Meso-oxidation of porphyrins: Convenient iron(III)-mediated synthesis of dioxoporphyrins

Article abstract of DOI:10.1055/s-0028-1088212

Iron(III)-mediated meso-oxidation reactions of 5,15-diarylporphyrins resulted in a variety of dioxoporphyrins in high yields. In the case of meso-amino-substituted diarylporphyrins, a variety of products was produced.

Full text of DOI:10.1055/s-0028-1088212

LETTER
945
meso-Oxidation of Porphyrins: Convenient Iron(III)-Mediated Synthesis of
Dioxoporphyrins
I
ron(III)-Mediated
o
S
ynthesis of
n
Dioxoporph
g
yrins -Mei Shen, Chao Liu, Xiao-Guang Chen, Qing-Yun Chen*
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
345 Lingling Road, Shanghai 200032, P. R. of China
Fax +86(21)64166128; E-mail: chenqy@mail.sioc.ac.cn
Received 11 December 2008
Using nickel(II) 5,15-diphenylporphyrin complex Ni1 as
the starting porphyrin under similar conditions resulted in
lower conversion and yield (Table 1, entry 6). Serious
degradation of porphyrins took place in the case of free
base 5,15-diphenylporphyrin H21 (Table 1, entry 7). The
selection of solvents was also critical for the success of the
reaction and DMF proved to be the best one (Table 1, en-
tries 3, 8–10). All these studies revealed that the oxidation
reaction was successfully done in the presence of 10
equivalents of FeCl3·6H2O in DMF at 130 °C.4 It should
be noted that the presence of a small amount of H2O (com-
ing from FeCl3·6H2O or moisture in DMF) was very im-
portant since the reaction did not proceed under extremely
Abstract: Iron(III)-mediated meso-oxidation reactions of 5,15-di-
arylporphyrins resulted in a variety of dioxoporphyrins in high
yields. In the case of meso-amino-substituted diarylporphyrins, a
variety of products was produced.
Key words: FeCl3·6H2O, oxidation, dioxoporphyrin
Dioxoporphyrins are a class of special electron-deficient
porphyrins. The oxo functionality interrupts the macro-
cycle conjugation and divides the porphyrin nucleus into
two separate dipyrromethane units.1 Their metal complex-
es show great affinity for many basic and popular ligands,
which render them valuable templates for the applications
in supramolecular chemistry.2 However, there are only a
few reports on their preparations, which might be ascribed
to their synthetic difficulty. To our best knowledge, the
main synthetic method was the thallium trifluoroacetate
mediated oxidation of porphyrins developed by Smith and
his co-workers.1d Although dioxoporphyrins could be pro-
duced in good yields by this method, the use of highly tox-
ic and expensive thallium trifluoroacetate limits its
application. Here we would like to present a convenient
and practical iron(III)-mediated synthesis of dioxopor-
phyrins.
Table 1 Iron(III)-Mediated Oxidation of 5,15-Diphenylporphyrins
M1a (M = Zn, Ni, or 2 H) under Various Conditionsa
Ph
Ph
N
N
N
N
N
N
N
N
FeCl3⋅6H2O
solvent, Δ
M
M
O
O
Ph
Ph
M1a
M2a
Our interests recently focused on the redox reactions of
porphyrins.3 In an attempt to utilize FeCl3·6H2O as an ox-
idant to promote the oxidative coupling of (5,15-diphe-
nylporphyrinato)zinc(II) (Zn1a) in DMF at 130 °C, we
were surprised not to obtain the expected oxidative cou-
pling products, but an interesting dioxoporphyrin Zn2a.
Encouraged by these results, we decided to investigate the
reaction conditions in detail. As shown in Table 1, the
equivalents of FeCl3·6H2O used had a significant effect on
the product yield (Table 1, entries 1–3). The use of 10
equivalents facilitated the oxidation reaction, permitting
the formation of Zn2a in high yield in shorter reaction
time (Table 1, entry 3). Higher reaction temperatures were
favorable for the formation of Zn2a because both the con-
version and yield decreased dramatically when the reac-
tions were performed at lower temperatures (Table 1,
entries 4 and 5). The central metal ions of the porphyrin
macrocycle also played an important role in the reaction.
Entry
M
[Fe]/
M1a
Solvent
Temp Conversion Yield
(°C)
130
130
130
60
(%)
(%)b
1
2
Zn
Zn
Zn
Zn
Zn
Ni
1
DMF
DMF
DMF
DMF
DMF
DMF
DMF
toluene
THF
0
0
5
67
100
45
0
55
85c
30
0
3
10
10
10
10
10
10
10
10
4
5
20
6
130
130
110
80
15
100
0
10
0d
0
7
2 H
Zn
Zn
Zn
8
9
0
0
10
CHCl3
60
0
0
a Reactions were carried out in DMF (10 mL) with M1a (50 mg, 1.0
equiv) for 24 h.
b Isolated yields.
SYNLETT 2009, No. 6, pp 0945–0948
x
x.
x
x.
2
0
0
9
c Reaction time: 5 h.
Advanced online publication: 16.03.2009
DOI: 10.1055/s-0028-1088212; Art ID: W19208ST
© Georg Thieme Verlag Stuttgart · New York
d Degradation of porphyrin was observed.

946
D.-M. Shen et al.
LETTER
Table 2 Iron(III)-Mediated Oxidation Reactions of Zn1 under Op-
timized Conditionsa
Ar
Ar
N
N
N
N
N
N
N
N
FeCl3⋅6H2O
Zn
O
Zn
O
DMF, 130 °C
R2
Ar
Ar
=
R1
Zn1
Zn2
Ar
R2
Entry Reactant R1
R2
Time Product
(h)
Yield
(%)b
1
2
3
4
5
Zn1a
Zn1b
Zn1c
Zn1d
Zn1e
H
H
H
5
5
Zn2a
Zn2b
Zn2c
Zn2d
Zn2e
85
88
95
75
82
Me
H
t-Bu
H
3
CF3
Cl
12
8
H
Figure 1 Two views of the X-ray crystal structure of (5,15-dioxo-
porphyrinato)Ni(II) Ni2a·2MeOH.
a Reactions were carried out in DMF (10 mL) with M2a (50 mg, 1.0
equiv) and FeCl3·6H2O (10 equiv) at 130 °C.
b Isolated yields.
mental analysis, as well as X-ray crystallography for
Ni2a. The X-ray crystallographic diffraction analysis of
Ni2a showed that the macrocycle was planar with two
methanol molecules coordinated to the central nickel(II)
ion (Figure 1), which revealed the electron-deficient char-
acter of dioxoporphyrins.4
dry conditions, which was advantageous for the operation
and workup.
Under the optimized conditions, various (5,15-diarylpor-
phyrinato)zinc(II) (Zn1) with different substituents at the
meso-phenyl group were successfully applied to the oxi-
dation reaction, providing good yields of the dioxopor-
phyrins Zn2 (Table 2). As expected, the reactivity of
substrates with an electron-donating group at the meso-
phenyl group was somewhat higher than that with an elec-
tron-withdrawing group. The dioxoporphyrins Zn2 were
easily demetalated by HCl to afford the free base dioxo-
porphyrins H22 in high yields (Scheme 1). Nickel(II) ion
insertion under routine conditions led to the correspond-
ing nickel(II) dioxoporphyrin complexes Ni2. All prod-
ucts were unambiguously characterized by their 1H NMR,
MS spectrometry, UV/vis spectroscopy, HRMS, or ele-
To further understand the effect of the meso-substituents
on the Fe(III)-mediated oxidation reaction, we attempted
to carry out the reactions on a variety of meso-substituted
diphenylporphyrins. Considering that electron-donating
groups facilitate the oxidation reaction, various meso-
amino-substituted diphenylporphyrins were subjected to
the reactions. Interestingly, different meso-amino substit-
uents gave rise to distinct results, indicating the diversity
and complexity of the oxidation reaction. For example,
when meso-amino-substituted porphyrin Ni35 was exam-
ined in the reaction, the intriguing head-to-tail dimer Ni45
was obtained in high yield. Nevertheless, utilizing meso-
Ar
Ar
Ar
Zn
Ar
N
N
N
N
NH
N
N
N
N
N
N
Ni(OAc)2⋅4H2O
HCl
Ni
O
O
O
O
O
O
DMF
CH2Cl2
HN
Ar
Ar
H22
Ni2
R2
Zn2a R1 = H, R2 = H
Zn2b R1 = Me, R2 = H
Zn2c R1 = H, R2 = tBu
Zn2d R1 = CF3, R2 = H
R1
Ar
=
R2
Scheme 1 Demetalation of Zn2 and nickel insertion reactions of H22
Synlett 2009, No. 6, 945–948 © Thieme Stuttgart · New York

LETTER
Iron(III)-Mediated Synthesis of Dioxoporphyrins
947
Ph
N
N
Ph
N
N
Ni3 (R1 = H, M = Ni)
FeCl3⋅6H2O
Ni
N
N
Ph
M
N
DMF, r.t., 10 min
Ni
N
N
Ph
NH
N
N
N
N
R1
NH2
Ni4 (90%)
Ph
Zn
Ph
Ph
Zn5 (R1 = Ph, M = Zn)
FeCl3⋅6H2O
N
N
N
N
N
N
N
Ph
Ph
Zn
DMF, r.t., 30 min
Ph
N
N
N
Ph
Zn6 (75%)
Ph
Ph
Ni
Ph
Ph
Ni
N
N
N
N
N
N
N
N
N
N
N
FeCl3⋅6H2O
NMe2
Ni
NMe2
Me2N
DMF, r.t., 10 min
N
Ph
Ph
Ph Ni7
Ni8 (85%)
Ph
Ni9 (R2 = H)
FeCl3⋅6H2O
N
N
N
Ni
N
Cl
Ph
DMF, 50 °C, 10 min
N
N
N
N
Ph
Ph
Ni10 (87%)
R2
Ni
N
N
Ni11 (R2 = Br)
FeCl3⋅6H2O
N
N
N
O
N
Ph
Ni
O
DMF,100 °C, 1 h
Ni2a (95%)
Ph
Scheme 2 Iron(III)-mediated oxidation reactions of various meso-amino-substituted porphyrins
amino-substituted porphyrin Zn55 as the starting porphy- diarylporphyrins in good yields. The meso-substituents of
rin afforded a fascinating azoporphyrin Zn65 in good the starting porphyrins play an important role in the oxi-
yield (Scheme 2). In the case of meso-N,N¢-dimethyl- dation reaction and different meso-substituents gave rise
amino-substituted porphyrin Ni7,6 oxidative coupling to distinct oxidation products. Due to the convenience and
occurred. Using meso-hexahydropyridine-substituted efficiency of the reaction, this method will allow quick ac-
porphyrin Ni96 as a substrate resulted in meso-chlorina- cess to various dioxoporphyrin, which might find a num-
tion. To our surprise, while the oxidation reaction was ber of applications. Detailed studies and explanations on
conducted on nickel(II) 5-bromo-15-hexahydropyridinyl- the mechanism are in progress.
10,20-diphenylporphyrin complex Ni11,6 dioxoporphyrin
Ni2a was obtained in excellent yield.
Supporting Information for this article is available online at
In summary, dioxoporphyrins were conveniently synthe-
http://www.thieme-connect.com/ejournals/toc/synlett.
sized by Fe(III)-mediated meso-oxidation of various 5,15-
Synlett 2009, No. 6, 945–948 © Thieme Stuttgart · New York

948
D.-M. Shen et al.
LETTER
Characterization Data for Selected Representative
Compounds
Dioxoporphyrin Zn2a
Acknowledgment
Financial support from the Natural Science Foundation of China
(Nos. 20772146, 20272026, D20032010, and 20532040) is grate-
fully acknowledged.
1H NMR (300 MHz, acetone-d6): d = 6.28–6.31 (m, 4 H,
b-H), 6.87–6.90 (m, 4 H, b-H), 7.33 (d, J = 3.6 Hz, 4 H,
PhH), 7.40–7.42 (m, 6 H, PhH). MS (MALDI): m/z = 555.1
[M + H+]. UV/vis (CH2Cl2): lmax (%) = 403 (13.0), 450
(6.7), 509 (2.6), 546 (5.6), 708 (1.0) nm. Anal. Calcd for
C32H18N4O2Zn·2MeOH: C, 65.86; H, 4.23; N, 9.04. Found:
C, 65.14; H, 4.07; N, 8.86.
References and Notes
(1) (a) Fuhrhop, J.-H. In Porphyrins and Metalloporphyrins;
Smith, K. M., Ed.; Elsevier Scientific Publications:
Amsterdam, 1975, 593–623. (b) Inhoffen, H. H.; Fuhrhop,
J.-H.; von der Haar, F. Liebigs Ann. Chem. 1966, 700, 92.
(c) Fuhrhop, J.-H. J. Chem. Soc., Chem. Commun. 1970,
781. (d) Barnett, G. H.; Evans, B.; Smith, K. M. Tetrahedron
1975, 31, 2711.
(2) (a) Watson, Z. C.; Bampos, N.; Sanders, J. K. M. New J.
Chem. 1998, 1135. (b) Marty, M.; Watson, Z. C.; Twyman,
L. J.; Nakash, M.; Sanders, J. K. M. Chem. Commun. 1998,
2265. (c) McCallien, D. W. J.; Sanders, J. K. M. J. Am.
Chem. Soc. 1995, 117, 6611.
(3) (a) Shen, D.-M.; Liu, C.; Chen, X.-G.; Chen, Q.-Y. J. Org.
Chem. 2009, 74, 206. (b) Liu, C.; Shen, D.-M.; Chen, Q.-Y.
J. Am. Chem. Soc. 2007, 129, 5814. (c) Jin, L.-M.; Chen, L.;
Yin, J.-J.; Guo, C.-C.; Chen, Q.-Y. Eur. J. Org. Chem. 2005,
3994. (d) Jin, L.-M.; Yin, J.-J.; Chen, L.; Guo, C.-C.; Chen,
Q.-Y. Synlett 2005, 2893.
Dioxoporphyrin H22a
1H NMR (300 MHz, CDCl3): d = 6.51 (br s, 4 H, b-H), 7.17
(d, J = 4.2 Hz, 4 H, b-H), 7.42–7.53 (m, 10 H, PhH), 14.02
(s, 2 H, NH). MS (MALDI): m/z = 493.2 [M + H+]. UV/vis
(CH2Cl2): lmax (%) = 408 (3.1), 472 (1.0), 499 (1.2) nm.
Anal. Calcd for C32H20N4O2·0.5EtOH: C, 76.88; H, 4.50; N,
10.87. Found: C, 76.37; H, 4.31; N, 10.45.
Dioxoporphyrin Ni2a
1H NMR (300 MHz, CDCl3): d = 6.20 (d, J = 4.2 Hz, 4 H,
b-H), 6.45 (d, J = 4.5 Hz, 4 H, b-H), 7.45 (s, 10 H, PhH).
MS (MALDI): m/z = 549.1 [M + H+]. UV/vis (CH2Cl2):
l
max (%) = 358 (14.4), 445 (35.4), 524 (8.1), 660 (1.0) nm.
Anal. Calcd for C32H18N4O2Ni: C, 68.85; H, 3.43; N, 10.04.
Found: C, 68.63; H, 3.49; N, 9.67. Crystal data: C34H26NiO4,
M = 613.30, triclinic, space group P-1, a = 7.6032 (11),
b = 8.6684 (12), c = 11.3434 (16) Å, a = 94.136 (2),
b = 100.890 (2), g = 108.289 (2)°, V = 690.11 (17) Å3,
T = 293 (2) K, Z = 1, Dc = 1.476 g/cm–3, 4091 reflections
measured, 2937 unique which were used in all calculations.
R(int) = 0.0734; R1 = 0.0465. The final wR(F2) was 0.0465
(all data). CCDC 711638 contains the supplementary
crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge
(4) Typical Procedure for the Fe(III)-Mediated Synthesis of
Dioxoporphyrins Zn2
A mixture of Zn1a (100 mg, 0.19 mmol, 1.0 equiv) and
FeCl3·6H2O (513 mg, 10 equiv) was stirred in DMF (20 mL)
in air at 130 °C for 5 h. After cooling to r.t., the reaction
mixture was diluted with CH2Cl2 (20 mL) and washed with
H2O three times. The organic layer was passed through dry
SiO2 and evaporated to dryness. The resulting solid was
crystallized from CH2Cl2–MeOH or purified by flash
column chromatography (SiO2, 300–400 mesh, PE–EtOAC
4:1) to produce the desired dioxoporphyrin Zn2a (90 mg,
85% yield).
Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
(5) Esdaile, L. J.; Jensen, P.; McMurtrie, J. C.; Arnold, D. P.
Angew. Chem. Int. Ed. 2007, 46, 2136.
(6) Liu, C.; Shen, D.-M.; Chen, Q.-Y. J. Org. Chem. 2007, 72,
2732.
Synlett 2009, No. 6, 945–948 © Thieme Stuttgart · New York