A new synthetic strategy towards 2,4,5-trisubstituted 1H-imidazoles and highly substituted pyrrolo[1,2-c]imidazoles by use of α-azidochalcones via Michael addition-cyclization followed by Wittig reaction

Article abstract of DOI:10.1016/j.tet.2017.09.042

Efficient and facile protocols for the preparation of highly functionalized 1H-imidazoles and 5H-pyrrolo[1,2-c]imidazoles are described. Heating a mixture of an α-azidochalcones and N,N,N′,N′-tetramethyl guanidine under neat conditions gave the corresponding 2,4,5-trisubstituted 1H-imidazole via Michael addition-cyclization in excellent yields. Subsequently, the prepared 1H-imidazoles undergo addition-Wittig reaction with acetylenic esters in presence of triphenylphosphine in dichloromethane to afford 5H-pyrrolo[1,2-c]imidazoles in high yields.

Full text of DOI:10.1016/j.tet.2017.09.042

Accepted Manuscript
A new synthetic strategy towards 2,4,5-trisubstituted 1H-imidazoles and highly
substituted pyrrolo[1,2-c]imidazoles by use of α-azidochalcones via Michael addition-
cyclization followed by Wittig reaction
Mehdi Adib, Fariba Peytam, Mahmoud Rahmanian-Jazi, Hamid Reza Bijanzadeh,
Massoud Amanlou
PII:
S0040-4020(17)30978-X
10.1016/j.tet.2017.09.042
TET 28993
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 18 April 2017
Revised Date: 14 September 2017
Accepted Date: 25 September 2017
Please cite this article as: Adib M, Peytam F, Rahmanian-Jazi M, Bijanzadeh HR, Amanlou
M, A new synthetic strategy towards 2,4,5-trisubstituted 1H-imidazoles and highly substituted
pyrrolo[1,2-c]imidazoles by use of α-azidochalcones via Michael addition-cyclization followed by Wittig
reaction, Tetrahedron (2017), doi: 10.1016/j.tet.2017.09.042.
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ACCEPTED MANUSCRIPT
A new synthetic strategy towards 2,4,5-trisubstituted
1H-imidazoles and highly substituted
pyrrolo[1,2-c]imidazoles by use of α-azidochalcones via
Michael addition-cyclization followed by Wittig reaction
Mehdi Adib, Fariba Peytam, Mahmoud Rahmanian-Jazi, Hamid Reza Bijanzadeh, Massoud Amanlou
Ar'
CO2R
C
O
N
Ar'
NMe2
NMe2
Ar
Ar'
+
(C6H5)3P
N
neat
Ar
NMe2
HN
+
N
Ar
CH2Cl2
90 °C, 30 min
C
NMe2
N3
N
r.t., 10 min
H
CO2R
O
RO2C
CO2R
1

ACCEPTED MANUSCRIPT
A new synthetic strategy towards 2,4,5-trisubstituted 1H-imidazoles
and highly substituted pyrrolo[1,2-c]imidazoles by use of α-
azidochalcones via Michael addition-cyclization followed by Wittig
reaction
Mehdi Adib,a,* Fariba Peytam,a Mahmoud Rahmanian-Jazi,a Hamid Reza
Bijanzadeh,b Massoud Amanlouc
a School of Chemistry, College of Science, University of Tehran, PO Box 14155-6455,
Tehran, Iran
b Department of Biophysics, Tarbiat Modares University, PO Box 14115-175, Tehran,
Iran
c
Department of Medicinal Chemistry, Drug Design and Development Research
Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
Abstract
Efficient and facile protocols for the preparation of highly functionalized 1H-
imidazoles and 5H-pyrrolo[1,2-c]imidazoles are described. Heating a mixture of an α-
azidochalcones and N,N,N',N'-tetramethyl guanidine under neat conditions gave the
corresponding 2,4,5-trisubstituted 1H-imidazole via Michael addition-cyclization in
excellent yields. Subsequently, the prepared 1H-imidazoles undergo addition-Wittig
reaction with acetylenic esters in presence of triphenylphosphine in dichloromethane
to afford 5H-pyrrolo[1,2-c]imidazoles in high yields.
Keywords: α-Azidochalcones, N,N,N',N'-tetramethyl guanidine, 2,4,5-trisubstituted
1H-imidazoles, 5H-pyrrolo[1,2-c]imidazoles, Michael addition-cyclization-Wittig
reaction.
*Corresponding author. Tel./fax: +98(21)66495291; E-mail: madib@khayam.ut.ac.ir
1

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1. Introduction
2-Aminoimidazoles are valuable scaffolds in pharmaceutical chemistry. They exhibit
different biological effects resulting in their extensive use as human β-secretase and
biofilm formation inhibitory activity, antibacterial, antimicrobial, anticancer, anti-
inflammatory, and antagonists of serotonergic and histaminergic receptors.1 Thus,
great attention has been focused for development of new approaches towards these
compounds.2
Pyrrolo[1,2-c]imidazoles have attracted great attention as common structural motifs in
naturally occurring compounds and pharmacologically important synthetic
compounds.3 Compounds having the pyrrolo[1,2-c]imidazole scaffold have been
shown to possess a broad range of biological activities including cardiotonic,
neuroprotective, antinociceptive, tissue-selective agonist of androgen receptor,
anxiolytic, antiviral, antibacterial, antifungal, and herbicidal properties.4
Over the last decade, α-azidochalcones have got one of the fascinating synthons in
organic synthesis. They have been widely applied to synthesize various nitrogen
containing five- or six-memebered rings such as pyrroles,5 indoles,6 pyrazoles,7
imidazoles,8 oxazoles,9 thiazoles,10 triazolines,5c,11 pyridines and pyrimidines,12
isoquinolines,13 pyrrolo[1,2-a]pyrazines14 and imidazo[1,2-a]pyridines.15
In 2014, a direct synthesis of 2-aminoimidazoles was reported by Yu and co-workers.
Heating a mixture of a vinyl azide and cyanamide in the presence of Et3N in ethanol
afforded the corresponding 2-aminoimidazoles in good yields.8b
Very recently, Guchhait and co-workers have reported an imidazole synthesis by
treating guanidine derivatives and 2-bromo-2-alkenones which afforded the
corresponding 2-aminoimidazoles.16
It has been reported that three-component reactions between triphenylphosphine,
acetylenic esters and various NH-acids such as 2-pyrrolylglyoxalate, 2-
indolecarboxaldehyde or imidazole-4-carbaldehyde afforded the corresponding
phosphorus ylides. The phosphorane intermediates underwent smooth intramolecular
Wittig reaction to afford 1H-pyrrolizines,17a 3H-pyrrolo[1,2-a]indoles17b and
pyrrolo[1,2-c]imidazoles,17c respectively, among other mono- and bicyclo
azaheterocyclic compounds.
As part of our ongoing effort to develop efficient strategies for the preparation of
biologically active heterocyclic compounds from readily accessible precursors,18
herein, we describe efficient synthetic routes leading to highly functionalized 1H-
2

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imidazoles and 5H-pyrrolo[1,2-c]imidazoles. This proposed protocol involves
Michael addition-cyclization of α-azidochalcones with N,N,N',N'-tetramethyl
guanidine (TMG) giving 2,4,5-trisubstituted 1H-imidazoles, which subsequently will
be treated with acetylenic esters in the presence of triphenylphosphine through
addition-intramolecular Wittig reaction to produce fully substituted 5H-pyrrolo[1,2-
c]imidazoles.
2. Result and discussion
First, to achieve the best conditions for synthesis of 2,4,5-trisubstituted 1H-imidazoles
3, α-azidochalcone 1a19 was selected as model substrate and the effects of several
solvents, reaction temperature and time as well as different equivalents of TMG were
investigated (Table 1). Initially, the reaction was carried out in the presence of 2 (1.0
equiv) in acetonitrile at ambient temperature for 30 min and 1H-imidazole 3a was
detected in 10% yield (entry 1). By rising the temperature to 50 °C and then refluxing
acetonitrile, 1H-imidazole 3a obtained in 20 and 37% yields, respectively (entries 2
and 3). However, increasing the time to 40 and 60 min had no effect on the yield
(entries 4 and 5). Subsequently, different quantities of 2 were evaluated to improve
the yield (entries 6−8). Increasing the amount of 2 to 1.5 and 2 equiv, led to the
desired product 3a in 45 and 62% yields, respectively (entries 6 and 7). However,
applying more quantities of 2 was ineffective (entry 8). By carrying out the reaction in
other solvents such as DMF, toluene (both at 80 and 100 °C), acetone (reflux) and
EtOH (reflux), 3a obtained in 25−68% yields (entries 9−14). The effect of neat
conditions at different temperatures and times with the optimized ratios was also
tested (entries 15–17). It could be seen that the best result was attained at 90 °C after
30 with a 1:2 molar ratios, in which 3a was obtained in 95% yield (entry 17).
Carrying out the reaction at this temperature beyond 30 min or at higher temperatures,
led to lower yields of 3a (entries 18 and 19). Thus, the optimal conditions for the
formation of 1H-imidazole 3a were determined: TMG 2 (2 equiv), under neat
conditions (no solvent) at 90 °C for 30 min (entry 17).
3

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Table 1. Condition screening for the reaction between α-azidochalcone 1a and
TMG 2a
H3C
O
NMe2
NMe2
N
+
H3C
HN
NMe2
N
H
O
N3
1a
2
3a
Entry Solvent TMG (equiv) temp (°C) Time (min) Yield (%)b
1
2
3
4
5
6
7
8
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN 1.5
CH3CN
CH3CN 2.5
DMF
DMF
Toluene
Toluene
Acetone 2
1
1
1
1
1
25
50
30
30
30
40
60
30
30
30
30
30
30
30
30
30
30
30
30
40
30
10
20
37
37
37
45
62
62
68
68
32
25
40
53
64
82
95
86
80
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
80
100
80
100
Reflux
Reflux
50
75
90
2
9
2
2
2
2
10
11
12
13
14
15
16
17
18
19
EtOH
─
─
─
─
2
2
2
2
2
2
90
110
─
aReaction conditions: α-azidochalcones (0.5 mmol), solvent (1.5 mL). bIsolated
yields.
After optimization of the reaction conditions, with the purpose of extending this
reaction, a series of different α-azidochalcones with electron-donating alkyl or
methoxy groups as well as electron-withdrawing chlorine, bromine and nitro groups
(1a−l) treated with TMG 2 in a 1:2 molar ratio under neat conditions at 90 °C. All the
reactions went to completion within 30 min. TLC and NMR analysis of the reaction
mixtures clearly indicated the formation of the corresponding 2,4,5-trisubstituted 1H-
imidazole 3a−l in excellent yields. The results are summarized in Table 2. The
1
13
structures of the isolated products were deduced on the basis of their IR, H, and C
NMR spectroscopy, mass spectrometry and elemental analysis.
4

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Table 2. Substrate scope for the synthesis of 2,4,5-trisubstituted 1H-imidazole 3a−l
under the optimized conditionsa,b
O
Ar'
NMe2
NMe2
Ar
Ar'
N
neat
Ar
+
HN
90 °C, 30 min
NMe2
N
N3
H
O
1a-l
2
3a-l
O
Br
Cl
Cl
N
N
N
N
NMe2
NMe2
N
H
NMe2
NMe2
N
N
H
N
H
O
O
H
O
O
3a, 95%
3b, 93%
3c, 91%
3d, 89%
Cl
Br
Cl
N
N
N
N
NMe2
NMe2
N
H
NMe2
N
H
NMe2
N
H
N
H
O
O
3h, 87%
O
O
3g, 94%
3e, 92%
3f, 89%
Cl
O
O2N
Br
Cl
N
N
N
N
NMe2
NMe2
NMe2
NMe2
N
H
N
H
N
H
N
H
O
O
O
O
3j, 85%
3i, 90%
3l, 92%
3k, 96%
aIsolated yields. bAll products were purified by recrystallization from EtOAc.
The presence of appropriately positioned NH and carbonyl functionalities in the
prepared 2,4,5-trisubstituted 1H-imidazoles 3 encouraged us to use these entities for
the preparation of bridgehead bicyclic 5:5 ring systems 5H-pyrrolo[1,2-c]imidazoles 5
through an intramolecular Wittig reaction. The reaction of 1H-imidazoles 3a−l with
acetylenic esters 4a,b in the presence of triphenylphosphine proceeded smoothly in
dichloromethane to afford highly substituted 5H-pyrrolo[1,2-c]imidazoles 5a−x in
high yields. The reactions were carried out at ambient temperature and completed
1
within 10 min. TLC and H NMR analysis of the reaction mixtures clearly indicated
formation of 5H-pyrrolo[1,2-c]imidazoles 5. Any product other than 5 and
triphenylphosphine oxide could not be detected by NMR spectroscopy. The results are
summarized in Table 3. Structure 5 was assigned to the isolated products on the basis
of their elemental analyses, mass spectrometry, as well as their 1H and 13C NMR and
IR spectral data.
5

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Table 3. Substrate scope for the synthesis of 5H-pyrrolo[1,2-c]imidazoles 5a−xa−c
Ar'
Ar'
N
N
Ar
CH2Cl2
NMe2
Ar
NMe2
(C6H5)3P
+
CO2R
+
C
C
RO2C
N
N
r.t., 10 min
H
O
RO2C
CO2R
5a-x
3a-l
4a,b
Br
N
N
N
N
N
N
N
Cl
Cl
NMe2
NMe2
NMe2
NMe2
NMe2
N
N
N
CO2Me
5c, 90%
CO2Et
5d, 90%
CO2Me
5a, 87%
CO2Et
5b, 82%
MeO2C
O
EtO2C
EtO2C
MeO2C
CO2Me
5e, 83%
MeO2C
Cl
O
Br
Cl
N
N
N
N
N
Cl
Cl
NMe2
NMe2
NMe2
NMe2
NMe2
N
N
N
N
N
CO2Et
5j, 84%
EtO2C
CO2Et
5h, 84%
CO2Et
5f, 81%
CO2Me
MeO2C
5g, 85%
EtO2C
CO2Me
5i, 88%
MeO2C
EtO2C
N
N
N
N
N
Br
Br
Cl
NMe2
Cl
NMe2
NMe2
N
NMe2
NMe2
N
N
N
N
CO2Me
MeO2C
CO2Me
5m, 91%
CO2Et
5n, 89%
MeO2C
EtO2C
CO2Et
5l, 85%
CO2Me
MeO2C
5k, 84%
EtO2C
5o, 81%
O
O
N
N
N
N
O2N
N
N
N
O2N
NMe2
NMe2
NMe2
N
N
NMe2
NMe2
N
CO2Et
EtO2C
5t, 76%
CO2Et
5p, 80%
CO2Me
EtO2C
MeO C
2 5s, 78%
CO2Et
EtO2C
5r, 83%
CO2Me
MeO2C
5q, 82%
Cl
Cl
N
N
N
N
N
Cl
Cl
Br
Br
NMe2
NMe2
NMe2
NMe2
N
N
N
CO2Me
MeO2C
5u, 95%
CO2Et
EtO2C
5v, 92%
CO2Me
5w, 93%
CO2Et
EtO2C
5x, 90%
MeO2C
b
aIsolated yields. In the case of compounds 5d, 5n and 5o, at first most of the by-product PPh3O was
separated by nucleation of its crystals into a 2:3 n-hexane/EtOAc solution of the reaction mixture, followed
by decreasing the polarity of the mother liquor to 1:1 n-hexane/EtOAc, from which the product was
c
crystallized. Other products were purified by crystallization from 1:1 n-hexane/EtOAc. All products were
subjected to a further recrystallization from 1:1 n-hexane/EtOAc for data collection.
A plausible mechanism for the formation of 1H-imidazoles 3 and 5H-pyrrolo[1,2-
c]imidazoles 5 is outlined in Scheme 1. The reaction is initiated by Michael addition
of TMG 2 to α-azidochalcone 1 by removal of a nitrogen molecule and formation of
intermediate 6. Intramolecular nucleophilic attack of N-atom to the adjacent iminium
give the 2,3-dihydro-1H-imidazole intermediate 7, which may undergo elimination of
dimethylamine as well as a proton shift to afford 5-aroyl-4-aryl-2-(dimethylamino)-
1H-imidazole 3 through 8. On the other hand, the 1:1 zwitter ionic intermediate 9
generated from the initial addition of triphenylphosphine to the acetylenic ester 4 may
be protonated by the NH-acid 3. Then, the positively charged ion 10 may be attacked
6

ACCEPTED MANUSCRIPT
by the conjugate base of NH-acid 11 to form the phosphorus ylide 12. Phosphorane
12 undergoes an intramolecular Wittig reaction to afford the bridgehead bicyclic
system 5H-pyrrolo[1,2-c]imidazole-5,6-dicarboxylate 5 through betaine intermediate
13.
O
O
N
O
_
O
_
Ar'
Ar'
Ar'
Ar'
Ar
Ar'
NH
Ar
Ar
N
N
Ar
N
Ar'
N
_
_
NHMe2
N2
H
+
O
HN
N
N
N
NH
N
N
H
N
+
+
N
N
Ar
N
N
N
8
N
3
1
2
6
7
Ar'
Ar'
Ar'
N
N
N
N
RO2C
RO2C
_
_
3
Ph3PO
O
O
_
N
Ar
CCO2R
CHCO2R
N
N
N
N
Ar
+
+
N
N
N
_
O
Ph3P
Ph3P
H
Ar
Ar
Ph3P
+
CO2R
H
+
_
Ph3P
CO2R
CO2R
RO2C
CO2R
13
CO2R
5
10
12
9
11
Scheme 1 Proposed reaction mechanism.
3. Conclusion
In conclusion, we have developed new strategies for the preparation of two valuable
aza-heterocycles 1H-imidazoles and 5H-pyrrolo[1,2-c]imidazoles by use of α-
azidochalcones. The use of easily available starting materials, efficiency and facility
of operation, short reaction times, catalyst-free and mild conditions, easy work-up
without any need to chromatography purification processes as well as high yields of
the products are the main advantages of the strategy.
4. Experimental
4.1. General
All chemicals were purchased from Merck (Germany) and were used without further
purification. Melting points were measured on an Electrothermal 9100 apparatus.
Elemental analyses for C, H and N were performed using a Heraeus CHN-O-Rapid
analyzer. Mass spectra were recorded on an Agilent Technologies (HP) 5973 mass
spectrometer operating at an ionization potential of 20 eV. IR spectra were recorded
on a Shimadzu IR-460 spectrometer. 1H and 13C NMR spectra were measured (CDCl3
solution) with Bruker DRX-300 (at 300.1 and 75.5 MHz) and Bruker DRX-500
AVANCE (at 500.1 and 125.8 MHz) instruments.
4.2. General procedure for the preparation of dibromochalcones: To a suspension
of the corresponding chalcone (50.0 mmol) in ether (200 mL) was added dropwise
7

ACCEPTED MANUSCRIPT
bromine (50.0 mmol) at 0 °C, which was stirred at the same temperature. After
completion of the reaction (monitored by TLC), the precipitate was filtered off and
washed with cold water. The products were enough pure that were used for the next
reaction without further purification.19
4.3. General procedure for the preparation of vinyl azides: To a solution of a
dibromochalcone (10.0 mmol) in DMF (45 mL) was added sodium azide (37.3 mmol)
at ambient temperature. It took nearly 3h that all the starting materials were
disappeared. Then the reaction mixture was poured into water and extracted with
dichloromethane. The organic extracts were washed with brine (2 × 40 mL), water (40
mL), dried over MgSO4 and evaporated in vacuo. The residue was crystallized from
n-hexane to afford the corresponding vinyl azides.19
4.4. General procedure for the preparation of 2,4,5-trisubstituted 1H-imidazoles
(3a–l): A mixture of the appropriate α-azidochalcone 1 (1 mmol) and N,N,N',N'-
tetramethyl guanidine 2 (2 mmol) was stirred at 90 °C for 30 min. After completion
the reaction, as was indicated by TLC monitoring, the mixture was cooled to ambient
temperature and the residue was recrystallized from EtOAc.
4.4.1. 2-(Dimethylamino)-5-(4-methylbenzoyl)-4-phenyl-1H-imidazole (3a)
Yellow crystals, mp 174 °C, yield: 0.290 g, 95%. IR (KBr) (νmax/cm–1): 3135 (NH),
1610 (C=O), 1526, 1487, 1438, 1375, 1348, 1322, 1301, 1278, 1230, 1173, 1074,
1042, 1013, 911, 855, 827, 780, 749, 697. EI-MS, m/z (%): 305 (M+, 100), 290 (9),
276 (20), 261 (8), 213 (8), 198 (37), 185 (17), 170 (15), 156 (20), 142 (6), 129 (5),
1
119 (40), 103 (6), 91 (45), 77 (6), 65 (16), 56 (11), 42 (6). H NMR (300.1 MHz,
CDCl3): δ 2.22 (s, 3H, CH3), 3.15 (s, 6H, NMe2), 6.83 (d, J = 8.0 Hz, 2H, 2CH), 7.01
(t, J = 7.5 Hz, 2H, 2CH), 7.09 (t, J = 7.5 Hz, 1H, CH), 7.19 (dd, J = 8.1, 1.3 Hz, 2H,
2CH), 7.31 (d, J = 8.0 Hz, 2H, 2CH), 10.25–10.95 (br, 1H, NH). 13C NMR (75.5
MHz, CDCl3): δ 21.4 (CH3), 38.3 (2NCH3), 124.2 (C), 127.4 (2CH), 127.5 (CH),
128.1 (2CH), 129.4 (2CH), 129.8 (2CH), 134.6, 135.6 and 141.3 (3C), 151.6 (CN3),
154.5 (C), 184.6 (C=O). Anal. Calcd for C19H19N3O (305.37): C, 74.73; H, 6.27; N,
13.76. Found: C, 74.59; H, 6.14; N, 13.55%.
4.4.2. 2-(Dimethylamino)-5-(4-chlorobenzoyl)-4-phenyl-1H-imidazole (3b)
Yellow crystals, mp 176–177 °C, yield: 0.302 g, 93%. IR (KBr) (νmax/cm–1): 3237
(NH), 1620 (C=O), 1546, 1483, 1373, 1322, 1277, 1233, 1173, 1080, 1011, 910, 835,
756, 695, 676, 617. EI-MS, m/z (%): 327 (M+ 37Cl, 35), 325 (M+ 35Cl, 100), 312 (10),
310 (30), 296 (44), 283 (5), 281 (14), 240 (16), 214 (15), 198 (54), 186 (9), 170 (15),
8

ACCEPTED MANUSCRIPT
159 (19), 139 (56), 129 (8), 111 (45), 102 (19), 89 (29), 71 (17), 57 (16), 43 (12). 1H
NMR (300.1 MHz, CDCl3): δ 3.17 (s, 6H, NMe2), 7.00 (d, J = 8.2 Hz, 2H, 2CH), 7.06
(dd, J = 8.1, 7.5 Hz, 2H, 2CH), 7.15 (t, J = 7.5 Hz, 1H, CH), 7.16 (d, J = 8.0 Hz, 2H,
2CH), 7.30 (d, J = 8.2 Hz, 2H, 2CH), 9.20–10.75 (br, 1H, NH). 13C NMR (75.5 MHz,
CDCl3): δ 38.0 (2NCH3), 123.3 (C), 127.29 (2CH), 127.34 (2CH), 127.9 (CH), 129.4
(2CH), 130.1 (2CH), 132.8, 136.1 and 136.7 (3C), 150.7 (CN3), 153.6 (C), 182.6
(C=O). Anal. Calcd for C18H16ClN3O (325.79): C, 66.36; H, 4.95; N, 12.90. Found:
C, 66.30; H, 5.03; N, 12.86%.
4.4.3. 4-(4-Bromophenyl)-2-(dimethylamino)-5-(4-methylbenzoyl)-1H-imidazole (3c)
Yellow crystals, mp 208 °C, yield: 0.349 g, 91%. IR (KBr) (νmax/cm–1): 3245 (NH),
1614 (C=O), 1571, 1543, 1481, 1443, 1375, 1317, 1231, 1170, 1104, 1069, 1009,
916, 826, 794, 760, 677. EI-MS, m/z (%): 385 (M+ 81Br, 85), 383 (M+ 79Br, 92), 354
(8), 304 (12), 276 (13), 264 (8), 250 (7), 237 (10), 196 (12), 184 (37), 169 (25), 119
(93), 102 (17), 91 (100), 65 (25). 1H NMR (300.1 MHz, CDCl3): δ 2.29 (s, 3H, CH3),
3.16 (s, 6H, NMe2), 6.90 (d, J = 7.9 Hz, 2H, 2CH), 7.06 (d, J = 8.6 Hz, 2H, 2CH),
7.16 (d, J = 8.6 Hz, 2H, 2CH), 7.28 (d, J = 8.1 Hz, 2H, 2CH), 9.77–9.92 (br, 1H, NH).
13C NMR (75.5 MHz, CDCl3): δ 21.4 (CH3), 38.2 (2NCH3), 121.9 and 124.0 (2C),
128.3 (2CH), 129.2 (2CH), 130.5 (2CH), 131.2 (2CH), 133.4, 135.3 and 141.8 (3C),
149.7 (CN3), 154.1 (C), 184.3 (C=O). Anal. Calcd for C19H18BrN3O (384.27): C,
59.39; H, 4.72; N, 10.94. Found: C, 59.31; H, 4.68; N, 10.79%.
4.4.4.
5-(4-Chlorobenzoyl)-2-(dimethylamino)-4-(4-methoxyphenyl)-1H-imidazole
(3d)
Yellow crystals, mp 216–218 °C, yield: 0.316 g, 89%. IR (KBr) (νmax/cm–1): 3248
(NH), 1608 (C=O), 1576, 1542, 1495, 1443, 1380, 1321, 1237, 1169, 1085, 1011,
913, 841, 798, 762, 719, 666. EI-MS, m/z (%): 357 (M+ 37Cl, 32), 355 (M+ 35Cl, 100),
340 (29), 326 (32), 311 (8), 285 (4), 270 (9), 244 (12), 228 (35), 216 (35), 200 (18),
186 (15), 159 (17), 139 (74), 111 (47), 75 (17), 56 (8), 42 (8). 1H NMR (300.1 MHz,
CDCl3): δ 3.14 (s, 6H, NMe2), 3.71 (s, 3H, OCH3), 6.57 (d, J = 8.7 Hz, 2H, 2CH),
7.02 (d, J = 8.4 Hz, 2H, 2CH), 7.08 (d, J = 8.7 Hz, 2H, 2CH), 7.30 (d, J = 8.4 Hz, 2H,
2CH), 9.60–10.85 (br, 1H, NH). 13C NMR (75.5 MHz, CDCl3): δ 37.9 (2NCH3), 54.9
(OCH3), 112.8 (2CH), 123.3 and 125.7 (2C), 127.3 (2CH), 130.1 (2CH), 130.7 (2CH),
136.36 and 136.41 (2C), 151.6 (CN3), 154.0 and 159.3 (2C), 182.3 (C=O). Anal.
Calcd for C19H18ClN3O2 (355.82): C, 64.13; H, 5.10; N, 11.81. Found: C, 63.89; H,
5.05; N, 11.70%.
9

ACCEPTED MANUSCRIPT
4.4.5. 4-(4-Chlorophenyl)-2-(dimethylamino)-5-(4-methylbenzoyl)-1H-imidazole (3e)
Yellow crystals, mp 209–210 °C, yield: 0.312 g, 92%. IR (KBr) (νmax/cm–1): 3170
(NH), 1614 (C=O), 1549, 1523, 1481, 1378, 1342, 1307, 1229, 1171, 1089, 1049,
1012, 958, 912, 828, 795, 759, 735, 706, 672. EI-MS, m/z (%): 341 (M+ 37Cl, 34), 339
(M+ 35Cl, 100), 324 (13), 310 (27), 295 (10), 248 (12), 232 (53), 219 (18), 204 (19),
193 (14), 184 (44), 150 (14), 137 (15), 119 (90), 91 (73), 82 (8), 65 (23), 56 (10), 42
(7). 1H NMR (300.1 MHz, CDCl3): δ 2.28 (s, 3H, CH3), 3.16 (s, 6H, NMe2), 6.89 (d, J
= 8.0 Hz, 2H, 2CH), 7.00 (d, J = 8.5 Hz, 2H, 2CH), 7.12 (d, J = 8.5 Hz, 2H, 2CH),
7.28 (d, J = 8.0 Hz, 2H, 2CH), 9.30–10.80 (br, 1H, NH). 13C NMR (75.5 MHz,
CDCl3): δ 21.0 (CH3), 38.0 (2NCH3), 123.6 (C), 127.2 (2CH), 127.9 (2CH), 128.9
(2CH), 130.6 (2CH), 131.9, 133.4, 134.8 and 141.6 (4C), 148.5 (CN3), 153.5 (C),
184.1 (C=O). Anal. Calcd for C19H18ClN3O (339.82): C, 67.15; H, 5.34; N, 12.37.
Found: C, 67.04; H, 5.41; N, 12.16%.
4.4.6. 5-(4-Chlorobenzoyl)-2-(dimethylamino)-4-(4-methylphenyl)-1H-imidazole (3f)
Yellow crystals, mp 221–222 °C, yield: 0.302 g, 89%. IR (KBr) (νmax/cm–1): 3246
(NH), 1617 (C=O), 1576, 1542, 1498, 1444, 1376, 1320, 1228, 1173, 1084, 1010,
913, 848, 825, 762, 726, 670. EI-MS, m/z (%): 341 (M+ 37Cl, 34), 339 (M+ 35Cl, 100),
324 (23), 310 (33), 295 (9), 228 (12), 212 (38), 200 (22), 184 (23), 170 (18), 139 (61),
1
130 (22), 111 (45), 102 (38), 91 (7), 75 (16), 65 (3), 56 (6), 42 (8). H NMR (300.1
MHz, CDCl3): δ 2.25 (s, 3H, CH3), 3.15 (s, 6H, NMe2), 6.86 (d, J = 7.9 Hz, 2H,
2CH), 7.01 (d, J = 8.5 Hz, 2H, 2CH), 7.04 (d, J = 7.9 Hz, 2H, 2CH), 7.30 (d, J = 8.5
Hz, 2H, 2CH), 9.51–10.85 (br, 1H, NH). 13C NMR (75.5 MHz, CDCl3): δ 21.1 (CH3),
38.3 (2NCH3), 123.7 (C), 127.6 (2CH), 128.3 (2CH), 129.6 (2CH), 130.4 (2CH),
130.6, 136.6, 136.9 and 138.1 (4C), 151.9 (CN3), 154.2 (C), 182.9 (C=O). Anal.
Calcd for C19H18ClN3O (339.82): C, 67.15; H, 5.34; N, 12.37. Found: C, 67.09; H,
5.28; N, 12.08%.
4.4.7. 5-(4-Bromobenzoyl)-2-(dimethylamino)-4-phenyl)-1H-imidazole (3g)
Yellow crystals, mp 189 °C, yield: 0.347 g, 94%. IR (KBr) (νmax/cm–1): 3228 (NH),
1616 (C=O), 1546, 1483, 1373, 1320, 1277, 1232, 1173, 1066, 1008, 908, 832, 755,
698, 672. EI-MS, m/z (%): 371 (M+ 81Br, 96), 369 (M+ 79Br, 100), 356 (14), 354 (15),
342 (21), 340 (22), 214 (12), 198 (46), 185 (40), 170 (12), 155 (28), 129 (6), 116 (11),
1
103 (14), 89 (25), 76 (19), 56 (11), 42 (5). H NMR (300.1 MHz, CDCl3): δ 3.16 (s,
6H, NMe2), 7.05 (dd, J = 7.6, 7.0 Hz, 2H, 2CH), 7.14−7.17 (m, 5H, 5CH), 7.23 (d, J =
13
8.5 Hz, 2H, 2CH), 9.10–10.80 (br, 1H, NH). C NMR (75.5 MHz, CDCl3): δ 38.3
10

ACCEPTED MANUSCRIPT
(2NCH3), 123.8 and 125.5 (2C), 127.6 (2CH), 128.2 (CH), 129.7 (2CH), 130.59
(2CH), 130.64 (2CH), 133.4 and 136.9 (2C), 151.7 (CN3), 154.2 (C), 183.0 (C=O).
Anal. Calcd for C18H16BrN3O (370.24): C, 58.39; H, 4.36; N, 11.35. Found: C, 58.14;
H, 4.44; N, 11.18%.
4.4.8. 5-Benzoyl-2-(dimethylamino)-4-phenyl-1H-imidazole (3h)
Yellow crystals, mp 179–180 °C, yield: 0.253 g, 87%. IR (KBr) (νmax/cm–1): 3258
(NH), 1609 (C=O), 1554, 1489, 1444, 1377, 1325, 1240, 1171, 1071, 1013, 913, 850,
782, 726, 691, 654. EI-MS, m/z (%): 291 (M+, 100), 276 (40), 262 (60), 247 (16), 214
(24), 198 (50), 186 (17), 178 (8), 170 (15), 159 (23), 142 (8), 129 (8), 116 (14), 105
1
(62), 89 (33), 77 (70), 67 (8), 51 (16), 42 (7). H NMR (300.1 MHz, CDCl3): δ 3.17
(s, 6H, NMe2), 6.99–7.10 (m, 5H, 5CH), 7.16−7.24 (m, 3H, 3CH), 7.39 (dd, J = 8.1,
13
1.3 Hz, 2H, 2CH), 9.60–10.80 (br, 1H, NH). C NMR (75.5 MHz, CDCl3): δ 38.0
(2NCH3), 123.6 (C), 127.08 (2CH), 127.10 (2CH), 127.5 (CH), 128.7 (2CH), 129.4
(2CH), 130.5 (CH), 133.4 and 137.8 (2C), 150.9 (CN3), 153.8 (C), 184.2 (C=O).
Anal. Calcd for C18H17N3O (291.35): C, 74.20; H, 5.88; N, 14.42. Found: C, 74.03; H,
5.64; N, 14.26%.
4.4.9. 5-Benzoyl-2-(dimethylamino)-4-(4-methoxyphenyl)-1H-imidazole (3i)
Yellow crystals, mp 176 °C, yield: 0.289 g, 90%. IR (KBr) (νmax/cm–1): 3220 (NH),
1604 (C=O), 1549, 1494, 1442, 1375, 1312, 1289, 1234, 1170, 1106, 1071, 1026,
912, 836, 788, 748, 720, 687, 635. EI-MS, m/z (%): 321 (M+, 100), 306 (34), 292
(36), 277 (14), 244 (12), 228 (25), 216 (31), 200 (13), 186 (10), 159 (8), 146 (37), 133
(10), 119 (30), 105 (69), 90 (7), 77 (63), 67 (7), 51 (11), 42 (6). 1H NMR (300.1 MHz,
CDCl3): δ 3.15 (s, 6H, NMe2), 3.69 (s, 3H, OCH3), 6.54 (d, J = 8.7 Hz, 2H, 2CH),
7.06 (t, J = 7.6 Hz, 2H, 2CH), 7.11 (d, J = 8.7 Hz, 2H, 2CH), 7.22 (t, J = 7.4 Hz, 1H,
13
CH), 7.40 (d, J = 7.0 Hz, 2H, 2CH), 9.60–10.72 (br, 1H, NH). C NMR (75.5 MHz,
CDCl3): δ 38.3 (2NCH3), 55.1 (OCH3), 113.0 (2CH), 123.6 and 126.3 (2C), 127.5
(2CH), 129.1 (2CH), 130.8 (CH), 131.0 (2CH), 138.3 (C), 151.2 (CN3), 154.1 and
159.3 (2C), 184.3 (C=O). Anal. Calcd for C19H19N3O2 (321.37): C, 71.01; H, 5.96; N,
13.08. Found: C, 70.89; H, 5.81; N, 13.00%.
4.4.10. 2-(Dimethylamino)-5-(4-nitrobenzoyl)-4-phenyl-1H-imidazole (3j)
Yellow crystals, mp 206 °C, yield: 0.286 g, 85%. IR (KBr) (νmax/cm–1): 3223 (NH),
1614 (C=O), 1547, 1440, 1381, 1317, 1236, 1176, 1107, 1070, 1010, 913, 880, 845,
777, 729, 666. EI-MS, m/z (%): 336 (M+, 100), 321 (57), 307 (63), 289 (13), 275
(12), 261 (15), 246 (8), 214 (14), 198 (24), 186 (19), 171 (8), 159 (20), 150 (19), 129
11

ACCEPTED MANUSCRIPT
(8), 116 (12), 104 (31), 89 (26), 76 (27), 67 (6), 56 (12), 44 (6). 1H NMR (300.1 MHz,
CDCl3): δ 3.21 (s, 6H, NMe2), 7.02 (t, J = 7.5 Hz, 2H, 2CH), 7.11–7.15 (m, 3H,
3CH), 7.47 (d, J = 8.6 Hz, 2H, 2CH), 7.87 (d, J = 8.6 Hz, 2H, 2CH), 9.00–10.52 (br,
1H, NH). 13C NMR (75.5 MHz, CDCl3): 38.5 (2NCH3), 122.7 (2CH), 123.8 (C),
127.8 (CH + 2CH), 128.8 (C), 129.8 (2 × 2CH), 132.6 and 143.8 (2C), 148.6 (CN3),
153.9 (C), 181.4 (C=O). Anal. Calcd for C18H16N4O3 (336.35): C, 64.28; H, 4.79; N,
16.66. Found: C, 64.04; H, 4.58; N, 16.51%.
4.4.11.
5-(4-Chlorobenzoyl)-4-(4-chlorophenyl)-2-(dimethylamino)-1H-imidazole
(3k)
Yellow crystals, mp 214–216 °C, yield: 0.345 g, 96%. IR (KBr) (νmax/cm–1): 3247
(NH), 1619 (C=O), 1575, 1535, 1486, 1442, 1379, 1315, 1227, 1172, 1088, 1010,
912, 832, 763, 673, 625. EI-MS, m/z (%): 363 (M+ 37Cl2, 10), 361 (M+ 37Cl35Cl, 68),
359 (M+ 35Cl2, 100), 344 (15), 330 (23), 248 (8), 232 (35), 220 (12), 204 (8), 184 (16),
163 (8), 150 (12), 139 (58), 123 (24), 111 (43), 100 (1), 87 (3), 75 (19), 56 (8), 42 (7).
1H NMR (300.1 MHz, CDCl3): δ 3.16 (s, 6H, NMe2), 7.05 (d, J = 8.6 Hz, 2H, 2CH),
7.07 (d, J = 8.4 Hz, 2H, 2CH), 7.11 (d, J = 8.6 Hz, 2H, 2CH), 7.31 (d, J = 8.4 Hz, 2H,
2CH), 9.26–10.80 (br, 1H, NH). 13C NMR (75.5 MHz, CDCl3): δ 38.3 (2NCH3),
123.8 (C), 127.8 (2CH), 127.9 (2CH), 130.4 (2CH), 131.0 (2CH), 132.0, 134.3, 136.4
and 137.5 (4C), 150.1 (CN3), 154.1 (C), 182.8 (C=O). Anal. Calcd for C18H15Cl2N3O
(360.24): C, 60.01; H, 4.20; N, 11.66. Found: C, 59.84; H, 4.13; N, 11.51%.
4.4.12. 5-(4-Bromobenzoyl)-2-(dimethylamino)-4-(4-methylphenyl)-1H-imidazole (3l)
Yellow crystals, mp 232 °C, yield: 0.352 g, 92%. IR (KBr) (νmax/cm–1): 3235 (NH),
1616 (C=O), 1573, 1541, 1497, 1443, 1380, 1318, 1226, 1172, 1107, 1065, 1007,
911, 847, 824, 760, 721, 669, 635. 373 371. EI-MS, m/z (%): 385 (M+ 81Br, 95), 383
(M+ 79Br, 100), 368 (13), 356 (17), 354 (18), 341 (4), 339 (5), 228 (9), 212 (25), 200
(18), 185 (35), 173 (12), 155 (27), 130 (12), 116 (9), 103 (28), 90 (5), 76 (10), 56 (6),
42 (5). 1H NMR (300.1 MHz, CDCl3): δ 2.26 (s, 3H, CH3), 3.17 (s, 6H, NMe2), 6.87
(d, J = 8.0 Hz, 2H, 2CH), 7.03 (d, J = 8.0 Hz, 2H, 2CH), 7.18 (d, J = 8.7 Hz, 2H,
2CH), 7.22 (d, J = 8.7 Hz, 2H, 2CH), 8.81–10.58 (br, 1H, NH). 13C NMR (75.5 MHz,
CDCl3): δ 21.1 (CH3), 38.4 (2NCH3), 123.5 and 125.5 (C), 128.3 (2CH), 129.6
(2CH), 129.9 (C), 130.5 (2CH), 130.6 (2CH), 136.8 and 138.4 (2C), 151.9 (CN3),
153.6 (C), 183.0 (C=O). Anal. Calcd for C19H18BrN3O (384.27): C, 59.39; H, 4.72; N,
10.94. Found: C, 59.16; H, 4.53; N, 10.75%.
12

ACCEPTED MANUSCRIPT
4.5. General procedure for the preparation of pyrrolo[1,2-c]imidazoles (5a–x):
To a magnetically stirred solution of triphenylphosphine (1 mmol) and the appropriate
imidazole 1 (1 mmol) in CH2Cl2 (1 mL) at 25 °C was added dropwise a solution of
the appropriate dialkyl acetylenedicarboxylate (1 mmol) in CH2Cl2 (1 mL) over 2
min. The mixture was stirred at 25 °C for 10 min. The solvent was removed and the
product was purified by recrystallization from n-hexane/EtOAc (1:1).
4.5.1. Dimethyl 3-(dimethylamino)-7-(4-methylphenyl)-1-phenyl-5H-pyrrolo[1,2-
c]imidazole-5,6-dicarboxylate (5a)
Orange crystals, mp 162–163 °C, yield: 0.375 g, 87%. IR (KBr) (νmax/cm–1): 1744 and
1707 (C=O), 1597, 1546, 1489, 1426, 1357, 1309, 1206, 1169, 1114, 1069, 983, 953,
924, 858, 768, 698. EI-MS, m/z (%): 431 (M+, 55), 372 (100), 356 (6), 312 (5), 298
(7), 270 (7), 255 (5), 242 (12), 227 (11), 215 (8), 202 (5), 189 (3), 170 (6), 156 (6),
148 (7), 84 (12), 77 (7), 59 (16). 1H NMR (300.1 MHz, CDCl3): δ 2.35 (s, 3H, CH3),
3.10 (s, 6H, NMe2), 3.64 and 3.80 (2s, 6H, 2OCH3), 5.64 (s, 1H, NCH), 6.92–7.02 (m,
13
2H, 2CH), 7.03–7.12 (m, 5H, 5CH), 7.17 (d, J = 8.1 Hz, 2H, 2CH). C NMR (75.5
MHz, CDCl3): δ 21.4 (CH3), 39.3 (2NCH3), 51.4 and 53.3 (2OCH3), 63.7 (CH), 121.8
(C), 127.3 (CH), 127.5 (2CH), 128.3 (2CH), 128.4 (C), 128.7 (2CH), 128.8 (2CH),
131.9, 132.8, 135.2, 139.0 and 146.3 (5C), 150.1 (CN3), 163.0 and 167.9 (2C=O).
Anal. Calcd for C25H25N3O4 (431.48): C, 69.59; H, 5.84; N, 9.74. Found: C, 69.50; H,
5.71; N, 9.66%.
4.5.2.
Diethyl
3-(dimethylamino)-7-(4-methylphenyl)-1-phenyl-5H-pyrrolo[1,2-
c]imidazole-5,6-dicarboxylate (5b)
Orange crystals, mp 120–121 °C, yield: 0.376 g, 82%. IR (KBr) (νmax/cm–1): 1741 and
1709 (C=O), 1577, 1548, 1484, 1426, 1353, 1307, 1191, 1156, 1066, 1024, 951, 903,
834, 768, 744, 696, 655. EI-MS, m/z (%): 459 (M+, 30), 405 (5), 386 (100), 358 (29),
312 (7), 298 (5), 269 (6), 255 (4), 241 (5), 227 (7), 215 (5), 202 (5), 170 (4), 127 (4),
119 (4), 105 (4), 84 (7), 77 (5). 1H NMR (300.1 MHz, CDCl3): δ 1.13 (t, J = 7.1 Hz,
3H, OCH2CH3), 1.28 (t, J = 7.1 Hz, 3H, OCH2CH3), 2.37 (s, 3H, CH3), 3.08 (s, 6H,
2
3
NMe2), 4.08 and 4.12 (2dq, J = 10.8, J = 7.1 Hz, 2H, OCH2CH3), 4.25 and 4.29
2
3
(2dq, J = 10.8, J = 7.1 Hz, 2H, OCH2CH3), 5.60 (s, 1H, NCH), 6.95–7.02 (m, 2H,
2CH), 7.04–7.12 (m, 4H, 4CH), 7.19 (d, J = 8.0 Hz, 2H, 2CH). 13C NMR (75.5 MHz,
CDCl3): δ 13.9 and 14.0 (2OCH2CH3), 21.3 (CH3), 39.2 (2NCH3), 60.2 and 62.1
(2OCH2CH3), 63.7 (CH), 122.3 (C), 127.0 (CH), 127.4 (2CH), 128.1 (2CH), 128.6
(2CH), 128.8 (2CH), 128.9, 132.6, 133.1, 135.5, 138.7 and 146.2 (6C), 150.4 (CN3),
13

ACCEPTED MANUSCRIPT
162.7 and 167.4 (2C=O). Anal. Calcd for C27H29N3O4 (459.54): C, 70.57; H, 6.36; N,
9.14. Found: C, 70.42; H, 6.39; N, 8.97%.
4.5.3. Dimethyl 7-(4-chlorophenyl)-3-(dimethylamino)-1-phenyl-5H-pyrrolo[1,2-
c]imidazole-5,6-dicarboxylate (5c)
Orange crystals, mp 132 °C, yield: 0.406 g, 90%. IR (KBr) (νmax/cm–1): 1746 and
1706 (C=O), 1586, 1541, 1485, 1427, 1358, 1303, 1211, 1169, 1083, 985, 955, 925,
850, 836, 808, 766, 699, 655. EI-MS, m/z (%): 453 (M+ 37Cl, 10), 451 (M+ 35Cl, 26),
394 (36), 392 (100), 376 (4), 318 (4), 290 (4), 255 (4), 227 (14), 214 (4), 200 (5), 180
(5), 162 (4), 139 (5), 105 (4), 77 (7), 59 (14), 42 (4). 1H NMR (300.1 MHz, CDCl3): δ
3.11 (s, 6H, NMe2), 3.64 and 3.81 (2s, 6H, 2OCH3), 5.65 (s, 1H, NCH), 7.00–7.15 (m,
13
5H, 5CH), 7.23 (d, J = 8.7 Hz, 2H, 2CH), 7.25 (d, J = 8.7 Hz, 2H, 2CH). C NMR
(75.5 MHz, CDCl3): δ 39.3 (2NCH3), 51.6 and 53.4 (2OCH3), 63.7 (CH), 122.2 (C),
127.6 (3CH), 128.2 (4CH), 129.7 (C), 130.4 (2CH), 131.8, 132.3, 135.0, 135.7 and
144.7 (5C), 150.3 (CN3), 162.9 and 167.7 (2C=O). Anal. Calcd for C24H22ClN3O4
(451.90): C, 63.79; H, 4.91; N, 9.30. Found: C, 63.60; H, 4.68; N, 9.14%.
4.5.4.
Diethyl
7-(4-chlorophenyl)-3-(dimethylamino)-1-phenyl-5H-pyrrolo[1,2-
c]imidazole-5,6-dicarboxylate (5d)
Orange crystals, mp 114 °C, yield: 0.431 g, 90%. IR (KBr) (νmax/cm–1): 1741 and
1701 (C=O), 1611, 1544, 1486, 1419, 1359, 1307, 1215, 1206, 1140, 1124, 1090,
1062, 1020, 975, 952, 922, 880, 835, 803, 771, 744, 695. EI-MS, m/z (%): 481 (M+
37Cl, 4), 479 (M+ 35Cl, 14), 408 (36), 406 (100), 380 (6), 378 (17), 307 (5), 261 (6),
1
227 (11), 202 (5), 189 (5), 139 (6), 113 (7), 99 (5), 85 (5), 77 (6), 57 (7), 43 (9). H
NMR (300.1 MHz, CDCl3): δ 1.13 (d, J = 7.1 Hz, 3H, OCH2CH3), 1.29 (d, J = 7.1
2
3
Hz, 3H, OCH2CH3), 3.10 (s, 6H, NMe2), 4.08 and 4.13 (2dq, J = 10.8, J = 7.1 Hz,
2
3
2H, OCH2CH3), 4.27 and 4.30 (2dq, J = 10.8, J = 7.1 Hz, 2H, OCH2CH3), 5.59 (s,
1H, NCH), 7.00–7.15 (m, 5H, 5CH), 7.25 (d, J = 8.8 Hz, 2H, 2CH), 7.27 (d, J = 8.8
Hz, 2H, 2CH). 13C NMR (75.5 MHz, CDCl3): δ 13.9 and 14.0 (2OCH2CH3), 39.1
(2NCH3), 60.3 and 62.2 (2OCH2CH3), 63.7 (CH), 122.5 (C), 127.2 (CH), 127.6
(2CH), 128.0 (2CH), 128.1 (2CH), 130.0 (C), 130.4 (2CH), 132.8, 132.9, 134.7, 136.5
and 144.7 (5C), 150.8 (CN3), 162.6 and 167.3 (2C=O). Anal. Calcd for C26H26ClN3O4
(479.96): C, 65.06; H, 5.46; N, 8.76. Found: C, 64.77; H, 5.51; N, 8.60%.
4.5.5.
Dimethyl
1-(4-bromophenyl)-3-(dimethylamino)-7-(4-methylphenyl)-5H-
pyrrolo[1,2-c]imidazole-5,6-dicarboxylate (5e)
14

ACCEPTED MANUSCRIPT
Orange crystals, mp 148–150 °C, yield: 0.422 g, 83%. IR (KBr) (νmax/cm–1): 1744 and
1712 (C=O), 1601, 1550, 1500, 1432, 1361, 1314, 1294, 1246, 1201, 1167, 1112,
1069, 1017, 996, 954, 912, 830, 796, 768, 733, 683, 630. EI-MS, m/z (%): 511 (M+
81Br, 13), 509 (M+ 79Br, 14), 452 (98), 450 (100), 371 (8), 296 (8), 269 (7), 241 (15),
227 (8), 215 (7), 196 (6), 169 (6), 155 (6), 141 (5), 127 (7), 59 (31), 42 (5). 1H NMR
(300.1 MHz, CDCl3): δ 2.41 (s, 3H, CH3), 3.05 (s, 6H, NMe2), 3.63 and 3.79 (2s, 6H,
2OCH3), 5.60 (s, 1H, NCH), 6.94 (d, J = 8.6 Hz, 2H, 2CH), 7.11 (d, J = 8.6 Hz, 2H,
2CH), 7.15 (d, J = 8.4 Hz, 2H, 2CH), 7.19 (d, J = 8.4 Hz, 2H, 2CH). 13C NMR (75.5
MHz, CDCl3): δ 21.4 (CH3), 39.1 (2NCH3), 51.3 and 53.2 (2OCH3), 63.5 (CH), 121.0
and 122.0 (2C), 128.63 (2CH), 128.64 (C), 128.8 (2CH), 129.5 (2CH), 130.5 (2CH),
132.1, 133.4, 134.9, 139.0 and 146.2 (5C), 150.7 (CN3), 163.1 and 167.9 (2C=O).
Anal. Calcd for C25H24BrN3O4 (510.38): C, 58.83; H, 4.74; N, 8.23. Found: C, 58.94;
H, 4.58; N, 8.07%.
4.5.6.
Diethyl
1-(4-bromophenyl)-3-(dimethylamino)-7-(4-methylphenyl)-5H-
pyrrolo[1,2-c]imidazole-5,6-dicarboxylate (5f)
Orange crystals, mp 157–158 °C, yield: 0.435 g, 81%. IR (KBr) (νmax/cm–1): 1745 and
1707 (C=O), 1584, 1547, 1505, 1478, 1427, 1355, 1308, 1209, 1187, 1156, 1125,
1110, 1064, 1023, 973, 902, 880, 831, 768, 745, 717, 677, 648. EI-MS, m/z (%): 539
(M+ 81Br, 13), 537 (M+ 79Br, 14), 466 (98), 464 (100), 438 (20), 436 (20), 393 (4), 385
(4), 312 (4), 269 (5), 241 (9), 227 (5), 215 (4), 127 (5), 42 (9). 1H NMR (300.1 MHz,
CDCl3): δ 1.11 (t, J = 7.1 Hz, 3H, OCH2CH3), 1.27 (t, J = 7.1 Hz, 3H, OCH2CH3),
2.40 (s, 3H, CH3), 3.05 (s, 6H, NMe2), 4.07 and 4.11 (2dq, 2J = 10.8, 3J = 7.1 Hz, 2H,
2
3
OCH2CH3), 4.25 and 4.29 (2dq, J = 10.8, J = 7.1 Hz, 2H, OCH2CH3), 5.57 (s, 1H,
NCH), 6.96 (d, J = 8.6 Hz, 2H, 2CH), 7.11 (d, J = 8.6 Hz, 2H, 2CH), 7.15 (d, J = 8.4
13
Hz, 2H, 2CH), 7.18 (d, J = 8.4 Hz, 2H, 2CH). C NMR (75.5 MHz, CDCl3): δ 13.9
and 14.0 (2OCH2CH3), 21.4 (CH3), 39.1 (2NCH3), 60.2 and 62.2 (2OCH2CH3), 63.7
(CH), 120.8 and 122.8 (2C), 128.6 (2CH), 128.7 (2CH), 128.9 (C), 129.5 (2CH),
130.5 (2CH), 132.2, 133.6, 134.6, 138.8 and 146.0 (5C), 150.6 (CN3), 162.6 and
167.3 (2C=O). Anal. Calcd for C27H28BrN3O4 (538.44): C, 60.23; H, 5.24; N, 7.80.
Found: C, 60.01; H, 5.13; N, 7.79%.
4.5.7.
Dimethyl
7-(4-chlorophenyl)3-(dimethylamino)-1-(4-methoxyphenyl)-5H-
pyrrolo[1,2-c]imidazole-5,6-dicarboxylate (5g)
Orange crystals, mp 158 °C, yield: 0.409 g, 85%. IR (KBr) (νmax/cm–1): 1749 and
1718 (C=O), 1574, 1545, 1507, 1477, 1434, 1357, 1313, 1197, 1165, 1113, 1064,
15

ACCEPTED MANUSCRIPT
1000, 949, 860, 831, 791, 772, 744, 717, 681, 650. EI-MS, m/z (%): 483 (M+ 37Cl, 4),
481 (M+ 35Cl, 13), 424 (34), 422 (100), 357 (8), 355 (23), 340 (4), 320 (4), 258 (7),
242 (4), 228 (5), 214 (8), 195 (9), 139 (11), 111 (7), 84 (9), 59 (15), 43 (5). 1H NMR
(300.1 MHz, CDCl3): δ 3.06 (s, 6H, NMe2), 3.62, 3.73 and 3.79 (3s, 9H, 3OCH3),
5.60 (s, 1H, NCH), 6.58 (d, J = 8.9 Hz, 2H, 2CH), 7.00 (d, J = 8.9 Hz, 2H, 2CH), 7.24
(d, J = 8.8 Hz, 2H, 2CH), 7.29 (d, J = 8.7 Hz, 2H, 2CH). 13C NMR (75.5 MHz,
CDCl3): δ 39.0 (2NCH3), 51.3, 53.2 and 55.1 (3OCH3), 63.4 (CH), 113.0 (2CH),
121.0 and 125.6 (2C), 128.2 (2CH), 129.3 (2CH), 130.3 (C), 130.4 (2CH), 131.9,
134.8, 136.8 and 145.0 (4C), 150.8 (CN3), 159.0 (C), 163.1 and 168.0 (2C=O). Anal.
Calcd for C25H24ClN3O5 (481.94): C, 62.31; H, 5.02; N, 8.72. Found: C, 61.20; H,
4.92; N, 8.57%.
4.5.8.
Diethyl
7-(4-chlorophenyl)3-(dimethylamino)-1-(4-methoxyphenyl)-5H-
pyrrolo[1,2-c]imidazole-5,6-dicarboxylate (5h)
Orange crystals, mp 165–166 °C, yield: 0.428 g, 84%. IR (KBr) (νmax/cm–1): 1752 and
1704 (C=O), 1601, 1545, 1498, 1441, 1365, 1297, 1249, 1172, 1093, 1065, 1021,
978, 926, 903, 837, 797, 728, 686, 633. EI-MS, m/z (%): 511 (M+ 37Cl, 5), 509 (M+
35Cl, 12), 438 (34), 436 (100), 410 (7), 408 (18), 258 (5), 237 (12), 222 (6), 214 (5),
1
195 (5), 135 (7), 119 (4), 105 (7), 77 (8), 42 (4). H NMR (300.1 MHz, CDCl3): δ
1.13 (t, J = 7.1 Hz, 3H, OCH2CH3), 1.29 (t, J = 7.1 Hz, 3H, OCH2CH3), 3.12 (s, 6H,
2
3
NMe2), 3.74 (s, 3H, OCH3), 4.08 and 4.12 (2dq, J = 10.8, J = 7.1 Hz, 2H,
2
3
OCH2CH3), 4.27 and 4.30 (2dq, J = 10.8, J = 7.1 Hz, 2H, OCH2CH3), 5.62 (s, 1H,
NCH), 6.58 (d, J = 8.8 Hz, 2H, 2CH), 7.03 (d, J = 8.8 Hz, 2H, 2CH), 7.23 (d, J = 8.5
13
Hz, 2H, 2CH), 7.28 (d, J = 8.5 Hz, 2H, 2CH). C NMR (75.5 MHz, CDCl3): δ 13.9
and 14.0 (2OCH2CH3), 39.4 (2NCH3), 55.1 (OCH3), 60.4 and 62.4 (2OCH2CH3), 64.0
(CH), 113.1 (2CH), 122.5 and 125.8 (2C), 128.2 (2CH), 129.6 (2CH), 130.0 (C),
130.4 (2CH), 131.6, 132.4, 134.9 and 144.4 (4C), 150.3 (CN3), 159.2 (C), 162.4 and
167.1 (2C=O). Anal. Calcd for C27H28ClN3O5 (509.98): C, 63.59; H, 5.53; N, 8.24.
Found: C, 63.36; H, 5.40; N, 8.19%.
4.5.9.
Dimethyl
1-(4-chlorophenyl)-3-(dimethylamino)-7-(4-methylphenyl)-5H-
pyrrolo[1,2-c]imidazole-5,6-dicarboxylate (5i)
Orange crystals, mp 175 °C, yield: 0.409 g, 88%. IR (KBr) (νmax/cm–1): 1740 and
1711 (C=O), 1580, 1543, 1481, 1427, 1356, 1319, 1281, 1201, 1151, 1114, 1062,
1004, 962, 877, 831, 773, 728, 683, 647. EI-MS, m/z (%): 467 (M+ 37Cl, 11), 465 (M+
35Cl, 31), 408 (34), 406 (100), 304 (4), 269 (4), 241 (9), 227 (4), 215 (4), 196 (4), 187
16

ACCEPTED MANUSCRIPT
(4), 169 (6), 155 (4), 139 (4), 127 (4), 59 (18), 42 (4). 1H NMR (300.1 MHz, CDCl3):
δ 2.40 (s, 3H, CH3), 3.09 (s, 6H, NMe2), 3.64 and 3.81 (2s, 6H, 2OCH3), 5.64 (s, 1H,
NCH), 6.96 (d, J = 8.6 Hz, 2H, 2CH), 7.01 (d, J = 8.6 Hz, 2H, 2CH), 7.12 (d, J = 8.2
13
Hz, 2H, 2CH), 7.17 (d, J = 8.2 Hz, 2H, 2CH). C NMR (75.5 MHz, CDCl3): δ 21.4
(CH3), 39.3 (2NCH3), 51.5 and 53.4 (2OCH3), 63.8 (CH), 122.4 (C), 127.6 (2CH),
128.2 (C), 128.6 (2CH), 128.8 (2CH), 129.4 (2CH), 130.6, 133.00, 133.04, 133.9,
139.2 and 146.0 (6C), 150.1 (CN3), 162.9 and 167.7 (2C=O). Anal. Calcd for
C25H24ClN3O4 (465.94): C, 64.44; H, 5.19; N, 9.02. Found: C, 64.39; H, 5.01; N,
8.78%.
4.5.10.
Diethyl
1-(4-chlorophenyl)-3-(dimethylamino)-7-(4-methylphenyl)-5H-
pyrrolo[1,2-c]imidazole-5,6-dicarboxylate (5j)
Orange crystals, mp 162–163 °C, yield: 0.414 g, 84%. IR (KBr) (νmax/cm–1): 1748 and
1699 (C=O), 1593, 1547, 1483, 1421, 1355, 1302, 1206, 1098, 1067, 1018, 955, 903,
829, 774, 718, 682, 649. EI-MS, m/z (%): 495 (M+ 37Cl, 5), 493 (M+ 35Cl, 15), 422
(34), 420 (100), 394 (6), 392 (18), 348 (5), 303 (4), 279 (4), 269 (4), 241 (7), 227 (4),
1
215 (4), 187 (4), 169 (4), 139 (5), 128 (4), 69 (2), 43 (2). H NMR (300.1 MHz,
CDCl3): δ 1.11 (t, J = 7.1 Hz, 3H, OCH2CH3), 1.27 (t, J = 7.1 Hz, 3H, OCH2CH3),
2.40 (s, 3H, CH3), 3.05 (s, 6H, NMe2), 4.06 and 4.11 (2dq, 2J = 10.8, 3J = 7.1 Hz, 2H,
2
3
OCH2CH3), 4.25 and 4.28 (2dq, J = 10.8, J = 7.1 Hz, 2H, OCH2CH3), 5.57 (s, 1H,
NCH), 6.95 (d, J = 8.6 Hz, 2H, 2CH), 7.01 (d, J = 8.6 Hz, 2H, 2CH), 7.14 (d, J = 8.2
13
Hz, 2H, 2CH), 7.18 (d, J = 8.2 Hz, 2H, 2CH). C NMR (75.5 MHz, CDCl3): δ 13.9
and 14.0 (2OCH2CH3), 21.4 (CH3), 39.1 (2NCH3), 60.2 and 62.1 (2OCH2CH3), 63.7
(CH), 122.7 (C), 127.5 (2CH), 128.6 (2CH), 128.7 (2CH), 128.9 (C), 129.2 (2CH),
131.7, 132.5, 133.5, 134.6, 138.8 and 146.0 (6C), 150.6 (CN3), 162.6 and 167.3
(2C=O). Anal. Calcd for C27H28ClN3O4 (493.98): C, 65.65; H, 5.71; N, 8.51. Found:
C, 65.48; H, 5.56; N, 8.25%.
4.5.11. Dimethyl 7-(4-chlorophenyl)-3-(dimethylamino)-1-(4-methylphenyl)-5H-
pyrrolo[1,2-c]imidazole-5,6-dicarboxylate (5k)
Orange crystals, mp 150–152 °C, yield: 0.391 g, 84%. IR (KBr) (νmax/cm–1): 1749 and
1711 (C=O), 1606, 1576, 1542, 1497, 1439, 1358, 1318, 1209, 1172, 1114, 1086,
1008, 960, 913, 825, 795, 764, 725, 676, 638. EI-MS, m/z (%): 467 (M+ 37Cl, 4), 465
(M+ 35Cl, 13), 408 (35), 406 (100), 341 (33), 339 (93), 324 (12), 310 (17), 237 (26),
222 (11), 212 (17), 200 (10), 184 (9), 169 (8), 139 (29), 111 (22), 77 (15), 59 (12), 43
1
(12). H NMR (300.1 MHz, CDCl3): δ 2.26 (s, 3H, CH3), 3.07 (s, 6H, NMe2), 3.64
17

ACCEPTED MANUSCRIPT
and 3.80 (2s, 6H, 2OCH3), 5.61 (s, 1H, NCH), 6.85 (d, J = 8.1 Hz, 2H, 2CH), 6.96 (d,
J = 8.1 Hz, 2H, 2CH), 7.26 (d, J = 8.3 Hz, 2H, 2CH), 7.30 (d, J = 8.6 Hz, 2H, 2CH).
13C NMR (75.5 MHz, CDCl3): δ 21.1 (CH3), 39.1 (2NCH3), 51.3 and 53.2 (2OCH3),
63.4 (CH), 121.4 (C), 127.9 (2CH), 128.2 (2CH), 128.3 (2CH), 129.9 and 130.3 (2C),
130.4 (2CH), 132.3, 134.8, 137.0, 137.1 and 145.1 (5C), 150.8 (CN3), 163.1 and
168.0 (2C=O). Anal. Calcd for C25H24ClN3O4 (465.93): C, 64.44; H, 5.19; N, 9.02.
Found: C, 64.56; H, 5.02; N, 8.77%.H, 4.38.
4.5.12.
Diethyl
7-(4-chlorophenyl)-3-(dimethylamino)-1-(4-methylphenyl)-5H-
pyrrolo[1,2-c]imidazole-5,6-dicarboxylate (5l)
Orange crystals, mp 138 °C, yield: 0.419 g, 85%. IR (KBr) (νmax/cm–1): 1746 and
1705 (C=O), 1602, 1572, 1543, 1494, 1430, 1355, 1304, 1211, 1185, 1163, 1118,
1111, 1089, 1066, 1021, 972, 959, 904, 879, 849, 826, 766, 726, 683, 646. EI-MS,
m/z (%): 495 (M+ 37Cl, 4), 493 (M+ 35Cl, 13), 422 (34), 420 (100), 394 (6), 392 (18),
1
332 (4), 242 (8), 227 (4), 213 (4), 187 (4), 169 (4), 139 (4), 4 (8), 43 (4). H NMR
(300.1 MHz, CDCl3): δ 1.12 (t, J = 7.1 Hz, 3H, OCH2CH3), 1.28 (t, J = 7.1 Hz, 3H,
OCH2CH3), 2.25 (s, 3H, CH3), 3.07 (s, 6H, NMe2), 4.07 and 4.11 (2dq, 2J = 10.8, 3J =
2
3
7.1 Hz, 2H, OCH2CH3), 4.26 and 4.29 (2dq, J = 10.8, J = 7.1 Hz, 2H, OCH2CH3),
5.58 (s, 1H, NCH), 6.85 (d, J = 8.0 Hz, 2H, 2CH), 6.97 (d, J = 8.1 Hz, 2H, 2CH), 7.26
(d, J = 8.7 Hz, 2H, 2CH), 7.29 (d, J = 8.7 Hz, 2H, 2CH). 13C NMR (75.5 MHz,
CDCl3): δ 13.9 and 14.0 (2OCH2CH3), 21.1 (CH3), 39.1 (2NCH3), 60.2 and 62.1
(2OCH2CH3), 63.6 (CH), 122.2 (C), 127.8 (2CH), 128.1 (2CH), 128.3 (2CH), 130.1
(C), 130.4 (2CH), 130.6, 132.4, 134.7, 136.7, 137.0 and 144.8 (6C), 150.8 (CN3),
162.6 and 167.4 (2C=O). Anal. Calcd for C27H28ClN3O4 (493.98): C, 65.65; H, 5.71;
N, 8.51. Found: C, 65.53; H, 5.58; N, 8.29%.
4.5.13. Dimethyl 7-(4-bromophenyl)-3-(dimethylamino)-1-phenyl-5H-pyrrolo[1,2-
c]imidazole-5,6-dicarboxylate (5m)
Orange crystals, mp 129–131 °C, yield: 0.450 g, 91%. IR (KBr) (νmax/cm–1): 1745 and
1698 (C=O), 1613, 1538, 1487, 1440, 1396, 1362, 1249, 1226, 1204, 1160, 1066,
1009, 910, 827, 773, 726, 697, 646. EI-MS, m/z (%): 497 (M+ 81Br, 12), 495 (M+ 79Br,
13), 469 (6), 467 (7), 438 (98), 436 (100), 410 (16), 408 (16), 357 (13), 330 (16), 296
(32), 272 (8), 256 (10), 242 (12), 228 (25), 214 (21), 189 (8), 175 (44), 148 (9), 127
1
(11), 113 (10), 105 (69), 77 (57), 59 (32), 44 (14). H NMR (300.1 MHz, CDCl3): δ
3.10 (s, 6H, NMe2), 3.64 and 3.81 (2s, 6H, 2OCH3), 5.64 (s, 1H, NCH), 7.00–7.13 (m,
13
5H, 5CH), 7.16 (d, J = 8.4 Hz, 2H, 2CH), 7.42 (d, J = 8.4 Hz, 2H, 2CH). C NMR
18

ACCEPTED MANUSCRIPT
(75.5 MHz, CDCl3): δ 39.2 (2NCH3), 51.5 and 53.3 (2OCH3), 63.7 (CH), 122.1 and
123.2 (2C), 127.5 (CH), 127.6 (2CH), 128.2 (2CH), 130.4 (C), 130.6 (2CH), 131.2
(2CH), 132.0, 132.3, 136.0 and 144.7 (4C), 150.5 (CN3), 162.9 and 167.7 (2C=O).
Anal. Calcd for C24H22BrN3O4 (496.35): C, 58.07; H, 4.47; N, 8.47. Found: C, 56.82;
H, 4.29; N, 8.35%.
4.5.14. Diethyl 7-(4-bromophenyl)-3-(dimethylamino)-1-phenyl-5H-pyrrolo[1,2-
c]imidazole-5,6-dicarboxylate (5n)
Orange crystals, mp 115 °C, yield: 0.465 g, 89%. IR (KBr) (νmax/cm–1): 1738 and
1708 (C=O), 1609, 1548, 1487, 1454, 1418, 1359, 1334, 1278, 1208, 1147, 1120,
1066, 1014, 970, 919, 873, 832, 772, 689. EI-MS, m/z (%): 525 (M+ 81Br, 14), 523
(M+ 79Br, 15), 452 (98), 450 (100), 424 (16), 422 (17), 371 (10), 343 (4), 298 (4), 282
(4), 255 (9), 228 (24), 202 (7), 162 (4), 141 (4), 128 (3), 114 (3), 77 (4), 42 (4).1H
NMR (500.1 MHz, CDCl3): δ 1.22 (t, J = 7.1 Hz, 3H, OCH2CH3), 1.38 (t, J = 7.1 Hz,
2
3
3H, OCH2CH3), 3.17 (s, 6H, NMe2), 4.18 and 4.21 (2dq, J = 10.8, J = 7.1 Hz, 2H,
2
3
OCH2CH3), 4.36 and 4.39 (2dq, J = 10.8, J = 7.1 Hz, 2H, OCH2CH3), 5.68 (s, 1H,
NCH), 7.12–7.21 (m, 5H, 5CH), 7.27 (d, J = 8.4 Hz, 2H, 2CH), 7.52 (d, J = 8.4 Hz,
2H, 2CH). 13C NMR (125.8 MHz, CDCl3): δ 14.17 and 14.25 (2OCH2CH3), 39.3
(2NCH3), 60.6 and 62.5 (2OCH2CH3), 63.9 (CH), 122.7 and 123.2 (2C), 127.5 (CH),
127.8 (2CH), 128.3 (2CH), 130.9 (2CH), 131.1 (C), 131.3 (2CH), 132.9, 133.0, 136.7
and 144.9 (4C), 151.1 (CN3), 162.8 and 167.6 (2C=O). Anal. Calcd for C26H26BrN3O4
(524.41): C, 59.55; H, 5.00; N, 8.01. Found: C, 59.63; H, 5.12; N, 7.72%.
4.5.15. Dimethyl 3-(dimethylamino)-1,7-diphenyl-5H-pyrrolo[1,2-c]imidazole-5,6-
dicarboxylate (5o)
Orange crystals, mp 98–99 °C, yield: 0.338 g, 81%. IR (KBr) (νmax/cm–1): 1746 and
1709 (C=O), 1587, 1544, 1488, 1430, 1415, 1358, 1283, 1242, 1207, 1114, 1071,
1005, 986, 960, 920, 874, 764, 732, 692, 644. EI-MS, m/z (%): 417 (M+, 18), 358
(100), 256 (6), 228 (11), 202 (6), 163 (6), 141 (4), 114 (4), 82 (3), 77 (5), 59 (13). 1H
NMR (300.1 MHz, CDCl3): δ 3.08 (s, 6H, NMe2), 3.61 and 3.80 (2s, 6H, 2OCH3),
5.64 (s, 1H, NCH), 6.92–7.10 (m, 5H, 5CH), 7.27–7.40 (m, 5H, 5CH). 13C NMR
(75.5 MHz, CDCl3): δ 39.2 (2NCH3), 51.3 and 53.2 (2OCH3), 63.6 (CH), 121.9 (C),
127.1 (CH), 127.5 (2CH), 128.0 (2CH), 128.1 (2CH), 128.75 (2CH), 128.83 (CH),
131.7, 132.5, 132.9, 136.1 and 146.2 (5C), 150.5 (CN3), 163.1 and 167.9 (2C=O).
Anal. Calcd for C24H23N3O4 (417.46): C, 69.05; H, 5.55; N, 10.07. Found: C, 68.76;
H, 5.41; N, 9.83%.
19

ACCEPTED MANUSCRIPT
4.5.16. Diethyl 3-(dimethylamino)-1,7-diphenyl-5H-pyrrolo[1,2-c]imidazole-5,6-
dicarboxylate (5p)
Orange crystals, mp 136–138 °C, yield: 0.356 g, 80%. IR (KBr) (νmax/cm–1): 1738 and
1705 (C=O), 1585, 1545, 1488, 1437, 1422, 1355, 1311, 1268, 1240, 1199, 1151,
1113, 1071, 1019, 953, 920, 877, 843, 767, 691. EI-MS, m/z (%): 445 (M+, 15), 372
(100), 344 (20), 298 (6), 284 (4), 255 (7), 228 (9), 202 (9), 163 (4), 141 (3), 128 (4),
105 (14), 77 (9). 1H NMR (300.1 MHz, CDCl3): δ 1.09 (t, J = 7.1 Hz, 3H, OCH2CH3),
1.29 (t, J = 7.1 Hz, 3H, OCH2CH3), 3.08 (s, 6H, NMe2), 4.06 and 4.11 (2dq, 2J = 10.8,
2
3
3J = 7.1 Hz, 2H, OCH2CH3), 4.27 and 4.30 (2dq, J = 10.8, J = 7.1 Hz, 2H,
OCH2CH3), 5.60 (s, 1H, NCH), 6.92–7.10 (m, 5H, 5CH), 7.28–7.40 (m, 5H, 5CH).
13C NMR (75.5 MHz, CDCl3): δ 13.9 and 14.0 (2OCH2CH3), 39.2 (2NCH3), 60.2 and
62.2 (2OCH2CH3), 63.7 (CH), 122.5 (C), 126.9 (CH), 127.5 (2CH), 127.9 (2CH),
128.0 (2CH), 128.6 (CH), 128.8 (2CH), 132.2, 133.0, 133.2, 136.2 and 146.1 (5C),
150.8 (CN3), 162.8 and 167.5 (2C=O). Anal. Calcd for C26H27N3O4 (445.51): C,
70.09; H, 6.11; N, 9.43. Found: C, 69.88; H, 5.93; N, 9.14%.
4.5.17. Dimethyl 3-(dimethylamino)-1-(4-methoxyphenyl)-7-phenyl-5H-pyrrolo[1,2-
c]imidazole-5,6-dicarboxylate (5q)
Orange crystals, mp 142–143 °C, yield: 0.367 g, 82%. IR (KBr) (νmax/cm–1): 1747 and
1711 (C=O), 1580, 1543, 1494, 1432, 1360, 1320, 1245, 1200, 1166, 1120, 1068,
1033, 985, 948, 922, 859, 833, 774, 727, 692, 645. EI-MS, m/z (%): 447 (M+, 14), 388
(100), 286 (4), 243 (4), 237 (7), 215 (4), 178 (8), 135 (3), 105 (5), 77 (5), 59 (8), 43
(4). 1H NMR (300.1 MHz, CDCl3): δ 3.10 (s, 6H, NMe2), 3.62, 3.71 and 3.81 (3s, 9H,
3OCH3), 5.64 (s, 1H, NCH), 6.53 (d, J = 8.8 Hz, 2H, 2CH), 7.00 (d, J = 8.8 Hz, 2H,
2CH), 7.27–7.42 (m, 5H, 5CH). 13C NMR (75.5 MHz, CDCl3): δ 39.3 (2NCH3), 51.3,
53.3 and 55.1 (3OCH3), 63.7 (CH), 113.0 (2CH), 121.5 and 124.5 (2C), 128.0 (2CH),
128.7 (2CH), 128.9 (CH), 129.5 (2CH), 131.6, 131.9, 135.5 and 146.1 (4C), 150.1
(CN3), 159.0 (C), 163.0 and 167.9 (2C=O). Anal. Calcd for C25H25N3O5 (447.48): C,
67.10; H, 5.63; N, 9.39. Found: C, 66.85 H, 5.46; N, 9.21%.
4.5.18. Diethyl 3-(dimethylamino)-1-(4-methoxyphenyl)-7-phenyl-5H-pyrrolo[1,2-
c]imidazole-5,6-dicarboxylate (5r)
Orange crystals, mp 130 °C, yield: 0.394 g, 83%. IR (KBr) (νmax/cm–1): 1739 and
1707 (C=O), 1579, 1545, 1495, 1442, 1362, 1304, 1247, 1193, 1164, 1107, 1066,
1025, 954, 897, 834, 772, 730, 690. EI-MS, m/z (%): 475 (M+, 15), 402 (100), 374
1
(20), 330 (8), 286 (6), 243 (5), 217 (7), 190 (6), 178 (10), 135 (7), 72 (6). H NMR
20

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(300.1 MHz, CDCl3): δ 1.08 (t, J = 7.1 Hz, 3H, OCH2CH3), 1.28 (t, J = 7.1 Hz, 3H,
OCH2CH3), 3.06 (s, 6H, NMe2), 3.71 (s, 3H, OCH3), 4.05 and 4.10 (2dq, 2J = 10.8, 3J
= 7.1 Hz, 2H, OCH2CH3), 4.26 and 4.29 (2dq, 2J = 10.8, 3J = 7.1 Hz, 2H, OCH2CH3),
5.58 (s, 1H, NCH), 6.52 (d, J = 8.9 Hz, 2H, 2CH), 6.99 (d, J = 8.9 Hz, 2H, 2CH),
7.20–7.40 (m, 5H, 5CH). 13C NMR (75.5 MHz, CDCl3): δ 13.8 and 14.0
(2OCH2CH3), 39.1 (2NCH3), 55.1 (OCH3), 60.1 and 62.1 (2OCH2CH3), 63.6 (CH),
112.9 (2CH), 121.8 and 125.9 (2C), 127.9 (2CH), 128.6 (CH), 128.7 (2CH), 129.2
(2CH), 132.3, 132.5, 136.2 and 146.1 (4C), 150.7 (CN3), 158.7 (C), 162.8 and 167.6
(2C=O). Anal. Calcd for C27H29N3O5 (475.54): C, 68.19; H, 6.15; N, 8.84. Found: C,
67.86; H, 5.91; N, 8.70%.
4.5.19. Dimethyl 3-(dimethylamino)-7-(4-nitrophenyl)-1-phenyl-5H-pyrrolo[1,2-
c]imidazole-5,6-dicarboxylate (5s)
Orange crystals, mp 148–149 °C, yield: 0.360 g, 78%. IR (KBr) (νmax/cm–1): 1746 and
1703 (C=O), 1588, 1536, 1521, 1487, 1422, 1341, 1310, 1221, 1168, 1113, 1072,
978, 952, 924, 851, 804, 767, 730, 697. EI-MS, m/z (%): 462 (M+, 16), 403 (100), 357
1
(23), 255 (5), 227 (9), 216 (4), 200 (4), 175 (4), 105 (3), 84 (5), 59 (11), 43 (4). H
NMR (300.1 MHz, CDCl3): δ 3.09 (s, 6H, NMe2), 3.63 and 3.83 (2s, 6H, 2OCH3),
5.66 (s, 1H, NCH), 6.95–7.12 (m, 5H, 5CH), 7.47 (d, J = 8.8 Hz, 2H, 2CH), 8.14 (d, J
13
= 8.8 Hz, 2H, 2CH). C NMR (75.5 MHz, CDCl3): δ 39.0 (2NCH3), 51.6 and 53.3
(2OCH3), 63.5 (CH), 122.4 (C), 123.1 (2CH), 127.6 (2CH), 127.7 (CH), 128.0 (2CH),
130.1 (2CH), 132.0, 132.5, 137.4, 138.8, 143.5 and 147.9 (6C), 151.1 (CN3), 162.7
and 167.7 (2C=O). Anal. Calcd for C24H22N4O6 (462.46): C, 62.33; H, 4.79; N, 12.12.
Found: C, 62.14; H, 4.70; N, 11.94%.
4.5.20. Dimethyl 3-(dimethylamino)-7-(4-nitrophenyl)-1-phenyl-5H-pyrrolo[1,2-
c]imidazole-5,6-dicarboxylate (5t)
Orange crystals, mp 138 °C, yield: 0.372 g, 76%. IR (KBr) (νmax/cm–1): 1748 and
1703 (C=O), 1585, 1548, 1522, 1486, 1448, 1425, 1346, 1310, 1220, 1188, 1173,
1110, 1072, 1020, 952, 919, 850, 774, 711, 646. EI-MS, m/z (%): 490 (M+, 13), 417
(100), 389 (15), 371 (6), 343 (18), 330 (4), 298 (8), 255 (13), 228 (11), 200 (4), 189
(4), 152 (4), 127 (2), 105 (4), 77 (5), 43 (4). 1H NMR (300.1 MHz, CDCl3): δ 1.11 (t,
J = 7.1 Hz, 3H, OCH2CH3), 1.30 (t, J = 7.1 Hz, 3H, OCH2CH3), 3.09 (s, 6H, NMe2),
2
3
2
4.07 and 4.11 (2dq, J = 10.8, J = 7.1 Hz, 2H, OCH2CH3), 4.27 and 4.32 (2dq, J =
3
10.8, J = 7.1 Hz, 2H, OCH2CH3), 5.63 (s, 1H, NCH), 6.95–7.13 (m, 5H, 5CH), 7.48
(d, J = 8.7 Hz, 2H, 2CH), 8.15 (d, J = 8.7 Hz, 2H, 2CH). 13C NMR (75.5 MHz,
21

ACCEPTED MANUSCRIPT
CDCl3): δ 13.9 and 14.0 (2OCH2CH3), 39.0 (2NCH3), 60.5 and 62.4 (2OCH2CH3),
63.7 (CH), 123.0 (2CH), 123.1 (C), 127.58 (CH), 127.64 (2CH), 127.9 (2CH), 130.1
(2CH), 132.2, 132.6, 137.0, 139.1, 143.3 and 147.8 (6C), 151.1 (CN3), 162.3 and
167.1 (2C=O). Anal. Calcd for C26H26N4O6 (490.51): C, 63.66; H, 5.34; N, 11.42.
Found: C, 63.51; H, 5.15; N, 11.13%.
4.5.21. Dimethyl 1,7-bis(4-chlorophenyl)-3-(dimethylamino)-5H-pyrrolo[1,2-
c]imidazole-5,6-dicarboxylate (5u)
Orange crystals, mp 163 °C, yield: 0.461 g, 95%. IR (KBr) (νmax/cm–1): 1743 and
1706 (C=O), 1578, 1536, 1483, 1426, 1353, 1279, 1234, 1204, 1149, 1119, 1092,
1063, 1004, 963, 876, 832, 775, 743, 683. EI-MS, m/z (%): 489 (M+ 37Cl2, 1.5), 487
(M+ 37Cl35Cl, 9), 485 (M+ 35Cl2, 14), 430 (11), 428 (67), 426 (100), 391 (3), 343 (2),
341 (13), 339 (18), 289 (4), 262 (6), 227 (7), 197 (6), 179 (6), 139 (5), 113 (4), 84 (7),
59 (15). 1H NMR (300.1 MHz, CDCl3): δ 3.07 (s, 6H, NMe2), 3.63 and 3.80 (2s, 6H,
2OCH3), 5.62 (s, 1H, NCH), 7.00 (s, 4H, 4CH), 7.23 (d, J = 8.3 Hz, 2H, 2CH), 7.31
13
(d, J = 8.6 Hz, 2H, 2CH). C NMR (75.5 MHz, CDCl3): δ 39.1 (2NCH3), 51.5 and
53.4 (2OCH3), 63.6 (CH), 122.5 (C), 127.8 (2CH), 128.4 (2CH), 129.3 (2CH), 129.9
(C), 130.3 (2CH), 131.0, 132.6, 133.1, 134.8, 135.1 and 144.4 (6C), 150.6 (CN3),
162.8 and 167.7 (2C=O). Anal. Calcd for C24H21Cl2N3O4 (486.35): C, 59.27; H, 4.35;
N, 8.64. Found: C, 59.06; H, 4.16; N, 8.59%.
4.5.22. Diethyl 1,7-bis(4-chlorophenyl)-3-(dimethylamino)-5H-pyrrolo[1,2-
c]imidazole-5,6-dicarboxylate (5v)
Orange crystals, mp 155 °C, yield: 0.472 g, 92%. IR (KBr) (νmax/cm–1): 1745 and
1708 (C=O), 1612, 1588, 1539, 1482, 1428, 1396, 1353, 1306, 1211, 1189, 1159,
1090, 1066, 1019, 973, 902, 879, 837, 768, 747, 723, 678, 641. EI-MS, m/z (%): 517
(M+ 37Cl2, 1), 515 (M+ 37Cl35Cl, 9), 513 (M+ 35Cl2, 13), 444 (11), 442 (66), 440 (100),
416 (2), 414 (13), 412 (21), 261 (8), 227 (9), 200 (5), 139 (7), 113 (5), 69 (5), 57 (5),
43 (7). 1H NMR (300.1 MHz, CDCl3): δ 1.11 (t, J = 7.1 Hz, 3H, OCH2CH3), 1.28 (t, J
= 7.1 Hz, 3H, OCH2CH3), 3.05 (s, 6H, NMe2), 4.07 and 4.11 (2dq, 2J = 10.8, 3J = 7.1
Hz, 2H, OCH2CH3), 4.26 and 4.29 (2dq, 2J = 10.8, 3J = 7.1 Hz, 2H, OCH2CH3), 5.58
(s, 1H, NCH), 7.00 (s, 4H, 4CH), 7.24 (d, J = 8.6 Hz, 2H, 2CH), 7.31 (d, J = 8.6 Hz,
2H, 2CH). 13C NMR (75.5 MHz, CDCl3): δ 13.9 and 14.0 (2OCH2CH3), 39.0
(2NCH3), 60.4 and 62.3 (2OCH2CH3), 63.7 (CH), 123.1 (C), 127.7 (2CH), 128.3
(2CH), 129.1 (2CH), 130.3 (2CH), 130.4, 131.5, 132.88, 132.94, 134.9, 135.0 and
22

ACCEPTED MANUSCRIPT
144.3 (7C), 150.8 (CN3), 162.4 and 167.2 (2C=O). Anal. Calcd for C26H25Cl2N3O4
(514.40): C, 60.71; H, 4.90; N, 8.17. Found: C, 60.33; H, 4.58; N, 7.87%.
4.5.23. Dimethyl 7-(4-bromophenyl)-3-(dimethylamino)-1-(4-methylphenyl)-5H-
pyrrolo[1,2-c]imidazole-5,6-dicarboxylate (5w)
Orange crystals, mp 138–139 °C, yield: 0.473 g, 93%. IR (KBr) (νmax/cm–1): 1741 and
1704 (C=O), 1567, 1539, 1499, 1427, 1356, 1331, 1307, 1278, 1242, 1199, 1147,
1115, 1066, 1004, 960, 876, 824, 782, 716, 683, 642. EI-MS, m/z (%): 511 (M+ 81Br,
15), 509 (M+ 79Br, 16), 452 (98), 450 (100), 371 (9), 286 (7), 269 (7), 243 (24), 237
1
(45), 222 (13), 215 (6), 194 (6), 162 (6), 105 (15), 77 (15), 59 (34), 42 (7). H NMR
(300.1 MHz, CDCl3): δ 2.26 (s, 3H, CH3), 3.20 (s, 6H, NMe2), 3.66 and 3.84 (2s, 6H,
2OCH3), 5.72 (s, 1H, NCH), 6.87 (d, J = 8.1 Hz, 2H, 2CH), 7.01 (d, J = 8.1 Hz, 2H,
2CH), 7.15 (d, J = 8.5 Hz, 2H, 2CH), 7.44 (d, J = 8.4 Hz, 2H, 2CH). 13C NMR (75.5
MHz, CDCl3): δ 21.3 (CH3), 39.7 (2NCH3), 51.3 and 53.2 (2OCH3), 63.4 (CH), 122.3
and 123.0 (2C), 127.8 (2CH), 128.3 (2CH), 130.1 (C), 130.6 (2CH), 131.11 (2CH),
131.13, 132.4, 136.9, 137.0 and 144.8 (5C), 150.8 (CN3), 163.1 and 167.9 (2C=O).
Anal. Calcd for C25H24BrN3O4 (510.38): C, 58.83; H, 4.74; N, 8.23. Found: C, 58.57;
H, 4.48; N, 8.05%.
4.5.24. Dimethyl 7-(4-bromophenyl)-3-(dimethylamino)-1-(4-methylphenyl)-5H-
pyrrolo[1,2-c]imidazole-5,6-dicarboxylate (5x)
Orange crystals, mp 148–149 °C, yield: 0.483 g, 90%. IR (KBr) (νmax/cm–1): 1742 and
1697 (C=O), 1597, 1583, 1569, 1539, 1501, 1419, 1360, 1324, 1295, 1212, 1190,
1103, 1067, 1016, 966, 906, 879, 820, 753, 719, 683, 632. EI-MS, m/z (%): 539 (M+
81Br, 16), 537 (M+ 79Br, 16), 466 (97), 464 (100), 436 (20), 434 (21), 385 (7), 269 (7),
1
242 (23), 227 (8), 215 (7), 169 (5), 119 (5), 91 (5), 69 (4), 42 (10). H NMR (300.1
MHz, CDCl3): δ 1.12 (t, J = 7.1 Hz, 3H, OCH2CH3), 1.28 (t, J = 7.1 Hz, 3H,
OCH2CH3), 2.25 (s, 3H, CH3), 3.06 (s, 6H, NMe2), 4.07 and 4.11 (2dq, 2J = 10.8, 3J =
2
3
7.1 Hz, 2H, OCH2CH3), 4.26 and 4.29 (2dq, J = 10.8, J = 7.1 Hz, 2H, OCH2CH3),
5.57 (s, 1H, NCH), 6.85 (d, J = 8.1 Hz, 2H, 2CH), 6.97 (d, J = 7.9 Hz, 2H, 2CH), 7.19
(d, J = 8.3 Hz, 2H, 2CH), 7.45 (d, J = 8.4 Hz, 2H, 2CH). 13C NMR (75.5 MHz,
CDCl3): δ 13.9 and 14.0 (2OCH2CH3), 21.1 (CH3), 39.1 (2NCH3), 60.3 and 62.2
(2OCH2CH3), 63.6 (CH), 122.2 and 122.9 (2C), 127.8 (2CH), 128.3 (2CH), 130.0
(C), 130.6 (2CH), 131.10 (2CH), 131.12, 132.4, 136.7, 137.0 and 144.8 (5C), 150.8
(CN3), 162.6 and 167.4 (2C=O). Anal. Calcd for C27H28BrN3O4 (538.43): C, 60.23; H,
5.24; N, 7.80. Found: C, 59.87; H, 5.11; N, 7.66%.
23

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Acknowledgement
This research was supported by the Research Council of the University of Tehran.
References and notes:
1. Berlinck, R. G. S.; Trindade-Silva, A. E.; Santos, M. F. C. Nat. Prod. Rep. 2012,
29, 1382−1406; Malamas, M. S.; Erdei, J.; Gunawan, I.; Turner, J.; Hu, Y.;
Wagner, E.; Fan, K.; Chopra, R.; Olland, A.; Bard, J.; Jacobsen, S.; Magolda, R.
L.; Pangalos, M.; Robichaud, A. J. J. Med. Chem. 2010, 53, 1146−1158; Richards,
J. J.; Ballard, T. E.; Huigens, R. W.; Melander, C. ChemBioChem. 2008, 9,
1267−1279; Zhang, H.; Khalil, Z.; Conte, M. M.; Plisson, F.; Capon, R. J.
Tetrahedron Lett. 2012, 53, 3784−3787; Crews, P.; Clark, D. P.; Tenney, K. J.
Nat. Prod. 2003, 66, 177−182; Li, W. T.; Hwang, D. R.; Song, J. S.; Chen, C. P.;
Chuu, J. J.; Hu, C. B.; Lin, H. L.; Huang, C. L.; Huang, C. Y.; Tseng, H. Y.; Lin,
C. C.; Chen, T. W.; Lin, C. H.; Wang, H. S.; Shen, C. C.; Chang, C. M.; Chao, Y.
S.; Chen, C. T. J. Med. Chem. 2010, 53, 2409−2417; Taniguchi, K.; Shigenaga,
S.; Ogahara, T.; Fujitsu T.; Matssuo, M. Chem. Pharm. Bull. 1993, 41, 301−309;
Olofson, A.; Yakushijin K.; Horne, D. A. J. Org. Chem. 1998, 63, 1248−1253.
2. Guo, X.; Chen, W.; Chen, B.; Huang, W.; Qi, W.; Zhang, G.; Yu, Y. Org. Lett.
2015, 17, 1157−1159; Giles, R. L.; Sullivan, J. D.; Steiner, A. M.; Looper, R. E.
Angew. Chem., Int. Ed. 2009, 48, 3116−3120; Gibbons, J. B.; Gligorich, K. M.;
Welm, B. E.; Looper, R. E. Org. Lett. 2012, 14, 4734−4737; Ermolat’ev, D. S.;
Bariwal, J. B.; Steenackers, H. P. L.; De Keersmaecker, S. C. J.; Van der Eycken,
E. V. Angew. Chem., Int. Ed. 2010, 49, 9465−9468; Zavesky, B. P.; Babij, N. R.;
Wolfe, J. P. Org. Lett. 2014, 16, 4952−4955; Ermolat’ev, D. S.; van der Eycken,
E. V. J. Org. Chem. 2008, 73, 6691−6697; Ermolat’ev, D. S.; Svidritsky, E. P.;
Babaev, E. V.; van der Eycken, E. V. Tetrahedron Lett. 2009, 50, 5218−5220;
Sämann, C.; Coya, E.; Knochel, P. Angew. Chem., Int. Ed. 2014, 53, 1430−1434;
Shibahara, F.; Yamauchi, T.; Yamaguchi, E.; Murai, T. J. Org. Chem. 2012, 77,
8815−8820; Bellina, F.; Rossi, R. Adv. Synth. Catal. 2010, 352, 1223−1276; Gore,
V. K.; Ma, V. V.; Norman, M. H.; Ognyanov, V. I.; Xi, N. US Pat. 2006/0084640
A1, 2006.
24

ACCEPTED MANUSCRIPT
3. Suffert, J. In Comprehensive Heterocyclic Chemistry III; Vol. 11; Katritzky, A.
R.; Ramsden, C. A.; Scriven, E. F. V.; Taylor, R. J. K., Eds.; Elsevier Science:
Oxford, 2008, Chapt. 2, pp 43–97.
4. Shaw, K. J. US Pat. 4,937,258, 1990; Marco, I.; Valhondo, M.; Martín-Fontecha,
M.; Vázquez-Villa, H.; Del Río, J.; Planas, A.; Sagredo, O.; Ramos, J. A.;
Torrecillas, I. R.; Pardo, L.; Frechilla, D.; Benhamú, B.; Loṕez-Rodríguez, M. L.
J. Med. Chem. 2011, 54, 7986−7999; Valhondo, M.; Marco, I.; Martín-Fontecha,
M.; Vázquez-Villa, H.; Ramos, J. A.; Berkels, R.; Lauterbach, T.; Benhamú, B.;
López-Rodríguez, M. L. J. Med. Chem. 2013, 56, 7851−7861; Sun, C.; Robl, J.
A.; Wang, T. C.; Huang, Y.; Kuhns, J. E.; Lupisella, J. A.; Beehler, B. C.; Golla,
R.; Sleph, P. G.; Seethala, R.; Fura, A.; Krystek, S. R.; An, Y.; Malley, M. F.;
Sack, J. S.; Salvati, M. E.; Grover, G. J.; Ostrowski, J.; Hamann, L. G. J. Med.
Chem. 2006, 49, 7596−7599; Fontanella, L.; Corsico, N.; Diena, A.; Occelli, E.
Farmaco. Ed. Sci. 1984, 39, 133−153; Nakajima, M.; Itoi, K.; Takamatsu, Y.;
Kinoshita, T.; Okazaki, T.; Kawakubo, K.; Shindo, M.; Honma, T.; Tohjigamori,
M.; Haneishi, T. J. Antibiotics 1991, 44, 293−300.
5. (a) Chiba, S.; Wang, Y. F.; Lapointe, G.; Narasaka, K. Org. Lett. 2008, 10,
313−316; (b) Wang, Y. F.; Toh, K. K.; Chiba, S.; Narasaka, K. Org. Lett. 2008,
10, 5019−5022; (c) Ng, E. P. J.; Wang, Y. F.; Hui, B. W. Q.; Lapointe, G.; Chiba,
S. Tetrahedron 2011, 67, 7728−7737; (d) Suresh, R.; Muthusubramanian, S.;
Nagaraj, M.; Manickam, G. Tetrahedron Lett. 2013, 54, 1779−1784; (e) Yu, W.;
Chen, W.; Liu, S.; Shao, J.; Shao, Z.; Lin, H.; Yu, Y. Tetrahedron 2013, 69,
1953−1957; (f) Dong, H.; Shen, M.; Redford, J. E.; Stokes, B. J.; Pumphrey, A.
L.; Driver, T. G. Org. Lett. 2007, 9, 5191−5194; (g) Chen, W.; Shao, J.; Li, Z.;
Giulianotti, M. A.; Yu, Y. Can. J. Chem. 2012, 90, 214−221; (h) Ng, E. P. J.;
Wang, Y. F.; Chiba, S. Synlett 2011, 783−786.
6. (a) Hong, D.; Chen, Z.; Lin, X.; Wang, Y. Org. Lett. 2010, 12, 4608−4611; (b)
Zhang, Y.; Liu, S.; Yu, W.; Hu, M.; Zhang, G.; Yu, Y. Tetrahedron 2013, 69,
2070−2074; (c) Shao, Z.; Pan, Q.; Chen, J.; Yu, Y.; Zhang, G. Tetrahedron 2012,
68, 6565−6568; (d) Stokes, B. J.; Dong, H.; Leislie, B. E.; Pumphrey, A. L.;
Driver, T. G. J. Am. Chem. Soc. 2007, 129, 7500−7501; (e) Bonnamour, J.; Bolm,
C. Org. Lett. 2011, 13, 2012−2014.
25

ACCEPTED MANUSCRIPT
7. (a) Li, Y.; Hong, D.; Lu, P.; Wang, Y. Tetrahedron Lett. 2011, 52, 4161−4163; (b)
Zhang, G.; Ni, H.; Chen, W.; Shao, J.; Liu, H.; Chen, B.; Yu, Y. Org. Lett. 2013,
15, 5967−5969; (c) Huang, W.; Liu, S.; Chen, B.; Guo, X.; Yu, Y. RSC Adv. 2015,
5, 32740−32743.
8. (a) Rajaguru, K.; Suresh, R.; Mariappan, A.; Muthusubramanian, S.; Bhuvanesh,
N. Org. Lett. 2014, 16, 744−747; (b) Liu, S.; Shao, J.; Guo, X.; Luo, J.; Zhao, M.;
Zhang, G.; Yu, Y. Tetrahedron 2014, 70, 1418−1421; (c) Hu, B.; Wang, Z.; Ai,
N.; Zheng, J.; Liu, X. H.; Shan, S.; Wang, Z. Org. Lett. 2011, 13, 6362−6365; (d)
Adiyala, P. R.; Borra, S.; Kamal, A.; Maurya, R. A. Eur. J. Org. Chem. 2016,
1269−1273; (e) Xiang, L.; Niu, Y.; Pang, X.; Yang, X.; Yan, R. Chem. Commun.
2015, 51, 6598−6600; (f) Tiwari, D. K.; Maurya, R. A.; Nanubolu, J. B. Chem.
Eur. J. 2016, 22, 526−530; (g) Shao, J.; Liu, X.; Shu, K.; Tang, P.; Luo, J.; Chen,
W.; Yu, Y. Org. Lett. 2015, 17, 4502−4505; (h) Luo, J.; Chen, W.; Shao, J.; Liu,
X.; Shu, K.; Tang, P.; Yu, Y. RSC Adv. 2015, 5, 55808−55811.
9. (a) Xie, H.; Yuan, D.; Ding, M. W. J. Org. Chem. 2012, 77, 2954−2958; (b)
Rajaguru, K.; Mariappan, A.; Suresh, R.; Manivannan, P.; Muthusubramanian, S.
Beilstein J. Org. Chem. 2015, 11, 2021−2028; (c) Suresh, R.; Muthusubramanian,
S.; Boominathan, M.; Manickam, G. Tetrahedron Lett. 2013, 54, 2315−2320; (d)
Hu, M.; He, X.; Niu, Z.; Yan, Z.; Zhou, F.; Shang, Y. Synthesis 2014, 46,
510−514.
10. (a) Xie, H.; Liu, J. C.; Wu, L.; Ding, M. W. Tetrahedron 2012, 68, 7984−7990;
(b) Chen, B.; Ni, H.; Guo, X.; Zhang, G.; Yu, Y. RSC Adv. 2014, 4, 44462−44465;
(c) Zhang, G.; Chen, B.; Guo, X.; Guo, S.; Yu, Y. Adv. Synth. Catal. 2015, 357,
1065−1069.
11. (a) Hong, D.; Zhu, Y.; Lin, X.; Wang, Y. Tetrahedron 2011, 67, 650−654; (b) Xu,
M.; Kuang, C.; Wang, Z.; Yang, Q.; Jianga, Y. Synthesis 2011, 2, 223−228.
12. (a) Wang, Y. F.; Chiba, S. J. Am. Chem. Soc. 2009, 131, 12570−12572; (b) Shao,
J.; Yu, W.; Shao, Z.; Yu, Y. Chem. Commun. 2012, 48, 2785−2787; (c) Hu, M.;
Wu, J.; Zhang, Y.; Qiu, F.; Yu, Y. Tetrahedron 2011, 67, 2676−2680; (d) Shao,
Z.; Pan, Q.; Chen, J.; Yu, Y.; Zhang, G. Tetrahedron 2012, 68, 6565−6568; (e)
Chen, Z. B.; Hong, D.; Wang, Y. G. J. Org. Chem. 2008, 74, 903−905; (f) Wang,
Y. F.; Toh, K. K.; Ng, E. P. J.; Chiba, S. J. Am. Chem. Soc. 2011, 133,
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ACCEPTED MANUSCRIPT
6411−6421; (g) Zhu, X.; Wang, Y. F.; Zhang, F. L.; Chiba, S. Chem. Asian J.
2014, 9, 2458−2462; (h) Wang, Y. F.; Toh, K. K.; Lee, J. Y.; Chiba, S. Angew.
Chem., Int. Ed. 2011, 50, 5927−5931; (i) Shu, K.; Shao, J.; Li, H.; Chen, B.; Tang,
P.; Liu, X.; Chen, W.; Yu, Y. RSC Adv. 2016, 6, 49123−49126.
13. Yang, Y. Y.; Shou, W. G.; Chen, Z. B.; Hong, D.; Wang, Y. G. J. Org. Chem.
2008, 73, 3928−3930.
14. Chen, W.; Hu, M.; Wu, J.; Zou, H.; Yu, Y. Org. Lett. 2010, 12, 3863−3865.
15. Adiyala, P. R.; Mani, G. S.; Nanubolu, J. B.; Shekar, K. C.; Maurya, R. A. Org.
Lett. 2015, 17, 4308−4311.
16. Guchhait, S. K.; Hura, N.; Shah, A. P. J. Org. Chem. 2017, in press DOI:
10.1021/acs.joc.6b03021.
17. (a) Yavari, I.; Adib, M. Tetrahedron 2001, 57, 5873−5878; (b) Yavari, I.; Adib,
M.; Sayahi, M. H. J. Chem. Soc., Perkin Trans. 1 2002, 13, 1517−1519; (c)
Hazeri, N.; Marandi, G.; Maghsoodlou, M. T.; Khorassani, S. M. H. Lett. Org.
Chem. 2011, 8, 12−15.
18. Adib, M.; Ayashi, N.; Heidari, F.; Mirzaei, P. Synlett 2016, 27, 1738−1742; Adib,
M.; Sheikhi, E.; Yazzaf, R.; Bijanzadeh, H. R.; Mirzaei P. Tetrahedron Lett. 2016,
57, 841−844; Adib, M.; Yasaei, Z.; Mirzaei P. Synlett 2016, 27, 383−386; Adib,
M.; Zainali, M.; Kim, I. Synlett 2016, 27, 1844−1847; Adib, M.; Soheilizad, M.;
Rajai-Daryasaraei, S.; Mirzaei, P. Synlett 2015, 26, 1101–1105; Adib, M.;
Soheilizad, M.; Zhu, L. G.; Wu, J. Synlett 2015, 26, 177−182; Adib, M.; Peytam,
F.; Zainali, M.; Zhu, L. G.; Wu, J. Tetrahedron Lett. 2015, 56, 4729−4732.
19. α-Azidochalcones 1 were prepared from the corresponding benzylidene
acetophenones in two steps according to: Nair, V.; George, T. G. Tetrahedron
Lett. 2000, 41, 3199−3201; Gilchrist, T. L.; Mendonca, R. ARKIVOC 2000 (v),
769−778.
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