Fast and eco-friendly synthesis of dipyrromethanes by H2SO4 SiO2 catalysis under solvent-free conditions

Article abstract of DOI:10.1002/cjoc.201090063

For the first time, sillica-supported sulfuric acid has been used as a heterogeneous, reusable and efficient catalystat room temperature to give the corresponding dipyrromethanes in a very short reaction time. The new reactionprocedure is simple and solvent is not required.

Full text of DOI:10.1002/cjoc.201090063

FULL PAPER
Fast and Eco-friendly Synthesis of Dipyrromethanes by
H2SO4•SiO2 Catalysis under Solvent-free Conditions
Zhang, Yan(张岩)
Liang, Jun(梁军)
Shang, Zhicai*(商志才)
Department of Chemistry, Zhejiang University, Hangzhou, Zhejiang 310027, China
For the first time, sillica-supported sulfuric acid has been used as a heterogeneous, reusable and efficient cata-
lyst at room temperature to give the corresponding dipyrromethanes in a very short reaction time. The new reaction
procedure is simple and solvent is not required.
Keywords dipyrromethane, H2SO4•SiO2, solvent-free, eco-friendly
Introduction
distillation of the excess pyrrole.12
Here, we are lucky to find that silica supported sul-
furic acid (H2SO4•SiO2) is an efficient and recyclable
catalyst for this reaction at room temperature. And to
the best of our knowledge there are no reports on the
use of this catalyst for this conversion. This fact has
prompted us to use H2SO4•SiO2 for the electrophilic
substitution of pyrrole with various aldehydes in a sim-
ple and practical manner.
As we know, green chemistry is defined as the de-
sign of chemical products and processes that reduce or
eliminate the use and generation of hazardous sub-
stances. For the purposes of this definition, synthetic
chemists have great interest in developing highly effi-
cient transformations for the preparation of organic
compounds. And one of the main themes of contempo-
rary synthetic organic chemistry is the use of environ-
mentally feasible reagents particularly in solvent-free
conditions and environmentally benign catalytic sys-
tems, which are also required to be efficient and eco-
nomic. Solvent-free organic reactions are usually rapid,
occur in high yields and have eco-friendly and eco-
nomic advantages. In addition, if these reactions can be
performed using reusable catalysts, they will become
more attractive. In this context, organic reactions under
solvent-free conditions at room temperature have been
achieved.
Dipyrromethanes are widely being used as important
building blocks for the synthesis of a variety of func-
tional porphyrins and porphyrin analogues,1 which can
be of wide interest in several areas, such as materials
science.2,3 And the development of pyrrole chemistry
has largely been associated with the synthesis of natural
products. Particularly, in the case of unsubstituted pyr-
role rings, the dipyrromethanes are then prone to give
further reactions leading to porphyrin complexes4 and
highly labile products, except in the specific case of
some polypyrrolic macrocycles.5 So efforts have been
made on the preparation of unsubstituted dipyrrome-
thanes. Those methods are generally based on the
acid-catalyzed condensation of the aldehydes and pyr-
role in organic solvent. But these methods suffer from
various disadvantages such as long reaction time,6-8 use
of expensive strong organic acids9 or Lewis acid10,11 and
usually involve a final workup that requires, at least, the
Results and discussion
Investigation of reaction conditions
To achieve the best results for this reaction (Scheme
1) we have studied the synthesis of 2,2'-dipyrryl(4-ani-
syl)methane as a model product at various temperatures
in the same reaction time (Table 1). In each reaction
condition, conversion of pyrrole (2 mmol) and 4-metho-
xybenzaldehyde (1 mmol) to 2,2'-dipyrryl(4-anisyl)-
methane was measured by HPLC. As shown in Table 1,
the most satisfactory results were obtained at the
temperature of 30 ℃. As the temperature elevated, the
regioselectivity changed and the amount of by-products
increased also. Upon finding the optical condition, a set
of reactions were carried out with a variety of aldehydes
(Table 2).
Table 1 Optimization of temperature
Temperature/℃
Reaction time/min
Conversion/%
20
30
45
60
80
2
2
2
2
2
42
44
35
20
18
*
E-mail: shangzc@zju.edu.cn
Received August 3, 2009; revised September 24, 2009; accepted October 27, 2009.
Chin. J. Chem. 2010, 28, 259— 262
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259

Zhang, Liang & Shang
FULL PAPER
Scheme 1 H2SO4•SiO2-catalyzed synthesis of dipyrromethane
in free solvent
column chromatography. Perhaps it is based on the fact
that this is a fast reaction in the presence of this catalyst.
Our findings reflect the wide applicability and use-
fulness of the method. Some previously reported data on
reaction conditions and the yield of product were com-
pared with our results (Table 3). As one can see our re-
sults show good comparability with previously reported
data in respect to reaction time although the yield was
not always the best.
Table 2 Synthesis of dipyrromethane by condensations of pyr-
role with aldehyde catalyzed by silica-supported sulfuric acid at
room temperature
Reusability of catalyst
We also investigated the reusability and recycling of
H2SO4•SiO2. The H2SO4•SiO2 has been reused simply
after filtering the catalyst, washing with acetone, and
drying under vacuum, which did not lose much of its
activity even after three runs (Table 4).
Time/ Yielda/
Entry
Aldehyde
Dipyrromethane
min
%
1
2
3
4
5
3a
3b
3c
3d
3e
2
63
Experimental
2
2
4
3
60
44
45
57
Analytical methods
The process of reactions was monitored by TLC on
1
silica. H NMR and 13C NMR spectra were recorded
with TMS as an internal standard using a Bruker
AMX-500 MHz spectrometer at 500 and 125 MHz, re-
spectively. IR spectra were measured with a Nicolet
Nexus FTIR 670 spectrophotometer.
Preparation of catalyst
To a slurry of silica gel (10 g, 200—400 mesh) in
dry diethyl ether (50 mL) was added commercially
available concentrated H2SO4 (3 mL) with shaking for 5
min. The solvent was evaporated under reduced pres-
sure resulting in free flowing H2SO4•SiO2, which was
then dried at 110 ℃ for 3 h.
6
3f
2
54
7
8
9
3g
3h
3i
3
4
4
55
58
60
Typical procedure
The aldehyde (1 mmol), pyrrole (2 mmol) and
H2SO4•SiO2 (50 mg) were mixed together in a 10 mL,
round-bottomed flask equipped with a magnetic stir bar
at room temperature for several minutes. After comple-
tion of the reaction, as indicated by TLC, the reaction
mixture was diluted with MeOH (5 mL×2) or ethyl
acetate (5 mL×2). The liquid was filtered off, the cata-
lyst washed with acetone (5 mL). Then the organic layer
was concentrated under reduced pressure to afford crude
product which was then purified by column chromatog-
raphy eluted with ethyl acetate and petroleum ether
mixture.
10
3j
5
51
11
12
3k
3l
4
1
57
49
Spectral data of all the compounds
1
3a Yellow solid, m.p. 109—111 ℃; H NMR
a Isolated yield after purification.
(CDCl3, 500 MHz) δ: 5.47 (s, 1H), 5.91 (s, 2H), 6.15 (q,
J＝2.9 Hz, 2H), 6.69 (t, J＝2.4 Hz, 2H), 7.20—7.33 (m,
5H, ArH), 7.92 (s, 2H, NH); IR (KBr) ν: 3421, 2960,
These results did not show a regular chemical be-
havior according to the substituent on the phenyl group;
that is, with either electron-releasing groups (Me, OMe,
Me2N) or electron-withdrawing groups (NO2), dipyr-
romethanes were synthesized in 50%—65% yields after
－
1
1598, 1510, 1492, 1261, 1029, 724, 700 cm .
1
3b Yellow solid, m.p. 127—129 ℃; H NMR
(CDCl3, 500 MHz) δ: 2.33 (s, 3H), 5.43 (s, 1H), 5.91 (s,
2H), 6.15 (d, J＝2.7 Hz, 2H), 6.68 (d, J＝1.1 Hz ,2H),
260
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Chin. J. Chem. 2010, 28, 259— 262

Fast and Eco-friendly Synthesis of Dipyrromethanes
Table 3 Comparison of our own results with previously reported data for synthesis of dipyrromethane
Dipyrromethane
Catalyst
Reaction condition
Yield/%
Ref.
6
3a
3b
3c
3h
80
71
65— 72
61
Solvent: pyrrole;
n(pyrrole)∶ n(aldehyde)＝ 20; 10— 15 h
Cation exchange resin
3a
3h
3l
75
37
25
HCl
Solvent: water; n(pyrrole)∶ n(aldehyde)＝ 2; 15 min
7
8
3a
3b
3d
3h
20
25
15— 20
35
Acetic acid
Solvent: V(THF)∶ V(acetic acid) (9∶ 1); 1 h
TFA
TFA
Excess pyrrole, 15 min
9
3b
49
3a
3h
3l
53
56
41
Solvent: pyrrole; V(pyrrole)∶ V(aldehyde)＝ 25
12
a
Table 4 Recycle experiment of H2SO4•SiO2
2H), 6.86 (d, J＝8.0 Hz, 1H), 6.92 (t, J＝7.4 Hz, 1H),
7.08 (d, J＝7.4 Hz, 1H), 7.19 (t, J＝7.5 Hz, 1H); 13C
NMR (CDCl3, 125 MHz) δ: 40.5, 107.3, 108.8, 121.8,
128.7, 129.0, 130.4, 131.2, 154.0; IR (KBr) ν: 3422,
2962, 1600, 1510, 1475, 1291, 1097, 744 cm . Anal.
calcd for C15H14N2O: C 75.61, H 5.92, N 11.76; found
C 75.55, H 5.90, N 11.73.
Run
1
Time/min
Yieldb/%
4
60
55
48
－
1
2
15
30
3
a Reactions performed with 1.0 mmol of 3-nitrobenzaldehyde, 2
meso-(2-Bromophenyl)dipyrromethane
(3g)
mmol of pyrrol, and 50 mg of H2SO4•SiO2 mixed for several min
under solvent-free condition at room temperature. Isolated
yields after column chromatography.
Light brown solid, m.p. 163—165 ℃; 1H NMR (CDCl3,
500 MHz) δ: 5.87 (t, J＝2.6 Hz, 3H), 6.15 (q, J＝2.9 Hz,
2H), 6.69 (d, J＝1.4 Hz, 2H), 7.10 (q, J＝1.4 Hz, 2H),
7.23 (t, J＝7.0 Hz, 1H), 7.56 (d, J＝7.9 Hz, 1H), 7.98 (s,
2H, NH); 13C NMR (CDCl3, 125 MHz) δ: 43.6, 107.7,
108.8, 117.6, 124.7, 128.0, 128.7, 130.2, 131.6, 133.2,
141.9; IR (KBr) ν: 3431, 3010, 1610, 1505, 1466, 1438,
b
7.09—7.25 (m, 4H, ArH), 7.93 (s, 2H, NH); IR (KBr) ν:
－
1
3421, 2980, 1603, 1510, 1412, 1262, 1035, 802 cm .
3c: Yellow solid, m.p. 99 — 100 ℃ ; 1H NMR
(CDCl3, 500 MHz) δ: 3.78 (s, 3H), 5.42 (s, 1H), 5.90 (d,
J＝1.4 Hz, 2H), 6.15 (q, J＝3.0 Hz, 2H), 6.68 (q, J＝
1.6 Hz, 2H), 6.84—6.86 (m, 2H), 7.12 (q, J＝4.8 Hz,
2H), 7.91 (s, 2H, NH); IR (KBr) ν: 3372, 2927, 1608,
－
1
1025, 748 cm . Anal. calcd for C15H13N2Br: C 59.82,
H 4.35, N 9.30; found C 59.79, H 4.36, N 9.28.
1
3h Yellow solid, m.p. 144—147 ℃; H NMR
－
1
1509, 1463, 1248, 1030, 839 cm ;
(CDCl3, 500 MHz) δ: 5.59 (s, 1H), 5.88 (s, 2H), 6.19 (q,
J＝2.8 Hz, 2H), 6.75 (t, J＝1.4 Hz, 2H), 7.37 (d, J＝8.7
Hz, 2H), 8.02 (s, 2H), 8.16 (d, J＝8.7 Hz, 2H); IR (KBr)
ν: 3396, 3361, 3099, 1602, 1588, 1513, 1490, 1347,
1
3d: Yellow solid, m.p. 115—117 ℃; H NMR
(CDCl3, 500 MHz) δ: 2.93 (s, 6H), 5.40 (s, 1H), 5.94 (s,
2H), 6.15 (q, J＝2.9 Hz, 2H), 6.67—6.72 (m, 4H), 7.90
(s, 2H, NH); IR (KBr) ν: 3423, 2919, 1661, 1601, 1550,
－
1
1029, 743, 728 cm .
－
1
1535, 1373, 1167, 825 cm .
3i Yellow solid, m.p. 131—133 ℃; IR (KBr) ν:
meso-(4-Hydroxyphenyl)dipyrromethane
(3e)
3393, 3352, 1579, 1561, 1513, 1468, 1353, 1027, 775,
－
1
1 1
Brown solid, m.p. 108—110 ℃; H NMR (CDCl3, 500
MHz) δ: 5.25 (s, 1H, OH), 5.34 (s, 2H), 5.87 (s, 2H),
6.13 (q, J＝3.0 Hz, 2H), 6.63—6.69 (m, 4H), 7.01 (d,
J＝8.5 Hz, 2H), 7.93 (s, 2H, NH); 13C NMR (CDCl3,
125 MHz) δ: 43.3, 107.3, 108.5, 115.6, 117.5, 129.8,
133.2, 134.5, 154.6; IR (KBr) ν: 3411, 3119, 1613, 1556,
733 cm ; H NMR (CDCl3, 500 MHz) δ: 5.58 (s, 1H),
5.88 (s, 2H), 6.19 (q, J＝2.7 Hz, 2H), 6.75 (d, J＝1.4
Hz, 2H), 7.49 (t, J＝7.9 Hz, 1H), 7.56 (d, J＝7.7 Hz,
1H), 8.04 (s, 2H, NH), 8.11 (t, J＝8.1 Hz, 2H).
meso-(2,3-Dihydroxyphenyl)dipyrromethane (3j)
1
Brown solid, m.p. 115—118 ℃; H NMR (CDCl3, 500
－
1
1512, 1436, 1260, 1095, 844 cm ; Anal. calcd for
C15H14N2O: C 75.61, H 5.89, N 11.76; found C 75.54, H
5.90, N 11.70.
MHz) δ: 5.51 (s, 1H), 6.02 (t, J＝0.8 Hz, 2H), 6.17 (q,
J＝2.8 Hz, 2H), 6.66 (q, J＝1.3 Hz, 1H), 6.72 (q, J＝
2.5 Hz, 2H), 6.79—6.85 (m, 2H), 8.21 (s, 2H, NH); 13C
NMR (CDCl3, 125 MHz) δ: 40.8, 107.2, 108.9, 114.7,
118.4, 121.7, 122.0, 129.2, 131.0, 141.4, 145.8; IR (KBr)
ν: 3385, 2924, 1596, 1555, 1474, 1281, 1028, 756, 726
meso-(2-Hydroxyphenyl)dipyrromethane
(3f)
Light red-brow oil; 1H NMR (DMSO, 500 MHz) δ: 5.57
(s, 1H), 6.0 (s, 2H), 6.17 (d, J＝2.2 Hz, 2H), 6.70 (s,
Chin. J. Chem. 2010, 28, 259— 262
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
261

Zhang, Liang & Shang
Diego, 2000, Chapter 11, pp. 201— 232.
FULL PAPER
cm . Anal. calcd for C15H14N2O2: C 70.85, H 5.55, N
－
1
11.02; found C 70.80, H 5.58, N 11.06.
2
3
4
Drain, C. M.; Hupp, J. T.; Suslick, K. S.; Wasielewski, M.
R.; Chen, X. J. Porphyrins Phthalocyanines 2002, 6, 243.
Hyun, A. R.; Kim, S. K.; Kang, I. N.; Park, J. W.; Shin, J.
Y.; Song, O. K. Mol. Cryst. Liq. Cryst. 2007, 463, 33.
Collman, J. P.; Gagne, R. R.; Reed, C. A.; Halbert, T. R.;
Lang, G.; Robinsonlc, W. T. J. Am. Chem. Soc. 1975, 97,
1427.
3k Brown solid, m.p. 78 — 80 ℃ ; 1H NMR
(CDCl3, 500 MHz) δ: 5.53 (s, 1H), 6.00 (s, 2H), 6.16 (t,
J＝3.3 Hz, 3H), 6.34 (q, J＝1.9 Hz, 1H), 6.72 (q, J＝
2.5 Hz, 2H), 7.40 (d, J＝0.9 Hz, 1H), 8.12 (s, 2H); IR
(KBr) ν: 3422, 2967, 2925, 1707, 1616, 1561, 1261,
－
1
1097, 803, 740 cm .
1
3l Pale yellow solid, m.p. 73—74 ℃; H NMR
5
(a) Jose, D. A.; Shukla, A. D.; Kumar, D. K.; Ganguly, B.;
Das, A. Inorg. Chem. 2005, 44, 2414.
(CDCl3, 500 MHz) δ: 4.00 (s, 2H), 6.06 (s, 2H), 6.17 (q,
J＝2.8 Hz, 2H), 6.68 (q, J＝2.3 Hz, 2H), 7.80 (s, 2H,
NH); IR (KBr) ν: 3379, 2922, 1565, 1469, 1422, 1091,
(b) Lindsey, J. S.; Schreiman, I. C.; Hsu, H. C.; Kearney, P.
C.; Marguerettaz, A. M. J. Org. Chem. 1987, 52, 827.
(c) Yu, L.; Lindsey, J. S. Tetrahedron 2001, 57, 9285.
(d) Wu, S.; Li, Z.; Ren, L.; Chen, B.; Liang, F.; Zhou, X.;
Jia, T.; Cao, X.-P. Bioorg. Med. Chem. 2006, 14, 2956.
Naik, R.; Joshi, P.; Kaiwar, S. P.; Deshpande, R. K. Tetra-
hedron 2003, 59, 2207.
－
1
1025, 791, 717 cm .
Conclusion
6
7
We have established for the first time, a novel,
eco-friendly and simple protocol for the synthesis of
dipyrromethanes using inexpensive H2SO4•SiO2. The
short reaction procedure and reusability of the catalyst
make this method one of the most efficient methods for
the synthesis of this class of compounds.
Sobral, A. J. F. N.; Rebanda, N. G. C. L.; da Silva, M.;
Lampreia, S. H.; Silva, M. R.; Beja, A. M.; Paixǎo, J. A.;
Gonsalves, A. M. d’A. R. Tetrahedron Lett. 2003, 44, 3971.
Vigmond, S. J.; Chang, M. C.; Kallury, K. M. R.; Thomp-
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© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2010, 28, 259— 262