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.