One-Pot Three-Component Synthesis of 2,4,5-Triaryl-1 H -imidazoles in the Presence of a Molecular Sieve Supported Titanium Catalyst under Mild Basic Conditions

Article abstract of DOI:10.1055/s-0037-1611155

A series of 2,4,5-trisubstituted-imidazoles has been synthesized with good to excellent yields by the one-pot condensation reaction of 1,2-dicarbonyl compounds, benzaldehydes, and ammonium acetate in the presence of 4 ? molecular sieves modified with titanium(IV) as an efficient heterogeneous catalyst. The catalyst could be recovered easily and reused without significant loss of activity.

Full text of DOI:10.1055/s-0037-1611155

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© Georg Thieme Verlag Stuttgart · New York
2018, 29, A–E
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Á. Magyar, Z. Hell
Letter
Synlett
One-Pot Three-Component Synthesis of 2,4,5-Triaryl-1H-imidazoles
in the Presence of a Molecular Sieve Supported Titanium Catalyst
under Mild Basic Conditions
Ágnes Magyar
Zoltán Hell*
R'
O
R'
O
Ti4+/4 Å MS
N
Budapest University of Technology and Economics,
Department of Organic Chemistry and Technology,
Műegyetem rkp. 3, 1111 Budapest, Hungary
magyar.agnes@mail.bme.hu
H
2 NH4OAc
R
100 °C, neat
then toluene
N
H
O
R
R'
R'
zhell@mail.bme.hu
R = H, halogen, methyl, methoxy, OH
15 examples
58–86% yield
Received: 16.08.2018
Accepted after revision: 09.11.2018
Published online: 30.11.2018
ing, that the elaboration of new MCRs and the development
of known multicomponent reactions are areas of consider-
able current interest.
DOI: 10.1055/s-0037-1611155; Art ID: st-2018-d0693-l
Several methods have been reported in the literature for
the synthesis of polysubstituted imidazoles. 2,4,5-Trisubsti-
tuted imidazoles are generally synthesized by the three-
component cyclocondensation of a 1,2-diketone, α-hy-
droxyketone, or α-ketomonoxime with an aldehyde
and ammonium acetate, under the influence of acidic cata-
lysts such as silica sulfuric acid,16 acetic acid,17 TiCl4/SiO2,18
InCl3·3H2O,19 UO2(NO3)2·6H2O supported on acidic alumi-
na,20 ceric ammonium nitrate (CAN),21 ionic liquids,22 and
microwave irradiation.23
Abstract A series of 2,4,5-trisubstituted-imidazoles has been synthe-
sized with good to excellent yields by the one-pot condensation reac-
tion of 1,2-dicarbonyl compounds, benzaldehydes, and ammonium ac-
etate in the presence of 4 Å molecular sieves modified with titanium(IV)
as an efficient heterogeneous catalyst. The catalyst could be recovered
easily and reused without significant loss of activity.
Keywords 2,4,5-triaryl-1H-imidazoles, multicomponent reactions, ti-
tanium, 4 Å molecular sieves, heterogeneous catalysis
Imidazole and its derivatives represent a highly import-
ant class of N-heterocycles that are the subject of intensive
current research due to their wide range of pharmacologi-
cal and biological properties.1 The potential and wide range
of application of the imidazole pharmacophore may be at-
tributed to its hydrogen bond donor–acceptor ability, as
well as its high affinity for metals, which are present in
many protein active sites (e.g., Zn, Fe, Mg).2 Substituted im-
idazoles have been demonstrated to be inhibitors of B-Raf
kinase,3 glucagon receptors,4 and p38 MAP kinase,5 or to act
as antibacterial,6 antifungal,7 anti-inflammatory,8 antitu-
mor agents,9 pesticides,10 and plant-growth regulators.11
Recent advances in green chemistry and organometallic ca-
talysis have extended the utilization of imidazoles as ionic
liquids12 and N-heterocyclic carbenes.13 They are also cen-
tral components of existing drugs such as losartan, irbesar-
tan,14 and trifenagrel15.
Many of the synthetic methods for imidazole synthesis
suffer from one or more disadvantages, such as harsh reac-
tion conditions,17 tedious workup procedure,17 and applica-
tion of hazardous and expensive catalysts and/or re-
agents.18–21 Thus the development of a simpler method re-
quiring milder conditions is synthetically significant.
Our research group works on the elaboration of new
heterogeneous catalytic methods for the preparation of or-
ganic compounds using supported metal catalysts. During
this work, several supported metal catalysts were used with
good to excellent yields in different organic syntheses, for
example 4 Å molecular sieves supported copper,24 lantha-
num,25 titanium,26 and zinc catalysts.27 In this communica-
tion we report a method for the one-pot three-component
synthesis of 2,4,5-triaryl-1H-imidazoles promoted by a het-
erogeneous, 4 Å molecular sieve supported titanium cata-
lyst.
Multicomponent reactions (MCRs) have been the focus
of much interest in recent years. They are one-pot processes
starting from three or more components and can provide
complex molecular structures with shortened reaction
times, increased yields, and less side products compared to
conventional reaction strategies. Therefore, it is not surpris-
In the literature, acidic catalysts have mainly been used
for the one-pot three-component preparation of 2,4,5-tri-
aryl-1H-imidazoles. There is an example for the use of a ti-
tanium compound, TiCl4/SiO2 as catalyst for this cyclization,
which is also acidic in nature. Our Ti4+/4 Å MS catalyst is
slightly basic in the bulk phase (pH = 7.35). As this catalyst
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–E

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Á. Magyar, Z. Hell
Letter
Synlett
O
O
Ti4+/4 Å MS
N
H
2 NH4OAc
Cl
N
H
100 °C, neat
then toluene
Cl
O
1a
2e
3
4e
Scheme 1 Ti4+/4 Å MS catalyzed synthesis of 4e
was used successfully for the THP protection of alcohols,
which is an acid-catalyzed conversion,26 we examined the
reaction of benzil, different aromatic aldehydes, and ammo-
nium acetate as nitrogen source in the presence of this catalyst.
Initially, we reacted benzil, 4-chlorobenzaldehyde, and
ammonium acetate (in 10 mol% excess) without solvent, at
100 °C (Scheme 1). After 1 h, the reaction mixture solidi-
fied, thus a small quantity of toluene had to be added. After
10 h, TLC analysis of the reaction mixture showed that the
benzil had been completely consumed. After the workup,
the desired product was obtained in 80% yield. When tolu-
ene was added at the outset of the reaction, the yield de-
creased significantly.
Substituted aromatic aldehydes reacted with benzil and
ammonium acetate in the presence of the Ti4+/4 Å MS cata-
lyst to give the corresponding 2,4,5-trisubstituted imidaz-
oles in good yields. In the reaction of 2-methoxybenzalde-
hyde (2j, Table 1, entry 10), based on the TLC analysis of the
reaction mixture, several products were obtained. Although
the desired product was present, it could not be purified
even after two attempts at recrystallization from ethanol.
Among the other products, only the intermediate diamine
(Scheme 2, compound A) could be identified.
We also examined the reaction with 2-nitro-, 3-nitro-,
4-nitro-, and p-dimethylaminobenzaldehyde, but in these
cases, no products were formed according to TLC analysis
and only intermediates could be detected. As an example
for aliphatic aldehydes, we examined the reaction of bu-
tanal, but due to its lower boiling point we had to reduce
the reaction temperature significantly (80 °C). Under these
conditions no product was formed and only the intermedi-
We examined the reaction using a range of aldehydes.
As the later addition of toluene gave a better result in our
initial study, we used these reaction conditions (neat for 1
h, then 1 mL toluene, 100 °C, 10 h) throughout. The results
are summarized in Table 1.
Table 1 Synthesis of 2,4,5-Trisubstituted Imidazoles Catalyzed by Ti4+/4 Å MSa
O
O
N
Ti4+/4 Å MS
H
2 NH4OAc
100 °C, neat
then toluene
R
N
H
O
R
1a
2
3
4a–m
Entry
R
Product
Yield (%)b
1
2
H
4a
4b
4c
4d
4e
4f
81
77
85
78
80
73
84
58
65
–
3-Br
3
4-Br
4
2-Cl
5
4-Cl
6
2-F
7
2-Me
3-Me
4-Me
2-MeO
3-MeO
4-MeO
2-OH
4g
4h
4i
8
9
10
11
12
13
4j
4k
4l
73
86
67
4m
a Reaction conditions: 1 mmol benzil, 1 mmol benzaldehyde, 2.2 mmol ammonium acetate, 0.1 g catalyst, neat for 1 h, then 1 mL toluene, 100 °C, 10 h.
a Isolated yield.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–E

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Letter
Synlett
Table 2 Application of 4,4′-dimethoxybenzil in the Ti4+/4 Å MS Catalyzed Synthesis of 2,4,5-Trisubstituted Imidazolesa
O
O
O
Ti4+/4 Å MS
O
N
H
2 NH4OAc
R
N
H
100 °C, neat
then toluene
O
R
O
O
1b
2
3
4n–o
Entry
R
Product
Yield (%)b
1
2
H
4n
4o
25
15
4-Br
a Reaction conditions: 1 mmol 4,4′-dimethoxybenzil, 1 mmol benzaldehyde, 2.2 mmol ammonium acetate, 0.1 g catalyst, neat for 1 h, then 1 mL toluene,
100 °C, 10 h.
b Conversion determined by 1H NMR spectroscopy.
ates could be detected. This temperature perhaps was not
high enough for the cyclization. In the reactions of trans-
cinnamaldehyde and 3-phenylpropionaldehyde complex
mixtures were obtained. With heteroaryl aldehydes (furfu-
ral, thiophene-2-carbaldehyde, and N-methyl-2-pyrrolecar-
boxaldehyde) the product could be detected by TLC analysis
of the reaction mixture but, probably due to the polymer-
ization of the aldehydes, their isolation was unsuccessful.
To investigate the scope of the reaction further, we ap-
plied 4,4′-dimethoxybenzil instead of benzil in the synthe-
sis. In these cases, the starting material was not consumed
after 10 h and further heating (20 h) resulted in substantial
decomposition. The results are summarized in Table 2.
According to the reported mechanisms,19,20 we propose
a plausible pathway for the formation of the 2,4,5-triaryl-
1H-imidazole derivatives (Scheme 2). Although the bulk
phase of the Ti4+/4 Å molecular sieve catalyst is slightly ba-
sic, the titanium is located on the surface of the support,
forming acidic sites.26 These areas of the catalyst might fa-
cilitate the reaction steps through the coordination of the
heteroatoms in the transition states. The reaction is pro-
posed to proceed through diamine intermediate A, which
may form by the activation of the carbonyl oxygen of the al-
dehyde by the Ti4+ cation, and subsequent condensation
with two molecules of ammonia. In the following step, in-
termediate A condenses with the carbonyl carbons of the
1,2-diketone followed by dehydration to afford the imino
intermediate B, which rearranges to the desired trisubsti-
tuted imidazole.
The lower reactivity of 4,4′-dimethoxybenzil might be
explained with the possibility of the formation of a complex
between the titanium ion and the methoxy group instead
of the carbonyl oxygen or the lower electrophilicity of the
carbonyls.
The workup of the reaction mixtures was very simple;
the catalyst was filtered off and washed with acetone. The
crude product obtained after the evaporation of the filtrate
was then recrystallized from ethanol. The reusability of the
catalyst was examined in the reaction of benzil, 4-chloro-
benzaldehyde, and ammonium acetate. After a 10 h reflux,
the reaction mixture was worked up as described above,
then the catalyst was heated at ca. 150 °C for 1 h. It was re-
used in three more runs without a notable decrease in its
activity. The isolated yields for the three successive runs
were 80%, 78%, 77%, respectively, clearly demonstrating the
practical recyclability of this catalyst.
Ti4+
H2N
O
NH2
H
H
2 NH4OAc
– H2O
R
R
A
O
In conclusion, titanium(IV) on a 4 Å molecular sieve
support has proved to be an effective catalyst for the one-
pot, three component synthesis of 2,4,5-triaryl-1H-imidaz-
oles under mild, slightly basic conditions,28–31 which is al-
most unprecedented in the literature. The catalyst can be
prepared readily and can be reused maintaining its activity.
– 2 H2O
O
H
N
N
H+ transfer
R
R
N
N
H
Funding Information
BH3
Scheme 2 Possible mechanism of the reaction
Á. M. is grateful to the József Varga Foundation for financial support.()
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–E

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Á. Magyar, Z. Hell
Letter
Synlett
References and Notes
(24) (a) Fodor, A.; Kiss, Á.; Debreczeni, N.; Hell, Z.; Gresits, I. Org.
Biomol. Chem. 2010, 8, 4575. (b) Magyar, Á.; Hell, Z. Monatsh.
Chem. 2016, 147, 1583.
(1) Lambardino, J. G.; Wiseman, E. H. J. Med. Chem. 1974, 17, 1182.
(2) Philips, A. P.; White, H. L.; Rosen, S. EP 58890, 1982.
(3) Takle, A. K.; Brown, M. J. B.; Davies, S.; Dean, D. K.; Francis, G.;
Gaiba, A.; Hird, A. W.; King, F. D.; Lovell, P. J.; Naylor, A.; Reith, A.
D.; Steadman, J. G.; Wilson, D. M. Bioorg. Med. Chem. Lett. 2006,
16, 378.
(4) de Laszlo, S. E.; Hacker, C.; Li, B.; Kim, D.; MacCoss, M.; Mantlo,
N.; Pivnichny, J. V.; Colwell, L.; Koch, G. E.; Cascieri, M. A.;
Hagmann, W. K. Bioorg. Med. Chem. Lett. 1999, 9, 641.
(5) Lee, J. C.; Laydon, J. T.; McDonnell, P. C.; Gallagher, T. F.; Kumar,
S.; Green, D.; McNulty, D.; Blumenthal, M. J.; Keys, J. R.; Vatter,
S. W. L.; Strickler, J. E.; McLaughlin, M. M.; Siemens, I. R.; Fisher,
S. M.; Livi, G. P.; White, J. R.; Adams, J. L.; Young, P. R. Nature
1994, 372, 739.
(6) Antolini, M.; Bozzoli, A.; Ghiron, C.; Kennedy, G. Bioorg. Med.
Chem. Lett. 1999, 9, 1023.
(7) Heeres, J.; Backx, L. J. J.; Mostmans, J. H.; Van Cutsem, J. J. Med.
Chem. 1979, 22, 1003.
(8) Khanna, I. K.; Weier, R. M.; Yu, Y.; Xu, X. D.; Koszyk, F. J.; Collins,
P. W.; Koboldt, C. M.; Veenhuizen, A. W.; Perkins, W. E.; Casler, J.
J.; Masferrer, J. L.; Zhang, Y. Y.; Gregory, S. A.; Seibert, K.;
Isakson, P. C. J. Med. Chem. 1997, 40, 1634.
(25) (a) Magyar, Á.; Hell, Z. Catal. Lett. 2016, 146, 1153. (b) Magyar,
Á.; Hell, Z. Period. Polytech. Chem. Eng. 2017, 61, 278.
(26) Magyar, Á.; Nagy, B.; Hell, Z. Catal. Lett. 2015, 145, 1876.
(27) Magyar, Á.; Hell, Z. Green Process Synth. 2018, 7, 316.
(28) 1H NMR and 13C NMR spectra were made on a BRUKER Avance-
300 instrument using TMS as an internal standard in DMSO-d6.
Melting points were determined on SETARAM DSC 92 appara-
tus, where the initial temperature was 25 °C, followed by pro-
gramming at 10 °C/min up to 300 °C under nitrogen atmo-
sphere. All compounds and solvents were purchased from
Merck Hungary Ltd.
(29) The catalyst was prepared according to the method described in
ref. 26. Samples were heated at 120 °C for 1 h before the reac-
tion. Figure 1 shows the SEM image of the catalyst. The charac-
teristic cuboctahedron shape of the molecular sieve support
can be seen, the particles are well defined both in shape and
size, and the titanium is evenly distributed on the surface of the
support.
(9) Wang, L.; Woods, K. W.; Li, Q.; Barr, K. J.; McCroskey, R. W.;
Hannick, S. M.; Gherke, L.; Credo, R. B.; Hui, Y.-H.; Marsh, K.;
Warner, R.; Lee, J. Y.; Zielinski-Mozng, N.; Frost, D.; Rosenberg,
S. H.; Sham, H. L. J. Med. Chem. 2002, 45, 1697.
(10) Maier, T.; Schmierer, R.; Bauer, K.; Bieringer, H.; Buerstell, H.;
Sachse, B. US 4820335, 1989; Chem. Abstr.; 1989, 111: 19494w
(11) Schmierer, R.; Mildenberger, H.; Buerstell, H. DE 361464, 1987;
Chem. Abstr.; 1988, 108: 37838
(12) For reviews, see: (a) Dupont, J.; de Souza, R. F.; Suarez, P. A. Z.
Chem. Rev. 2002, 102, 3667. (b) Chowdhury, S.; Mohan, R. S.;
Scott, J. L. Tetrahedron 2007, 63, 2363.
(13) For reviews, see: (a) Bourissou, D.; Guerret, O.; Gabbai, F. P.;
Bertrand, G. Chem. Rev. 2000, 100, 39. (b) Arnold, P. L.; Liddle, S.
T. Chem. Commun. 2006, 3959. (c) Kühl, O. Chem. Soc. Rev. 2007,
36, 592.
Figure 1
(14) Boersma, C.; Atthobari, J.; Gansevoort, R. T.; de Jong, P. E.; de
Zeeuw, D.; Annemans, L. J.; Postma, M. J. PharmacoEconomics
2006, 24, 523.
(30) General Procedure for the One-Pot Synthesis of 2,4,5-Triaryl-
1H-imidazoles
(15) Abrahams, S. L.; Hazen, R. J.; Batson, A. G.; Phillips, A. P. J. Phar-
macol. Exp. Ther. 1989, 249, 359.
A mixture of benzil (1 mmol, 0.21 g), aldehyde (1 mmol),
ammonium acetate (2.2 mmol, 0.17 g), and Ti4+/4A (0.1 g) was
stirred in a 10 mL flask at 100 °C. After 1 h toluene (1 mL) was
added because the precipitated product impeded stirring of the
melt. The stirring was continued, and progress of the reaction
was monitored by TLC. After completion (10 h), the mixture was
cooled to room temperature, diluted with acetone (10 mL), any
solid was filtered off, and the filtrate was evaporated. The
product was purified by recrystallization from ethanol.
(31) 2,4,5-Triphenyl-1H-imidazole (4a)
(16) Shaabani, A.; Rahmati, A. J. Mol. Catal. A Chem. 2006, 249, 246.
(17) (a) Wang, J.; Mason, R.; VanDerveer, D.; Feng, K.; Bu, X. R. J. Org.
Chem. 2003, 68, 5415. (b) Puratchikody, A.; Gopalakrishnan, S.;
Nallu, M. Indian J. Pharm. Sci. 2005, 67, 725.
(18) Safari, J.; Khalili, S. D.; Banitaba, S. H. Synth. Commun. 2011, 41,
2359.
(19) Das Sharma, S.; Hazarika, P.; Konwar, D. Tetrahedron Lett. 2008,
49, 2216.
(20) Satyanarayana, V. S. V.; Sivakumar, A. Chem. Pap. 2011, 65, 519.
(21) Shaabani, A.; Maleki, A.; Behnam, M. Synth. Commun. 2009, 39,
102.
White solid, mp 278 °C (lit.: 274–276 °C20). 1H NMR (300 MHz):
δ = 7.22–7.57 (m, 13 H), 8.09 (d, 2 H), 12.70 (br s, 1 H) ppm. 13
C
(22) Siddiqui, S. A.; Narkhede, U. C.; Palimkar, S. S.; Daniel, T.; Lahoti,
R. J.; Srinivasan, K. V. Tetrahedron 2005, 61, 3539.
NMR (75 MHz): δ = 125.20, 126.53, 127.09, 127.79, 128.20,
128.26, 128.47, 128.69, 130.36, 131.10, 135.19, 137.12, 145.52
ppm.
2-(2-Chlorophenyl)-4,5-diphenyl-1H-imidazole (4b)
White solid, mp 197 °C (lit.: 196–198 °C32). 1H NMR (300 MHz):
δ = 7.28–7.51 (m, 10 H), 7.55 (d, 2 H), 7.61 (t, 1 H), 7.81 (t, 1 H),
12.65 (b rs, 1 H) ppm. 13C NMR (75 MHz): δ = 126.51, 127.13,
127.68, 127.99, 128.15, 128.62, 130.01, 130.15, 130.87, 131.48,
(23) (a) Wolkenberg, S. E.; Wisnoski, D. D.; Leister, W. H.; Wang, Y.;
Zhao, Z.; Lindsley, C. W. Org. Lett. 2004, 6, 1453. (b) Bogevig, A.;
Kumaragurubaran, N.; Juhl, K.; Zhuang, W.; Jørgensen, K. A.
Angew. Chem. Int. Ed. 2002, 41, 1790. (c) Usyatinsky, A. Y.;
Khmelnitsky, Y. L. Tetrahedron Lett. 2000, 41, 5031.
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131.55, 135.08, 136.86, 143.35 ppm.
126.25, 127.00, 127.58, 128.24, 128.68, 128.92, 129.14, 129.43,
130.03, 130.11, 130.78, 131.61, 135.72, 137.54, 138.31, 146.11
ppm.
4,5-Diphenyl-2-(4-methylphenyl)-1H-imidazole (4i)
White solid, mp 239 °C (lit.: 230–233 °C18). 1H NMR (300 MHz):
δ = 2.35 (s, 3 H), 7.22 (t, 1 H), 7.29 (t, 4 H), 7.37 (t, 1 H), 7.44 (t, 2
H), 7.50 (d, 2 H), 7.56 (d, 2 H), 7.98 (d, 2 H), 12.60 (br s, 1 H)
ppm. 13C NMR (75 MHz): δ = 21.40, 125.67, 126.95, 127.56,
128.20, 128.43, 128.66, 128.91, 129.13, 129.74, 131.66, 135.76,
137.42, 138.16, 146.16 ppm.
4,5-Diphenyl-2-(3-methoxyphenyl)-1H-imidazole (4k)
White solid, mp 266 °C (lit.: 259–262 °C18). 1H NMR (300 MHz):
δ = 3.84 (s, 3 H), 6.95 (d, 1 H), 7.26–7.57 (m, 11 H), 7.68–7.71
(m, 2 H), 12.70 (br s, 1 H) ppm. 13C NMR (300 MHz): δ = 55.72,
110.7, 114.72, 118.13, 127.02, 127.57, 128.31, 128.69, 128.99,
129.16, 130.0, 130.11, 130.31, 131.59, 132.15, 135.64, 136.04,
137.58, 145.86, 160.06 ppm.
4,5-Diphenyl.2-(4-methoxyphenyl)-1H-imidazole (4l)
White solid, mp 228.5 °C (lit.: 228–231 °C18). 1H NMR (300
MHz): δ = 3.82 (s, 3 H), 7.05 (d, 2 H), 7.21 (t, 1 H), 7.29 (t, 2 H),
7.36 (t, 1 H), 7.44 (t, 2 H), 7.50 (d, 2 H), 7.55 (d, 2 H), 7.79 (s, 2
H), 8.03 (d, 2 H), 12.51 (br s, 1 H) ppm. 13C NMR (75 MHz): δ =
55.21, 114.09, 123.14, 126.39, 126.69, 127.04, 127.60, 128.14,
128.35, 128.62, 131.24, 135.33, 136.76, 145.62, 159.41 ppm.
4-(4,5-Diphenyl-1H-imidazol-2-yl)-phenol (4m)
2-(4-Chlorophenyl)-4,5-diphenyl-1H-imidazole (4c)
White solid, mp 264 °C (lit.: 261–262 °C19). 1H NMR (300 MHz):
δ = 7.23–7.56 (m, 12 H), 8.11 (d, 2 H), 12.79 (br s, 1 H) ppm. 13
C
NMR (75 MHz): δ = 126.56, 126.80, 127.03, 127.83, 128.16,
128.39, 128.63, 128.73, 129.17, 130.89, 132.71, 134.97, 137.27,
144.38 ppm.
2-(3-Bromophenyl)-4,5-diphenyl-1H-imidazole (4d)
White solid, mp 306 °C (lit.: 301–303 °C18). 1H NMR (300 MHz):
δ = 7.24–7.57 (m, 13 H), 8.10 (d, 1 H), 8.32 (s, 1 H), 12.84 (br s, 1
H) ppm. 13C NMR (75 MHz): δ = 121.93, 123.81, 126,49, 126,89,
127.29, 127.71, 128.01, 128.17, 128.45, 130.57, 130.72, 132.27,
134.68, 137.19, 143.64 ppm.
2-(4-Bromophenyl)-4,5-diphenyl-1H-imidazole (4e)
White solid, mp 260 °C (lit.: 252–254 °C16) ppm. 1H NMR (300
MHz): δ = 7.21–7.53 (m, 10 H), 7.68 (d, 2 H), 8.05 (d, 2 H), 12.83
(br s, 1 H) ppm. 13C NMR (75 MHz): δ = 121.90, 126.63, 126.98,
127.62, 127.97, 128.19, 128.69, 129.10, 129.52, 129.71, 130.06,
132.18, 144.99 ppm.
2-(2-Fluorophenyl)-4,5-diphenyl-1H-imidazole (4f)
White solid, mp 208 °C (lit.: 205.5–206 °C33). 1H NMR (300
MHz): δ = 7.23–7.55 (m, 13 H), 8.00 (t, 1 H), 12.56 (br s, 1 H)
ppm. 13C NMR (75 MHz): δ = 116.66, 116.82, 119.21, 125.18,
125.21, 127.08, 127.69, 128.33, 128.69, 129.04, 130.14, 130.91,
131.37, 135.49, 137.71, 141.34, 158.35, 160.33 ppm.
4,5-Diphenyl-2-(2-methylphenyl)-1H-imidazole (4g)
Light-yellow solid, mp 214 °C (lit.: 215 °C34). 1H NMR (300
MHz): δ = 6.94–7.01 (m, 2 H), 7.28 (t, 2 H), 7.30–7.49 (m, 5 H),
7.54 (d, 4 H), 8.06 (d, 1 H), 13.02 (br s, 1 H). 13C NMR (75 MHz):
δ = 112.88, 116.82, 118.84, 124.94, 128.62, 130.06, 145.87,
156.70 ppm.
White solid, mp 253 °C (lit.: 252 °C33). H NMR (300 MHz): δ =
1
2.65 (s, 3 H), 7.21 (t, 1 H), 7.29–7.37 (m, 6 H), 7.43 (t, 2 H), 7.52
(d, 2 H), 7.56 (d, 2 H), 7.72 (t, 1 H), 12.49 (br s, 1 H) ppm. 13C
NMR (75 MHz): δ = 21.63, 126.21, 126.88, 127.52, 127.96,
128.12, 128.67, 128.72, 128.84, 129.13, 129.21, 130.49, 131.59,
135.89, 136.77, 137.11, 146.61 ppm.
4,5-Diphenyl-2-(3-methylphenyl)-1H-imidazole (4h)
White solid, mp 299 °C (lit.: 296–298 °C20). 1H NMR (300 MHz):
δ = 2.39 (s, 3 H), 7.20–7.55 (m, 12 H), 7.88 (d, 1 H), 7.94 (s, 1 H),
12.64 (br s, 1 H) ppm. 13C NMR (75 MHz): δ = 21.62, 122.88,
(32) Shaterian, H. R.; Ranjbar, M. J. Mol. Liq. 2011, 160, 40.
(33) E. I. du Pont de Nemours and Co. Belgian Patent BE 635804,
1963; Chem. Abstr.; 1965, 63: 1795
(34) Jayabharathi, J.; Thanikachalam, V.; Srinivasan, N.; Jayamorthy,
K.; Perumal, M. V. J. Fluoresc. 2011, 21, 1813.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–E