An efficient synthesis of 6-arylbenzo[4,5]imidazo[2,1-a] isoquinolines via sequential α-arylation of carbonyl and deacylation catalyzed by CuI

Article abstract of DOI:10.1039/c7ob01022b

Dibenzoyl methane was found to undergo α-arylation of carbonyl and deacylation reaction with 2-(2-bromophenyl)-1H-benzo[d]imidazoles catalyzed by CuI in the presence of Cs₂CO₃, and provided an efficient synthesis of 6-arylbenzo[4,5]i

Full text of DOI:10.1039/c7ob01022b

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Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
benzene
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An Efficient Synthesis of 6-Arylbenzo[4,5]imidazo[2,1-
a]isoquinolines via Sequential α-Arylation of Carbonyl and
Deacylation Catalyzed by CuI
Received 00th January 20xx,
Accepted 00th January 20xx
Wei-Qing Miao, Jian-Quan Liu*, Xiang-Shan Wang*
DOI: 10.1039/x0xx00000x
www.rsc.org/
The dibenzoyl methane was found to undergo α-arylation of carbonyl and deacylation reaction with 2-(2-bromophenyl)-
1H-benzo[d]imidazoles catalyzed by CuI in the presence of Cs2CO3, and provided an efficient synthesis of 6-
arylbenzo[4,5]imidazo[2,1-a]isoquinolines via subsequent intra-molecular nucleophilic addition and dehydration.
benzo[4,5]imidazo[2,1-a]isoquinolines (Scheme 1, (3)).5 However,
there still exist some disadvantages in the reported methodology,
such as unavailable reactants (phenylbromoethyne), and expensive
Pd catalyst. Moreover, there are two ways of the addition reaction
between amino and acetylenic bond, and they likely result in two
types of the presumptive products which are benzoimidazo[2,1-
a]isoquinolines and benzoimidazo[2,1-a]isoindole derivatives. In
2011, Fu’s group8 reported that the product was benzoimidazo[2,1-
a]isoindoles when the reaction of 2-(2-bromophenyl)-1H-
benzo[d]imidazole and phenylacetylene was treated in DMSO
catalyzed by CuI/pipecolinic acid.
Introduction
Benzimidazoles and isoquinolines are both bio-active molecules in
pharmaceutical chemistry, and their best-known applications are
using as the proton pump inhibitor and a lymphocyte antigen,
respectively. The representative drugs are Pantoprazole1 and
Lifitegrast2 (Figure 1), which are used for the treatment of erosive
esophagitis and keratoconjunctivitis sicca in clinical practice. The
benzimidazole annelleted isoquinoline, that is benzoimidazo-
isoquinoline, is a tetracyclic heterocycle bearing both above-
mentioned active moieties which get much attention in recent
years.3-7
Previous work
NH2
Ph
N
N
Ph
Br
NH2
O
(1)
Cat.
Pd(PPh3)2Cl2
Cl
CHO
CHO
O
O
OCH3 OCH3
N
N
N
F
H
N
Ph
S
Br
N
N
H
F
O
NH2
Pd(OAc)2
CO2H O
Cl
Ph
CHO
+
+
N
CuI, PPh3
NH2
(2)
(3)
SO2CH3
Pantoprazole
Lifitegrast
Ph
Figure 1. The interesting drugs containing benzimidazole or isoquinoline
N
N
N
Pd(OAc)2
Ph
Br
+
N
H
Ph
As an important member of this family, 6-arylbenzo
[4,5]imidazo[2,1-a]isoquinolines are mainly synthesized by a two-
component reaction of o-phenylenediamine and 2-phenylethynyl
benzaldehyde in the presence of various catalysts,3 or three-
component reaction of 2-bromobenzaldehyde, phenylacetylene,
1,2-phenylene-diamine catalyzed by Pd(OAc)2 under microwave-
accelerated process (Scheme 1, (1) and (2)).4 In addition,
nucleophilic addition of benzimidazoles and alkynyl bromides
promoted by palladium is also an efficient method to synthesize
This work
Deacylation
- PhCO2H
N
N
N
N
(PhCO)2CH2
CuI, Cs2CO3
(4)
N
H
N
H
Dehydration
Br
PhCO
Ph
COPh
Scheme 1. Approaches to benzo[4,5]imidazo[2,1-a]isoquinolines
In recent years, it is easy to undergo the deacylation between aryl
halide and 1,3-dicarbonyl compounds,9,10 especially for pentane-
dione. However, as far as we know there is no report concerning
about the deacylation reaction of dibenzoyl methane. Therefore,
we reason that using 2-(2-bromophenyl)-1H-benzo[d]imidazole as a
reactant to react with dibenzoyl methane, sequential α-arylation of
carbonyl and deacylation would take place via controlling the
reaction conditions, and then the intra-molecular amino group
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should attack the carbonyl to give 6-arylbenzo[4,5]imidazo[2,1- than that of Cs2CO3 catalyzed by CuI. Subsequently, CuI along with
a]isoquinoline through a subsequent dehydration (Scheme 1, (4)). various ligands, for example L-proline (L1), N-methylglycine (L2),
Furthermore, it should give a single desired product without the by- triphenyl phosphine (L3) and phenanthroline (L4) were used to the
products of benzoimidazo[2,1-a]isoindoles according to theoretical model reaction. However, to our surprise, the ligands we tested
analysis. As our continuous study on copper-catalyzed organic were all ineffective for this procedure. In fact, 1,3-dicarbonyl
reaction to polycyclic heterocycles,11 herein, we would like to report compounds, such as acetylacetone, are good ligands for copper (I)
the one-pot reaction of 2-(2-bromophenyl)-1H-benzo[d]imidazole themselves. We wonder that the dibenzoylmethane is not only the
and dibenzoyl methane catalyzed by copper for the synthesis of 6- reactant, but also the ligand for CuI in the reaction. Therefore, the
arylbenzo[4,5]imidazo[2,1-a]isoquinoline derivatives.
ratio of the reactants (2a : 1a) was finally taken into consideration
to improve the yield of 3a, such as 1.1 : 1, 1.2 : 1 and 1.3 : 1. It was
found that the 1.2 : 1 was a suitable ratio for this conversion to give
3a in the highest yield (85%).
Results and discussion
Under the optimized reaction condition that is catalyzed by 5 mol%
CuI along with 20 mol% excess of dibenzoylmethane in dioxane at
70 °C, we studied the scope of the novel domino reaction with 2-(2-
bromophenyl)-1H-benzo[d]imidazoles 1 first (Table 2). Various kinds
of substituent groups including electron-withdrawing, such as F and
Cl, electron-donating, such as methyl and methoxy group for R1 and
R2 on the benzene ring, were all proved to be suitable for the
optimal conditions, and gave the desired 3a-3l in good yields. Then,
dibenzoylmethane with methoxy or chloro, such as 1,3-di(4-
methoxyphenyl)propane-1,3-dione (2b) and 1,3-di(4-chlorophenyl)
propane-1,3-dione (2c) also delivered the satisfied results (3m-3t).
Aliphatic 1,3-dicarbonyl compounds that we tried such as heptane-
3,5-dione (2d) gave the same results as those of dibenzoylmethane,
and 3u, 3v were obtained in 69% and 76% yields, respectively.
Table 2. The scope of 1 and 2 to benzoimidazoisoquinolines catalyzed by CuI
Table 1. Optimization of the model reactiona
Entry
1
Cat.
CuI
Ligands
2a:1a
1:1
Bases
Yields (%)
38
17
16
0
-
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
Na2CO3
K2CO3
2
CuBr
CuCl
Cu
-
1:1
3
-
1:1
4
-
1:1
R2
R2
N
N
N
R3
R3
CuI
5
Cu(OAc)2
CuI
-
1:1
0
R1
R1
+
N
H
Cs2CO3
6
-
1:1
42
58
66
52
47
62
60
54
56
74
85
85
O
O
70 o
C
Br
R3
7
CuI
-
1:1
Dioxane
2
3
8
CuI
-
1:1
Cs2CO3
Et3N
1
9
CuI
-
1:1
N
N
N
N
N
N
N
10
11
12
13
14
15
16
17
CuI
-
1:1
DBU
F
Cl
N
CuI
L1
L2
L3
L4
-
1:1
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
CuI
1:1
Ph
Ph
Ph
Ph
CuI
1:1
3a, 85%
3d, 80%
3b, 84%
3c, 83%
CuI
1:1
Cl
F
F
OMe
N
N
N
CuI
1.1:1
1.2:1
1.3:1
N
N
N
N
CuI
-
N
CuI
-
Ph
Ph
Ph
Ph
aReaction conditions: 1a (136 mg, 0.5 mmol), catalyst (0.025 mmol), ligands (0.1
mmol), base (1.0 mmol), dioxane (10.0 mL), 70 °C, 12 h.
3e, 84%
3h, 75%
3f, 83%
3g, 80%
OMe
OMe
F
Cl
O
N
N
N
N
N
N
N
N
O
At the outset of our study and based on the previous
achievements,10a dibenzoyl methane did not undergo the
deacylation of aryl halide and 1,3-dicarbonyl compounds catalyzed
by CuI in the presence of K3PO4. Perhaps the best reason is that the
alkalinity of K3PO4 is too weak, so NaHCO3 was selected to replace
K3PO4 to promote the model reaction of 2-(2-bromophenyl)-1H-
benzo[d]imidazole (1a) and dibenzoyl methane (2a) in the presence
of CuI at 70 °C for 12 h (Table 1). To our delight, the desired
deacylation took place and the subsequent nucleophilic addition,
dehydration also occurred under the same reaction conditions to
give 6-phenylbenzo[4,5]imidazo[2,1-a]isoquinoline (3a) in 38% yield.
Although the yield was not satisfactory, this result prompted us to
screen other copper sources, such as CuBr and CuCl, but they all
gave slightly lower yields, and Cu and Cu(OAc)2 were not able to
promote the reaction. In order to further to improve the reaction
yields, different bases, such as Na2CO3, K2CO3 and Cs2CO3 were
tested for this transformation, and Cs2CO3 gave the best result in
66% yield. In addition, organic bases, for example, Et3N and DBU
were also used to promote the reaction, but they gave lower yields
Ph
3i, 78%
Ph
3l, 80%
Ph
3j, 75%
Ph
3k, 80%
Cl
N
N
N
N
N
N
N
N
Cl
F
4-MeOC6H4
4-MeOC6H4
3p, 82%
4-MeOC6H4
3n, 80%
4-MeOC6H4
3m, 84%
3o, 78%
F
Cl
OMe
F
N
N
N
N
N
N
N
N
4-MeOC6H4
4-ClC6H4
4-MeOC6H4
4-MeOC6H4
3s
3q, 81%
3t, 78%
3r
, 80%
, 82%
N
N
N
Cl
N
Et
3u, 69%
Et
3v, 76%
aReaction conditions: 1a ( 0.5 mmol), 2 (0.6 mmol), CuI (5 mg, 0.025 mmol), Cs2CO3
(325 mg, 1.0 mmol), dioxane (10.0 mL), 70 °C.
Quite unexpectedly, acetylacetone (2e) was also used to react with
1 (Scheme 2). Under the same reaction conditions, the desired
2 | J. Name., 2012, 00, 1-3
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deacylation did not take place, but providing the non-deacylation the final product 3. Perhaps, the activity of carbonyl group plays a
but dehydration products 4a, 4b in 62% and 68% yields, respectively. key role in the transformation. The carbonyl group in acetylacetone
These result were obviously different from those of dehydration.9,10 has the highest activity, so the amino group attacks it directly
R
before deacylation to give 4.
R
N
N
O
O
CuI, 70 oC
+
N
Cs2CO3
Dioxane
N
Experimental
H
Br
O
Melting points were determined in open capillaries and are
uncorrected. IR spectra were recorded on a Tensor 27 spectrometer
in KBr pellet. NMR spectra were obtained from a solution in DMSO-
d6 with Me4Si as internal standard using a Bruker-400 spectrometer.
HRMS analyses were carried out using a Bruker-micro-TOF-Q-MS
analyzer.
1
2e
4a
4b
: R = F, 62%
: R = Cl, 68%
Scheme 2. The reaction involving acetylacetone
General procedure for the syntheses of 3
It should be noted that if the center-asymmetric 1-(4-(tert-
butyl)phenyl)-3-(4-methoxyphenyl)propane-1,3-dione (2f) was used
for challenging the chemoselectivity of deacylation (Scheme 3). It
was found that two expected products (3n and 3w) were obtained
in almost the same yields (32% and 36%) which indicated there is
no chemoselectivity for deacylation between tert-butyl and
methoxy groups on benzene ring.
A reaction flask with high vacuum valve was charged with 2-(2-
bromophenyl)-1H-benzo[d]imidazole (0.5 mmol), dibenzoyl
methane or acetylacetone (0.6 mmol), CuI (5 mg, 0.025 mmol),
Cs2CO3 (325 mg, 1.0 mmol). After three times in vacuum and
oxygen of replacement, dioxane (10.0 mL) was injected into the
mixture. And then, the reaction mixture was stirred at 70 °C under
an argon balloon before reaching completion, which was monitored
by TLC. The solvent was recovered by distillation under reduced
pressure, and then purified by chromatography over silica gel to
give 3 or 4 using ethyl acetate and petroleum ether (1:4) as an
eluent.
N
N
N
Cl
+
Cl
2f, CuI
Cl
N
N
N
H
Cs2CO3
70 o
C
Br
Dioxane
3n, 32%
1
3w, 36%
O
6-Phenylbenzo[4,5]imidazo[2,1-a]isoquinoline (3a). Yield 85% (125
mg). Pale white solid, m.p. 182-183 °C (Lit.5 178-179 °C). 1H NMR
(CDCl3, 400 MHz): δH 6.49 (d, J = 8.4 Hz, 1H), 6.92 (s, 1H), 6.99-7.03
(m, 1H), 7.38-7.41 (m, 1H), 7.60-7.67 (m, 5H), 7.68-7.75 (m, 3H),
7.99 (d, J = 8.4 Hz, 1H), 8.88-8.92 (m, 1H). 13C NMR (CDCl3, 100
MHz): δC 112.6, 114.1, 119.7, 121.3, 122.9, 124.2, 125.1, 126.7,
127.9, 129.0, 129.4, 129.9, 130.1, 130.7, 131.6, 134.7, 137.5, 144.2,
Scheme 3. The reaction including center-asymmetric 2f
148.3. IR (KBr):
ν 3067, 3021, 1633, 1607, 1528, 1494, 1449, 1331,
1311, 1274, 1233, 1174, 1159, 1119, 1014, 960, 918, 835, 799, 737,
707, 700 cm-1. HRMS (TOF, APCI, m/z): Calcd for C21H15N2 [M + H]+
295.1235, found 295.1237.
3-Methyl-6-phenylbenzo[4,5]imidazo[2,1-a]isoquinoline (3b). Yield
84% (129 mg). Pale white solid, m.p. 199-201 °C (Lit.5 193-195 °C).
1H NMR (CDCl3, 400 MHz): δH 2.55 (s, 3H), 6.47 (d, J = 8.4 Hz, 1H),
6.84 (s, 1H), 6.96-7.00 (m, 1H), 7.36-7.39 (m, 1H), 7.51-7.52 (m, 2H),
7.59-7.66 (m, 5H), 7.97 (d, J = 8.0 Hz, 1H), 8.77 (d, J = 8.8 Hz, 1H). 13
C
NMR (CDCl3, 100 MHz): δC 21.9, 112.5, 114.0, 119.5, 120.6, 121.0,
124.1, 125.0, 126.4, 129.0, 129.4, 129.5, 129.8, 130.7, 131.7, 134.8,
137.5, 140.5, 144.3, 148.5. IR (KBr):
ν 3080, 3051, 2922, 1609, 1528,
1474, 1450, 1321, 1293, 1275, 1234, 1169, 1148, 1130, 1108, 1074,
1019, 891, 820, 774, 769, 757, 739, 699 cm-1. HRMS (TOF, APCI,
m/z): Calcd for C22H17N2 [M + H]+ 309.1392, found 309.1394.
3-Chloro-6-phenylbenzo[4,5]imidazo[2,1-a]isoquinoline (3c). Yield
83% (136 mg). Pale yellow solid, m.p. 185-186 °C (Lit.5 175-177 °C).
1H NMR (CDCl3, 400 MHz): δH 6.47 (d, J = 8.4 Hz, 1H), 6.82 (s, 1H),
6.99-7.04 (m, 1H), 7.38-7.42 (m, 1H), 7.58-7.64 (m, 5H), 7.65-7.70
(m, 2H), 7.97 (d, J = 8.4 Hz, 1H), 8.81 (d, J = 8.8 Hz, 1H). 13C NMR
Scheme 4. The plausible reaction mechanism
(CDCl3, 100 MHz):
126.7, 128.4, 129.1, 129.3, 130.1, 130.6, 132.7, 134.2, 136.2, 138.8,
144.2, 147.7. IR (KBr): 2985, 2830, 1632, 1606, 1551, 1492, 1477,
δC 111.4, 114.1, 119.7, 121.2, 121.6, 124.5, 125.9,
According to literature,10a a plausible reaction mechanism was
outlined in Scheme 4. 1 goes through an oxidative addition with 5
to give 6, 6 then reacts with 2 in the presence of base (Cs2CO3) to
ν
1447, 1398, 1358, 1329, 1273, 1188, 1174, 1153, 1083, 1009, 892,
form intermediate 7, followed by a reductive elimination to deliver 799, 774, 740, 704 cm-1. HRMS (TOF, APCI, m/z): Calcd for
C21H14ClN2 [M + H]+ 329.0846, found 329.0827.
intermediate product 8. And then, 9 is obtained via a retro-Claisen
deacylation9 losing
a molecule of benzoic acid. At last, the
3-Fluoro-6-phenylbenzo[4,5]imidazo[2,1-a]isoquinoline (3d). Yield
80% (125 mg). Pale yellow solid, m.p. 192-193 °C; 1H NMR (CDCl3,
subsequent nucleophilic addition and dehydration occur to afford
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400 MHz): δ
H 6.47 (d, J = 8.4 Hz, 1H), 6.85 (s, 1H), 6.98-7.02 (m, 1H), 7.59-7.64 (m, 5H), 7.96 (d, J = 8.0 Hz, 1H), 8.25 (s, 1H). 13C NMR
7.35-7.42 (m, 3H), 7.58-7.67 (m, 5H), 7.96 (d, J = 8.4 Hz, 1H), 8.87- (CDCl3, 100 MHz): δC 56.1, 56.5, 105.5, 107.1, 112.1, 114.1, 117.0,
8.90 (m, 1H). 13C NMR (CDCl3, 100 MHz):
C 111.7 (d, J(F-C) = 22.0 Hz), 119.2, 120.6, 124.1, 126.6, 129.0, 129.5, 129.7, 130.7, 134.8, 136.1,
111.8, 114.1, 116.6 (d, J(F-C) = 23.0 Hz), 119.5 (d, J(F-C) = 2.0 Hz), 119.6, 144.3, 148.2, 150.1, 151.9. IR (KBr): 3058, 2995, 2974, 1652, 1615,
121.4, 124.4, 127.8 (d, J(F-C) = 10.0 Hz), 129.1, 129.3, 130.1, 130.6, 1600, 1503, 1489, 1470, 1454, 1443, 1383, 1322, 1296, 1286, 1235,
133.5 (d, J(F-C) = 10.0 Hz), 134.3, 138.8, 144.2, 147.8, 163.7 (d, J(F-C) 1176, 1131, 1108, 1067, 1029, 1015, 997, 867, 852, 763, 736, 707
249.0 Hz). IR (KBr):
3065, 3027, 1659, 1620, 1578, 1532, 1495, cm-1. HRMS (TOF, APCI, m/z): Calcd for C23H19N2O2 [M + H]+
δ
ν
=
ν
1472, 1451, 1420, 1391, 1369, 1337, 1322, 1296, 1239, 1154, 1146, 355,1447, found 355.1447.
1117, 1075, 964, 947, 895, 824, 774, 760, 704 cm-1. HRMS (TOF,
APCI, m/z): Calcd for C21H14FN2 [M + H]+ 313.1141, found 313.1146.
6-Phenylbenzo[4,5]imidazo[2,1-a][1,3]dioxolo[4,5-g]isoquinoline
(3j). Yield 75% (127 mg). Pale yellow solid, m.p. 203-204 °C; 1H NMR
2-Chloro-6-phenylbenzo[4,5]imidazo[2,1-a]isoquinoline (3e). Yield (CDCl3, 400 MHz): δH 6.14 (s, 2H) 6.49 (d, J = 8.4 Hz, 1H), 6.80 (s, 1H),
84% (138 mg). Pale yellow solid, m.p. 213-215 °C (Lit.5 217-219 °C). 6.95-6.99 (m, 1H), 7.08 (s, 1H), 7.35-7.39 (m, 1H), 7.58-7.65 (m, 5H),
1H NMR (CDCl3, 400 MHz): δH 6.49 (d, J = 8.4 Hz, 1H), 6.87 (s, 1H), 7.94 (d, J = 8.4 Hz, 1H), 8.24 (s, 1H). 13C NMR (CDCl3, 100 MHz): δC
7.00-7.04 (m, 1H), 7.39-7.42 (m, 1H), 7.60-7.67 (m, 7H), 7.98 (d, J = 101.8, 103.5, 104.7, 112.4, 114.1, 118.4, 119.3, 120.7, 124.2, 128.2,
8.4 Hz, 1H), 8.88 (s, 1H). 13C NMR (CDCl3, 100 MHz):
119.9, 121.6, 124.0, 124.5, 124.6, 128.06, 128.09, 129.1, 129.30, IR (KBr): 3007, 2954, 1597, 1530, 1486, 1469, 1456, 1409, 1394,
δ
C 111.8, 114.2, 129.0, 129.5, 129.8, 130.6, 134.6, 136.1, 144.3, 148.3, 148.5, 150.3.
ν
129.33, 129.8, 130.0, 130.5, 133.8, 134.3, 137.8, 144.2. IR (KBr):
ν
1350, 1279, 1244, 1185, 1078, 1037, 1001, 872, 845, 811, 783, 739,
3064, 3019, 1595, 1529, 1450, 1419, 1401, 1389, 1324, 1273, 1183, 705 cm-1. HRMS (TOF, APCI, m/z): Calcd for C22H15N2O2 [M + H]+
1158, 1081, 1029, 990, 935, 877, 853, 840, 814, 766, 736, 707 cm-1. 339.1134, found 339.1134.
HRMS (TOF, APCI, m/z): Calcd for C21H14ClN2 [M + H]+ 329.0846,
found 329.0828.
2-Chloro-9,10-dimethyl-6-phenylbenzo[4,5]imidazo[2,1-
a]isoquinoline (3k). Yield 80% (142 mg). Pale white solid, m.p. 282-
1
2-Fluoro-6-phenylbenzo[4,5]imidazo[2,1-a]isoquinoline (3f). Yield 283 °C; H NMR (CDCl3, 400 MHz):
δ
H 2.13 (s, 3H), 2.38 (s, 3H), 6.20
83% (129 mg). Pale white solid, m.p. 185-186 °C; 1H NMR (CDCl3, (s, 1H), 6.83 (s, 1H), 7.56-7.66 (m, 7H), 7.72 (s 1H), 8.84 (s, 1H). 13C
400 MHz): H 6.49 (d, J = 8.4 Hz, 1H), 6.89 (s, 1H), 7.00-7.04 (m, 1H), NMR (CDCl3, 100 MHz): δC 20.4, 20.8, 111.2, 114.2, 119.6, 124.1,
7.38-7.42 (m, 2H), 7.59-7.66 (m, 5H), 7.69-7.73 (m, 1H), 7.98 (d, J = 124.4, 128.0, 128.9, 129.1, 129.4, 129.6, 129.9, 130.1, 130.8, 133.6,
8.4 Hz, 1H), 8.53 (dd, J = 2.4, 9.2 Hz, 1H). 13C NMR (CDCl3, 100 MHz): 133.7, 134.5, 137.8, 142.9, 146.5. IR (KBr):
3026, 2998, 2964, 2944,
δC 110.5 (d, J(F-C) = 24.0 Hz), 111.8, 114.2, 118.8 (d, J(F-C) = 23.0 Hz), 2917, 1594, 1552, 1529, 1497, 1472, 1461, 1420, 1395, 1382, 1371,
119.8, 121.6, 124.4, 124.5, 128.1 (d, J(F-C) = 2.0 Hz), 128.9 (d, J(F-C) 1298, 1237, 1134, 1076, 1059, 999, 945, 919, 881, 841, 799, 770,
8.0 Hz), 129.0, 129.4, 130.0, 130.7, 134.4, 136.8 (d, J(F-C) = 3.0 Hz), 726, 705 cm-1. HRMS (TOF, APCI, m/z): Calcd for C23H18ClN2 [M + H]+
δ
ν
=
144.1, 147.5 (d, J(F-C) = 4.3 Hz), 162.0 (d, J(F-C) = 247.0 Hz). IR (KBr):
ν
357.1159, found 357.1160.
3065, 1613, 1529, 1493, 1448, 1397, 1370, 1336, 1276, 1240, 1174,
1156, 1117, 1097, 1009, 955, 877, 855, 794, 737, 709 cm-1. HRMS
(TOF, APCI, m/z): Calcd for C21H14FN2 [M + H]+ 313.1141, found
313.1145.
2-Fluoro-9,10-dimethyl-6-phenylbenzo[4,5]imidazo[2,1-
a]isoquinoline (3l). Yield 80% (136 mg). Pale yellow solid, m.p. 226-
1
227 °C; H NMR (CDCl3, 400 MHz):
δH 2.13 (s, 3H), 2.38 (s, 3H), 6.20
(s, 1H), 6.85 (s, 1H), 7.34-7.39 (m, 1H), 7.57-7.72 (m, 7H), 8.49 (dd, J
(3g). = 2.4, 9.6 Hz, 1H). 13C NMR (CDCl3, 100 MHz):
C 20.4, 20.8, 110.2 (d,
Yield 80% (130 mg). Pale yellow solid, m.p. 185-186 °C (Lit.5 186- J(F-C) = 23.0 Hz), 111.3, 114.3, 118.4 (d, J(F-C) = 24.0 Hz), 119.6, 124.6
188 °C). 1H NMR (CDCl3, 400 MHz):
H 4.07 (s, 3H), 6.51 (d, J = 8.4 Hz, (d, J(F-C) = 9.0 Hz), 127.9 (d, J(F-C) = 2.0 Hz), 128.8 (d, J(F-C) = 9.0 Hz),
1H), 6.89 (s, 1H), 6.99-7.03 (m, 1H), 7.31 (dd, J = 4.0, 8.4 Hz, 1H), 129.2, 129.5, 129.8, 130.8, 133.6, 134.6, 136.8, 142.8, 146.8, 146.9,
2-Methoxy-6-phenylbenzo[4,5]imidazo[2,1-a]isoquinoline
δ
δ
7.38-7.42 (m, 1H), 7.60-7.67 (m, 6H), 8.00 (d, J = 8.0 Hz, 1H), 8.27 (s, 161.9 (d, J(F-C) = 246.0 Hz). IR (KBr):
ν 3054, 2970, 1531, 1482, 1463,
1H). 13C NMR (CDCl3, 100 MHz): δC 56.0, 105.1, 112.4, 114.2, 119.6, 1427, 1393, 1332, 1309, 1231, 1194, 1183, 1156, 1125, 1088, 1030,
120.97, 121.13, 124.2, 125.7, 128.3, 128.9, 129.6, 129.7, 130.8, 953, 927, 873, 810, 792, 761, 736, 705 cm-1. HRMS (TOF, APCI, m/z):
134.8, 135.3, 144.2, 148.1, 159.5. IR (KBr): ν
3040, 2927, 1527, 1484, Calcd for C23H18FN2 [M + H]+ 341.1454, found 341.1424.
1450, 1347, 1317, 1254, 1220, 1181, 1151, 1122, 1100, 1062, 1030,
926, 849, 764, 730, 712, 702 cm-1. HRMS (TOF, APCI, m/z): Calcd for
C22H17N2O [M + H]+ 325.1341, found 325.1316.
6-(4-Methoxyphenyl)-3-methylbenzo[4,5]imidazo[2,1-
a]isoquinoline (3m). Yield 84% (142 mg). Pale white solid, m.p. 193-
1
194 °C; H NMR (CDCl3, 400 MHz):
δH 2.56 (s, 3H), 3.97 (s, 3H), 6.58
1-Fluoro-6-phenylbenzo[4,5]imidazo[2,1-a]isoquinoline (3h). Yield (d, J = 8.4 Hz, 1H), 6.83 (s, 1H), 7.00-7.04 (m, 1H), 7.11 (d, J = 8.8 Hz,
75% (117 mg). Pale yellow solid, m.p. 184-186 °C; 1H NMR (CDCl3, 2H), 7.37-7.40 (m, 1H), 7.51-7.53 (m, 4H), 7.96 (d, J = 8.0 Hz, 1H),
400 MHz): δ
H 6.45 (d, J = 8.4 Hz, 1H), 6.91 (s, 1H), 7.01-7.05 (m, 1H), 8.75-8.77 (m, 1H). 13C NMR (CDCl3, 100 MHz): δC 21.9, 55.5, 112.5,
7.38-7.42 (m, 2H), 7.51 (d, J = 7.6 Hz, 1H), 7.60-7.67 (m, 6H), 8.09 (d, 114.1, 114.3, 119.5, 120.5, 121.0, 124.0, 125.0, 126.4, 127.1, 129.4,
J = 8.4 Hz, 1H). 13C NMR (CDCl3, 100 MHz):
δC 112.1 (d, J(F-C) = 2.0 Hz), 130.7, 131.9, 137.4, 140.4, 144.3, 148.3, 148.6, 160.7. IR (KBr):
ν
112.3 (d, J(F-C) = 11.0 Hz), 113.9, 114.5 (d, J(F-C) = 21.0 Hz), 120.5, 3063, 3034, 3007, 2949, 2932, 1640, 1607, 1559, 1533, 1507, 1477,
121.8, 122.4 (d, J(F-C) = 4.1 Hz), 124.3, 129.1, 129.3, 129.7, 130.1, 1463, 1449, 1410, 1379, 1325, 1302, 1291, 1249, 1185, 1173, 1108,
130.5 (d, J(F-C) = 9.0 Hz), 134.0 (d, J(F-C) = 2.5 Hz), 134.3, 138.5, 144.6 963, 928, 896, 826, 796, 743, 702 cm-1. HRMS (TOF, APCI, m/z):
(d, J(F-C) = 2.3 Hz), 144.7 (d, J(F-C) = 8.1 Hz), 160.1 (d, J(F-C) = 259.0 Hz). Calcd for C23H19N2O [M + H]+ 339.1497, found 339.3498.
IR (KBr):
ν 3059, 1642, 1565, 1521, 1472, 1443, 1388, 1343, 1320,
1275, 1234, 1153, 1085, 1066, 1032, 969, 924, 845, 778, 759, 742,
710, 693 cm-1. HRMS (TOF, APCI, m/z): Calcd for C21H14FN2 [M + H]+
313.1141, found 313.1149.
3-Chloro-6-(4-methoxyphenyl)benzo[4,5]imidazo[2,1-
a]isoquinoline (3n). Yield 80% (143 mg). Pale yellow solid, m.p. 226-
228 °C; 1H NMR (CDCl3, 400 MHz):
δ
H 3.96 (s, 3H), 6.59 (d, J = 8.4 Hz,
1H), 6.79 (s, 1H), 7.03-7.06 (m, 1H), 7.12 (d, J = 8.8 Hz, 2H), 7.39-
2,3-Dimethoxy-6-phenylbenzo[4,5]imidazo[2,1-a]isoquinoline (3i). 7.42 (m, 1H), 7.51 (d, J = 8.4 Hz, 2H), 7.61-7.63 (m, 1H), 7.69 (s, 1H),
Yield 78% (138 mg). Pale white solid, m.p. 195-196 °C; 1H NMR 7.97 (d, J = 8.0 Hz, 1H), 8.80 (d, J = 8.4 Hz, 1H). 13C NMR (CDCl3, 100
(CDCl3, 400 MHz): δH 4.04 (s, 3H), 4.16 (s, 3H), 6.50 (d, J = 8.4 Hz, MHz): δC 55.5, 111.5, 114.2, 114.4, 119.7, 121.2, 121.5, 124.4, 125.8,
1H), 6.85 (s, 1H), 6.95-6.99 (m, 1H), 7.11 (s, 1H), 7.36-7.40 (m, 1H), 126.6, 126.7, 128.2, 130.6, 130.7, 132.8, 136.1, 138.7, 144.2, 147.7,
4 | J. Name., 2012, 00, 1-3
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160.9. IR (KBr):
ν
3053, 3008, 2981, 2955, 1635, 1604, 1569, 1531, 7.66-7.73 (m, 2H), 8.48 (d, J = 8.8 Hz, 1H).
δ
C 20.4, 20.9, 55.6, 110.2
1507, 1465, 1447, 1379, 1330, 1318, 1275, 1233, 1199, 1150, 1079, (d, J(F-C) = 23.6 Hz), 111.5, 114.2, 114.4, 118.3 (d, J(F-C) = 23.5 Hz),
1019, 959, 922, 871, 839, 823, 788, 742, 696 cm-1. HRMS (TOF, APCI, 119.6, 124.4 (d, J(F-C) = 9.4 Hz), 127.0, 128.0 (d, J(F-C) = 2.0 Hz), 128.7
m/z): Calcd for C22H16ClN2O [M + H]+ 359.0951, found 359.0951.
(d, J(F-C) = 8.4 Hz), 129.2, 130.69, 130.75, 133.6, 136.6, 136.7, 142.8,
160.7, 161.8 (d, J(F-C) = 246.1 Hz). IR (KBr): 3032, 2968, 2940, 1613,
ν
1570, 1509, 1486, 1463, 1428, 1387, 1339, 1310, 1298, 1255, 1198,
1174, 1130, 1095, 1029, 1003, 945, 939, 867, 838, 808, 775, 739,
695 cm-1. HRMS (TOF, APCI, m/z): Calcd for C24H20FN2O [M + H]+
371.1560, found 371.1560.
3-Fluoro-6-(4-methoxyphenyl)benzo[4,5]imidazo[2,1-
a]isoquinoline (3o). Yield 78% (133 mg). Pale white solid, m.p. 196-
197 °C; 1H NMR (CDCl3, 400 MHz):
δH 3.96 (s, 3H), 6.58 (d, J = 8.4 Hz,
1H), 6.82 (s, 1H), 7.02-7.06 (m, 1H), 7.11 (d, J = 8.4 Hz, 2H), 7.34-
7.42 (m, 3H), 7.51 (d, J = 8.4 Hz, 2H), 7.96 (d, J = 8.0 Hz, 1H), 8.86-
8.89 (m, 1H). 13C NMR (CDCl3, 100 MHz): δC 55.5, 111.5 (d, J(F-C)
=
2-Chloro-6-(4-chlorophenyl)benzo[4,5]imidazo[2,1-a]isoquinoline
22.0 Hz), 111.8 (d, J(F-C) = 3.2 Hz), 114.2, 114.4, 116.4 (d, J(F-C) = 24.0 (3t). Yield 78% (141 mg). Pale white solid, m.p. 188-189 °C; 1H NMR
Hz), 119.4 (d, J(F-C) = 2.0 Hz), 119.6, 121.3, 124.3, 126.6, 127.8 (d, J(F- (CDCl3, 400 MHz): δH 6.59 (d, J = 8.4 Hz, 1H), 6.86 (s, 1H), 7.07-7.11
= 9.0 Hz), 130.6, 130.7, 133.6 (d, J(F-C) = 10.0 Hz), 138.7, 144.2, (m, 1H), 7.41-7.45 (m, 1H), 7.54-7.61 (m, 4H), 7.63-7.67 (m, 2H),
C)
147.9, 160.9, 163.7 (d, J(F-C) = 248.0 Hz). IR (KBr):
ν
3057, 3002, 2983, 7.99 (d, J = 8.4 Hz, 1H), 8.88 (s, 1H). 13C NMR (CDCl3, 100 MHz): δC
2939, 1638, 1606, 1563, 1507, 1472, 1450, 1380, 1337, 1302, 1275, 112.2, 113.9, 120.1, 121.9, 124.1, 124.62, 124.64, 128.1, 129.4,
1250, 1173, 1141, 1110, 1099, 1023, 962, 946, 864, 831, 795, 744, 129.6, 130.5, 130.6, 130.7, 132.7, 134.1, 136.3, 136.5, 144.2, 147.1.
733 cm-1. HRMS (TOF, APCI, m/z): Calcd for C22H16FN2O [M + H]+ IR (KBr):
ν 3048, 3025, 1603, 1529, 1490, 1471, 1449, 1421, 1388,
343.1247, found 343.1241.
1325, 1312, 1275, 1232, 1156, 1111, 1092, 1017, 966, 886, 879, 855,
839, 759, 738 cm-1. HRMS (TOF, APCI, m/z): Calcd for C21H13Cl2N2 [M
+ H]+ 363.0456, found 363.0433.
2-Chloro-6-(4-methoxyphenyl)benzo[4,5]imidazo[2,1-
a]isoquinoline (3p). Yield 82% (147 mg). Pale white solid, m.p. 194-
195 °C; 1H NMR (CDCl3, 400 MHz):
δ
H 3.99 (s, 3H), 6.63 (d, J = 8.4 Hz, 6-Ethylbenzo[4,5]imidazo[2,1-a]isoquinoline (3u). Yield 69% (85
1H), 6.85 (s, 1H), 7.04-7.08 (m, 1H), 7.11 (d, J = 8.4 Hz, 2H), 7.40- mg). Pale white solid, m.p. 110-113 °C; 1H NMR (CDCl3, 400 MHz):
7.43 (m, 1H), 7.51 (d, J = 8.4 Hz, 2H), 7.60-7.67 (m, 2H), 8.00 (d, J =
δH 1.56 (t, J = 7.6 Hz, 3H), 3.40 (q, J = 7.6 Hz, 2H), 6.81 (s, 1H), 7.35-
8.4 Hz, 1H), 8.88 (s, 1H). 13C NMR (CDCl3, 100 MHz): δC 55.5, 111.8, 7.39 (m, 1H), 7.49-7.53 (m, 1H), 7.60-7.68 (m, 3H), 8.03-8.07 (m, 2H),
114.3, 114.4, 119.8, 121.6, 123.9, 124.4, 124.6, 126.7, 128.0, 129.9, 8.83 (d, J = 7.2 Hz, 1H). 13C NMR (CDCl3, 100 MHz): δC 12.0, 26.6,
130.5, 130.7, 130.8, 133.6, 137.7, 144.2, 147.2, 160.8. IR (KBr):
3030, 3004, 2963, 2930, 1610, 1530, 1508, 1473, 1439, 1421, 1389, 130.8, 131.7, 140.4, 144.3, 148.5. IR (KBr):
ν
108.6, 114.4, 120.0, 121.8, 122.3, 124.2, 125.0, 126.0, 127.2, 130.0,
3054, 3014, 2960, 2875,
ν
1326, 1296, 1276, 1251, 1177, 1112, 1030, 926, 879, 846, 832, 786, 1560, 1527, 1454, 1430, 1378, 1339, 1325, 1294, 1245, 1220, 1181,
768, 743, 725, 688 cm-1. HRMS (TOF, APCI, m/z): Calcd for 1127, 1036, 1018, 945, 855, 838, 802, 735, 696 cm-1. HRMS (TOF,
C22H16ClN2O [M + H]+ 359.0951, found 359.0937.
ESI, m/z): Calcd for C17H15N2 [M + H]+ 247.1235, found 247.1238.
2-Fluoro-6-(4-methoxyphenyl)benzo[4,5]imidazo[2,1-
3-Chloro-6-ethylbenzo[4,5]imidazo[2,1-a]isoquinoline (3v). Yield
a]isoquinoline (3q). Yield 81% (139 mg). Pale yellow solid, m.p. 191- 76% (106 mg). Pale white solid, m.p. 178-180 °C; 1H NMR (CDCl3,
193 °C; 1H NMR (CDCl3, 400 MHz):
δH 3.97 (s, 3H), 6.60 (d, J = 8.4 Hz, 400 MHz): δH 1.52 (t, J = 7.2 Hz, 3H), 3.33 (q, J = 7.2 Hz, 2H), 6.66 (s,
1H), 6.87 (s, 1H), 7.03-7.07 (m, 1H), 7.11 (d, J = 8.4 Hz, 2H), 7.38- 1H), 7.34-7.38 (m, 1H), 7.48-7.52 (m, 1H), 7.53-7.61 (m, 2H), 7.99-
7.43 (m, 2H), 7.51 (d, J = 8.4 Hz, 2H), 7.69-7.73 (m, 1H), 7.98 (d, J = 8.02 (m, 2H), 8.72 (d, J = 8.8 Hz, 1H). 13C NMR (CDCl3, 100 MHz): δC
8.0 Hz, 1H), 8.51-8.54 (m, 1H). 13C NMR (CDCl3, 100 MHz): δC 55.5, 11.8, 26.5, 107.3, 114.4, 120.0, 120.5, 122.0, 124.4, 125.2, 126.5,
110.4 (d, J(F-C) = 23.5 Hz), 111.9, 114.29, 114.33, 118.7 (d, J(F-C) = 23.4 127.6, 130.6, 132.8, 135.9, 141.8, 144.3, 147.8. IR (KBr):
ν 3067,
Hz), 119.8, 121.5, 124.3, 124.4, 126.8, 128.2 (d, J(F-C) = 1.8 Hz), 128.8 3048, 2965, 2879, 1605, 1576, 1529, 1478, 1453, 1425, 1397, 1379,
(d, J(F-C) = 8.3 Hz), 130.7, 130.8, 136.7 (d, J(F-C) = 2.6 Hz), 144.1, 160.8, 1333, 1283, 1236, 1180, 1123, 1080, 1032, 970, 922, 878, 829, 764,
161.9 (d, J(F-C) = 246.6 Hz). IR (KBr):
ν
3049, 3004, 2976, 2932, 1615, 734, 705 cm-1. HRMS (TOF, ESI, m/z): Calcd for C17H14ClN2 [M + H]+
1605, 1574, 1559, 1506, 1487, 1451, 1428, 1382, 1335, 1318, 1284, 281.0846, found 281.0845.
1249, 1229, 1173, 1108, 1029, 955, 890, 854, 783, 743, 733, 698 cm-
1. HRMS (TOF, APCI, m/z): Calcd for C22H16FN2O [M + H]+ 343.1247,
6-(4-(tert-Butyl)phenyl)-3-chlorobenzo[4,5]imidazo[2,1-
a]isoquinoline (3w). Yield 36% (69 mg). Pale white solid, m.p. 213-
215 °C; 1H NMR (CDCl3, 400 MHz):
H 1.49 (s, 9H), 6.55 (d, J = 8.4 Hz,
1H), 6.84 (s, 1H), 7.03-7.07 (m, 1H), 7.41-7.45 (m, 1H), 7.54 (d, J =
found 343.1248.
δ
2-Methoxy-6-(4-methoxyphenyl)benzo[4,5]imidazo[2,1-
a]isoquinoline (3r). Yield 80% (142 mg). Pale white solid, m.p. 146- 8.4 Hz, 2H), 7.63-7.66 (m, 3H), 7.71-7.72 (m, 1H), 7.99 (d, J = 8.4 Hz,
1
147 °C; H NMR (CDCl3, 400 MHz): δ δC 31.4, 35.0,
H 3.96 (s, 3H), 4.06 (s, 3H), 6.61 1H), 8.84 (d, J = 8.8 Hz, 1H). 13C NMR (CDCl3, 100 MHz):
(d, J = 8.4 Hz, 1H), 6.86 (s, 1H), 7.01-7.05 (m, 1H), 7.11 (d, J = 8.4 Hz, 111.4, 114.2, 119.7, 121.2, 121.5, 124.4, 125.8, 125.9, 126.7, 128.2,
2H), 7.28-7.31 (m, 1H), 7.38-7.42 (m, 1H), 7.52 (d, J = 8.4 Hz, 2H), 128.9, 130.7, 131.3, 132.8, 136.1, 139.0, 144.2, 147.7, 153.5. IR
7.65 (d, J = 8.8 Hz, 1H), 8.00 (d, J = 8.0 Hz, 1H), 8.26 (s, 1H). 13C NMR (KBr):
ν
3051, 2965, 2953, 1554, 1540, 1528, 1507, 1489, 1472,
C 55.5, 56.0, 105.1, 112.5, 114.26, 114.34, 119.5, 1449, 1426, 1395, 1379, 1327, 1275, 1231, 1188, 1156, 1130, 1116,
121.0, 121.1, 124.2, 125.8, 127.1, 128.3, 130.9, 135.1, 140.6, 150.7, 1079, 1018, 925, 891, 834, 764, 738, 681 cm-1. HRMS (TOF, APCI,
153.3, 157.2, 159.4, 160.6. IR (KBr):
3048, 3024, 2957, 2925, 1619, m/z): Calcd for C25H22ClN2 [M + H]+ 385.1472, found 385.1470.
(CDCl3, 100 MHz):
δ
ν
1574, 1531, 1508, 1493, 1479, 1449, 1386, 1332, 1317, 1292, 1249,
1211, 1185, 1172, 1131, 1105, 1027, 957, 886, 837, 788, 767, 745
cm-1. HRMS (TOF, APCI, m/z): Calcd for C23H19N2O2 [M + H]+
355.1447, found 355.1445.
1-(2-Fluoro-6-methylbenzo[4,5]imidazo[2,1-a]isoquinolin-5-
yl)ethan-1-one (4a). Yield 62% (91 mg). Pale white solid, m.p. 180-
181 °C; 1H NMR (CDCl3, 400 MHz):
δH 2.73 (s, 3H), 3.03 (s, 3H), 7.41-
7.46 (m, 2H), 7.51-7.59 (m, 2H), 8.07 (d, J = 8.0 Hz, 1H), 8.14 (d, J =
2-Fluoro-6-(4-methoxyphenyl)-9,10-
8.4 Hz, 1H), 8.56 (dd, J = 2.4, 8.8 Hz, 1H). 13C NMR (CDCl3, 100 MHz):
dimethylbenzo[4,5]imidazo[2,1-a]isoquinoline (3s). Yield 82% (152 δC 18.5, 33.4, 111.0 (d, J(F-C) = 23.5 Hz), 114.4, 119.0 (d, J(F-C) = 23.6
1
mg). Pale yellow solid, m.p. 200-201 °C; H NMR (CDCl3, 400 MHz): Hz), 120.4, 122.6, 123.3, 124.2 (d, J(F-C) = 9.5 Hz), 124.7, 124.8 (d, J(F-
δH 2.17 (s, 3H), 2.38 (s, 3H), 3.97 (s, 3H), 6.35 (s, 1H), 6.82 (s, 1H),
= 2.1 Hz), 125.9 (d, J(F-C) = 8.4 Hz), 130.6 (d, J(F-C) = 2.7 Hz), 131.6,
C)
7.11 (d, J = 8.4 Hz, 2H), 7.34-7.38 (m, 1H), 7.50 (d, J = 8.4 Hz, 2H), 144.4, 146.6, 161.8 (d, J(F-C) = 247.9 Hz), 204.0. IR (KBr):
ν 2956,
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2925, 2852, 1692, 1662, 1632, 1604, 1530, 1463, 1431, 1392, 1377,
1363, 1327, 1221, 1189, 880, 826, 794, 769, 735, 706, 662, 636 cm-1.
2947; (h) S. J. Cai, F. Wang, C. J. Xi, J. Org. Chem. 2012, 77,
2331-2336.
HRMS (TOF, APCI, m/z): Calcd for C18H14FN2O [M + H]+ 293.1090, 10. (a) C. He, S. Guo, L. Huang, A. W. Lei, J. Am. Chem. Soc. 2010,
found 293.1080.
132, 8273-8275; (b) J. Ke, C. He, H. Y. Liu, H. Xu, A. W. Lei,
Chem. Commun. 2013, 49, 6767-6769; (c) Y. Chen, Y. J. Wang,
Z. M. Sun, D. W. Ma, Org. Lett. 2008, 10, 625-628; (d) H. Shi, A.
Braun, L. Wang, H. L. Steven, N. Vasdev, T. Ritter, Angew.
Chem. Int. Ed. 2016, 55, 1-6; (e) X. J. Yang, A. R. Reinhold, R. L.
Rosati, K. C. Liu, Org. Lett. 2000, 2, 4025-4027; (f) A. Ohkubo,
K. Sakamoto, K. I. Miyata, H. Taguchi, K. Seio, M. Sekine, Org.
Lett. 2005, 7, 5389-5392; (g) S. J. Xia, H. Y. Zhang, J. Org. Chem.
2014, 79, 6135-6142; (h) C. Y. Liu, H. L. Chen, C. M. Ko, C. T.
Chen, Tetrahedron 2011, 67, 872-876.
1-(2-Chloro-6-methylbenzo[4,5]imidazo[2,1-a]isoquinolin-5-
yl)ethan-1-one (4b). Yield 68% (105 mg). Pale white solid, m.p. 228-
229 °C; 1H NMR (CDCl3, 400 MHz):
δH 2.73 (s, 3H), 3.03 (s, 3H), 7.42-
7.47 (m, 2H), 7.56-7.60 (m, 1H), 7.64 (dd, J = 2.4, 8.8 Hz, 1H), 8.07 (d,
J = 8.0 Hz, 1H), 8.14 (d, J = 8.4 Hz, 1H), 8.90 (s, 1H). 13C NMR (CDCl3,
100 MHz): δC 18.6, 33.5, 114.4, 120.4, 122.6, 123.2, 123.5, 124.97,
124.99, 125.00, 126.4, 130.8, 131.58, 131.59, 134.0, 144.4, 146.3,
203.9. IR (KBr):
ν 3076, 2989, 2924, 1697, 1625, 1601, 1546, 1527,
11. (a) D. S. Chen, G. L. Dou, Y. L. Li, Y. Liu, X. S. Wang, J. Org. Chem.
2013, 78, 5700-5704; (b) C. Li, W. T. Zhang, X. S. Wang, J. Org.
Chem. 2014, 79, 5847-5851; (c) D. S. Chen, M. M. Zhang, Y. L.
Li, Y. Liu, X. S. Wang, Tetrahedron 2014, 70, 2889-2893; (d) C.
Li, W. T. Zhang, X, S. Wang, Tetrahedron 2014, 70, 8919-8924;
(e) B. B. Feng, J. Q. Liu, X. S. Wang, J. Org. Chem. 2017, 82,
1817-1822.
1477, 1419, 1388, 1370, 1356, 1320, 1293, 1269, 1252, 1193, 1158,
1083, 1018, 1004, 974, 930, 885, 828, 773, 737, 623 cm-1. HRMS
(TOF, APCI, m/z): Calcd for C18H14ClN2O [M + H]+ 309.0795, found
309.0793.
Conclusions
In conclusion, we developed
a novel procedure for rapid
construction of 6-arylbenzo[4,5]imidazo[2,1-a]isoquinolines in good
yields. This copper-catalyzed domino reaction of 2-(2-
bromophenyl)-1H-benzo[d]imidazoles and dibenzoyl methanes
provided an efficient synthesis of fused tetracyclic heterocycles
bearing both benzimidazole and isoquinoline moieties.
Acknowledgements
We are grateful to the Major Natural Science Foundation of Jiangsu
Province (14KJA150004), a project funded by the Priority Academic
Program Development of Jiangsu Higher Education Institutions of
Jiangsu Province for financial support.
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