Silver-mediated Cα(sp3)-H functionalization of primary amines: An oxidative C-N coupling strategy for the synthesis of two different types of 1,2,4,5-tetrasubstituted imidazoles

Article abstract of DOI:10.1002/ejoc.201403465

A new silver(I)-mediated Cα(sp³)-H bond functionalization of primary amines and subsequent oxidative C-N cross-coupling reaction has been demonstrated. This protocol provides a simple, highly efficient, and straightforward approach to form significantly diverse 1,2,4,5-tetrasubstituted imidazoles. In this course of the reaction, a stoichiometric amount of Ag₂CO₃ was employed. Upon completion of reaction, the silver species was successfully recycled and reused without any loss of activity. Good to excellent yields of the products were readily achieved by using this selective oxidative C-N coupling, which was promoted by a crucial silver(I) salt.

Full text of DOI:10.1002/ejoc.201403465

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FULL PAPER
DOI: 10.1002/ejoc.201403465
Silver-Mediated Cα(sp3)–H Functionalization of Primary Amines: An
Oxidative C–N Coupling Strategy for the Synthesis of Two Different Types of
1,2,4,5-Tetrasubstituted Imidazoles
Rajib Sarkar[a] and Chhanda Mukhopadhyay*[a]
Keywords: Nitrogen heterocycles / C–H activation / Cross-coupling / Cyclization / Silver / Amines
A new silver(I)-mediated Cα(sp3)–H bond functionalization of
primary amines and subsequent oxidative C–N cross-cou-
pling reaction has been demonstrated. This protocol provides
a simple, highly efficient, and straightforward approach to
form significantly diverse 1,2,4,5-tetrasubstituted imidazoles.
In this course of the reaction, a stoichiometric amount of
Ag2CO3 was employed. Upon completion of reaction, the sil-
ver species was successfully recycled and reused without any
loss of activity. Good to excellent yields of the products were
readily achieved by using this selective oxidative C–N cou-
pling, which was promoted by a crucial silver(I) salt.
slight preference for sigma over pi coordination.[8] These
features distinguish silver(I) species as a good class of cata-
lysts for the development of autotandem catalysis that in-
volves the dual activation of C–H and unsaturated C–C
bonds. Very recently, a number of silver-mediated oxidative
coupling transformations to form C–C and C–N bonds
were investigated by Lei et al., in which the efficiency of
silver(I) towards the oxidative coupling transformation of
terminal alkynes was remarkably notable.[7,9] However,
these early studies revealed the relative ease of C(sp)–H
bond functionalizations by using silver species to form di-
rect C–C or C–N bonds (see Scheme 1). So, in the field of
oxidative cross-coupling research, silver(I)-induced C(sp3)–
H bond functionalization to form a new C–C or C–N bond
is still very challenging and not easily investigated.
Introduction
A selective and efficient synthetic method for the prepa-
ration of the widely distributed and biologically significant
molecule imidazole has been a continuous objective in the
field of synthetic organic chemistry.[1] Imidazoles are an im-
portant class of nitrogen-containing five-membered hetero-
cycles and are the core structures of many natural products
and various biologically active molecules, such as histidine,
histamine, and biotin.[2] Compounds that contain an imid-
azole moiety also have many pharmacological properties
and play important roles in biochemical processes.[3] Al-
though a number of synthetic methods have been reported
in the literature,[4] straightforward and regioselective routes
for the construction of this potent molecule are still highly
attractive.
On the basis of the known capabilities of silver(I), we
designed the direct oxidative construction of 1,2,4,5-tetra-
substituted imidazoles by activating the Cα(sp3)–H of pri-
mary amines and subsequently carrying out an oxidative
C–N cross-coupling reaction. However, the Cα(sp3)–H bond
functionalization of primary amines is quite difficult and
has many challenges. A few examples of Cα(sp3)–H bond
functionalization of amines followed by an oxidative cycli-
zation have been previously investigated by employing com-
mon transition-metal catalysts such as CuI or NiII.[10] How-
ever, in the first case, the CuI was utilized for the Cα(sp3)–
H bond functionalization of benzylamines to form 2,4,5-
trisubstituted oxazole derivatives only. In the later case, the
formation of imidazoles required a high temperature for a
long period of time. Furthermore, in both reactions, the
activity of the catalyst was limited, as there was only one
type of primary amine in the reaction, and the simultaneous
use of two different types of primary amines in the reaction
was not investigated. Thus, these reactions very much lack
the versatility for the scope of this reaction.
In the last few decades, the functionalization of carbon-
hydrogen bonds by employing oxidative coupling transfor-
mations to form new carbon–carbon and carbon–hetero-
atom (N, O, and S) bonds has been thoroughly examined.[5]
In this emerging field, a significant development was at-
tained by using various transition-metal catalysts for the
metalation of C–H bonds.[6] Compared to the traditional
transition-metal-catalyzed coupling reactions, a silver(I)-
mediated oxidative coupling between two different carbon-
hydrogen or heteroatom-hydrogen bonds has the inherent
advantage of avoiding the prefunctionalization of the sub-
strates.[7] More interestingly, silver(I) species exhibit both
carbophilic and oxophilic Lewis acid characteristics, with a
[a] Department of Chemistry, University of Calcutta,
92 APC Road, Kolkata 700009, India
E-mail: cmukhop@yahoo.co.in
http://www.caluniv.ac.in/academic/chemistry.html
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201403465.
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R. Sarkar, C. Mukhopadhyay
FULL PAPER
Scheme 1. Silver-mediated C–H bond functionalizations followed by oxidative cyclization (DMF = N,N-dimethylformamide).
As part of our continuous efforts on silver-induced oxi- Table 1. Optimization of the reaction conditions for the formation
of 1-benzyl-2,4,5-triphenyl-1H-imidazole (2a).
dative cross-coupling transformations, we herein present the
silver(I)-mediated Cα(sp3)–H bond functionalization of pri-
mary amines and subsequent oxidative C–N coupling trans-
formation to form two different types of highly diverse
1,2,4,5-tetrasubstituted imidazoles. These reactions are car-
ried out at moderate temperatures as well as in a short
period of time. Although a stoichiometric amount of
Ag2CO3 was employed, the silver species was successfully
recycled after the reaction for the next Cα(sp3)–H bond
Entry Temp. [°C] [Ag] [equiv.]
Solvent
% Yield[a]
functionalization and oxidative cyclization.
1
80
80
80
80
80
80
80
80
80
80
80
80
45
25
AgOAc (2)
AgNO2 (2)
AgNO3 (2)
AgClO4 (2)
AgI (2)
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
DMF
28
–
–
2
3
4
Results and Discussion
12
18
35
45
32
53
15
88
40
55
30
5
6
To synthesize 1,2,4,5-tetrasubstituted imidazoles by oxi-
dative cross-coupling transformations, we first chose the re-
action between benzil (1aa, 1 mmol) and benzylamine (1ba,
2 mmol) to form 1-benzyl-2,4,5-triphenyl-1H-imidazole
(2a). Initially, a number of probable transition-metal salts,
including those with FeIII, AuIII, or PtII, were investigated
under different reaction conditions, but we did not reach
our desired goal. On the basis of the known ability of silver
Ag2O (2)
7
8
9
10
11
12
13
14
Ag2CO3 (2)
Ag2CO3 (2)
Ag2CO3 (2)
Ag2CO3 (2)
Ag2CO3 (2)
Ag2CO3 (1)
Ag2CO3 (2)
Ag2CO3 (2)
DMSO[b]
toluene
DCE[b]
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
carbonate towards oxidative coupling, we proposed that it [a] Isolated yield. [b] DMSO = dimethyl sulfoxide, DCE = 1,2-
dichloroethane.
might be the appropriate catalyst for this oxidative cross-
coupling transformation. Interestingly, we found that the
employment of silver carbonate (2.0 equiv.) in 1,4-dioxane efficient, straightforward approach to the 1,2,4,5-tetrasub-
(5 mL) at 80 °C effectively catalyzed the formation of 1- stituted imidazoles encouraged us to further examine the
benzyl-2,4,5-triphenyl-1H-imidazole (2a) in excellent yield. feasibility of this oxidative protocol towards an efficient
We also observed that the use of any additives such as imidazole synthesis. We studied the scope of the reaction
KOAc, NaOAc, K2CO3, Cs2CO3, 1,8-diazabicyclo[5.4.0]un- by using various electron-rich as well as electron-deficient
dec-7-ene (DBU), or HOAc along with the silver carbonate benzylamines with different 1,2-diketones, and, as a result,
did not increase the yield of the reaction, and 1.0 equiv. of we prepared a number of 1,2,4,5-tetrasubstituted imid-
Ag2CO3 only afforded a 40% yield of the isolated product azoles 2a–2u (see Table 2). In all of the reactions, the prod-
(see Table 1, Entry 12). Further research was carried out in uct yields were quite satisfactory.
various solvents to determine how the catalytic activity of
different silver salts compared to Ag2CO3 (see Table 1).
In continuation of our work, we performed two different
crossover oxidative coupling reactions to study the elec-
Hence, Ag2CO3 (2.0 equiv.) in 1,4-dioxane at 80 °C for tronic effects on the reaction course (see Schemes 2 and 3).
10 h was best in terms of both the Cα(sp3)–H functionaliza- First, we studied the reaction of benzil with the combina-
tion of the primary amine and the oxidative cyclization to tion of an unsubstituted benzylamine and the activated 3,4-
afford the desired compound 2a in good yield within a short dimethoxybenzylamine, which afforded 2b (28% yield) and
time (see Table 1, Entry 11). This unanticipated and highly 3b (27% yield) as the major products, each with a 3,4-di-
2
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Oxidative C–N Coupling Strategy for the Synthesis of Imidazoles
Table 2. Library synthesis of of 1,2,4,5-tetrasubstituted imidazoles methoxybenzyl group at C-2 (see Scheme 2). On the other
2a–2u.[a]
hand, the reaction of benzil with an unsubstituted benzyl-
amine and the deactivated 4-bromobenzylamine afforded 2a
(25% yield) and 4a (24% yield) as the major products, each
with a phenyl group at C-2 (see Scheme 3).
We also investigated the scope of highly deactivated
benzylamines, such as 2-nitrobenzylamine, but we did not
find evidence of the corresponding 1,2,4,5-tetrasubstituted
imidazole. The analysis of the results of the two crossover
experiments (see Schemes 2 and 3) clearly indicates that
electron-rich benzylamines are better suited for the forma-
tion of intermediates II and III than electron-deficient ones
(see Scheme 4). After the successful study of the reaction
between 1,2-diketones (1 mmol) and primary amines with
the –CH2–NH2 group (2 mmol) to form 1,2,4,5-tetrasubsti-
tuted imidazoles, we investigated the reaction between a
1,2-diketone and a primary amine that contained a –CH2–
NH2 group in the presence of a another primary amine that
did not contain the –CH2–NH2 group to form other highly
diverse 1,2,4,5-tetrasubstituted imidazoles. Interestingly, the
reaction furnished the corresponding 1,2,4,5-tetrasubsti-
tuted imidazoles 5a–5p (see Table 3) in good yields under
the given optimized reaction conditions.
All of the synthesized 1,2,4,5-tetrasubstituted imidazoles
were characterized by spectral and analytical methods. Fi-
nally, we confirmed the structures of the imidazole deriva-
tives by using the single-crystal X-ray diffraction study of
the two representative compounds 2j and 5d (see Figure 1).
A plausible reaction mechanism was proposed for this
silver-mediated Cα(sp3)–H functionalization of primary
amines and the subsequent cyclization to form 1,2,4,5-tetra-
substituted imidazoles through an oxidative cross-coupling
transformation (see Scheme 4).[7,11] First, the reaction be-
tween the 1,2-diketone and a primary amine gives addition
product I. Next, the C(sp3)–H functionalization by Ag2CO3
leads to the formation of intermediate II, and the subse-
quent addition of another primary amine converts II into
intermediate III, which is possibly stabilized by the sur-
rounding AgI species.[12] Finally, the silver-mediated oxidat-
ive cyclization of III furnishes the desired product IV (i.e.,
2a–2u and 5a–5p) through two single-electron oxidations.
To realize the reaction mechanism of this silver-mediated
Cα(sp3)–H functionalization of primary amines and subse-
quent cyclization to form 1,2,4,5-tetrasubstituted imid-
azoles, we performed one typical experiment with 9,10-
phenanthraquinone (1ab) and 4-bromobenzylamine (1bb,
[a] Percentage yield provided for each structure.
see Scheme 5). Initially, we mixed 1 equiv. of 9,10-phen-
Scheme 2. Crossover experiment involving benzil, benzylamine, and 3,4-dimethoxybenzylamine.
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Scheme 3. Crossover experiment involving benzil, benzylamine, and 4-bromobenzylamine.
Table 3. Library synthesis of 1,2,4,5-tetrasubstituted imidazoles 5a–
5p.[a]
Scheme 4. Mechanism of the formation of 1,2,4,5-tetrasubstituted
imidazoles 2a–2u and 5a–5p.
anthraquinone (1ab, 1 mmol) with 1 equiv. 4-bromobenz-
ylamine (1bb, 1 mmol) in 1,4-dioxane (5 mL) at room tem-
1
perature (25 °C) and monitored the reaction by H NMR
spectroscopic analysis. Primarily, the 1H NMR spectrum (in
[D6]DMSO) of the reaction mixture showed only the pres-
ence of starting materials. Therefore, we added 2 equiv. of
Ag2CO3 to the reaction and stirred the mixture for up to
3 h at room temperature. At this stage, we recorded another
1H NMR spectrum (in [D6]DMSO) of the reaction mixture,
which showed the formation of intermediate A. Later, inter-
mediate A was converted in situ into intermediate B. The
reaction mixture was stirred for an additional 2 h at room
1
temperature. When the H NMR spectrum of the reaction
mixture was finally recorded, no signal was observed. This
result might indicate the formation of insoluble complex B.
Thereafter, the reaction mixture was equally divided into
three parts, and each part was studied differently under dif-
ferent reaction conditions (see Scheme S1). First a portion
was heated at 80 °C for 8 h, which afforded only 2-(4-
bromophenyl)phenanthro[9,10-d]oxazole (6a) as the prod-
uct. The second portion was hydrolyzed with water, which
mainly gave the two products 4-bromobenzaldehyde (6b)[13]
[a] Percentage yield provided for each structure.
1
and 9,10-phenanthraquinone (1ab).[14] Finally, 4-bromo- imidazole (2p) as the only product. The results of the H
benzylamine (1bb, 0.5 mmol) was added to the third por- NMR study as well as the formation of 2p, 6a, 6b, and 1ab
tion, which was then heated at 80 °C for 8 h to give 1-(4- supported the probable formation of complex A followed
bromobenzyl)-2-(4-bromophenyl)-1H-phenanthro[9,10-d]- by the formation of complex B in the reaction medium.
4
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Oxidative C–N Coupling Strategy for the Synthesis of Imidazoles
Scheme 6. Reaction with recycled Ag2CO3.
Conclusions
In summary, this study led us to discover the ability of
silver(I) species to mediate the Cα(sp3)-H functionalization
of primary amines followed by an oxidative C–N coupling/
cyclization to form two different types of highly diverse
1,2,4,5-tetrasubstituted imidazoles. Furthermore, AgI selec-
tively formed one highly diverse 1,2,4,5-tetrasubstituted
Figure 1. X-ray structures of 2j and 5d.
These studies definitely help to understand the reaction imidazole when a mixture of primary amines was used in
mechanism of this silver(I)-mediated oxidative C–N cou- the reaction course. In this oxidative coupling protocol, we
pling/cyclization.
have efficiently utilized aliphatic amines and both electron-
After the reaction, the silver species was successfully rich as well as electron-deficient benzylamines, including
recycled[9a] and then reused in the reaction of benzil and heteroaromatic benzylamines, with various 1,2-diketones.
benzylamine under the standard reaction conditions. The Hence, the coupling reaction reported herein represents a
comparable yield of this reaction (85%) with that obtained highly efficient, straightforward approach that is promoted
by the same reaction with fresh Ag2CO3 demonstrates the by a crucial silver(I) species for the formation of 1,2,4,5-
retention of the activity of the silver species after being re- tetrasubstituted imidazoles. Good to excellent yields of the
cycled (see Scheme 6).
products were achieved with this protocol.
Scheme 5. Extended experiments with 9,10-phenanthraquinone (1ab) and 4-bromobenzylamine (1bb).
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80 °C)]. 1H NMR (300 MHz, CDCl3): δ = 8.78 (d, J = 7.5 Hz, 1
H, ArH), 8.66 (d, J = 8.1 Hz, 1 H, ArH), 8.57 (d, J = 8.1 Hz, 1 H,
ArH), 7.82 (d, J = 7.8 Hz, 1 H, ArH), 7.62–7.50 (m, 4 H, ArH),
7.42–7.07 (m, 10 H, ArH), 5.68 (s, 2 H, CH2) ppm. 13C NMR
(75 MHz, CDCl3): δ = 153.0, 137.9, 137.0, 130.4, 129.6, 129.3,
129.2, 128.7, 128.2, 127.8, 127.3, 127.2, 127.0, 126.6, 125.6, 124.8,
Experimental Section
General Methods: The 1H and 13C spectroscopic data were recorded
with a Bruker 300 MHz instrument at 300 and 75 MHz, respec-
tively. Chemical shifts are reported in parts per million (ppm)
downfield from TMS (tetramethylsilane) as the internal reference.
Coupling constants (J) are reported in Hertz (Hz), and the spin
multiplicities are reported as s (singlet), br. s (broad singlet), d
(doublet), t (triplet), q (quartet), and m (multiplet). IR spectra were
recorded on a Perkin–Elmer Spectrophotometer RX/FT-IR sys-
tem. The positions of the bands are reported in reciprocal centime-
ters (cm–1). The CHN analyses were carried out on a 2400 Series
II CHNS Analyzer, Perkin–Elmer USA. X-ray diffraction was done
on a Bruker SMART diffractometer that was equipped with a
graphite monochromator and Mo-Kα (λ = 0.71073 Å) radiation.
Melting points were measured by using an open capillary tube in
an electric melting point apparatus. The progress of the reaction
was monitored by TLC analysis using silica gel (300–400 mesh).
Column chromatography was performed with silica gel (60–
120 mesh). HRMS analysis of the compounds were performed by
the electron spray ionization (ESI) technique at 25–70 eV in a
Micromass Q-tof-Micro Quadruple mass spectrometer at The In-
dian Association for the Cultivation of Science, Jadavpur, Kolkata
700032, India. All the available reagents were purchased from com-
mercial sources and used without purification. The solvents that
were used for the reactions were distilled for purity.
124.2, 123.0, 122.9, 122.7, 121.0, 50.7 ppm. IR (KBr): ν = 1604,
˜
1498, 1456, 1473, 1357, 773, 753, 736, 720, 696 cm–1. C28H20N2
(384.48): calcd. C 87.47, H 5.24, N 7.29; found C 87.39, H 5.20, N
7.25.
1-(4-Chlorobenzyl)-2-(4-chlorophenyl)-4,5-diphenyl-1H-imidazole
(2d): (see Table 2, Entry 4). White solid (81 % yield); m.p. 158–
160 °C. Rf = 0.40 [10 % EtOAc/petroleum ether (60–80 °C)]. 1H
NMR (300 MHz, CDCl3): δ = 7.57–7.51 (m, 4 H, ArH), 7.37–7.24
(m, 5 H, ArH), 7.20–7.09 (m, 7 H, ArH), 6.67 (d, J = 8.4 Hz, 2 H,
ArH), 5.00 (s, 2 H, CH2) ppm. 13C NMR (75 MHz, CDCl3): δ =
146.8, 138.4, 135.7, 135.1, 134.2, 133.4, 130.9, 130.6, 130.3, 130.1,
129.3, 129.0, 128.9, 128.1, 127.3, 126.8, 126.6, 47.7 ppm. IR (KBr):
ν = 2362, 1482, 1093, 1013, 829, 764, 731, 696 cm–1. C H Cl N
˜
28 20
2
2
(455.39): calcd. C 73.85, H 4.43, N 6.15; found C 73.78, H 4.39, N
6.12.
2-(Naphthalen-1-yl)-1-[(naphthalen-1-yl)methyl]-4,5-diphenyl-1H-
imidazole (2e): (see Table 2, Entry 5). White solid (85% yield); m.p.
218–222 °C. Rf = 0.43 [12% EtOAc/petroleum ether (60–80 °C)].
1H NMR (300 MHz, CDCl3): δ = 8.13 (d, J = 7.2 Hz, 1 H, ArH),
7.82–7.74 (m, 5 H, ArH), 7.67–7.51 (m, 4 H, ArH), 7.44–7.21 (m,
13 H, ArH), 6.89 (d, J = 7.2 Hz, 1 H, ArH), 5.41 (s, 2 H,
CH2) ppm. 13C NMR (75 MHz, CDCl3): δ = 146.8, 138.1, 134.6,
133.6, 133.1, 132.8, 132.7, 131.0, 130.8, 129.8, 129.7, 128.8, 128.5,
128.2, 128.1, 127.8, 126.8, 126.4, 126.0, 126.0, 125.5, 125.1, 124. 8,
General Synthesis of 1,2,4,5-Tetrasubstituted Imidazoles 2a–2u: A
mixture of the 1,2-diketone (1 mmol), the primary amine that con-
tained
a –CH2–NH2 group (2 mmol), and silver carbonate
(2.0 equiv.) in 1,4-dioxane (5 mL) was stirred at 80 °C for 10 h. The
progress of the reaction was monitored by TLC. Upon completion
of the reaction, the solid was removed by filtration and washed
with dichloromethane. The solvent of the filtrate was then removed
under vacuum, and the resulting crude product was purified by
column chromatography over silica gel [60–120 mesh; ethyl acetate/
petroleum ether (60–80 °C)]. No further purification was needed.
123.8, 121.8, 46.1 ppm. IR (KBr): ν = 1599, 1500, 1442, 1401, 953,
˜
780, 782, 699 cm–1. HRMS (ESI-TOF): calcd. for C36H26N2 [M +
H]+ 487.2174; found 487.2167. C36H26N2 (486.61): calcd. C 88.86,
H 5.39, N 5.76; found C 88.77, H 5.36, N 5.71.
1-(4-Methylbenzyl)-2-p-tolyl-1H-phenanthro[9,10-d]imidazole (2f):
(see Table 2, Entry 6). White solid (88% yield), m.p. 226–228 °C;
ref.[10b] m.p. 226–230 °C. Rf = 0.46 [12% EtOAc/petroleum ether
1-Benzyl-2,4,5-triphenyl-1H-imidazole (2a): (see Table 2, Entry 1).
White solid (88% yield), m.p. 162–164 °C; ref.[10b] m.p. 160–
164 °C). Rf = 0.48 [12% EtOAc/petroleum ether (60–80 °C)]. 1H
NMR (300 MHz, CDCl3): δ = 7.58–7.50 (m, 4 H, ArH), 7.37–7.05
(m, 14 H, ArH), 6.74–6.72 (m, 2 H, ArH), 5.04 (s, 2 H, CH2) ppm.
13C NMR (75 MHz, CDCl3): δ = 147.9, 137.9, 137.3, 134.3, 130.9,
130.8, 129.9, 128.8, 128.7, 128.6, 128.4, 127.9, 127.1, 126.6, 126.2,
1
(60–80 °C)]. H NMR (300 MHz, CDCl3): δ = 8.86 (d, J = 7.8 Hz,
1 H, ArH), 8.75 (d, J = 8.1 Hz, 1 H, ArH), 8.66 (d, J = 8.1 Hz, 1
H, ArH), 7.94 (d, J = 8.1 Hz, 1 H, ArH), 7.70 (t, J = 6.9 Hz, 1 H,
ArH), 7.63–7.55 (m, 3 H, ArH), 7.49 (t, J = 7.8 Hz, 1 H, ArH),
7.36 (t, J = 7.5 Hz, 1 H, ArH), 7.21 (d, J = 8.1 Hz, 2 H, ArH),
7.13 (d, J = 7.5 Hz, 2 H, ArH), 7.05 (d, J = 7.5 Hz, 2 H, ArH),
5.74 (s, 2 H, CH2), 2.37 (s, 3 H, CH3), 2.31 (s, 3 H, CH3) ppm. 13
C
125.8, 48.1 ppm. IR (KBr): ν = 3051, 1603, 1498, 1445, 1027,
˜
758 cm–1. C28H22N2 (386.50): calcd. C 87.01, H 5.74, N 7.25; found
C 86.93, H 5.69, N 7.20.
NMR (75 MHz, CDCl3): δ = 153.2, 139.6, 137.9, 137.4, 134.0,
130.0, 129.5, 129.4, 129.1, 128.2, 127.6, 127.4, 127.2, 127.0, 126.6,
125.6, 125.5, 124.6, 124.1, 123.0, 122.7, 121.1, 50.5, 21.4, 21.0 ppm.
1-(3,4-Dimethoxybenzyl)-2-(3,4-dimethoxyphenyl)-4,5-diphenyl-1H-
imidazole (2b): (see Table 2, Entry 2). Yellow solid (92% yield); m.p.
140–142 °C. Rf = 0.53 [40% EtOAc/petroleum ether (60–80 °C)].
1H NMR (300 MHz, CDCl3): δ = 7.68 (br. s, 2 H, ArH), 7.60–7.15
(m, 10 H, ArH), 6.80–6.68 (m, 2 H, ArH), 6.35–6.27 (m, 2 H, ArH),
5.00 (s, 2 H, CH2), 3.78 (s, 3 H, OCH3), 3.73 (s, 3 H, OCH3), 3.67
(s, 3 H, OCH3), 3.62 (s, 3 H, OCH3) ppm. 13C NMR (75 MHz,
CDCl3): δ = 149.1, 148.5, 148.3, 147.7, 147.4, 137.2, 133.9, 130.5,
129.6, 129.3, 128.3, 128.1, 127.5, 126.3, 125.8, 122.9, 121.0, 118.1,
IR (KBr): ν = 2346, 1516, 1476, 824, 754, 720 cm–1. C30H24N2
˜
(412.53): calcd. C 87.35, H 5.86, N 6.79; found C 87.27, H 5.80, N
6.72.
1-Benzyl-4,5-dimethyl-2-phenyl-1H-imidazole (2 g): (see Table 2,
Entry 7). Light brown solid (71% yield); m.p. 148–150 °C. Rf =
0.58 [10 % EtOAc/petroleum ether (60–80 °C)]. 1H NMR
(300 MHz, CDCl3): δ = 7.42–7.39 (m, 2 H, ArH), 7.27–7.21 (m, 6
H, ArH), 6.92 (d, J = 7.5 Hz, 2 H, ArH), 5.05 (s, 2 H, CH2), 2.18 (s,
3 H, CH3), 1.94 (s, 3 H, CH3) ppm. 13C NMR (75 MHz, CDCl3): δ
= 146.4, 137.2, 133.7, 131.0, 128.8, 128.4, 128.3, 128.2, 127.4, 125.5,
117.9, 111.9, 110.8, 109.0, 55.2, 55.1, 55.1, 47.2 ppm. IR (KBr): ν
˜
= 2371, 1608, 1508, 1498, 1495, 1252, 1233, 1025, 765, 699 cm–1.
C32H30N2O4 (506.60): calcd. C 75.87, H 5.97, N 5.53; found C
75.80, H 5.94, N 5.46.
123.8, 47.9, 12.7, 8.9 ppm. IR (KBr): ν = 3051, 2882, 2438, 1502,
˜
1471, 1344, 11215, 859, 672 cm–1. C18H18N2 (262.35): calcd. C
82.41, H 6.92, N 10.68; found C 82.34, H 6.85, N 10.65.
1-Benzyl-2-phenyl-1H-phenanthro[9,10-d]imidazole (2c): (see
Table 2, Entry 3). White solid (85% yield), m.p. 240–242 °C; ref.[10b]
4,5-Bis(4-bromophenyl)-1-(3,4-dimethoxybenzyl)-2-(3,4-dimeth-
m.p. 238–242 °C. Rf = 0.45 [12 % EtOAc/petroleum ether (60– oxyphenyl)-1H-imidazole (2h): (see Table 2, Entry 8). Yellow
6
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Job/Unit: O43465
/KAP1
Date: 07-01-15 18:27:26
Pages: 12
Oxidative C–N Coupling Strategy for the Synthesis of Imidazoles
gummy solid (87% yield). Rf = 0.55 [50% EtOAc/petroleum ether
(60–80 °C)]. H NMR (300 MHz, CDCl3): δ = 7.40 (d, J = 8.4 Hz,
OCH3), 3.73 (s, 3 H, OCH3) ppm. 13C NMR (75 MHz, CDCl3): δ
= 160.7, 159.1, 153.0, 137.8, 130.9, 129.0, 128.2, 127.4, 127.1, 126.9,
1
2 H, ArH), 7.34–7.31 (m, 2 H, ArH), 7.26–7.23 (m, 2 H, ArH), 126.8, 126.6, 125.4, 124.6, 124.1, 123.0, 122.8, 122.6, 121.0, 114.7,
7.11–7.09 (m, 2 H, ArH), 7.02–6.99 (t, J = 6.9 Hz, 1 H, ArH),
7.63–7.55 (m, 3 H, ArH), 7.49 (t, J = 7.8 Hz, 1 H, ArH), 7.36 (m,
2 H, ArH), 6.80 (d, J = 8.7 Hz, 1 H, ArH), 6.66 (d, J = 8.4 Hz, 1
H, ArH), 6.31 (d, J = 8.4 Hz, 1 H, ArH), 6.21 (br. s, 1 H, ArH),
4.93 (s, 2 H, CH2), 3.80 (s, 3 H, OCH3), 3.74 (s, 3 H, OCH3), 3.69
(s, 3 H, OCH3), 3.62 (s, 3 H, OCH3) ppm. 13C NMR (75 MHz,
CDCl3): δ = 149.8, 149.1, 148.9, 148.4, 137.1, 133.1, 132.4, 132.1,
131.1, 129.7, 128.6, 128.3, 123.1, 121.4, 120.3, 118.3, 112.2, 111.2,
114.1, 55.3, 55.2, 50.2 ppm. IR (KBr): ν = 2928, 2837, 2346, 1610,
˜
1512, 1475, 1246, 1177, 1029, 754, 722 cm–1. C30H24N2O2 (444.53):
calcd. C 81.06, H 5.44, N 6.30; found C 81.01, H 5.43, N 6.25.
1-(3,4-Dimethoxybenzyl)-2-(3,4-dimethoxyphenyl)-1H-phenanthro-
[9,10-d]imidazole (2m): (see Table 2, Entry 13). Light yellow solid
(91% yield); m.p. 200–202 °C. Rf = 0.58 [50% EtOAc/petroleum
1
ether (60–80 °C)]. H NMR (300 MHz, CDCl3): δ = 8.87 (d, J =
7.8 Hz, 1 H, ArH), 8.79 (d, J = 8.1 Hz, 1 H, ArH), 8.70 (d, J =
8.1 Hz, 1 H, ArH), 7.96 (d, J = 8.1 Hz, 1 H, ArH), 7.73 (t, J =
7.8 Hz, 1 H, ArH), 7.64 (t, J = 7.5 Hz, 1 H, ArH), 7.54 (t, J =
6.9 Hz, 1 H, ArH), 7.41 (t, J = 7.2 Hz, 1 H, ArH), 7.30–7.26 (m,
2 H, ArH), 6.91 (d, J = 8.1 Hz, 1 H, ArH), 6.84–6.74 (m, 3 H,
ArH), 5.73 (s, 2 H, CH2), 3.91 (s, 3 H, OCH3), 3.85 (s, 3 H, OCH3),
3.77 (s, 3 H, OCH3), 3.68 (s, 3 H, OCH3) ppm. 13C NMR (75 MHz,
CDCl3): δ = 153.0, 150.3, 149.8, 148.9, 148.6, 129.6, 129.1, 128.2,
127.2, 126.7, 125.5, 124.7, 124.2, 123.0, 122.9, 122.7, 122.2, 121.0,
118.0, 112.5, 111.8, 111.2, 108.6, 55.9, 55.9, 55.6, 50.6 ppm. IR
111.0, 109.2, 55.8, 55.7, 48.0 ppm. IR (KBr): ν = 2343, 1612, 1527,
˜
1480, 1455, 1192, 1033, 825, 761 cm–1. C32H28Br2N2O4 (664.39):
calcd. C 57.85, H 4.25, N 4.22; found C 57.79, H 4.18, N 4.20.
1-(4-Bromobenzyl)-2-(4-bromophenyl)-4,5-diphenyl-1H-imidazole
(2i): (see Table 2, Entry 9). Off-white solid (78% yield); m.p. 128–
130 °C. Rf = 0.45 [12 % EtOAc/petroleum ether (60–80 °C)]. 1H
NMR (300 MHz, CDCl3): δ = 7.55 (d, J = 7.5 Hz, 2 H, ArH),
7.47–7.37 (m, 5 H, ArH), 7.34–7.27 (m, 5 H, ArH), 7.22–7.08 (m,
4 H, ArH), 6.59 (d, J = 8.4 Hz, 2 H, ArH), 4.96 (s, 2 H, CH2) ppm.
13C NMR (75 MHz, CDCl3): δ = 146.9, 136.3, 134.2, 131.9, 131.0,
130.6, 130.5, 130.4, 129.6, 129.1, 129.0, 128.4, 128.3, 128.1, 127.7,
(KBr): ν = 2934, 2341, 1607, 1509, 1491, 1459, 1251, 1136, 1023,
˜
757, 723 cm–1. C32H28N2O4 (504.58): calcd. C 76.17, H 5.59, N
5.55; found C 76.06, H 5.51, N 5.48.
126.9, 126.8, 123.5, 121.6, 47.8 ppm. IR (KBr): ν = 2359, 1508,
˜
1248, 1066, 838, 773, 716 cm–1. C28H20Br2N2 (544.29): calcd. C
61.79, H 3.70, N 5.15; found C 61.70, H 3.67, N 5.08.
1-Benzyl-4,5-bis(4-bromophenyl)-2-phenyl-1H-imidazole (2n): (see
Table 2, Entry 14). White solid (79 % yield), m.p. 128–130 °C;
ref.[10b] m.p. 128–131 °C. Rf = 0.39 [10% EtOAc/petroleum ether
1-(4-Methylbenzyl)-4,5-diphenyl-2-p-tolyl-1H-imidazole (2j): (see
Table 2, Entry 10). White solid (90 % yield), m.p. 132–134 °C;
ref.[10b] m.p. 132–135 °C. Rf = 0.41 [12% EtOAc/petroleum ether
1
(60–80 °C)]. H NMR (300 MHz, CDCl3): δ = 7.59–7.58 (m, 2 H,
ArH), 7.39–7.15 (m, 12 H, ArH), 6.99–6.96 (m, 2 H, ArH), 6.75–
6.74 (m, 2 H, ArH), 5.02 (s, 2 H, CH2) ppm. 13C NMR (75 MHz,
CDCl3): δ = 148.7, 137.5, 137.1, 133.2, 132.5, 132.2, 131.3, 130.5,
129.7, 129.2, 129.0, 128.8, 128.7, 128.4, 127.6, 125.9, 123.3, 120.6,
1
(60–80 °C)]. H NMR (300 MHz, CDCl3): δ = 7.59–7.52 (m, 4 H,
ArH), 7.28–7.26 (m, 3 H, ArH), 7.20–7.14 (m, 7 H, ArH), 6.97 (d,
J = 7.8 Hz, 2 H, ArH), 6.67 (d, J = 7.5 Hz, 2 H, ArH), 5.02 (s, 2
H, CH2), 2.32 (s, 3 H, CH3), 2.24 (s, 3 H, CH3) ppm. 13C NMR
(75 MHz, CDCl3): δ = 148.0, 138.6, 137.9, 136.8, 134.6, 131.1,
131.0, 129.8, 129.2, 129.1, 128.8, 128.8, 128.6, 128.4, 128.1, 127.9,
48.5 ppm. IR (KBr): ν = 2353, 1588, 1338, 1136, 801, 754 cm–1.
˜
C28H20Br2N2 (544.29): calcd. C 61.79, H 3.70, N 5.15; found C
61.76, H 3.61, N 5.04.
126.7, 126.1, 125.8, 47.9, 21.2, 20.9 ppm. IR (KBr): ν = 3023, 2940,
˜
1-(4-Chlorobenzyl)-2-(4-chlorophenyl)-1H-phenanthro[9,10-d]imid-
azole (2o): (see Table 2, Entry 15). White solid (75% yield); m.p.
258–260 °C. Rf = 0.42 [12% EtOAc/petroleum ether (60–80 °C)].
1H NMR (300 MHz, CDCl3): δ = 8.86–8.68 (m, 3 H, ArH), 7.87
(d, J = 8.1 Hz, 1 H, ArH), 7.74–7.56 (m, 6 H, ArH), 7.45–7.34 (m,
4 H, ArH), 7.13 (d, J = 6.9 Hz, 2 H, ArH), 5.76 (s, 2 H, CH2) ppm.
13C NMR (75 MHz, CDCl3): δ = 131.0, 129.8, 129.2, 127.6, 126.9,
2366, 1599, 1499, 1482, 1450, 1390, 1335, 822, 780, 703 cm–1
.
C30H26N2 (414.55): calcd. C 86.92, H 6.32, N 6.76; found C 86.83,
H 6.25, N 6.73.
2-(Furan-2-yl)-1-[(furan-2-yl)methyl]-1H-phenanthro[9,10-d]imid-
azole (2k): (see Table 2, Entry 11). Brown solid (81% yield); m.p.
102–104 °C. Rf = 0.52 [15% EtOAc/petroleum ether (60–80 °C)].
1H NMR (300 MHz, CDCl3): δ = 8.74–8.67 (m, 2 H, ArH), 8.57
(d, J = 8.1 Hz, 1 H, ArH), 8.08 (d, J = 6.9 Hz, 1 H, ArH), 7.64–
7.37 (m, 6 H, ArH), 6.93–6.92 (m, 1 H, ArH), 6.50 (br. s, 1 H,
ArH), 6.23 (br. s, 1 H, ArH), 6.06 (br. s, 1 H, ArH), 5.87 (s, 2 H,
CH2) ppm. 13C NMR (75 MHz, CDCl3): δ = 149.7, 144.7, 143.9,
143.3, 142.6, 138.0, 129.4, 128.3, 127.2, 127.0, 126.7, 125.8, 125.1,
124.2, 123.0, 122.8, 120.9, 112.2, 111.7, 110.8, 108.1, 45.1 ppm. IR
123.0, 59.4, 53.4 ppm. IR (KBr): ν = 2923, 2342, 1607, 1490, 1474,
˜
1408, 1350, 1094, 1014, 841, 759 cm–1. C28H18Cl2N2 (453.37):
calcd. C 74.18, H 4.00, N 6.18; found C 74.15, H 3.99, N 6.09.
1-(4-Bromobenzyl)-2-(4-bromophenyl)-1H-phenanthro[9,10-d]imid-
azole (2p): (see Table 2, Entry 16). White solid (76% yield); m.p.
230–232 °C. Rf = 0.49 [12% EtOAc/petroleum ether (60–80 °C)].
1H NMR (300 MHz, CDCl3): δ = 8.75 (d, J = 7.8 Hz, 2 H, ArH),
8.67–8.66 (m, 1 H, ArH), 7.93 (d, J = 8.4 Hz, 2 H, ArH), 7.58–
7.39 (m, 9 H, ArH), 7.01 (d, J = 8.4 Hz, 2 H, ArH), 5.68 (s, 2 H,
CH2) ppm. 13C NMR (75 MHz, CDCl3): δ = 152.0, 132.7, 132.2,
131.0, 129.4, 129.1, 128.6, 128.4, 127.5, 127.3, 127.1, 126.9, 126.3,
(KBr): ν = 2336, 1629, 1541, 1493, 1441, 1220, 1163, 782 cm–1.
˜
C24H16N2O2 (364.40): calcd. C 79.11, H 4.43, N 7.69; found C
79.03, H 4.40, N 7.61.
1-(4-Methoxybenzyl)-2-(4-methoxyphenyl)-1H-phenanthro[9,10-d]-
imidazole (2l): (see Table 2, Entry 12). White solid (89% yield); m.p.
122–124 °C. Rf = 0.47 [30% EtOAc/petroleum ether (60–80 °C)].
1H NMR (300 MHz, CDCl3): δ = 8.85 (d, J = 8.4 Hz, 1 H, ArH),
8.74 (d, J = 8.4 Hz, 1 H, ArH), 8.65 (d, J = 8.4 Hz, 1 H, ArH),
125.9, 125.1, 124.4, 123.5, 122.6, 120.7, 50.3 ppm. IR (KBr): ν =
˜
2338, 1601, 1505, 1451, 1421, 1377, 1035, 861, 772 cm–1
.
C28H18Br2N2 (542.27): calcd. C 62.02, H 3.35, N 5.17; found C
61.96, H 3.32, N 5.11.
7.93 (d, J = 8.1 Hz, 1 H, ArH), 7.70 (t, J = 7.5 Hz, 1 H, ArH), 1-(4-Methoxybenzyl)-2-(4-methoxyphenyl)-4,5-diphenyl-1H-imid-
7.60 (d, J = 7.8 Hz, 3 H, ArH), 7.48 (t, J = 7.2 Hz, 1 H, ArH), azole (2q): (see Table 2, Entry 17). Off-white solid (90% yield), m.p.
7.36 (t, J = 7.5 Hz, 1 H, ArH), 7.21 (d, J = 8.1 Hz, 2 H, ArH), 152–154 °C; ref.[10b] m.p. 152–154 °C. Rf = 0.44 [30% EtOAc/petro-
7.13 (d, J = 7.5 Hz, 2 H, ArH), 7.05 (d, J = 7.5 Hz, 1 H, ArH),
7.07 (d, J = 8.1 Hz, 2 H, ArH), 6.93 (d, J = 8.4 Hz, 2 H, ArH),
6.84 (d, J = 8.1 Hz, 2 H, ArH), 5.68 (s, 2 H, CH2), 3.80 (s, 3 H,
leum ether (60–80 °C)]. 1H NMR (300 MHz, CDCl3): δ = 7.60–
7.56 (m, 4 H, ArH), 7.29–7.27 (m, 3 H, ArH), 7.21–7.08 (m, 5 H,
ArH), 6.90–6.87 (m, 2 H, ArH), 6.68 (br. s, 4 H, ArH), 4.98 (s, 2
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7

Job/Unit: O43465
/KAP1
Date: 07-01-15 18:27:26
Pages: 12
R. Sarkar, C. Mukhopadhyay
FULL PAPER
H, CH2), 3.73 (s, 3 H, OCH3), 3.66 (s, 3 H, OCH3) ppm. 13C NMR CDCl3): δ = 148.8, 148.1, 147.8, 137.9, 134.2, 131.0, 130.8, 129.9,
(75 MHz, CDCl3): δ = 159.9, 158.6, 147.7, 137.6, 134.5, 131.1, 129.7, 129.0, 128.8, 128.7, 128.5, 128.2, 128.1, 127.9, 126.7, 126.3,
130.9, 130.2, 129.6, 129.5, 128.6, 128.3, 127.8, 127.0, 126.6, 126.0,
118.5, 111.0, 109.5, 55.7, 55.6, 47.8 ppm. IR (KBr): ν = 2933, 2834,
˜
123.4, 113.8, 113.8, 55.1, 55.0, 47.5 ppm. IR (KBr): ν = 2380, 1700,
2369, 1603, 1509, 1459, 1237, 1139, 1026, 774, 696 cm–1
30H26N2O2 (446.55): calcd. C 80.69, H 5.87, N 6.27; found C
80.65, H 5.81, N 6.22.
.
˜
1611, 1437, 1242, 1178, 1032, 842, 698 cm–1. C30H26N2O2 (446.55):
calcd. C 80.69, H 5.87, N 6.27; found C 80.61, H 5.86, N 6.23.
C
2-(Furan-2-yl)-1-[(furan-2-yl)methyl]-4,5-diphenyl-1H-imidazole
(2r): (see Table 2, Entry 18). Brown gummy solid (74% yield); Rf =
0.40 [20 % EtOAc/petroleum ether (60–80 °C)]. 1H NMR
(300 MHz, CDCl3): δ = 7.45–7.02 (m, 12 H, ArH), 6.84–6.82 (m,
1 H, ArH), 6.44–6.42 (m, 1 H, ArH), 6.12–6.11 (m, 1 H, ArH),
5.75–5.74 (m, 1 H, ArH), 5.12 (s, 2 H, CH2) ppm. 13C NMR
(75 MHz, CDCl3): δ = 149.8, 145.1, 142.8, 142.2, 138.8, 138.0,
133.9, 131.2, 130.1, 130.0, 128.9, 128.0, 126.9, 126.5, 111.5, 110.4,
1-Benzyl-2-(3,4-dimethoxyphenyl)-4,5-diphenyl-1H-imidazole (3b):
Light yellow solid (27% yield); m.p. 158–160 °C. Rf = 0.39 [40%
EtOAc/petroleum ether (60–80 °C)]. H NMR (300 MHz, CDCl3):
δ = 7.51–7.48 (m, 2 H, ArH), 7.23–7.04 (m, 13 H, ArH), 6.81–6.75
(m, 3 H, ArH), 5.00 (s, 2 H, CH2), 3.78 (s, 3 H, OCH3), 3.59 (s, 3
H, OCH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 149.6, 148.7,
147.9, 137.8, 137.8, 134.4, 130.9, 129.8, 128.7, 128.5, 128.0, 127.2,
126.7, 126.2, 125.8, 123.5, 121.5, 112.2, 111.0, 55.8, 55.5, 48.1 ppm.
1
107.8, 41.9 ppm. IR (KBr): ν = 2353, 1613, 1588, 1511, 1446, 1383,
˜
IR (KBr): ν = 2926, 2361, 1714, 1630, 1442, 1249, 1185, 1058,
˜
1074, 767 cm–1. C24H18N2O2 (366.42): calcd. C 78.67, H 4.95, N
7.65; found C 78.63, H 4.90, N 7.62.
764 cm–1. C30H26N2O2 (446.55): calcd. C 80.69, H 5.87, N 6.27;
found C 80.61, H 5.84, N 6.22.
2-(Naphthalen-1-yl)-1-(naphthalen-1-ylmethyl)-1H-phenanthro[9,10-d]-
imidazole (2s): (see Table 2, Entry 19). Light brown solid (79 %
yield); m.p. 244–246 °C. Rf = 0.36 [10% EtOAc/petroleum ether
1-(4-Bromobenzyl)-2,4,5-triphenyl-1H-imidazole (4a): White solid
(24% yield); m.p. 172–174 °C. Rf = 0.45 [12% EtOAc/petroleum
ether (60–80 °C)]. H NMR (300 MHz, CDCl3): δ = 7.50–7.46 (m,
1
1
(60–80 °C)]. H NMR (300 MHz, CDCl3): δ = 8.87 (d, J = 7.8 Hz,
4 H, ArH), 7.29–7.01 (m, 13 H, ArH), 6.53 (d, J = 8.4 Hz, 2 H,
ArH), 4.93 (s, 2 H, CH2) ppm. 13C NMR (75 MHz, CDCl3): δ =
147.7, 138.0, 136.2, 134.0, 131.4, 130.8, 130.6, 129.6, 128.7, 128.5,
128.3, 127.8, 127.4, 126.5, 126.2, 125.7, 121.0, 47.4 ppm. IR (KBr):
1 H, ArH), 8.76 (d, J = 8.4 Hz, 1 H, ArH), 8.70 (d, J = 8.1 Hz, 1
H, ArH), 7.92–7.85 (m, 3 H, ArH), 7.78–7.60 (m, 6 H, ArH), 7.56–
7.41 (m, 6 H, ArH), 7.29 (t, J = 7.5 Hz, 1 H, ArH), 7.21–7.13 (m,
2 H, ArH), 6.92 (d, J = 6.9 Hz, 1 H, ArH), 6.02 (s, 2 H, CH2) ppm.
13C NMR (75 MHz, CDCl3): δ = 151.4, 138.1, 133.8, 133.7, 133.0,
131.8, 130.3, 129.7, 129.2, 129.1, 128.6, 128.4, 128.3, 127.6, 127.5,
127.4, 127.2, 126.8, 126.7, 126.4, 126.1, 125.8, 125.7, 125.0, 124.8,
124.2, 123.8, 123.2, 123.1, 123.0, 122.8, 121.8, 121.0, 48.8 ppm. IR
ν = 2343, 1498, 1261, 1109, 867, 779 cm–1. C H BrN (465.39):
˜
28 21
2
calcd. C 72.26, H 4.55, N 6.02; found C 72.20, H 4.49, N 5.99.
1-Benzyl-2-(4-bromophenyl)-4,5-diphenyl-1H-imidazole (4b): White
solid (12% yield); m.p. 146–148 °C. Rf = 0.46 [12% EtOAc/petro-
leum ether (60–80 °C)]. 1H NMR (300 MHz, CDCl3): δ = 7.47–
7.42 (m, 2 H, ArH), 7.36 (br. s, 4 H, ArH), 7.27–7.01 (m, 11 H,
ArH), 6.69–6.67 (m, 2 H, ArH), 4.95 (s, 2 H, CH2) ppm. 13C NMR
(75 MHz, CDCl3): δ = 146.8, 137.1, 134.2, 131.6, 130.9, 130.6,
130.3, 129.6, 128.8, 128.6, 128.0, 127.4, 126.7, 126.4, 125.7, 123.2,
(KBr): ν = 1612, 1523, 1458, 1411, 1053, 791, 708 cm–1. C H N
˜
36 24
2
(484.60): calcd. C 89.23, H 4.99, N 5.78; found C 89.22, H 4.92, N
5.75.
1-Butyl-4,5-diphenyl-2-propyl-1H-imidazole (2t): (see Table 2, En-
try 20).[10b] Yellow gummy solid (62 % yield); Rf = 0.65 [10 %
48.2 ppm. IR (KBr): ν = 2353, 1511, 1263, 1082, 847, 763 cm–1.
˜
1
EtOAc/petroleum ether (60–80 °C)]. H NMR (300 MHz, CDCl3):
C
28H21BrN2 (465.39): calcd. C 72.26, H 4.55, N 6.02; found C
δ = 7.41–7.32 (m, 5 H, ArH), 7.26–7.24 (m, 2 H, ArH), 7.10–6.99
(m, 3 H, ArH), 3.64 (t, J = 7.8 Hz, 2 H, NCH2), 2.67 (t, J = 8.1 Hz,
2 H, CH2), 1.88–1.80 (m, 2 H, CH2), 1.41–1.36 (m, 2 H, CH2),
1.11–0.99 (m, 5 H, 1 CH2, 1 CH3), 0.68 (t, J = 7.5 Hz, 3 H,
CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 147.6, 136.2, 134.8,
131.6, 130.8, 128.6, 128.1, 127.8, 127.7, 126.4, 125.6, 43.2, 32.6,
72.19, H 4.51, N 5.93.
General Synthesis of 1,2,4,5-Tetrasubstituted Imidazoles 5a–5r: A
mixture of the 1,2-diketone (1 mmol), the primary amine with a
–CH2–NH2 group (1 mmol), another primary amine without any
–CH2–NH2 group (1 mmol), and silver carbonate (2.0 equiv.) in
1,4-dioxane (5 mL) was stirred at 80 °C for 10 h. The progress of
the reaction was monitored by TLC. Upon completion of the reac-
tion, the solid was removed by filtration and washed with dichloro-
methane. The solvent of the filtrate was then removed under vac-
uum, and the resulting crude product was purified by column
chromatography over 60–120 mesh silica gel [ethyl acetate/petro-
leum ether (60–80 °C)]. No further purification was needed.
29.2, 21.7, 19.5, 13.9, 13.2 ppm. IR (KBr): ν = 2912, 2845, 1606,
˜
1464, 1072, 766, 692 cm–1. C22H26N2 (318.46): calcd. C 82.97, H
8.23, N 8.80; found C 82.90, H 8.21, N 8.72.
2-Ethyl-4,5-diphenyl-1-propyl-1H-imidazole (2u): (see Table 2, En-
try 21). White solid (60% yield); m.p. 78–80 °C. Rf = 0.65 [10%
1
EtOAc/petroleum ether (60–80 °C)]. H NMR (300 MHz, CDCl3):
δ = 7.36–7.27 (m, 5 H, ArH), 7.23–7.20 (m, 2 H, ArH), 7.08–6.95
(m, 3 H, ArH), 3.57 (t, J = 6.3 Hz, 2 H, NCH2), 2.70 (q, J =
7.5 Hz, 2 H, CH2), 1.46–1.31 (m, 5 H, CH2, CH3), 0.64 (t, J =
7.5 Hz, 3 H, CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 148.8,
136.3, 134.8, 131.7, 130.9, 128.8, 128.2, 128.0, 127.8, 126.5, 125.7,
1-(3,4-Dimethylphenyl)-2,4,5-triphenyl-1H-imidazole (5a): (see
Table 3, Entry 1). White solid (74% yield); m.p. 164–166 °C. Rf =
0.39 [12 % EtOAc/petroleum ether (60–80 °C)]. 1H NMR
(300 MHz, CDCl3): δ = 7.66 (d, J = 7.8 Hz, 2 H, ArH), 7.53–7.51
(m, 2 H, ArH), 7.30–7.18 (m, 11 H, ArH), 7.01 (d, J = 7.8 Hz, 1
H, ArH), 6.84–6.80 (m, 2 H, ArH), 2.22 (s, 3 H, CH3), 2.12 (s, 3
H, CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 147.0, 138.2,
137.5, 136.8, 134.7, 134.6, 131.2, 131.1, 130.9, 130.8, 130.1, 129.3,
128.9, 128.3, 128.2, 127.9, 127.5, 126.6, 125.7, 19.7, 19.5 ppm. IR
45.1, 23.9, 20.6, 12.6, 10.9 ppm. IR (KBr): ν = 2923, 2838, 1592,
˜
1458, 1070, 783, 703 cm–1. C20H22N2 (290.41): calcd. C 82.72, H
7.64, N 9.65; found C 82.68, H 7.61, N 9.61.
1-(3,4-Dimethoxybenzyl)-2,4,5-triphenyl-1H-imidazole (3a): Yellow
gummy solid (15% yield); Rf = 0.41 [40% EtOAc/petroleum ether
(KBr): ν = 3025, 1601, 1499, 1478, 1445, 959, 768, 704, 692 cm–1.
˜
1
(60–80 °C)]. H NMR (300 MHz, CDCl3): δ = 7.66–7.63 (m, 2 H,
C29H24N2 (400.52): calcd. C 86.97, H 6.04, N 6.99; found C 86.88,
H 6.01, N 6.97.
ArH), 7.57–7.54 (m, 2 H, ArH), 7.40–7.32 (m, 7 H, ArH), 7.26–
7.11 (m, 4 H, ArH), 6.65 (d, J = 8.1 Hz, 1 H, ArH), 6.28 (d, J =
8.1 Hz, 1 H, ArH), 6.20 (s, 1 H, ArH), 5.03 (s, 2 H, CH2), 3.78 (s,
1-(4-Bromophenyl)-2-p-tolyl-1H-phenanthro[9,10-d]imidazole (5b):
3 H, OCH3), 3.63 (s, 3 H, OCH3) ppm. 13C NMR (75 MHz, (see Table 3, Entry 2). Orange solid (77% yield); m.p. 196–198 °C.
8
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Oxidative C–N Coupling Strategy for the Synthesis of Imidazoles
Rf = 0.41 [12 % EtOAc/petroleum ether (60–80 °C)]. 1H NMR
7.00 (m, 10 H, ArH), 6.99 (d, J = 7.8 Hz, 1 H, ArH), 6.76–6.72
(300 MHz, CDCl3): δ = 8.75 (d, J = 7.8 Hz, 1 H, ArH), 8.61 (d, J (m, 2 H, ArH), 2.20 (s, 3 H, CH3), 2.10 (s, 3 H, CH3) ppm. 13C
= 8.4 Hz, 1 H, ArH), 8.55 (d, J = 8.1 Hz, 1 H, ArH), 7.64–7.49 NMR (75 MHz, CDCl3): δ = 145.7, 138.2, 137.7, 137.1, 134.3,
(m, 4 H, ArH), 7.38 (t, J = 7.2 Hz, 1 H, ArH), 7.30 (d, J = 7.2 Hz, 131.3, 131.0, 130.5, 130.2, 129.4, 129.0, 128.3, 128.1, 127.4, 126.6,
2 H, ArH), 7.22–7.15 (m, 3 H, ArH), 7.06 (d, J = 8.1 Hz, 1 H, 125.5, 122.5, 19.6, 19.4 ppm. IR (KBr): ν = 3048, 1604, 1505, 1431,
˜
ArH), 7.00 (d, J = 7.2 Hz, 2 H, ArH), 2.22 (s, 3 H, CH3) ppm. 13C
988, 194, 719 cm–1. C29H23BrN2 (479.42): calcd. C 72.65, H 4.84,
NMR (75 MHz, CDCl3): δ = 151.1, 139.0, 137.9, 137.4, 133.2, N 5.84; found C 72.58, H 4.80, N 5.77.
130.7, 129.3, 129.2, 129.0, 128.2, 127.7, 127.3, 127.2, 127.1, 126.3,
2,4,5-Triphenyl-1-m-tolyl-1H-imidazole (5h): (see Table 3, Entry 8).
125.6, 124.8, 124.1, 123.6, 123.0, 122.8, 120.5, 21.1 ppm. IR (KBr):
White solid (73% yield); m.p. 182–184 °C. Rf = 0.43 [12% EtOAc/
petroleum ether (60–80 °C)]. 1H NMR (300 MHz, CDCl3): δ = 7.54
(d, J = 8.4 Hz, 2 H, ArH), 7.38–7.35 (m, 2 H, ArH), 7.14–6.97 (m,
13 H, ArH), 6.75 (br. s, 2 H, ArH), 2.09 (s, 3 H, CH3) ppm. 13C
ν = 3044, 1605, 1499, 1457, 1023, 785, 712 cm–1. C28H19BrN2
˜
(463.38): calcd. C 72.58, H 4.13, N 6.05; found C 72.54, H 4.08, N
5.99.
1-(3-Methoxyphenyl)-2,4,5-triphenyl-1H-imidazole (5c): (see NMR (75 MHz, CDCl3): δ = 147.5, 139.7, 138.9, 137.7, 135.2,
Table 3, Entry 3). White solid (73% yield); m.p. 146–148 °C. Rf =
131.8, 131.6, 131.4, 131.3, 129.6, 129.5, 129.4, 128.9, 128.7, 128.5,
0.34 [20 % EtOAc/petroleum ether (60–80 °C)]. 1H NMR 128.0, 127.1, 126.1, 21.7 ppm. IR (KBr): ν = 3051, 1601, 1490,
˜
(300 MHz, CDCl3): δ = 7.66–7.53 (m, 2 H, ArH), 7.52–7.49 (m, 2 1444, 962, 776, 696 cm–1. HRMS (ESI-TOF): calcd. for C28H22N2
H, ArH), 7.30–7.17 (m, 12 H, ArH), 6.86–6.72 (m, 1 H, ArH), [M + H]+ 387.1861; found 387.1859. C28H22N2 (386.50): calcd. C
6.68–6.66 (m, 1 H, ArH), 6.58–6.57 (m, 1 H, ArH), 3.61 (s, 3 H,
OCH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 159.8, 146.8, 138.2,
138.1, 134.5, 131.0, 130.7, 130.6, 129.6, 128.8, 128.3, 128.2, 128.1,
128.0, 127.9, 127.3, 126.5, 120.7, 114.3, 113.9, 55.3 ppm. IR (KBr):
87.01, H 5.74, N 7.25; found C 86.96, H 5.73, N 7.21.
1-Cyclohexyl-2-(3,4-dimethoxyphenyl)-4,5-diphenyl-1H-imidazole
(5i): (see Table 3, Entry 9). Yellow solid (79 % yield); m.p. 124–
126 °C. Rf = 0.54 [50 % EtOAc/petroleum ether (60–80 °C)]. 1H
NMR (300 MHz, CDCl3): δ = 7.44 (br. s, 7 H, ArH), 7.18–7.01
(m, 5 H, ArH), 6.93 (d, J = 8.1 Hz, 1 H, ArH), 4.03–3.87 (m, 7 H,
NCH, 2 OCH3), 1.85–1.82 (m, 2 H, 2 CH), 1.64–1.42 (m, 5 H, 5
ν = 3055.4, 1602.5, 1488.2, 1463.8, 761.7, 710.1, 690.6 cm–1
.
˜
C28H22N2O (402.49): calcd. C 83.56, H 5.51, N 6.96; found C
83.48, H 5.43, N 6.91.
1-Isopropyl-2-(4-methoxyphenyl)-4,5-diphenyl-1H-imidazole (5d): CH), 1.10–0.98 (m, 2 H, CH2), 0.80–0.76 (m, 1 H, CH) ppm. 13C
(see Table 3, Entry 4). White solid (78% yield); m.p. 166–168 °C.
NMR (75 MHz, CDCl3): δ = 149.5, 148.6, 147.4, 137.4, 134.5,
132.4, 132.0, 128.8, 128.6, 128.5, 128.0, 127.9, 127.7, 126.5, 125.8,
Rf = 0.51 [30 % EtOAc/petroleum ether (60–80 °C)]. 1H NMR
(300 MHz, CDCl3): δ = 7.54 (d, J = 8.4 Hz, 2 H, ArH), 7.54–7.43 124.7, 122.4, 113.2, 110.7, 58.2, 55.8, 33.4, 26.0, 24.9 ppm. IR
(m, 7 H, ArH), 7.16–7.07 (m, 3 H, ArH), 6.99 (d, J = 8.7 Hz, 2 H, (KBr): ν = 3036, 1596, 1483, 1421, 1038, 788, 704 cm–1
.
˜
ArH), 4.46–4.41 (m, 1 H, NCH), 3.84 (s, 3 H, OCH3), 1.24 (s, 3
C29H30N2O2 (438.57): calcd. C 79.42, H 6.89, N 6.39; found C
H, CH3), 1.21 (s, 3 H, CH3) ppm. 13C NMR (75 MHz, CDCl3): δ 79.38, H 6.85, N 6.32.
= 160.0, 147.2, 137.4, 134.5, 132.4, 132.0, 131.2, 128.6, 128.5, 127.7,
2-Phenyl-1-m-tolyl-1H-phenanthro[9,10-d]imidazole (5j): (see
Table 3, Entry 10). White solid (70% yield); m.p. 168–170 °C. Rf =
0.46 [20 % EtOAc/petroleum ether (60–80 °C)]. 1H NMR
(300 MHz, CDCl3): δ = 8.72 (d, J = 8.1 Hz, 1 H, ArH), 8.59–8.50
126.5, 125.8, 124.5, 113.6, 55.1, 49.1, 23.0 ppm. IR (KBr): ν = 3036,
˜
1612, 1491, 1433, 1002, 751 cm–1. C25H24N2O (368.48): calcd. C
81.49, H 6.57, N 7.60; found C 81.48, H 6.53, N 7.55.
2,4,5-Triphenyl-1-o-tolyl-1H-imidazole (5e): (see Table 3, Entry 5). (m, 2 H, ArH), 7.55–7.40 (m, 4 H, ArH), 7.32–7.23 (m, 2 H, ArH),
White solid (74% yield); m.p. 162–164 °C. Rf = 0.41 [12% EtOAc/
7.14–7.04 (m, 8 H, ArH), 2.23 (s, 3 H, CH3) ppm. 13C NMR
petroleum ether (60–80 °C)]. 1H NMR (300 MHz, CDCl3): δ = (75 MHz, CDCl3): δ = 150.7, 140.2, 138.5, 137.1, 131.2, 130.4,
7.57–7.54 (m, 2 H, ArH), 7.39–7.36 (m, 2 H, ArH), 7.20–7.02 (m,
15 H, ArH), 1.80 (s, 3 H, CH3) ppm. 13C NMR (75 MHz, CDCl3):
δ = 146.7, 138.4, 136.3, 136.1, 134.5, 130.9, 130.7, 130.6, 129.4,
129.0, 128.2, 128.1, 127.9, 127.3, 126.6, 126.5, 17.6 ppm. IR (KBr):
130.3, 130.0, 129.7, 129.4, 129.3, 129.2, 128.7, 128.2, 128.0, 127.1,
126.1, 126.0, 125.4, 127.7, 124.0, 123.0, 122.8, 122.7, 120.8, 116.5,
21.2 ppm. IR (KBr): ν = 3032, 1603, 1471, 1456, 1378, 989, 758,
˜
728, 703 cm–1. C28H20N2 (384.48): calcd. C 87.47, H 5.24, N 7.29;
ν = 3061, 1602, 1495, 1441, 960, 764, 696 cm–1. C H N (386.50): found C 87.43, H 5.18, N 7.25.
˜
28 22
2
calcd. C 87.01, H 5.74, N 7.25; found C 86.95, H 5.68, N 7.18.
2-(4-Chlorophenyl)-1-isopropyl-4,5-diphenyl-1H-imidazole (5k): (see
1-(3,4-Dimethylphenyl)-2-phenyl-1H-phenanthro[9,10-d]imidazole Table 3, Entry 11). White solid (72% yield); m.p. 152–154 °C. Rf =
(5f): (see Table 3, Entry 6). White solid (76 % yield); m.p. 222–
224 °C. Rf = 0.45 [12 % EtOAc/petroleum ether (60–80 °C)]. 1H
NMR (300 MHz, CDCl3): δ = 8.90 (d, J = 8.1 Hz, 1 H, ArH),
0.43 [12 % EtOAc/petroleum ether (60–80 °C)]. 1H NMR
(300 MHz, CDCl3): δ = 7.54–7.29 (m, 11 H, ArH), 7.16–7.05 (m,
3 H, ArH), 4.45–4.36 (m, 1 H, NCH), 1.23 (s, 3 H, CH3), 1.21 (s,
8.70–8.62 (m, 2 H, ArH), 7.71 (t, J = 7.8 Hz, 1 H, ArH), 7.63–7.55 3 H, CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 146.1, 138.0,
(m, 3 H, ArH), 7.46–7.40 (m, 1 H, ArH), 7.27–7.20 (m, 8 H, ArH), 135.0, 134.3, 132.0, 131.2, 130.6, 129.1, 128.8, 128.6, 128.5, 128.1,
2.36 (s, 3 H, CH3), 2.25 (s, 3 H, CH3) ppm. 13C NMR (75 MHz,
CDCl3): δ = 150.9, 138.6, 138.3, 137.2, 136.2, 131.0, 130.7, 129.6,
129.3, 129.1, 128.6, 128.2, 128.0, 127.3, 127.1, 126.1, 125.4, 124.6,
128.0, 127.8, 126.6, 126.1, 49.3, 23.1 ppm. IR (KBr): ν = 3049,
˜
1596, 1484, 1429, 1242, 789, 698 cm–1. C24H21ClN2 (372.90): calcd.
C 77.30, H 5.68, N 7.51; found C 77.27, H 5.65, N 7.44.
123.9, 123.1, 123.0, 122.7, 120.9, 19.7, 19.6 ppm. IR (KBr): ν =
˜
1-(3-Methoxyphenyl)-2-phenyl-1H-phenanthro[9,10-d]imidazole (5l):
(see Table 3, Entry 12). White solid (71% yield); m.p. 172–174 °C.
Rf = 0.38 [20 % EtOAc/petroleum ether (60–80 °C)]. 1H NMR
(300 MHz, CDCl3): δ = 8.87 (d, J = 7.8 Hz, 1 H, ArH), 8.70–8.62
(m, 2 H, ArH), 7.70 (t, J = 7.2 Hz, 1 H, ArH), 7.62–7.59 (m, 3 H,
ArH), 7.46–7.38 (m, 2 H, ArH), 7.28–7.23 (m, 5 H, ArH), 7.09–
7.05 (m, 2 H, ArH), 6.96 (br. s, 1 H, ArH), 3.70 (s, 3 H,
3044, 1613, 1499, 1452, 1379, 826, 759, 727, 696 cm–1. C29H22N2
(398.51): calcd. C 87.41, H 5.56, N 7.03; found C 87.38, H 5.50, N
6.95.
2-(4-Bromophenyl)-1-(3,4-dimethylphenyl)-4,5-diphenyl-1H-imid-
azole (5g): (see Table 3, Entry 7). White solid (71 % yield); m.p.
144–146 °C. Rf = 0.47 [12% EtOAc/petroleum ether (60–80 °C)].
1H NMR (300 MHz, CDCl3): δ = 7.76 (d, J = 8.4 Hz, 1 H, ArH), OCH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 160.7, 150.8, 139.6,
7.53 (d, J = 7.8 Hz, 2 H, ArH), 7.41–7.39 (m, 1 H, ArH), 7.33– 137.3, 130.6, 130.5, 129.2, 129.1, 128.8, 128.2, 128.1, 128.0, 127.2,
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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R. Sarkar, C. Mukhopadhyay
129.5, 129.0, 128.6, 127.5, 127.3, 126.6, 126.3, 126.1, 125.5, 123.8,
FULL PAPER
126.2, 125.5, 124.8, 124.0, 123.0, 122.9, 122.7, 121.2, 120.9, 115.6,
114.4, 55.5 ppm. IR (KBr): ν = 3058, 1601, 1589, 1495, 1471, 1453,
123.5, 122.9, 121.0, 120.9 ppm. IR (KBr): ν = 2365.0, 2341.9,
˜
˜
840, 773, 759, 696 cm–1. C28H20N2O (400.48): calcd. C 83.98, H
5.03, N 7.00; found C 83.93, H 4.98, N 6.95.
1477.7, 1070.0, 1008.3, 827.3, 759.6, 724.7, 670.4 cm–1.
C21H12BrNO (374.24): calcd. C 67.40, H 3.23, N 3.74; found C
67.34, H 3.16, N 3.78.
1-(4-Chlorophenyl)-2-(4-methoxyphenyl)-1H-phenanthro[9,10-d]-
imidazole (5m): (see Table 3, Entry 13). Off-white solid (75% yield);
m.p. 232–234 °C. Rf = 0.39 [30 % EtOAc/petroleum ether (60–
4-Bromobenzaldehyde (6b): White solid (24% yield), m.p. 56–58 °C;
ref.[13] m.p. 55–58 °C. Rf = 0.59 [3% EtOAc/petroleum ether (60–
80 °C)]. 1H NMR (300 MHz, CDCl3): δ = 8.85 (d, J = 8.1 Hz, 1 80 °C)]. 1H NMR (300 MHz, [D6]DMSO): δ = 9.95 (s, 1 H, CHO),
H, ArH), 8.71 (d, J = 8.4 Hz, 1 H, ArH), 8.65 (d, J = 8.1 Hz, 1 H, 7.78 (br. s, 4 H, ArH) ppm. 13C NMR (75 MHz, [D6]DMSO): δ =
ArH), 7.71 (t, J = 7.5 Hz, 1 H, ArH), 7.61 (t, J = 8.4 Hz, 1 H,
ArH), 7.54–7.36 (m, 7 H, ArH), 7.26 (t, J = 7.5 Hz, 1 H, ArH),
7.15 (d, J = 8.4 Hz, 1 H, ArH), 6.80 (d, J = 8.7 Hz, 2 H, ArH),
192.3, 135.2, 132.3, 131.2, 128.7 ppm. IR (KBr): ν = 2858.2, 2757.9,
˜
1710.7, 1690.0, 1665.1, 1588.3, 1573.5, 1479.0, 1384.5, 1289.0,
1204.8, 1154.0, 1065.7, 1008.7, 834.8, 810.6 cm–1. C7H5BrO
3.76 (s, 3 H, OCH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 160.1, (185.02): calcd. C 45.44, H 2.72; found C 45.40, H 2.71.
150.9, 137.3, 137.2, 135.6, 130.8, 130.4, 130.3, 129.1, 128.2, 127.6,
127.2, 126.9, 126.3, 125.4, 124.8, 124.1, 123.0, 122.7, 122.4, 120.4,
Phenanthrene-9,10-dione (1ab): Orange solid (21% yield), m.p. 208–
210 °C; ref.[14] m.p. 208–210 °C. Rf = 0.53 [10% EtOAc/petroleum
113.7, 55.2 ppm. IR (KBr): ν = 3043, 1609, 1504, 1459, 947, 782,
˜
1
ether (60–80 °C)]. H NMR (300 MHz, [D6]DMSO): δ = 8.23 (d,
719 cm–1. C28H19ClN2O (434.92): calcd. C 77.33, H 4.40, N 6.44;
found C 77.29, H 4.39, N 6.42.
J = 8.1 Hz, 2 H, ArH), 7.99 (dd, J = 7.8 Hz, J = 1.2 Hz, 2 H, ArH),
7.77–7.72 (m, 2 H, ArH), 7.50 (t, J = 7.5 Hz, 2 H, ArH) ppm. 13C
1-(3-Nitrophenyl)-2-phenyl-1H-phenanthro[9,10-d]imidazole (5n): NMR (75 MHz, [D6]DMSO): δ = 173.8, 130.3, 130.1, 126.0, 124.2,
(see Table 3, Entry 14). Yellow solid (68% yield); m.p. 228–230 °C.
124.0, 119.3 ppm. IR (KBr): ν = 1673.8, 1650.9, 1591.5, 1450.7,
˜
Rf = 0.40 [20 % EtOAc/petroleum ether (60–80 °C)]. 1H NMR
1293.8, 1281.8, 1228.8, 924.8, 763.2, 715.5 cm–1. C14H8O2 (208.22):
(300 MHz, CDCl3): δ = 8.89 (d, J = 7.8 Hz, 1 H, ArH), 8.72–8.63 calcd. C 80.76, H 3.87; found C 80.75, H 3.85.
(m, 2 H, ArH), 8.43 (d, J = 8.1 Hz, 1 H, ArH), 8.35–8.34 (m, 1 H,
CCDC-1006486 (for 2j) and -1006487 (for 5d) contain the supple-
ArH), 7.78–7.62 (m, 4 H, ArH), 7.50–7.45 (m, 3 H, ArH), 7.32–
7.22 (m, 4 H, ArH), 7.04 (d, J = 8.4 Hz, 1 H, ArH) ppm. 13C NMR
(75 MHz, CDCl3): δ = 151.1, 148.9, 139.9, 137.7, 135.2, 130.9,
129.8, 129.6, 129.3, 129.2, 128.4, 128.3, 127.7, 127.4, 127.0, 126.4,
125.9, 125.1, 124.5, 124.3, 124.2, 123.1, 122.8, 122.4, 120.2 ppm.
mentary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
Supporting Information (see footnote on the first page of this arti-
cle): Copies of 1H and 13C NMR spectra of products 2a–2u, 3a,
3b, 4a, 4b, 5a–5p, 6a, 6b, and 1ab.
IR (KBr): ν = 3059, 1602, 1524, 1474, 1450, 1377, 777, 753, 721,
˜
695 cm–1. C27H17N3O2 (415.45): calcd. C 78.06, H 4.12, N 10.11;
found C 77.95, H 4.09, N 10.04.
4,5-Diphenyl-1-o-tolyl-2-p-tolyl-1H-imidazole (5o): (see Table 3, En- Acknowledgments
try 15). White solid (76% yield); m.p. 126–128 °C. Rf = 0.45 [12%
1
One of the authors (R. S.) thanks the Council of Scientific and
EtOAc/petroleum ether (60–80 °C)]. H NMR (300 MHz, CDCl3):
δ = 7.63 (d, J = 7.5 Hz, 2 H, ArH), 7.33 (d, J = 8.1 Hz, 2 H, ArH),
7.24–7.06 (m, 12 H, ArH), 6.99 (d, J = 8.1 Hz, 2 H, ArH), 2.24 (s,
3 H, CH3), 1.85 (s, 3 H, CH3) ppm. 13C NMR (75 MHz, CDCl3):
δ = 146.8, 138.2, 138.0, 136.3, 136.0, 134.5, 130.9, 130.6, 130.5,
129.3, 128.9, 128.8, 128.2, 128.0, 127.9, 127.8, 127.3, 126.5, 126.4,
Industrial Research (CSIR), New Delhi, for his fellowship (SRF).
We also thank the CAS Instrumentation Facility, University of Cal-
cutta for the spectroscopic data.
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8.74 (d, J = 8.1 Hz, 1 H, ArH), 8.68 (d, J = 8.4 Hz, 1 H, ArH),
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148.2, 140.2, 138.8, 136.9, 130.3, 129.7, 129.4, 128.9, 128.0, 127.8,
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993, 755, 709 cm–1. C30H24N2O2 (444.53): calcd. C 81.06, H 5.44,
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2 H, ArH), 8.63 (d, J = 7.2 Hz, 1 H, ArH), 8.35 (d, J = 8.1 Hz, 1
H, ArH), 8.26 (d, J = 8.4 Hz, 2 H, ArH), 7.78–7.74 (m, 6 H,
ArH) ppm. 13C NMR (75 MHz, CDCl3): δ = 161.3, 135.6, 132.2,
1
10
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Oxidative C–N Coupling Strategy for the Synthesis of Imidazoles
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Published Online: ᭿
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11

Job/Unit: O43465
/KAP1
Date: 07-01-15 18:27:26
Pages: 12
R. Sarkar, C. Mukhopadhyay
FULL PAPER
Nitrogen Heterocycles
R. Sarkar, C. Mukhopadhyay* ....... 1–12
Silver-Mediated Cα(sp3)–H Functionali-
zation of Primary Amines: An Oxidative
C–N Coupling Strategy for the Synthesis
of Two Different Types of 1,2,4,5-Tetrasub-
stituted Imidazoles
A new silver(I)-mediated Cα(sp3)–H bond
functionalization of primary amines fol-
lowed by an oxidative C–N cross-coupling
reaction to form highly diverse 1,2,4,5-
tetrasubstituted imidazoles has been dem-
onstrated. This protocol provides a simple,
highly efficient, and straightforward ap-
proach, which is promoted by a silver spec-
ies, to give the products in good to excellent
yields.
Keywords: Nitrogen heterocycles / C–H ac-
tivation / Cross-coupling / Cyclization / Sil-
ver / Amines
12
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