Three-component reaction for the C2-functionalization of 1-substituted imidazoles with acetylenic ketones and isocyanates

Article abstract of DOI:10.1016/j.tet.2011.08.069

An efficient method for the direct C2-amidation of 1-substituted imidazoles with acetylenic ketones and isocyanates is reported. This three-component procedure has the advantages of catalyst-free, operational simplicity, mild reaction conditions, and good to excellent yields.

Full text of DOI:10.1016/j.tet.2011.08.069

Tetrahedron 67 (2011) 8338e8342
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Three-component reaction for the C2-functionalization of 1-substituted
imidazoles with acetylenic ketones and isocyanates
*
*
Yang Shen, Shuying Cai, Chi He, Xufeng Lin , Ping Lu, Yanguang Wang
Department of Chemistry, Zhejiang University, Hangzhou 310027, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 9 July 2011
Received in revised form 14 August 2011
Accepted 23 August 2011
Available online 27 August 2011
An efficient method for the direct C2-amidation of 1-substituted imidazoles with acetylenic ketones and
isocyanates is reported. This three-component procedure has the advantages of catalyst-free, operational
simplicity, mild reaction conditions, and good to excellent yields.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Multicomponent reactions
Cascade reactions
Huisgen zwitterion
Imidazoles
Heterocycles
1. Introduction
Previously, we have utilized the Huisgen zwitterions to synthesize
pyrazolines and triazolinones.8 In continuation of our efforts to de-
Functionalized imidazoles are an important class of heterocyclic
compounds in organic chemistry because they are common struc-
tural units in a number of natural products and pharmaceuticals
and useful building blocks for the construction of various bi-
ologically active molecules and functional materials.1 Imidazole-
based drugs, such as Cimetidine, Etomidate, and Ketoconazole are
currently in clinical use.2 Other applications of imidazole de-
rivatives include the imidazole-tailored ionic liquids and stable
nucleophilic carbenes.3 Consequently, efforts are focused on the
development of methods for the synthesis and functionalization of
the imidazole nucleus.4
Multicomponent reactions (MCRs) have emerged as a powerful
and bond-forming efficient tool in organic, combinatorial, and
medicinal chemistry.5 Using this strategy, C2-founctionalizations of
1-substituted imidazoles have been successfully performed.6 Con-
sidering the continued importance of the imidazole derivatives in
both biological and chemical fields, new direct approaches remain
highly valuable to the contemporary collection of synthetic
methods.
velop MCRs,9 herein we report a multicomponent reaction strategy
for the direct C2-amidation of 1-substituted imidazoles with acet-
ylenic ketones and isocyanates.
2. Results and discussion
Exhaustive studies of the reaction conditions for the synthesis of
imidazole 4a from phenyl acetylenic ketone 1a with phenyl-
isocyanate 2a and N-methylimidazole 3a were conducted (Table 1).
We first examined the reaction temperature and reaction time in
dichloromethane (DCM), and found that the yield was slightly de-
pendent upon the reaction temperature and the time (Table 1,
entries 1e5). Furthermore, we examined several organic solvents
and found that a remarkable solvent effect existed in this model
reaction at room temperature. These results showed that DCM was
the most suitable solvent for this transformation among others,
such as acetonitrile, toluene, and chloroform (Table 1, entries 5e8).
Thus, the most suitable reaction conditions for the formation of 4a
were stablished (Table 1, entry 5).
With the optimized reaction conditions in hand, we next ex-
plored the protocol with a variety of acetylenic ketones and iso-
cyanates, and the results were presented in Table 2. From the
results of Table 2, the protocol has proven to be useful multicom-
ponent reaction of acetylenic ketones 1aei with isocyanates 2aek
and imidazoles 3aec in DCM at room temperature in the absence of
any catalyst to afford the corresponding products 4a-u in 72e98%
The reactions of zwitterionic adducts of nucleophiles for various
organic transformations have received considerable attention.7
* Corresponding authors. Tel./fax: þ86 571 87951512; e-mail addresses: lxfok@
zju.edu.cn (X. Lin), orgwyg@zju.edu.cn (Y. Wang).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.08.069

Y. Shen et al. / Tetrahedron 67 (2011) 8338e8342
8339
Table 1
Optimization of reaction conditions for the synthesis of 4aa
Entry
Temp (ꢀC)
Solvent
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
0
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH3CN
PhMe
24
24
1
71
84
72
78
84
67
57
Reflux
rt
rt
rt
rt
rt
rt
8
Fig. 1. X-ray crystal structure of 4c.
24
24
48
24
CHCl3
23
Furthermore, a tentative mechanism for this three-component
reaction is proposed in Scheme 1. Firstly, the zwitterion A is de-
rived from initial nucleophilic addition of imidazole 3a to acetyle-
nic ketone 1a.4,5 Then, the imidazole carbene intermediate B forms
via proton transfer from position 2 of the imidazole ring to the
carbanionic center of A. Then, the imidazole carbene intermediate
B nucleophilically attacks the central carbon of isocyanate 2a to
form the zwitterionic adduct C, which undergoes an intramolecular
conjugated additioneelimination to yield the final product 4a.
Bold values in the table means the optimized reaction conditions.
a
Reaction conditions: 1a (1.0 mmol), 2a (1.0 mmol), 3a (1.0 mmol), the indicated
solvent (5 mL).
b
Yield of isolated product.
Table 2
Scope of the reactiona
COPh
COPh
COPh
O
N
+
N
N
Entry
1 (R1)
2 (R2)
3 (R3)
Yieldb (%)
N
N
Ph
H3C
N
N
N
1
2
3
4
5
6
7
8
1a (Ph)
2a (Ph)
2a
2a
2a
2a
2a
2a
2a
3a(Me)
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
4a/87
4b/91
4c/93
4d/78
4e/73
4f/88
4g/98
4h/72
4i/74
4j/78
4k/82
4l/96
4m/90
4n/74
4o/92
4p/97
4q/76
4r/95
4s/83
4t/90
CH3
3a
1a
CH3
CH3
1b (4-ClC6H4)
1c (4-BrC6H4)
1d (4-MeOC6H4)
1e (4-NO2C6H4)
1f (4-MeC6H4)
1g (Furan-2-)
B
A
Ph
Ph
N
C O
2a
1h (n-C6H13
1i (PhCH]CH)
)
O
N
Ph
9
2a
O
10
11
12
13
14
15
16
17
18
19
20
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
2b (4-MeC6H4)
2c (4-BrC6H4)
2d (2-BrC6H4)
2e (3-AcOC6H4)
2f (4-NO2C6H4)
2g (4-CH3OC6H4)
2h (4-FC6H4)
2i (3-ClC6H4)
2j (EtOCOCH2)
2k (Cyclohexyl)
2a
O
O
NPh
N
N
N
Ph
Ph
NPh
O
N
N
H3C
N
CH3
CH3
O
4a
D
C
Scheme 1. Possible mechanism for the formation of 4.
3a
3a
3a
3. Conclusion
3b (PhCH2)
In summary, we have developed an efficient method for the
direct C2-amidation of 1-substituted imidazoles via a three-
component reaction of 1-substituted imidazoles with acetylenic
ketones and isocyanates under mild conditions. The major features
of this procedure include: (1) high synthetic efficiency, (2) atom
economics, and (3) catalyst-free.
21
1a
2a
4u/82
a
Reaction conditions: 1 (1.0 mmol), 2 (1.0 mmol), 3 (1.0 mmol), CH2Cl2 (5 mL),
room temperature, 24 h.
b
Yield of isolated products.
4. Experimental section
4.1. General experimental
yields. It should be noted that the reactions with the alkyl acety-
lenic ketone 1i, alkyl isocyanates 2jek or 1-methyl-1H-benzo[d]
imidazole 3c proceeded smoothly, leading to good yields of prod-
ucts 4 (Table 2, entries 8, 18, 19, and 21).
Infrared spectra were obtained on an FTIR spectrometer. 1H
NMR spectra were recorded on 400 MHz spectrometer unless noted
otherwise and the chemical shifts were reported relative to internal
standard TMS (0 ppm). The following abbreviations are used to
describe peak patterns where appropriate: br¼broad, s¼singlet,
d¼doublet, t¼triplet, q¼quartet, m¼multiplet. Coupling constants
The structures of products 4aeu were characterized by 1H NMR,
13C NMR, IR and HRMS spectra. The structure of compound 4c
(Table 2, entry 3) was unambiguously confirmed by single-crystal
X-ray analysis (Fig. 1).10

8340
Y. Shen et al. / Tetrahedron 67 (2011) 8338e8342
are reported in hertz (Hz). 13C NMR were recorded on 100 MHz
unless noted otherwise and referenced to the internal solvent sig-
nals (central peak is 77.0 ppm for CDCl3 or 40.0 ppm for DMSO-d6).
MS and HRMS were obtained using EI ionization. Melting points
were measured with micro melting point apparatus.
170e172 ꢀC; IR: 1674, 1595, 1513, 1420, 1264, 1178, 1074, 849 cmꢁ1
1H NMR (CDCl3, 400 MHz):
;
d
9.48 (d, J¼13.6 Hz, 1H), 8.23 (d,
J¼8.8 Hz, 2H), 7.89 (d, J¼8.8 Hz, 2H), 7.59e7.49 (m, 3H), 7.30 (d,
J¼7.2 Hz, 2H), 7.16 (s, 1H), 7.08 (s, 1H), 5.88 (d, J¼13.6 Hz, 1H), 3.97
(s, 3H) ppm; 13C NMR (CDCl3, 100 MHz):
d 189.2, 160.1, 150.0, 149.2,
DCM was distilled from phosphorous pentoxide, and CH3CN was
distilled from CaH2, while THF and toluene were distilled from Na/
benzophenone, respectively. The propynones were prepared via
the nucleophilic addition of ethynylmagnesium bromides to alde-
hydes and then oxidation with IBX.11
143.8, 138.1, 138.0, 130.3, 129.5, 129.4, 129.3, 128.3, 126.6, 123.8,
107.2, 36.2 ppm; HRMS (EI): m/z calcd for C20H16N4O4 ([M]þ):
376.1172; found: 376.1176.
4.2.6. (E)-1-Methyl-N-(3-oxo-3-p-tolylprop-1-enyl)-N-phenyl-1H-
imidazole-2-carboxamide (4f). Yellow solid, mp 142e144 ꢀC; IR:
1658, 1583, 1399, 1250, 1148, 1030, 973, 815 cmꢁ1; 1H NMR (CDCl3,
4.2. General procedure for the synthesis of imidazoles 4
400 MHz):
d
9.33 (d, J¼13.6 Hz, 1H), 7.67 (d, J¼8.0 Hz, 2H),
To a solution of acetylenic ketone 1 (1.0 mmol) and N-alky-
limmidazole 3 (1.0 mmol) in DCM (5 mL) was slowly added iso-
cyanate 2 (1.0 mmol) through a syringe under nitrogen atmosphere
over 3e5 min. The reaction mixture was stirred at room tempera-
ture for 24 h. After the solvent was removed under reduced pres-
sure, the residue was subject to flash chromatography on silica gel
(petroleum ether/ethyl acetate, 2:1 to 1:1) to afford pure 4.
7.56e7.46 (m, 3H), 7.30 (d, J¼7.6 Hz, 2H), 7.18 (d, J¼8.4 Hz, 2H) 7.14
(s, 1H), 7.04 (s, 1H), 5.98 (d, J¼13.6 Hz, 1H), 3.94 (s, 3H), 2.36 (s, 3H)
ppm; 13C NMR (CDCl3, 100 MHz):
d 189.8, 160.1, 146.5, 142.9, 138.2,
138.1, 135.8, 129.8, 129.0, 128.9, 128.8, 128.2, 128.1, 125.8, 107.5, 35.6,
21.5 ppm; HRMS (EI): m/z calcd for C21H19N3O2 ([M]þ): 345.1477;
found: 345.1479.
4.2.7. (E)-N-(3-(Furan-2-yl)-3-oxoprop-1-enyl)-1-methyl-N-phenyl-
4.2.1. (E)-1-Methyl-N-(3-oxo-3-phenylprop-1-enyl)-N-phenyl-1H-
imidazole-2-carboxamide (4a). Yellow solid, mp 149e151 ꢀC; IR:
1646, 1570, 1402, 1251, 1168, 1040, 954, 643 cmꢁ1; 1H NMR (CDCl3,
1H-imidazole-2-carboxamide (4g). Yellow solid, mp 188e190 ꢀC;
IR: 1644, 1569, 1490, 1410, 1251, 1173, 1080, 1034 cmꢁ1 1H NMR
;
(CDCl3, 500 MHz):
d
9.38 (d, J¼14.0 Hz, 1H), 7.56e7.47 (m, 4H), 7.29
400 MHz):
d
9.35 (d, J¼13.6 Hz, 1H), 7.75e7.73 (m, 2H), 7.54e7.49
(d, J¼7.5 Hz, 2H), 7.15 (s, 1H), 7.07e7.06 (m, 2H), 6.47e6.46 (m, 1H),
(m, 2H), 7.47e7.45 (m, 2H), 7.39e7.37 (m, 2H), 7.30e7.28 (m, 2H),
7.13 (s,1H), 7.03 (s, 1H), 5.96 (d, J¼13.6 Hz,1H), 3.93 (s, 3H) ppm; 13C
5.89 (d, J¼14.0 Hz, 1H), 3.95 (s, 3H) ppm; 13C NMR (CDCl3,
125 MHz):
d 178.5, 160.3, 153.7, 146.2, 146.0, 138.3, 138.2, 130.0,
NMR (CDCl3, 100 MHz):
d
190.4, 160.1, 147.0, 138.4, 138.1, 132.2,
129.3, 129.0, 128.3, 126.2, 116.6, 112.4, 107.1, 35.9 ppm; HRMS (EI):
129.9, 129.1, 128.9, 128.3, 128.2, 128.1, 125.9, 107.6, 35.7 ppm; HRMS
m/z calcd for C18H15N3O2 ([M]þ): 321.1113; found: 321.1118.
(EI): m/z calcd for C20H17N3O2 ([M]þ): 331.1321; found: 331.1324.
4.2.8. (E)-1-Methyl-N-(3-oxooct-1-enyl)-N-phenyl-1H-imidazole-2-
4.2.2. (E)-N-(3-(4-Chlorophenyl)-3-oxoprop-1-enyl)-1-methyl-N-
carboxamide (4h). Colorless oil; IR: 1651, 1626, 1456, 1402, 1277,
phenyl-1H-imidazole-2-carboxamide
157e159 ꢀC; IR: 1659, 1583, 1397, 1249, 1203, 1149, 1029, 971 cmꢁ1
1H NMR (CDCl3, 400 MHz):
J¼8.8 Hz, 2H), 7.54e7.41 (m, 2H), 7.48e7.44 (m, 1H), 7.32 (d,
J¼8.4 Hz, 2H), 7.28e7.25 (m, 2H), 7.13 (s, 1H), 7.03 (s, 1H), 5.88 (d,
J¼13.2 Hz, 1H), 3.92 (s, 3H) ppm; 13C NMR (CDCl3, 100 MHz):
(4b). Yellow solid,
mp
;
1248, 1156, 968 cmꢁ1 1H NMR (CDCl3, 400 MHz):
; d 9.21 (d,
J¼14.4 Hz, 1H), 7.43e7.32 (m, 3H), 7.13e7.11 (m, 2H), 7.03 (s, 1H),
6.95 (s, 1H) 5.14 (d, J¼14.0 Hz, 1H), 3.86 (s, 3H), 2.38 (t, J¼7.6 Hz,
2H), 1.54e1.47 (m, 2H), 1.24e1.17 (m, 4H), 0.80e0.77 (m, 3H) ppm;
d
9.35 (d, J¼13.2 Hz, 1H), 7.67 (d,
13C NMR (CDCl3, 100 MHz):
d 200.2, 159.7, 144.8, 138.2, 137.8, 129.8,
128.8, 128.7, 128.2, 125.8, 112.1, 40.5, 35.8, 31.5, 24.3, 22.4, 13.9 ppm;
d
189.4, 160.3, 147.8, 138.8, 138.3, 137.0, 130.2, 129.9, 129.4, 129.3,
HRMS (EI): calcd for C19H23N3O2 ([M]þ): 325.1790; found: 325.1784.
128.9, 128.4, 126.3, 107.2, 36.1 ppm; HRMS (EI): m/z calcd for
C20H16ClN3O2 ([M]þ): 365.0931; found: 365.0934.
4.2.9. 1-Methyl-N-((1E,4E)-3-oxo-5-phenylpenta-1,4-dienyl)-N-phe-
nyl-1H-imidazole-2-carboxamide (4i). Yellow oil; IR: 1669, 1610,
1568, 1405, 1248, 1162, 1093, 728 cmꢁ1; 1H NMR (CDCl3, 500 MHz):
4.2.3. (E)-N-(3-(4-Bromophenyl)-3-oxoprop-1-enyl)-1-methyl-N-
phenyl-1H-imidazole-2-carboxamide (4c). Light yellow solid, mp
d
9.36 (d, J¼13.5 Hz, 1H), 7.51e7.31 (m, 6H), 7.29e7.25 (m, 3H),
175e177 ꢀC; IR: 1659, 1580, 1395, 1288, 1202, 1149, 1028, 817 cmꢁ1
;
7.22e7.20 (m, 2H), 7.08 (s, 1H), 7.00 (s, 1H), 6.82 (d, J¼15.5 Hz, 1H),
1H NMR (CDCl3, 400 MHz):
d
9.36 (d, J¼13.6 Hz, 1H), 7.60 (d,
5.46 (d, J¼13.5 Hz, 1H), 3.87 (s, 3H) ppm; 13C NMR (CDCl3,
J¼8.0 Hz, 2H), 7.55e7.45 (m, 5H), 7.29e7.25 (m, 2H), 7.13 (s, 1H),
125 MHz): d 188.5, 159.8, 145.8, 142.0, 138.1, 138.0, 134.9, 130.2,
7.04 (s, 1H), 5.87 (d, J¼13.6 Hz, 1H), 3.93 (s, 3H) ppm; 13C NMR
129.9, 129.0, 128.9, 128.8, 128.7, 128.2, 126.1, 125.4, 111.5, 35.9 ppm;
HRMS (EI): m/z calcd for C22H19N3O2 ([M]þ): 357.1477; found:
357.1470.
(CDCl3, 100 MHz):
d 189.6, 160.3, 147.9, 138.3, 138.2, 137.5, 131.9,
130.2, 130.0, 129.4, 129.3, 128.4, 127.4, 126.3, 107.2, 36.1 ppm; HRMS
(EI): m/z calcd for C20H16BrN3O2 ([M]þ): 409.0426; found:
409.0434.
4.2.10. (E)-1-Methyl-N-(3-oxo-3-phenylprop-1-enyl)-N-p-tolyl-1H-
imidazole-2-carboxamide (4j). Yellow solid, mp 139e141 ꢀC; IR:
1647, 1561, 1508, 1404, 1247, 1211, 1015, 768 cmꢁ1; 1H NMR (CDCl3,
4.2.4. (E)-N-(3-(4-Methoxyphenyl)-3-oxoprop-1-enyl)-1-methyl-N-
phenyl-1H-imidazole-2-carboxamide (4d). Light yellow soliꢁd1, mp
400 MHz):
d
9.35 (d, J¼13.6 Hz, 1H), 7.78e7.76 (m, 2H), 7.50e7.46
177e178 ꢀC; IR 1657, 1583, 1399, 1251, 1152, 1015, 817 cm
;
1H
(m, 1H), 7.41e7.33 (m, 4H), 7.19e7.15 (m, 3H), 7.04 (s, 1H), 6.00 (d,
J¼13.6 Hz, 1H), 3.94 (s, 3H) 2.44 (s, 3H) ppm; 13C NMR (CDCl3,
NMR (CDCl3, 400 MHz):
d
9.31 (d, J¼13.2 Hz, 1H), 7.76 (d, J¼9.2 Hz,
2H), 7.57e7.46 (m, 3H), 7.31 (d, J¼8.0 Hz, 2H), 7.15 (s, 1H), 7.04 (s,
100 MHz): d 190.7, 160.4, 147.4, 139.1, 138.7, 138.4, 135.5, 132.4,
1H), 6.87 (d, J¼8.8 Hz, 2H), 5.99 (d, J¼13.2 Hz, 1H), 3.95 (s, 3H), 3.83
130.8, 129.3, 128.5, 128.3, 128.0, 126.1, 107.7, 35.9, 21.5 ppm; HRMS
(s, 3H) ppm; 13C NMR (CDCl3, 100 MHz):
d
188.9, 163.3, 160.4, 146.4,
(EI): m/z calcd for C21H19N3O2 ([M]þ): 345.1477; found: 345.1479.
138.6, 138.5,131.6,130.6,130.1,129.3,129.1,128.5,126.0,113.8,107.6,
55.6, 35.9 ppm; HRMS (EI): m/z calcd for C21H19N3O3 ([M]þ):
361.1426; found, 361.1425.
4.2.11. (E)-N-(4-Bromophenyl)-1-methyl-N-(3-oxo-3-phenylprop-1-
enyl)-1H-imidazole-2-carboxamide
159e161 ꢀC; IR: 1649, 1563, 1420, 1247, 1158, 1012, 798, 702 cmꢁ1
1H NMR (CDCl3, 400 MHz):
9.31 (d, J¼13.6 Hz, 1H), 7.78e7.76 (m,
2H), 7.68e7.66 (m, 2H), 7.51e7.37 (m, 3H), 7.20 (d, J¼8.8 Hz, 2H),
(4k). Yellow
solid,
mp
;
4.2.5. (E)-1-Methyl-N-(3-(4-nitrophenyl)-3-oxoprop-1-enyl)-N-phe-
d
nyl-1H-imidazole-2-carboxamide
(4e). Yellow
solid,
mp

Y. Shen et al. / Tetrahedron 67 (2011) 8338e8342
8341
7.14 (s, 1H), 7.06 (s,1H), 5.91 (d, J¼13.6 Hz,1H), 3.94 (s, 3H) ppm; 13
C
137.8, 135.3, 132.3, 130.8, 129.3, 129.2, 128.6, 128.4, 128.2, 126.6,
126.2, 107.6, 35.8 ppm; HRMS (EI): m/z calcd for C20H16ClN3O2
NMR (CDCl3, 100 MHz):
d
190.1, 159.6, 146.4, 138.3, 137.8, 137.2,
133.2, 132.4, 130.0, 129.0, 128.4, 128.1, 126.1, 122.9, 107.6, 35.8 ppm;
HRMS (EI): m/z calcd for C20H16BrN3O2 ([M]þ): 409.0426; found:
409.0419.
([M] ): 365.0931; found: 365.0936.
þ
4.2.18. (E)-Ethyl
2-(1-methyl-N-(3-oxo-3-phenylprop-1-enyl)-1H-
imidazole-2-carboxamido)acetate
(4r). White
solid,
mp
4.2.12. (E)-N-(2-Bromophenyl)-1-methyl-N-(3-oxo-3-phenylprop-1-
102e103 ꢀC; IR: 1738,1649,1588,1568,1409,1275,1198,1133 cmꢁ1
;
enyl)-1H-imidazole-2-carboxamide
141e143 ꢀC; IR: 1684, 1654, 1564, 1405, 1247, 1160, 1014, 778 cmꢁ1
1H NMR (CDCl3, 400 MHz):
9.25 (br s, 1H), 7.76e7.71 (m, 3H),
(4l). White
solid,
mp
1H NMR (CDCl3, 400 MHz):
7.51e7.42 (m, 3H), 7.15 (s, 1H), 7.02 (s, 1H), 6.31 (d, J¼14.0 Hz, 1H),
4.78 (br s, 2H), 4.24 (q, J¼7.6 Hz, 2H), 3.93 (s, 3H), 1.28 (t, J¼7.2 Hz,
d
9.19 (br s, 1H), 7.88 (d, J¼7.2 Hz, 2H),
;
d
7.51e7.48 (m, 3H), 7.40e7.33 (m, 3H), 7.07e7.03 (m, 2H), 5.84 (d,
J¼14.0 Hz, 1H), 3.95 (s, 3H) ppm; 13C NMR (CDCl3, 100 MHz):
3H) ppm; 13C NMR (CDCl3, 100 MHz):
d 190.2, 167.5, 159.9, 138.5,
137.6, 132.2, 129.0, 128.4, 128.2, 126.1, 105.1, 76.5, 61.8, 35.8,
14.1 ppm; HRMS (EI): m/z calcd for C18H19N3O4 ([M]þ): 341.1376;
found: 341.1368.
d
190.5, 158.8, 138.4, 137.7, 137.2, 133.8, 132.3, 130.6, 130.5, 129.0,
128.5, 128.3, 128.2, 125.8, 125.7, 122.6, 107.8, 35.8 ppm; HRMS (EI):
m/z calcd for C20H16BrN3O2 ([M]þ): 409.0426; found: 409.0436.
4.2.19. (E)-N-Cyclohexyl-1-methyl-N-(3-oxo-3-phenylprop-1-enyl)-
1H-imidazole-2-carboxamide (4s). White solid, mp 141e143 ꢀC; IR:
1642, 1549, 1409, 1255, 1203, 1042, 1116, 781 cmꢁ1; 1H NMR (CDCl3,
4.2.13. (E)-N-(3-Acetylphenyl)-1-methyl-N-(3-oxo-3-phenylprop-1-
enyl)-1H-imidazole-2-carboxamide (4m). Dark yellow solid, mp
178e180 ꢀC; IR: 1660, 1565, 1442, 1252, 1170, 1015, 697 cmꢁ1
;
1H
400 MHz):
d
8.53 (d, J¼14.0 Hz,1H), 7.90 (d, J¼8.0 Hz, 2H), 7.52e7.41
NMR (CDCl3, 400 MHz):
d
9.38 (d, J¼13.2 Hz, 1H), 8.07 (d, J¼5.6 Hz,
(m, 3H), 7.12 (s, 1H), 7.00 (s, 1H), 6.69 (d, J¼14.0 Hz, 1H), 4.22e4.15
1H), 7.88 (s, 1H), 7.75e7.65 (m, 3H), 7.54e7.46 (m, 2H), 7.40e7.36
(m, 2H), 7.13 (s, 1H), 7.05 (s, 1H), 5.91 (d, J¼13.2 Hz, 1H), 3.94 (s, 3H),
(m, 1H), 3.88 (s, 3H), 2.25e2.16 (m, 2H), 1.88e1.69 (m, 5H),
1.42e1.22 (m, 3H) ppm; 13C NMR (CDCl3, 100 MHz):
d 190.7, 161.9,
2.62 (s, 3H) ppm; 13C NMR (CDCl3, 100 MHz):
d
190.4, 160.3, 159.6,
146.1, 138.9, 138.8, 132.1, 128.8, 128.3, 128.1, 125.6, 104.7, 58.4, 35.8,
29.2, 26.3, 25.3 ppm; HRMS (EI): m/z calcd for C20H23N3O2 ([M]þ):
337.1790; found: 337.1790.
147.3,138.5,138.2, 132.2, 130.6, 129.1, 129.0, 128.3, 128.1, 125.8, 115.1,
107.4, 55.5, 35.7 ppm; HRMS (EI): m/z calcd for C22H19N3O3 ([M]þ):
373.1426; found: 373.1434.
4.2.20. (E)-1-Benzyl-N-(3-oxo-3-phenylprop-1-enyl)-N-phenyl-1H-
imidazole-2-carboxamide (4t). White solid, mp 179e180 ꢀC; IR:
1649, 1561, 1420, 1250, 1206, 1158, 1009, 695 cmꢁ1; 1H NMR (CDCl3,
4.2.14. (E)-1-Methyl-N-(4-nitrophenyl)-N-(3-oxo-3-phenylprop-1-
enyl)-1H-imidazole-2-carboxamide
185e187 ꢀC; IR: 1647, 1565, 1517, 1400, 1252, 1173, 1035, 670 cmꢁ1
1H NMR (CDCl3, 500 MHz):
(4n). Yellow
solid,
mp
;
400 MHz):
(m, 4H), 7.40e7.32 (m, 5H), 7.22e7.07 (m, 6H), 5.96 (d, J¼13.6 Hz,
1H), 5.50 (s, 2H) ppm; 13C NMR (CDCl3, 100 MHz):
190.2, 160.2,
d
9.18 (d, J¼13.2 Hz, 1H), 7.76e7.74 (m, 2H), 7.51e7.44
d
9.28 (d, J¼14.0 Hz, 1H), 8.40 (d,
J¼8.5 Hz, 2H), 7.75 (d, J¼7.5 Hz, 2H), 7.51e7.50 (m, 3H), 7.40 (t,
J¼7.5 Hz, 2H), 7.10 (s, 1H), 7.07 (s, 1H), 5.98 (d, J¼14.0 Hz, 1H), 3.97
d
146.2, 138.4, 138.1, 136.2, 132.2, 129.8, 129.1, 128.9, 128.3, 128.2,
128.1, 128.0, 127.7, 124.5, 107.8, 51.4 ppm; HRMS (EI): m/z calcd for
C26H21N3O2 ([M]þ): 407.1634; found: 407.1635.
(s, 3H) ppm; 13C NMR (CDCl3, 125 MHz):
d 190.0, 159.5, 147.8, 145.8,
144.5, 138.3, 137.6, 132.8, 129.9, 129.6, 128.7, 128.3, 126.7, 125.5,
108.0, 36.2 ppm; HRMS (EI): m/z calcd for C20H16N4O4 ([M]þ):
376.1172; found: 376.1175.
4.2.21. (E)-1-Methyl-N-(3-oxo-3-phenylprop-1-enyl)-N-phenyl-1H-
benzo[d]imidazole-2-carboxamide
185e186 ꢀC; IR: 1647, 1563, 1484, 1296, 1225, 1163, 1020, 694 cmꢁ1
1H NMR (CDCl3, 400 MHz):
9.21 (d, J¼13.6 Hz, 1H), 7.85e7.77 (m,
3H), 7.58e7.48 (m, 4H), 7.44e7.35 (m, 7H), 6.06 (d, J¼13.6 Hz, 1H),
4.03 (s, 3H) ppm; 13C NMR (CDCl3, 100 MHz):
190.4, 161.1, 145.9,
142.8, 141.5, 138.2, 137.6, 135.8, 132.3, 130.0, 129.2, 128.4, 128.2,
128.1, 125.4, 123.6, 121.6, 110.2, 108.8, 31.7 ppm; HRMS (EI): m/z
calcd for C24H19N3O2 ([M]þ): 381.1477; found: 381.1476.
(4u). White
solid,
mp
;
4.2.15. (E)-N-(4-Methoxyphenyl)-1-methyl-N-(3-oxo-3-phenyl-
prop-1-enyl)-1H-imidazole-2-carboxamide (4o). Light yellow solid,
mp 150e151 ꢀC; IR: 1650, 1565, 1408, 1251, 1168, 1014, 776,
d
639 cmꢁ1
;
1H NMR (CDCl3, 400 MHz):
d
9.33 (d, J¼13.6 Hz, 1H),
d
7.76e7.74 (m, 2H), 7.48e7.35 (m, 3H), 7.20e7.04 (m, 3H), 7.04e7.02
(m, 3H), 5.99 (d, J¼13.6 Hz, 1H), 3.91 (s, 3H) 3.85 (s, 3H) ppm; 13C
NMR (CDCl3, 100 MHz):
d 190.3, 1630.3, 159.5, 147.3, 138.4, 138.1,
132.2, 130.5, 129.1, 129.0, 128.3, 128.1, 125.8, 115.1, 1107.3, 55.4,
35.7 ppm; HRMS (EI): m/z calcd for C21H19N3O3 ([M]þ): 361.1426;
found: 361.1430.
Acknowledgements
This work was supported by the National Natural Science
Foundation of China (No. 20972137; J0830413) and the Natural
Science Foundation of Zhejiang Province (R407106).
4.2.16. (E)-N-(4-Fluorophenyl)-1-methyl-N-(3-oxo-3-phenylprop-1-
enyl)-1H-imidazole-2-carboxamide
180e181 ꢀC; IR: 1647, 1567, 1504, 1399, 1249, 1170, 1013, 778 cmꢁ1
1H NMR (CDCl3, 400 MHz):
(4p). White
solid,
mp
;
d
9.35 (d, J¼13.2 Hz, 1H), 7.78e7.75 (m,
Supplementary data
2H), 7.51e7.38 (m, 3H), 7.31e7.21 (m, 4H), 7.14 (s, 1H), 7.05 (s, 1H),
5.97 (d, J¼13.2 Hz, 1H), 3.95 (s, 3H) ppm; 13C NMR (CDCl3,
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tet.2011.08.069.
100 MHz):
d 190.2, 160.0, 146.9, 138.3, 137.9, 134.0, 132.3, 130.1,
130.0, 129.1, 128.3, 128.1, 126.1, 117.1, 107.4, 35.8 ppm; HRMS (EI): m/
z calcd for C20H16FN3O2 ([M]þ): 349.1227; found: 349.1227.
References and notes
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;
d
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J¼7.2 Hz, 2H), 7.52e7.47 (m, 3H), 7.43e7.32 (m, 3H), 7.25e7.22 (m,
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