Sulfamic acid as an efficient and cost-effective catalyst for the synthesis of 2,4,5-triarylimidazoles and 2-arylphenanthrimidazoles

Article abstract of DOI:10.1515/HC.2011.040

A simple and efficient synthesis of 2,4,5-triarylimidazoles and 2-arylphenanthrimidazoles was developed using the onepot, three-component condensation reaction of an aromatic aldehyde, benzil or 9,10-phenanthroquinone and ammonium acetate in refluxing ethanol in the presence of the catalyst sulfamic acid. 2011 · Copyright by Walter de Gruyter.

Full text of DOI:10.1515/HC.2011.040

Heterocycl. Commun., Vol. 17(5-6), pp. 223–226, 2011 • Copyright © by Walter de Gruyter • Berlin • Boston. DOI 10.1515/HC.2011.040
Sulfamic acid as an efficient and cost-effective catalyst for
the synthesis of 2,4,5-triarylimidazoles and
2-arylphenanthrimidazoles
Hua-Nan Peng1,*, Xiao-Ming Peng2, Da-Gui Zheng1,
scolecite (Gadekara et al., 2009), L-proline (Samai et al.,
2009), ytterbium perfluorooctanesulfonate (Shen et al., 2008),
F e i Y u 1 and Min Rao1
tetrabutylammonium bromide (Chary et al., 2008), silica sul-
1 Key Laboratory of Applied Organic Chemistry, Higher
furic acid (Shaabani et al., 2007), indium trichloride (Sharma
Institutions of Jiangxi Province, Shangrao Normal
et al., 2008), potassium dodecatungstocobaltate (Nagarapu et
University, Shangrao 334001, China
al., 2007) and silica perchloric acid (Kantevari et al., 2007).
2 Department of Chemistry, Nanchang University, Xuefu
The reaction can also be performed in acetic acid under reflux
Road 999, Nanchang 330031, China
conditions (Puratchikody and Doble, 2007), under microwave
*Corresponding author
e-mail: huananpeng@126.com
irradiation (Chauveau et al., 2010; Damavandi, 2011) and in
ionic liquid (Zang et al., 2010).
In recent years, sulfamic acid (NH2SO3H) has success-
fully been used as a solid acid catalyst for various organic
synthetic transformations (An et al., 2007; Heravi et al.,
Abstract
2007; Heydari et al., 2007; Kamal et al., 2007; Li et al.,
A simple and efficient synthesis of 2,4,5-triarylimidazoles
2007; Upadhyaya et al., 2007; Mitragotri et al., 2008).
and 2-arylphenanthrimidazoles was developed using the one-
The benefits of its use include low cost, eco-friendliness,
pot, three-component condensation reaction of an aromatic
ease of handling, low toxicity, excellent product yields
aldehyde, benzil or 9,10-phenanthroquinone and ammonium
and high reactivity. These features prompted us to explore
acetate in refluxing ethanol in the presence of the catalyst sul-
the three-component condensation reactions of aldehydes,
famic acid.
benzil or 9,10-phenantherenquinone and ammonium ace-
tate in the presence of a catalytic amount of NH2SO3H to
Keywords: one-pot condensation; phenanthrimidazoles;
synthesize the corresponding 2,4,5-triarylimidazoles and
sulfamic acid; 2,4,5-triarylimidazoles.
2-arylphenanthrimidazoles.
Introduction
Results and discussion
Substituted imidazoles have gained remarkable importance
as herbicidal (Viktor et al., 1975), fungicidal (Heeres et al.,
1979), anti-inflammatory (Lombardino and Wiseman, 1974)
and antibacterial agents (Sharma et al., 2009) and as inhibi-
tors of P38 MAP kinase (Laufer et al., 2010). In addition,
imidazole derivatives have been widely used as precursors
to N-heterocyclic carbenes in organometallic catalysis and as
ionic liquids in green chemistry (Kim et al., 2005; Jiménez
et al., 2008). Several substituted imidazoles also show car-
diovascular and antitrypanosomal activities (Malhotra et al.,
2011; Samant and Sukhthankar, 2011). In light of these prop-
erties, the synthesis of substituted imidazole derivatives has
received considerable attention in recent years.
2,4,5-Triphenylimidazole was first synthesized more than
a century ago by the three-component condensation of a 1,2-
dicarbonyl compound, aldehyde and ammonia (Japp and
Robinson, 1882; Radziszewski, 1882). Recently, numerous
syntheticmethodsforthepreparationofanalogouscompounds
have been developed using similar three-component conden-
sation in the presence of different catalysts. These catalysts
include molecular iodine (Kidwai et al., 2007; Behmadi et al.,
2009), trifluoroacetic acid (Mohammadizadeha et al., 2009),
Different acidic catalysts in the reaction of benzaldehyde (2
mmol), benzil (2 mmol) and ammonium acetate (6 mmol)
were compared (Table 1). The catalysts included F3CCOOH,
H3BO3, CH3SO3H, p-CH3C6H5SO3H, NH2SO3H and
p-NH2C6H5SO3H, each at an amount equal to 10 mmol%. As
can be seen from entries 1–6, NH2SO3H is the most effective
catalyst in terms of product 4a yield (85%). Next, the amount
of NH2SO3H was varied and it was found that 10 mmol% of
the catalyst was the optimal quantity for catalysis. The yield
was further improved by increasing the amount of NH4OAc
from 6 mmol to 10 mmol (entry 11).
Next, a wide range of substituted benzaldehydes were
tested under the optimized conditions. The results are given
in Table 2. Interestingly, the electronic properties of the sub-
stituents have virtually no effect on yields. More specifically,
the reaction of a benzaldehyde with an electron-donating or
an electron-withdrawing group furnishes product 4 in high
yield.
In a similar way, phenanthraquinone 5 was allowed to
react with five substituted benzaldehydes. As shown in Table
3, these reactions produce the desired 2-arylphenanthrimida-
zoles 6 in excellent yields, and the substituent on the aldehyde,
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224 H.-N. Peng et al.
Table 1 Optimizing the reaction conditionsa.
Experimental section
General
CHO
O
N
Catalyst
+
+
NH4OAc
Ethanol, reflux
N
H
Melting points were determined on X4 melting point apparatus and
are uncorrected. Infrared (IR) spectra were recorded using KBr discs
on a Nicolet 6700 fourier transform infrared (FT-IR) spectrophoto-
meter. 1H-NMR spectra were recorded on the Varian Inova-300 MHz
spectrometer using tetramethylsilane (TMS) as internal standard and
DMSO-d6 as a solvent. Mass spectra (EI, 70 eV) were obtained on a
Shimadzu SIL-10AAuto Injector liquid chromatography-mass spec-
trometry (LC-MS). Thin layer chromatography (TLC) was carried
out on GF254 silica gel plates.
O
1
2
3
4a
Entry
Catalyst
Catalyst
NH4OAc Time Yield
(mmol%)
(mmol)
(h)
(%)b
1
2
3
4
5
6
7
8
F3CCOOH
H3BO3
CH3SO3H
p-CH3C6H5SO3H
p-NH2C6H5SO3H
NH2SO3H
10
10
10
10
10
10
2 .5
5
6
6
6
6
6
6
6
6
6
5
5
5
5
5
5
5
5
5
5
4
65
69
73
77
80
85
7 5
8 0
85
89
93
General procedure for the preparation of 2,4,5-
triarylimidazoles 4 and 2-arylphenanthrimidazoles 6
NH2SO3H
NH2SO3H
A mixture of benzil or phenanthraquinone (2 mmol), a benzalde-
hyde (2 mmol), ammonium acetate (10 mmol) and sulfamic acid
(10 mmol%) in ethanol (10 ml) was stirred and heated under reflux
until the reaction was completed as monitored by TLC. Then, the
mixture was poured onto crushed ice and the resulting solid was fil-
tered and crystallized from ethanol. Known compounds 4a–k (Table
2), 6a and 6g (Table 3) showed 1H nuclear magnetic resonance
(NMR) spectra that were virtually identical with those reported.
9
10
11
NH2SO3H
NH2SO3H
NH2SO3H
15
10
10
8
10
aThe amount of benzaldehyde was 2 mmol and benzil was 2 mmol;
bisolated yields.
whether electron-donating or -withdrawing, has no effect on
the yield.
2-(4-Trifluoromethylphenyl)-4,5-diphenyl-1H-imidazole
(4l) White crystals; H NMR: δ 8.27 (d, J=8 Hz, 2H), 7.83 (d, J=
1
8 Hz, 2H), 7.59–7.18 (m, 10H); IR: 3402, 3057, 1602, 1588, 1496,
1441 cm-1; MS: m/z 365 ([M+1]+, 100).
Conclusions
We have developed a simple and efficient three-component
condensation reaction for the synthesis of 2,4,5-triarylimida-
zoles and 2-arylphenanthrimidazoles using sulfamic acid as
an efficient, cost-effective and eco-friendly catalyst.
2-(2,4-Dichlorophenyl)-1H-phenanthro[9,10-d]imidazole
(6b) White crystals; 1H NMR: δ 8.84 (d, J=8 Hz, 2H), 8.59 (d, J=
8 Hz, 2H), 7.94 (d, J=8 Hz, 1H), 7.87 (s, 1H), 7.73–7.60 (m, 5H); IR:
3440, 3083, 1614, 1588, 1515 cm-1; MS: m/z 363 (M+, 100).
Table 2 Sulfamic acid catalyzed synthesis of 2,4,5-triarylimidazoles 4a–l.
O
O
N
NH2SO3H
Ar
ArCHO
+
+
NH4OAc
Ethanol, reflux
N
H
1
2
3
4a-l
Entry
2
Aryl
Time (h) Product Yield (%)a
Mp (°C)b
(found)
Mp (°C)
(reported)Literature
1
2
3
4
5
6
7
8
2a C6H5
4
5
4
4
3
3
4
3
4
4
4
5
4a
4b
4c
4d
4e
4f
4g
4h
4i
93
94
95
91
92
95
93
95
92
89
90
90
277–279
177–179
235–238
267–268
199–201
>300
231–232
263–265
256–257
241–243
265–267
273–275
274–276c
175–178d
233–235d
265e
2b 2,4-Cl2C6H3
2c 4-MeC6H4
2d 4-BrC6H4
2e
2f
2-ClC6H4
3-NO2C6H4
195–196c
>300d
2g 4-OMeC6H4
2h 4-ClC6H4
227–228c
262–264d
256–259d
242e
9
2i
2j
4-N(Me)2C6H4
2-Furyl
10
11
12
4j
4k
4l
2k 4-OHC6H4
2l 4-F3CC6H4
268–269c
aIsolated yields; bafter crystallization; c(Gadekara et al., 2009); d(Samai et al., 2009); e(Chary et al., 2008).
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Synthesis of 2,4,5-triarylimidazoles and 2-arylphenanthrimidazole 225
Table 3 Sulfamic acid catalyzed synthesis of 2-arylphenanthrimidazoles 6.
O
O
N
NH2SO3H
Ar
ArCHO
+
+
NH4OAc
Ethanol, reflux
N
H
5
2
3
6
Entry
2
Aryl
Time Product Yield (%)a Mp (°C)b
Mp (°C)
(found)
(reported)Literature
314–315c
1
2
3
4
5
2a C6H5
2b 2,4-Cl2C6H3
2d 4-BrC6H4
2g 4-OMeC6H4
2l 4-F3CC6H4
5
4
4
4
5
6a
6b
6d
6g
6l
93
90
91
92
93
>300
245–246
264–267
250–253
241–243
254–255c
aIsolated yields; bafter recrystallization; c(Behmadi et al., 2009).
2-(4-Bromophenyl)-1H-phenanthro[9,10-d]imidazole
(6d) White crystals; 1H NMR: δ 8.83 (d, J=8 Hz, 2H), 8.53 (d, J=
8 Hz, 2H), 8.24 (d, J=8 Hz, 2H), 7.79 (d, J=8 Hz, 2H, Ar–H), 7.72 (t,
J=8 Hz, 2H), 7.62 (t, J=8 Hz, 2H); IR: 3425, 3069, 1653, 1616, 1539,
1475, 1457 cm-1; MS: m/z 373 (M+, 90), 375 ([M+2]+, 100).
Gadekara, L. S.; Maneb, S. R.; Katkara, S. S.; Arbada, B. R.; Landea,
M. K. Scolecite as an efficient heterogeneous catalyst for the
synthesis of 2,4,5-triarylimidazoles. Cent. Eur. J. Chem. 2009,
7, 550–554.
Heeres, J.; Backx, L. J.; Mostmans, J. H.; Van Cutsem, J.Antimycotic
imidazoles. Part 4. synthesis and antifungal activity of ketocon-
azole, a new potent orally active broad-spectrum antifungal
agent. J. Med. Chem. 1979, 22, 1003–1005.
2-(4-Trifluoromethylphenyl)-1H-phenanthro[9,10-d]imidazole
1
(6l) White crystals, H NMR: δ 8.93 (t, J=8 Hz, 2H), 8.65 (t, J=
Heravi, M. M.; Ranjbar, L.; Derikvand, F.; Bamoharram, F. F.
Sulfamic acid as a cost-effective catalyst instead of metal-con-
taining acids for the one-pot synthesis of β-acetamido ketones. J.
Mol. Catal. A. Chem. 2007, 276, 226–229.
8 Hz, 2H), 8.59 (d, J=8 Hz, 2H), 8.04 (d, J=8 Hz, 2H), 7.88–7.68
(m, 4H); IR: 3458, 3077, 1619, 1588, 1529, 1454 cm-1. MS: m/z 363
([M+1]+, 100).
Heydari, A.; Khaksar, S.; Pourayoubi, M.; Mahjoub, A. R. Sulfamic
acid: an efficient, cost-effective and recyclable solid acid cata-
lyst for the three-component synthesis of α-amino nitriles.
Tetrahedron Lett. 2007, 48, 4059–4060.
Japp, F. R.; Robinson, H. H.; Constitution des lophins und des
amwins. Chem. Ber. 1882, 15, 1268–1270.
Jiménez, M. V.; Pérez-Torrente, J. J.; Bartolomé, M. I.; Gierz, V.;
Lahoz, F. J.; Oro, L. A. Rhodium(I) complexes with hemilabile
N-heterocyclic carbenes: efficient alkyne hydrosilylation cata-
lysts. Organometallics 2008, 27, 224–234.
Kamal, A.; Prasad, B. R.; Reddy, A. M.; Khan, M. N. Sulfamic acid
as an efficient and recyclable catalyst for the ring opening of
epoxides with amines and anilines: an easy synthesis of β-amino
alcohols under solvent-free conditions. Catal. Commun. 2007, 8,
1876–1880.
Acknowledgments
We acknowledge financial support from the Research Program of
Science and Technology from the Bureau of Education of Jiangxi
Province, China (No.: GJJ10736) and the Youth Science Foundation
of Jiangxi Educational Committee, China (No.: GJJ11232).
References
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.
Kantevari, S.; Vuppalapati, S. V.; Biradar, D. O.; Nagarapu, L. Highly
efficient, one-pot, solvent-free synthesis of tetrasubstituted imi-
dazoles using HClO4-SiO2 as novel heterogeneous catalyst. J.
Mol. Catal. A. Chem. 2007, 266, 109–113.
Behmadi, H.; Roshani, M.; Saadati, S. M. Synthesis of phenan-
thrimidazole from 9,10-phenanthraquinone and aldehydes by
molecular iodine as catalyst. Chinese Chem. Lett. 2009, 20,
5–8.
Kidwai, M.; Mothsra, P.; Bansal, V.; Somvanshi, R. K.; Ethayathulla,
A. S.; Dey, S.; Singh, T. P. One-pot synthesis of highly substi-
tuted imidazoles using molecular iodine: a versatile catalyst. J.
Mol. Catal. A. Chem. 2007, 265, 177–182.
Kim, E. J.; Koa, S. Y.; Dziadulewicz, E. K. Mitsunobu alkylation of
imidazole: a convenient route to chiral ionic liquids. Tetrahedron
Lett. 2005, 46, 631–633.
Laufer, S.; Hauser, D.; Stegmiller, T.; Bracht, C.; Ruff, K.; Schattel,
V.; Albrecht, W.; Koch, P. Tri- and tetrasubstituted imidazoles as
p38α mitogen-activated protein kinase inhibitors. Bioorg. Med.
Chem. Lett. 2010, 20, 6671–6675.
Chary, M. V.; Keerthysri, N. C.; Vupallapati, S. V.; Lingaiah, N.;
Kantevari, S. Tetrabutylammonium bromide (TBAB) in isopro-
panol: an efficient, novel, neutral and recyclable catalytic sys-
tem for the synthesis of 2,4,5-trisubstituted imidazoles. Catal.
Commun. 2008, 9, 2013–2017.
Chauveau, E.; Marestin, C.; Schiets, F.; Mercier, R. Synthesis of
2,4,5-triarylimidazoles in aqueous solution, under microwave
irradiation. Green Chem. 2010, 12, 1018–1022.
Damavandi, S. New approach to the multicomponent one-pot syn-
thesis of 2-aryl-1H- phenanthro[9,10-d]imidazoles. Heterocycl.
Commun. 2011, 17, 79–81.
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Download Date | 10/10/14 10:06 PM

226 H.-N. Peng et al.
Li, Z. J.; Sun, Y. J.; Ren, X. H.; Wei, P.; Shi, Y. H.; Ouyang, P. K.
Sulfamic acid catalyzed direct condensation of aldehydes,
amines, and TMSCN to α-aminonitriles at ambient temperature.
Synlett. 2007, 5, 803–805.
Lombardino, J. G.; Wiseman, E. H. Preparation and antiinflamma-
tory activity of some nonacidic trisubstituted imidazoles. J. Med.
Chem. 1974, 17, 1182–1188.
Samant, B. S.; Sukhthankar, M. G. Compounds containing 2-sub-
stituted imidazole ring for treatment against human African try-
panosomiasis. Bioorg. Med. Chem. Lett. 2011, 21, 1015–1018.
Shaabani, A.; Rahmati, A.; Farhangi, E.; Badri, Z. Silica sulfuric acid
promoted the one-pot synthesis of trisubstituted imidazoles under
conventional heating conditions or using microwave irradiation.
Catal. Commun. 2007, 8, 1149–1152.
Malhotra, V.; Pathak, S. R.; Nath, R.; Mukherjee, D.; Shanker, K.
Substituted imidazole derivatives as novel cardiovascular agents.
Bioorg. Med. Chem. Lett. 2011, 21, 936–939.
Mitragotri, S. D.; Pore, D. M.; Desai, U. V.; Wadgaonkar, P. P.
Sulfamic acid: an efficient and cost-effective solid acid catalyst
for the synthesis of α-aminophosphonates at ambient tempera-
ture. Catal. Commun. 2008, 9, 1822–1826.
Mohammadizadeha, M. R.; Hasaninejada, A.; Bahramzadeha, M.
Trifluoroacetic acid as an efficient catalyst for one-pot, four-
component synthesis of 1,2,4,5-tetrasubstituted imidazoles under
microwave-assisted, solvent-free conditions. Synth. Commun.
2009, 39, 3232–3242.
Sharma, S. D.; Hazarika, P.; Konwar, D. An efficient and one-pot
synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imi-
dazoles catalyzed by InCl3·3H2O. Tetrahedron Lett. 2008, 49,
2216–2220.
Sharma, D.; Narasimhan, B.; Kumar, P.; Judge, V.; Narang, R.;
Clercq, E. D.; Balzarini, J. Synthesis, antimicrobial and antivi-
ral evaluation of substituted imidazole derivatives. Eur. J. Med.
Chem. 2009, 44, 2347–2353.
Shen, M. G.; Cai, C.; Yi, W. B. Ytterbium perfluorooctanesul-
fonate as an efficient and recoverable catalyst for the synthe-
sis of trisubstituted imidazoles. J. Fluorine Chem. 2008, 129,
541–544.
Nagarapu, L.; Apuri, S.; Kantevari, S. Potassium dodecatungstoco-
baltate trihydrate (K5CoW12O40·3H2O): a mild and efficient reus-
able catalyst for the one-pot synthesis of 1,2,4,5-tetrasubstituted
imidazoles under conventional heating and microwave irradia-
tion. J. Mol. Catal. A. Chem. 2007, 266, 104–108.
Puratchikody, A.; Doble, M. Antinociceptive and antiinflammatory
activities and QSAR studies on 2-substituted-4,5-diphenyl-1H-
imidazoles. Bioorg. Med. Chem. 2007, 15, 1083–1090.
Radziszewski, B. Ueber die Constitution des Lophins und verwandter
verbindungen. Chem. Ber. 1882, 15, 1493–1496.
Upadhyaya, D. J.; Barge, A.; Stefaniab, R.; Cravottoa, G. Efficient,
solventless N-Boc protection of amines carried out at room tem-
perature using sulfamic acid as recyclable catalyst. Tetrahedron
Lett. 2007, 48, 8318–8322.
Viktor, A.; Katalin, G.; Gyorgyi, B.; Zsuzsanna, N.; Miklos, H.;
Bela, R.; Erzsebet, G.; Terez, S.; Josef, D.; Szilagyi, G.; et al.
Substituted imidazole pesticides. GB Patent 1407723, 1975;
Chem. Abstr. 1973, 84, 17351.
Zang, H. J.; Su, Q. H.; Mo, Y. M.; Cheng, B. W.; Jun, S. Ionic liquid
[EMIM]OAc under ultrasonic irradiation towards the first syn-
thesis of trisubstituted imidazoles. Ultrason. Sonochem. 2010,
17, 749–751.
Samai, S.; Nandi, G. C.; Singh, P.; Singh, M. S. L-Proline: an effi-
cient catalyst for the one-pot synthesis of 2,4,5-trisubstituted
and 1,2,4,5-tetrasubstituted imidazoles. Tetrahedron 2009, 65,
10155–10161.
Received August 30, 2011; accepted October 19, 2011
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