Synthesis of Trinuclear Benzimidazole-Fused Hybrid Scaffolds by Transition Metal-Free Tandem C(sp2)?N Bond Formation under Microwave Irradiation

Article abstract of DOI:10.1002/ejoc.202100419

2-(2-Bromoaryl)- and 2-(2-bromovinyl)benzimidazoles have been coupled and cyclized with 2-methoxy- and 2-aryloxybenzimidazoles as building blocks in the presence of a base under microwave irradiation to give a class of trinuclear N-fused hybrid scaffolds, benzo[4,5]imidazo[1,2-a]benzo[4,5]imidazo[1,2-c]quinazolines and -pyrimidines, respectively, in good yields. 2-(2-Bromoaryl)- and 2-(2-bromovinyl)imidazoles also reacted with 2-methoxybenzimidazoles in the presence of base under microwave irradiation to give a class of trinuclear N-fused hybrid scaffolds, benzo[4,5]imidazo[1,2-a]imidazo[1,2-c]quinazolines and -pyrimidines, respectively, in similar yields. This process seems to proceed via an initial C(sp²)-N coupling by an addition-elimination nucleophilic aromatic substitution (S_NAr) and subsequent cyclization accompanied by extrusion of alcohols.

Full text of DOI:10.1002/ejoc.202100419

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Synthesis of Trinuclear Benzimidazole-Fused Hybrid
Scaffolds by Transition Metal-Free Tandem C(sp2)À N Bond
Formation under Microwave Irradiation
Pham Duy Quang Dao[a] and Chan Sik Cho*[a]
2-(2-Bromoaryl)- and 2-(2-bromovinyl)benzimidazoles have
been coupled and cyclized with 2-methoxy- and 2-aryloxybenzi-
midazoles as building blocks in the presence of a base under
microwave irradiation to give a class of trinuclear N-fused
hybrid scaffolds, benzo[4,5]imidazo[1,2-a]benzo[4,5]imidazo[1,2-
c]quinazolines and -pyrimidines, respectively, in good yields. 2-
(2-Bromoaryl)- and 2-(2-bromovinyl)imidazoles also reacted
with 2-methoxybenzimidazoles in the presence of base under
microwave irradiation to give a class of trinuclear N-fused
hybrid scaffolds, benzo[4,5]imidazo[1,2-a]imidazo[1,2-c]
quinazolines and -pyrimidines, respectively, in similar yields.
This process seems to proceed via an initial C(sp2)-N coupling
by an addition-elimination nucleophilic aromatic substitution
(SNAr) and subsequent cyclization accompanied by extrusion of
alcohols.
Introduction
oxidative cycliztion of 2-(2-bromophenyl)benzimidazole with
benzimidazole as a building block in the presence of CuI/
Pd(OAc)2/Cu(OAc)2 or CuCl2/1,10-phenanthroline (Scheme 1,
route b).[7,8] Such a similar construction of scaffold A using
benzimidazole as a building block was also exemplified by Pd-
catalyzed C(sp2)À N coupling and cross-dehydrogenative C-
(sp2)À H/NÀ H coupling between 2-phenylbenzimidazole and
benzimidazole (Scheme 1, route c).[9] During the course of our
recent efforts directed toward copper-catalyzed and transition
metal-free synthesis of polynuclear N-fused hybrid scaffolds via
a C(sp2)À N coupling, we also recently reported that 2-(2-
bromophenyl)benzimidazoles were coupled and cyclized with
cyclic ureas as building blocks in the presence of CuI to produce
scaffold A (Scheme 1, route d).[10,11] In contrast to these
precedents, the first transition metal-free construction of
scaffold A was achieved by a base-mediated nucleophilic
aromatic substitution (SNAr) between 2-(2-bromophenyl)
benzimidazoles and 2-aminobenzimidazoles as building blocks
(Scheme 1, route e).[12,13] The present work started during the
course of the development of a building block for the
construction of scaffold A by such a transition metal-free
C(sp2)À N bond formation. This work shows another example for
transition metal-free construction of scaffolds A by the reaction
of 2-(2-bromoaryl)benzimidazoles with 2-methoxy- and 2-
aryloxybenzimidazoles as building blocks with broad substrate
scope (Scheme 1, route f). This protocol can also be extended
to the reaction of 2-(2-bromovinyl)benzimidazoles and 2-(2-
bromoaryl)- and 2-(2-bromovinyl)imidazoles with such building
blocks to synthesize a class of trinuclear N-fused hybrid
scaffolds (Scheme 1, routes g–i).
It is known that polynuclear N-fused hybrid scaffolds exhibit a
distinct spectrum of biological activities and photoelectronic
properties that are not shown in each homonuclear scaffold.[1]
Various synthetic methods of polynuclear N-fused hybrid
scaffolds have been developed and further efforts to develop a
green construction of such scaffolds still remain a challenging
area.[1] In connection with this report, transition metal-catalyzed
C(sp2)À N bond forming reactions such as palladium-catalyzed
Buchwald-Hartwig coupling and copper-catalyzed Ullmann-type
coupling have been of fundamental interest and played a key
role in the synthesis of N-heterocyclic compounds.[2–4] However,
these transition metal-catalyzed C(sp2)À N bond forming reac-
tions have some drawbacks such as requiring expensive
consumable transition metal catalysts and ligands, involving
tedious stepwise procedures and contamination with undesir-
able toxic trace metals in final products. In recent years,
transition metal-free C(sp2)À N bond forming reactions have also
been achieved and drawn a considerable interest.[5]
Several approaches for the synthesis of scaffold A using
benzimidazoles as building blocks have recently been disclosed
(Scheme 1). Lv and coworkers reported that bis(o-iodophenyl)
carbodiimide reacts with benzimidazole in the presence of CuI
and 1,10-phenanthroline to give scaffold A via a sequence
involving an initial nucleophilic addition followed by double
cyclizations by copper-catalyzed intramolecular C(sp2)À N cou-
pling and C(sp2)À C coupling (Scheme 1, route a).[6] Scaffold A
can also be synthesized by stepwise C(sp2)À N coupling and
[a] Dr. P. D. Q. Dao, Prof. C. S. Cho
Department of Applied Chemistry
Kyungpook National University
Results and Discussion
80 Daehakro, Bukgu, Daegu 41566, Republic of Korea
E-mail: cscho@knu.ac.kr
Table 1 shows several attempted results for the transition
metal-free construction of trinuclear N-fused hybrid scaffold 3a
Supporting information for this article is available on the WWW under
https://doi.org/10.1002/ejoc.202100419
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Scheme 1. Synthetic routes for trinuclear N-fused hybrid scaffolds.
by the reaction of 2-(2-bromophenyl)-1H-benzo[d]imidazole
(1a) with 2-methoxy-1H-benzo[d]imidazole (2a) as a building
block under various conditions.[11,14,15] Treatment of 1a with an
complete conversion of 1a along with the formation of several
unidentified products (Table 1, entries 9, 10, and 15). Other
bases such as KOH, K2CO3, and Cs2CO3 were not effective for the
formation of 3a (Table 1, entries 11–13). However, the reaction
did not proceed at all in the absence of a base, and 1a was
recovered intact (Table 1, entry 16). It is unclear why the
reactivity is different according to the kind of base.[5f] DMF was
shown to be the solvent of choice. Further optimization with
solvents such as DMSO and HMPA under the employed
conditions resulted in no increased yield of 3a (Table 1,
entries 17 and 18). On the other hand, treatment of 1a and 2a
°
equimolar amount of 2a in DMF at 130 C for 2 h in the
presence of K3PO4 under microwave irradiation (100 W of initial
power) afforded 3a in 38% isolated yield with incomplete
conversion of 1a (Table 1, entry 1).[16,17] The yield of 3a was not
significantly affected by the molar ratio of 2a to 1a, and the
yield slightly increased with the increase in the molar ratio up
to 1.5 (Table 1, entries 1–3). Performing the reaction under the
increased amount of K3PO4 up to 3 to 1a also resulted in a
slightly increased yield of 3a with complete conversion of 1a
(Table 1, entries 2, 4, and 5). No significant change of the yield
of 3a was observed with prolonging the reaction time (Table 1,
entries 4 and 6). Higher reaction temperature resulted in an
increased yield of 3a with complete conversion of 1a, whereas
lower reaction temperature produced 3a in a lower yield with
incomplete conversion of 1a (Table 1, entries 7 and 8). Among
bases examined under the employed conditions, CsF was
revealed to be the base of choice (Table 1, entry 14).[18] KOtBu,
NaOtBu, and CsCl showed a similar activity as K3PO4 with
°
under usual heating conditions (screw-capped vial, 150 C, 24 h)
did not afford 3a at all (Table 1, entry 19).
Various
2-(2-bromoaryl)-
and
2-(2-bromovinyl)
benzimidazoles 1 were subjected to the reaction with 2-
methoxybenzimidazoles under the optimized reaction condi-
tions (entry 14 of Table 1) in order to investigate the scope of
the reaction, and several representative experimental results are
shown in Table 2.[14,15] 2-(2-Bromoaryl)benzimidazoles 1b—e
having electron-donating and -withdrawing substituents on
bromoaryl moiety were readily coupled and cyclized with 2-
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Table 1. Optimization of conditions for the reaction between 1a and 2a.[a]
Entry
[2a]/
[1a]
Base/
[1a]
Base
Solvent
Temp [oC]
Time [h]
Conv of 1a [%]
Yield[b] [%]
1
2
3
4
5
6
7
8
1.0
1.5
2.0
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
2.0
2.0
2.0
3.0
4.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
-
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
KOtBu
NaOtBu
KOH
K2CO3
Cs2CO3
CsF
CsCl
–
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMSO
HMPA
DMF
130
130
130
130
130
130
150
110
150
150
150
150
150
150
150
150
150
150
150
2
2
2
2
2
3
2
2
2
2
2
2
2
2
2
2
2
2
24
67
81
85
38
46
47
53
54
52
63
33
67
61
29
trace
51
76
69
0
100
100
100
100
72
100
100
69
44
94
100
100
0
9
10
11
12
13
14
15
16
17
18
19[c]
3.0
3.0
3.0
CsF
CsF
CsF
66
93
36
21
60
0
[a] Reaction conditions: 1a (0.3 mmol), solvent (3 mL), under microwave irradiation (100 W of the initial power). [b] Isolated yield. [c] Usual heating.
methoxybenzimdazole 2a to give the corresponding trinuclear
N-fused hybrid scaffolds 3b–e in 53–70% yields. 2-(2-Bromo-
phenyl)benzimidazole 1a also reacted with dimethyl- and
cyano-substituted and benzo-fused 2-methoxybenzimidazoles
(2b, 2d and 2f) to produce the corresponding trinuclear N-
fused hybrid scaffolds 3f–h in similar yields. The expected
products from the reactions of 1a with 2c and 2e, not shown
in Table 2, were isolated in 71% and 60% yields, respectively,
and confirmed by HRMS, however, they could not be further
confirmed by NMR because of their hard solubility in NMR
solvents. 2-(2-Bromophenyl)benzimidazoles (1f and 1g) having
dimethyl and dimethoxy substituents on benzimidazole moiety
were also coupled and cyclized with 2a to form the correspond-
ing trinuclear scaffolds (3i and 3j) in 71% and 59% yields,
respectively. Although the expected product from 1h and 2a
was isolated in 75% yield and confirmed by HRMS, it could not
also be identified by NMR because of its hard solubility in NMR
solvents. The reaction of cyclic 2-(2-bromovinyl)benzimidazoles
(1i and 1j) with 2-methoxybenzimidazoles (2a and 2c) also
took place to afford the coupled and cyclized products 3k–m in
similar yields. Similar treatment of acyclic 2-(2-bromovinyl)
benzimidazoles 1k–n having straight and branched alkyl chain
and phenyl substituents on vinyl moiety with 2a under the
employed conditions also afforded the corresponding trinuclear
N-fused hybrid scaffolds 3n–q in similar yields, irrespective of
the identity of such substituents.[14,19] Here again, from the
reaction of 1k with 2-methoxybenzimidazoles (2b, 2c and 2f),
the corresponding trinuclear N-fused hybrid scaffolds 3r–t were
also formed in 60–68% yields. To the best of our knowledge,
limited examples are found for the synthetic method of such a
trinuclear N-fused hybrid scaffold like 3k–t.[11,12]
Based on the reaction of 2-(2-bromoaryl)- and 2-(2-
bromovinyl)benzimidazoles with 2-methoxybenzimidazoles, the
present protocol can be extended to the reaction with 2-(2-
bromoaryl)- and 2-(2-bromovinyl)imidazoles 4 as shown in
Table 3.[19,20] 2-(2-Bromoaryl)imidazoles 4b–d having electron-
donating and -withdrawing substituents on bromoaryl moiety
invariably reacted with 2a under the optimized conditions to
give the corresponding trinuclear N-fused hybrid scaffolds 5b–
d, irrespective of the position and electronic nature of such
substituents. The reaction of 2-(2-bromophenyl)imidazole 4a
with
dimethyl-
and
dichloro-substituted
2-meth-
oxybenzimidazoles (2b and 2c) also afforded the correspond-
ing trinuclear N-fused hybrid scaffolds 5e and 5f, respectively
in similar yields. As is the case for the reaction between 1a and
2c, not shown in Table 3, 4a likewise reacted with 2f to give
the expected product in 53% yield. However, it also could not
be further confirmed by NMR because of its hard solubility in
NMR solvents. Diheteroaryl-substituted 2-(2-bromophenyl)
imidazole 4e also coupled and cyclized with 2a to give the
corresponding product 5g in 73% yield, whereas none of the
expected scaffold 5h was produced from the reaction of
dimethyl-substituted 2-(2-bromophenyl)imidazole 4f with 2a.
The reaction of cyclic 2-(2-bromovinyl)imidazole 4g with 2a
also proceeded to give scaffold 5i in 65% yield. Treatment of
acyclic 2-(2-bromovinyl)imidazoles 4h–k with 2-meth-
oxybenzimidazoles (2a–c and 2f) also triggers coupling and
cyclization to produce the corresponding trinuclear N-fused
hybrid scaffolds 5j–p in similar yields, irrespective of the
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Table 2. Substrate scope for the reaction of 1 with 2.[a]
Table 3. Substrate scope for the reaction of 4 with 2.[a]
[a] Reaction conditions: 4 (0.3 mmol), 2 (0.45 mmol), CsF (0.9 mmol), DMF
°
(3 mL), under microwave irradiation (100 W of the initial power), 150 C,
2 h.
ods of trinuclear scaffolds like 5a–g, no reports have been
found for those of trinuclear scaffolds like 5i–p.[11,21]
On the other hand, a cascade reaction starting from 2-
bromobenzaldehyde (6) and benzil (7) renders the synthesis of
5a practical and sustainable (Scheme 2).[22] Treatment of 6 with
equimolar amount of 7 in the presence of NH4OAc in acetic acid
[a] Reaction conditions: 1 (0.3 mmol), 2 (0.45 mmol), CsF (0.9 mmol), DMF
°
(3 mL), under microwave irradiation (100 W of the initial power), 150 C,
2 h.
°
and EtOH at 70 C for 1 h under microwave irradiation (100 W of
initial power) followed by removal of solvent, washing with
water and drying under vacuum produced a white precipitate.
identity of substituents on vinyl moiety and the kind of 2-
methoxybenzimidazoles. In contrast to limited synthetic meth-
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Further addition of 2a, CsF and DMF to the microwave reaction
tube containing a white precipitate and reaction under micro-
wave irradiation (100 W of initial power) afforded 5a in 59%
yield.
Although the details of the reaction scheme are not certain,
a plausible pathway based on additional experimental observa-
tions and literatures is proposed in Scheme 3. An initial
nucleophilic attack of deprotonated 2 to the carbon attached to
Br in 1a produces a resonance-stabilized carbanion, Meisen-
heimer complex 8.[23,24] This is followed by conventional
addition-elimination nucleophilic aromatic substitution to form
a CÀ N coupled intermediate 9.[24] We carried out several control
experiments to isolate such a CÀ N coupled intermediate 9.
Performing the reaction of 1a with 2a for a shorter reaction
time (30 min) under the employed conditions resulted in only
lower yield of 3a (37%) with lower conversion of 1a (59%)
without the formation of the CÀ N coupled intermediate.
However, fortunately, similar treatment of 1a with 2c and 2f
for 30 min afforded CÀ N coupled intermediates (11 and 12) in
11 and 24% yields, respectively along with lower yields of
trinuclear N-fused scaffolds (Scheme 4, (1) and (2)). The
intermediate 12 thus isolated was readily cyclized under the
employed conditions to give 3h in 78% yield with 91%
conversion of 12. Subsequent intramolecular nucleophilic
addition in intermediate 9 forms an intermediate 10, which is
followed by β-elimination to give 3a with an extrusion of
alcohol. The following experimental results show an evidence
for the extrusion of such an alcohol during the course of
reaction. Treatment of 1a with 2-methoxybenzimidazole surro-
gates, 2-phenoxy- and 2-(2-naphthoxy)benzimidazoles (2g and
Scheme 2. A Cascade reaction.
Scheme 3. A proposed reaction pathway.
Scheme 4. Control experiments.
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118.9, 116.2, 114.7, 111.8, 111.5, 56.1, 55.8. HRMS (EI): m/z [M+]
calcd for C15H13BrN2O 332.0160; found, 332.0158.
2h) under the employed conditions gave 3a in 80% and 67%
yields, respectively along with concomitant formation of 2-
naphthol (13) (54% yield) in the reaction with 2h (Scheme 4,
(3)).[25] Similarly, when 1o, N-methyl-substituted analogue of 1a,
was treated with 2h under the optimized conditions, 2-meth-
oxynaphthalene (14) by β-elimination was also formed in 9%
yield with concomitant formation of 3a (16%) and many
unidentifiable products (Scheme 4, (4)).
General procedure for the synthesis of 2.
Synthesis of 2c and 2f: 1,2-Arylenediamines (3.0 mmol) in acetic
acid (7 mL) was added tetramethoxymethane (0.449 g, 3.3 mmol) at
room temperature, and the mixture was stirred for 4 h. The solvent
was removed under reduced pressure and the residue was
dissolved in ethyl acetate. Then the mixture was washed with water
(3 times) and brine (1 time), dried over Na2SO4, and evaporated the
solvent to give 2c and 2f.[15]
Conclusions
5,6-Dichloro-2-methoxy-1H-benzo[d]imidazole (2c). According to
the general procedure, the product 2c was obtained as a pale red
A class of trinuclear N-fused hybrid scaffolds was constructed
by the reaction of 2-(2-bromoaryl)- and 2-(2-bromovinyl)
imidazoles as well as 2-(2-bromoaryl)- and 2-(2-bromovinyl)
benzimidazoles with 2-methoxy- and 2-aryloxybenzimidazoles
as building blocks in the presence of CsF under microwave
irradiation. A reaction pathway involving the formation of a
C(sp2)À N coupled intermediate by nucleophilic aromatic sub-
stitution and subsequent extrusion of an alcohol was proposed
for this green process. The present reaction would be served as
a green route for designing and developing biologically active
compounds and organic electronic materials. Further challenges
on the construction of polynuclear N-fused hybrid scaffolds
using this protocol and development of an unprecedented
chemical reaction based on an outcome arose during the
course of mechanism study are under way.
1
°
solid (0.478 g, 73%); mp 242–244 C. H NMR (DMSO-d6, 500 MHz) δ
12.13 (br s, 1H), 7.53 (s, 2H), 4.06 (s, 3H). 13C NMR (DMSO-d6,
125 MHz) δ 160.4, 136.9, 122.6, 114.5, 56.8. HRMS (EI): m/z [M+]
calcd for C8H6Cl2N2O 215.9857; found, 215.9854.
2-Methoxy-1H-naphtho[2,3-d]imidazole (2f). According to the
general procedure, the product 2f was obtained as a brown solid
(0.315 g, 53%); mp 246–248 C. 1H NMR (DMSO-d6, 500 MHz) δ
°
10.80 (br s, 1H), 7.90-7.88 (m, 2H), 7.81–7.79 (m, 1H), 7.32-7.28 (m,
3H), 4.13 (s, 3H). 13C NMR (DMSO-d6, 125 MHz) δ 161.9, 156.2, 131.1,
128.4, 128.2, 127.3, 126.8, 123.2, 122.9, 103.6, 56.8. HRMS (EI): m/z
[M+] calcd for C12H20N2O 198.0793; found, 198.0795.
Synthesis of 2g and 2h: 2g was synthesized by the reaction
between 2-chlorobenzimidazole (0.458 g, 3.0 mmol) and sodium
phenoxide (0.464 g, 4.0 mmol) in phenol according to the reported
procedure.[24] On the other hand, 2h was synthesized by the
modified procedure. To
a mixture of 2-chlorobenzimidazole
(0.458 g, 3.0 mmol) and 2-naphthol (0.577 g, 4.0 mmol) in DMF
°
(5 mL) was added NaOH (0.600 g, 15 mmol) and stirred at 120 C for
Experimental Section
12 h. Removal of the solvent under reduced pressure left a crude
mixture, which was purified by column chromatography (dichloro-
methane/MeOH=99/1) to give 2h.
1
General information. H and 13C NMR spectra were analyzed by a
Bruker Avance Digital 500 spectrometer using TMS as an internal
standard in CDCl3, CD2Cl2, 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 sensor is vessel volume
independent and is used in a feedback loop with the on-board
computer to control the temperature rise rate and control point of
the vessel contents. The products were isolated by TLC (a glass
plate coated with Kieselgel 60 GF254, Merck). The starting com-
pounds 1, 4 and building blocks 2 were prepared by known
methods.[11,14,15,25] Other commercially available organic and inor-
ganic reagents were used without further purification.
2-(Naphthalen-2-yloxy)-1H-benzo[d]imidazole (2h). According to
the general procedure, the product 2h was obtained as a brown
1
°
solid (0.250 g, 32%); mp 241–243 C. H NMR (DMSO-d6, 500 MHz) δ
8.03-8.06 (m, 3H), 7.75–7.72 (m, 1H), 7.69-7.67 (m, 1H), 7.62–759 (m,
1H), 7.57–7.54 (m, 2H), 7.30–7.24 (m, 2H), 5.73 (s, 1H). 13C NMR
(DMSO-d6, 125 MHz) δ 150.2, 145.2, 139.5, 132.4, 130.2, 129.8, 129.7,
128.6, 127.6, 125.6, 122.6, 122.4, 121.2, 117.6, 117.2, 109.8, 108.4.
HRMS (EI): m/z [M+] calcd for C17H12N2O 260.0950; found, 260.0954.
General procedure for the synthesis of 3: To a 10 mL microwave
reaction tube was added 1 (0.3 mmol), 2 (0.45 mmol), CsF (0.137 g,
0.9 mmol), and DMF (3 mL). After stirring the reaction mixture at
°
room temperature for 5 min, it was heated at 150 C for 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 (dichloromethane/MeOH=99/1) to give 3. All
products were characterized spectroscopically as shown below.
General procedure for the synthesis of 1: 2-(2-Bromoaryl)- and 2-
(2-bromovinyl)-benzimidazoles were synthesized by the reaction
between the corresponding aldehydes (5 mmol) and 1,2-phenyl-
enediamines (5 mmol) using NaHSO3 according to the reported
procedure.[11,14] Except for 1e, all are known.
Benzo[4,5]imidazo[1,2-a]benzo[4,5]imidazo[1,2-c]quinazoline
(3a).[12] Purified by TLC (dichloromethane/MeOH=99/1, 2 times);
1
°
white solid (70 mg, 76%); mp 229–231 C. H NMR (CDCl3, 500 MHz)
2-(2-Bromo-4,5-dimethoxyphenyl)-1H-benzo[d]imidazole (1e). Pu-
rified by column chromatography (hexane/ethyl acetate=10:3);
δ 8.66-8.64 (m, 1H), 8.60 (d, J=7.8 Hz, 1H), 8.12 (d, J=8.4 Hz, 1H),
7.92-7.88 (m, 2H), 7.65-7.62 (m, 1H), 7.50-7.47 (m, 2H), 7.42-7.39 (m,
1H), 7.33-7.30 (m, 1H), 7.28-7.25 (m, 1H). 13C NMR (CDCl3, 125 MHz)
δ 144.4, 143.8, 142.4, 141.5, 134.0, 131.9, 130.3, 129.9, 126.5, 125.3,
125.2, 124.3, 124.1, 123.0, 119.9, 119.6, 114.9, 114.8, 114.4, 112.5.
white solid (1.22 g, 73%); mp 195–197 C. 1H NMR (DMSO-d6,
°
500 MHz) δ 812.60 (s, 1H), 7.71-7.52 (m, 2H), 7.35 (s, 1H), 7.31 (s,
1H), 7.25-7.19 (m, 2H), 3.87 (s, 3H), 3.82 (s, 3H). 13C NMR (DMSO-d6,
125 MHz) δ 150.5, 150.3, 148.0, 143.2, 134.5, 124.1, 122.4, 121.5,
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7-Chlorobenzo[4,5]imidazo[1,2-a]benzo[4,5]imidazo[1,2-c]
quinazoline (3b). Purified by TLC (dichloromethane/MeOH=99/1,
130.6, 130.4, 128.1, 128.0, 126.8, 125.7 (125.69), 125.7 (125.66),
125.3, 125.0 (125.03), 125.0 (124.96), 124.7, 120.5, 119.8, 116.9,
115.2, 114.9, 114.5, 109.8. HRMS (EI): m/z [M+] calcd for C24H14N4
358.1218; found, 358.1220.
1
°
2 times); white solid (72 mg, 70%); mp 226–228 C. H NMR (CDCl3,
500 MHz) δ 8.85-8.83 (m, 1H), 8.80 (d, J=2.4 Hz, 1H), 8.37 (d, J=
9.0 Hz, 1H), 8.15-8.14 (m, 1H), 8.02-7.98 (m, 2H), 7.79 (dd, J=8.9 and
2.5 Hz, 1H), 7.63-7.57 (m, 2H), 7.56-7.48 (m, 2H). 13C NMR (CDCl3,
125 MHz) δ 132.1, 131.6, 130.4, 130.2, 126.7, 126.3, 125.7, 125.5,
124.9, 124.7, 124.5 (124.54), 124.5 (124.50), 123.5, 120.4, 120.0,
116.5, 115.1, 112.6. HRMS (EI): m/z [M+] calcd for C20H11ClN4
342.0672; found, 342.0674.
2,3-Dimethylbenzo[4,5]imidazo[1,2-a]benzo[4,5]imidazo[1,2-c]
quinazoline (3i).[11] Purified by TLC (dichloromethane/MeOH=99/1,
1
°
2 times); white solid (72 mg, 71%); mp 240–242 C. H NMR (CDCl3,
500 MHz) δ 8.70 (dd, J=7.9 and 1.4 Hz, 1H), 8.50 (s, 1H), 8.33 (d, J=
8.4 Hz, 1H), 8.12 (d, J=7.8 Hz, 1H), 7.93-7.91 (m, 1H), 7.77–7.74 (m,
1H), 7.68 (s, 1H), 7.54–7.51 (m, 1H), 7.47–7.39 (m, 2H), 2.52 (s, 3H),
2.46 (s, 3H). 13C NMR (CDCl3, 125 MHz) δ 143.9, 142.7, 142.4, 142.0,
134.6, 134.0 (134.04), 134.0 (134.00), 131.6, 130.3, 128.8, 126.5,
125.3, 124.2, 123.0, 120.0, 119.7, 115.0, 114.9, 114.8, 112.7, 20.7,
20.6.
7-Methoxybenzo[4,5]imidazo[1,2-a]benzo[4,5]imidazo[1,2-c]
quinazoline (3c).[12] Purified by TLC (dichloromethane/MeOH=99/
1, 2 times); white solid (63 mg, 62%); mp 267–269 C. 1H NMR
°
(CDCl3, 500 MHz) δ 8.84-8.81 (m, 1H), 8.27 (d, J=9.2 Hz, 1H), 8.15 (d,
J=3.0 Hz, 1H), 8.09 (d, J=8.0 Hz, 1H), 7.99–7.96 (m, 1H), 7.95–7.93
(m, 1H), 7.59-7.54 (m, 2H), 7.48–7.40 (m, 2H), 7.34 (dd, J=9.1 and
3.0 Hz, 1H), 4.00 (s, 3H). 13C NMR (CDCl3, 125 MHz) δ 157.0, 144.7,
143.8, 142.5, 141.5, 130.5, 130.1, 128.4, 125.4, 124.5, 124.1, 123.0,
120.9, 120.1, 119.6, 116.6, 115.6, 115.1, 112.5, 108.0, 56.0.
1,4-Dimethoxybenzo[4,5]imidazo[1,2-a]benzo[4,5]imidazo[1,2-c]
quinazoline (3j).[12] Purified by TLC (dichloromethane/MeOH=99/1,
1
°
2 times); white solid (65 mg, 59%); mp 247–249 C. H NMR (CDCl3,
500 MHz) δ 8.93 (dd, J=7.9 and 1.4 Hz, 1H), 8.41 (d, J=8.4 Hz, 1H),
8.20-8.19 (m, 1H), 7.99–7.97 (m, 1H), 7.83-7.79 (m, 1H), 7.57-7.54 (m,
1H), 7.50–7.44 (m, 2H), 7.01 (d, J=7.8 Hz, 1H), 6.91 (d, J=8.7 Hz,
1H), 4.15 (s, 3H), 4.10 (s, 3H). 13C NMR (CDCl3, 125 MHz) δ 146.2,
145.0, 142.4, 142.2, 141.9, 136.4, 134.1, 132.1, 130.9, 127.3, 125.3,
124.2, 123.3, 122.7, 120.8, 115.0, 114.8, 112.7, 109.8, 105.8, 59.0,
56.2.
8-Methylbenzo[4,5]imidazo[1,2-a]benzo[4,5]imidazo[1,2-c]
quinazoline (3d).[12] Purified by TLC (dichloromethane/MeOH=99/
1, 2 times); white solid (66 mg, 68%); mp 238–240 C. 1H NMR
°
(CDCl3, 500 MHz) δ 8.79–8.76 (m, 1H), 8.57 (d, J=8.1 Hz, 1H), 8.09
(d, J=9.0 Hz, 1H), 8.08 (s, 1H), 7.96-7.93 (m, 1H), 7.91–7.89 (m, 1H),
7.56–7.52 (m, 2H), 7.46–7.39 (m, 2H), 7.32 (d, J=8.0 Hz, 1H), 2.60 (s,
3H). 13C NMR (CDCl3, 125 MHz) δ 144.9, 143.9, 143.2, 142.6, 141.9,
131.3, 130.4, 130.2, 126.6, 126.5, 125.3, 124.3, 124.2, 123.0, 120.1,
119.5, 115.3, 115.0, 112.8, 112.0, 22.4.
6,7,8,9-Tetrahydrobenzo[4,5]imidazo[1,2-a]benzo[4,5]imidazo
[1,2-c]quinazoline (3k).[12] Purified by TLC (dichloromethane/
MeOH=99/1); white solid (65 mg, 69%); mp 262–264 C. 1H NMR
°
(CDCl3, 500 MHz) δ 8.67–8.63 (m, 1H), 7.91-7.87 (m, 1H), 7.80–7.78
(m, 1H), 7.69 (d, J=8.3 Hz, 1H), 7.50-7.44 (m, 2H), 7.33–7.30 (m, 1H),
7.13-7.11 (m, 1H), 3.23-3.21 (m, 2H), 3.01-2.99 (m, 2H), 2.10-2.05 (m,
2H), 1.98-1.94 (m, 2H). 13C NMR (CDCl3, 125 MHz) δ 142.2, 141.8,
137.5, 129.6 (129.59), 129.6 (129.55), 125.1, 124.0, 123.4, 121.9,
119.5, 119.3, 114.7, 113.2, 109.1, 27.0, 23.0, 22.0, 20.8.
7,8-Dimethoxybenzo[4,5]imidazo[1,2-a]benzo[4,5]imidazo[1,2-c]
quinazoline (3e). Purified by TLC (dichloromethane/MeOH=99/1, 2
1
°
times); white solid (59 mg, 53%); mp 286–288 C. H NMR (CDCl3,
500 MHz) δ 8.73-8.69 (m, 1H), 7.91–7.84 (m, 4H), 7.55 (s, 1H), 7.54–
7.49 (m, 2H), 7.44–7.41 (m, 1H), 7.36–7.33 (m, 1H), 4.05 (s, 3H), 3.99
(s, 3H). 13C NMR (CDCl3, 125 MHz) δ 152.6, 147.1, 144.7, 143.8, 142.5,
141.6, 130.3, 129.7, 128.9, 125.2, 124.2, 123.9, 122.8, 120.1, 119.2,
114.9, 112.0, 107.0, 106.8, 98.1, 56.4 (56.43), 56.4 (56.36). HRMS (EI):
m/z [M+] calcd for C22H16N4O2 368.1273; found, 368.1275.
12,13-Dichloro-6,7,8,9-tetrahydrobenzo[4,5]imidazo[1,2-a]benzo
[4,5]imidazo[1,2-c]quinazoline (3l).[12] Purified by TLC (dichloro-
°
methane/MeOH=99/1); white solid (72 mg, 63%); mp 269–271 C.
1H NMR (CDCl3, 500 MHz) δ 8.53–8.51 (m, 1H), 7.87 (d, J=7.6 Hz,
1H), 7.83 (s, 2H), 7.49–7.42 (m, 2H), 3.18–3.15 (m, 2H), 3.04–3.01 (m,
2H), 2.14–2.09 (m, 2H), 2.00–1.95 (m, 2H). 13C NMR (CDCl3, 125 MHz)
δ 145.9, 144.0, 142.9, 141.7, 136.8, 129.3, 128.6, 128.2, 125.6, 125.5,
123.8, 120.5, 119.5, 114.6, 114.5, 110.3, 26.8, 23.0, 21.9, 20.7.
12,13-Dimethylbenzo[4,5]imidazo[1,2-a]benzo[4,5]imidazo[1,2-c]
quinazoline (3f).[9] Purified by TLC (dichloromethane/MeOH=99/1,
1
°
2 times); white solid (66 mg, 65%); mp 315–317 C. H NMR (CDCl3,
500 MHz) δ 8.80-8.77 (m, 1H), 8.75 (dd, J=7.9 and 1.4 Hz, 1H), 8.32
(d, J=8.4 Hz, 1H), 8.00–7.96 (m, 1H), 7.85 (s, 1H), 7.81-7.78 (m, 1H),
7.63 (s, 1H), 7.58-7.52 (m, 3H), 2.45 (s, 3H), 2.40 (s, 3H). 13C NMR
(CDCl3, 125 MHz) δ 144.7, 143.9, 141.3, 141.0, 134.4, 133.3, 132.1
(132.14), 132.1 (132.05), 130.5, 128.6, 126.7, 125.3, 125.2, 124.3,
120.4, 119.6, 115.1, 115.0, 114.6, 113.2, 20.9, 20.3.
1,4-Dimethoxy-6,7,8,9-tetrahydrobenzo[4,5]imidazo[1,2-a]benzo
[4,5]imidazo[1,2-c]quinazoline (3m).[12] Purified by TLC (dichloro-
°
methane/MeOH=99/1); white solid (60 mg, 54%); mp 273–275 C.
1H NMR (CDCl3, 500 MHz) δ 7.95–7.93 (m, 2H), 7.44–7.41 (m, 1H),
7.31–7.28 (m, 1H), 6.95 (d, J=8.7 Hz, 1H), 6.87 (d, J=8.7 Hz, 1H),
4.14 (s, 3H), 4.06 (s, 3H), 3.42-3.40 (m, 2H), 3.16-3.14 (m, 2H), 2.15–
2.10 (m, 2H), 1.99–1.96 (m, 2H). 13C NMR (CDCl3, 125 MHz) δ 146.7,
146.0, 142.2, 142.0, 137.3, 136.6, 130.4, 123.9, 122.1, 121.9, 120.4,
113.4, 109.7, 108.6, 105.4, 58.9, 56.0, 27.3, 23.4, 22.3, 20.9.
Benzo[4,5]imidazo[1,2-a]benzo[4,5]imidazo[1,2-c]quinazoline-13-
carbonitrile (3g).[11] Purified by TLC (dichloromethane/MeOH=99/
1, 2 times); white solid (56 mg, 56%); mp 313–316 C. 1H NMR
°
(CDCl3, 500 MHz) δ 8.81 (dd, J=7.9 and 1.4 Hz, 1H), 8.77-8.74 (m,
1H), 8.35 (d, J=8.4 Hz, 1H), 8.26 (d, J=8.6 Hz, 1H), 8.23 (d, J=
1.3 Hz, 1H), 8.01-7.98 (m, 1H), 7.88-7.85 (m, 1H), 7.74 (dd, J=8.6 and
1.5 Hz, 1H), 7.67-7.64 (m, 1H), 7.62–7.58 (m, 2H). 13C NMR (CDCl3,
125 MHz) δ 144.5, 144.1, 143.6, 142.8, 133.7, 133.1, 132.6, 130.5,
127.2, 126.7 (126.74), 126.7 (126.68), 126.1, 125.2, 124.5, 120.2,
115.3, 115.2, 115.1, 113.8, 108.1.
6-Methyl-7-phenylbenzo[4,5]imidazo[1,2-a]benzo[4,5]imidazo
[1,2-c]pyrimidine (3n).[12] Purified by TLC (dichloromethane/
MeOH=99/1); white solid (70 mg, 67%); mp 236–238 C. 1H NMR
°
(CDCl3, 500 MHz) δ 8.87-8.83 (m, 1H), 8.02-7.99 (m, 1H), 7.85 (d, J=
7.9 Hz, 1H), 7.74-7.67 (m, 3H), 7.59-7.54 (m, 4H), 7.32-7.29 (m, 1H),
6.92-6.89 (m, 1H), 5.92 (d, J=8.4 Hz, 1H), 2.39 (s, 3H). 13C NMR
(CDCl3, 125 MHz) δ 147.1, 144.2, 142.3, 142.1, 137.5, 131.8, 130.5,
129.9, 129.7 (129.72), 129.7 (129.70), 129.6, 125.4, 124.2, 123.9,
121.8, 119.6, 119.3, 115.0, 112.8, 109.4, 12.8.
Benzo[4,5]imidazo[1,2-c]naphtho[2’,3’:4,5]imidazo[1,2-a]
quinazoline (3h). Purified by TLC (dichloromethane/MeOH=99/1,
1
°
2 times); white solid (61 mg, 57%); mp 326–328 C. H NMR (CDCl3,
500 MHz) δ 8.88–8.86 (m, 1H), 8.80 (dd, J=7.9 and 1.5 Hz, 1H), 8.56
(s, 1H), 8.55 (d, J=9.9 Hz, 1H), 8.36 (s, 1H), 8.10-8.03 (m, 2H), 8.01-
7.99 (m, 1H), 7.93–7.89 (m, 1H), 7.62-7.56 (m, 3H), 7.55-7.51 (m, 2H).
13C NMR (CDCl3, 125 MHz) δ 145.0, 144.1, 143.7, 142.3, 134.5, 132.4,
6-Isopropyl-7-phenylbenzo[4,5]imidazo[1,2-a]benzo[4,5]imidazo
[1,2-c]pyrimidine (3o). Purified by TLC (dichloromethane/MeOH=
99/1); white solid (73 mg, 65%); mp 334–336 C. 1H NMR (CDCl3,
°
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500 MHz) δ 8.91-8.87 (m, 1H), 8.03-8.00 (m, 1H), 7.85 (d, J=8.0 Hz,
2-(2-Bromophenyl)-4,5-di(furan-2-yl)-1H-imidazole (4e). According
to the general procedure, the product 4e was obtained as a brown
H), 7.75–7.67 (m, 3H), 7.59–7.52 (m, 4H), 7.31–7.28 (m, 1H), 6.90-6.86
(m, 1H), 5.70 (d, J=8.4 Hz, 1H), 3.09 (sept, J=7.0 Hz, 1H), 1.56 (d,
J=7.0 Hz, 6H). 13C NMR (CDCl3, 125 MHz) δ 145.3, 144.2, 142.5,
142.3, 136.4, 132.3, 130.4, 129.7, 129.6, 129.2, 125.3, 124.1, 123.8,
121.7, 119.8, 119.7, 119.3, 118.7, 115.0, 112.8, 29.3, 21.1. HRMS (EI):
m/z [M+] calcd for C25H20N4 376.1688; found, 376.1685.
1
°
solid (0.710 g, 40%); mp 102–104 C. H NMR (DMSO-d6, 500 MHz) δ
12.87 (s, 1H), 7.81 (s, 1H), 7.78 (dd, J=6.5 and 0.6 Hz, 1H), 7.72 (s,
1H), 7.66 (dd, J=7.6 and 1.6 Hz, 1H), 7.53-7.49 (m, 1H), 7.44-7.40 (m,
1H), 6.94 (d, J=2.7 Hz, 1H), 6.73 (d, J=2.5 Hz, 1H), 6.65 (s, 1H), 6.58
(s, 1H). 13C NMR (DMSO-d6, 125 MHz) δ 149.3, 145.4, 144.4, 142.6,
141.8, 133.1, 132.0, 131.9, 130.9, 128.9, 127.6, 122.0, 119.0, 111.8,
111.4, 108.1, 106.8. HRMS (EI): m/z [M+] calcd for C17H11BrN2O2
354.0004; found, 354.0004.
6-Butyl-7-phenylbenzo[4,5]imidazo[1,2-a]benzo[4,5]imidazo[1,2-
c]pyrimidine (3p).[12] Purified by TLC (dichloromethane/MeOH=99/
1); white solid (70 mg, 60%); mp 210–212 C. 1H NMR (CDCl3,
°
500 MHz) δ 8.89-8.85 (m, 1H), 8.04-8.00 (m, 1H), 7.86 (d, J=8.0 Hz,
1H), 7.74-7.66 (m, 3H), 7.59-7.54 (m, 4H), 7.32-7.29 (m, 1H), 6.92-6.89
(m, 1H), 5.84 (d, J=8.4 Hz, 1H), 2.80-2.76 (m, 2H), 1.76-1.70 (m, 2H),
1.37-1.30 (m, 2H), 0.81 (t, J=7.4 Hz, 3H). 13C NMR (CDCl3, 125 MHz)
δ 146.6, 144.3, 142.4, 142.2, 137.4, 131.7, 130.5, 129.8 (129.85), 129.8
(129.80), 129.5, 125.3, 124.1, 123.8, 121.8, 119.7, 119.3, 115.0, 114.3,
112.8, 31.8, 26.9, 22.7, 13.8.
2-(2-Bromocyclohex-1-en-1-yl)-4,5-diphenyl-1H-imidazole
(4g).
According to the general procedure, the product 4g was obtained
1
°
as a white solid (1.157 g, 61%); mp 227–229 C. H NMR (DMSO-d6,
500 MHz) δ 12.23 (s, 1H), 7.49-7.18 (m, 10H), 2.65-2.63 (m, 2H), 2.57-
2.54 (m, 2H), 1.76-1.74 (m, 4H). 13C NMR (DMSO-d6, 125 MHz) δ
145.7, 136.0, 135.3, 131.0, 128.9, 128.6, 128.1, 128.0, 127.5, 127.1,
126.7, 126.4, 122.5, 36.9, 31.3, 24.0, 21.6. HRMS (EI): m/z [M+] calcd
for C21H19BrN2 378.0732; found, 378.0730.
6,7-Diphenylbenzo[4,5]imidazo[1,2-a]benzo[4,5]imidazo[1,2-c]
pyrimidine (3q).[11] Purified by TLC (dichloromethane/MeOH=99/
(Z)-2-(1-Bromo-1-phenylprop-1-en-2-yl)-4,5-diphenyl-1H-
1); white solid (78 mg, 63%); mp 280–281 C. 1H NMR (CDCl3,
imidazole (4h). According to the general procedure, the product
°
1
°
500 MHz) δ 8.91–8.89 (m, 1H), 7.97 (d, J=7.6 Hz, 1H), 7.79 (d, J=
8.0 Hz, 1H), 7.59-7.50 (m, 3H), 7.48-7.42 (m, 4H), 7.39-7.37 (m, 2H),
7.34–7.26 (m, 4H), 6.92–6.89 (m, 1H), 5.93 (d, J=8.4 Hz, 1H). 13C
NMR (CDCl3, 125 MHz) δ 146.6, 144.4, 142.6, 142.3, 138.4, 132.1,
131.4, 131.2, 130.4, 130.1, 130.0, 129.8, 129.0, 128.2, 128.0, 125.4,
124.4, 124.0, 121.9, 120.1, 119.4, 115.4, 114.9, 113.3.
4h was obtained as a white solid (0.851 g, 41%); mp 214–217 C. H
NMR (DMSO-d6, 500 MHz) δ 11.73 (s, 1H), 7.50-7.15 (m, 15H), 2.44 (s,
3H). 13C NMR (DMSO-d6, 125 MHz) δ 144.4, 140.4, 136.1, 134.9, 130.9,
129.4, 128.8, 128.6, 128.2, 128.0 (128.04), 128.0 (128.00), 127.8,
127.6, 127.0, 126.8, 126.4, 124.9, 24.0. HRMS (EI): m/z [M+] calcd for
C24H19BrN2 414.0732; found, 414.0729.
6,10,11-Trimethyl-7-phenylbenzo[4,5]imidazo[1,2-a]benzo[4,5]
imidazo[1,2-c]pyrimidine (3r). Purified by TLC (dichloromethane/
(Z)-2-(1-Bromo-3-methyl-1-phenylbut-1-en-2-yl)-4,5-diphenyl-1H-
imidazole (4i). According to the general procedure, the product 4i
1
MeOH=99/1); white solid (68 mg, 60%); mp >350 C. 1H NMR
was obtained as a white solid (0.510 g, 23%); mp 164–167 C. H
°
°
(CD2Cl2, 500 MHz) δ 8.80-8.79 (m, 1H), 7.95–7.93 (m, 1H), 7.75–768
(m, 3H), 7.59–7.55 (m, 4H), 7.32 (s, 1H), 5.65 (s, H), 2.35 (s, 3H), 2.32
(s, 3H), 2.02 (s, 3H). 13C NMR (CD2Cl2, 125 MHz) δ 144.8, 141.1, 139.5,
138.1, 133.5, 132.4, 131.0, 130.7, 130.5, 130.2, 129.9, 128.6, 125.5,
123.9, 119.8, 119.5, 115.2, 113.7, 109.2, 20.6, 20.4, 12.9. HRMS (EI):
m/z [M+] calcd for C25H20N4 376.1688; found, 376.1687.
NMR (DMSO-d6, 500 MHz) δ 11.81 (s, 1H), 7.43-7.41 (m, 2H), 7.33-
7.16 (m, 11H), 7.10-7.08 (m, 2H), 3.41 (sept, J=6.8 Hz, 1H), 1.18 (d,
J=6.9 Hz, 6H). 13C NMR (DMSO-d6, 125 MHz) δ 141.7, 140.1. 139.1,
135.9, 135.2, 131.0, 129.0, 128.5, 128.1, 127.9, 127.8, 127.6, 127.4,
126.9, 126.5, 126.3, 124.4, 35.4, 20.3. HRMS (EI): m/z [M+] calcd for
C26H23BrN2 442.1045; found, 442.1043.
10,11-Dichloro-6-methyl-7-phenylbenzo[4,5]imidazo[1,2-a]benzo
[4,5]imidazo[1,2-c]pyrimidine (3s). Purified by TLC (dichlorome-
(Z)-2-(1-Bromo-1-phenylhex-1-en-2-yl)-4,5-diphenyl-1H-imidazole
(4j). According to the general procedure, the product 4j was
1
1
°
°
thane/MeOH=99/1); white solid (85 mg, 68%); mp 278–280 C. H
obtained as a pale yellow solid (0.412 g, 18%); mp 140–142 C. H
NMR (CDCl3, 500 MHz) δ 8.76–8.74 (m, 1H), 8.00-7.99 (m, 1H), 7.90
(s, 1H), 7.78–7.71 (m, 3H), 7.59–7.57 (m, 2H), 7.54–7.52 (m, 2H), 5.89
(s, 1H), 2.40 (s, 3H). 13C NMR (CDCl3, 125 MHz) δ 146.7, 144.2, 143.3,
141.7, 136.8, 131.0 (130.97), 131.0 (130.95), 129.9, 129.8, 129.6,
128.7, 128.2, 125.8, 125.5, 124.4, 120.3, 119.9, 114.9, 114.3, 110.5,
12.8. HRMS (EI): m/z [M+] calcd for C23H14Cl2N4 416.0596; found,
416.0594.
NMR (DMSO-d6, 500 MHz) δ 11.75 (s, 1H), 7.45-7.11 (m, 15H), 2.89–
2.86 (m, 2H), 1.56–1.49 (m, 2H), 1.45-1.38 (m, 2H), 0.93 (t, J=7.3 Hz,
3H). 13C NMR (DMSO-d6, 125 MHz) δ 143.8, 140.4, 136.1, 135.0, 133.7,
130.9, 129.4, 128.6, 128.5, 128.0, 127.9, 127.7, 127.6, 126.9, 126.8,
126.3, 124.6, 36.9, 29.3, 21.8, 13.8. HRMS (EI): m/z [M+] calcd for
C27H25BrN2 456.1201; found, 456.1197.
(Z)-2-(2-Bromo-1,2-diphenylvinyl)-4,5-diphenyl-1H-imidazole (4k).
6-Methyl-7-phenylbenzo[4,5]imidazo[1,2-c]naphtho[2’,3’:4,5]
imidazo[1,2-a]pyrimidine (3t). Purified by TLC (dichloromethane/
According to the general procedure, the product 4k was obtained
1
°
as a white solid (0.382 g, 16%); mp 220–222 C. H NMR (DMSO-d6,
MeOH=99/1); white solid (77 mg, 64%); mp 336–338 C. 1H NMR
500 MHz) δ 12.71 (s, 1H), 7.51-7.47 (m, 4H), 7.43-7.40 (m, 2H), 7.36-
7.25 (m, 8H), 7.22-7.15 (m, 4H), 7.07-7.06 (m, 2H). 13C NMR (DMSO-
d6, 125 MHz) δ 146.6, 139.9, 138.5, 136.4, 135.1, 134.7, 130.9, 129.6
(129.63), 129.6 (129.55), 128.6 (128.63), 128.6 (128.55), 128.3, 128.1,
128.0 (128.03). 128.0 (127.98), 127.6, 127.5, 127.1, 126.9, 126.5,
125.6. HRMS (EI): m/z [M+] calcd for C29H21BrN2 476.0888; found,
476.0885.
°
(CDCl3, 500 MHz) δ 8.89-8.87 (m, 1H), 8.25 (s, 1H), 8.01-7.99 (m, 1H),
7.94 (d, J=8.2 Hz, 1H), 7.82-7.79 (m, 1H), 7.76-7.73 (m, 2H), 7.62-7.57
(m, 4H), 7.42-7.38 (m, 2H), 7.31-7.29 (m, 1H), 6.26 (s, 1H), 2.41 (s, 3H).
13C NMR (CDCl3, 125 MHz) δ 147.4, 144.6, 144.3, 142.0, 137.9, 131.8,
130.9, 130.6, 130.4, 130.1, 129.8, 129.7, 129.2, 128.1, 127.7, 125.6,
124.7, 124.1, 119.7, 115.7, 115.1, 110.1, 108.7, 12.8. HRMS (EI): m/z
[M+] calcd for C27H18N4 398.1531; found, 398.1533.
General procedure for the synthesis of 5: To a 10 mL microwave
reaction tube was added 4 (0.3 mmol), 2 (0.45 mmol), CsF (0.137 g,
0.9 mmol), and DMF (3 mL). After stirring the reaction mixture at
General procedure for the synthesis of 4: To a 50 mL round-
bottomed flask was added aldehyde (5 mmol), benzil or furil
(5 mmol), NH4OAc (20 mmol), acetic acid (1.5 mL), and ethyl alcohol
(15 mL). The mixture was refluxed for 20 h, then the solvents were
evaporated under reduced pressure to obtain the solid which was
washed with water (3 times) and crystallized (DCM/hexane) to give
4.[20] All new compounds were characterized spectroscopically as
shown below.
°
room temperature for 5 min, it was heated at 150 C for 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
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1
°
was purified by TLC (dichloromethane/MeOH=200/1) to give 5. All
products were characterized spectroscopically as shown below.
1); pale brown solid (85 mg, 73%); mp 245–247 C. H NMR (CDCl3,
500 MHz) δ 8.74 (dd, J=7.9 and 1.0 Hz, 1H), 8.34 (d, J=8.4 Hz, 1H),
8.14–8.12 (m, 1H), 7.79–7.71 (m, 3H), 7.54-7.51 (m, 2H), 7.41–7.37
(m, 2H), 6.91 (d, J=3.2 Hz, 1H), 6.72–6.71 (m, 1H), 6.58 (d, J=3.3 Hz,
1H), 6.45–6.46 (m, H). 13C NMR (CDCl3, 125 MHz) δ 147.7, 143.9,
142.9, 142.2, 142.1, 141.2, 140.5, 137.6, 133.1, 131.1, 130.3, 125.9,
125.3, 124.2, 123.3, 120.9, 114.8, 114.7, 114.5, 114.2, 112.8, 111.4,
111.3,108.9. HRMS (EI): m/z [M+] calcd for C24H14N4O2 390.1117;
found, 390.1118.
1,2-Diphenylbenzo[4,5]imidazo[1,2-a]imidazo[1,2-c]quinazoline
(5a).[11] Purified by TLC (dichloromethane/MeOH=200/1); white
1
°
solid (96 mg, 78%); mp 289–291 C. H NMR (CDCl3, 500 MHz) δ 8.78
(dd, J=7.9 and 1.5 Hz, 1H), 8.42 (d, J=8.4 Hz, 1H), 8.20 (d, J=
7.8 Hz, 1H), 7.78-7.74 (m, 1H), 7.67-7.50 (m, 9H), 7.44-7.36 (m, 2H),
7.32-7.27 (m, 3H). 13C NMR (CDCl3, 125 MHz) δ 142.1, 133.5, 132.8,
132.1, 130.5 (130.48), 130.5 (130.45), 130.2, 130.0, 128.9, 128.3,
128.1, 128.0, 127.5, 125.5, 125.3, 124.0, 123.2, 120.8, 116.8, 116.6,
115.2, 114.8, 112.8.
1,2-Diphenyl-4,5,6,7-tetrahydrobenzo[4,5]imidazo[1,2-a]imidazo
[1,2-c]quinazoline (5i). Purified by TLC (dichloromethane/MeOH=
1
°
200/1); white solid (81 mg, 65%); mp 290–292 C. H NMR (CDCl3,
6-Methyl-1,2-diphenylbenzo[4,5]imidazo[1,2-a]imidazo[1,2-c]
quinazoline (5b). Purified by TLC (dichloromethane/MeOH=200/
500 MHz) δ 7.94 (d, J=8.3 Hz, 1H), 7.63-7.61 (m, 1H), 7.59–7.57 (m,
4H), 7.51–7.46 (m, 3H), 7.33–7.30 (m, 1H), 7.28–7.21 (m, 4H), 3.41-
3.39 (m, 2H), 3.15-3.12 (m, 2H), 2.15–2.10 (m, 2H), 2.01–1.97 (m, 2H).
13C NMR (CDCl3, 125 MHz) δ 142.8, 142.0, 141.8, 141.6, 133.9, 133.8,
132.1, 130.1, 129.8, 128.6, 128.2, 128.0, 127.3, 124.3, 123.7, 121.8,
120.4, 113.4, 109.7, 27.0, 23.1, 22.4, 21.1. HRMS (EI): m/z [M+] calcd
for C28H22N4 438.1844; found, 414.1843.
1); white solid (75 mg, 59%); mp 268–270 C. 1H NMR (CD2Cl2,
°
500 MHz) δ 8.60 (d, J=8.1 Hz, 1H), 8.27 (d, J=9.3 Hz, 1H), 8.26 (s,
1H), 7.62–7.51 (m, 8H), 7.47–7.38 (m, 3H), 7.30–7.24 (m, 3H), 2.67 (s,
3H). 13C NMR (CD2Cl2, 125 MHz) δ 142.4, 142.2, 142.1, 142.0, 141.4,
134.3, 133.3, 132.5, 130.9, 130.7, 129.2, 128.6, 128.5, 128.3, 127.8,
127.0, 125.7, 125.4, 124.4, 123.4, 120.5, 115.6, 113.5, 113.2, 22.5.
HRMS (EI): m/z [M+] calcd for C29H20N4 424.1688; found, 424.1686.
4-Methyl-1,2,5-triphenylbenzo[4,5]imidazo[1,2-a]imidazo[1,2-c]
pyrimidine (5j). Purified by TLC (dichloromethane/MeOH=200/1);
5-Methoxy-1,2-diphenylbenzo[4,5]imidazo[1,2-a]imidazo[1,2-c]
1
°
white solid (89 mg, 66%); mp 200–202 C. H NMR (CDCl3, 500 MHz)
quinazoline (5c). Purified by TLC (dichloromethane/MeOH=200/1);
δ 7.70-7.60 (m, 7H), 7.56–7.48 (m, 6H), 7.30-7.22 (m, 3H), 7.20–7.17
(m, 1H), 6.86–6.83 (m, 1H), 5.90 (d, J=8.4 Hz, 1H), 2.40 (s, 3H). 13C
NMR (CDCl3, 125 MHz) δ 143.3, 142.4, 134.0, 133.9, 132.2, 132.1,
130.2, 130.1, 130.0, 129.5 (129.53), 129.5 (129.51), 128.7, 128.3,
128.2, 128.0, 127.4, 124.9, 123.6, 121.5, 120.0, 112.8, 109.7, 12.7.
HRMS (EI): m/z [M+] calcd for C31H22N4 450.1844; found, 450.1846.
1
°
white solid (81 mg, 61%); mp 272–274 C. H NMR (CDCl3, 500 MHz)
δ 8.33 (d, J=9.2 Hz, 1H), 8.21 (d, J=2.9 Hz, 1H), 8.15 (d, J=7.8 Hz,
1H), 7.65–7.61 (m, 5H), 7.54–7.49 (m, 3H), 7.41–7.26 (m, 6H), 4.05 (s,
3H). 13C NMR (CDCl3, 125 MHz) δ 157.0, 142.1, 140.7, 133.6, 132.1,
130.1, 130.0, 128.9, 128.3, 128.1 (128.12), 128.1 (128.07), 127.5,
127.0, 125.9, 123.7, 122.9, 120.8, 119.1, 116.3, 112.5, 107.1, 56.1.
HRMS (EI): m/z [M+] calcd for C29H20N4O 440.1637; found, 440.1637.
4-Isopropyl-1,2,5-triphenylbenzo[4,5]imidazo[1,2-a]imidazo[1,2-c]
pyrimidine (5k). Purified by TLC (dichloromethane/MeOH=200/1);
5-Fluoro-1,2-diphenylbenzo[4,5]imidazo[1,2-a]imidazo[1,2-c]
quinazoline (5d). Purified by TLC (dichloromethane/MeOH=200/
1
°
white solid (96 mg, 67%); mp 284–286 C. H NMR (CDCl3, 500 MHz)
δ 7.71-7.63 (m, 7H), 7.59-7.46 (m, 6H), 7.32-7.21 (m, 3H), 7.17-7.13
(m, 1H), 6.81-6.78 (m, 1H), 5.67 (d, J=8.4 Hz, 1H), 3.04 (sept, J=
7.0 Hz, 1H), 1.59 (d, J=7.1 Hz, 6H). 13C NMR (CDCl3, 125 MHz) δ
141.8, 141.7, 141.6, 141.4, 134.1, 132.9, 132.6, 132.2, 130.5, 130.2,
130.0, 129.7, 129.6, 128.7, 128.1 (128.15), 128.1 (128.08), 128.0,
127.3, 123.8, 123.5, 121.4, 119.9, 118.9, 112.8, 29.3, 21.3. HRMS (EI):
m/z [M+] calcd for C33H26N4 478.2157; found, 478.2155.
1); white solid (90 mg, 70%); mp 300–302 C. 1H NMR (CDCl3,
°
500 MHz) δ 8.45 (dd, J=8.5 and 2.9 Hz, 1H), 8.38 (dd, J=9.2 and
4.2 Hz, 1H), 8.12 (d, J=8.2 Hz, 1H), 7.67–7.60 (m, 5H), 7.57-7.50 (m,
3H), 7.48–7.38 (m, 3H), 7.34–7.27 (m, 3H). 13C NMR (CDCl3, 125 MHz)
1
δ 159.7 (d, JC-F =244.7 Hz), 142.4, 142.0, 141.0, 139.9, 133.2, 132.0,
130.0, 129.8, 129.3, 129.0, 128.3, 128.2, 128.0, 127.7, 126.2, 124.1,
4
3
123.3, 121.0, 117.9, 117.7 (d, JC-F =3.9 Hz), 116.6 (d, JC-F =8.3 Hz),
112.4, 111.5 (d, 2JC-F =25.0 Hz). HRMS (EI): m/z [M+] calcd for
C28H17FN4 428.1437; found, 428.1433.
4-Butyl-1,2,5-triphenylbenzo[4,5]imidazo[1,2-a]imidazo[1,2-c]
pyrimidine (5l). Purified by TLC (dichloromethane/MeOH=200/1);
1
°
white solid (90 mg, 61%); mp 227–229 C. H NMR (CDCl3, 500 MHz)
10,11-Dimethyl-1,2-diphenylbenzo[4,5]imidazo[1,2-a]imidazo[1,2-
c]quinazoline (5e). Purified by TLC (dichloromethane/MeOH=200/
δ 7.71–7.62 (m, 7H), 7.55–7.49 (m, 6H), 7.30-7.22 (m, 3H), 7.19-7.15
(m, 1H), 6.85-6.81 (m, 1H), 5.80 (d, J=8.4 Hz, 1H), 2.79–2.76 (m, 2H),
1.81-1.75 (m, 2H), 1.39-1.32 (m, 2H), 0.86 (t, J=7.4 Hz, 3H). 13C NMR
(CDCl3, 125 MHz) δ 142.8, 142.3, 141.7, 141.6, 134.0, 133.9, 132.2,
132.0, 130.2 (130.22), 130.2 (130.20), 129.6, 129.4, 128.7, 128.2
(128.20), 128.2 (128.17), 128.0, 127.4, 124.5, 123.6, 121.4, 119.9,
114.5, 112.8, 32.0, 26.7, 22.7, 13.8. HRMS (EI): m/z [M+] calcd for
C34H28N4 492.2314; found, 492.2316.
1); white solid (84 mg, 64%); mp 310–312 C. 1H NMR (CDCl3,
°
500 MHz) δ 8.76 (dd, J=7.9 and 1.5 Hz, 1H), 8.38 (d, J=8.4 Hz, 1H),
7.94 (s, 1H), 7.76-7.73 (m, 1H), 7.64–7.59 (m, 4H), 7.56-7.42 (m, 4H),
7.30–7.22 (m, 3H), 2.49 (s, 3H), 2.36 (s, 3H). 13C NMR (CDCl3,
125 MHz) δ 141.9, 140.7, 140.5, 133.7, 133.2, 132.9 (132.95), 132.9
(132.91), 132.1, 130.3, 130.1, 129.3, 128.9, 128.8, 128.3, 128.1, 128.0,
127.4, 125.6, 125.4, 125.0, 121.0, 115.1, 114.7, 113.2, 20.9, 20.1.
HRMS (EI): m/z [M+] calcd for C30H22N4 438.1844; found, 438.1847.
1,2,4,5-Tetraphenylbenzo[4,5]imidazo[1,2-a]imidazo[1,2-c]
pyrimidine (5m). Purified by TLC (dichloromethane/MeOH=200/1);
10,11-Dichloro-1,2-diphenylbenzo[4,5]imidazo[1,2-a]imidazo[1,2-
c]quinazoline (5f). Purified by TLC (dichloromethane/MeOH=200/
1
°
white solid (88 mg, 57%); mp 308–309 C. H NMR (CDCl3, 500 MHz)
δ 7.68-7.65 (m, 2H), 7.58–7.48 (m, 7H), 7.46–7.39 (m, 6H), 7.30–7.18
(m, 7H), 6.87-6.84 (m, 1H), 5.90 (d, J=8.4 Hz, 1H). 13C NMR (CDCl3,
125 MHz) δ 142.9, 142.7, 142.0, 141.7, 134.8, 133.7, 132.4, 132.2,
131.7, 131.5, 130.8, 130.1, 129.9, 129.8, 128.9, 128.8, 128.2, 128.1
(128.08), 128.1 (128.06), 127.8, 127.6, 127.4, 124.7, 123.9, 121.6,
120.1, 115.6, 113.3. HRMS (EI): m/z [M+] calcd for C36H24N4 512.2001;
found, 512.2000.
1); white solid (83 mg, 58%); mp 304–306 C. 1H NMR (CDCl3,
°
500 MHz) δ 8.78 (dd, J=7.9 and 1.4 Hz, 1H), 8.29 (s, 1H), 8.23 (d, J=
8.4 Hz, 1H), 7.80–7.76 (m, 1H), 7.74 (s, 1H), 7.65–7.49 (m, 8H), 7.31-
7.26 (m, 3H). 13C NMR (CDCl3, 125 MHz) δ 142.6, 142.3, 141.6, 140.5,
133.2, 132.1, 132.0, 130.7, 129.7, 129.3, 129.2, 129.1, 128.3, 128.2
(128.25), 128.2 (128.17), 127.9, 127.7, 126.8, 126.0, 125.7, 121.7,
115.3, 114.5, 114.2. HRMS (EI): m/z [M+] calcd for C28H16Cl2N4
478.0752; found, 478.0750.
4,8,9-Trimethyl-1,2,5-triphenylbenzo[4,5]imidazo[1,2-a]imidazo
[1,2-c]pyrimidine (5n). Purified by TLC (dichloromethane/MeOH=
1,2-Di(furan-2-yl)benzo[4,5]imidazo[1,2-a]imidazo[1,2-c]
quinazoline (5g). Purified by TLC (dichloromethane/MeOH=200/
1
°
200/1); white solid (76 mg, 53%); mp 283–285 C. H NMR (CDCl3,
500 MHz) δ 7.68-7.60 (m, 7H), 7.52–7.47 (m, 5H), 7.32 (s, 1H), 7.29–
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7.22 (m, 3H), 5.59 (s, 1H), 2.40 (s, 3H), 2.22 (s, 3H), 2.01 (s, 3H). 13C
1-(2-(1H-Benzo[d]imidazol-2-yl)phenyl)-2-methoxy-1H-naphtho
[2,3-d]imidazole (12). Purified by TLC (dichloromethane/MeOH=
NMR (CDCl3, 125 MHz) δ 142.3, 141.1, 140.1, 134.1, 134.0, 132.6,
132.4, 132.2, 130.2, 130.1, 130.0, 129.6, 129.4, 128.8, 128.6, 128.2,
128.0, 127.8, 127.3, 124.7, 120.0, 113.2, 109.0, 20.6, 20.0, 12.6. HRMS
(EI): m/z [M+] calcd for C33H26N4 478.2157; found, 478.2155.
1
°
99/1, 2 times); pale yellow solid (28 mg, 24%); mp 229–231 C. H
NMR (DMSO-d6, 500 MHz) δ 12.74 (br s, 1H), 7.90–7.88 (m, 2H), 7.83–
7.75 (m, 3H), 7.71–7.63 (m, 2H), 7.57–7.54 (m, 2H), 7.48-7.45 (m, 1H),
7.33–7.20 (m, 4H), 4.13 (s, 3H). 13C NMR (DMSO-d6, 125 MHz) δ161.9,
156.2, 150.4, 143.2, 134.5, 133.4, 132.4, 132.2, 131.3, 131.1, 129.3,
129.2, 127.8, 127.4, 126.8, 123.2, 122.6, 121.5, 119.1, 111.6, 103.6,
56.8. HRMS (EI): m/z [M+] calcd for C25H18N4 390.1481; found,
390.1485.
8,9-Dichloro-4-methyl-1,2,5-triphenylbenzo[4,5]imidazo[1,2-a]
imidazo[1,2-c]pyrimidine (5o). Purified by TLC (dichloromethane/
1
°
MeOH=200/1); white solid (79 mg, 51%); mp 290–292 C. H NMR
(CDCl3, 500 MHz) δ 7.75-7.67 (m, 3H), 7.65 (s, 1H), 7.64-7.58 (m, 4H),
7.56–7.48 (m, 5H), 7.30–7.23 (m, 3H), 5.87 (s, 1H), 2.41 (s, 3H). 13C
NMR (CDCl3, 125 MHz) δ 142.9, 141.2, 133.7, 133.6, 132.2, 131.4,
130.8, 130.1 (130.08), 130.1 (130.07), 130.0, 129.8, 129.1, 128.6,
128.5, 128.4, 128.3, 128.0, 127.8, 125.2, 125.1, 121.0, 114.5, 114.4,
110.9, 12.8. HRMS (EI): m/z [M+] calcd for C31H20Cl2N4 518.1065;
found, 518.1063.
Acknowledgements
This work was supported by the National Research Foundation of
Korea (NRF) grant funded by the Korea government (Ministry of
Science and ICT) (2020R1F1A1054806).
4-Methyl-1,2,5-triphenylimidazo[1,2-c]naphtho[2’,3’:4,5]imidazo
[1,2-a]pyrimidine (5p). Purified by TLC (dichloromethane/MeOH=
200/1); pale yellow solid (102 mg, 68%); mp 244–246 C. 1H NMR
°
(CDCl3, 500 MHz) δ 7.98 (s, 1H), 7.82 (d, J=8.2 Hz, 1H), 7.78–7.75 (m,
1H), 7.72-7.69 (m, 2H), 7.67–7.63 (m 4H), 7.58–7.51 (m, 5H), 7.40 (d,
J=8.3 Hz, 1H), 7.34–7.23 (m, 5H), 6.25 (s, 1H), 2.43 (s, 3H). 13C NMR
(CDCl3, 125 MHz) δ 144.2, 143.8, 142.6, 141.5, 134.5, 133.7, 132.2
(132.22), 132.2 (132.15), 130.7, 130.3 (130.34), 130.3 (130.26), 130.2,
130.0, 129.6, 129.0, 128.8, 128.3, 128.2, 128.1, 127.6, 127.5, 125.1,
124.3, 123.8, 116.3, 110.0, 109.0, 12.6. HRMS (EI): m/z [M+] calcd for
C35H24N4 500.2001; found, 500.1998.
Conflict of Interest
The authors declare no conflict of interest.
Keywords: Aromatic substitution · Cross-coupling · Microwave
chemistry · Nucleophilic substitution · Nitrogen heterocycles
General procedure for a cascade reaction: To a 10 mL microwave
reaction tube was added
6 (0.093 g, 0.5 mmol), 7 (0.105 g,
0.5 mmol), NH4OAc (0.193 g, 1.5 mmol), acetic acid (0.5 mL), and
ethyl alcohol (5 mL). After stirring the reaction mixture at room
[1] For reviews, see: a) A. F. Pozharskii, A. T. Soldatenkov, A. R. Katritzky,
Heterocycles in Life and Society: An Introduction to Heterocyclic Chemistry,
Biochemistry and Applications, John Wiley & Sons, West Sussex, 2011;
b) T. Eicher, S. Hauptmann, A. Speicher, The Chemistry of Heterocycles:
Structure, Reactions, Synthesis, and Applications, Wiley-VHC, Weinheim,
2012; c) X.-X. Guo, D.-W. Gu, Z. Wu, W. Zhang, Chem. Rev. 2015, 115,
1622–1651; d) S. K. Manna, T. Das, S. Samanta, ChemistrySelect 2019, 4,
8781–8790.
°
temperature for 5 min, it was heated at 70 C for 1 h under
microwave irradiation (100 W of initial power) followed by removal
of solvent, washing with water and drying under vacuum produced
a white precipitate. Then, 2a (0.111 g, 0.75 mmol), CsF (0.228 g,
1.5 mmol), and DMF (3 mL) to the microwave reaction tube
containing a white precipitate and continued reaction under
°
microwave irradiation (100 W of initial power) at 150 C for 2 h. The
[2] For reviews on Buchwald-Hartwig coupling, see: a) P. Ruiz-Castillo, S. L.
Buchwald, Chem. Rev. 2016, 116, 12564–12649; b) A. Biffis, P. Centomo,
A. D. Zotto, M. Zecca, Chem. Rev. 2018, 118, 2249–2295; c) M. M. Heravi,
Z. Kheilkordi, V. Zadsirjan, M. Heydari, J. Organomet. Chem. 2018, 861,
17–104; d) P. A. Forero-Cortés, A. M. Haydl, Org. Process Res. Dev. 2019,
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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 (dichloromethane/
MeOH=200/1) to afford 5a (0.121 g, 59%).
General procedure for mechanism studies for the isolation of a C-
N
coupled intermediate: 1a (0.082 g, 0.3 mmol), 2c or 2f
(0.45 mmol), CsF (0.137 g, 0.9 mmol), and DMF (3 mL) were added
to a 5 mL microwave reaction tube. After stirring the reaction
°
mixture at room temperature for 5 min, it was heated at 150 C for
30 min 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 (dichloromethane/
MeOH=99/1) to give 11, 12.
1-(2-(1H-Benzo[d]imidazol-2-yl)phenyl)-5,6-dichloro-2-methoxy-
1H-benzo[d]imidazole (11). Purified by TLC (dichloromethane/
MeOH=99/1, 2 times); pale yellow solid (14 mg, 11%); mp 248–
1
°
251 C. H NMR (DMSO-d6, 500 MHz) δ 12.71 (br s, 1H), 7.82 (dd, J=
8.0 and 1.1 Hz, 1H), 7.76 (dd, J=7.7 and 1.7 Hz, 1H), 7.72–7.51 (m,
5H), 7.48-7.45 (m, 1H), 7.24–7.23 (m 2H), 4.06 (s, 3H). 13C NMR
(CDCl3:MeOD-d4 (15:1), 125 MHz) δ 160.4, 150.5, 134.0, 133.8, 132.5,
131.4, 131.3, 127.9, 123.6, 122.7, 121.4, 119.4, 118.4, 111.4, 57.2.
HRMS (EI): m/z [M+] calcd for C21H14Cl2N4O 408.0545; found,
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Eur. J. Org. Chem. 2021, 1–12
www.eurjoc.org
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© 2021 Wiley-VCH GmbH
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Full Papers
doi.org/10.1002/ejoc.202100419
Dao, H. K. Lee, H.-S. Sohn, N. S. Yoon, C. S. Cho, ACS Omega 2017, 2,
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Manuscript received: April 7, 2021
Revised manuscript received: May 20, 2021
Accepted manuscript online: May 24, 2021
Eur. J. Org. Chem. 2021, 1–12
www.eurjoc.org
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© 2021 Wiley-VCH GmbH
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These are not the final page numbers!

FULL PAPERS
Dr. P. D. Q. Dao, Prof. C. S. Cho*
1 – 12
Synthesis of Trinuclear Benzimida-
zole-Fused Hybrid Scaffolds by
Transition Metal-Free Tandem
C(sp2)À N Bond Formation under
Microwave Irradiation
A class of trinuclear N-fused hybrid
scaffolds was constructed by transi-
tion metal-free C(sp2)-N coupling and
cyclization of 2-(2-bromoaryl)- or 2-(2-
bromovinyl)benzimidazoles with 2-
methoxy- or 2-aryloxybenzimidazoles
under microwave irradiation.