Construction of Binuclear Benzimidazole-Fused Quinazolinones and Pyrimidinones Using Aryl Isocyanates as Building Blocks by Transition-Metal-Free C(sp2)-N Coupling

Article abstract of DOI:10.1021/acs.joc.0c02067

A class of binuclear N-fused hybrid scaffolds was constructed by the reaction of 2-(2-bromoaryl)- and 2-(2-bromovinyl)benzimidazoles with aryl isocyanates as building blocks in the presence of a base under microwave irradiation. A nucleophilic addition followed by an unprecedented transition-metal-free C(sp2)-N coupling is proposed as a reaction pathway of this green process.

Full text of DOI:10.1021/acs.joc.0c02067

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Note
Construction of Binuclear Benzimidazole-Fused Quinazolinones and
Pyrimidinones Using Aryl Isocyanates as Building Blocks by
Transition-Metal-Free C(sp2)−N Coupling
Pham Duy Quang Dao and Chan Sik Cho*
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ABSTRACT: A class of binuclear N-fused hybrid scaffolds was
constructed by the reaction of 2-(2-bromoaryl)- and 2-(2-
bromovinyl)benzimidazoles with aryl isocyanates as building
blocks in the presence of a base under microwave irradiation. A
nucleophilic addition followed by an unprecedented transition-
metal-free C(sp2)−N coupling is proposed as a reaction pathway
of this green process.
any synthetic methods of polynuclear N-fused hybrid
scaffolds have been achieved due to their intrinsic
2(1H)-ones via an amidinyl radical (Scheme 2d).7 Ma et al.
recently have shown that scaffolds A can be accessed by
subsequent treatment of I2/TBHP and o-benzenediamines
starting from indoles (Scheme 2e).8 Despite advancing
synthetic methods for scaffold A, these precedents still have
some drawbacks such as multistep process, limitation of scope,
and expensive reagents or catalysts. In connection with this
report, it is known that a C(sp2)−N bond forming reaction is
of great importance in developing new, mild, and cheap
synthetic methodologies.1 Thus, many traditional transition-
metal-catalyzed versions as well as recent transition-metal-free
versions have been developed for such a C(sp2)−N
coupling.10,11 As part of our ongoing studies on copper-
catalyzed and transition-metal-free synthesis of polynuclear N-
fused hybrid scaffolds via a C(sp2)−N coupling, we recently
reported that 2-(2-bromoaryl)- and 2-(2-bromovinyl)-
benzimidazoles reacted with 2-aminoazoles in the presence
of a base to form trinuclear N-fused hybrid scaffolds via a
transition-metal-free double C(sp2)−N coupling involving
nucleophilic aromatic substitution (SNAr).12−14 The present
work started during the course of the extension of such a
transition-metal-free C(sp2)−N coupling to synthesize poly-
nuclear N-fused hybrid scaffolds. This work shows the
construction of benzimidazole-fused quinazolinones, 5-
arylbenzo[4,5]imidazo[1,2-c]quinazolin-6(5H)-ones (Scheme
1, A) from 2-(2-bromoaryl)benzimidazoles and aryl isocya-
M
biological activities and optical properties that are not shown in
each homonuclear scaffold.1 In contrast to well-known
synthetic methods and biological activities of each homo-
nuclear scaffold (benzimidazole and quinazolinone) of scaffold
A,2,3 several synthetic examples are only found for N-fused
hybrid scaffold A (Schemes 1 and 2).4−8 Even though the
Scheme 1. Binuclear N-Fused Hybrid Scaffolds Containing
Benzimidazole
biological activities of scaffold A were not explored yet, scaffold
C, analogue of scaffold A, has been tested for their biological
activities (Scheme 1).9 Sharma et al. reported that 2-(2-
aminophenyl)benzimidazole reacts with ethyl chloroformate in
pyridine to give binuclear N-fused hybrid scaffold A via double
nucleophilic acyl substitution (Scheme 2a).4 Molina and
coworkers also demonstrated that iminophosphoranes derived
from 2-(2-azidophenyl)benzimidazole and triphenylphosphine
with carbon dioxide trigger aza-Wittig reaction to produce
scaffold A (Scheme 2b).5 It is reported that 2-(2-nitrophenyl)-
benzimidazoles are found to be reductively cyclized with aryl
isocyanates in the presence of TiCl4/Zn to give scaffold A
irrespective of aryl isocyanates (Scheme 2c).6 Such a scaffold A
also can be constructed by the electrochemical C−H/N−H
cross-coupling of 4-imino-3-phenyl-3,4-dihydroquinazolin-
Received: August 27, 2020
https://dx.doi.org/10.1021/acs.joc.0c02067
© XXXX American Chemical Society
J. Org. Chem. XXXX, XXX, XXX−XXX
A

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Note
Scheme 2. Synthetic Routes for Scaffold A
Table 1. Optimization of Conditions for the Reaction of 1a
with 2a
a
[2a]/
entry [1a]
temp
(°C)
time
(h)
conv. of
1a (%)
yield
(%)
base
solvent
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
1.0
1.5
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K2CO3
KOtBu
Cs2CO3
KOH
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMSO
xylene
DMF
130
130
130
130
150
110
130
130
130
130
130
130
130
130
130
1
1
1
2
1
1
1
1
1
1
1
1
1
1
24
68
81
100
100
100
86
100
71
100
31
37
53
71
69
70
49
70
42
70
12
0
b
29
0
41
66
CsF
0
K3PO4
K3PO4
K3PO4
trace
27
42
c
84
a
Reaction conditions: 1a (0.3 mmol), base (0.6 mmol), DMF (3
mL), under microwave irradiation (100 W of initial power).
b
c
K3PO4(0.9 mmol). Usual heating (screw-capped vial, 130 °C, 24 h).
KOH and CsF were not effective at all for the formation of 3a
(Table 1, entries 11 and 12). Among solvents examined under
the employed conditions, DMF was shown to be the solvent of
choice in terms of the yield of 3a and complete conversion of
1a (Table 1, entries 3, 13, and 14). On the other hand,
performing the reaction under usual heating conditions
produced 3a in only 42% yield with incomplete conversion
of 1a (Table 1, entry 15). The best result in terms of both
product yield and complete conversion of 1a was obtained
using the reaction conditions shown in entry 3 of Table 1. Not
shown in Table 1, similar treatment of triflate analogue of 1a,
2-(1H-benzo[d]imidazol-2-yl)phenyl trifluoromethanesulfo-
nate with 2a under the conditions of entry 3 of Table 1 also
afforded 3a in 72% yield with complete conversion of 1a.
After obtaining the optimized conditions, the reaction scope
was investigated by subjecting many 2-(2-bromoaryl)- and 2-
(2-bromovinyl)benzimidazoles 1 with aryl isocyanates 2, and
the representative results are shown in Table 2.16 2-(2-
Bromophenyl)benzimidazole 1a was successfully coupled and
cyclized with various aryl isocyanates 2a−h which have
electron-donating and -withdrawing substituents to yield the
corresponding benzimidazole-fused quinazolinones 3a−h in
moderate to good yields. With 2b and 2c, higher molar ratio of
2 to 1a and prolonging reaction time were needed for the
allowable formation of such scaffolds (3b and 3c). Scaffolds 3b
and 3c were formed in 21 and 34% yields, respectively, under
[2]/[1a] = 2.0. 2-(2-Bromophenyl)benzimidazole 1a also
reacted with 1-naphthyl isocyanate (2i) to give the
corresponding N-fused hybrid scaffold 3i in similar yield.
From the reaction of several 2-(2-bromoaryl)benzimidazoles
1b−f having electron-donating and -withdrawing substituents
on the bromoaryl or benzimidazole moiety with 2a, the
nates as building blocks via such a transition-metal-free
C(sp2)−N coupling as a key step (Scheme 2). To the best
of our knowledge, this is the first example for transition-metal-
free coupling of C(sp2) and N of a urea.15 This protocol can
also be extended to the reaction of 2-(2-bromovinyl)-
benzimidazoles with aryl isocyanates to form binuclear N-
fused hybrid scaffolds B (Scheme 1).
Treatment of 2-(2-bromophenyl)-1H-benzo[d]imidazole
(1a) with equimolar amount of phenyl isocyanate (2a) in
DMF in the presence of K3PO4 (2 equiv) at 130 °C for 1 h
under microwave irradiation (100 W of initial power) afforded
binuclear N-fused hybrid scaffold, 5-phenylbenzo[4,5]imidazo-
[1,2-c]quinazolin-6(5H)-one (3a) in 37% isolated yield with
68% conversion of 1a (Table 1, entry 1). The yield of 3a
increased with the increase in the molar ratio of 2a to 1a up to
2 equiv with complete conversion of 1a (Table 1, entries 2 and
3). No significant change of the yield of 3a was observed with
prolonging the reaction time or higher reaction temperature
(Table 1, entries 4 and 5). However, lower reaction
temperature resulted in lower yield of 3a with incomplete
conversion of 1a (Table 1, entry 6). Performing the reaction
under the increased amount of K3PO4 (3 equiv to 1a) also
resulted in no significant change of the yield of 3a (Table 1,
entry 7).13a The reaction also proceeded in the presence of
other bases such as K2CO3, KOtBu, and Cs2CO3 under the
employed conditions, but the yields of 3a were generally lower
than that obtained with K3PO4 except for KOtBu, which
showed a similar activity as K3PO4 with complete conversion
of 1a (Table 1, entries 8−10). However, other bases such as
B
https://dx.doi.org/10.1021/acs.joc.0c02067
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Note
a
Table 2. Scope of Reaction
a
Reaction conditions: 1 (0.3 mmol), 2 (0.6 mmol), K3PO4 (0.6 mmol), DMF (3 mL), under microwave irradiation (100 W of initial power), 130
b
c
°C, 1 h. [2]/[1] = 3, 2 h. [2]/[1] = 3, 150 °C, 2 h.
corresponding binuclear N-fused hybrid scaffolds 3j−n were
also formed in 50−73% yields. Benzo-fused 2-(2-
bromophenyl)benzimidazole 1g was also readily coupled and
cyclized with 2a to give the corresponding scaffold 3o in 66%
yield. Similar treatment of 2-(2-bromovinyl)benzimidazoles
1h−k having alkyl and phenyl substituents on the vinyl moiety
C
https://dx.doi.org/10.1021/acs.joc.0c02067
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Note
with aryl isocyanates 2 under modified reaction conditions
(molar ratio [2]/[1] = 3.0, 150 °C, 2 h) invariably afforded the
corresponding benzimidazole-fused pyrimidinones 3p−t irre-
spective of the identity of such substituents. Scaffolds 3p−t
were formed in 25−36% yields under [2]/[1] = 2.0.
under the employed conditions gave a nucleophilic addition
product 10 in 73% yield (eq 2). Fortunately, we also confirmed
On the other hand, a one-pot step by step gram scale
procedure starting from 2-bromobenzaldehyde (4) and
benzene-1,2-diamine (5) renders the synthesis of 3a practical.
Initial treatment of 4 with equimolar amount of 5 in the
presence of NaHSO3 in H2O at 100 °C followed by removal of
H2O and inorganic components by decantation afforded a
yellow solid.16 Further addition of 2a, K3PO4 and DMF to the
flask containing a yellow solid and stirring at 150 °C for 30 h
gave 3a in 44% yield (eq 1).
that a similar treatment of 1a with 2a for a shorter reaction
time (30 min) under the employed conditions afforded the
nucleophilic addition intermediate 6a and the cyclized product
3a in 28 and 37% yields, respectively, with 81% conversion of
1a (eq 3). The intermediate 6a thus isolated was readily
Based on additional experiments to delineate the mechanism
and literature, the reaction pathway seems to proceed via an
initial formation of a urea 6 by nucleophilic addition of the N−
H of 1a to isocyanate 2 (Scheme 3).17 Subsequent intra-
cyclized under the optimized conditions to give the desired
product 3a in 85% yield (eq 4). This results clearly support the
Scheme 3. Reaction Pathway
formation of intermediate 6 during the course of the reaction.
Furthermore, although not yet elucidated, in contrast to the
reaction with aryl isocyanate, performing the reaction of 1a
with cyclohexyl isocyanate (2j) under the employed conditions
only afforded the nucleophilic addition intermediate 6b in 63%
yield without the formation of the expected cyclized product
3u (eq 3). A reviewer also suggested that product 3 would be
formed by an alternative mechanism through 6π-electro-
cyclization of an intermediate 8 derived from 1a and 2
(Scheme 3).20
Finally, the substrate scope of the present reaction was
expanded with several readily available compounds. Treatment
of 1a with phenyl isothiocyanate (11) under the employed
conditions afforded the corresponding N-fused hybrid scaffold
12 in 44% yield along with several unidentifiable side products
(eq 5). Performing the reaction of 2-(2-bromophenyl)indole
molecular nucleophilic attack of the carbamoyl NH to the
carbon attached to Br in 6 forms a resonance-stabilized
carbanion, Meisenheimer complex 7.18 This is followed by the
loss of the leaving group to complete an addition−elimination
nucleophilic aromatic substitution for the production of 3. The
ortho-substituted benzimidazole ring in 6 lowers the energy of
the transition state that forms such a Meisenheimer complex 7
by further electron delocalization.18,19 The following additional
experimental observations are worth noting as evidence for the
formation of such a nucleophilic addition intermediate 6.
Treatment of 2-phenyl-1H-benzo[d]imidazole (9) with 2a
13 with 2a under the employed conditions afforded the
coupling and cyclized product 14 in only 24% yield with 46%
conversion of 13 (eq 6). However, similar reaction of 2-(2-
bromophenyl)imidazole 15 with 2a resulted in the formation
of nucleophilic addition product 16 in 50% yield with 68%
conversion of 15 (eq 7).
In summary, we developed a transition-metal-free con-
struction of binuclear N-fused hybrid scaffolds by the
treatment of 2-(2-bromoaryl)- and 2-(2-bromovinyl)-
benzimidazoles with aryl isocyanates as building blocks in
D
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Note
124.4, 124.1, 119.5, 115.8, 115.5, 113.1, 17.4. HRMS (EI) m/z: [M]+
Calcd for C21H15N3O 325.1215; Found 325.1217.
5-(m-Tolyl)benzo[4,5]imidazo[1,2-c]quinazolin-6(5H)-one (3c).
3c was purified by TLC (dichloromethane/MeOH = 200/1, 2
1
times) as a pale yellow solid (0.061 g, 62%); mp 218−221 °C. H
NMR (500 MHz, CDCl3) δ 8.59 (dd, J = 7.8 and 1.5 Hz, 1H), 8.44
(d, J = 8.0 Hz, 1H), 7.94 (d, J = 8.1 Hz, 1H), 7.56−7.50 (m, 2H),
7.47−7.36 (m, 4H), 7.25−7.23 (m, 2H), 6.73 (d, J = 8.2 Hz, 1H),
2.48 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3) δ 147.0, 146.9,
144.0, 140.8, 139.3, 136.0, 131.9, 131.3, 130.5, 130.3, 129.7, 126.1,
125.6, 125.4, 124.0, 119.5, 116.5, 115.5, 113.0, 21.4. HRMS (EI) m/z:
[M]+ Calcd for C21H15N3O 325.1215; Found 325.1212.
5-(p-Tolyl)benzo[4,5]imidazo[1,2-c]quinazolin-6(5H)-one (3d).
3d was purified by TLC (dichloromethane/MeOH = 200/1, 2
1
times) as a white solid (0.050 g, 51%); mp 263−266 °C. H NMR
the presence of a base under microwave irradiation. This
process involves an unprecedented example of transition-
metal-free C(sp2)−N coupling as a key step. Further challenges
on the green construction of polynuclear N-fused hybrid
scaffolds using this protocol are under way.
(500 MHz, CDCl3) δ 8.58 (dd, J = 7.8 and 1.4 Hz, 1H), 8.43 (d, J =
8.1 Hz, 1H), 7.93 (d, J = 8.1 Hz, 1H), 7.53−7.49 (m, 1H), 7.46−7.41
(m, 4H), 7.38−7.35 (m, 1H), 7.32 (d, J = 8.2 Hz, 2H), 6.74 (d, J =
8.4 Hz, 1H), 2.50 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3) δ
147.0, 146.9, 143.9, 139.8, 139.4, 131.9, 131.3, 131.1, 128.9, 125.6,
125.3, 124.4, 123.9, 116.4, 115.5, 113.0, 21.4. HRMS (EI) m/z: [M]+
Calcd for C21H15N3O 325.1215; Found 325.1213.
5-(4-Methoxyphenyl)benzo[4,5]imidazo[1,2-c]quinazolin-6(5H)-
one (3e). 3e was purified by TLC (dichloromethane/MeOH = 200/1,
2 times) as a pale yellow solid (0.054 g, 53%); mp 271−273 °C. H
NMR (500 MHz, CDCl3) δ 8.60−8.58 (m, 1H), 8.45−8.43 (m, 1H),
7.95−7.93 (m, 1H), 7.54−7.50 (m, 1H), 7.48−7.43 (m, 2H), 7.40−
7.33 (m, 3H), 7.17−7.14 (m, 2H), 6.77 (d, J = 8.4 Hz, 1H), 3.92 (s,
3H). 13C{1H} NMR (125 MHz, CDCl3) δ 160.3, 147.1, 147.0, 144.0,
139.6, 131.9, 131.3, 130.2, 128.6, 125.6, 125.4, 124.4, 124.0, 119.5,
116.5, 115.7, 115.5, 113.1, 55.7. HRMS (EI) m/z: [M]+ Calcd for
C21H15N3O2 341.1164; Found 341.1166.
EXPERIMENTAL SECTION
■
General Information. 1H (500 MHz) and 13C NMR (125 MHz)
spectra were recorded in CDCl3 or DMSO-d6. High-resolution mass
data were obtained using electronic ionization (HRMS, magnetic
sector-electric sector double focusing mass analyzer) at the Korea
Basic Science Center (Daegu). Melting points were measured on a
microscopic melting point apparatus (Stanford Research Inc.
MPA100 automated melting point apparatus). All reactions were
carried out in a sealed tube under microwave irradiation (CEM,
Discover LabMate), and the reaction temperature was maintained by
an external infrared sensor. The products were isolated by TLC (a
glass plate coated with Kieselgel 60 GF254, Merck). The starting
compounds 1 and 9 were prepared by a known method from the
corresponding aldehydes and o-phenylenediamine.12d,14,16 2-(2-
Bromophenyl)indole 13 and 2-(2-bromophenyl)imidazole 15 were
synthesized by reported methods, respectively.21,22 Other commer-
cially available organic and inorganic reagents were used without
further purification.
1
5-(4-Fluorophenyl)benzo[4,5]imidazo[1,2-c]quinazolin-6(5H)-
one (3f). 3f was purified by TLC (dichloromethane/MeOH = 200/1,
1
2 times) as a pale yellow solid (0.062 g, 62%); mp 266−269 °C. H
NMR (500 MHz, CDCl3) δ 8.60 (d, J = 7.7 Hz, 1H), 8.41 (d, J = 8.0
Hz, 1H), 7.93 (d, J = 8.0 Hz, 1H), 7.54−7.51 (m, 1H), 7.48−7.39 (m,
5H), 7.37−7.34 (m, 2H), 6.71 (d, J = 8.4 Hz, 1H). 13C{1H} NMR
1
4
(125 MHz, CDCl3) δ 163.0 (d, JC−F = 248.9 Hz), 146.9 (d, JC−F
=
1.8 Hz), 144.0, 139.2, 132.0 (132.00), 132.0 (131.99), 131.2 (d, 3JC−F
= 9 Hz), 125.7, 125.5, 124.2, 119.6, 117.6 (d, 2JC−F = 23.2 Hz) 116.2,
115.4, 113.2. HRMS (EI) m/z: [M]+ Calcd for C20H12FN3O
329.0964; Found 329.0965.
General Procedure for the Synthesis of 3, 12, 14, and 16. To
a 10 mL microwave reaction tube, 1 (0.3 mmol), 2 (0.6 mmol for 3a
and 3d−o; 0.9 mmol for 3b, 3c, and 3p−t), K3PO4 (0.128 g, 0.6
mmol), and DMF (3 mL) were added. After stirring the reaction
mixture at room temperature for 5 min, it was heated at 130−150 °C
for 1−2 h under microwave irradiation (100 W of initial power). The
reaction mixture was cooled to room temperature and filtered through
a short silica gel column to eliminate inorganic salts using ethyl
acetate. Removal of the eluent under reduced pressure left a crude
mixture, which was purified by TLC to give 3. All new products were
characterized spectroscopically, as shown below. The reactions for the
synthesis of 12, 14, and 16 were similarly carried out with
experimental procedure for the synthesis of 3.
5-Phenylbenzo[4,5]imidazo[1,2-c]quinazolin-6(5H)-one (3a). 3a
was purified by TLC (dichloromethane/MeOH = 200/1, 2 times) as
a white solid (0.066 g, 71%); mp 263−265 °C. 1H NMR (500 MHz,
CDCl3) δ 8.60 (dd, J = 7.8 and 1.5 Hz, 1H), 8.43 (d, J = 8.0 Hz, 1H),
7.94 (d, J = 8.1 Hz, 1H), 7.69−7.66 (m, 2H), 7.63−7.60 (m, 1H),
7.54−7.50 (m, 1H), 7.46−7.43 (m, 4H), 7.40−7.37 (m, 1H), 6.71 (d,
J = 8.4 Hz, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 147.0, 146.8,
144.0, 139.3, 136.2, 131.9, 131.3, 130.5, 129.7, 129.3, 125.7, 125.4,
124.5, 124.0, 119.5, 116.4, 115.5, 113.1. HRMS (EI) m/z: [M]+ Calcd
for C20H13N3O 311.1059; Found 311.1057.
5-(3-Chlorophenyl)benzo[4,5]imidazo[1,2-c]quinazolin-6(5H)-
one (3g). 3g was purified by TLC (dichloromethane/MeOH = 200/
1) as a white solid (0.057 g, 55%); mp 260−263 °C. H NMR (500
MHz, CDCl3) δ 8.59 (dd, J = 7.8 and 1.1 Hz, 1H), 8.41 (d, J = 8.0
Hz, 1H), 7.93 (d, J = 8.1 Hz, 1H), 7.63−7.61 (m, 2H), 7.54−7.51 (m,
1H), 7.49−7.44 (m, 3H), 7.41−7.36 (m, 2H), 6.70 (d, J = 8.4 Hz,
1H). 13C{1H} NMR (125 MHz, CDCl3) δ 146.8, 146.6, 143.9, 138.8,
137.2, 136.1, 132.0, 131.4, 131.2, 130.1, 129.8, 127.7, 125.8, 125.6,
124.6, 124.3, 119.6, 116.1, 115.4, 113.1. HRMS (EI) m/z: [M]+ Calcd
for C20H12ClN3O 345.0669; Found 345.0668.
5-(4-Chlorophenyl)benzo[4,5]imidazo[1,2-c]quinazolin-6(5H)-
one (3h). 3h was purified by TLC (dichloromethane/MeOH = 200/
1) as a white solid (0.063 g, 61%); mp 243−246 °C. H NMR (500
MHz, CDCl3) δ 8.60−8.58 (m, 1H), 8.40 (d, J = 8.0 Hz, 1H), 7.93
(d, J = 8.0 Hz, 1H), 7.65−7.63 (m, 2H), 7.54−7.51 (m, 1H), 7.46−
7.44 (m, 2H), 7.41−7.38 (m, 3H), 6.71 (d, J = 8.3 Hz, 1H). 13C{1H}
NMR (125 MHz, CDCl3) δ 146.8, 146.6, 143.9, 138.9, 135.8, 134.6,
132.0, 131.2, 130.8, 130.7, 125.8, 125.5, 124.6, 124.3, 119.6, 116.1,
115.4, 113.1. HRMS (EI) m/z: [M]+ Calcd for C20H12ClN3O
345.0669; Found 345.0669.
1
1
5-(o-Tolyl)benzo[4,5]imidazo[1,2-c]quinazolin-6(5H)-one (3b).
3b was purified by TLC (dichloromethane/MeOH = 200/1, 2
5-(Naphthalen-1-yl)benzo[4,5]imidazo[1,2-c]quinazolin-6(5H)-
one (3i). 3i was purified by TLC (dichloromethane/MeOH = 200/1)
as a white solid (0.076 g, 70%); mp 267−269 °C. H NMR (500
MHz, CDCl3) δ 8.66−8.65 (m, 1H), 8.43 (d, J = 8.0 Hz, 1H), 8.12
(d, J = 8.3 Hz, 1H), 8.04 (d, J = 8.3 Hz, 1H), 7.98 (d, J = 8.1 Hz, 1H),
7.74−7.71 (m, 1H), 7.64 (dd, J = 7.2 and 1.1 Hz, 1H), 7.59−7.52 (m,
3H), 7.47−7.43 (m, 2H), 7.40−7.34 (m, 2H), 6.53−6.51 (m, 1H).
1
times) as a white solid (0.050 g, 51%); mp 230−233 °C. H NMR
1
(500 MHz, CDCl3) δ 8.62 (dd, J = 7.8 and 1.4 Hz, 1H), 8.45 (d, J =
8.1 Hz, 1H), 7.95 (d, J = 8.1 Hz, 1H), 7.55−7.44 (m, 6H), 7.41−7.38
(m, 1H), 7.33 (d, J = 7.5 Hz, 1H), 6.62 (d, J = 8.2 Hz, 1H), 2.15 (s,
3H). 13C{1H} NMR (125 MHz, CDCl3) δ 147.1, 146.3, 144.0, 138.6,
137.0, 134.9, 132.2, 132.0, 131.3, 130.0, 129.2, 128.1, 125.7, 125.5,
E
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The Journal of Organic Chemistry
pubs.acs.org/joc
Note
13C{1H} NMR (125 MHz, CDCl3) δ 147.1, 146.8, 144.0, 139.3,
4-Methyl-2,3-diphenylbenzo[4,5]imidazo[1,2-c]pyrimidin-1(2H)-
one (3p). 3p was purified by TLC (dichloromethane/MeOH = 200/
135.0, 132.5, 132.1, 131.4, 130.4, 130.3, 128.9, 127.9, 127.7, 127.1,
126.1, 125.7, 125.5, 124.5, 124.2, 131.9, 119.6, 116.6, 115.6, 113.1.
HRMS (EI) m/z: [M]+ Calcd for C24H15N3O 361.1215; Found
361.1213.
1
1, 2 times) as a white solid (0.063 g, 60%); mp 211−214 °C. H
NMR (500 MHz, CDCl3) δ 8.89−8.87 (m, 1H), 8.04−8.00 (m, 1H),
7.88 (d, J = 8.1 Hz, 1H), 7.74−7.68 (m, 3H), 7.61−7.53 (m, 4H),
7.37−7.32 (m, 2H), 6.96−6.93 (m, 1H), 5.94 (d, J = 8.4 Hz, 1H),
2.41 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3) δ 147.1, 144.2,
142.4, 137.6, 131.8, 130.5, 129.7 (129.72), 129.7 (129.66), 129.4,
125.5, 124.2, 124.0, 121.9, 121.3, 119.7, 119.4, 115.0, 112.9, 12.8.
HRMS (EI) m/z: [M]+ Calcd for C23H17N3O 351.1372; Found
351.1375.
2-Fluoro-5-phenylbenzo[4,5]imidazo[1,2-c]quinazolin-6(5H)-
one (3j). 3j was purified by TLC (dichloromethane/MeOH = 200/1)
1
as a white solid (0.072 g, 73%); mp 331−333 °C. H NMR (500
MHz, CDCl3) δ 8.44 (d, J = 8.1 Hz, 1H), 8.27 (dd, J = 8.2 and 3.0
Hz, 1H), 7.95 (d, J = 8.1 Hz, 1H), 7.69−7.66 (m, 2H), 7.63−7.60 (m,
1H), 7.57−7.52 (m, 1H), 7.49−7.43 (m, 3H), 7.18−7.14 (m, 1H),
6.69 (dd, J = 9.3 and 4.3 Hz, 1H). 13C{1H} NMR (125 MHz, CDCl3)
δ 159.0 (d, 1JC−F = 244.0 Hz), 146.5, 146.0 (d, 4JC−F = 3.4 Hz), 143.9,
136.1, 135.7, 131.3, 130.6, 129.9, 129.2, 125.9, 124.9, 119.7, 119.5 (d,
4-Isopropyl-2,3-diphenylbenzo[4,5]imidazo[1,2-c]pyrimidin-
1(2H)-one (3q). 3q was purified by TLC (dichloromethane/MeOH =
200/1, 2 times) as a white solid (0.077 g, 68%); mp 219−223 °C. 1H
NMR (500 MHz, CDCl3) δ 8.91−8.88 (m, 1H), 8.04−8.00 (m, 1H),
7.86 (d, J = 7.8 Hz, 1H), 7.73−7.67 (m, 3H), 7.59−7.52 (m, 5H),
7.32−7.29 (m, 1H), 6.91−6.88 (m, 1H), 5.71 (d, J = 8.4 Hz, 1H),
3.09 (sept, J = 7.1 Hz, 2H), 1.55 (d, J = 7.1 Hz, 6H). 13C{1H} NMR
(125 MHz, CDCl3) δ 145.3, 144.2, 142.5, 136.5, 132.3, 130.4, 129.7
(129.68), 129.7 (129.66), 129.2, 125.3, 124.1, 123.8, 121.7, 119.7,
119.3, 118.7, 114.9, 112.8, 29.3, 21.1. HRMS (EI) m/z: [M]+ Calcd
for C25H21N3O 379.1685; Found 379.1686.
3
3
2JC−F = 24.1 Hz), 118.3 (d, JC−F = 8.1 Hz), 115.5, 114.3 (d, JC−F
=
8.9 Hz), 111.1 (d, 2JC−F = 25.1 Hz). HRMS (EI) m/z: [M]+ Calcd for
C20H12FN3O 329.0964; Found 329.0963.
2-Methoxy-5-phenylbenzo[4,5]imidazo[1,2-c]quinazolin-6(5H)-
one (3k). 3k was purified by TLC (dichloromethane/MeOH = 200/
1, 2 times) as a pale yellow solid (0.051 g, 50%); mp 337−339 °C. 1H
NMR (500 MHz, DMSO-d6) δ 8.32 (d, J = 7.9 Hz, 1H), 7.92−7.90
(m, 1H), 7.70−7.67 (m, 2H), 7.64−7.61 (m, 1H), 7.58−7.56 (m,
2H), 7.54−7.51 (m, 1H), 7.48−7.45 (m, 1H), 7.19 (dd, J = 9.2 and
3.0 Hz, 1H), 6.52 (d, J = 9.2 Hz, 1H), 3.90 (s, 3H). 13C{1H} NMR
(125 MHz, CDCl3) δ 156.3, 147.0, 146.6, 143.9, 136.3, 133.5, 131.4,
130.5, 129.6, 129.3, 125.7, 124.5, 121.2, 119.4, 118.0, 115.6, 113.7,
106.4, 56.1. HRMS (EI) m/z: [M]+ Calcd for C21H15N3O2 341.1164;
Found 341.1167.
2-(4-Chlorophenyl)-4-isopropyl-3-phenylbenzo[4,5]imidazo[1,2-
c]pyrimidin-1(2H)-one (3r). 3r was purified by TLC (dichloro-
methane/MeOH = 200/1, 2 times) as a pale yellow solid (0.061 g,
1
62%); mp 206−209 °C. H NMR (500 MHz, CDCl3) δ 8.45 (d, J =
8.1 Hz, 1H), 7.92 (d, J = 8.1 Hz, 1H), 7.52−7.48 (m, 1H), 7.41−7.38
(m, 1H), 7.25−7.17 (m, 5H), 7.11−7.08 (m, 4H), 2.80 (sept, J = 7.1
Hz, 2H), 1.48 (d, J = 7.1 Hz, 6H). 13C{1H} NMR (125 MHz, CDCl3)
δ 147.7, 144.5, 142.5, 137.7, 133.4, 130.2, 129.9, 129.8, 128.9, 128.6,
128.3, 128.1, 125.5, 123.5, 119.3, 115.8, 115.5, 29.9, 21.1. HRMS (EI)
m/z: [M]+ Calcd for C25H20ClN3O 413.1295; Found 413.1293.
4-Butyl-2,3-diphenylbenzo[4,5]imidazo[1,2-c]pyrimidin-1(2H)-
one (3s). 3s was purified by TLC (dichloromethane/MeOH = 200/1,
3-Methyl-5-phenylbenzo[4,5]imidazo[1,2-c]quinazolin-6(5H)-
one (3l). 3l was purified by TLC (dichloromethane/MeOH = 200/1,
1
2 times) as a white solid (0.062 g, 63%); mp 310−312 °C. H NMR
(500 MHz, CDCl3) δ 8.47 (d, J = 8.1 Hz, 1H), 8.42 (d, J = 8.1 Hz,
1H), 7.92 (d, J = 8.1 Hz, 1H), 7.70−7.66 (m, 2H), 7.64−7.61 (m,
1H), 7.53−7.49 (m, 1H), 7.45−7.41 (m, 3H), 7.21 (dd, J = 8.1 and
0.7 Hz, 1H), 6.48 (s, 1H), 2.34 (s, 3H). 13C{1H} NMR (125 MHz,
CDCl3) δ 147.2, 147.0, 144.0, 143.0, 139.3, 136.2, 131.3, 130.5, 129.6,
129.3, 125.6, 125.4, 125.3, 124.2, 119.3, 116.5, 115.4, 110.7, 22.1.
HRMS (EI) m/z: [M]+ Calcd for C21H15N3O 325.1215; Found
325.1217.
1
2 times) as a white solid (0.094 g, 73%); mp 227−230 °C. H NMR
(500 MHz, CDCl3) δ 8.89−8.86 (m, 1H), 8.04−8.01 (m, 1H), 7.86
(d, J = 8.0 Hz, 1H), 7.74−7.66 (m, 3H), 7.59−7.54 (m, 5H), 7.33−
7.29 (m, 1H), 6.92−6.89 (m, 1H), 5.84 (d, J = 8.4 Hz, 1H), 2.80−
2.77 (m, 2H), 1.76−1.70 (m, 2H), 1.37−1.30 (m, 2H), 0.81 (t, J =
7.4 Hz, 3H). 13C{1H} NMR (125 MHz, CDCl3) δ 146.6, 144.3,
142.4, 142.2, 137.4, 130.5, 129.9, 129.5, 125.4, 124.1, 123.8, 121.8,
119.7, 119.4, 115.0, 114.3, 112.9, 31.8, 26.9, 22.7, 13.8. HRMS (EI)
m/z: [M]+ Calcd for C26H23N3O 393.1841; Found 393.1842.
2,3,4-Triphenylbenzo[4,5]imidazo[1,2-c]pyrimidin-1(2H)-one
(3t). 3t was purified by TLC (dichloromethane/MeOH = 200/1, 2
9,10-Dimethyl-5-phenylbenzo[4,5]imidazo[1,2-c]quinazolin-
6(5H)-one (3m). 3m was purified by TLC (dichloromethane/MeOH
= 200/1) as a white solid (0.070 g, 69%); mp 277−279 °C. 1H NMR
(500 MHz, DMSO-d6) δ 8.67 (s, 1H), 7.80 (dd, J = 8.0 and 1.1 Hz,
1H), 7.74 (dd, J = 7.7 and 1.7 Hz, 1H), 7.55−7.52 (m, 1H), 7.47−
7.42 (m, 4H), 7.30−7.26 (m, 2H), 6.98−6.95 (m, 1H), 2.34 (s, 3H),
2.32 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3) δ 142.1, 140.8,
140.7, 133.8, 133.0, 132.3, 130.4, 130.3, 129.4, 129.1, 128.9, 128.4,
128.2, 128.1, 127.6, 125.6, 125.1, 121.1, 114.8, 113.4, 21.0, 20.2.
HRMS (EI) m/z: [M]+ Calcd for C22H17N3O 339.1372; Found
339.1374.
1
times) as a white solid (0.082 g, 61%); mp 318−320 °C. H NMR
(500 MHz, CDCl3) δ 8.93−8.91 (m, 1H), 7.99−7.97 (m, 1H), 7.92−
7.90 (m, 1H), 7.61−7.27 (m, 14H), 6.96−6.93 (m, 1H), 5.94−5.96
(m, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 146.6, 144.5, 142.6,
142.4, 138.5, 132.1, 130.4, 130.1, 129.8, 129.0, 128.2, 128.1, 125.4,
124.4, 124.1, 122.0, 120.2, 119.5, 115.5, 114.9, 113.3. HRMS (EI) m/
z: [M]+ Calcd for C28H19N3O 413.1528; Found 413.1530.
9,10-Dichloro-5-phenylbenzo[4,5]imidazo[1,2-c]quinazolin-
6(5H)-one (3n). 3n was purified by TLC (dichloromethane/MeOH =
2-(2-Bromophenyl)-N-cyclohexyl-1H-benzo[d]imidazole-1-car-
1
200/1) as a white solid (0.073 g, 64%); mp 249−252 °C. H NMR
boxamide (6b). 6b was purified by TLC (dichloromethane/MeOH =
1
(500 MHz, CDCl3) δ 8.26 (dd, J = 7.9 and 1.7 Hz, 1H), 7.89 (s, 1H),
7.70 (dd, J = 8.1 and 1.1 Hz, 1H), 7.62 (s, 1H), 7.50−7.47 (m, 1H),
7.37−7.30 (m, 3H), 7.21−7.17 (m, 1H), 7.10−7.08 (m, 2H).
13C{1H} NMR (125 MHz, CDCl3) δ 151.7, 142.5, 134.1, 133.5,
99/1) as a pale yellow solid (0.077 g, 64%); mp 248−250 °C. H
NMR (500 MHz, DMSO-d6) δ 12.72 (s, 1H), 9.26 (d, J = 7.7 Hz,
1H), 7.91 (dd, J = 7.9 and 1.5 Hz, 1H), 7.63 (d, J = 7.6 Hz, 1H), 7.52
(d, J = 7.7 Hz, 1H), 7.28−7.18 (m, 2H), 6.83 (d, J = 8.3 Hz, 1H),
6.68−6.65 (m, 1H), 3.59−3.53 (m, 1H), 2.02−2.00 (m, 2H), 1.79−
1.76 (m, 2H), 1.62−1.59 (m, 1H), 1.50−1.34 (m, 5H). 13C{1H}
NMR (125NHz, DMSO-d6) δ 152.5, 146.7, 142.6, 133.4, 130.9,
127.7, 122.5, 121.4, 118.1, 114.0, 110.7, 110.2, 49.5, 32.3, 25.5, 23.8.
HRMS (EI) m/z: [M]+ Calcd for C20H20BrN3O 397.0790; Found
397.0788.
132.9, 132.8, 131.7, 129.8, 129.6, 128.2, 127.6, 127.0, 125.7, 124.7,
121.6, 121.1, 120.3, 112.4. HRMS (EI) m/z: [M]+ Calcd for
C20H11Cl2N3O 379.0279; Found 379.0283.
7-Phenylbenzo[h]benzo[4,5]imidazo[1,2-c]quinazolin-8(7H)-one
(3o). 3o was purified by TLC (dichloromethane/MeOH = 200/1) as
a white solid (0.072 g, 66%); mp 258−261 °C. 1H NMR (500 MHz,
CDCl3) δ 8.63 (d, J = 8.6 Hz, 1H), 8.46 (d, J = 8.1 Hz, 1H), 7.96 (d, J
= 8.1 Hz, 1H), 7.90−7.88 (m, 2H), 7.56−7.43 (m, 8H), 7.30−7.27
(m, 1H), 7.12−7.09 (m, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ
147.6, 146.0, 136.7, 135.4, 129.7, 129.2, 128.9, 128.7, 127.3, 126.8,
125.9, 125.4, 124.5, 121.9, 121.2, 119.5, 115.6. HRMS (EI) m/z:
[M]+ Calcd for C24H15N3O 361.1215; Found 361.1213.
5-Phenylbenzo[4,5]imidazo[1,2-c]quinazoline-6(5H)-thione (12).
12 was purified by TLC (dichloromethane/MeOH = 99/1) as a white
solid (0.043 g, 44%); mp 275−277 °C. 1H NMR (500 MHz, CDCl3)
δ 9.44 (d, J = 8.4 Hz, 1H), 8.68−8.64 (m, 1H), 7.96 (d, J = 8.0 Hz,
1H), 7.70−7.67 (m, 2H), 7.64−7.56 (m, 2H), 7.48−7.41 (m, 3H),
7.37−7.35 (m, 2H), 6.60−6.56) (m, 1H). 13C{1H} NMR (125 MHz,
F
https://dx.doi.org/10.1021/acs.joc.0c02067
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
1
CDCl3) δ 171.8, 144.7, 144.5, 140.4, 138.8, 133.4, 131.9, 130.6, 129.4,
129.3, 126.4, 125.4, 125.1, 123.9, 119.5, 118.1, 117.3, 114.5. HRMS
(EI) m/z: [M]+ Calcd for C20H13N3S 327.0830; Found 327.0828.
5-Phenylindolo[1,2-c]quinazolin-6(5H)-one (14). 14 was purified
by TLC (dichloromethane/hexane = 1/1) as a white solid (0.022 g,
1, 2 times) as a white solid (0.033 g, 28%); mp 225−227 °C. H
NMR (500 MHz, CDCl3) δ 8.17−8.15 (m, 1H), 7.61−7.57 (m, 5H),
7.39−7.36 (m, 4H), 7.33−7.31 (m, 2H), 6.98−6.94 (m, 1H), 5.96 (br
s, 1H). 13C{1H} NMR (125 MHz, DMSO-d6) δ 152.5, 150.4, 148.6,
139.7, 133.4, 132.4, 132.2, 131.3, 128.8, 127.8, 122.6, 121.8, 121.5,
119.1, 118.2, 115.6, 113.9, 111.6. HRMS (EI) m/z: [M]+ Calcd for
C20H14BrN3O 391.0320; Found 391.0318.
1
24%); mp 269−271 °C. H NMR (500 MHz, CDCl3) δ 8.66−8.62
(m, 1H), 8.03−7.99 (m, 1H), 7.76−7.71 (m, 1H), 7.65−7.62 (m,
2H), 7.59−7.55 (m, 1H), 7.44−7.42 (m, 2H), 7.41−7.35 (m, 2H),
7.25−7.21 (m, 2H), 7.17 (s, 1H), 6.59−6.55 (m, 1H). 13C{1H} NMR
(125 MHz, CDCl3) δ 147.7, 137.0, 136.9, 134.5, 133.3, 130.3, 130.0,
129.5, 129.2, 128.8, 123.9, 123.8, 123.6, 123.4, 120.1, 116.4, 116.2,
115.1, 98.7. HRMS (EI) m/z: [M]+ Calcd for C21H14N2O 310.1106;
Found 310.1102.
Cyclization of 6a to 3a. To a 10 mL microwave reaction tube, 6a
(0.078 g, 0.2 mmol), K3PO4 (0.079 g, 0.4 mmol), and DMF (3 mL)
were added. After stirring the reaction mixture at room temperature
for 5 min, it was heated at 130 °C for 1 h under microwave irradiation
(100 W of initial power). A workup procedure similar to that
described above afforded 3a (0.053 g, 85%).
2-(2-Bromophenyl)-N,4,5-triphenyl-1H-imidazole-1-carboxa-
mide (16). 16 was purified by TLC (dichloromethane/MeOH = 99/
ASSOCIATED CONTENT
* Supporting Information
■
1
1, 2 times) as a white solid (0.074 g, 50%); mp 220−222 °C. H
sı
NMR (500 MHz, CDCl3) δ 9.28 (br s, 1H), 7.67 (d, J = 7.2 Hz, 2H),
7.51−7.45 (m, 4H), 7.42−7.29 (m, 9H), 7.26−7.20 (m, 2H), 7.03−
6.99 (m, 1H), 6.86−6.83 (m, 1H). 13C{1H} NMR (125 MHz,
CDCl3) δ 145.8, 143.0, 142.3, 136.6, 134.4, 130.9, 129.5, 129.3, 129.0,
128.3, 128.2, 128.1, 127.3, 126.9, 126.4, 125.5, 122.0, 120.6, 118.2,
115.4, 114.0. HRMS (EI) m/z: [M]+ Calcd for C28H20BrN3O
493.0790; Found 493.0792.
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c02067.
1
Copies of H and 13C NMR spectra of all products
(PDF)
FAIR data file, including the primary NMR FID files, for
compounds 3a−3t, 6a, 6b, 10, 12, 14, and 16 (ZIP)
Larger Scale Synthesis of 3a. To a 10 mL microwave reaction
tube, 1a (1.093 g, 4 mmol), 2a (0.953 g, 8 mmol), K3PO4 (1.698 g, 8
mmol), and DMF (6 mL) were added. After stirring the reaction
mixture at room temperature for 5 min, it was heated at 130 °C for 1
h under microwave irradiation (100 W of initial power). The workup
procedure was similar to that described above except for eluent
(dichloromethane/MeOH = 99/1) in purifying crude mixture using
TLC to produce 3a (0.735 g, 59%).
AUTHOR INFORMATION
Corresponding Author
■
Chan Sik Cho − Department of Applied Chemistry, Kyungpook
National University, Bukgu, Daegu 41566, Republic of Korea;
orcid.org/0000-0001-6416-1741; Email: cscho@knu.ac.kr
One-Pot Step by Step Procedure for the Synthesis of 3a. To
a 50 mL round bottomed flask, 2-bromobenzaldehyde (4) (1.112 g, 6
mmol), benzene-1,2-diamine (5) (0.649 g, 6 mmol), NaHSO3 (6.868
g, 66 mmol), and H2O (20 mL) were charged. After the reaction
mixture was stirred at 100 °C for 3 h, H2O and inorganic components
were removed by decantation using H2O several times. To the flask
containing a yellow solid dried under a reduced pressure for several
hours, 2a (1.429 g, 12 mmol), K3PO4 (2.547 g, 12 mmol), and DMF
(10 mL) were added. The reaction mixture was stirred at 150 °C for
30 h, cooled to room temperature, and filtered through a short silica
gel column to eliminate inorganic salts using ethyl acetate. Removal of
the eluent under reduced pressure left a crude mixture, which was
purified by TLC (dichloromethane/MeOH = 200/1, 2 times) to give
3a (0.822 g, 44%).
Procedure for the Reaction of 9 with 2a. To a 10 mL
microwave reaction tube, 9 (0.058 g, 0.3 mmol), 2a (0.071 g, 0.6
mmol), K3PO4 (0.128 g, 0.6 mmol), and DMF (3 mL) were added.
After stirring the reaction mixture at room temperature for 5 min, it
was heated at 130 °C for 1 h under microwave irradiation (100 W of
initial power). A workup procedure similar to that described above
afforded 10.
N,2-Diphenyl-1H-benzo[d]imidazole-1-carboxamide (10). 10
was purified by TLC (dichloromethane/MeOH = 97/3) as a white
solid (0.069 g, 73%); mp 261−263 °C. 1H NMR (500 MHz, CDCl3)
δ 10.27 (br s, 1H), 8.38 (dd, J = 8.0 and 1.7 Hz, 1H), 7.68 (d, J = 7.2
Hz, 2H), 7.64 (dd, J = 8.1 and 1.2 Hz, 1H), 7.49 (d, J = 7.2 Hz, 2H),
7.45−7.31 (m, 6H), 7.27−7.20 (m, 2H). 13C{1H} NMR (125 MHz,
CDCl3) δ 143.9, 138.0, 134.6, 133.8, 131.6, 130.9, 130.0, 129.9, 129.0,
128.3, 128.04, 127.98, 127.8, 127.7, 127.1, 119.0. HRMS (EI) m/z:
[M]+ Calcd for C20H15N3O 313.1215; Found 313.1218.
Author
Pham Duy Quang Dao − Department of Applied Chemistry,
Kyungpook National University, Bukgu, Daegu 41566,
Republic of Korea; orcid.org/0000-0002-2537-1874
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02067
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the National Research
Foundation of Korea (NRF) grant funded by the Korea
government (Ministry of Science and ICT)
(2020R1F1A1054806).
REFERENCES
■
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Experimental Procedure for Mechanism Study. To a 10 mL
microwave reaction tube, 1a (0.082 g, 0.3 mmol), 2a (0.071 g, 0.6
mmol), K3PO4 (0.128 g, 0.6 mmol), and DMF (3 mL) were added.
After stirring the reaction mixture at room temperature for 5 min, it
was heated at 130 °C for 30 min under microwave irradiation (100 W
of initial power). A workup procedure similar to that described above
afforded 6a and 3a.
2-(2-Bromophenyl)-N-phenyl-1H-benzo[d]imidazole-1-carboxa-
mide (6a). 6a was purified by TLC (dichloromethane/MeOH = 200/
G
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