New approach to the multicomponent one-pot synthesis of 2-aryl-1H-phenanthro[9,10-d]imidazoles

Article abstract of DOI:10.1515/HC.2011.018

A novel, acid catalyzed multicomponent one-pot synthesis of 2-aryl-1H-phenanthro[9,10-d]imidazole compounds derived from aromatic aldehydes, 9,10-phenanthrenequinone and ammonium acetate under ultrasonic irradiation is reported. A wide range of aromatic aldehydes readily undergo condensation with 9,10-phenanthrenequinone and ammonium acetate under optimized conditions to afford the desired imidazoles of good purity in excellent yields. Copyright by Walter de Gruyter Berlin Boston.

Full text of DOI:10.1515/HC.2011.018

Heterocycl. Commun., Vol. 17(1-2), pp. 79–81, 2011 • Copyright © by Walter de Gruyter • Berlin • Boston. DOI 10.1515/HC.2011.018
New approach to the multicomponent one-pot synthesis of
2-aryl-1H-phenanthro[9,10-d]imidazoles
(Sharma et al., 2008). These examples utilized a one-pot three-
component reaction of 1,2-dicarbonyl compounds, aldehydes,
ammonium acetate, and various catalysts. However, benzil
and benzoin compounds were mainly examined for the syn-
thesis of 2,4,5-triphenylimidazoles. In the present study, the
reaction of 9,10-phenanthrenequinone with various aromatic
aldehydes and ammonium acetate under ultrasonic irradiation
using various catalysts was examined, and the correspond-
ing 2-aryl-1H-phenanthro[9,10-d]imidazole derivatives 1–13
were obtained in excellent yields (Scheme 1).
Saman Damavandi
Department of Chemistry, Islamic Azad University,
Sarvestan Branch, Sarvestan, Iran
e-mail: Saman_Damavandi@yahoo.com
Abstract
A novel, acid catalyzed multicomponent one-pot synthesis of
2-aryl-1H-phenanthro[9,10-d]imidazole compounds derived
from aromatic aldehydes, 9,10-phenanthrenequinone and
ammonium acetate under ultrasonic irradiation is reported. A
wide range of aromatic aldehydes readily undergo condensa-
tion with 9,10-phenanthrenequinone and ammonium acetate
under optimized conditions to afford the desired imidazoles
of good purity in excellent yields.
Results and discussion
In our initial search for appropriate reaction conditions, we
chose the reaction of benzaldehyde, 9,10-phenanthrenequi-
none and ammonium acetate as a model. The reactions were
conducted with a variety of catalysts and solvents as depicted
in Table 1. In entries 1–8, the catalytic efficiency of Yb(OTf)3,
La(OTf)3, Cu(OTf)2, Zn(OTf)2, HOTf, CH3SO3H, CF3COOH
and p-toluenesulfonic acid (p-TSA) was studied. In all cases
5 mol % of the catalyst was used and the reaction was carried
out in ethanol and under ultrasonic irradiation. As shown in
Table 1, the best result was obtained when p-TSA was used as
a catalyst (entry 8). The effects of the solvent on the reaction
were also investigated as indicated by entries 8–14 in Table
1. The best results were obtained for the reaction conducted
in ethanol and acetonitrile (entries 8 and 14, respectively).
Accordingly, ethanol was chosen as the solvent for further
reactions.
To generalize the scope of this reaction and its utility as
a new synthetic approach to 2-aryl-1H-phenanthro[9,10-d]
imidazole derivatives 1–13, the methodology was extended
by including 13 different aromatic aldehydes. The aldehydes
contain electron withdrawing groups (such as nitro group, hal-
ogen) or electron-donating groups (such as methoxy group),
and in each case moderate to excellent yields of the desired
products were obtained under the optimized conditions;
hence, demonstrating the versatility of the methodology. It is
worthy to note that the condensation of 2-chlorobenzaldehyde
and 2-flurobenzaldehyde afforded the desired 2-(4-chloro)-1-
H-phenanthro[9,10-d]imidazole and 2-(2-fluorophenyl)-1-
H-phenanthro[9,10-d]imidazole, respectively (9, 10) in good
yield indicating that steric hindrance is not a factor in this reac-
tion. The reaction of 1-naphthalenecarboxaldehyde also gave
the corresponding product 11 in high yield. The mechanism
for this reaction is likely to involve the formation of an aminal
intermediate, followed by condensation with 9,10-phenan-
threnequinone, intramolecular cyclization, and subsequently
Keywords: 2-aryl-1H-phenanthro[9,10-d]imidazole;
one-pot synthesis; ultrasonic irradiation.
Introduction
One-pot multicomponent reactions (MCRs) that convert more
than two reactants directly into their products are of interest
to chemists, owing to conserving atom economy and fostering
the benign synthesis of organic compounds. MCRs are part of
the latest advanced solutions for decreasing the discovery and
development times for new drugs, and potentially reducing
the development costs and complexity in the process. Thus,
useful structural variations can be increased (Weber et al.,
1999; Bienayme et al., 2000).
Compounds with an imidazole moiety have biological
and pharmaceutical importance. For example, several substi-
tuted imidazoles are inhibitors of p38 MAP kinase (Lee et
al., 1994). Highly substituted imidazoles such as lepidilines
exhibit micromolar cytotoxicity against several human can-
cer cell lines (Cui et al., 2003). Trifenagrel is a potent 2,4,5-
triarylimidazole that reduces platelet aggregation in several
animal species and humans (Abrahams et al., 1989).
In 1882, Radziszewski and Japp reported the first syn-
thesis of 2,4,5-triphenylimidazoles from the reaction of 1,2-
dicarbonyl compounds with various aldehydes and ammonia
(Radziszewski, 1882). Recently, a literature survey reveals
several methods for the synthesis of 2,4,5-triarylimidazoles
using boric acid (Shelke et al., 2009), zeolite HY/silica gel
(Balalaie and Arabanian, 2000), tetrabutylammonium bro-
mide (Salehi et al., 2011), sulfanilic acid (Mohammed et al.,
2007), ionic liquid (Siddiqui et al., 2005), and InCl3⋅3H2O
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80 S. Damavandi
O
O
N
Catalyst
+ ArCHO + NH4OAc
Ar
US irradiation
N
H
1-13
Ar=C6H5 - (1); 4-NO2C6H4 - (2); 4-CH3OC6H4 - (3); 4-ClC6H4 - (4); 4-CH3C6H4 - (5);
4-HOC6H4 - (6); 4-(N,N-dimethyl)C6H4 - (7); 2-furanyl - (8); 2-ClC6H4 - (9);
2-FC6H4 - (10); 1-naphthyl - (11); 3-ClC6H4 - (12); 2,4-dimethylC6H4 - (13)
Scheme 1 Synthesis of 2-aryl-1H-phenanthro[9,10-d]imidazole derivatives 1–13.
refer to isolated products. The IR spectra were recorded in KBr disks
[1,5] sigmatropic proton shift to afford the corresponding
2-aryl-1H-phenanthro[9,10-d]imidazole derivative.
on a Shimadzu-IR 470 spectrophotometer and the results are report-
1
ed in cm-1. The H NMR spectra were recorded on a Bruker 100-
MHz spectrometer in DMSO-d6 as the solvent with TMS as internal
standard. Sonication was performed in a Shanghai Branson-CQX
ultrasonic cleaner with a frequency of 40 kHz and a nominal power
of 100 W. Flash column chromatography was performed with 300-
and 400-mesh silica gel, and analytical thin layer chromatography
was performed on precoated silica gel plates (60F-254). Elemental
analyses were performed on a Thermo Finnigan EA1112 elemental
analyzer.
Conclusion
We have developed a novel, efficient, ultrasonic irradiation,
and p-TSA catalyzed method for the synthesis of 2-aryl-1H-
phenanthro[9,10-d]imidazole derivatives by a one-pot three-
component reaction of aldehyde, 9,10-phenanthrenequinone
and ammonium acetate. Particularly valuable features of this
synthetic process are excellent yields, mild reaction condi-
tions, easy work-up, and short reaction time.
General procedure for preparation of 2-aryl-1H-
phenanthro[9,10-d]imidazole derivatives
A mixture of aromatic aldehyde (1 mmol), 9,10-phenanthrenequino-
ne (1 mmol), ammonium acetate (3.5 mmol), and 5 mol % of p-TSA
in ethanol (10 ml) was stirred at room temperature under ultrasonic
irradiation using ultrasonic cleaner with a frequency of 40 KHz and
a nominal power 100 W for the appropriate time. After completion of
the reaction, as indicated by TLC, the catalyst was removed by filtra-
tion and evaporation of the solvent afforded the crude product, which
was purified by silica gel column chromatography using petroleum
ether/ethyl acetate (9:1). The selected compounds are characterized
as follows.
Experimental
General
Chemicals were either prepared in our laboratories or purchased
from Merck, Fluka, and Aldrich Chemical Companies. All yields
Table 1 2-Aryl-1H-phenanthro[9,10-d]imidazole synthesis cataly-
zed by different catalysts under ultrasonic irradiation.
2-Phenyl-1H-phenanthro[9,10-d]imidazole (1) After 6 min the
yield was 94%; mp 328–330°C; IR: 3405 (N-H), 1552 (C=C), 1590
(C=N); H NMR: δ 6.95–7.45 (m, 9H, Ar), 7.75 (d, 2H, J=7.5 Hz),
8.10 (d, 2H, J=5.2 Hz), 12.25 (s, NH). Analysis calculated for
C21H14N2: C, 85.69; H, 4.79; N, 9.52. Found: C, 85.33; H, 4.55; N,
9.44.
Entry
Catalyst
Solvent
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
Yield (%)a,b
1
1
2
3
4
5
6
7
8
Yb(OTf)3
La(OTf)3
Cu(OTf)2
Zn(OTf)2
HOTf
CH3SO3H
CF3COOH
p-TSA
p-TSA
p-TSA
p-TSA
p-TSA
88
85
80
82
80
84
88
94
93
78
88
82
75
92
2-(4-Nitrophenyl)-1H-phenanthro[9,10-d]imidazole (2) After
8 min the yield was 93%; mp 336–338°C; IR: 3435 (N-H), 1555
1
EtOH
(C=C), 1585 (C=N), 1340 (NO2), 1525 (NO2); H NMR: δ 7.10–
9
ClCH2CH2Cl
CH2Cl2
CH3OH
THF
Toluene
CH3CN
7.65 (m, 10H, Ar), 8.04 (d, 2H, J=8 Hz), 11.95 (s, 1H, NH). Analysis
calculated for C21H13N3O2: C, 74.25; H, 3.90; N, 12.22. Found: C,
74.33; H, 3.86; N, 12.38.
10
11
12
13
14
p-TSA
p-TSA
2-(4-Methoxyphenyl)-2H-phenanthro[9,10-d]imidazole
(3) After 5.5 min the yield was 91%; mp 255–256°C; IR: 3405
(N-H), 1552 (C=C), 1590 (C=N); 1H NMR: δ 3.72 (s, 3H), 6.90–7.35
(m, 8H, Ar), 7.88 (d, 2H, J=7.5 Hz), 8.10 (d, 2H, J=7.5 Hz), 12.30 (s,
NH). Analysis calculated for C22H16N2O: C, 81.46; H, 4.97; N, 8.64.
Found: C, 80.95; H, 4.90; N, 8.55.
aReaction conditions: solvent (10 ml), benzaldehyde (1 mmol), 9,10-
phenanthrenequinone (1 mmol), ammonium acetate (3.5 mmol), 5 mol
% of catalyst, room temperature and under US irradiation (6 min).
bIsolated yield.
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2-Aryl-1H-phenanthro[9,10-d]imidazoles 81
2-(4-Chlorophenyl)-1H-phenanthro[9,10-d]imidazole (4) After
6.5 min the yield was 92%; mp 275–276°C; IR: 3420 (N-H), 1425–
1540 (C=C), 1595 (C=N). 1H NMR 7.05–7.55 (m, 8H, Ar), 7.6–7.95
(m, 2H, Ar), 8.10 (d, 2H, J=7 Hz), 12.14 (s, NH). Analysis calculated
for C21H13ClN2: C, 76.71; H, 3.99; N, 8.52. Found: C, 76.61; H, 3.98;
N, 8.46.
for C21H13N2Cl: C, 76.71; H, 3.99; N, 8.52. Found: C, 76.63; H,
4.04; N, 8.51.
2-(2,4-Dimethylphenyl)-1H-phenanthro[9,10-d]imidazole
(13) After 6 min the yield was 93%; mp 277–278°C; IR: 3410
(N-H), 1405–1655 (C=C), 1660 (C=N); 1H NMR: δ 2.25 (s, 3H,
Me), 2.30 (s, 3H, Me), 7.10–7.40 (m, 5H, Ar), 7.55–8.15 (m, 7H,
Ar), 12.15 (s, NH). Analysis calculated for C23H18N2: C, 85.68; H,
5.63; N, 8.69. Found: C, 85.58; H, 5.59; N, 8.62.
2-p-Tolyl-1H-phenanthro[9,10-d]imidazole (5) After 7 min the
yield was 92%; mp 270–271°C; IR: 3405 (N-H), 1425–1525 (C=C),
1605 (C=N); 1H NMR: δ 2.20 (s, 3H), 7.10–7.50 (m, 8H, Ar), 7.70–
7.90 (m, 2H, Ar), 8.05 (d, 2H, J=5.2 Hz), 12.10 (s, NH). Analysis
calculated for C22H16N2: C, 85.69; H, 5.23; N, 9.08. Found: C, 85.60;
H, 5.20; N, 8.97.
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2-(4-Hydroxyphenyl)-1H-phenanthro[9,10-d]imidazole (6)
After 7 min the yield was 90%; mp 350–352°C; IR: 3345 (N-H),
1415–1530 (C=C), 1609 (C=N); 1H NMR: δ 6.95–7.55 (m, 6H, Ar),
7.67–7.86 (m, 4H, Ar), 8.02 (d, 2H, J=4.5 Hz), 9.75 (s, OH), 13.10 (s,
NH). Analysis calculated for C21H14N2O: C, 81.27; H, 4.55; N, 9.03.
Found: C, 80.96; H, 4.51; N, 8.97.
2-(4-N,N-dimethylanilino)-1H-phenanthro[9,10-d]imidazole
(7) After 6 min the yield was 92%; mp 266–268°C; IR: 3510 (O-H,
N-H), 1420–1552 (C=C), 1592 (C=N); 1H NMR: δ 2.90 (s, Me),
3.05 (s, Me), 7–7.75 (m, 7H, Ar), 7.80–8.10 (m, 5H, Ar), 12.10 (s,
NH). Analysis calculated for C23H19N3: C, 81.87; H, 5.68; N, 12.45.
Found: C, 81.81; H, 5.65; N, 12.38.
2-(Furan-2-yl)-1H-phenanthro[9,10-d]imidazole (8) After
7
min the yield was 88%; an oil; IR: 3410 (N-H), 1415–1530 (C=C),
1608 (C=N); 1H NMR: δ 7.07–7.55 (m, 7H, Ar), 7.70–8.05 (m, 2H,
Ar), 8.15 (d, 2H, J=5.2 Hz), 12.12 (s, NH). Analysis calculated for
C19H12N2O: C, 80.27; H, 4.25; N, 9.85. Found: C, 80.02; H, 4.21;
N, 9.79.
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2-(2-Chlorophenyl)-1H-phenanthro[9,10-d]imidazole (9) After
7.5 min the yield was 91%; an oil; IR: 3385 (N-H), 1416–1605
1
(C=C), 1635 (C=N). H NMR δ 7.05–7.50 (m, 4H, Ar), 7.70–8.10
(m, 8H, Ar), 11.95 (s, NH). Analysis calculated for C21H13N2Cl: C,
76.71; H, 3.99; N, 8.52. Found: C, 76.55; H, 3.91; N, 8.55.
2-(2-Fluorophenyl)-1H-phenanthro[9,10-d]imidazole (10)
After 7 min the yield was 90%; mp 320–322°C; IR: 3440 (N-H),
1465–1614 (C=C), 1630 (C=N); 1H NMR: δ 6.90–7.40 (m, 5H, Ar),
7.60–7.85 (m, 5H, Ar), 8.10 (d, 2H, J=7 Hz), 12.10 (s, NH). Analysis
calculated for C21H13N2F: C, 80.75; H, 4.20; N, 8.97. Found: C,
80.64; H, 4.19; N, 8.94.
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2-(Naphthalen-1-yl)-1H-phenanthro[9,10-d]imidazole (11)
After 8 min the yield was 94%; an oil; IR: 3390 (N-H), 1414–1536
(C=C), 1602 (C=N); 1H NMR: δ 7–7.50 (m, 6H, Ar), 7.75–8.15 (m,
9H, Ar), 12.12 (s, NH). Analysis calculated for C25H16N2: C, 87.18;
H, 4.68; N, 8.13. Found: C, 87.08; H, 4.61; N, 8.02.
2-(3-Chlorophenyl)-1H-phenanthro[9,10-d]imidazole
(12) After 6.5 min the yield was 93%; mp 305–307°C; IR: 3425
(N-H), 1410–1625 (C=C), 1640 (C=N); 1H NMR: δ 7.10–7.55 (m,
6H, Ar), 7.65–8.0 (m, 6H, Ar), 12.03 (s, NH). Analysis calculated
Received April 28, 2011; accepted May 24, 2011
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