Novel synthesis of meso-tetraarylporphyrins by using I2 as catalyst and air as oxidant under thermal or UV conditions

Article abstract of DOI:10.1246/cl.2008.112

An efficient and novel synthesis of meso-tetraarylporphyrins is accomplished through iodine-catalyzed condensation of pyrrole, and aryl aldehydes and subsequent oxidation by air under thermal or ultraviolet (UV) irradiation conditions. The advantages of this procedure include good yields and a green nature. Copyright

Full text of DOI:10.1246/cl.2008.112

112
Chemistry Letters Vol.37, No.1 (2008)
Novel Synthesis of meso-Tetraarylporphyrins by Using I2 as Catalyst
and Air as Oxidant under Thermal or UV Conditions
Le Duan,1 Yu-Lu Wang,ꢀ1 Xue-Sen Fan,1 and Jin-Ye Wangꢀ2;y
1College of Chemical and Environmental Science, Henan Normal University, Xinxiang 453007, Henan, P. R. China
2Shanghai Institute of Organic Chemistry, Chinese Academy of Science, Shanghai 200032, P. R. China
(Received November 2, 2007; CL-071211; E-mail: wyl@henannu.edu.cn)
An efficient and novel synthesis of meso-tetraarylporphyrins
Ar
Ar
Ar
4 ArCHO
is accomplished through iodine-catalyzed condensation of
pyrrole, and aryl aldehydes and subsequent oxidation by air
under thermal or ultraviolet (UV) irradiation conditions. The
advantages of this procedure include good yields and a green
nature.
N
H
(1)
I2/CH2Cl2
rt
+
HN
NH
H
N
4
N
H
Ar
Step I
(2)
(condensation)
porphyrinogen (3)
Ar
Ar
N
N
Due to their unique structure and properties, porphyrins
have attracted great interests in a variety of fields encompassing
catalysis,1 molecular electronic devices,2 photodynamic therapy
agents,3 etc. In the mean time, various methods have been report-
ed for the preparation of porphyrin derivatives. In particular,
tetraarylporphyrins were firstly prepared by Rothemund4 in
1939. Since then, substantial improvements have been gained.5,6
Recently, efforts have been made to prepare tetraarylporphyrins
from pyrrole and aldehyde via a two-step procedure by employ-
ing various acids,7 clays,8 and cation-exchange resins9 as cata-
lysts, and TCQ10 and DDQ11 as oxidants. While these improved
procedures offered novel alternatives, further improvements are
still needed owing to disadvantages such as low yields,5,8 tedious
procedures,6a,6b expensive catalysts,7,9 or deleterious oxidants
used in the above-mentioned methods.6–11
It is well known that iodine is an inexpensive and readily
available reagent, and has been used as catalyst,12 and oxidant13
in organic synthesis. Consequently, it is our first objective to em-
ploy iodine as both catalyst and oxidant to facilitate the synthesis
of tetraphenylporphyrin (TPP, 4) from aryl aldehyde (1) and pyr-
role (2). However, it was soon observed that with quantitative
amount of iodine, only the intermediate (porphyrinogen, 3)14
was formed by stirring the mixture of 1, 2, and iodine at rt for
several hours.
Bearing in mind that air is an inexhaustible and clean source
of oxygen and has been used as oxidant,15 efforts were then made
to employ air with the assistance of both heat and UV-light16 to
promote the oxidation process and with silica gel as supporter in
the preparation of 4. Thus, the reaction mixture after Step I com-
pletion was mixed uniformly with silica gel and put into an oven
for 15 min at 200 ꢁC. Upon cooling, the adsorbed reaction mix-
ture was purified by column chromatography to give 4 in 41%
yield (Method A).
Alternatively, the reaction mixture from 1 and 2 was con-
centrated and applied on a preparative silica gel TLC plate and
developed. The zone corresponding to 3 on the developed
TLC plate was put under a UV lamp and irradiated. It turned into
a brown color upon irradiation. Further treatment gave 4 in a
yield of 51% (Method B) (Scheme 1).
air(O2)
HN
NH
heating or UV irradiating
Ar
Ar
Step II
(oxidation)
porphyrin(4)
Scheme 1. Synthesis porphyrins in two-step.
Table 1. Study of the effect of the quantity of I2 on Step Ia
Entry
I2/mmol
Time/min
Polymer/gb
Yield/%c
1
2
3
4
5
6
1
2
5
0.197
0.085
0.024
0
2
11
40
51
49
44
0.5
0.2
0.1
0.05
0.01
20
30
70
360
0
0
aReaction of pyrrole (4 mmol, 0.268 g) and benzaldehyde (4 mmol,
0.424 g) rt and in 10-mL CH2Cl2. bBlack polymer formed from I2-cat-
alyzed self-polymerization of pyrrole. cAccording to Method B.
results were listed in Table 1. It showed that catalytic amount
of iodine is enough for the preparation of 4 and actually
2.5 mol % of iodine gave the best result. It is also observed that
with more than 2.5 mol % of iodine, the yield of 4 decreased and
by-product was formed as black polymer. On the other hand,
with less than 2.5 mol % of iodine, the reaction was very sluggish
and needed much longer time to be completed.
Furthermore, different solvents including CH3CN, CH3OH,
C2H5OH, THF, C2H5OC2H5, CHCl3, and CH2Cl2 were
screened for the condensation of 1 and 2. Among the solvents
used, CH2Cl2 turned out to be the best in terms of both yield
and reaction time. As for the reaction temperature, it was found
out that the condensation carried out at room temperature (20 ꢁC)
gave the best result. Otherwise, by-product17 was detected when
higher temperature was employed.
In order to investigate the scope and generality of this novel
method, a series of aryl aldehyde substrates were then tried. The
results were listed in Table 2. It indicated that various aldehyde
substrates can successfully participate in this two-step proc-
ess,18,19 and an increase in steric hindrance and the presence of
electron-withdrawing groups at the benzaldehyde results in a
general decrease in the yield of porphyrin formation.
To exclude the possibility that iodine may be the actual
oxidant instead of oxygen in air at high temperature or under
UV irradiation, catalytic amount of iodine was then tried. The
Copyright Ó 2008 The Chemical Society of Japan

Chemistry Letters Vol.37, No.1 (2008)
113
Table 2. Synthesis of various meso-tetraarylporphyrins
Yield/%a
Entry PhCHO
2
3
C. M. Drain, K. C. Russell, J. M. Lehn, Chem. Commun. 1996,
337.
a) K. Driaf, P. Krausz, B. Verneuil, M. Spiro, J. C. Blais,
G. Bolbach, Tetrahedron Lett. 1993, 34, 1027. b) A. Wiene,
Y. M. Shaker, J. C. Brandt, S. Mebs, M. O. Senge, Tetrahedron
2005, 61, 5535.
P. Rothemund, J. Am. Chem. Soc. 1939, 61, 2912.
A. D. Adler, F. R. Longo, J. D. Finarelli, J. Golldmacher,
J. Assour, L. Korsakoff, J. Org. Chem. 1967, 32, 476.
a) J. S. Lindsey, H. C. Hsu, I. C. Schreiman, Tetrahedron Lett.
1986, 27, 4969. b) J. S. Lindsey, R. W. Wagner, J. Org. Chem.
1989, 54, 828. c) R. W. Wagner, T. E. Johnson, J. S. Lindsey,
Tetrahedron 1997, 53, 6755.
Time/min
Step I MA MB
I2
/mmol %
MA
MB
1
2
H
2.5
trace
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
30
20
25
40
45
55
30
30
35
45
40
60
15
10
5
120
90
41
52
51
60
p-MeO
p-Me
p-Cl
3
90
47
39
55
46
4
5
4
10
10
15
5
120
150
150
90
5
p-F
15
21
6
p-NO2
m-Me
m-MeO
m-Br
o-Cl
trace
38
trace
55
6
7
8
10
10
10
10
10
120
120
120
120
150
22
19
28
25
9
10
11
12
31
26
36
33
7
8
G. R. Geier, III, Y. Cirigh, F. Li, D. M. Haynes, J. S. Lindsey,
Org. Lett. 2000, 2, 1745.
a) M. Onaka, T. Shinoda, Y. Izumi, E. Nolen, Tetrahedron
Lett. 1993, 34, 2625. b) T. Shinoda, Y. Izumi, M. Onaka,
J. Chem. Soc., Chem. Commun. 1995, 1801.
o-Br
o-MeO
24
30
aIsolated yields.
...
H
9
R. Naik, P. Joshi, S. P. Kaiwar, R. K. Deshpande, Tetrahedron
2003, 59, 2207.
O
C
I2
OH
H
Ar
H
+
N
H
Ar
N
H
N
Ar
10 a) J. S. Lindsey, K. A. MacCrum, J. S. Tyhonas, Y.-Y. Chuang,
J. Org. Chem. 1994, 59, 579. b) O. Shoji, S. Okada, A. Satake,
Y. Kobuke, J. Am. Chem. Soc. 2005, 127, 2201.
11 a) S. Hiroto, A. Osuka, J. Org. Chem. 2005, 70, 4054. b) A.
Hoshino, Y. Ohgo, M. Nakamura, Tetrahedron Lett. 2005,
46, 4961. c) S. Kitaoka, K. Nobuoka, Y. Ishikawa, Tetrahedron
2005, 61, 7678.
I2
(1)
(2)
Ar
Ar
Ar
H
Ar
N
H
N
H
HN
NH
N
N
H
N
H
H
Ar
12 a) B. P. Bandgar, K. A. Shaikh, Tetrahedron Lett. 2003, 44,
1959. b) T. Saito, T. Horikoshi, T. Otain, Y. Matsuda, T.
Karakasa, Tetrahedron Lett. 2003, 44, 6513. c) B. P. Bandgar,
S. V. Bettigeri, N. S. Joshi, Synth. Commun. 2004, 34, 1447.
d) Y. Li, Y.-L. Wang, J.-Y. Wang, Chem. Lett. 2006, 35, 460.
13 a) J. S. Yadav, B. V. S. Rdeey, G. Sabitha, G. S. K. K. Reddy,
Synthesis 2000, 1532. b) A. Itoh, T. Kodama, Y. Masaki,
Chem. Lett. 2001, 686.
(3)
Scheme 2. A proposed pathway by I2 catalysis.
The results in Table 2 also showed that the reaction times of
Method A (MA) are much shorter compared to Method B (MB)
whereas the yields of MB are 5–10% higher than MA.
Based on the literature,12a a pathway for the formation of 3
from 1 and 2 under the catalysis of iodine is proposed in
Scheme 2. It is suggested that with its mild Lewis acidity iodine
can activate the carbonyl group of the aldehydes and accelerate
the condensation process.
In conclusion, iodine was found to be a mild and effective
catalyst and oxygen in air with the assistance of heating or UV
irradiation acted as effective oxidant in the preparation of TPP.
With its high efficiency, green nature, and simple operational
procedure, the method reported here may be used as a novel
alternative for preparation of TTP derivatives.
14 D. Dolphin, J. Heterocycl. Chem. 1970, 7, 275.
15 C. M. Drian, X. Gong, Chem. Commun. 1997, 2117.
16 S. Hirashima, A. Itoh, Green Chem. 2007, 9, 318.
17 G. R. Geier, III, J. S. Lindsey, J. Org. Chem. 1999, 64, 1596.
18 Typical procedure: To a flask was added CH2Cl2 (10 mL), I2
(0.1 mmol, 0.254 g) and benzaldehyde (4 mmol, 0.424 g). The
resulting solution was stirred for 5 min at room temperature
(20 ꢁC). Then, pyrrole (4 mmol, 0.268 g) was added and the
mixture was stirred for another 30 min. Upon completion, the
mixture was treated as described in Method A or Method B.
Method A: The mixture was decanted into a dish charged with
2-g silica gel and mixed uniformly (no massive pellet). It was
then put into an oven for 15 min at 200 ꢁC. After being cooled
to room temperature, the silica gel charged with the reaction
mixture was purified by column chromatography (silica gel; di-
chloromethane/petroleum ether, 1:3) to give 4 in 41% yield.
Method B: The mixture was concentrated under reduced pres-
sure and the residue was applied on a preparative silica gel
TLC plate and developed with 20% ethyl acetate in petroleum
ether. The zone corresponding to 3 on the developed TLC plate
was put under a UV lamp (18 W) and irradiated for 2 h. It
turned into a brown color and was scraped from the plate.
The adsorbent was extracted with CH2Cl2. After removal of
the solvent, 4 was obtained in 51% yield.
This work was supported by the National Program on
Key Basic Research Projects of China (973 Program, 2005,
No. CB724306).
References and Notes
y
Present address: Biomedical Engineering, Shanghai Jiao
Tong University, 1954 Huashan Road, Shanghai, 200030,
P. R. China.
a) J. F. Bartoli, O. Brigaud, P. Battioni, D. Mansuy, J. Chem.
Soc., Chem. Commun. 1991, 440. b) P. L. Anelli, S. Banfi, F.
Legramandi, F. Montanari, G. Pozzi, S. Quici, J. Chem. Soc.,
Perkin Trans. 1 1993, 1345. c) H. Sharghi, H. Naeimi, J. Chem.
Res. 1999, 310. d) M. Shamsipur, A. Soleymanpour, M.
Akhond, H. Sharghi, A. R. Hasaniejad, Sens. Actuators B
2003, 89, 9.
1
19 Supporting Information is available electronically on the CSJ-
Journal Web site, http://www.csj.jp/journals/chem-lett/index.
html.
Published on the web (Advance View) December 19, 2007; doi:10.1246/cl.2008.112