Silica gel, an effective catalyst for the reaction of electron-deficient nitro-olefins with nitrogen heterocycles

Article abstract of DOI:10.1080/00397910903340694

The reaction of electron-deficient olefins with nitrogen heterocycles such as pyrrole and indole was examined in the presence of silica gel at room temperature under stirring at solvent-free conditions. It was found that silica gel is an effective catalys

Full text of DOI:10.1080/00397910903340694

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Silica Gel, an Effective Catalyst for the
Reaction of Electron-Deficient Nitro-
Olefins with Nitrogen Heterocycles
Abdullah M. A. Shumaila a & Radhika S. Kusurkar a
a Department of Chemistry, University of Pune, Pune, India
Version of record first published: 25 Aug 2010.
To cite this article: Abdullah M. A. Shumaila & Radhika S. Kusurkar (2010): Silica Gel, an Effective
Catalyst for the Reaction of Electron-Deficient Nitro-Olefins with Nitrogen Heterocycles, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
40:19, 2935-2940
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Synthetic Communications1, 40: 2935–2940, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903340694
SILICA GEL, AN EFFECTIVE CATALYST FOR THE
REACTION OF ELECTRON-DEFICIENT NITRO-OLEFINS
WITH NITROGEN HETEROCYCLES
Abdullah M. A. Shumaila and Radhika S. Kusurkar
Department of Chemistry, University of Pune, Pune, India
The reaction of electron-deficient olefins with nitrogen heterocycles such as pyrrole and
indole was examined in the presence of silica gel at room temperature under stirring at
solvent-free conditions. It was found that silica gel is an effective catalyst for this conjugate
addition. This work resulted in the formation of monosubstituted pyrroles selectively as a
major product except in a few cases where disubstituted pyrroles were also formed as side
products. Thus, a simple, rapid, efficient, environmentally benign, and solvent-free method
was established.
Keywords: Conjugate addition reaction; indole; nitro-olefins; pyrrole; silica gel
INTRODUCTION
Synthetic methods for C-alkyl pyrroles and C-alkyl indoles are in demand
because of their importance as building blocks for the synthesis of biologically active
compounds and natural products.[1] It is well documented that indole has good
nucleophilicity from C-3, as pyrrole has from C-2. The conjugate addition of nitro-
gen heterocycles to electron-deficient olefins is one of the routes toward alkylated
pyrroles and indoles and has been developed with various catalysts such as indium
trichloride,[2] bismuth trichloride,[3] iodine,[4] sulfamic acid,[5] and aluminium dodecyl
sulfate trihydrate [Al(DS)3 ꢀ 3H2O],[6] ytterbium triflate [Yb(OTf)3 ꢀ 3H2O],[7]
CeCl3 ꢀ 7H2O, and NaI ꢀ SiO2.[8] Protic solvents and Lewis acids have some limita-
tions because they involve use of toxic reagents and require careful control of the
acidity to prevent side reactions such as dimerization or polymerization. Although
recently microwave methodology has been used,[9] there is still a need to develop
an environmentally friendly method devoid of toxic acidic reagents and solvents.
Use of silica gel as a solid and mild acidic catalysts is well reported and is
receiving considerable attention from synthetic chemists.[10,11] In the present study,
we planned to use silica gel for conjugate additions of pyrrole and indole on
electron-deficient nitro-olefins.
Received July 23, 2009.
Address correspondence to Radhika S. Kusurkar, Department of Chemistry, University of Pune,
Pune 411 007, India. E-mail: rsk@chem.unipune.ac.in
2935

2936
A. M. A. SHUMAILA AND R. S. KUSURKAR
RESULTS AND DISCUSSION
Reaction between pyrrole and b-nitrostyrene 4a was carried out by loading
both of these compounds on silica gel and stirring at room temperature. 2-Alkyl pyr-
role 5a was obtained as a major product in 89% yield along with 2,5-dialkyl pyrrole
6a in minor amounts 6% (Scheme 1; Table 1, entry 1). Thus, after achieving a
successful, high-yielding, rapid Michael addition using silica gel, the reaction was
generalized using nitro olefins 4b, 4c, and 4e, where surprisingly the reaction was
more selective and afforded exclusively 2-alkyl pyrroles (Scheme 1; Table 1, entries
2, 3, and 5). However, during the Michael addition using other nitro olefins 4d,
4f, and 4g, 2,5-dialkyl pyrroles were also obtained in very minor amounts along with
major monoalkylated products (Scheme 1; Table 1, entries 4, 6, and 7). Reaction of
methyl-substituted nitro-olefins 4h, 4i, and 4j with pyrrole gave an inseparable
Scheme 1. Michael addition of pyrroles on nitro-olefins.
Table 1. Time, yield, and mp of Michael adducts from pyrrole
2-Alkyl pyrrole 5
Mp (ꢁC)
2,5-Dialkyl pyrrole 6
Michael
adducts
Entry
Time (h)
Yield (%)
Yield (%)
Mp (ꢁC)
1
2
a
b
c
d
e
f
1.5
3
89
83
80
83
80
79
85
77
75
80
81
75–77 (lit.[3] mp 77–77.5 ꢁC)
146–147
6
Oily liquid
—
—
—
9
3
3
Oily liquid
Oily liquid
123–124
—
Oily liquid
4
2.5
3
5
—
10
8
—
Oily liquid
Oily liquid
6
2.5
3
>250
Oily ꢂliquid
7
g
h
i
8
3.5
3.5
3.5
2.5
—
—
—
—
—
—
—
—
ꢂ
ꢂ
9
10
11
j
k
64–66
Notes. Yield calculated according to the recovered starting electrophile. An asterisk (ꢂ) indicates
products are mixtures of diastereomers.

SILICA GEL AS AN EFFECTIVE CATALYST
2937
Scheme 2. Michael addition of indole on nitro-olefins.
mixture of diastereomers of the 2-alkyl pyrroles 5h, 5i, and 5j as the only products
(Scheme 1; Table 1, entries 8–10).
Reactivity of substituted pyrroles was studied using reactions of N-substituted
pyrroles, namely N-methyl pyrrole 2 and N-benzoyl pyrrole 3, with b-nitrostyrene
4a. In the case of N-methyl pyrrole, 2-alkyl pyrrole 5k was obtained exclusively in
81% yield (Table 1, entry 11) and in the case of N-benzoyl pyrrole, no reaction
was observed. The latter can be attributed to decreased reactivity of pyrrole due
to the electron-withdrawing N-benzoyl substituent.
After establishing good catalytic activity of silica gel for Michael additions
of pyrroles and substituted pyrroles, indole was used for these reactions. Thus, a
mixture of indole and b-nitrostyrene 4a was loaded on silica gel and was stirred
at room temperature for 30 min, affording product 8, which was fully character-
ized by spectral techniques. Reactions of various other nitro-olefins 4b–g and
indole under similar reaction conditions furnished products 9–14. The results
are summarized in Scheme 2 and Table 2. The structures of all products were
confirmed using infrared (IR), 1H NMR, 13C NMR, and gas chromatography–
mass spectrometry (GC-MS).
Table 2. Time, yield, and mp of Michael adducts from indoles
Entry
Michael adducts
Time (h)
Yield (%)
Mp (ꢁC)
1
2
3
4
5
6
7
8
9
0.5
2.5
2.5
0.5
2.5
0.5
2.5
92
79
82
80
78
85
87
99–101 (lit. mp 99 ꢁC)a
143–145 (lit. mp 145 ꢁC)a
144–146 (lit. mp 145 ꢁC)a
69 (lit. mp 69 ꢁC)a
10
11
12
13
14
143 (lit. mp 142 ꢁC)a
93–95 (lit. mp 94 ꢁC)a
151 (lit. mp 150–152 ꢁC)a
Note. Yield calculated according to the recovered starting electrophile.
aRef. [9b].

2938
A. M. A. SHUMAILA AND R. S. KUSURKAR
CONCLUSION
A simple, efficient, environmentally benign, and solvent-free silica gel–
catalyzed method was established for the conjugate addition of pyrrole and indole.
All reactions were very clean, and no polymerization was observed, in contrast to
earlier reported reactions using different catalysts.
EXPERIMENTAL
Methods
1
All recorded melting points are uncorrected. The H and 13C NMR spectra
were recorded as d values in CDCl3 with reference to tetramethylsilane (TMS) as
1
internal standard on a Varian Mercury instrument, 300 MHz and 200 MHz for H
NMR and 75 MHz and 50 MHz for 13C NMR. Fourier transform (FT)–IR spectra
were recorded on a Perkin-Elmer 1600. Mass spectra were recorded on a Shimadzu
QP 5050. Elemental analyses were recorded on Flash E.A.1112 Thermo instrument.
General Procedure
A mixture of indole (0.0024 mol) and nitro-olefins 4a–g (0.002 mol) or pyrrole
1–3 (0.02 mol) and nitro-olefins 4a–j (0.01 mol) was loaded on silica gel (60–120
mesh) and stirred at room temperature. After the reaction was completed as judged
by thin-layer chromatography (TLC), the same silica gel was loaded on a silica-gel
column. The chromatographic separation was carried out by using hexane–ethyl
acetate to furnish the products.
Selected Data
Compound 5c. Yield 80%. Oily liquid; IR (KBr) (cmꢃ1): 3356, 1551, 1335; 1H
NMR (200 MHz, CDCl3): 4.56–4.83 (m, 3H), 5.79 (s, 2H), 5.94 (brs, 1H), 6.02–6.06
(m, 1H), 6.54–6.65 (m, 4H), 7.91 (brs, 1H); 13C NMR (50 MHz, CDCl3): 42.7, 53.1,
79.3, 96.2, 101.3, 105.6, 108.2, 108.7, 118.3, 121.3, 128.9, 131.8, 147.4, 148.3; MS: m=z
260 Mþ, 213 (100%), 200, 183, 92, 77, 65.
Compound 5e. Yield 80%. Mp 123–124 ꢁC; IR (KBr) n (cmꢃ1): 3404, 1551,
1
1358; H NMR (300 MHz, CDCl3): 4.85 (dd, J ¼ 11.0, 15.4 Hz, 1H), 4.95–5.08 (m,
2H), 6.09 (brs, 1H), 6.18 (d, J ¼ 2.2 Hz, 1H), 6.72 (brs, 1H), 7.4 (d, J ¼ 8.5 Hz,
2H), 7.97 (brs, 1H), 8.17 (d, J ¼ 8.5 Hz, 2H); 13C NMR (75 MHz, CDCl3): 42.6,
78.5, 106.4, 108.9, 118.9, 124.2, 127.0, 128.8, 145.3, 147.3; MS m=z 261 Mþ, 214
(100%), 201, 167, 139, 115, 93.
Compound 5g. Yield 85%. Oily liquid; IR (KBr) n (cmꢃ1): 3384, 1517, 1340;
1H NMR (300 MHz, CDCl3): 3.76 (s, 3H), 4.69–4.85 (m, 2H), 4.94 (d, J ¼ 11.3,
6.6 Hz, 1H), 6.03 (brs, 1H), 6.12 (q, J ¼ 5.8, 2.8 Hz, 1H), 6.64 (t, J ¼ 2.8 Hz, 1H),
6.83 (d, J ¼ 8.8 Hz, 2H), 7.11 (d, J ¼ 8.8 Hz, 2H), 7.82 (brs, 1H); 13C NMR
(75 MHz, CDCl3): 42.2, 55.3, 79.3, 105.4, 108.5, 114.4, 117.9, 128.9, 129.1, 129.7,
159.1; MS: m=z 246 Mþ, 199 (100%), 186, 92, 77.

SILICA GEL AS AN EFFECTIVE CATALYST
2939
Compound 6g. Mixture of diastereomers 8% yield. Oily liquid; IR (KBr) n
1
(cmꢃ1): 3348, 1575, 1386; H NMR (300 MHZ, CDCl3): 3.76 (s, 6H), 3.77 (s, 6H)
4.61–4.78 (m, 8H), 4.8–4.93 (m, 4H), 5.98 (m, 4H), 6.79–6.83 (m, 8H), 7.03 (d,
J ¼ 8.8 Hz, 8H), 7.5 (2xbs, 2H); 13C NMR (75 MHz, CDCl3): 42.1, 55.2, 79.2,
79.3, 105.7, 106.1, 114.1, 114.3, 114.4, 128.7, 128.8, 129.5, 129.57, 129.6, 159.0, 159.1.
Compound 5i. Mixture of two diastereomers in the ratio of 2.5:1. Yield 75%;
mp 163–165 ꢁC; IR (KBr), n (cmꢃ1): 3360, 1550, 1387; 1H NMR (300 MHz, CDCl3):
1.44 (d, J ¼ 6.6 Hz, 3H), 1.66 (d, J ¼ 6.6 Hz, 3H), 3.84 (m, 12H, four singlets overlap-
ping), 4.41 (d, J ¼ 10.17 Hz, 1H), 4.48 (d, J ¼ 10.17 Hz, 1H), 5.04–5.2 (m, 2H), 6.1
(brs, 2H), 6.15 (brs, 2H), 6.6–6.9 (m, 8H), 7.9 (brs, 2H,); 13C NMR (75 MHz,
CDCl3): 18.9, 19.1, 48.8, 49.2, 55.7, 55.8, 55.9, 86.8, 86.9, 105.6, 106.5, 108.4,
108.8, 111.0, 111.2, 111.3, 117.7, 119.3, 120.5, 128.3, 129.5, 129.9, 130.7, 148.3,
148.4, 148.9, 149.1; MS m=z 290 Mþ, 243, 228, 216 (100%), 200, 154, 142, 130, 77.
Compound 5j. Mixture of two diastereomers in the ratio of 4.7:1. Yield 80%;
mp 153–155 ꢁC; IR (KBr) n (cmꢃ1): 3393, 1524, 1348; 1H NMR (300 MHz, CDCl3):
1.47 (d, J ¼ 6.6 Hz, 3H), 1.69 (d, J ¼ 6.6 Hz, 3H), 4.56 (d, J ¼ 10.45 Hz, 1H), 4.69 (d,
J ¼ 9.9 Hz, 1H), 5.21 (m, 2H), 6.14 (brs, 2H), 6.19 (brs, 2H), 6.68 (brs, 2H), 7.38–7.46
(m, 4H), 8.0 (brs, 2H), 8.14 (d, J ¼ 8.25 Hz, 2H), 8.2 (d, J ¼ 8 Hz, 2H); 13C NMR
(75 MHz, CDCl3): 18.8, 19.1, 48.9, 49.5, 86.0, 86.6, 106.8, 107.0, 108.9, 109.4,
118.5, 118.6, 124.1, 124.2, 128.5, 129.3, 144.9, 145.6.
ACKNOWLEDGMENTS
We are grateful to Mr. B. S. Kalshetti for IR spectra, Mrs. J. P. Choudhary for
NMR spectra, and Mr. D. S. Shishupal for GC-MS. A. M. A. S. is thankful to
Ministry of Higher Education in Yemen for the award of a fellowship.
REFERENCES
1. (a) Thomas, L. G. In Heterocyclic Chemistry; 3rd ed.; Longman: England, 1997; parts 1, 2,
and 5; (b) Sundberg, R. D. Pyrroles and their benzo derivatives, synthesis and applica-
tions. In Comprehensive Heterocyclic Chemistry; A. R. Katrizky, C. W. Ress (Eds.);
Pergamon: Oxford, 1984; vol. 4, pp. 313–376; (c) Saxton, J. E. Recent progress in the
chemistry of the monoterpenoid indole alkaloids. Nat. Prod. Rep. 1997, 14, 559; (d)
Toyota, M.; Ihara, N. Recent progress in the chemistry of non-monoterpenoid indole
alkaloids. Nat. Prod. Rep. 1998, 15, 327; (e) Leonid, I.; Belen, K. Relative stabilities of
hetarenium ions: Factors controlling positional selectivities of electrophilic substitution
and acid-induced transformations of pyrrole, furan, and thiophene derivatives. Hetero-
cycles 1994, 37, 2029; (f) Sundberg, R. J. The Chemistry of Indoles; Academic Press:
New York, 1969; p. 113.
2. Yadav, J. S.; Abraham, S.; Reddy, B. V. S.; Sabitha, G. InCl3-catalysed conjugate
addition of indoles with electron-deficient olefiens. Synthesis. 2001, 2165–2169.
3. Zhan, Z.-P.; Yu, J.-L.; Yang, W.-Z. Bismuth trichloride–catalyzed C-alkylation of
pyrroles with electron-deficient olefins. Synth. Commun. 2006, 36, 1373–1382.
4. Lin, C.; Hsu, J.; Sastry, M. N. V.; Fang, H.; Tu, Z.; Liu, J.-T.; Ching-Fa, Y. I2-catalyzed
Michael addition of indole and pyrrole to nitroolefins. Tetrahedron. 2005, 61,
11751–11757.

2940
A. M. A. SHUMAILA AND R. S. KUSURKAR
5. An, L.-T.; Zou, J.-P.; Zhang, L.-L.; Zhang, Y. Sulfamic acid–catalyzed Michael addition
of indoles and pyrrole to electron-deficient nitroolefins under solvent-free condition.
Tetrahedron Lett. 2007, 48, 4297–4300.
6. Firouzabadi, H.; Iranpoor, N.; Nowrouzi, F. The facile and efficient Michael addition of
indoles and pyrrole to a,b-unsaturated electron-deficient compounds catalyzed by alumi-
num dodecyl sulfate trihydrate [Al(DS)3] ꢀ 3H2O in water. Chem. Commun. 2005, 789–791.
7. Harrington, P. E.; Kerr, M. A. Reaction of indoles with electron deficient olefins catalyzed
by Yb(OTf)3 ꢀ 3H2O. Synlett. 1996, 1047–1050.
8. Bartoli, G.; Bosco, M.; Giuli, S.; Giuliani, A.; Lucarelli, L.; Marcantoni, E.; Sambri, L.;
Torregiani, E. Efficient preparation of 2-indolyl-1-nitroalkane derivatives employing
nitroalkenes as versatile Michael acceptors: New practical linear approach to alkyl
9H-b-carboline-4-carboxylate. J. Org. Chem. 2005, 70, 1941–1944.
9. (a) Zhan, Z-P.; Yang, W-Z.; Yang, R-F.; Microwave-assisted addition of pyrroles to
electron-deficient olefins: A rapid entry to C-alkyl pyrroles. Synlett. 2005, 16, 2425–
2428; (b) Kusurkar, R. S.; Alkobati, N. A. H.; Gokule, A. S.; Chaudhari, P. M.;
Waghchaure, P. B. Thermal and microwave-assisted conjugate additions of indole on
electron-deficient nitro-olefins. Synth. Commun. 2006, 36, 1075–1081.
10. (a) Coma, A. Inorganic solid acids and their use in acid-catalyzed hydrocarbon reactions.
Chem. Rev. 1995, 95, 559–614; (b) Isobe, K. Cubane-type clusters as potential models for
inorganic solid surface Biginelli reactions. Acc. Chem. Res. 1993, 26, 524–529.
11. (a) Kamitori, Y.; Hojo, M.; Masuda, R.; Izumi, T.; Tsukamoto, S. Silica gel as an effective
catalyst for the alkylation of phenols and some heterocyclic aromatic compounds. J. Org.
Chem. 1984, 49, 4161–4165; (b) Kotsuki, H.; Hayashida, K.; Shimanouchi, T.; Nishizawa,
H. High-pressure organic chemistry, 19: High-pressure-promoted, silica gel–catalyzed
reaction of epoxides with nitrogen heterocycles. J. Org. Chem. 1996, 61, 984–990; (c)
Chavan, F.; Madje, B.; Bharad, J.; Ubale, M.; Ware, M.; Shingare, M.; Shinde, N. Silica
gel–supported NaHSO4-catalyzed organic reaction: An efficient synthesis of coumarins.
Bull. Catal. Soc. Ind. 2008, 7, 41–45.