Synthesis of meso-substituted dipyrromethanes using iodine-catalysis

Article abstract of DOI:10.1016/j.tetlet.2010.06.122

This Letter presents a non-conventional synthesis of meso-substituted dipyrromethanes, using molecular iodine as the catalyst. Various aromatic dipyrromethanes were obtained in good yields after a preliminary study using nitrobenzaldehyde. The reactants a

Full text of DOI:10.1016/j.tetlet.2010.06.122

Tetrahedron Letters 51 (2010) 4630–4632
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Tetrahedron Letters
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Synthesis of meso-substituted dipyrromethanes using iodine-catalysis
Pierre-Antoine Faugeras, Benjamin Boëns, Pierre-Henri Elchinger, Julien Vergnaud, Karine Teste,
*
Rachida Zerrouki
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 presents a non-conventional synthesis of meso-substituted dipyrromethanes, using molecular
iodine as the catalyst. Various aromatic dipyrromethanes were obtained in good yields after a preliminary
study using nitrobenzaldehyde. The reactants and reagents were used as such, without prior distillation.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 29 March 2010
Revised 23 June 2010
Accepted 25 June 2010
Available online 1 July 2010
Keywords:
Dipyrromethane
Iodine catalysis
Microwave activation
Dipyrromethanes are key chemical compounds, involved in
numerous syntheses, such as porphyrin synthesis1 or formation
of polypyrrolic polymers.2 Since the Woodward and Mac Donald
works,3 they have earned the status of building blocks in organic
chemistry. The growing interest on these molecules led chemists
to find new ways in order to increase yields and improve reaction
conditions. We can notice the widely used synthesis, developed by
Lindsey and co-worker,4 using an acid catalyst, that is, trifluoroace-
tic acid or BF3-etherate, and a large excess of pyrrole (100 equiv).
During the past two decades, new syntheses of meso-substituted
dipyrromethanes5 have emerged to reduce this excess of pyrrole
and/or to replace the inconvenient strong acid-catalyst.
Scheme 1. Synthesis of 5-(4-nitrophenyl)dipyrromethane.
In parallel, molecular iodine has recently emerged as an inter-
esting and inexpensive catalyst. It has been used for its mild Le-
wis-acidity in numerous reactions such as electrophilic addition,6
heterocycle synthesis,7 or, more recently, porphyrin synthesis.8 In
line with our previous works, we have investigated the synthesis
of several meso-substituted dipyrromethanes, using molecular io-
dine as the catalyst, under microwave irradiation.
First, we have proceeded to a preliminary study of the reaction
conditions, using 4-nitrobenzaldehyde as the starting product.
These reactions were conducted under microwave irradiation, with
undistilled dichloromethane, undistilled pyrrole, and by using
molecular iodine as the catalyst (Scheme 1).
Table 1
Influence of the pyrrole/aldehyde ratioa
Entry
I2 (equiv)
Pyrrole/aldehyde ratio
Isolated yield (%)
1
2
3
4
5
0.1
0.1
0.1
0.1
0
40:1
10:1
5:1
2:1
10:1
40
84
70
45
b
—
a
The reactions were performed with 1 mmol of 4-nitrobenzaldehyde and
0.1 mmol of molecular iodine, under microwave irradiation (1 min, 30 °C, 300 W) in
10 mL of dichloromethane.
b
TLC did not show dipyrromethane formation.
The results, summarized in Table 1, show the great influence of
the reactants ratio (pyrrole/aldehyde). Indeed, a great excess of
pyrrole (entry 1) or a stoichiometric ratio (entry 4) led to moderate
yields. The best yield (84%) was obtained with a 10:1 ratio (entry 2),
which is safer than the most common methods (reactants ratio
higher than 25:1).
This study also confirmed the role of molecular iodine as a Le-
wis-acid catalyst, because its absence did not conduce to the de-
sired product (entry 5).
* 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).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.06.122

P.-A. Faugeras et al. / Tetrahedron Letters 51 (2010) 4630–4632
4631
Considering these good results, and in order to generalize this
method, we applied it to the synthesis of various meso-substituted
aromatic dipyrromethanes (Scheme 2).
Different dipyrromethanes have been chosen for their interest
in porphyrin synthesis1 (Table 2) and the results were compared
to the literature best yields. This method gave the products in good
yields. In the case of the 5-(4-nitrophenyl)dipyrromethane and the
5-(4-methoxyphenyl)dipyrromethane, the iodine method led to
the products in, respectively, 84% and 90% yields, which is higher
than the Dan and Shu9 synthesis (66% and 80%), consisting of the
use of ceric ammonium nitrate.
The synthesis of the 5-(4-carboxymethyl)dipyrromethane was
significantly improved by the I2/MW procedure (90%), compared
to the more classical TFA-catalyzed synthesis,10 which gives the
product in 35% yield. The 5-(4-hydroxyphenyl)dipyrromethane,
known as to be difficult to synthesize, was obtained by the simple
Cozzi and co-worker method,11 and conducted in water, catalyst-
free, after 24 h, in 27% yield. The procedure developed here con-
duced to the final product in a twice higher yield, after one-minute
irradiation. At last, the scalable synthesis of Laha et al.12 afforded 5-
phenyldipyrromethane in 82% yield, using InCl3, with a large ex-
cess of pyrrole (100 equiv) and is solvent-free. Pyrrole is recovered
after the reaction. In this case, the iodine method conduced to the
product in a lesser yield of 60%.
Figure 1. (1) Pyrrole used in this work (undistilled), (2) distilled pyrrole.
vent or being solvent-free, without any catalyst or any excess of
pyrrole, in a large scale, and avoiding inconvenient purification.
Taking advantage of its inexpensive and powerful catalyst and
its use of undistilled reagents (Fig. 1), this new and rapid method
of dipyrromethane synthesis afforded various products in good
yields. In addition, we have obtained promising results with this
method, in a larger scale, for the synthesis of the 5-(4-nitro-
phenyl)dipyrromethane. Its interest relies on the further use in
porphyrin conjugate synthesis.
However, until this day, it is important to notice that none of
the numerous dipyrromethane syntheses affords the desired com-
pound with all of these parameters: high yields, use of a green sol-
The strength of this pathway is the use of a limited excess of
pyrrole and a very short reaction time that limits the polymeriza-
tion of pyrrole and makes the further separation easier.
References and notes
1. (a) Geier, G. R., III; Lindsey, J. S. Tetrahedron 2004, 60, 11435–11444; (b) Ryppa,
C.; Senge, M. O.; Hatscher, S. S.; Kleinpeter, E.; Wacker, P.; Schilde, U.; Wiehe, A.
Chem. Eur. J. 2005, 11, 3427–3442.
2. Ak, M.; Gancheva, V.; Terlemezyan, L.; Tanyeli, C.; Toppare, L. Eur. Polym. J.
2008, 44, 2567–2573.
3. Woodward, R. B. Angew. Chem. 1960, 72, 651–662.
4. Lee, C.-H.; Lindsey, J. S. Tetrahedron 1994, 50, 11427–11440.
5. (a) Sobral, A. J. F. N.; Rebanda, N. G. C. L.; Da Silva, M.; Lampreia, S. H.; Silva, M.
R.; Beja, A. M.; Paixão, J. A.; Gonsalves, A. M. A. R. Tetrahedron Lett. 2003, 44,
3971–3973; (b) Sobhani, S.; Safaei, E.; Hasaninejad, A.-R.; Rezazadeh, S. J.
Organomet. Chem. 2009, 694, 3027–3031; (c) Naik, R.; Joshi, P.; Kaiwar, S. P.;
Deshpande, R. K. Tetrahedron 2003, 59, 2207–2213.
6. (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.
Scheme 2. Synthesis of various meso-substituted dipyrromethanes.
7. (a) Banik, B. K.; Samajdar, S.; Banik, I. J. Org. Chem. 2004, 69, 213–216; (b)
Stepien´ , M.; Sessler, J. L. Org. Lett. 2007, 9, 4785–4787.
8. (a) Lucas, R.; Vergnaud, J.; Teste, K.; Zerrouki, R.; Sol, V.; Krausz, P. Tetrahedron
Lett. 2008, 49, 5537–5539; (b) Boëns, B.; Faugeras, P.-A.; Vergnaud, J.; Lucas, R.;
Teste, K.; Zerrouki, R. Tetrahedron 2010, 66, 1994–1996.
Table 2
Comparison of the yields with best methods found in the literature
Aldehyde
Isolated yielda (%)
Literature best yield (%)
9. Dan, H.; Shu, T. Chem. Mag. 2004, 6.
10. Ka, J.-W.; Lee, C.-H. Tetrahedron 2000, 41, 4609–4613.
11. Zoli, L.; Cozzi, P. G. ChemSusChem 2009, 2, 218–220.
12. Laha, K. J.; Dhanalekshmi, S.; Taniguchi, M.; Ambroise, A.; Lindsey, J. S. Org.
Process Res. Dev. 2003, 7, 799–812.
84
669
13. General procedure: aldehyde (1 mmol), iodine (25 mg, 0.1 mmol) and then
pyrrole (694 lL, 10 mmol) were added successively to 10 mL dichloromethane,
90
90
55
60
809
3510
2711
8212
without particular precautions. Benzaldehyde, pyrrole and dichloromethane
are used as such, without prior distillation. After microwave irradiation (1 min,
30 °C, 300 W), TLC showed total conversion of aldehyde. The mixture was
evaporated on florisil and purified by automated flash chromatography using a
gradient of petroleum ether/chloroform as the eluent. Pure products were
obtained as solids. All physicochemical and spectroscopic properties coincided
with literature data.
5-(4-Nitrophenyl)dipyrromethane: mp = 159 °C, lit.: 159–160 °C. 1H NMR
(400 MHz, CDCl3): d 5.58 (s, 1H, mesoH), 5.87 (d, 2H, J = 5.7 Hz, 2C3–H), 6.17
(dd, 2H, J = 2.8, 5.7, 2C4–H), 6.74 (dd, 2H, J = 2.8, 1.2, 2C5–H), 7.36 (d, 2H, J = 8.6,
H-Ar), 7.98 (br s, 2H, N–H), 8.16 (d, 2H, J = 8.6, Ar-H). 5-(4-Methoxy-
phenyl)dipyrromethane: mp = 99 °C, lit.: 99 °C. 1H NMR (400 MHz, CDCl3): d
3.78 (s, 3H, CH3), 5.40 (s, 1H, mesoH), 5.90 (m, 2H, 2C3–H), 6.14 (dd, 2H, J = 2.8,
5.9, 2C4–H), 6.67 (m, 2H, 2C5–H), 6.84 (d, 2H, J = 8.7, H-Ar), 7.12 (d, 2H, J = 8.7,
Ar-H), 7.92 (br s, 2H, N–H). 5-(4-Methoxycarbonylphenyl)dipyrromethane:
mp = 164 °C, lit.: 162–163 °C. 1H NMR (400 MHz, DMSO): d 3.82 (s, 3H, CH3),
5.44 (br s, 1H, mesoH), 5.66 (br d, 2H, J = 5.3 Hz, 2C3–H), 5.90 (dd, 2H, J = 2.6,
5.3, 2C4–H), 6.62 (br d, 2H, J = 2.6, 2C5–H), 7.29 (d, 2H, J = 8.2, H-Ar), 7.88 (d, 2H,
a
Conditions: aldehyde (1 mmol), pyrrole (10 mmol), molecular iodine
(0.1 mmol), under microwave irradiation (1 min, 30 °C, 300 W), in 10 mL of
13
dichloromethane.

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P.-A. Faugeras et al. / Tetrahedron Letters 51 (2010) 4630–4632
J = 8.2, Ar-H), 10.61 (br s, 2H, N–H). 5-(4-hydroxyphenyl)dipyrromethane:
Phenyldipyrromethane: mp = 100 °C, lit.: 100–101 °C. 1H NMR (400 MHz,
CDCl3): d 5.45 (br s, 1H, mesoH), 5.90 (m, 2H, 2C3–H), 6.14 (dd, 2H, J = 2.8,
5.8, 2C4–H), 6.67 (br d, 2H, J = 2.8, 2C5–H), 7.20 (m, 2H, H-Ar), 7.25 (m, 2H, Ar-
H), 7.88 (br s, 2H, N–H).
mp = 158 °C, lit.: 158–160 °C. 1H NMR (400 MHz, CDCl3): d 5.40 (s, 1H, mesoH),
5.90 (m, 2H, 2C3–H), 6.14 (dd, 2H, J = 2.8, 5.8, 2C4–H), 6.67 (m, 2H, 2C5–H), 6.75
(d, 2H, J = 8.5, H-Ar), 7.05 (d, 2H, J = 8.5, Ar-H), 7.96 (br s, 2H, N–H). 5-