A facile and rapid iodine-catalyzed meso-tetraphenylporphyrin synthesis using microwave activation

Article abstract of DOI:10.1016/j.tetlet.2008.07.058

This Letter describes a rapid, easy and efficient one-pot procedure for tetraphenylporphyrin synthesis using iodine-catalysis and microwave activation. Commercial pyrrole, benzaldehyde and dichloromethane were being used as such, without prior distillatio

Full text of DOI:10.1016/j.tetlet.2008.07.058

Tetrahedron Letters 49 (2008) 5537–5539
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A facile and rapid iodine-catalyzed meso-tetraphenylporphyrin synthesis
using microwave activation
*
Romain Lucas, Julien Vergnaud, Karine Teste, Rachida Zerrouki , Vincent Sol, Pierre Krausz
Laboratoire de Chimie des Substances Naturelles EA1069, Faculté des Sciences et Techniques, 123 Avenue Albert Thomas, F-87060 Limoges, France
a r t i c l e i n f o
a b s t r a c t
Article history:
This Letter describes a rapid, easy and efficient one-pot procedure for tetraphenylporphyrin synthesis
using iodine-catalysis and microwave activation. Commercial pyrrole, benzaldehyde and dichlorometh-
ane were being used as such, without prior distillation.
Received 29 May 2008
Revised 7 July 2008
Accepted 9 July 2008
Available online 12 July 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Tetraphenylporphyrin
Iodine catalysis
Microwave-activated synthesis
Since the pioneering synthesis by Fischer in the 1920s, research
on porphyrins evolved dramatically. These tetrapyrrolic macro-
cyles are key biological compounds. Their photo-electro and bio-
chemical properties opened a wide field of applications in, for
olefins or a
,b-unsaturated ketones.10 These two reactions take
advantage of the mild Lewis-acidity of iodine, which first activates
the carbonyl group. Mechanistic similarities between these reac-
tions and porphyrinogen formation suggest that iodine could cata-
lyze the condensation between pyrrole and aldehyde, leading to a
new porphyrin synthesis method. On the other hand, the use of
microwave activation resulted in a dramatic decrease of reaction
times of various steps during porphyrin or metalloporphyrin syn-
1
example, electronic/electrooptical and nonlinear optics, selective
2
3
catalysis, or material chemistry. One of these applications is the
well-known use of porphyrins as photosensitizers in photody-
4
namic therapy which accounts for the importance of these dyes
in bioconjugation chemistry. Porphyrin macrocycle synthesis
5
11
theses. This Letter reports the coupling of iodine-catalysis and
1
2
has attracted a lot of interest during one century. meso-Tetraaryl-
porphyrins have been particularly concerned since they can be
used in a large variety of model studies.
microwave activation allowing an efficient and rapid one-pot
synthesis of tetraphenylporphyrin. meso-Tetrasubstituted porphy-
rins are particularly useful to generate mono-functionalized por-
1
3
meso-Tetraphenylporphyrin can be synthesized by a one-step
cyclocondensation of monopyrrole, with benzaldehyde, in the
presence of a catalyst and an oxidant. Several catalyst-oxidant sys-
tems have been studied over 40 years, including notably Brönsted-
acid catalysis with aerobic oxidation in the Adler–Longo proce-
phyrins like monoamino- or mononitroporphyrins.
A preliminary study using pyrrole, benzaldehyde and iodine in
dichloromethane has been conducted (Scheme 1) and at first, the
influence of pyrrole and benzaldehyde (equimolar) concentrations
has been studied (Table 1).
6
dure and Lewis-acid catalysis with an organic oxidant (DDQ or
These results show that a catalytic amount of iodine (0.2 equiv)
is sufficient to ensure the production of tetraphenylporphyrin (en-
7
para-chloranil) developed by Lindsey et al. More recent methods
1
4
introduced oxidizing co-solvents, clays, ionic liquids, hydrogen
peroxide in acetic acid, mixtures of xylene and chloroacetic acid,
transition metal salts or vapour phase synthesis without any sol-
tries 1–3). It was also observed that higher concentrations of re-
agents led to the formation of by-products which appeared as a
black polymer (entries 4 and 5).
8
vent or catalyst.
Reaction yields (27–30%) were found virtually independent of
iodine amounts (in the 0.05–0.2 equiv range) when the reaction
In parallel, molecular iodine has emerged as a really interesting,
inexpensive, and readily available catalyst for carrying out numer-
À1
À2
was conducted with high concentrations of reagents (10 mol/L)
9
ous organic reactions. Iodine catalysis has been recently used in
(Table 2, entries 1–3). Lower reagent concentration (10 mol/L,
the selective and efficient conjugate additions of pyrrole to nitro-
the actual concentration used for Lindsey’s method) in the pres-
2
ence of 0.2 equiv I gave 47% yield, although a longer activation
time (20 min) was needed to complete the first reaction step (Table
2, entry 4). The same was true when smaller amounts of iodine
*
Corresponding author. Tel.: +33 5 55 45 72 24; fax: +33 5 55 45 72 02.
E-mail address: rachida.zerrouki@unilim.fr (R. Zerrouki).
0
040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.07.058

5
538
R. Lucas et al. / Tetrahedron Letters 49 (2008) 5537–5539
Scheme 1. Microwave-assisted meso-tetraphenylporphyrin synthesis.
Table 1
Acknowledegements
Effect of pyrrole and benzaldehyde concentrationsa
Financial support from the MENRT and the ‘Conseil Régional du
Limousin’ is gratefully acknowledged. The authors thank Dr. Mi-
chel Guilloton for his help in writing the manuscript.
Entry
Reagent
concentration (mol/L)
Activation time (min)
first/second
1 Isolated yield (%)
À2
1
2
3
4
5
10
20; 1
10; 1
5; 1
30; —
30; —
41
43
26
0
À2
5 Â 10
À1
10
References and notes
À1
2 Â 10
À1
3 Â 10
0
1. (a) Lin, V. S.-Y.; DiMagno, S. G.; Therien, M. J. Science 1994, 264, 1105–
1
3
111; (b) Drain, C. M.; Russell, K. C.; Lehn, J.-M. Chem. Commun. 1996, 337–
38; (c) Anderson, H. L. Chem. Commun. 1999, 2323–2330; (d) Clausen, C.;
a
2
Conditions: I (0.2 equiv), activation (100 W; 30 °C). Reaction times allowing
virtual completion (checked by TLC: disappearance of the benzaldehyde spot).
Gryko, D. T.; Dabke, R. B.; Dontha, N.; Bocian, D. F.; Kuhr, W. G.; Lindsey, J.
S. J. Org. Chem. 2000, 65, 7363–7370; (e) Guldi, D. M. Chem. Soc. Rev. 2002,
3
1, 22–36.
2.
(a) Wijesekera, T. P.; Dolphin, D. In Metalloporphyrins in Catalytic Oxidations;
Sheldon, R. A., Ed.; Marcel Dekker: New York, 1994; pp 193–231; (b) Bhyrappa,
P.; Young, J. K.; Moore, J. S.; Suslick, K. S. J. Am. Chem. Soc. 1996, 118, 5708–
5711; (c) Gross, Z.; Galili, N.; Simkhovich, L. Tetrahedron Lett. 1999, 40, 1571–
1574; (d) Liu, W.-S.; Zhang, R.; Huang, J.-S.; Che, C.-M.; Peng, S.-M. J. Organomet.
Chem. 2001, 634, 34–38; (e) Rose, E.; Andrioletti, B.; Zrig, S.; Quelquejeu-
Ethève, M. Chem. Soc. Rev. 2005, 34, 573–583.
Table 2
Effects of I
2
concentration and MW activationa
Entry
I
2
(equiv)
Reagent
concentration
Activation
conditions
Activation time
(min)
Isolated
yield (%)
3. Kadish, K. M.; Smith, K.; Guillard, R. In The Porphyrin Handbook; Academic: New
(mol/L)
first/second
York, 2000; Vol. 6; pp 43–131.
4
.
(a) DeLaney, T. F.; Glatstein, E. Compr. Ther. 1988, 14, 43–55; (b) Peng, Q.;
Warloe, T.; Berg, K.; Moan, J.; Kongshaug, M.; Giercksky, K.-E.; Nesland, J. M.
Cancer 1997, 79, 2282–2308; (c) Sternberg, E. D.; Dolphin, D.; Brückner, C.
Tetrahedron 1998, 54, 4151–4202; (d) Hsi, R. A.; Rosenthal, D. I.; Glatstein, E.
Drugs 1999, 57, 725–734.
À1
1
2
3
4
5
6
7
8
0.2
0.1
0.05
0.1
0.2
0.1
0.025
0.2
10
10
10
10
10
10
10
10
30 °C–100 W
30 °C–100 W
30 °C–100 W
30 °C–100 W
35 °C–300 W
35 °C–300 W
35 °C–300 W
40 °C–400 W
5; 1
5; 1
8; 1
20; 1
1; 1
1; 1
2; 1
1/12; 1/6
27
30
28
47
35
32
33
18
À1
À1
À2
À1
À1
À1
À1
5. (a) Hudson, R.; Boyle, R. W. J. Porphyrins Phthalocyanines 2004, 8, 954–975; (b)
Hudson, R.; Carcenac, M.; Smith, K.; Madden, L.; Clarke, O. J.; PéIlegrin, A.;
Greenman, J.; Boyle, R. W. Br. J. Cancer 2005, 92, 1442–1449; (c) Lucas, R.;
Granet, R.; Sol, V.; Le Morvan, C.; Policar, C.; Rivière, E.; Krausz, P. e-Polymers
2007, 89.
a
Conditions: pyrrole and benzaldehyde (1 mmol). Reaction times allowing vir-
tual completion (checked by TLC: disappearance of the benzaldehyde spot).
6. Adler, A. D.; Longo, F. R.; Finarelli, J. D.; Goldmacher, J.; Assour, J.; Korsakoff, J. J.
Org. Chem. 1967, 32, 476; Kim, J. B.; Adler, A. D.; Longo, F. R. In The Porphyrins;
Dolphin, D., Ed.; Academic Press: New York, 1978; Vol. 1, pp 85–100.
7.
Lindsey, J. S.; Schreiman, I. C.; Hsu, H. C.; Kearney, P. C.; Marguerettaz, A. M. J.
Org. Chem. 1987, 52, 827–836.
8.
Kumar, A.; Maji, S.; Dubey, P.; Abhilash, G. J.; Pandey, S.; Sarkar, S. Tetrahedron
Lett. 2007, 48, 7287–7290 and references cited therein.
(
less than 0.1 equiv) were tested (Table 2, entry 3 compared to
entries 1 and 2, and entry 7 compared to entries 5 and 6).
Different conditions of temperature and power of activation
were also tested (Table 2). Data reported in this table show that
9. (a) Banik, B. K.; Samajdar, S.; Banik, I. J. Org. Chem. 2004, 69, 213–216; (b) Wang,
S.-Y. Synlett 2004, 2642–2643; (c) Stepie n´ , M.; Sessler, J. L. Org. Lett. 2007, 9,
4785–4787; (d) Kidwai, M.; Bansal, V.; Mothsra, P.; Saxena, S.; Somvanshi, R.
K.; Dey, S.; Singh, T. P. J. Mol. Catal. A: Chem. 2007, 268, 76–81.
10. (a) Lin, C.; Hsu, J.; Sastry, N. V.; Fang, H.; Tu, Z.; Liu, J.-T.; Ching-Fa, Y.
Tetrahedron 2005, 61, 11751–11757; (b) Das, B.; Chowdhury, N.; Damodar, K.
Tetrahedron Lett. 2007, 48, 2867–2870.
À1
high reagent concentration (10 mol/L), led to an optimal result
(
35%) after only 1 min of activation at 35 °C and with a 300 W
power. On the other hand, increased power (400 W, reaction com-
pletion in 15 s checked by TLC) resulted in a yield drop, certainly
due to high polymerization.
The use of excess iodine, expected to directly oxidize porphyri-
nogen, resulted in the vanishing of the benzaldehyde spot; how-
ever, a black polymer was produced instead of the desired final
compound.
1
1. (a) Nascimento, B. F. O.; Pineiro, M.; d’A Rocha Gonsalves, A. M.; Silva, M. R.;
Beja, A. M.; Paixào, J. A. J. Porphyrins Phthalocyanines 2007, 11, 77–84; (b) De
Paula, R.; Faustina, M. A. F.; Pinto, D. C. G. A.; Neves, G. P. M. S.; Cavaleiro, J. A. S.
J. Heterocycl. Chem. 2008, 45, 453–459; (c) Saltsman, I.; Gross, Z. Tetrahedron
Lett. 2008, 49, 247–249.
1
1
2. Microwave irradiations were performed by the means of an Ethos 1600
MicroSynth reactor from Milestone. Temperature was measured with an ATC-
FO/Ethos fiber optic thermometer.
3. Luguya, R.; Jaquinot, L.; Fronczek, F.; Vicente, M. G. H.; Smith, K. M. Tetrahedron
This method presents several interesting advantages: reason-
ably good yields (35–47%), the use of undistilled reagents and sol-
2
004, 60, 2757–2763.
14. General procedure (e.g., Table 2, entry 5): Benzaldehyde (101
iodine (51 mg, 0.2 equiv) then pyrrole (70 L, 1 mmol) were added
successively to 10 mL CH Cl , without particular precautions. After the first
l
L, 1 mmol),
l
vent,
a short reaction time and the use of high reagent
2
2
concentration- by comparison with Lindsey’s method. An exten-
sion of this method towards the synthesis of unsymmetrical por-
phyrins is currently under study.
activation (300 W, 35 °C, 1 min), TLC showed total conversion of benzaldehyde.
para-Chloranil (0.75 equiv, 184 mg) was then added and a second activation
was performed (300 W, 35 °C, 1 min). The mixture was evaporated on florisil

R. Lucas et al. / Tetrahedron Letters 49 (2008) 5537–5539
5539
and purified by flash chromatography using CH
eluent. Pure product was obtained as purple solid (54 mg, 135%). All
physicochemical properties coincided with literature data. NMR
2
Cl
2
/petroleum ether (50:50) as
(400 MHz, CDCl
7.79 (12H, m, Hm–Ph and Hp–Ph), À2.77 (2H, pyrrole NH); C NMR (100 MHz,
CDCl ): 142.2, 134.6, 131.1, 127.7, 126.7, 120.1, 118.7.
3
): 8.84 (8H, s, Pyrrole–H), 8.20–8.23 (8H, m, Ho–Ph), 7.72–
13
a
H
3