Synthesis of indolyl imidazole derivatives via base-promoted tandem reaction of N-[2-(1-alkynyl)phenyl]carbodiimides with isocyanides

Article abstract of DOI:10.1021/jo402552c

An efficient route to indolyl imidazole derivatives has been developed through a base-promoted tandem reaction of N-[2-(1-alkynyl)phenyl]carbodiimides with isocyanides in DMSO at 40 °C. The present tandem process allows the assembly of a variety of indolyl imidazole derivatives in moderate to good yields.

Full text of DOI:10.1021/jo402552c

Note
pubs.acs.org/joc
Synthesis of Indolyl Imidazole Derivatives via Base-Promoted
Tandem Reaction of N‑[2-(1-Alkynyl)phenyl]carbodiimides with
Isocyanides
Wenyan Hao, Yuanyuan Jiang, and Mingzhong Cai*
College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang 330022, People’s Republic of China
S
* Supporting Information
ABSTRACT: An efficient route to indolyl imidazole deriva-
tives has been developed through a base-promoted tandem
reaction of N-[2-(1-alkynyl)phenyl]carbodiimides with iso-
cyanides in DMSO at 40 °C. The present tandem process
allows the assembly of a variety of indolyl imidazole derivatives
in moderate to good yields.
onstruction of natural product-like compounds with
privileged scaffolds that are prone to display different
terminal nitrogen atom is electron-rich. By far the most
important reactions involve nucleophilic attack of a reagent E−
Nu that may add by stepwise or concerted paths.15 Prompted
by the advancement of carbodiimide chemistry, we envision
that N-[2-(1-alkynyl)phenyl]carbodiimides would be powerful
intermediates for the production of N-heterocycles with
privileged structures. Therefore, we started to study the
reactions of N-[2-(1-alkynyl)phenyl]carbodiimides 1 with 2-
isocyanoacetates 2, with an aim to enrich our natural product-
like libraries of quinazolines 3. To our surprise, the desired
quinazoline 3 was not observed, and an unexpected compound
4 was isolated instead (Scheme 1).
We reasoned that in the presence of a base, the formal [3 +
2] cycloaddition of 2-isocyanoacetate 2 to a carbodiimide
moiety in compound 1 would occur first to produce
intermediate A. Intermediate A could then undergo proto-
nolysis and isomerization to afford intermediate C. Finally, an
intramolecular cyclization of intermediate C would happen to
give the target product 3 (Scheme 2).
To optimize the transformation, a set of experiments were
subsequently carried out using phenyl(2-phenylethynylphenyl)-
carbodiimide (1a) and ethyl 2-isocyanoacetate (2a) as model
substrates, and the results are summarized in Table 1. As shown
in Table 1, in the presence of DBU as a base, the reaction in
acetonitrile at 80 °C gave the desired ethyl 1-phenyl-5-(2-
phenyl-1H-indol-1-yl)-1H-imidazole-4-carboxylate 3a in 24%
yield (Table 1, entry 1). Next, a series of bases were examined.
It is evident that Cs2CO3 was the best choice, leading to the
desired product 3a in 32% yield (Table 1, entry 2). The
structure of 3a was further confirmed by X-ray diffraction
analysis (see Figure 1 in the Supporting Information). Taking
into account the activation of the acetylenic bond, different
Lewis acids as the catalyst in the presence of Cs2CO3 were
screened in acetonitrile at 80 °C, but the results were not
satisfactory (Table 1, entries 11−14). In the absence of the
C
biological activities are in great demand. Among these
privileged scaffolds, the indole unit is abundant in natural
heterocycles and acts as the functional core in the structures of
various fragrances, dyes, agricultural chemicals, and pharma-
ceuticals.1 The synthesis of indoles has been an active research
field due to their structural diversity as well as numerous
applications of natural and synthetic indole derivatives. Over
the past several decades, enormous efforts have been devoted to
the development of these heteroaromatic compounds, and a
variety of approaches have been successfully developed.2 For
instance, the venerable Fischer indole synthesis was represented
as one of the most powerful and versatile routes for the
synthesis of indole heterocycles, although this method often
suffers from several drawbacks such as using strong acids;
certain carcinogenic, unstable, and not readily available
hydrazines; and poor regioselectivity with nonsymmetric
ketones.3 The synthesis of indoles catalyzed by transition
metals such as palladium,4 copper,5 iron,6 and rhodium7 has
been highlighted by Larock and other researchers. However,
there are few methods reported for the preparation of the
indolyl imidazole skeletons, especially an imidazole ring on the
indole nitrogen.8 Considering the importance of imidazole
derivatives,9 development of an efficient and practical route for
the preparation of indolyl imidazoles is of highly desirable.
Isocyanide addition chemistry has also attracted much
attention recently, and the important progress of isocyanide
additions for the construction of N-heterocyclic compounds has
been witnessed.10−13 For instance, Wu and co-workers reported
the synthesis of tetrahydroindeno[2,1-b]pyrroles via a base-
promoted reaction of (E)-2-alkynylphenylchalcone with 2-
isocyanoacetate.10a Carbodiimide has been widely used in
heterocyclic synthesis, cycloaddition reactions, and peptide and
nucleotide coupling reactions as a diversity of reagent in the
field of organic synthesis because of its special electronic
properties.14 The carbodiimide molecule has two centers of
reactivity: the central carbon atom is electrophilic, and the
Received: November 18, 2013
Published: March 20, 2014
© 2014 American Chemical Society
3634
dx.doi.org/10.1021/jo402552c | J. Org. Chem. 2014, 79, 3634−3640

The Journal of Organic Chemistry
Note
Scheme 1
Scheme 2. Proposed Mechanism for the Generation of Indol-1-yl-1H-imidazole-4-carboxylates via Base-Promoted Tandem
Reaction of N-[2-(1-Alkynyl)phenyl]carbodiimides 1 and 2-Isocyanoacetates 2
base, the reaction failed when catalytic CuI was added into the
reaction (Table 1, entry 15). Switching to other Lewis acids,
such as PdCl2, Pd(OAc)2, FeCl3, etc. also did not produce the
desired outcome (Table 1, entries 16−19). We next examined
the solvent effect (Table 1, entries 20−23). When DMSO was
employed as the solvent, the yield increased to 42% (Table 1,
entry 23). When the reaction temperature was reduced to 60
°C, the reaction was completed with a yield of 55% (Table 1,
entry 26). The highest yield of 62% was obtained when Cs2CO3
in DMSO at 40 °C was used (Table 1, entry 25).
Under the optimized reaction conditions [Cs2CO3 (2.0
equiv), DMSO, 40 °C], the scope of the reactions was
investigated, and the results are shown in Table 2. All reactions
proceeded smoothly, leading to the desired indolyl imidazole
derivatives in moderate to good yields. For example, when we
changed ethyl 2-isocyanoacetate (2a) to tert-butyl 2-isocyanoa-
cetate (2b) or 1-isocyanomethanesulfonyl-4-methylbenzene
(TosMIC, 2c),16 the corresponding products 3b and 3c were
obtained in 71% and 76% yield, respectively (Table 2, entries 2
and 3). The reaction worked well when the R2 group in the
substrate N-[2-(1-alkynyl)phenyl]carbodiimides 1 was an
electron-rich or electron-deficient aryl group (Table 2, entries
4−6). To our surprise, when the R2 group in the substrate N-
[2-(1-alkynyl)phenyl]carbodiimides 1 was an alkyl group such
as n-butyl or n-hexyl, the desired products were not obtained.
However, when the R2 group was a cyclopropyl group, the
desired product 3g was obtained in 60% yield (Table 2, entry
7). For the R3 group in the N-[2-(1-alkynyl)phenyl]-
carbodiimides 1, both aryl and alkyl groups were all tolerated.
For instance, the reaction of isocyanoacetate 2a and compound
1 with a tolyl group attached on the position of R3 gave rise to
the corresponding product 3k in 64% yield (Table 2, entry 11).
While the R3 position was changed to an n-butyl group, the
expected product 3l was afforded in 60% yield (Table 2, entry
12). Reactions of ethyl 2-isocyanoacetate 2a and N-[2-(1-
alkynyl)phenyl]carbodiimides 1 with different substitutions on
the aromatic ring were studied. As expected, all reactions
proceeded smoothly to furnish the desired products in good
yields (such as 3m in 60% yield, 3n in 61% yield). The products
3i and 3j were obtained in lower yields due to the formation of
byproducts unidentified.
It was found that when TosMIC (2c) reacted with N-[2-(1-
alkynyl)phenyl]carbodiimide 1 under the same conditions, the
yield dramatically increased. Therefore, the tandem reactions of
TosMIC (2c) with various N-[2-(1-alkynyl)phenyl]-
carbodiimides 1 were investigated. Generally the reactions
proceeded successfully under the optimal conditions to afford
the corresponding indolyl imidazole derivatives 3o−3x in good
yields (Table 2, entries 15−24). For instance, 1-(4-
fluorophenyl)-5-(2-phenyl-1H-indol-1-yl)-4-(p-tolylsulfonyl)-
1H-imidazole 3r was obtained in 85% yield, and 5-(5-methyl-2-
phenyl-1H-indol-1-yl)-1-phenyl-4-(p-tolylsulfonyl)-1H-imida-
zole 3w was obtained in 81% yield. The reaction also proceeded
effectively when the R2 group in the N-[2-(1-alkynyl)phenyl]-
carbodiimides 1 was an electron-rich or electron-deficient aryl
group (Table 2, entries 15−17). For the R3 group in the
substrate 1, both aryl and alkyl groups were well tolerated.
In conclusion, we have described an efficient route for the
construction of indolyl imidazole derivatives via a base-
promoted cascade reaction of N-[2-(1-alkynyl)phenyl]-
carbodiimides with isocyanides. The reaction could be
performed under mild conditions with high efficiency. In the
reaction, a [3 + 2] cycloaddition of isocyanide to carbodiimide
and the intramolecular cyclization are involved. More trans-
formations incorporating carbodiimides and 2-isocyanoacetates
to synthesize biologically interesting molecules is ongoing in
our laboratory, and the results will be reported in due course.
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The Journal of Organic Chemistry
Note
2H), 6.58 (s, 1H), 6.31−6.33 (m, 2H), 4.13−4.29 (m, 2H), 1.00 (t, J =
7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 161.6, 140.4, 139.2,
135.9, 133.7, 131.5, 129.3, 129.1, 128.7, 128.6, 128.3, 127.8, 127.7,
123.8, 123.1, 121.5, 120.8, 111.0, 104.4, 60.8, 13.9. MS (EI, 70 eV) m/
Table 1. Initial Studies for the Tandem Reaction of
Phenyl(2-phenylethynylphenyl)carbodiimide 1a with Ethyl
a
2-Isocyanoacetate 2a
+
z: 407 [M]+. HRMS calcd for C26H22N3O2 (M + H+): 408.1707,
found 408.1701. Anal. Calcd for C26H21N3O2: C, 76.64; H, 5.19; N,
10.31. Found: C, 76.36; H, 5.24; N, 10.18.
tert-Butyl 1-Phenyl-5-(2-phenyl-1H-indol-1-yl)-1H-imida-
zole-4-carboxylate (3b). Yellow solid (61.8 mg, 71%). Mp 199−
201 °C. IR (KBr): 3052, 2973, 1721, 1598, 1569, 1501, 1457, 1410,
1153, 748 cm−1. 1H NMR (400 MHz, CDCl3): δ 7.64 (s, 1H), 7.61 (d,
J = 7.6 Hz, 1H), 7.11−7.27 (m, 5H), 7.11−7.14 (m, 2H), 7.01−7.05
(m, 2H), 6.86 (d, J = 7.6 Hz, 2H), 6.56 (s, 1H), 6.32 (d, J = 8.0 Hz,
2H), 1.13 (s, 9H). 13C NMR (100 MHz, CDCl3): δ 160.7, 140.0,
139.3, 135.8, 133.7, 131.6, 130.5, 129.8, 129.2, 128.6, 128.5, 128.3,
127.7, 123.9, 122.9, 121.3, 120.7, 111.0, 103.8, 81.1, 27.6. MS (EI, 70
T
yield
c
b
entry
Lewis acid
base
DBU
solvent
(°C) t (h)
(%)
1
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
DMF
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
25
40
60
100
12
12
12
24
24
24
20
20
20
20
12
12
12
12
24
24
24
24
24
24
24
24
12
24
12
12
3
24
2
Cs2CO3
K3PO4
32
3
25
+
eV) m/z: 435 [M]+. HRMS calcd for C28H26N3O2 (M + H+):
4
DABCO
Na2CO3
K2CO3
n-BuLi
trace
trace
trace
7
5
436.2020, found 436.2009. Anal. Calcd for C28H25N3O2: C, 77.22; H,
5.79; N, 9.65. Found: C, 76.97; H, 5.64; N, 9.49.
6
7
1-Phenyl-5-(2-phenyl-1H-indol-1-yl)-4-(p-tolylsulfonyl)-1H-
imidazole (3c). Yellow solid (74.4 mg, 76%). Mp 175−177 °C. IR
(KBr): 2920, 1596, 1566, 1502, 1324, 1151, 1082, 761 cm−1. 1H NMR
(400 MHz, CDCl3): δ 7.78−7.82 (d, J = 8.0 Hz, 2H), 7.68 (s, 1H),
7.61 (d, J = 6.8 Hz, 1H), 7.16−7.26 (m, 6H), 7.00−7.10 (m, 5H), 6.77
(d, J = 7.6 Hz, 2H), 6.60 (s, 1H), 6.26 (d, J = 7.6 Hz, 2H), 2.40 (s,
3H). 13C NMR (100 MHz, CDCl3): δ 144.6, 140.9, 140.0, 137.4,
137.3, 136.2, 133.0, 131.1, 129.6, 129.3, 129.1, 128.7, 128.4, 128.2,
127.9, 127.7, 127.1, 124.0, 123.2, 121.8, 120.9, 111.3, 105.1, 21.6. MS
(EI, 70 eV) m/z: 489 [M]+. HRMS calcd for C30H24N3O2S+ (M +
H+): 490.1584, found 490.1571. Anal. Calcd for C30H23N3O2S: C,
73.60; H, 4.74; N, 8.58. Found: C, 73.42; H, 4.96; N, 8.39.
8
NaOH
KOH
10
9
11
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
t-BuOK
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
8
CuI
32
PdCl2
Pd(OAc)2
FeCl3
32
32
32
CuI
NR
trace
trace
trace
trace
trace
trace
trace
42
PdCl2
Pd(OAc)2
FeCl3
Ethyl 5-[2-(4-Chlorophenyl)-1H-indol-1-yl]-1-phenyl-1H-imi-
dazole-4-carboxylate (3d). Yellow solid (50.4 mg, 57%). Mp 168−
169 °C. IR (KBr): 3054, 1721, 1637, 1567, 1500, 1451, 1152, 802, 766
CuI + PdCl2
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
1
cm−1. H NMR (400 MHz, CDCl3): δ 7.68 (s, 1H), 7.62 (d, J = 7.6
DCE
Hz, 1H), 7.21−7.30 (m, 4H), 7.06−7.12 (m, 4H), 6.79 (d, J = 8.8 Hz,
2H), 6.58 (s, 1H), 6.37 (d, J = 7.6 Hz, 2H), 4.15−4.30 (m, 2H), 1.03
(t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 161.5, 139.3,
139.0, 136.0, 133.9, 133.6, 130.5, 130.0, 129.4, 129.2, 128.9, 128.8,
128.5, 123.8, 123.5, 121.7, 121.0, 111.0, 104.8, 60.8, 13.9. MS (EI, 70
Toluene
d
DMSO
DMSO
DMSO
DMSO
DMSO
25
62
55
+
eV) m/z: 441 [M]+. HRMS calcd for C26H21ClN3O2 (M + H+):
40
442.1317, found 442.1305. Anal. Calcd for C26H20ClN3O2: C, 70.66;
H, 4.56; N, 9.50. Found: C, 70.44; H, 4.65; N, 9.33.
a
Reaction was performed with 1a (0.2 mmol), 2a (0.4 mmol), and
base (0.4 mmol) in solvent (2 mL). 0.1 equiv of Lewis acid catalyst
was used. Isolated yield based on phenyl(2-phenylethynylphenyl)-
carbodiimide 1a. Different bases such as t-BuOK, KOH, K3PO4,
K2CO3, and DBU were tested with DMSO as the solvent, and Cs2CO3
was also found to be the best choice.
b
Ethyl 5-[2-(4-Methoxyphenyl)-1H-indol-1-yl]-1-phenyl-1H-
imidazole-4-carboxylate (3e). Yellow solid (57.7 mg, 66%). Mp
172−174 °C. IR (KBr): 3050, 2977, 1725, 1611, 1598, 1580, 1501,
c
d
1
1455, 1250, 1176, 836, 751 cm−1. H NMR (400 MHz, CDCl3): δ
7.66 (s, 1H), 7.58−7.60 (m, 1H), 7.18−7.24 (m, 4H), 7.07 (t, J = 8.0
Hz, 2H), 6.79 (d, J = 8.8 Hz, 2H), 6.66 (d, J = 8.4 Hz, 2H), 6.50 (s,
1H), 6.38 (d, J = 7.6 Hz, 2H), 4.13−4.29 (m, 2H), 3.77 (s, 3H), 1.01
(t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 161.6, 159.3,
140.3, 139.1, 135.9, 133.7, 131.0, 129.3, 129.0, 128.8, 128.6, 124.1,
123.9, 122.8, 121.4, 120.6, 113.7, 110.8, 103.6, 60.7, 55.3, 13.9. MS (EI,
EXPERIMENTAL SECTION
■
General Methods. H and 13C NMR spectra were recorded with
1
CDCl3 as the solvent and TMS as an internal standard. The starting N-
[2-(1-alkynyl)phenyl]carbodiimides were prepared according to the
reported literature procedure.17 The other chemicals were purchased
from commercial sources and used as received, unless otherwise noted.
General Procedure for the Synthesis of Indolyl Imidazole
Derivatives via a Tandem Reaction of N-[2-(1-Alkynyl)phenyl]-
carbodiimides 1 with Isocyanides 2. A mixture of N-[2-(1-
alkynyl)phenyl]carbodiimide 1a (0.2 mmol), 2-isocyanoacetate 2a (0.4
mmol), and Cs2CO3 (0.4 mmol) in DMSO (2.0 mL) was stirred at 40
°C for 12 h. After completion of reaction as indicated by TLC, the
mixture was concentrated and directly purified by flash column
chromatography (EtOAc/petroleum ether, 1:2) to give the desired
product 3a.
+
70 eV) m/z: 437 [M]+. HRMS calcd for C27H24N3O3 (M + H+):
438.1812, found 438.1801. Anal. Calcd for C27H23N3O3: C, 74.13; H,
5.30; N, 9.60. Found: C, 73.89; H, 5.17; N, 9.43.
Ethyl 5-[2-(p-Tolyl)-1H-indol-1-yl]-1-phenyl-1H-imidazole-4-
carboxylate (3f). Yellow solid (57.3 mg, 68%). Mp 174−176 °C. IR
(KBr): 2952, 2923, 2854, 1727, 1597, 1570, 1500, 1455, 1248, 1171,
803, 752 cm−1. 1H NMR (400 MHz, CDCl3): δ 7.78 (s, 1H), 7.70 (d, J
= 7.8 Hz, 1H), 7.28−7.35 (m, 4H), 7.15 (t, J = 7.6 Hz, 2H), 7.04 (d, J
= 7.8 Hz, 2H), 6.86 (d, J = 7.8 Hz, 2H), 6.65 (s, 1H), 6.48 (d, J = 7.6
Hz, 2H), 4.23−4.37 (m, 2H), 2.40 (s, 3H), 1.09 (t, J = 7.0 Hz, 3H).
13C NMR (100 MHz, CDCl3): δ 161.6, 140.6, 139.2, 137.7, 136.1,
135.9, 133.7, 131.0, 129.3, 129.0, 128.8, 128.7, 127.6, 123.9, 120.8,
Ethyl 1-Phenyl-5-(2-phenyl-1H-indol-1-yl)-1H-imidazole-4-
120.7, 111.0, 104.1, 104.0, 60.8, 21.3, 13.9. MS (EI, 70 eV) m/z: 421
carboxylate (3a). Yellow solid (50.5 mg, 62%). Mp 185−187 °C.
+
[M]+. HRMS calcd for C27H24N3O2 (M + H+): 422.1863, found
IR (KBr): 3052, 1720, 1600, 1577, 1500, 1454, 1154, 760 cm−1. H
1
422.1843. Anal. Calcd for C27H23N3O2: C, 76.94; H, 5.50; N, 9.97.
Found: C, 76.69; H, 5.27; N, 9.78.
NMR (400 MHz, CDCl3): δ 7.65 (s, 1H), 7.61−7.63 (m, 1H), 7.17−
7.29 (m, 5H), 7.10−7.13 (m, 2H), 7.02−7.06 (m, 2H), 6.84−6.86 (m,
3636
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The Journal of Organic Chemistry
Note
Table 2. Synthesis of Indolyl Imidazole Derivatives via a Tandem Reaction of N-[2-(1-Alkynyl)phenyl]carbodiimides 1 with
a
Isocyanides 2
b
entry
R1
R2
R3
R4
product
yield (%)
1
H
H
H
H
H
H
H
H
H
H
H
H
Me
Cl
H
H
H
H
H
H
H
H
Me
Cl
H
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
COOEt
COOBut
Ts
3a
3b
3c
3d
3e
3f
62
71
76
57
66
68
60
65
51
47
64
60
60
61
76
78
80
85
65
67
77
70
81
79
75
2
3
4
4-ClC6H4
COOEt
COOEt
COOEt
COOEt
COOEt
COOEt
COOEt
COOEt
COOEt
COOEt
COOEt
Ts
5
4-MeOC6H4
6
4-MeC6H4
7
cyclopropyl
3g
3h
3i
8
Ph
4-FC6H4
4-O2NC6H4
4-MeOC6H4
4-MeC6H4
n-C4H9
Ph
9
Ph
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
Ph
3j
Ph
3k
3l
Ph
Ph
3m
3n
3o
3p
3q
3r
Ph
Ph
4-ClC6H4
Ph
4-MeOC6H4
Ph
Ts
4-MeC6H4
Ph
Ts
Ph
4-FC6H4
4-MeOC6H4
4-MeC6H4
cyclohexyl
n-C4H9
Ph
Ts
Ph
Ts
3s
3t
Ph
Ts
Ph
Ts
3u
3v
3w
3x
3y
Ph
Ts
Ph
Ts
Ph
Ph
Ts
COOBut
4-ClC6H4
Ph
a
Reaction was performed with N-[2-(1-alkynyl)phenyl]carbodiimide 1 (0.2 mmol), isocyanide 2 (0.4 mmol), Cs2CO3 (0.4 mmol) in DMSO (2 mL)
b
at 40 °C for 12 h. Isolated yield.
1
Ethyl 5-(2-Cyclopropyl-1H-indol-1-yl)-1-phenyl-1H-imida-
zole-4-carboxylate (3g). Yellow solid (44.6 mg, 60%). Mp 117−
119 °C. IR (KBr): 2980, 1731, 1597, 1583, 1499, 1458, 1249, 1166,
1252, 1179, 752 cm−1. H NMR (400 MHz, CDCl3): δ 7.62 (s, 1H),
7.61 (d, J = 9.2 Hz, 1H), 7.12−7.27 (m, 6H), 6.90 (d, J = 7.2 Hz, 2H),
6.84 (d, J = 8.0 Hz, 2H), 6.60 (s, 1H), 6.24 (d, J = 8.0 Hz, 2H), 4.10−
4.28 (m, 2H), 0.99 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3):
δ 161.2, 156.1, 147.2, 139.7, 138.8, 138.7, 135.3, 131.1, 128.7, 128.6,
128.1, 127.5, 124.7, 124.4, 123.6, 122.1, 121.2, 110.9, 105.0, 61.1, 13.8.
MS (EI, 70 eV) m/z: 452 [M]+. HRMS calcd for C26H21N4O4+ (M +
H+): 453.1557, found 453.1536. Anal. Calcd for C26H20N4O4: C,
69.02; H, 4.46; N, 12.38. Found: C, 68.79; H, 4.27; N, 12.25.
Ethyl 1-(4-Methoxyphenyl)-5-(2-phenyl-1H-indol-1-yl)-1H-
imidazole-4-carboxylate (3j). Yellow solid (41.1 mg, 47%). Mp
157−159 °C. IR (KBr): 2924, 1720, 1593, 1516, 1456, 1251, 1178,
1
747 cm−1. H NMR (400 MHz, CDCl3): δ 7.95 (s, 1H), 7.46−7.48
(m, 1H), 7.26−7.30 (m, 3H), 7.06−7.12 (m, 4H), 6.98−7.00 (m, 1H),
6.10 (s, 1H), 4.00−4.14 (m, 2H), 1.33−1.38 (m, 1H), 0.86−0.89 (t, J
= 7.2 Hz, 3H), 0.70−0.75 (m, 1H), 0.62−0.67 (m, 1H), 0.53−0.60 (m,
1H), 0.16−0.22 (m, 1H). 13C NMR (100 MHz, CDCl3): δ 161.4,
144.1, 139.3, 136.4, 134.3, 129.8, 128.9, 128.6, 123.9, 122.1, 120.9,
120.2, 114.0, 109.7, 99.5, 60.5, 13.7, 7.9, 7.4, 6.4. MS (EI, 70 eV) m/z:
371 [M]+. HRMS calcd for C23H22N3O2+ (M + H+): 372.1707, found
372.1690. Anal. Calcd for C23H21N3O2: C, 74.38; H, 5.70; N, 11.31.
Found: C, 74.13; H, 5.48; N, 11.16.
839, 750 cm−1. H NMR (400 MHz, CDCl3): δ 7.64 (d, J = 8.4 Hz,
1
1H), 7.63 (s, 1H), 7.17−7.29 (m, 6H), 6.96 (d, J = 7.2 Hz, 2H), 6.63
(s, 1H), 6.57 (d, J = 8.4 Hz, 2H), 6.29 (d, J = 8.8 Hz, 2H), 4.16−4.30
(m, 2H), 3.74 (s, 3H), 1.03 (t, J = 7.0 Hz, 3H). 13C NMR (100 MHz,
CDCl3): δ 161.6, 142.2, 136.1, 131.6, 129.0, 128.7, 128.3, 127.7, 125.3,
123.1, 121.5, 120.8, 114.3, 110.9, 104.3, 60.7, 55.5, 13.8. MS (EI, 70
Ethyl 1-(4-Fluorophenyl)-5-(2-phenyl-1H-indol-1-yl)-1H-imi-
dazole-4-carboxylate (3h). Yellow solid (55.3 mg, 65%). Mp 203−
205 °C. IR (KBr): 3051, 2977, 1723, 1601, 1510, 1455, 1222, 1162,
1
841, 749 cm−1. H NMR (400 MHz, CDCl3): δ 7.62 (d, J = 4.8 Hz,
1H), 7.61 (s, 1H), 7.13−7.28 (m, 6H), 6.90 (d, J = 7.2 Hz, 2H), 6.73
(t, J = 8.6 Hz, 2H), 6.60 (s, 1H), 6.25−6.29 (m, 2H), 4.14−4.30 (m,
2H), 1.00 (t, J = 7.0 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 162.3
+
eV) m/z: 437 [M]+. HRMS calcd for C27H24N3O3 (M + H+):
438.1812, found 438.1796. Anal. Calcd for C27H23N3O3: C, 74.13; H,
5.30; N, 9.60. Found: C, 73.87; H, 5.08; N, 9.47.
1
(d, JCF = 247 Hz), 161.5, 140.1, 139.2, 135.9, 131.5, 130.9, 129.6,
129.1, 128.7, 128.4, 127.9, 127.6, 125.9 (d, 3JCF = 8 Hz), 123.3, 121.7,
120.9, 116.3 (d, 2JCF = 23 Hz), 110.9, 104.5, 60.8, 13.8. MS (EI, 70 eV)
m/z: 425 [M]+. HRMS calcd for C26H21FN3O2+ (M + H+): 426.1612,
found 426.1598. Anal. Calcd for C26H20FN3O2: C, 73.40; H, 4.74; N,
9.87. Found: C, 73.18; H, 4.51; N, 9.69.
Ethyl 5-(2-Phenyl-1H-indol-1-yl)-1-(p-tolyl)-1H-imidazole-4-
carboxylate (3k). Yellow solid (54.0 mg, 64%). Mp 186−188 °C.
IR (KBr): 3049, 2977, 1723, 1564, 1516, 1442, 1248, 1161, 762 cm−1.
1H NMR (400 MHz, CDCl3): δ 7.62 (s, 1H), 7.61 (d, J = 9.2 Hz, 1H),
7.12−7.27 (m, 6H), 6.90 (d, J = 7.2 Hz, 2H), 6.84 (d, J = 8.0 Hz, 2H),
6.60 (s, 1H), 6.24 (d, J = 8.0 Hz, 2H), 4.12−4.26 (m, 2H), 2.24 (s,
3H), 0.99 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 161.6,
140.5, 139.4, 138.8, 136.1, 131.6, 131.1, 130.9, 129.8, 129.1, 128.7,
Ethyl 1-(4-Nitrophenyl)-5-(2-phenyl-1H-indol-1-yl)-1H-imi-
dazole-4-carboxylate (3i). Yellow solid (46.2 mg, 51%). Mp
208−210 °C. IR (KBr): 3053, 2977, 1721, 1599, 1525, 1502, 1347,
3637
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The Journal of Organic Chemistry
Note
128.3, 127.7, 123.7, 123.1, 121.5, 120.8, 110.9, 104.3, 60.7, 21.0, 13.8.
MS (EI, 70 eV) m/z: 421 [M]+. HRMS calcd for C27H24N3O2+ (M +
H+): 422.1863, found 422.1846. Anal. Calcd for C27H23N3O2: C,
76.94; H, 5.50; N, 9.97. Found: C, 76.75; H, 5.23; N, 9.79.
1-Phenyl-5-[2-(p-tolyl)-1H-indol-1-yl]-4-(p-tolylsulfonyl)-1H-
imidazole (3q). Yellow solid (80.6 mg, 80%). Mp 173−174 °C. IR
(KBr): 2928, 1611, 1599, 1501, 1455, 1320, 1250, 1176, 751 cm−1. 1H
NMR (400 MHz, CDCl3): δ 7.80 (d, J = 8.4 Hz, 2H), 7.67 (s, 1H),
7.58−7.60 (m, 1H), 7.18−7.26 (m, 5H), 7.02−7.07 (m, 3H), 6.88 (d, J
= 7.6 Hz, 2H), 6.69 (d, J = 8.0 Hz, 2H), 6.56 (s, 1H), 6.31−6.33 (m,
2H), 2.40 (s, 3H), 2.29 (s, 3H). 13C NMR (100 MHz, CDCl3): δ
144.5, 141.2, 140.0, 137.8, 137.5, 137.4, 136.2, 133.2, 130.0, 129.6,
129.3, 129.1, 129.0, 128.8, 128.4, 128.3, 127.7, 124.1, 123.1, 121.8,
120.8, 111.2, 104.7, 21.7, 21.2. MS (EI, 70 eV) m/z: 503 [M]+. HRMS
calcd for C31H26N3O2S+ (M + H+): 504.1740, found 504.1718. Anal.
Calcd for C31H25N3O2S: C, 73.93; H, 5.00; N, 8.34. Found: C, 73.77;
H, 5.12; N, 8.18.
Ethyl 1-Butyl-5-(2-phenyl-1H-indol-1-yl)-1H-imidazole-4-
carboxylate (3l). Yellow solid (46.5 mg, 60%). Mp 74−76 °C. IR
(KBr): 3059, 2957, 2870, 1700, 1588, 1563, 1420, 1267, 1186, 1073,
1
765 cm−1. H NMR (400 MHz, CDCl3): δ 7.90 (s, 1H), 7.76−7.81
(m, 3H), 7.52−7.54 (m, 2H), 7.46 (t, J = 7.8 Hz, 3H), 7.36−7.41 (m,
1H), 7.30−7.32 (m, 1H), 6.57 (s, 1H), 4.46−4.52 (m, 2H), 3.82 (s,
2H), 1.49−1.52 (m, 3H), 1.29−1.32 (m, 2H), 0.94−0.99 (m, 2H),
0.66 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 162.3, 139.6,
135.1, 135.1, 129.2, 128.7, 128.6, 127.4, 127.0, 125.8, 124.2, 115.7,
115.4, 115.1, 60.3, 54.9, 30.2, 19.7, 14.7, 13.6. MS (EI, 70 eV) m/z:
387 [M]+. HRMS calcd for C24H26N3O2+ (M + H+): 388.2020, found
388.2009. Anal. Calcd for C24H25N3O2: C, 74.40; H, 6.50; N, 10.84.
Found: C, 74.16; H, 6.31; N, 10.69.
1-(4-Fluorophenyl)-5-(2-phenyl-1H-indol-1-yl)-4-(p-tolylsul-
fonyl)-1H-imidazole (3r). Yellow solid (86.3 mg, 85%). Mp 213-215
°C. IR (KBr): 2953, 2924, 2854, 1599, 1580, 1462, 1456, 1377, 1261,
1
802 cm−1. H NMR (400 MHz, CDCl3): δ 7.74 (d, J = 8.0 Hz, 2H),
7.71 (d, J = 8.0 Hz, 1H), 7.59 (s, 1H), 7.54 (d, J = 7.2 Hz, 1H), 7.44−
7.49 (m, 1H), 7.22 (d, J = 8.0 Hz, 1H), 7.11−7.17 (m, 3H), 6.99−7.03
(m, 3H), 6.73 (d, J = 7.2 Hz, 2H), 6.64 (t, J = 8.4 Hz, 2H), 6.55 (s,
1H), 6.12−6.15 (m, 1H), 2.33 (s, 3H). 13C NMR (100 MHz, CDCl3):
δ 162.4 (d, 1JCF = 249 Hz), 144.8, 140.6, 139.9, 137.2, 137.0, 136.3 (d,
Ethyl 5-(5-Methyl-2-phenyl-1H-indol-1-yl)-1-phenyl-1H-imi-
dazole-4-carboxylate (3m). Yellow solid (50.6 mg, 60%). Mp 182−
184 °C. IR (KBr): 3045, 2976, 1727, 1596, 1568, 1501, 1416, 1249,
1
1170, 806, 758 cm−1. H NMR (400 MHz, CDCl3): δ 7.65 (s, 1H),
7.41 (s, 1H), 7.16−7.22 (m, 2H), 7.09−7.13 (m, 4H), 7.03−7.07 (m,
2H), 6.84−6.86 (m, 2H), 6.52 (s, 1H), 6.32−6.34 (m, 2H), 4.19−4.29
(m, 2H), 2.48 (s, 3H), 1.06 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz,
CDCl3): δ 161.6, 140.4, 137.6, 135.8, 133.7, 131.7, 131.1, 130.8, 129.2,
129.0, 128.6, 128.2, 127.6, 127.6, 124.7, 123.8, 120.6, 110.6, 104.1,
60.7, 21.5, 13.9. MS (EI, 70 eV) m/z: 421 [M]+. HRMS calcd for
2JCF = 25 Hz), 130.9, 129.8, 129.5, 128.9, 128.5, 128.3, 128.1 (d, 3JCF
=
7 Hz), 127.5, 127.3, 126.0, 121.0, 120.8, 116.3, 111.1, 105.1, 104.9,
21.6. MS (EI, 70 eV) m/z: 507 [M]+. HRMS calcd for
C30H23FN3O2S+ (M + H+): 508.1490, found 508.1478. Anal. Calcd
for C30H22FN3O2S: C, 70.99; H, 4.37; N, 8.28. Found: C, 70.75; H,
4.56; N, 8.09.
+
C27H24N3O2 (M + H+): 422.1863, found 422.1841. Anal. Calcd for
1-(4-Methoxyphenyl)-5-(2-phenyl-1H-indol-1-yl)-4-(p-tolyl-
sulfonyl)-1H-imidazole (3s). Yellow solid (67.5 mg, 65%). Mp
162−164 °C. IR (KBr): 2963, 2935, 1595, 1567, 1511, 1454, 1325,
1251, 1147, 808 cm−1. 1H NMR (400 MHz, CDCl3): δ 7.82 (d, J =7.2
Hz, 2H), 7.71 (d, J = 8.0 Hz, 1H), 7.60 (s, 1H), 7.19−7.26 (m, 5H),
7.04−7.11 (m, 3H), 6.87 (d, J = 7.2 Hz, 2H), 6.62 (s, 1H), 6.50 (d, J =
8.0 Hz, 2H), 6.20 (d, J = 8.0 Hz, 2H), 3.66 (s, 3H), 2.40 (s, 3H). 13C
NMR (100 MHz, CDCl3): δ 144.6, 141.0, 140.1, 137.4, 137.2, 136.6,
136.4, 131.2, 129.8, 129.6, 128.7, 128.5, 128.3, 128.1, 127.8, 125.8,
125.5, 121.9, 121.7, 121.0, 120.8, 114.4, 105.1, 55.5, 21.7. MS (EI, 70
eV) m/z: 519 [M]+. HRMS calcd for C31H26N3O3S+ (M + H+):
520.1689, found 520.1688. Anal. Calcd for C31H25N3O3S: C, 71.66; H,
4.85; N, 8.08. Found: C, 71.42; H, 4.98; N, 7.92.
C27H23N3O2: C, 76.94; H, 5.50; N, 9.97. Found: C, 76.76; H, 5.71; N,
9.78.
Ethyl 5-(5-Chloro-2-phenyl-1H-indol-1-yl)-1-phenyl-1H-imi-
dazole-4-carboxylate (3n). Yellow solid (53.9 mg, 61%). Mp
183−185 °C. IR (KBr): 3045, 1721, 1598, 1567, 1499, 1451, 1245,
1
1172, 1154, 760 cm−1. H NMR (400 MHz, CDCl3): δ 7.65 (s, 1H),
7.59 (d, J = 2.0 Hz, 1H), 7.20−7.25 (m, 3H), 7.12−7.16 (m, 3H),
7.05−7.09 (m, 2H), 6.83−6.86 (m, 2H), 6.53 (s, 1H), 6.30−6.33 (m,
2H), 4.20−4.30 (m, 2H), 1.08 (t, J = 7.2 Hz, 3H). 13C NMR (100
MHz, CDCl3): δ 161.4, 141.8, 137.6, 136.0, 133.5, 131.7, 131.0, 130.4,
129.7, 129.4, 128.8, 128.4, 128.1, 127.7, 127.2, 123.8, 123.4, 120.3,
112.0, 103.8, 60.9, 14.0. MS (EI, 70 eV) m/z: 441 [M]+. HRMS calcd
for C26H21ClN3O2+ (M + H+): 442.1317, found 442.1301. Anal. Calcd
for C26H20ClN3O2: C, 70.66; H, 4.56; N, 9.50. Found: C, 70.41; H,
4.32; N, 9.39.
1-Phenyl-5-[2-(4-chlorophenyl)-1H-indol-1-yl]-4-(p-tolylsul-
fonyl)-1H-imidazole (3o). Yellow solid (79.7 mg, 76%). Mp 176−
178 °C. IR (KBr): 2919, 1595, 1498, 1417, 1394, 1185, 892, 714 cm−1.
1H NMR (400 MHz, CDCl3): δ 7.79 (d, J = 8.0 Hz, 2H), 7.71 (s, 1H),
1-(p-Tolyl)-5-(2-phenyl-1H-indol-1-yl)-4-(p-tolylsulfonyl)-1H-
imidazole (3t). Yellow solid (67.5 mg, 67%). Mp 191−193 °C. IR
(KBr): 2956, 2924, 1596, 1567, 1515, 1455, 1328, 1149, 815, 706
1
cm−1. H NMR (400 MHz, CDCl3): δ 7.81 (d, J = 8.0 Hz, 2H), 7.62
(s, 1H), 7.18−7.27 (m, 6H), 7.05−7.11 (m, 4H), 6.84 (t, J = 7.6 Hz,
3H), 6.62 (s, 1H), 6.19 (d, J = 8.0 Hz, 2H), 2.41 (s, 3H), 2.24 (s, 3H).
13C NMR (100 MHz, CDCl3): δ 144.6, 141.0, 140.1, 139.4, 137.4,
7.61 (d, J = 6.8 Hz, 1H), 7.52−7.54 (m, 1H), 7.18−7.28 (m, 5H),
7.04−7.08 (m, 4H), 6.73 (d, J = 8.4 Hz, 2H), 6.60 (s, 1H), 6.33 (d, J =
7.6 Hz, 2H), 2.42 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 144.8,
140.1, 139.7, 138.4, 137.7, 137.2, 136.4, 134.0, 133.0, 132.3, 129.8,
129.7, 129.0, 128.9, 128.6, 128.5, 128.4, 127.8, 124.0, 121.1, 121.0,
111.2, 105.6, 21.7. MS (EI, 70 eV) m/z: 523 [M]+. HRMS calcd for
C30H23ClN3O2S+ (M + H+): 524.1194, found 524.1193. Anal. Calcd
for C30H22ClN3O2S: C, 68.76; H, 4.23; N, 8.01. Found: C, 68.47; H,
4.46; N, 7.82.
136.4, 136.2, 131.2, 130.6, 130.1, 129.9, 129.8, 129.5, 128.7, 128.5,
128.4, 128.2, 127.8, 123.9, 121.0, 120.8, 105.1, 105.0, 21.7, 21.1. MS
(EI, 70 eV) m/z: 503 [M]+. HRMS calcd for C31H26N3O2S+ (M +
H+): 504.1740, found 504.1728. Anal. Calcd for C31H25N3O2S: C,
73.93; H, 5.00; N, 8.34. Found: C, 73.68; H, 4.79; N, 8.15.
1-Cyclohexyl-5-(2-phenyl-1H-indol-1-yl)-4-(p-tolylsulfonyl)-
1H-imidazole (3u). Yellow solid (76.3 mg, 77%). Mp 238−239 °C.
IR (KBr): 2935, 2852, 1596, 1555, 1492, 1448, 1316, 1145, 749, 700
1
cm−1. H NMR (400 MHz, CDCl3): δ 8.14 (d, J = 7.6 Hz, 2H), 8.03
1-Phenyl-5-[2-(4-methoxyphenyl)-1H-indol-1-yl]-4-(p-tolyl-
sulfonyl)-1H-imidazole (3p). Yellow solid (81.1 mg, 78%). Mp
222−224 °C. IR (KBr): 2922, 1647, 1596, 1500, 1438, 1384, 1150,
(d, J = 8.4 Hz, 2H), 7.88 (s, 1H), 7.66−7.68 (m, 1H), 7.41−7.45 (m,
2H), 7.26−7.39 (m, 6H), 6.74 (s, 1H), 3.81−3.87 (m, 1H), 2.37 (s,
3H), 2.04−2.07 (m, 1H), 1.55−1.57 (m, 1H), 1.37−1.43 (m, 3H),
1.16−1.26 (m, 2H), 0.83−0.98 (m, 3H). 13C NMR (100 MHz,
CDCl3): δ 143.7, 139.4, 138.3, 135.2, 132.4, 130.7, 130.0, 129.6, 128.9,
128.7, 128.5, 128.1, 127.9, 127.7, 126.4, 124.5, 115.2, 69.2, 31.5, 30.8,
25.8, 25.7, 25.3, 21.6. MS (EI, 70 eV) m/z: 495 [M]+. HRMS calcd for
C30H30N3O2S+ (M + H+): 496.2053, found 496.2032. Anal. Calcd for
C30H29N3O2S: C, 72.70; H, 5.90; N, 8.48. Found: C, 72.54; H, 5.65;
N, 8.29.
1
707, 676 cm−1. H NMR (400 MHz, CDCl3): δ 7.80 (d, J = 8.0 Hz,
2H), 7.68 (s, 1H), 7.58 (d, J = 7.6 Hz, 1H), 7.16−7.28 (m, 5H), 7.00−
7.07 (m, 3H), 6.73 (d, J = 8.4 Hz, 2H), 6.61 (d, J = 8.4 Hz, 2H), 6.52
(s, 1H), 6.32 (d, J = 8.4 Hz, 2H), 3.76 (s, 3H), 2.41 (s, 3H). 13C NMR
(100 MHz, CDCl3): δ 144.6, 140.8, 139.8, 137.4, 137.2, 133.0, 129.7,
129.6, 129.3, 129.1, 128.7, 128.4, 128.2, 128.1, 124.0, 123.5, 113.7,
113.6, 111.0, 104.2, 104.1, 55.3, 21.6. MS (EI, 70 eV) m/z: 519 [M]+.
HRMS calcd for C31H26N3O3S+ (M + H+): 520.1689, found 520.1685.
Anal. Calcd for C31H25N3O3S: C, 71.66; H, 4.85; N, 8.08. Found: C,
71.37; H, 4.99; N, 7.87.
1-Butyl-5-(2-phenyl-1H-indol-1-yl)-4-(p-tolylsulfonyl)-1H-
imidazole (3v). Yellow solid (65.7 mg, 70%). Mp 131−133 °C. IR
(KBr): 2959, 2925, 1626, 1588, 1557, 1493, 1317, 1302, 1142, 1086,
3638
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The Journal of Organic Chemistry
Note
1
761 cm−1. H NMR (400 MHz, CDCl3): δ 8.00 (d, J = 8.0 Hz, 2H),
REFERENCES
■
7.87 (s, 1H), 7.80−7.82 (m, 2H), 7.75 (d, J = 7.2 Hz, 1H), 7.46−7.50
(m, 2H), 7.31−7.43 (m, 6H), 6.57 (s, 1H), 3.78 (s, 2H), 2.41 (s, 3H),
1.14−1.21 (m, 2H), 0.85−0.95 (m, 2H), 0.57 (t, J = 7.4 Hz, 3H). 13C
NMR (100 MHz, CDCl3): δ 143.6, 139.5, 137.0, 134.7, 134.3, 129.8,
129.6, 129.3, 129.1, 129.0, 128.7, 127.7, 127.5, 126.5, 125.5, 124.2,
116.8, 115.4, 115.3, 56.5, 30.5, 21.6, 19.6, 13.5. MS (EI, 70 eV) m/z:
469 [M]+. HRMS calcd for C28H28N3O2S+ (M + H+): 470.1897, found
470.1876. Anal. Calcd for C28H27N3O2S: C, 71.62; H, 5.80; N, 8.94.
Found: C, 71.38; H, 5.58; N, 8.76.
5-(5-Methyl-2-phenyl-1H-indol-1-yl)-1-phenyl-4-(p-tolylsul-
fonyl)-1H-imidazole (3w). Yellow solid (81.6 mg, 81%). Mp 240−
242 °C. IR (KBr): 3060, 1596, 1570, 1502, 1467, 1330, 1216, 1151,
1086, 810, 760 cm−1. 1H NMR (400 MHz, CDCl3): δ 7.83 (d, J = 8.4
Hz, 2H), 7.67 (s, 1H), 7.40 (s, 1H), 7.14−7.28 (m, 4H), 7.01−7.06
(m, 6H), 6.71−6.73 (m, 2H), 6.52 (s, 1H), 6.26−6.28 (m, 2H), 2.49
(s, 3H), 2.40 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 144.6, 140.9,
138.5, 137.4, 136.1, 133.2, 131.3, 131.2, 130.0, 129.6, 129.3, 129.1,
128.9, 128.4, 128.2, 127.7, 127.6, 127.1, 124.8, 123.9, 120.7, 111.0,
104.8, 21.6, 21.5. MS (EI, 70 eV) m/z: 503 [M]+. HRMS calcd for
C31H26N3O2S+ (M + H+): 504.1740, found 504.1731. Anal. Calcd for
C31H25N3O2S: C, 73.93; H, 5.00; N, 8.34. Found: C, 73.65; H, 5.23;
N, 8.16.
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New York, 1970. (b) Brown, R. K. In Indoles; Houlihan, W. J., Ed.;
Wiley-Interscience: New York, 1972. (c) Sharma, V.; Kumar, P. D. J.
Heterocycl. Chem. 2010, 47, 491. (d) Kaushik, N. K.; Kaushik, N.; Attri,
P.; Kumar, N.; Kim, C. H.; Verma, A. K.; Choi, E. H. Molecules 2013,
18, 6620.
(2) For recent reviews on indole synthesis, see: (a) Marco, B.; Astrid,
E. Angew. Chem., Int. Ed. 2009, 48, 9608. (b) Taber, D. F.; Tirunahari,
P. K. Tetrahedron 2011, 67, 7195. (c) Cacchi, S.; Fabrizi, G.;
Goggiamani, A. Org. React. 2012, 76, 281.
(3) Fischer, E.; Jourdan, F. Chem. Ber. 1883, 16, 2241.
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2006, 8, 3271. (i) Han, X.; Lu, X. Org. Lett. 2010, 12, 3336. (j) Alvarez,
5-(5-Chloro-2-phenyl-1H-indol-1-yl)-1-phenyl-4-(p-tolylsul-
fonyl)-1H-imidazole (3x). Yellow solid (82.8 mg, 79%). Mp 182−
184 °C. IR (KBr): 2917, 1652, 1597, 1498, 1437, 1317, 1149, 710, 661
́
R.; Martınez, C.; Madich, Y.; Denis, J. G.; Aurrecoechea, J. M.; de
Lera, A. R. Chem.Eur. J. 2010, 16, 12746.
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see: (a) Ohno, H.; Ohta, Y.; Oishi, S.; Fujii, N. Angew. Chem., Int. Ed.
2007, 46, 2295. (b) Ohta, Y.; Chiba, H.; Oishi, S.; Fujii, N.; Ohno, H.
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D.; Ding, K. Chem. Commun. 2009, 7581. (e) Chen, Z.; Zheng, D.;
Wu, J. Org. Lett. 2011, 13, 848.
cm−1. H NMR (400 MHz, CDCl3): δ 7.75 (s, 1H), 7.64 (d, J = 8.0
1
Hz, 2H), 7.49 (s, 1H), 7.21 (d, J = 7.8 Hz, 2H), 7.11−7.16 (m, 2H),
7.06 (d, J = 8.4 Hz, 1H), 6.93−7.01 (m, 5H), 6.67 (d, J = 7.6 Hz, 2H),
6.50 (s, 1H), 6.23(d, J = 7.6 Hz, 2H), 2.33 (s, 3H). 13C NMR (100
MHz, CDCl3): δ 144.5, 141.9, 137.9, 136.8, 136.5, 132.4, 131.9, 130.1,
129.4, 129.2, 128.1, 127.8, 127.1, 126.9, 126.8, 123.6, 123.0, 119.9,
112.0, 103.9, 21.3. MS (EI, 70 eV) m/z: 523 [M]+. HRMS calcd for
C30H23ClN3O2S+ (M + H+): 524.1194, found 524.1179. Anal. Calcd
for C30H22ClN3O2S: C, 68.76; H, 4.23; N, 8.01. Found: C, 68.47; H,
4.51; N, 7.89.
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(a) Jana, S.; Clements, M. D.; Sharp, B. K.; Zheng, N. Org. Lett. 2010,
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tert-Butyl 5-[2-(4-Chlorophenyl)-1H-indol-1-yl]-1-phenyl-1H-
imidazole-4-carboxylate (3y). Yellow solid (70.5 mg, 75%). Mp
260−262 °C. IR (KBr): 2970, 1724, 1597, 1578, 1500, 1455, 1256,
1154, 840, 797 cm−1.1H NMR (400 MHz, CDCl3): δ 7.68 (s, 1H),
7.62 (d, J = 8.0 Hz, 1H), 7.20−7.31 (m, 4H), 7.05−7.13 (m, 4H), 6.80
(d, J = 8.4 Hz, 2H), 6.56 (s, 1H), 6.37 (d, J = 7.6 Hz, 2H), 1.14 (s,
9H). 13C NMR (100 MHz, CDCl3): δ 160.6, 139.4, 138.7, 136.0,
133.9, 133.7, 130.7, 130.1, 129.3, 128.9, 128.7, 128.5, 123.8, 123.3,
121.6, 120.9, 111.0, 104.3, 81.3, 27.7. MS (EI, 70 eV) m/z: 469 [M]+.
+
HRMS calcd for C28H25ClN3O2 (M + H+): 470.1630, found
470.1622. Anal. Calcd for C28H24ClN3O2: C, 71.56; H, 5.15; N,
8.94. Found: C, 71.35; H, 5.34; N, 8.78.
ASSOCIATED CONTENT
■
S
* Supporting Information
Copies of 1H and 13C NMR spectra for the products and X-ray
crystal data of compound 3a. This material is available free of
charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*Fax: (+86)-791-8812-0388. E-mail: mzcai@jxnu.edu.cn.
Notes
The authors declare no competing financial interest.
(10) (a) Zheng, D.; Li, S.; Luo, Y.; Wu, J. Org. Lett. 2011, 13, 6402.
(b) Qiu, G.; Wu, J. Chem. Commun. 2012, 48, 6046. (c) Zheng, D.; Li,
S.; Wu, J. Chem. Commun. 2012, 48, 8568. (d) Zheng, D.; Li, S.; Wu, J.
Org. Lett. 2012, 14, 2655. (e) Li, S.; Wu, J. Chem. Commun. 2012, 48,
8973.
ACKNOWLEDGMENTS
■
Financial support from National Natural Science Foundation of
China (No. 20864008) is gratefully acknowledged.
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The Journal of Organic Chemistry
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