Synthesis of Binuclear Isoquinoline- and Pyridine-Fused Benzimidazole-4,7-diones by Magnetic MOF-199-Catalyzed C–C Coupling/Cyclization Followed by Oxidation

Article abstract of DOI:10.1002/ejoc.201900635

2-(2-bromoaryl)-4,7-dimethoxy-1H-benzo[d]imidazoles and (Z)-2-(2-bromovinyl)-4,7-dimethoxy-1H-benzo[d]imidazoles react with 1,3-diketones by microwave irradiation in DMF in the presence of a catalytic amount of recyclable Fe₃O₄@SiO₂@MOF-199 along with a base to give binuclear isoquinoline- and pyridine-fused benzimidazoles, respectively. Treatment of such binuclear N-fused hybrid scaffolds with ceric ammonium nitrate in acetonitrile/H₂O or HBr/FeCl₃ in H₂O affords binuclear isoquinoline- and pyridine-fused benzimidazole-4,7-diones in good to high yields.

Full text of DOI:10.1002/ejoc.201900635

A Journal of
Accepted Article
Title: Synthesis of Binuclear Isoquinoline– and Pyridine–Fused
Benzimidazole–4,7–diones by Magnetic MOF-199-Catalyzed C–C
Coupling/Cyclization Followed by Oxidation
Authors: Thi Duyen Diep, Pham Duy Quang Dao, and chan sik Cho
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201900635
Link to VoR: http://dx.doi.org/10.1002/ejoc.201900635
Supported by

10.1002/ejoc.201900635
European Journal of Organic Chemistry
FULL PAPER
Synthesis of Binuclear Isoquinoline– and Pyridine–Fused
Benzimidazole–4,7–diones by Magnetic MOF-199-Catalyzed C–C
Coupling/Cyclization Followed by Oxidation
Thi Duyen Diep,[a] Pham Duy Quang Dao,[a] and Chan Sik Cho*[a]
Abstract: 2–(2–Bromoaryl)–4,7–dimethoxy–1H–benzo[d]imidazoles
and (Z)–2–(2–bromovinyl)–4,7–dimethoxy–1H–benzo[d]imidazoles
react with 1,3-diketones by microwave irradiation in DMF in the
presence of a catalytic amount of recyclable Fe3O4@SiO2@MOF–
199 along with a base to give binuclear isoquinoline– and pyridine–
fused benzimidazoles, respectively. Treatment of such binuclear N–
fused hybrid scaffolds with ceric ammonium nitrate in acetonitrile–
H2O or HBr/FeCl3 in H2O affords binuclear isoquinoline– and
pyridine–fused benzimidazole–4,7–diones in good to high yields.
the extension of such a coupling and cyclocondensation reaction
to develop binuclear N–fused hybrid scaffolds,
benzo[4,5]imidazo[2,1–a]isoquinoline–8,11–diones (Scheme 1,
C) and benzo[4,5]imidazo[1,2–a]pyridine–6,9–diones (Scheme 1,
D). This report describes the synthesis of binuclear N–fused
hybrid scaffolds (Scheme 1, C and D) by initial core-shell
magnetic
(Fe3O4@SiO2@MOF-199)–catalyzed coupling and cyclization of
2–(2–bromoaryl)–4,7–dimethoxy–1H–benzo[d]imidazoles and
metal
organic
framework
MOF-199
(Z)–2–(2–bromovinyl)–4,7–dimethoxy–1H–benzo[d]imidazoles
with 1,3–diketones to produce binuclear N–fused hybrid
scaffolds (Scheme 1, A’ and B’) followed by oxidation. The core-
shell magnetic MOF-199 can be synthesized easily by the
reaction of magnetic nanoparticle Fe3O4@SiO2 core with
Cu(OH)2 shell as copper source followed by the treatment of
benzene tricarboxylic acid according to the reported method.[12]
MOF-199 has been used as a copper surrogate for several
organic transformations, whereas no reports are found for such
transformations with the core-shell magnetic MOF-199.[13] We
present here first application of the magnetic MOF-199 to C-C
bond formation with recyclability.
Introduction
Besides homonuclear N–heterocyclic compounds, binuclear N–
fused hybrid scaffolds have been received a considerable
interest due to characteristic biological activities and optical
properties that are not shown in each homonuclear N–
heterocyclic compound.[1] In connection with this report, many
synthetic methods and biological activities of isoquinoline– or
pyridine–containing compounds are well studied and
documented.[2,3] It is also known that a class of homonuclear
benzimidazole–based 1,4–quinones (1H–benzo[d]imidazole–
4,7–diones) exhibit a wide range of biological activities, such as
cytotoxic, antitumor, anticancer, and antiproliferative activities
and apply to the development of bioreductive quinone–based
drugs.[4,5] However, except for one report for the synthesis of
pyridine-fused benzimidazole–4,7–diones (Scheme 1, D),[6] no
reports are found for the synthetic route and biological activity of
Scheme 1. Binuclear N–fused hybrid scaffolds.
binuclear
isoquinoline–fused
benzimidazole–4,7–diones
(Scheme 1, C). During the course of our efforts directed toward
transition metal–catalyzed and transition metal–free cyclization
reactions,[7] we recently focused on developing new synthetic
methods for binuclear and trinuclear N–fused hybrid scaffolds.[8]
Among them, it is reported that 2–(2–bromoaryl)benzimidazoles
and 2–(2–bromovinyl)benzimidazoles are found to be coupled
and cyclized with 1,3–diketones in the presence of CuI to give
benzo[4,5]imidazo[2,1–a]isoquinolines (Scheme 1, A) and
Results and Discussion
The reaction conditions were optimized with 2–(2–
bromophenyl)–4,7–dimethoxy–1H–benzo[d]imidazole (1a) and
1,3–diphenylpropane–1,3–dione (2a) as model substrates to get
precursors (Scheme 1, A’ and B’) of binuclear N–fused hybrid
scaffolds (Scheme 1, C and D) effectively, and representative
results are summarized in Table 1. Treatment of 1a with 2a
under similar conditions used for the synthesis of binuclear N–
fused hybrid scaffolds (Scheme 1, A and B) afforded 8,11–
dimethoxy–6–phenylbenzo[4,5]imidazo[2,1–a]isoquinoline (3a)
in 42% isolated yield with 67% conversion (Table 1, entry 1).
When 1a was treated with equimolar amount of 2a at 120 oC for
1 h in the presence of Fe3O4@SiO2@MOF–199 (5 mol%) along
with Cs2CO3 under microwave irradiation (100 W of initial power),
3a was produced in 80% yield with complete conversion of 1a
(Table 1, entry 2).[12] The yield of 3a was not significantly
affected by the molar ratio of [2a]/[1a] (Table 1, entries 2–4).
benzo[4,5]imidazo[1,2–a]pyridines
(Scheme
1,
B),
respectively.[9-11] The present study started during the course of
[a]
Thi Duyen Diep
Pham Duy Quang Dao
Professor, Chan Sik Cho
Department of Applied Chemistry
Kyungpook National University
80 Daehakro, Bukgu, Daegu 41566, Republic of Korea
E-mail: cscho@knu.ac.kr
Supporting information for this article is given via a link at the end of
the document.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900635
European Journal of Organic Chemistry
FULL PAPER
Table 1. Optimization of conditions for the reaction of 1a with 2a.[a]
Table 2. Scope of reaction.[a]
Entry
[2a]/ Cu catalyst
[1a]
Base
Temp
(oC)
Time
(h)
Yield
[b]
1[c]
2
1.5
1
CuI
K3PO4
130
24
1
42
80
77
77
44
69
38
53
55
46
44
74
Fe3O4@SiO2@MOF-199 Cs2CO3 120
Fe3O4@SiO2@MOF-199 Cs2CO3 120
Fe3O4@SiO2@MOF-199 Cs2CO3 120
Fe3O4@SiO2@MOF-199 Cs2CO3 100
Fe3O4@SiO2@MOF-199 Cs2CO3 100
Fe3O4@SiO2@MOF-199 Cs2CO3 150
3
1.5
2
1
4
1
5
1.5
1.5
1.5
1
1
6
2.5
1
7
8
Fe3O4@SiO2@MOF-199 K2CO3
Fe3O4@SiO2@MOF-199 K3PO4
120
120
1
9
1
1
10
11
12
1
Fe3O4@SiO2@MOF-199 NaOtBu 120
Fe3O4@SiO2@MOF-199 NaOAc 120
1
1
1
1
Fe3O4@SiO2@MOF-199 CsF
120
1
[a]
All reactions were carried out with 1a (0.3 mmol), Cu catalyst (0.015
mmol), base (0.6 mmol), and DMF (3 mL) under microwave irradiation (100
[b]
[c]
W of initial power) unless otherwise stated.
mmol) under usual heating (screw-capped vial).
Isolated yield.
CuI (0.03
Lower reaction temperature resulted in lower yield of 3a with
incomplete conversion of 1a (Table 1, entries 5 and 6).
Performing the reaction at higher reaction temperature gave
rather lower yield of 3a with several unidentifiable side products
(Table 1, entry 7). Other bases such as K2CO3, K3PO4, NaOtBu,
and NaOAc can be used in place of Cs2CO3, but the yields of 3a
were lower than that obtained with Cs2CO3 (Table 1, entries 2
and 8–11). CsF showed similar activity as Cs2CO3 for the
present reaction (Table 1, entry 12).[14] The catalytic system
using Fe3O4@SiO2@MOF–199 could be recovered and reused
3 times without any significant loss of catalytic activity, the yield
of 3a being observed from 80% (1st reuse), 77% (2nd reuse), to
75% (3rd reuse).
Table 2 shows the representative results for the coupling and
cyclocondensation of various 2–(2–bromoaryl)–4,7–dimethoxy–
1H–benzo[d]imidazoles
and
(Z)–2–(2–bromovinyl)–4,7–
dimethoxy–1H–benzo[d]imidazoles 1a–i with 1,3-diketones 2a–k
under the optimized conditions (entry 2 of Table 1). The startings
1a–i were synthesized by the reaction between the
corresponding aldehydes and 3,6-dimethoxybenzene-1,2-
diamine using NaHSO3.[15] 2-(2-Bromophenyl)–4,7–dimethoxy–
1H–benzo[d]imidazole (1a) reacted with various 1,3-
diarylpropane-1,3-diones 2b–f having electron-donating and
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900635
European Journal of Organic Chemistry
FULL PAPER
cyclocondensation is also exemplified by copper-catalyzed
cyclization reactions of aryl and vinyl halides with 1,3-dicarbonyl
compounds.[8d,9,17] We confirmed that a similar treatment of 1a
with 2a using MOF-199, [Cu3(BTC)2(H2O)3]n (BTC = benzene-
1,3,5-tricarboxylate) in place of Fe3O4@SiO2@MOF-199 under
the conditions of entry 2 of Table 1 afforded 3a in 74% yield.
However, 3a was not formed at all in the presence of Fe3O4 or
Fe3O4@SiO2. It is known that Cu2 dimeric units in MOF-199 are
coordinated by four carboxylate ions as paddle-wheel and two
water molecules in axial positions.[18] The catalytic activity for the
present reaction seems to be shown by dissociation of such
axial water molecules in DMF. X-ray diffraction (XRD)
experiments with the fresh and reused (after third run)
Fe3O4@SiO2@MOF-199 showed that the crystallinity of the
catalyst was kept unchanged during the course of the reaction
(Figure 1). We recently reported that MOF-199 catalyzes C-C
coupling between β-bromo-α,β-unsaturated carboxylic acids and
terminal alkynes.[19]
[a]
All reactions were carried out with 1 (0.3 mmol), 2 (0.3 mmol),
Fe3O4@SiO2@MOF-199 (0.015 mmol), Cs2CO3 (0.6 mmol), and
DMF (3 mL) at 120 oC for 1 h under microwave irradiation (100 W of
initial power) unless otherwise stated.
Fe3O4@SiO2@MOF-199 (0.03 mmol).
[b]
[c]
For
3
h.
withdrawing substituents to give the corresponding isoquinoline–
fused benzimidazoles 3b–f. The products were formed
invariably irrespective of the position and electronic nature of the
substituent. The reaction of 1a with 1,3–diheteroaryl–1,3–dione
2g also proceeded to give the corresponding N–fused scaffold
3g. However, prolonging the reaction time was needed for an
allowable formation of 3g. Similar treatment of 1a with 2h under
the employed conditions gave N–fused scaffold 3h in only 14%
yield along with considerable amount of 4,7-dimethoxy-2-phenyl-
1H-benzo[d]imidazole by debromination of 1a (43% yield).[8e]
The reaction of 1a with 1,3–dialkyl–1,3–diones 2i–k also took
place to afford the coupled and cyclized products 3i–k
irrespective of the identity of alkyl substituents. Here again,
prolonging the reaction time and higher loading of the catalyst
(10 mol% based on 1a) were needed for the effective formation
of 3i–k. Several 2–(2–bromoaryl)benzimidazoles 1b–d having
electron–donating and –withdrawing substituents on bromoaryl
moiety are also coupled and cyclized with 1,3–diphenyl–1,3–
dione (2a) to give the corresponding binuclear N–fused hybrid
scaffolds 3l–n in 56–62% yields. Treatment of cyclic 2–(2–
bromovinyl)benzimidazoles (1e and 1f) with 2a under the
employed conditions also afforded the coupled and cyclized
products (3o and 3p) in similar yields. As is the case for the
reaction between analogue of 1f, 2–(1–bromo–3,4–
Figure 1. The XRD patterns of (a) fresh (b) reused (after third run).
All binuclear N–fused hybrid scaffolds shown in Table 2 except
for 3g and 3h could be transformed into unprecedented
isoquinoline– and pyridine–fused benzimidazolequinones (4a-q)
in 63–92% yields by treatment of either ceric ammonium nitrate
(CAN) in aqueous acetonitrile[20] or aqueous 48% HBr/FeCl3 in
H2O (Table 3).[21] The oxidation of 3i, 3k, 3m, and 3q-s did not
proceed with CAN oxidation system at all, but proceeded readily
with HBr/FeCl3 oxidation system toward the corresponding
products (4g, 4i, 4k, and 4o-q). Not fully understood, 3g and 3h
were scarcely oxidized to the corresponding binuclear N-fused
hybrid scaffolds under such oxidation conditions, and several
unidentified products were formed with complete conversion of
3g and 3h.
dihydronaphthalen–2–yl)–1H–benzo[d]
imidazole
and
cyclohexane–1,3–dione, no dehydrogenation product of the
coupled and cyclized scaffold 3p was observed at all.[9] Similar
treatment of acyclic 2–(2–bromovinyl)benzimidazoles 1g–i
having alkyl and phenyl substituents on vinyl moiety with 2a
under prolonging the reaction time and higher loading of the
catalyst (10 mol% based on 1a) also afforded the corresponding
pyridine-fused benzimidazoles 3q-s. However, the product yield
was lower than that when previously described 2–(2–
Table 3. Oxidation of 3 to 4.[a]
bromoaryl)benzimidazoles
and
cyclic
2–(2–
bromovinyl)benzimidazoles were used.
It appears that the reaction proceeds via initial copper-catalyzed
C–C coupling between 1a and 2a followed by deacylation and
cyclocondensation. It is known that aryl and vinyl halides are
coupled with 1,3-dicarbonyl compounds in the presence of a
copper or a palladium catalyst.[8d,9,16,17] Such a deacylative
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900635
European Journal of Organic Chemistry
FULL PAPER
quinone-based drugs and organic electronic materials. Further
challenges on the synthesis of polynuclear N-fused hybrid
scaffolds including benzimidazolequinone using the present
protocol are under way.
Experimental Section
1
General: H (500 MHz) and 13C NMR (125 MHz) spectra were recorded
on a Bruker Avance Digital 500 spectrometer using TMS as an internal
standard in CDCl3, CD2Cl2 or DMSO-d6. Melting points were measured
on a microscopic melting point apparatus (Stanford Research Inc.
MPA100 automated melting point apparatus). X-ray diffraction (XRD)
experiments were performed in a Bragg-Brentam θ/2θ Rigaku D/Max-
2500 diffractometer using a Cu source working at 40 kV and 200 mA
over the range of 5-90o (2θ). IR spectra were recorded on Shimadzu
FTIR-8400S infra-red spectrophotometer. High-resolution mass data
were obtained using electronic ionization or fast atom bombardment
(HRMS, magnetic sector-electric sector double focusing mass analyzer)
at the Korea Basic Science Center (Daegu). The products were isolated
by TLC (a glass plate coated with Kieselgel 60 GF254, Merck). 2-(2-
Bromoaryl)-4,7-dimethoxy-1H-benzo[d]imidazoles
and
(Z)-2-(2-
bromovinyl)-4,7-dimethoxy-1H-benzo[d]imidazoles 1a-i were prepared
from the corresponding aldehydes and 3,6-dimethoxybenzene-1,2-
diamine according to the reported method (see Supporting Information
for characterization data and copies of 1H and 13C NMR spectra of 1a-
i).[15,20c,22] Other commercially available organic and inorganic reagents
were used without further purification.
General procedure for the synthesis of 3a-s: To a 5 mL microwave
reaction tube was added
1
(0.3 mmol),
2
(0.3 mmol),
Fe3O4@SiO2@MOF–199 (0.015–0.03 mmol), Cs2CO3 (0.195 g, 0.6
mmol), and DMF (3 mL). After stirring the reaction mixture at rt for 10 min,
o
it was heated 120 C for 1–3 h by microwave irradiation (100 W of initial
power). The reaction mixture was cooled and filtered through a short
silica gel column to eliminate inorganic salts using ethyl acetate.
Removal of the eluent using evaporator under reduced pressure left a
crude mixture, which was purified by TLC (hexane/ethyl acetate = 2/1) to
give 3. For the catalyst reuse experiment, the reaction mixture except for
the catalyst, which was fixed with a magnet, was removed from the tube
by washing with ethyl acetate. The catalyst remained in the tube was
washed with ethanol, dried under vacuo and subjected to next run by
charging with 1, 2, Cs2CO3, and DMF. All new products thus obtained
were characterized spectroscopically as shown below.
[a]
All reactions were carried out with 3 (0.1 mmol), CAN (0.4 mmol),
and acetonitrile/H2O (4 mL) at rt for 20 min unless otherwise stated.
[b]
Aqueous 48% HBr (1 mL) at reflux for 3 h/ aqueous FeCl3 (0.7 M,
8,11-Dimethoxy-6-phenylbenzo[4,5]imidazo[2,1-a]isoquinoline (3a):
Pale yellow solid (85 mg, 80%); mp 142-144 oC. 1H NMR (500 MHz,
CDCl3) δ 3.08 (s, 3H), 4.08 (s, 3H), 6.44 (d, J = 8.6 Hz, 1H), 6.75 (d, J =
8.6 Hz, 1H), 6.93 (s, 1H), 7.40-7.45 (m, 3H), 7.47-7.50 (m, 3H), 7.61-7.65
(m, 2H), 7.67-7.70 (m, 1H), 8.98-9.00 (m, 1H). 13C NMR (125 MHz,
CDCl3) δ 55.3, 56.1, 102.8, 103.9, 114.5, 122.1, 122.9, 125.5, 126.4,
126.9, 127.6, 128.0, 128.1, 129.9, 131.5, 136.8, 138.6, 139.5, 141.7,
145.5, 148.5. HRMS (EI) m/z: (M+) Calcd for C23H18N2O2 354.1368,
Found 354.1369.
1 mL) at rt for 18 h.
Conclusions
In summary, we have shown that 2–(2–bromoaryl)–4,7–
dimethoxy–1H–benzo[d]imidazoles and (Z)–2–(2–bromovinyl)–
4,7–dimethoxy–1H–benzo[d]imidazoles
are
deacylatively
8,11-Dimethoxy-6-(o-tolyl)benzo[4,5]imidazo[2,1-a]isoquinoline (3b):
Pale yellow solid (74 mg, 67%); mp 139-140 oC. 1H NMR (500 MHz,
CDCl3) δ 1.98 (s, 3H), 3.09 (s, 3H), 4.07 (s, 3H), 6.44 (d, J = 8.6 Hz, 1H),
6.73 (d, J = 8.6 Hz, 1H), 6.89 (s, 1H), 7.25-7.28 (m, 1H), 7.29-7.30 (m,
1H), 7.35 (dt, J = 7.5 and 1.5 Hz, 1H), 7.42 (dd, J = 7.4 and 1.4 Hz, 1H),
7.63-7.69 (m, 3H), 9.02-9.05 (m, 1H). 13C NMR (125 MHz, CDCl3) δ 19.4,
55.9, 56.1, 102.6, 103.8, 114.5, 122.4, 123.0, 125.4, 125.7, 126.3, 127.7,
128.4, 129.2, 129.3, 130.0, 131.3, 136.8, 137.2, 138.4, 139.2, 142.1,
145.5, 148.2. HRMS (EI) m/z: (M+) Calcd for C24H20N2O2 368.1525,
Found 368.1522.
coupled and cyclized with 1,3-diketones under microwave
irradiation in the presence of recyclable Fe3O4@SiO2@MOF–
199 to give binuclear N–fused hybrid scaffolds, 8,11–
dimethoxybenzo[4,5]imidazo[2,1–a]isoquinolines
dimethoxybenzo[4,5]imidazo[1,2–a]pyridines,
and
respectively.
6,9-
Oxidation of such binuclear N-fused hybrid scaffolds with ceric
ammonium nitrate in acetonitrile–H2O or HBr/FeCl3 in H2O
afforded a new class of binuclear N–fused hybrid scaffolds,
benzo[4,5]imidazo[2,1–a]isoquinoline–8,11–diones
benzo[4,5]imidazo[1,2–a]pyridine–6,9–diones. The
and
present
reaction would provide a useful route for developing bioreductive
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900635
European Journal of Organic Chemistry
FULL PAPER
8,11-Dimethoxy-6-(m-tolyl)benzo[4,5]imidazo[2,1-a]isoquinoline (3c):
Pale yellow solid (77 mg, 69%); mp 148-150 oC. 1H NMR (500 MHz,
CDCl3) δ 2.32 (s, 3H), 3.01 (s, 3H), 3.99 (s, 3H), 6.37 (d, J = 8.5 Hz, 1H),
6.67 (d, J = 8.5 Hz, 1H), 6.84 (s, 1H), 7.15-7.20 (m, 2H), 7.22-7.24 (m,
2H), 7.52-7.55 (m, 2H), 7.58-7.60 (m, 1H), 8.89-8.92 (m, 1H). 13C NMR
(125 MHz, CDCl3) δ 21.5, 55.5, 56.1, 102.9, 103.9, 114.5, 122.2, 123.0,
124.2, 125.5, 126.5, 127.6 (127.55), 127.6 (127.64), 128.0, 128.9, 130.0,
131.6, 136.8, 137.7, 138.8, 139.5, 141.8, 145.6, 148.6. HRMS (EI) m/z:
(M+) Calcd for C24H20N2O2 368.1525, Found 368.1527.
129.9, 131.6, 136.0, 137.1, 141.6, 146.0, 148.7. HRMS (EI) m/z: (M+)
Calcd for C18H16N2O2 292.1212, Found 292.1210.
6-Isopropyl-8,11-dimethoxybenzo[4,5]imidazo[2,1-a]isoquinoline
(3j): Pale yellow solid (60 mg, 62%); mp 178-181 oC. 1H NMR (500 MHz,
CDCl3) δ 1.30 (d, J = 6.7 Hz, 6H), 3.91 (s, 3H), 4.02 (s, 3H), 4.60 (sept, J
= 6.7 Hz, 1H), 6.70 (d, J = 8.5 Hz, 1H), 6.77 (d, J = 8.5 Hz, 1H), 6.85 (s,
1H), 7.48-7.51 (m, 1H), 7.52-7.56 (m, 1H), 7.58-7.59 (m, 1H), 8.90 (d, J =
8.0 Hz, 1H). 13C NMR (125 MHz, CDCl3) δ 23.0, 31.0, 56.2, 56.5, 103.8
(103.77), 103.8 (103.78), 107.9, 122.7, 122.8, 125.6, 125.8, 127.0, 129.9,
131.7, 137.2, 141.6, 146.1, 146.8, 149.0. HRMS (EI) m/z: (M+) Calcd for
C20H20N2O2 320.1525, Found 320.1527.
8,11-Dimethoxy-6-(p-tolyl)benzo[4,5]imidazo[2,1-a]isoquinoline (3d):
Pale yellow solid (73 mg, 66%); mp 139-140 oC. 1H NMR (500 MHz,
CDCl3) δ 2.37 (s, 3H), 3.02 (s, 3H), 3.99 (s, 3H), 6.37 (d, J = 8.6 Hz, 1H),
6.67 (d, J = 8.6 Hz, 1H), 6.84 (s, 1H), 7.15-7.17 (m, 2H), 7.29-7.31 (m,
2H), 7.52-7.57 (m, 2H), 7.58-7.61 (m, 1H), 8.89-8.92 (m, 1H). 13C NMR
(125 MHz, CDCl3) δ 21.5, 55.4, 56.2, 103.0, 104.0, 114.4, 122.2, 122.9,
125.6, 126.4, 127.0, 127.6, 128.6, 130.0, 131.7, 136.8 (136.77), 136.8
(136.83), 138.1, 138.8, 141.9, 145.6, 148.7. HRMS (EI) m/z: (M+) Calcd
for C24H20N2O2 368.1525, Found 368.1522.
8,11-Dimethoxy-6-pentylbenzo[4,5]imidazo[2,1-a]isoquinoline (3k):
Pale yellow solid (64 mg, 61%); mp 164-167 oC. 1H NMR (500 MHz,
CDCl3) δ 0.88 (t, J = 7.1 Hz, 3H), 1.29-1.42 (m, 4H), 1.67-1.72 (m, 2H),
3.50 (t, J = 7.7 Hz, 2H), 3.98 (s, 3H), 4.09 (s, 3H), 6.75 (d, J = 8.6 Hz,
1H), 6.83 (d, J = 8.6 Hz, 1H), 6.84 (s, 1H); 7.54-7.56 (m, 1H), 7.59-7.63
(m, 2H), 8.94-8.96 (m, 1H). 13C NMR (125 MHz, CDCl3) δ 14.2, 22.7,
28.6, 31.8, 36.4, 56.1, 56.2, 103.4, 103.6, 111.4, 122.5, 122.8, 125.4,
125.8, 126.9, 129.9, 131.6, 137.2, 140.5, 141.6, 146.0, 149.0. HRMS (EI)
m/z: (M+) Calcd for C22H24N2O2 348.1838, Found 348.1834.
8,11-Dimethoxy-6-(4-methoxyphenyl)benzo[4,5]imidazo[2,1-
a]isoquinoline (3e): Pale yellow solid (77 mg, 67%); mp 162-163 oC. 1H
NMR (500 MHz, CDCl3) δ 3.17 (s, 3H), 3.89 (s, 3H), 4.08 (s, 3H), 6.46 (d,
J = 8.6 Hz, 1H), 6.76 (d, J = 8.6 Hz, 1H), 6.91 (s, 1H), 6.95-6.98 (m, 2H),
7.39-7.43 (m, 2H), 7.60-7.65 (m, 2H), 7.66-7.69 (m, 1H), 8.98-9.00 (m,
1H). 13C NMR (125 MHz, CDCl3) δ 55.5, 55.6, 56.1, 102.8, 103.9, 113.3,
114.2, 122.7, 125.5, 126.3, 127.5, 128.3, 128.6, 129.4, 129.9, 131.6,
132.2, 138.5, 141.7, 145.5, 148.6, 159.7. HRMS (EI) m/z: (M+) Calcd for
C24H20N2O3 384.1474, Found 384.1477.
8,11-Dimethoxy-3-methyl-6-phenylbenzo[4,5]imidazo[2,1-
1
a]isoquinoline (3l): Pale yellow solid (65 mg, 59%); mp 153-155 oC. H
NMR (500 MHz, CDCl3) δ 2.46 (s, 3H), 3.01 (s, 3H), 4.00 (s, 3H), 6.36 (d,
J = 8.5 Hz, 1H), 6.67 (d, J = 8.5 Hz, 1H), 6.81 (s, 1H); 7.34-7.37 (m, 3H),
7.38-7.42 (m, 4H), 8.80 (d, J = 8.0 Hz, 1H). 13C NMR (125 MHz, CDCl3) δ
22.0, 55.5, 56.2, 102.7, 104.0, 114.7, 120.7, 122.1, 125.5, 126.3, 127.0,
128.1, 128.2, 129.5, 131.8, 136.7, 138.7, 139.6, 140.4, 141.8, 145.5,
148.8. HRMS (EI) m/z: (M+) Calcd for C24H20N2O2 368.1525, Found
368.1522.
6-(4-Fluorophenyl)-8,11-dimethoxybenzo[4,5]imidazo[2,1-
a]isoquinoline (3f): Pale yellow solid (70 mg, 63%); mp 169-171 oC. H
1
NMR (500 MHz, CDCl3) δ 3.10 (s, 3H), 4.00 (s, 3H), 6.38 (d, J = 8.5 Hz,
1H), 6.68 (d, J = 8.5 Hz, 1H), 6.82 (s, 1H), 7.03-7.07 (m, 2H), 7.36-7.39
(m, 2H), 7.54-7.57 (m, 2H), 7.58-7.61 (m, 1H), 8.89-8.92 (m, 1H). 13C
NMR (125 MHz, CDCl3) δ 55.5, 56.2, 102.9, 104.1, 114.6, 115.0 (d, J =
21.6 Hz), 122.0, 123.0, 125.6, 126.5, 127.9, 129.0 (d, J = 8.1 Hz), 130.1,
131.4, 135.7 (d, J = 3.5 Hz), 136.9, 137.6, 141.6, 145.7, 148.6, 162.8 (d,
J = 245.6 Hz). HRMS (EI) m/z: (M+) Calcd for C23H17FN2O2 372.1274,
Found 372.1277.
2,8,11-Trimethoxy-6-phenylbenzo[4,5]imidazo[2,1-a]isoquinoline
(3m): Pale yellow solid (65 mg, 56%); mp 173-175 oC. 1H NMR (500 MHz,
CDCl3) δ 3.09 (s, 3H), 4.04 (s, 3H), 4.09 (s, 3H), 6.44 (d, J = 8.5 Hz, 1H),
6.76 (d, J = 8.5 Hz, 1H), 6.91 (s, 1H), 7.25 (dd, J = 8.6 and 2.6 Hz, 1H),
7.40-7.45 (m, 3H), 7.46-7.49 (m, 2H), 7.61 (d, J = 8.6 Hz, 1H), 8.36 (d, J
= 2.7 Hz, 1H). 13C NMR (125 MHz, CDCl3) δ 55.5, 56.2 (56.17), 56.2
(56.20), 102.7, 103.8, 105.6, 114.6, 121.0, 122.3, 124.3, 125.8, 127.0,
128.0, 128.1, 128.2, 136.5, 136.8, 139.8, 141.9, 145.5, 148.5, 159.5.
HRMS (EI) m/z: (M+) Calcd for C24H20N2O3 384.1474, Found 384.1471.
8,11-Dimethoxy-6-(pyridin-3-yl)benzo[4,5]imidazo[2,1-a]isoquinoline
(3g): Pale yellow solid (61 mg, 57%); mp 167-169 oC. 1H NMR (500 MHz,
CDCl3) δ 3.60 (s, 3H), 4.01 (s, 3H), 6.55 (d, J = 8.6 Hz, 1H), 6.59 (d, J =
8.6 Hz, 1H), 6.60-6.62 (m, 1H), 7.09-7.16 (m, 2H), 7.37-7.44 (m, 3H),
7.58-7.60 (m, 1H), 7.61-7.63 (m, 2H). 13C NMR (125 MHz, CDCl3) δ 55.9,
56.1, 102.2, 104.3, 121.0, 126.6, 126.8, 127.8, 128.5, 128.6, 128.8,
129.4, 129.7 (129.71), 129.7 (129.72), 130.5, 132.6, 135.1, 138.0, 141.6,
146.2, 153.3. HRMS (EI) m/z: (M+) Calcd for C22H17N3O2 355.1321,
Found 355.1324.
2-Fluoro-8,11-dimethoxy-6-phenylbenzo[4,5]imidazo[2,1-
a]isoquinoline (3n): Pale yellow solid (69 mg, 62%); mp 191-192 oC. 1H
NMR (500 MHz, CDCl3) δ 3.01 (s, 3H), 4.01 (s, 3H), 6.38 (d, J = 8.6 Hz,
1H), 6.69 (d, J = 8.6 Hz, 1H), 6.84 (s, 1H), 7.28 ( dt, J = 8.5 and 2.7 Hz,
1H), 7.35-7.37 (m, 3H), 7.39-7.41 (m, 2H), 7.60 (dd, J = 8.7 and 5.2 Hz,
1H), 8.58 (dd, J = 9.5 and 2.3 Hz, 1H). 13C NMR (125 MHz, CDCl3) δ
55.5, 56.3, 103.2, 104.2, 110.9 (d, J = 23.7 Hz), 113.9, 118.8 (d, J = 23.6
Hz), 122.3, 124.6 (d, J = 9.7 Hz), 127.1, 128.1, 128.3, 128.8 (d, J = 8.3
Hz), 136.8, 138.1 (d, J = 2.6 Hz), 139.4. 141.8, 145.7, 147.8 (147.80),
147.8 (147.84), 162.0 (d, J = 246.6 Hz). HRMS (EI) m/z: (M+) Calcd for
C23H17FN2O2 372.1274, Found 372.1273.
6-(Furan-2-yl)-8,11-dimethoxybenzo[4,5]imidazo[2,1-a]isoquinoline
(3h): White solid (14 mg, 14%); mp 167-169 oC. 1H NMR (500 MHz,
CDCl3) δ 3.48 (s, 3H), 4.08 (s, 3H), 6.56-6.57 (m, 2H), 6.74 (d, J = 3.3 Hz,
1H), 6.78 (d, J = 8.5 Hz, 1H), 7.12 (s, 1H), 7.48 (d, J = 1.9 Hz, 1H), 7.63-
7.67 (m, 2H), 7.69-7.71 (m, 1H), 8.97-8.99 (m, 1H). 13C NMR (125 MHz,
CDCl3) δ 56.1, 56.9, 102.9, 103.9, 108.1, 111.0, 115.8, 122.3, 123.6,
125.5, 126.6, 128.3, 128.8, 129.9, 130.7, 136.6, 142.2, 142.3, 145.5,
148.1, 151.0. HRMS (EI) m/z: (M+) Calcd for C21H16N2O3 344.1161,
Found 344.1158.
8,11-Dimethoxy-6-phenyl-1,2,3,4-tetrahydrobenzo[4,5]imidazo[2,1-
a]isoquinoline (3o): Yellow solid (75 mg, 70%); mp 176-178 oC. 1H
NMR (500 MHz, CDCl3) δ 1.82-1.89 (m, 4H), 2.68-2.70 (m, 2H), 3.00 (s,
3H), 3.13-3.15 (m, 2H), 3.95 (s, 3H), 6.27 (d, J = 8.5 Hz, 1H), 6.38 (s, 1H),
6.64 (d, J = 8.5 Hz, 1H), 7.32-7.35 (m, 5H). 13C NMR (125 MHz, CDCl3) δ
22.3, 22.7, 24.6, 29.0, 55.4, 56.0, 101.3, 104.0, 117.0, 121.1, 124.1,
127.1, 127.9, 128.1, 137.2, 137.7, 138.8, 139.6, 142.1, 145.4, 150.2.
HRMS (EI) m/z: (M+) Calcd for C23H22N2O2 358.1681, Found 358.1678.
8,11-Dimethoxy-6-methylbenzo[4,5]imidazo[2,1-a]isoquinoline (3i):
Pale yellow solid (56 mg, 64%); mp 182-183 oC. 1H NMR (500 MHz,
CDCl3) δ 3.02 (d, J = 1.0 Hz, 3H), 3.98 (s, 3H), 4.09 (s, 3H), 6.76 (d, J =
8.6 Hz, 1H), 6.83 (d, J = 8.6 Hz, 1H), 6.839-6.843 (m, 1H), 7.55-7.59 (m,
1H), 7.60-7.61 (m, 2H), 8.95-8.96 (m, 1H). 13C NMR (125 MHz, CDCl3) δ
24.6, 56.1, 56.2, 103.6, 103.7, 112.3, 122.4, 122.6, 125.2, 125.8, 126.9,
10,13-Dimethoxy-8-phenyl-1,2-
dihydrobenzo[f]benzo[4,5]imidazo[2,1-a]isoquinoline (3p): Yellow
o
1
solid (72 mg, 59%); mp 187-189 C. H NMR (500 MHz, CDCl3) δ 3.04-
3.07 (m, 2H), 3.09 (s, 3H), 3.49-3.52 (m, 2H), 4.05 (s, 3H), 6.37 (d, J =
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900635
European Journal of Organic Chemistry
FULL PAPER
8.5 Hz, 1H), 6.74 (d, J = 8.5 Hz, 1H), 7.11 (s, 1H); 7.26-7.33 (m, 3H),
7.43-7.46 (m, 3H), 7.49-7.52 (m, 2H), 7.71-7.73 (m, 1H). 13C NMR (125
MHz, CDCl3) δ 22.6, 28.0, 55.4, 56.0, 101.6, 104.1, 111.1, 121.4, 123.7,
124.1, 127.1, 127.2, 128.0, 128.3, 128.6, 128.7, 132.5, 133.2, 137.7,
138.4, 139.8, 140.4, 142.1, 145.4, 149.8. HRMS (EI) m/z: (M+) Calcd for
C27H22N2O2 406.1681, Found 406.1679.
9.01 (m, 1H). 13C NMR (125 MHz, CDCl3) δ 19.7, 119.6, 122.6, 125.6,
125.7, 126.8, 127.0, 129.3, 129.7 (129.68), 129.7 (129.71), 130.0, 131.3
(131.28), 131.3 (131.35), 134.4, 136.0, 137.2, 137.4, 138.9, 144.5, 148.7,
174.4, 182.5. IR (KBr): ṽ = 663, 710, 755, 834, 1034, 1216, 1300, 1454,
1491, 1527, 1657 (C=O), 1674 (C=O), 1940, 2850, 2919, 3063 cm-1.
HRMS (EI) m/z: (M+) Calcd for C22H14N2O2 338.1055, Found 338.1055.
6,9-Dimethoxy-4-methyl-1,3-diphenylbenzo[4,5]imidazo[1,2-
6-(m-Tolyl)benzo[4,5]imidazo[2,1-a]isoquinoline-8,11-dione
(4c):
a]pyridine (3q): Yellow solid (58 mg, 49%); mp 198-200 oC. 1H NMR
(500 MHz, CDCl3) δ 2.74 (s, 3H), 3.10 (s, 3H), 4.06 (s, 3H), 6.39 (d, J =
8.5 Hz, 1H), 6.73 (s, 1H), 6.76 (d, J = 8.5 Hz, 1H), 7.38-7.42 (m, 4H),
7.44-7.47 (m, 6H). 13C NMR (125 MHz, CDCl3) δ15.4, 55.4, 56.1, 101.5,
104.2, 117.1, 121.3, 123.0, 127.1, 127.8, 128.0, 128.2, 128.5, 129.3,
138.2, 139.0, 139.5 (139.45), 139.5 (139.55), 139.8, 142.3, 145.5, 151.0.
HRMS (EI) m/z: (M+) Calcd for C26H22N2O2 394.1681, Found 394.1683.
Orange solid (26 mg, 76%); mp 197-199 C. H NMR (500 MHz, CDCl3)
δ 2.39 (s, 3H), 6.48 (d, J = 10.3 Hz, 1H), 6.65 (d, J = 10.3 Hz, 1H), 7.19-
7.32 (m, 5H), 7.66-7.71 (m, 2H), 7.72-7.75 (m, 1H), 8.87-8.90 (m, 1H).
13C NMR (125 MHz, CDCl3) δ 21.7, 119.4, 122.6, 124.6, 125.6, 126.9,
127.1, 128.2, 128.3, 129.2, 130.3, 131.3, 131.7, 134.4, 136.3, 137.8,
138.4, 138.8, 144.8, 149.2, 174.5, 182.6. IR (KBr): ṽ = 654, 706, 751, 830,
888, 956, 1034, 1090, 1214, 1302, 1350, 1454, 1530, 1596, 1659 (C=O),
1665 (C=O), 1937, 2850, 2917, 3058 cm-1. HRMS (EI) m/z: (M+) Calcd
for C22H14N2O2 338.1055, Found 338.1056.
o
1
4-Butyl-6,9-dimethoxy-1,3-diphenylbenzo[4,5]imidazo[1,2-a]pyridine
(3r): Yellow solid (65 mg, 50%); mp 190-192 oC. 1H NMR (500 MHz,
CDCl3) δ 0.80 (t, J = 7.4 Hz, 3H), 1.28-1.36 (m, 2H), 1.72-1.79 (m, 2H),
3.09 (s, 3H), 3.15-3.18 (m, 2H), 4.06 (s, 3H), 6.38 (d, J = 8.6 Hz, 1H),
6.67 (s, 1H), 7.76 (d, J = 8.6 Hz, 1H), 7.35-7.47 (m, 10H). 13C NMR (125
MHz, CDCl3) δ 14.0, 22.9, 28.2, 31.8, 55.4, 56.3, 101.4, 104.5, 117.4,
121.2, 126.9, 127.7, 127.9, 128.0, 128.2, 128.5, 129.1, 138.3, 138.8,
139.5, 139.9, 140.0, 142.3, 145.5, 150.6. HRMS (EI) m/z: (M+) Calcd for
C29H28N2O2 436.2151, Found 436.2152.
6-(p-Tolyl)benzo[4,5]imidazo[2,1-a]isoquinoline-8,1-dione
(4d):
o
1
Orange solid (29 mg, 85%); mp 201-203 C. H NMR (500 MHz, CDCl3)
δ 2.49 (s, 3H), 6.55 (d, J = 10.3 Hz, 1H), 6.72 (d, J = 10.3 Hz, 1H), 7.29-
7.32 (m, 3H), 7.38-7.40 (m, 2H), 7.72-7.77 (m, 2H), 7.78-7.81 (m, 1H),
8.95-8.97 (m, 1H). 13C NMR (125 MHz, CDCl3) δ 21.7, 119.4, 122.6,
125.6, 126.9, 127.1, 127.3, 129.1, 129.2, 131.2, 131.8, 133.6, 134.4,
137.8, 138.9, 139.5, 144.8, 149.3, 174.5, 182.6. IR (KBr): ṽ = 669, 706,
751, 813, 835, 901, 931, 1036, 1090, 1223, 1296, 1371, 1451, 1496,
1512, 1599, 1659 (C=O), 1670 (C=O), 1805, 1942, 2850, 2921, 3063 cm-
1. HRMS (FAB) m/z: [M + H]+ Calcd for C22H15N2O2 339.1134, Found
339.1137.
6,9-Dimethoxy-1,3,4-triphenylbenzo[4,5]imidazo[1,2-a]pyridine (3s):
Yellow solid (71 mg, 52%); mp 189-191 oC. 1H NMR (500 MHz, CDCl3) δ
3.11 (s, 3H), 3.97 (s, 3H), 6.40 (d, J = 8.5 Hz, 1H), 6.73 (d, J = 8.5 Hz,
1H), 6.88 (s, 1H); 7.20-7.22 (m, 5H), 7.25-7.30 (m, 3H), 7.44-7.46 (m,
3H), 7.47-7.49 (m, 2H), 7.52-7.54 (m, 2H). 13C NMR (125 MHz, CDCl3) δ
55.4, 56.1, 101.7, 104.5, 117.5, 121.0, 126.9, 127.0, 127.4, 127.6, 128.0,
128.1, 128.2, 128.5, 129.9, 131.9, 135.5, 138.7, 139.5, 139.7, 139.8,
140.7, 142.2, 145.5, 150.2. HRMS (EI) m/z: (M+) Calcd for C31H24N2O2
456.1838, Found 456.1835.
6-(4-Methoxyphenyl)benzo[4,5]imidazo[2,1-a]isoquinoline-8,11-
dione (4e): Orange solid (28 mg, 80%); mp 132-134 oC. 1H NMR (500
MHz, CDCl3) δ 3.84 (s, 3H), 6.48 (d, J = 10.3 Hz, 1H), 6.65 (d, J = 10.3
Hz, 1H), 6.93-6.95 (m, 2H), 7.19 (s, 1H), 7.34-7.37 (m, 2H), 7.64-7.70 (m,
2H), 7.71-7.73 (m, 1H), 8.86-8.88 (m, 1H). 13C NMR (125 MHz, CDCl3) δ
113.9, 119.2, 122.5, 125.5, 127.0 (126.96), 127.0 (126.99), 128.9
(128.85), 128.9, 129.1, 131.2, 131.8, 134.3, 137.6, 138.9, 144.8, 149.3,
160.5, 174.4, 182.6. IR (KBr): ṽ = 712, 753, 832, 1029, 1174, 1249, 1300,
1455, 1509, 1603, 1661 (C=O), 2032, 2837, 2925, 3065 cm-1. HRMS (EI)
m/z: (M+) Calcd for C22H14N2O3 354.1004, Found 354.1005.
General procedure for the oxidation of 3 to 4: For oxidation of 3a-f, 3j,
3l, and 3n-p, a solution of ceric ammonium nitrate (0.219 g, 0.4 mmol) in
acetonitrile/H2O (9/1, 2 mL) was added dropwise to a cold stirred solution
of 3 (0.1 mmol) in acetonitrile/H2O (7/3, 2 mL). After the reaction mixture
was stirred at an ambient temperature for 30 min, it was poured into cold
water and extracted with ethyl acetate (30-40 mL). Evaporation of the
solvent under reduced pressure and recrystallization from
dichloromethane and hexane mixture afforded 4. For oxidation of 3i, 3k,
3m, and 3q-s, to a 10 mL round-bottom flask was added 3 (0.1 mmol)
and aqueous 48% hydrobromic acid (1 mL) and the resulting mixture was
allowed to react under reflux for 3 h. After the reaction mixture was
cooled and evaporated under reduced pressure, aqueous FeCl3 solution
(0.7 M, 1 mL) was charged and stirred at room temperature for 20 h. The
reaction mixture was poured into H2O and extracted with CHCl3.
Removal of the collected organic layer left a crude mixture, which was
purified by TLC to give 4.
6-(4-Fluorophenyl)benzo[4,5]imidazo[2,1-a]isoquinoline-8,11-dione
(4f): Orange solid (28 mg, 81%); mp 192-194 oC. 1H NMR (500 MHz,
CDCl3) δ 6.48 (d, J = 10.3 Hz, 1H), 6.67 (d, J = 10.3 Hz, 1H), 7.11-7.15
(m, 2H), 7.23 (s, 1H), 7.40-7.43 (m, 2H), 7.69-7.76 (m, 3H), 8.89-8.91 (m,
1H). 13C NMR (125 MHz, CDCl3) δ 115.7 (d, J = 21.8 Hz), 119.7, 122.7,
125.6, 126.8, 127.1, 129.5, 129.6 (d, J = 8.3 Hz), 131.4, 131.6, 132.6 (d,
J = 3.8 Hz), 134.5, 136.6, 138.9, 144.9, 149.2, 163.4 (d, J = 248.2 Hz),
174.6, 182.5. IR (KBr): ṽ = 667, 708, 755, 835, 931, 1017, 1036, 1161,
1236, 1300, 1455, 1496, 1594, 1659 (C=O), 1667 (C=O), 1940, 2850,
2923, 3063 cm-1. HRMS (EI) m/z: (M+) Calcd for C21H11FN2O2 342.0805,
Found 342.0809.
6-Phenylbenzo[4,5]imidazo[2,1-a]isoquinoline-8,11-dione
(4a):
6-Methylbenzo[4,5]imidazo[2,1-a]isoquinoline-8,11-dione
(4g):
o
1
o
1
Orange solid (30 mg, 92%); mp 148-150 C. H NMR (500 MHz, CDCl3)
δ 6.54 (d, J = 10.3 Hz, 1H), 6.72 (d, J = 10.3 Hz, 1H), 7.32 (s, 1H), 7.48-
7.55 (m, 5H), 7.75-7.77 (m, 2H), 7.78-7.83 (m, 1H), 8.96-8.98 (m, 1H).
13C NMR (125 MHz, CDCl3) δ119.4, 122.5, 125.5, 126.7, 127.0, 127.5,
128.4, 129.2, 129.4, 131.2, 131.5, 134.3, 136.3, 137.5, 138.7, 144.7,
149.1, 174.4, 182.42. IR (KBr): ṽ = 663, 694, 752, 837, 900, 1034, 1096,
1222, 1302, 1373, 1455, 1496, 1530, 1599, 1656 (C=O), 1674 (C=O),
1946, 2916, 3071 cm-1. HRMS (EI) m/z: (M+) Calcd for C21H12N2O2
324.0899, Found 324.0901.
Orange solid (17 mg, 65%); mp 183-185 C. H NMR (500 MHz, CDCl3)
δ 3.06 (d, J = 0.8 Hz, 3H), 6.78 (s, 2H), 7.15 (s, 1H), 7.66-7.72 (m, 3H),
8.88-8.90 (m, 1H). 13C NMR (125 MHz, CDCl3) δ 23.2, 117.4, 122.2,
125.7, 126.0, 127.2, 128.5, 131.2, 131.9, 134.3, 135.5, 139.8, 145.2,
149.4, 175.6, 182.5. IR (KBr): ṽ = 645, 706, 757, 839, 971, 1031, 1081,
1229, 1304, 1356, 1487, 1602, 1650 (C=O), 1674 (C=O), 1974, 2852,
2920, 3051 cm-1. HRMS (EI) m/z: (M+) Calcd for C16H10N2O2 162.0742,
Found 162.0743.
6-Isopropylbenzo[4,5]imidazo[2,1-a]isoquinoline-8,11-dione
(4h):
6-(o-Tolyl)benzo[4,5]imidazo[2,1-a]isoquinoline-8,11-dione
(4b):
Orange solid (21 mg, 73%); mp oC. 1H NMR (500 MHz, CDCl3) δ 1.36 (d,
J = 6.7 Hz, 6H), 4.68 (sept, J = 6.7 Hz, 1H), 6.79 (d, J = 10.2 Hz, 1H),
6.82 (d, J = 10.2 Hz, 1H), 7.64-7.80 (m, 4H), 8.91-8.93 (m, 1H). 13C NMR
(125 MHz, CDCl3) δ 22.0, 30.2, 112.9, 122.3, 125.6, 126.3, 127.3, 128.4,
o
1
Orange solid (31 mg, 91%); mp 170-173 C. H NMR (500 MHz, CDCl3)
δ 2.08 (s, 3H), 6.51 (d, J = 10.3 Hz, 1H), 6.71 (d, J = 10.3 Hz, 1H), 7.29
(s, 1H), 7.33-7.38 (m, 3H), 7.48-7.51 (m, 1H), 7.77-7.82 (m, 3H), 8.98-
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900635
European Journal of Organic Chemistry
FULL PAPER
131.3, 131.7, 133.8, 140.1, 145.5, 146.0, 149.6, 175.2, 182.4. IR (KBr): ṽ
= 660, 697, 755, 837, 903, 1036, 1096, 1219, 1304, 1454, 1495, 1527,
1656 (C=O), 1672 (C=O), 1944, 2852, 2923, 3069 cm-1. HRMS (EI) m/z:
(M+) Calcd for C16H10N2O2 290.1055, Found 290.1052.
136.1, 136.6, 137.8, 139.7, 140.2, 146.6, 150.2, 173.5, 183.0. IR (KBr): ṽ
= 661, 706, 755, 835, 972, 1036, 1086, 1219, 1300, 1410, 1491, 1599,
1644 (C=O), 1672 (C=O), 1959, 2836, 2960, 3056 cm-1. HRMS (EI) m/z:
(M+) Calcd for C25H16N2O2 376.1212, Found 376.1214.
6-Pentylbenzo[4,5]imidazo[2,1-a]isoquinoline-8,11-dione (4i): Orange
solid (20 mg, 63%); mp 164-167 oC. 1H NMR (500 MHz, CDCl3) δ 0.91 (t,
J = 7.2 Hz, 3H), 1.33-1.38 (m, 2H), 1.40-1.46 (m, 2H), 1.61-1.67 (m, 2H),
3.54 (t, J = 7.7 Hz, 2H), 6.78 (d, J = 10.4 Hz, 1H), 6.80 (d, J = 10.4 Hz,
1H), 7.18 (s, 1H), 7.66-7.74 (m, 3H), 8.91 (d, J = 8.1 Hz, 1H). 13C NMR
(125 MHz, CDCl3) δ 14.1, 22.6, 28.5, 31.2, 34.9, 116.4, 122.3, 125.7,
162.2, 137.1, 128.5, 131.2, 131.8, 134.1, 140.0 (139.97), 140.0 (140.04),
145.4, 149.6, 175.4, 182.5. IR (KBr): ṽ = 706, 753, 852, 968, 1034, 1081,
1223, 1300, 1351, 1487, 1603, 1650 (C=O), 1674 (C=O), 1989, 2863,
2921, 3039 cm-1. HRMS (EI) m/z: (M+) Calcd for C20H18N2O2 318.1368,
Found 318.1371.
4-Methyl-1,3-diphenylbenzo[4,5]imidazo[1,2-a]pyridine-6,9-dione
(4o): Red solid (24 mg, 67%); mp 211-213 oC. 1H NMR (500 MHz,
CDCl3) δ 2.76 (s, 3H), 6.56 (d, J = 10.3 Hz, 1H), 6.71 (d, J = 10.3 Hz, 1H),
7.11 (s, 1H), 7.41-7.55 (m, 10H). 13C NMR (125 MHz, CDCl3) δ 15.2,
122.3, 125.0, 125.6, 127.5, 128.4, 128.6, 128.8, 129.1, 129.5, 134.2,
136.2, 138.2, 138.9, 139.6, 142.8, 146.4, 151.3, 173.7, 183.0. IR (KBr): ṽ
= 643, 699, 759, 845, 985, 1053, 1102, 1216, 1313, 1403, 1483, 1594,
1648 (C=O), 1672 (C=O), 1961, 2852, 2919, 3054 cm-1. HRMS (EI) m/z:
(M+) Calcd for C24H16N2O2 364.1212, Found 364.1208.
4-Butyl-1,3-diphenylbenzo[4,5]imidazo[1,2-a]pyridine-6,9-dione (4p):
Red solid (28 mg, 68%); mp 204-207 oC. 1H NMR (500 MHz, CDCl3) δ
0.79 (t, J = 7.4 Hz,3H), 1.28-1.34 (m, 2H), 1.66-1.72 (m, 2H), 3.17 (t, J =
8.0 Hz, 2H), 6.56 (d, J = 10.3 Hz, 1H), 6.70 (d, J = 10.3 Hz, 1H), 7.05 (s,
1H), 7.39-7.41 (m, 2H), 7.44-7.53 (m, 8H). 13C NMR (125 MHz, CDCl3) δ
13.9, 22.8, 28.0, 32.2, 122.6, 124.9, 127.4, 128.4 (128.35), 128.4
(128.44), 128.8, 128.9, 129.5, 130.6, 134.3, 136.2, 138.6, 138.7, 139.6,
142.9, 146.4, 151.0, 173.6, 183.1. IR (KBr): ṽ = 665, 697, 759, 854, 918,
1039, 1081, 1180, 1221, 1296, 1397, 1494, 1594, 1646 (C=O), 1672
(C=O), 1959, 2859, 2958, 3056 cm-1. HRMS (EI) m/z: (M+) Calcd for
C27H22N2O2 406.1681, Found 406.1678.
3-Methyl-6-phenylbenzo[4,5]imidazo[2,1-a]isoquinoline-8,11-dione
(4j): Orange solid (28 mg, 84%); mp 172-174 oC. 1H NMR (500 MHz,
CD2Cl2) δ 2.50 (s, 3H), 6.41 (d, J = 10.3 Hz, 1H), 6.57 (d, J = 10.3 Hz,
1H), 7.19 (s, 1H), 7.38-7.45 (m, 5H), 7.52-7.54 (m, 1H), 7.56 (s, 1H), 8.66
(d, J = 8.3 Hz, 1H). 13C NMR (125 MHz, CD2Cl2) δ 20.9, 118.4, 119.6,
124.1, 125.9, 126.0, 126.5, 127.5, 128.2, 130.1, 131.1, 133.4, 135.8,
136.7, 137.9, 141.1, 143.9, 148.3, 173.6, 181.7. IR (KBr): ṽ = 663, 697,
774, 822, 908, 1030, 1094, 1212, 1260, 1300, 1364, 1466, 1496, 1633
(C=O), 1655 (C=O), 1944, 2852, 2919, 2958, 3058 cm-1. HRMS (EI) m/z:
(M+) Calcd for C22H14N2O2 338.1055, Found 338.1058.
1,3,4-Triphenylbenzo[4,5]imidazo[1,2-a]pyridine-6,9-dione (4q): Red
solid (30 mg, 70%); mp 199-201 oC. 1H NMR (500 MHz, CDCl3) δ 6.50 (d,
J = 10.3 Hz, 1H), 6.68 (d, J = 10.3 Hz, 1H), 7.06-7.08 (m, 2H), 7.22-7.25
(m, 5H), 7.30-7.33 (m, 2H), 7.37-7.40 (m, 1H), 7.45-7.48 (m, 1H), 7.51-
7.55 (m, 2H), 7.76 (s, 1H), 8.03-8.04 (m, 2H). 13C NMR (125 MHz,
CDCl3) δ 125.4, 127.5, 128.0, 128.2, 128.8, 129.1 (129.07), 129.1
(129.11), 129.5, 129.6, 129.7, 131.3, 131.9, 132.9, 134.0, 134.4, 134.8,
137.9 (137.87), 137.9 (137.92), 139.6, 146.6, 148.6, 173.5, 182.5. IR
(KBr): ṽ = 619, 699, 759, 839, 898, 1027, 1068, 1214, 1313, 1446, 1476,
1600, 1659 (C=O), 1675 (C=O), 1952, 2850, 2925, 3062 cm-1. HRMS
(EI) m/z: (M+) Calcd for C29H18N2O2 426.1368, Found 426.1364..
2-Methoxy-6-phenylbenzo[4,5]imidazo[2,1-a]isoquinoline-8,11-dione
(4k): Orange solid (24 mg, 67%); mp 179-181 oC. 1H NMR (500 MHz,
CDCl3) δ 4.05 (s, 3H), 6.55 (d, J = 10.3 Hz, 1H), 6.72 (d, J = 10.3 Hz, 1H),
7.28 (s, 1H), 7.37 (dd, J = 8.7 and 2.6 Hz, 1H), 7.47-7.54 (m, 5H), 7.73 (d,
J = 8.7 H, 1H), 8.30 (d, J = 2.6 Hz, 1H). 13C NMR (125 MHz, CDCl3) δ
56.2, 104.8, 119.3, 122.7, 124.0, 126.0, 127.5, 128.4, 128.7, 129.1,
134.2, 135.2, 136.5, 138.9, 144.6, 148.7, 160.4, 174.3, 182.7. IR (KBr): ṽ
= 661, 695, 753, 832, 877, 1019, 1034, 1086, 1214, 1251, 1377, 1463,
1496, 1614, 1661 (C=O), 1942, 2852, 2921, 2962, 3069 cm-1. HRMS (EI)
m/z: (M+) Calcd for C22H14N2O3 354.1004, Found 354.1002.
2-Fluoro-6-phenylbenzo[4,5]imidazo[2,1-a]isoquinoline-8,11-dione
(4l): Orange solid (31 mg, 90%); mp 140-142 oC. 1H NMR (500 MHz,
CDCl3) δ 6.48 (d, J = 10.3 Hz, 1H), 6.67 (d, J = 10.3 Hz, 1H), 7.24 (s, 1H),
7.40-7.50 (m, 6H), 7.76 ( dd, J = 8.8 and 5.1 Hz, 1H), 8.54 (dd, J = 9.0
and 2.6 Hz, 1H). 13C NMR (125 MHz, CDCl3) δ 110.8 (d, J = 24.0 Hz),
118.8, 120.5 (d, J = 23.8 Hz), 124.3 (d, J = 10.2 Hz), 127.0, 127.6, 128.3,
128.6, 128.8, 129.6, 129.7 (d, J = 8.7 Hz), 134.6, 136.2, 137.1 (d, J = 2.5
Hz), 138.9, 144.7, 162.7 (d, J = 249.5 Hz), 174.5, 182.4. IR (KBr): ṽ =
667, 697, 727, 819, 897, 1034, 1083, 1195, 1242, 1305, 1373, 1496,
1596, 1659 (C=O), 1669 (C=O), 1961, 2933, 3069 cm-1. HRMS (EI) m/z:
(M+) Calcd for C21H11FN2O2 342.0805, Found 342.0808.
Acknowledgments
This research was supported by Basic Science Research
Program through the National Research Foundation of Korea
(NRF)
funded
by
the
Ministry
of
Education
(2017R1D1A1B03028226). P.D.Q.D. thanks Y.M. Park Internal
Medicine of Geoje Medical Center (Gyeongnam, Republic of
Korea) for partial financial support during his stay in the Republic
of Korea.
6-Phenyl-1,2,3,4-tetrahydrobenzo[4,5]imidazo[2,1-a]isoquinoline-
o
8,11-dione (4m): Orange solid (24 mg, 72%); mp 160-162 C. 1H NMR
Keywords: Isoquinoline • Pyridine • Benzimidazole–4,7–dione •
Heterocycles • Heterogeneous catalysis
(500 MHz, CDCl3) δ 1.83-1.91 (m, 4H), 2.76-2.78 (m, 2H), 3.14-3.16 (m,
2H), 6.44 (d, J = 10.3 Hz, 1H), 6.58 (d, J = 10.3 Hz, 1H), 6.77 (s, 1H),
7.32-7.34 (m, 2H), 7.39-7.42 (m, 2H), 7.43-7.46 (m, 1H). 13C NMR (125
MHz, CDCl3) δ 21.9, 22.3, 24.3, 29.0, 122.0, 124.8, 126.8, 127.5, 128.3,
129.4, 134.0, 136.3, 138.5, 139.5, 140.4, 146.0, 150.4, 173.7, 183.1. IR
(KBr): ṽ = 665, 697, 764, 843, 908, 1021, 1086, 1212, 1298, 1320, 1431,
1489, 1599, 1650 (C=O), 1674 (C=O), 1968, 2867, 2934, 3056 cm-1.
HRMS (EI) m/z: (M+) Calcd for C21H16N2O2 328.1212, Found 328.1210.
[1]
For recent reviews, see: a) J. Alvarez-Builla, J. J. Vaquero in Modern
Heterocyclic Chemistry, J. Alvarez-Builla, J. J Vaquero, J. Barluenga,
Eds.; Wiley-VCH, Weinheim, 2011, Vol. 4, Chapter 22, pp. 1989-2070.
b) Y. Liu, J.-P. Wan, Org. Biomol. Chem. 2011, 9, 6873. c) T. Liu, H. Fu,
Synthesis 2012, 44, 2805. d) X.-X. Guo, D.-W. Gu, Z. Wu, W. Zhang,
Chem. Rev. 2015, 115, 1622.
[2]
[3]
For pyridines, see: a) M. D. Hill, Chem. Eur. J. 2010, 16, 12052; b) G. D.
Henry, Tetrahedron 2004, 60, 6043.
8-Phenyl-1,2-dihydrobenzo[f]benzo[4,5]imidazo[2,1-a]isoquinoline-
10,13-dione (4n): Red solid (26 mg, 70%); mp 186-189 oC. 1H NMR (500
MHz, CDCl3) δ 3.06-3.09 (m, 2H), 3.48-3.51 (m, 2H), 6.55 (d, J = 10.3 Hz,
1H), 6.69 (d, J = 10.3 Hz, 1H), 7.33-7.38 (m, 3H), 7.48-7.59 (m, 6H),
7.75-7.76 (m, 1H). 13C NMR (125 MHz, CDCl3) δ 22.4, 27.7, 116.2, 124.4,
125.0, 125.8, 127.5, 127.7, 128.4, 129.0, 129.6, 129.9, 131.3, 134.1,
For isoquinolines, see: a) R. He, Z.-T. Huang, Q.-Y. Zheng, C. Wang,
Tetrahedron Lett. 2014, 55, 5705; b) S. Haider, A. G. Chittiboyina, I. A.
Khan, Curr. Org. Chem. 2018, 22, 148.
[4]
For biological activities of benzimidazole-based 1,4-quinone-containing
compounds, see: a) L. O’Donovan, M. P. Carty, F. Aldabbagh, Chem.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900635
European Journal of Organic Chemistry
FULL PAPER
Commun. 2008, 5592; b) J. J. Newsome, M. A. Colucci, M. Hassani, H.
D. Beall, C. J. Moody, Org. Biomol. Chem. 2007, 5, 3665; c) O.
Lavergne, A.-C. Fernandes, L. Bréhu, A. Sidhu, M.-C. Brézak, G.
Prévost, B. Ducommun, M.-O. Contour-Galcera, Bioorg. Med. Chem.
Lett. 2006, 16, 171; d) P. G. Baraldi, A. Bovero, F. Fruttarolo, D. Preti,
M. A. Tabrizi, M. G. Pavani, R. Romagnoli, Med. Res. Rev. 2004, 24,
475.
4261; d) F. Wang, H. Liu, H. Fu, Y. Jiang, Y. Zhao, Org. Lett. 2009, 11,
2469.
[17] a) S. L. Ho, C. S. Cho, H.-S. Sohn, Synthesis 2015, 47, 216; b) X. Fan,
Y. He, L. Cui, S. Guo, J. Wang, X. Zhang, Eur. J. Org. Chem. 2012,
673; c) V. Kavala, C.-C. Wang, D. K. Barange, C.-W. Kuo, P.-O. Lei,
C.-F. Yao, J. Org. Chem. 2012, 77, 5022; d) S. Cai, F. Wang, C. Xi, J.
Org. Chem. 2012, 77, 2331; e) T. Kálai, B. Bognár, D. Zsolnai, Z.
Berente, K. Hideg, Synthesis 2012, 44, 3655; f) C. C. Malakar, D.
Schmidt, J. Conrad, U. Beifuss, Org. Lett. 2011, 13, 1972.
[18] S. S. Y. Chui, S. M. F. Lo, J. P. H. Charmant, A. G. Orpen, I. D.
Williams, Science 1999, 283, 1148.
[5]
For synthetic methods and biological activities of [1,2-a]alicyclic
compound-fused benzimidazolequinones, see: a) E. Moriarty, F.
Aldabbagh, Tetrahedron Lett. 2009, 50, 5251; b) S. Hehir, L.
O’Donovan, M. P. Carty, F. Aldabbagh, Tetrahedron 2008, 64, 4196; c)
M. Lynch, S. Hehir, P. Kavanagh, D. Leech, J. O’Shaughnessy, M. P.
Carty, F. Aldabbagh, Chem. Eur. J. 2007, 13, 3218; d) J.
O’Shaughnessy, F. Aldabbagh, Synthesis 2005, 1069; e) E. B. Skibo, I.
Islam, W. G. Schulz, R. Zhou, L. Bess, R. Boruah, Synlett 1996, 297.
N. Batenko, A. Kricka, S. Belyakov, B. Turovska, R. Valters.
Tetarhedron Lett. 2016, 57, 292.
[19] S. L. Ho, I. C. Yoon, C. S. Cho, H.-J. Choi, J. Organomet. Chem. 2015,
791, 13.
[20]
a) G. A. M. Jardim, J. F. Bower, E. N. da Silva Júnior, Org. Lett. 2016,
18, 4454; b) V. Sanna, S. Nurra, N. Pala, S. Marceddu, D. Pathania, N.
Neamati, M. Sechi, J. Med. Chem. 2016, 59, 5209; c) A. Gellis, H.
Kovacic, N. Boufatah, P. Vanelle, Eur. J. Med. Chem. 2008, 43, 1858;
d) L. Garuti, M. Roberti, D. Pizzirani, A. Pession, E. Leoncini, V. Cenci,
S. Hrelia, Il Farmaco 2004, 59, 663.
[6]
[7]
a) P. D. Q. Dao, S. L. Ho, H.-J. Lim, C. S. Cho, J. Org. Chem. 2018, 83,
4140; b) P. D. Q. Dao, S. L. Ho, C. S. Cho, ACS Omega 2018, 3,
12114.
[21] a) E. Moriarty, M. Carr, S. Bonham, M. P. Carty, F. Aldabbagh, Eur. J.
Med. Chem. 2010, 45, 3762; b) F. Alvarez, A. Ghérardi, P. Nebois, M.-
E. Sarciron, A.-F. Pétavy, N. Walchshofer, Bioorg. Med. Chem. Lett.
2002, 12, 977.
[8]
a) P. D. Q. Dao, H. K. Lee, H.-S. Sohn, N. S. Yoon, C. S. Cho, ACS
Omega 2017, 2, 2953; b) S. L. Ho, P. D. Q. Dao, C. S. Cho, Synlett
2017, 28, 1811; c) P. D. Q. Dao, C. S. Cho, S. L. Ho, H.-S. Sohn, Cur.
Org. Chem. 2018, 22, 85; d) H. K. Lee, P. D. Q. Dao, Y. Kim, C. S. Cho,
Synthesis 2018, 50, 3243; e) P. D. Q. Dao, S. L. Ho, C. S. Cho, ACS
Omega 2018, 3, 5643; (f) D. Y. Kim, P. D. Q. Dao, C. S. Cho, ACS
Omega 2018, 3, 17456.
[22] N. Boufatah, A. Gellis, J. Maldonado, P. Vanelle, Tetrahedron 2004, 60,
9131-9137.
[9]
B. W. Yang, P. D. Q. Dao, N. S. Yoon, C. S. Cho, J. Organomet. Chem.
2017, 851, 136.
[10] For
synthetic
methods
and
biological
activities
of
benzo[4,5]imidazo[2,1–a]isoquinolines, see: a) L. W. Deady, P. M. Loria,
T. Rodemann, Aust. J. Chem. 1998, 51, 941; b) V. K. Pandey, A.
Shukla, Indian J. Chem. Sect. B 1999, 38, 1381; c) G. Dyker, W. Stirner,
G. Henkel, Eur. J. Org. Chem. 2000, 1433; d) N. Okamoto, K. Sakurai,
M. Ishikura, K. Takeda, R. Yanada, Tetrahedron Lett. 2009, 50, 4167;
e) H.-C. Ouyang, R.-Y. Tang, P. Zhong, X.-G. Zhang, J.-H. Li, J. Org.
Chem. 2011, 76, 223; f) V. Rustagi, T. Aggarwal, A. K. Verma, Green
Chem. 2001, 13, 1640; g) V. Rustagi, R. Tiwari, A. K. Verma, Eur. J.
Org. Chem. 2012, 4590; h) S. Nandi, S. Samanta, S. Jana, J. K. Ray,
Tetrahedron Lett. 2010, 51, 5294; i) M. Sun, H. Wu, J. Zheng, W. Bao,
Adv. Synth. Catal. 2012, 354, 835; j) J. Peng, G. Shang, C. Chen, Z.
Miao, B. Li, J. Org. Chem. 2013, 78, 1242; k) V. P. Reddy, T. Iwasaki,
N. Kambe, Org. Biomol. Chem. 2013, 11, 2249; l) J. Jie, H. Li, S. Wu, Q.
Chai, H. Wang, X. Yang, RSC Adv. 2017, 7, 20548.
[11] For synthetic methods and biological activities and optical properties of
benzo[4,5]imidazo[1,2–a]pyridines, see: a) E. A. M. Badawey, T. Kappe,
Eur. J. Med. Chem. 1999, 34, 663; b) H. Takeshita, J. Watanabe, Y.
Kimura, K. Kawakami, H. Takahashi, M. Takemura, A. Kitamura, K.
Someya, K. Nakajima, Bioorg. Med. Chem. Lett. 2010, 20, 3893; c) A. J.
Mdakala, R. K. Gessner, P. W. Gitari, N. October, K. L. White, A.
Hudson, F. Fakorede, D. M. Shackleford, M. Kaiser, C. Yeates, S. A.
Charman, K. J. Chibale, J. Med. Chem. 2011, 54, 4581; d) K. Hirano, Y.
Oderaotoshi, S. Minakata, M. Komatsu, Chem. Lett. 2001, 30, 1262; e)
H. Yang, Y. Q. Ge, J. Jia, J. W. Wang, J. Luminescence 2011, 131, 749.
[12] L. Huang, M. He, B. Chen, B. Hu, J. Mater. Chem. A 2015, 3, 11587.
[13] a) A. Dhakshinamoorthy, A. M. Asiri, H. Garcia, Chem. Commun. 2017,
53, 10851. b) A. H. Chughtai, N. Ahmad, H. A. Younus, A. Laypkov, F.
Verpoort, Chem. Soc. Rev. 2015, 44, 6804. c) A. Dhakshinamoorthy, H.
Garcia, Chem. Soc. Rev. 2014, 43, 5750. d) A. Dhakshinamoorthy, M.
Opanasenko, J. Čejka, H. Garcia, Adv. Synth. Catal. 2013, 355, 247. e)
J.Y. Lee, O. K. Farha, J. Roberts, K. A. Scheidt, S.B. T. Nguyen, J. T.
Hupp, Chem. Soc. Rev. 2009, 38, 1450.
[14] K. M. Khan, I. Khan, S. Perveen, M. I. Malik, J. Fluorine Chem. 2014,
158, 1.
[15] Y.-Q. Jiang, S.-H. Jia, X.-Y. Li, Y.-M. Sun, W. Li, W.-W. Zhang, G.-Q.
Xu, Chem. Pap. 2018, 72, 1265.
[16] a) X. Xie, G. Cai, D. Ma, Org. Lett. 2005, 7, 4693; b) S. F. Yip, H. Y.
Cheung, Z. Zhou, F. Y. Kwong, Org. Lett. 2007, 9, 3469; c) J. G.
Zeevaart, C. J. Parkinson, C. B. de Koning, Tetrahedron Lett. 2004, 45,
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900635
European Journal of Organic Chemistry
FULL PAPER
Entry for the Table of Contents
FULL PAPER
Cyclization
Thi Duyen Diep, Pham Duy Quang Dao,
Chan Sik Cho*
Page No. – Page No.
Synthesis of Binuclear Isoquinoline–
and Pyridine–Fused Benzimidazole–
4,7–diones by Magnetic MOF-199-
Catalyzed C–C Coupling/Cyclization
Followed by Oxidation
A new synthetic method of binuclear isoquinoline– and pyridine–fused
benzimidazole–4,7–diones via a recyclable copper-catalyzed coupling and
cyclization followed by oxidation has been developed.
This article is protected by copyright. All rights reserved.