni (2a) crystallized by diffusion of MeOH into a
CH2Cl2 solution. Crystal data. M ) 805.20, triclinic, space group P-1,
a ) 9.9480(12), b ) 12.8818(15), c ) 14.3014(17) Å, R ) 70.874(2),
ꢀ ) 73.322(2), γ ) 80.864(2)°, V ) 1654.4(3) Å3, T ) 293(2) K, Z )
2, Dc ) 1.616 g cm-3, µ(Mo KR) ) 3.040 mm-1, 9774 reflections
measured, 7009 unique which were used in all calculations. R1 (all data)
) 0.0774. R1 ) 0.0620. CCDC 709027.
(10) C42H27BrN4Ni·0.5C4H10O (3a) crystallized by diffusion of MeOH
into a CH2Cl2 solution. Crystal data. M ) 763.36, monoclinic, space group
P2(1)/n, a ) 15.7750(16), b ) 12.4675(13), c ) 17.5806(18) Å, R ) 90.00,
ꢀ ) 93.757(2), γ ) 90.00°, V ) 3450.2(6) Å3, T ) 293(2) K, Z ) 4, Dc
) 1.470 g/cm3, µ(Mo KR) ) 1.761 mm-1, 17857 reflections measured,
6405 unique which were used in all calculations. R1 (all data) ) 0.1233. R1
) 0.0872. CCDC 709028 .
similar conditions, 1b and 1c could also be subjected to
smooth degradation to provide the corresponding chlorophins
and bacteriophins. The reaction of 1d was carried out in a
sealed tube using DMSO/THF (1:1, v/v) as solvent due to
its poor solubility in DMSO. 2d and 3d can be obtained from
the reaction catalyzed by CuBr, but 5d was yielded in the
absence of CuBr. The various spectra of 5d are analogous
to those of 5a (Figure 1). Fortunately, single crystals of 5d
were obtained from its acetone/CH2Cl2/pyridine (100:10:1,
2726
Org. Lett., Vol. 11, No. 13, 2009

v:v:v) solution into which petroleum ether was allowed to
slowly diffuse.
distances.2f,15 However, on the contrary, the average Ni-N
bond distance found in the strongly ruffled 5d is 1.933 Å,
which is much longer than that in 4a2e (1.912 Å) but quite
near that found in the slightly ruffled NiTPP (average Ni-N
bond distance, 1.931 Å; rms of the C20N4Ni mean plane,
0.263 Å).16 This might be attributed to the extremely
increased flexibility of the bacteriphin core compared with
that of chlorophin and porphyrin.
A single-crystal X-ray diffraction study of 5d12,13 (Figure
3) shows that two opposite pyrrolic units of the parent
The pursuit for long-wavelength absorbing chromophores has
led to the synthesis of porphyrin isomers, expanded porphyrins,
and porphyrins containing moieties other than pyrroles as
building blocks.17 The synthesis of bacteriophins with unique
spectroscopic properties by degradation of two ꢀ,ꢀ′-bonds of
the parent porphyrins demonstrated here provide an alternative
promising possibility toward that aim. We propose that the
extremely intense and near-infrared absorption of these bacte-
riophins results from their lower symmetry and greater defor-
mation of the macrocycle from planarity compared with
porphyrins, in a way similar to that of bacteriochlorins.18 In
contrast to the total synthesis of the parent bacteriophin (i.e.,
the non-meso-aryl substituted macrocycle) and isobacteriophin
starting from substituted pyrroles over several steps with the
best yield, no more than 5%, our facile preparation of bacte-
riophins is straightforward and comparatively high yielding.
Figure 3. Top view (solvated molecules and hydrogen atoms are
In conclusion, we have shown a novel and convenient
approach to chlorophins and bacteriophins starting from the
easily available tetrabromoporphyrins. Although the reaction
mechanism is not yet clear, degradation of two pyrrolic units
and the method using the anion of E-benzaldoxime are novel
to the field of porphyrin chemistry. Furthermore, the intense
near-infrared absorption of bacteriophins shows promise as
photosensitizers in PDT and as building blocks in electro-
optical materials. Further studies on the reaction mechanism,
the extension of this reaction to other metal complexes, and
the transformation of the products are now in progress.
omitted for clarity) and side view (solvated molecules, hydrogen
atoms, and the meso-aryl substituents have been omitted for clarity)
of the X-ray crystal structure of 5d. Thermal ellipsoids are shown
at the 50% probability level.
porphyrin have been degraded to aldimine linkage without
any other change in the connectivity of the 18 π aromatic
macrocycle, which makes it possible to take some compara-
tive studies between porphyrin and bacteriophin, both
experimentally and theoretically, such as their resonance
energies.14 The C-C and C-N bond lengths found in the
macrocycle of 5d are within expectation for a fully conju-
gated chromophore. Examination of the conformation of 5d
reveals that it deviates to an astonishing degree from
planarity. In a manner similar to that of 4a,2e it takes up a
ruffled11 conformation (rms of the C16N4Ni mean plane,
0.502 Å) but much more pronounced than 4a (rms of the
C18N4Ni mean plane, 0.368 Å).2e The median Ni-N dis-
tances have been used to quantify the distortion of nickel(II)
porphyrins, and it is commonly considered that the more
planar the conformation, the larger the Ni-N bond
Acknowledgment. The authors are grateful to Professor
Jia-Bi Chen (Shanghai Institute of Organic Chemistry),
Associate Professor Jie Sun (Shanghai Institute of Organic
Chemistry), Dr. Zhen-Xia Chen (Fudan University), and
Professor Min-Qin Chen (Fudan University) for the resolu-
tion of the X-ray crystal structures. We also thank financial
support from the National Natural Science Foundation of
China (Nos. 20272076, 20772146 and D20032010).
Supporting Information Available: Experimental details,
characterization data for all new compounds, and crystal-
lographic data in CIF format for 2a, 3a, and 5d. This material
is available free of charge via the Internet at http://pubs.acs.org.
(11) (a) Shelnutt, J. A.; Song, X. Z.; Ma, J. G.; Jia, S. L.; Jantzen, W.;
Medforth, C. J. Chem. Soc. ReV. 1998, 27, 31. (b) Ravikanth, M.;
Chandrashekar, T. K. Struct. Bonding (Berlin) 1995, 82, 107. (c) Scheidt,
W. R.; Lee, Y. L. Struct. Bonding (Berlin) 1987, 64, 1
.
(12) Crystal data of C72H92N4Ni·C5H5N (5d). M ) 1151.31, orthorhom-
bic, space group Ccca, a ) 27.770(16), b ) 35.78(2), c ) 8.445(5) Å,
R ) 90.00, ꢀ ) 90.00, γ ) 90.00°, V ) 8391(8) Å3, T ) 293(2) K, Z )
4, Dc ) 0.911 g/cm3, µ(Mo KR) ) 0.268 mm-1, 16471 reflections measured,
3692 unique which were used in all calculations. R1 (all data) ) 0.1248.
R1 ) 0.0997. CCDC 709029.
OL901052W
(15) Barkigia, K. M.; Renner, M. W.; Furenlid, L. R.; Medforth, C. J.;
Smith, K. M.; Fajer, J. J. Am. Chem. Soc. 1993, 115, 3627
.
(16) Fleischer, E. B.; Miller, C. K.; Webb, L. E. J. Am. Chem. Soc.
1964, 86, 2342.
(13) Although the X-ray crystallographic analysis of 5d was somewhat
less precise due to static and possible dynamic disorders of the tert-butyl
group and the coordinated solvents, the data of the other atoms are good
enough for analysis.
(17) The Porphyrin Handbook; Kadish, K. M., Smith, K. M., Guilard,
R., Eds.; Academic Press: San Diego, CA, 2000; Vols. 2, pp 1-199 and
references therein.
(14) (a) George, P. Chem. ReV. 1975, 75, 85. (b) Campbell, C. J.;
(18) Gouterman, M. In The Porphyrins; Dolphin, D., Ed.; Academic
Press: New York, 1978; Vol. 3, pp 1-156.
Rusling, J. F.; Bru¨ckner, C. J. Am. Chem. Soc. 2000, 122, 6679
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2727