Copper-catalyzed one-pot synthesis of substituted benzimidazo[1,2-a] quinolines

Article abstract of DOI:10.1055/s-0030-1258146

A one-pot procedure for the synthesis of substituted benzimidazo[1,2-a] quinolines from the corresponding benzimidazoles and 2-bromobenzaldehydes has been developed. The titled products were prepared through Knoevenagel condensation and copper-catalyzed intramolecular Ullmann-type coupling in moderate to good yields. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0030-1258146

2794
PAPER
Copper-Catalyzed One-Pot Synthesis of Substituted
Benzimidazo[1,2-a]quinolines
One-Pot Synthes
i
n
nzimidazo[1
g
,2-
a
]quinoli
-
College of Chemical Engineering and Materials Science, Zhejiang University of Technology, Hangzhou 310014, P. R. of China
Fax +86(571)88320415; E-mail: jhwei828@zjut.edu.cn
Received 19 March 2010; revised 27 April 2010
substrate scope and substituent effects compared with
those from the group of Cai.
Abstract: A one-pot procedure for the synthesis of substituted benz-
imidazo[1,2-a]quinolines from the corresponding benzimidazoles
and 2-bromobenzaldehydes has been developed. The titled products
were prepared through Knoevenagel condensation and copper-
catalyzed intramolecular Ullmann-type coupling in moderate to
good yields.
Initially, benzimidazole-2-acetonitrile (1a) and 2-bro-
mobenzaldehyde (2a) were chosen as model substrates.
Since the condensation in the first step proceeded easily in
the presence of a catalytic amount of piperidine, we fo-
cused our efforts on the coupling reaction (Table 1). Us-
ing copper(I) iodide (0.1 equiv) as the catalyst and 1,10-
phenanthroline (0.2 equiv) as the ligand and with potassi-
um carbonate (2 equiv) as the base in refluxing tetrahy-
drofuran for five hours (entry 1) gave 3a in 48% isolated
yield. Varying the solvent (entries 2–6) showed that diox-
ane was the best and it was used in the next step of the op-
timization process.
Key words: Knoevenagel condensation, copper catalyst, Ullmann
coupling, quinoline synthesis, cascade process
Substituted benzimidazoles and their azino-fused deriva-
tives show a wide range of biological activity such as an-
tiviral, anticancer, antibacterial, antifungal, DNA
intercalator, etc.1
Unsubstituted benzimidazo[1,2-a]quinoline was first pre-
pared in 1938 by Morgan and Stewart via classical con-
densation from 2-aminoquinoline and picric acid.2
Substituted benzimidazo[1,2-a]quinolines have been syn-
thesized by photochemical dehydrocyclization and dehy-
drohalogenation cyclization of acyclic benzimidazolyl-
substituted acrylonitriles3 and by palladium-catalyzed in-
tramolecular Buchwald–Hartwig amination of 2-(2-bro-
moanilino)quinolines.4
We then evaluated the ligands and bases in the model re-
action. The results shown in Table 2, entries 1–4, show
that 1,10-phenanthroline is the better ligand for this C–N
coupling reaction. The yield did not increase when the re-
action temperature and time were increased (entry 5). The
bases were also investigated and it was found that the
yield with cesium carbonate was comparable to that with
potassium carbonate, while potassium phosphate was less
satisfactory (entries 4, 6, and 7).
Recently, aza-fused polycyclic quinolines were synthe-
sized by Cai et al. via a copper-catalyzed cascade process.
Cai’s method could be applied to a wide range of 2-halo-
genated arylaldehydes to yield the corresponding prod-
ucts.5 Herein we wish to report a novel one-pot synthesis
of substituted benzimidazo[1,2-a]quinolines that firstly
uses the Knoevenagel condensation6 of the corresponding
2-bromobenzaldehydes and substituted benzimidazoles,
followed by copper-catalyzed intramolecular Ullmann-
type coupling reaction (Scheme 1).7 Reaction conditions
such as base, ligand, solvent, and temperature were care-
fully investigated. The results obtained show different
The optimized reaction conditions for the formation of 3a
were applied to a wide range of substrates and the results
Table 1 Optimization of the Solventa
N
N
CN
CHO
1. piperidine
solvent, r.t.
CN
+
N
2. CuI, 1,10-phen
K2CO3
N
H
Br
1a
2a
3a
Entry
Solvent
THF
Temp (°C) Time (h)
Yieldb (%)
48
R2
R1
1
2
3
4
5
6
reflux
reflux
90
8
8
N
N
R3
R2
R1
1. piperidine
solvent
CHO
Br
N
MeCN
toluene
dioxane
DMSO
DMF
56
+
N
H
12
8
trace
84
2. CuI, ligand
base
1
2
90
R3
90
12
8
trace
20
3
90
Scheme 1 One-pot synthesis of benzimidazo[1,2-a]quinolines
a Reaction conditions: 1. 1a (0.5 mmol), 2a (0.6 mmol), piperidine
(0.1 mmol), solvent (2 mL), r.t., 3 h; 2. CuI (0.05 mmol), 1,10-
phenanthroline (0.1 mmol), K2CO3 (1 mmol), 90 °C, 5–7 h.
b Isolated yield based on 1a.
SYNTHESIS 2010, No. 16, pp 2794–2798
Advanced online publication: 01.07.2010
DOI: 10.1055/s-0030-1258146; Art ID: P04410SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
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0

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One-Pot Synthesis of Substituted Benzimidazo[1,2-a]quinolines
2795
1
Table 2 Optimization of the Ligand and Basea
although it was an isomeric mixture as identified by H
and 13C NMR (entry 6). A similar result was obtained in
the reaction of 1b with 2b, which was probably caused by
isomerization of the benzimidazole ring in the intermedi-
ate (entry 8). Among the benzaldehydes screened, the
yields with substrates containing an electron-withdrawing
group are generally higher than those with an electron-
donating group.
N
N
CN
CHO
Br
1. piperidine
dioxane, r.t.
CN
+
N
2. CuI, ligand
base
N
H
1a
2a
3a
Entry
Ligandb
Base
Time (h) Yieldc (%)
The above results promoted us to examine the reaction of
imidazo[4,5-b]pyridine-2-acetonitrile (1e) with 2-bro-
mobenzaldehyde (2a) (Scheme 2). As expected, the reac-
tion proceeded smoothly to give 3m in 35% yield.
1
2
3
4
5
6
7
A
B
C
D
D
D
D
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K3PO4
Cs2CO3
8
27
8
20
8
trace
84
After carrying out the cascade process for the synthesis of
substituted benzimidazo[1,2-a]quinolines 3a–l, we won-
dered whether this strategy could be extended to the syn-
thesis of unsubstituted benzimidazo[1,2-a]quinoline (3n).
However, this one-pot method failed to afford product 3n
due to the limitations of the Knoevenagel condensation.
To our delight, unsubstituted benzimidazo[1,2-a]quino-
line (3n) was obtained from intramolecular coupling of
pre-synthesized 2-(2-bromostyryl)benzimidazole (4a) in
60% yield (Scheme 3).8
8
12
8
84d
79
8
83
a Reaction conditions: 1. 1a (0.5 mmol), 2a (0.6 mmol), piperidine
(0.1 mmol), dioxane (2 mL), r.t., 3 h; 2. CuI (0.05 mmol), ligand (0.1
mmol), base (1 mmol), 90 °C, 5–7 h.
b Ligands: A, L-proline; B, N-methylglycine; C, N,N-dimethylgly-
cine; D, 1,10-phenanthroline.
In order to improve the yield of 3n, further optimization
was investigated including solvent, ligand, and tempera-
ture. The results (Table 4) show that the intramolecular
C–N coupling reaction proceeded smoothly at relative
low temperatures (76 °C) in acetonitrile under CuI/L-pro-
line catalysis to afford the desired product 3n in excellent
yield (90%).
c Isolated yield based on 1a.
d The intramolecular coupling reaction was performed at reflux.
N
N
CN
CHO
Br
CN
1. piperidine
dioxane, r.t.
N
+
N
N
H
2. CuI,1,10-phen
K2CO3, 90 °C
N
In conclusion, we have developed a one-pot, efficient,
general, and practical cascade process for the synthesis of
benzimidazo[1,2-a]quinoline derivatives in moderate to
good yields. Benzimidazole-2-acetonitriles with electron-
withdrawing group or electron-donating group all afford-
ed the corresponding products in good yields. Catalyzed
by copper, unsubstituted benzimidazo[1,2-a]quinoline
was obtained by intramolecular Ullmann-type coupling in
excellent yield. These results are different from those of
Cai. Further studies on the practical applications of these
compounds is underway in our laboratory.
1e
2a
3m (35%)
Scheme 2 One-pot synthesis of 3m
CHO
N
N
Ac2O
+
reflux, 2 h
N
N
H
Br
H
1f
2a
Br
4a
CuI, 1,10-phen
dioxane
N
N
N
All reactions were carried out in the Schlenk tubes under N2 atmo-
sphere and solvents were purified and dried by standard procedures.
Reactions were followed by TLC using SILG/UV 254 silica gel
plates, which were visualized via a UV fluorescent lamp. Melting
points were obtained using micro melting point apparatus and are
uncorrected. 1H and 13C NMR spectrums were obtained on a Bruker
500 MHz instrument. LR-MS and HRMS were obtained by using EI
and ESI ionizations.
K2CO3, 90 °C
N
H
Br
4a
3n (60%)
Scheme 3 Synthesis of unsubstituted benzimidazo[1,2-a]quinoline
(3n)
Copper-Catalyzed One-Pot Synthesis of Substituted Benzimi-
dazo[1,2-a]quinolines 3; General Procedure
are summarized in Table 3. 2-Bromobenzaldehydes 2a–e
reacted well with benzimidazole-2-acetonitriles 1a–c to
give the corresponding products 3a–h in moderate to good
yields (entries 1–8), however, the reactions of 2-bro-
mobenzaldehydes 2a,b,e,f with ethyl 2-benzimidazolyl-
acetate 1d afforded the desired products 3i–l in relatively
low yields (entries 9–12). To our delight, 5-methylbenz-
imidazole-2-acetonitrile (1b) gave 3f in excellent yield,
To a soln of substituted benzimidazole 1 (0.5 mmol) and 2-bro-
mobenzaldehyde 2 (0.6 mmol) in dioxane (2 mL) in a Schlenk tube
was added piperidine (0.1 mmol) using a syringe. The mixture was
stirred at r.t. for 3 h under N2 and then CuI (0.05 mmol), 1,10-
phenanthroline (0.1 mmol), and K2CO3 (1 mmol) were added suc-
cessively to the soln under N2. The mixture was heated at 90 °C for
the appropriate time until TLC monitoring indicated no further im-
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2796
B.-W. Zhou et al.
PAPER
Table 3 One-Pot Synthesis of Substituted Benzimidazo[1,2-a]quinolinesa
8
7
R2
9
R1
5
N
6
R3
R2
CHO
Br
1. piperidine
dioxane, r.t.
N
10
N
+
11
12
R1
2. CuI,1,10-phen
K2CO3, 90 °C
N
H
1
4
1
2
2 R3
3
3
Entry
Substrates
Product
Yieldb (%)
1
R1
R2
2
R3
3
R3
1
2
1a
1a
1a
1a
1a
1b
1c
1b
1d
1d
1d
1d
CN
CN
CN
CN
CN
CN
CN
CN
H
2a
2b
2c
2d
2e
2a
2a
2b
2a
2f
H
3a
3b
3c
3d
3e
3fc
3g
3hc
3i
H
84
75
68
43
79
88
81
72
40
45
20
37
H
5-OMe
4-Me
5-OH
5-Cl
H
3-OMe
2-Me
3-OH
3-Cl
H
3
H
4
H
5
H
6
Me
Cl
Me
H
7
H
H
8
5-OMe
H
3-OMe
H
9
CO2Et
CO2Et
CO2Et
CO2Et
10
11
12
H
4-Cl
5-OMe
5-Cl
3j
2-Cl
3-OMe
3-Cl
H
2b
2e
3k
3l
H
a Conditions: 1. 1 (0.5 mmol), 2 (0.6 mmol), piperidine (0.1 mmol), dioxane (2 mL), r.t., 3 h; 2. CuI (0.05 mmol), 1,10-phenanthroline (0.1
mmol), K2CO3 (1 mmol), 90 °C, 5–7 h.
b Isolated yield based on benzimidazole.
c The product is a mixture of isomers.
provement in the conversion. The mixture was washed with CH2Cl2
(3 × 15 mL) and filtered using a funnel. The filtrate was dried (an-
hyd Na2SO4) and concentrated in vacuo. The residue was purified
by column chromatography (silica gel, CH2Cl2–EtOAc, 30:1).
13C NMR (125 MHz, DMSO-d6): d = 155.8, 143.9, 143.6, 139.9,
130.3, 130.2, 124.9, 123.4, 122.4, 121.6, 120.2, 117.2, 115.4, 114.5,
112.6, 101.5, 55.7.
MS (EI): m/z = 273 [M]+.
HRMS (EI): m/z [M]+ for C17H11N3O: 273.0902; found: 273.0909.
Benzimidazo[1,2-a]quinoline-6-carbonitrile (3a)
Yellow solid; mp 254 °C.
2-Methylbenzimidazo[1,2-a]quinoline-6-carbonitrile (3c)
Yellow solid; mp 270 °C.
1H NMR (500 MHz, CDCl3): d = 8.64 (d, J = 9.0 Hz, 1 H), 8.41 (d,
J = 8.0 Hz, 1 H), 8.21 (s, 1 H), 8.19–8.16 (m, 1 H), 7.96–7.93 (m, 2
H), 7.65–7.57 (m, 3 H).
13C NMR (125 MHz, CDCl3): d = 144.6, 144.5, 138.8, 136.5, 133.0,
130.9, 130.8, 125.4, 125.1, 124.0, 121.5, 121.4, 115.5, 114.9, 114.0,
103.1.
MS (EI): m/z = 243 [M]+.
HRMS (EI): m/z [M]+ calcd for C16H9N3: 243.0796; found:
1H NMR (500 MHz, DMSO-d6): d = 8.85 (d, J = 8.0 Hz, 1 H), 8.78
(s, 1 H), 8.64 (s, 1 H), 8.06–8.01 (m, 2 H), 7.65–7.57 (m, 2 H), 7.52
(d, J = 7.5 Hz, 1 H), 2.71 (s, 3 H).
13C NMR (125 MHz, DMSO-d6): d = 145.1, 144.6, 143.8, 140.4,
136.0, 131.0, 130.5, 126.5, 125.0, 123.4, 120.1, 119.0, 115.5, 115.4,
115.1, 99.9, 21.8.
MS (EI): m/z = 257 [M]+.
HRMS (EI): m/z [M]+ for C17H11N3: 257.0953; found: 257.0961.
243.0800.
3-Methoxybenzimidazo[1,2-a]quinoline-6-carbonitrile (3b)
Yellow solid; mp 250 °C.
1H NMR (500 MHz, DMSO-d6): d = 8.64–8.56 (m, 3 H), 7.97 (d,
J = 8.0 Hz, 1 H), 7.60–7.50 (m, 3 H), 7.48–7.44 (m, 1 H), 3.89 (s, 3
3-Hydroxybenzimidazo[1,2-a]quinoline-6-carbonitrile (3d)
Yellow solid; mp >300 °C.
1H NMR (500 MHz, DMSO-d6): d = 10.23 (s, 1 H), 8.72–8.64 (m,
3 H), 7.99 (d, J = 8.0 Hz, 1 H), 7.60–7.54 (m, 2 H), 7.47–7.44 (m, 2
H).
H).
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One-Pot Synthesis of Substituted Benzimidazo[1,2-a]quinolines
2797
9-Chlorobenzimidazo[1,2-a]quinoline-6-carbonitrile (3g)
Yellow solid; mp 290 °C.
Table 4 Optimization of the Conditions for the Synthesis of Unsub-
stituted Benzimidazo[1,2-a]quinolinea
1H NMR (500 MHz, DMSO-d6): d = 8.86–8.83 (m, 3 H), 8.15 (d,
J = 7.5 Hz, 1 H), 8.03–7.98 (m, 2 H), 7.69 (t, J = 7.5 Hz, 1 H), 7.66–
7.63 (m, 1 H).
13C NMR (125 MHz, DMSO-d6): d = 145.2, 142.4, 141.1, 135.4,
133.8, 131.2, 130.9, 128.0, 125.5, 125.4, 121.3, 121.2, 116.3, 115.1,
114.5, 101.2.
CuI, ligand
solvent
N
N
N
K2CO3
N
H
Br
4a
3n
MS (EI): m/z = 277 [M]+.
Entry
Solvent
Ligandb
Temp (°C) Yieldc (%)
HRMS (EI): m/z [M] for C16H8ClN3: 277.0407; found: 277.0414.
1
2
3
4
5
6
7
8
dioxane
dioxane
dioxane
DMSO
THF
D
E
90
60
86
74
56
45
90
73
59
3-Methoxy-9/10-methylbenzimidazo[1,2-a]quinoline-6-carbo-
nitrile (3h)
Yellow solid; mp 182 °C.
90
1H NMR (500 MHz, CDCl3): d = 8.35–8.30 (m, 1 H), 8.05 (d,
J = 8.5 Hz, 0.5 H), 7.97–7.93 (m, 2 H), 7.83 (s, 0.5 H), 7.41–7.36
(m, 1.5 H), 7.31–7.26 (m, 0.5 H), 7.19–7.17 (m, 1 H), 3.95 (s, 3 H),
2.64 (s, 1.5 H), 2.57 (s, 1.5 H).
13C NMR (125 MHz, CDCl3): d = 156.2, 144.7, 144.1, 143.7, 142.4,
137.7, 137.5, 135.2, 133.9, 130.8, 130.8, 130.7, 128.7, 126.9, 125.3,
122.3, 122.2, 121.4, 121.2, 120.8, 120.7, 116.5, 116.5, 115.0, 114.9,
113.4, 113.0, 111.7, 111.6, 103.3, 103.1, 55.8, 22.3, 21.7.
A
A
A
A
E
90
90
reflux
76
MeCN
MeCN
MeCN
76
MS (EI): m/z = 287 [M]+.
D
76
HRMS (EI): m/z [M]+ for C18H13N3O: 287.1059; found: 287.1074.
a Conditions: 4a (0.5 mmol), CuI (0.05 mmol), ligand (0.1 mmol),
K2CO3 (1 mmol), solvent (2 mL), 8 h.
b Ligand: A, L-proline; D, 1,10-phenanthroline; E, N,N-dimethyleth-
ylenediamine.
Ethyl Benzimidazo[1,2-a]quinoline-6-carboxylate (3i)
Green solid; mp 119 °C.
c Isolated yield based on 4a.
1H NMR (500 MHz, CDCl3): d = 8.61 (d, J = 8.5 Hz, 1 H), 8.43 (s,
1 H), 8.39 (d, J = 8.5 Hz, 1 H), 8.18 (q, J = 8.0 Hz, 1 H), 7.94 (q,
J = 8.0 Hz, 1 H), 7.86–7.82 (m, 1 H), 7.58–7.49 (m, 3 H), 4.58 (q,
J = 7.0 Hz, 2 H), 1.51 (t, J = 7.0 Hz, 3 H).
13C NMR (125 MHz, CDCl3): d = 163.9, 145.2, 145.0, 136.8, 135.5,
131.9, 131.0, 130.5, 124.7, 124.5, 123.2, 121.8, 121.7, 120.1, 115.2,
113.7, 61.8, 14.4.
13C NMR (125 MHz, DMSO-d6): d = 154.4, 144.0, 143.6, 140.3,
130.3, 129.2, 124.8, 123.3, 122.6, 122.2, 120.2, 117.3, 115.6, 114.8,
114.5, 101.3.
MS (EI): m/z = 259 [M]+.
HRMS (EI): m/z [M]+ for C16H9N3O: 259.0746; found: 259.0766.
MS (EI): m/z = 290 [M]+.
HRMS (EI): m/z [M]+ for C18H14N2O2: 290.1055; found: 290.1068.
3-Chlorobenzimidazo[1,2-a]quinoline-6-carbonitrile (3e)
Yellow solid; mp 263 °C.
1H NMR (500 MHz, DMSO-d6): d = 8.76 (d, J = 9.0 Hz, 1 H), 8.67
(s, 1 H), 8.61 (d, J = 8.0 Hz, 1 H), 8.20 (d, J = 2.5 Hz, 1 H), 8.01–
7.99 (m, 1 H), 7.92 (q, J = 9.0 Hz, 1 H), 7.63–7.55 (m, 2 H).
13C NMR (125 MHz, DMSO-d6): d = 144.2, 143.7, 139.4, 134.4,
132.9, 130.4, 129.8, 129.0, 125.3, 124.0, 122.6, 120.4, 117.9, 115.1,
114.7, 102.6.
MS (EI): m/z = 277 [M]+.
HRMS (EI): m/z [M]+ for C16H8ClN3: 277.0407; found: 277.0412.
Ethyl 2-Chlorobenzimidazo[1,2-a]quinoline-6-carboxylate (3j)
Yellow solid; mp 129 °C.
1H NMR (500 MHz, CDCl3): d = 8.60 (d, J = 1.0 Hz, 1 H), 8.40 (s,
1 H), 8.35–8.33 (m, 1 H), 8.20 (d, J = 7.5 Hz, 1 H), 7.88 (d, J = 8.5
Hz, 1 H), 7.61–7.54 (m, 2 H), 7.51 (q, J = 8.5 Hz, 1 H), 4.58 (q,
J = 7.0 Hz, 2 H), 1.51 (t, J = 7.0 Hz, 3 H).
13C NMR (125 MHz, CDCl3): d = 163.6, 144.9, 138.2, 137.1, 134.7,
131.9, 130.2, 125.1, 125.1, 123.7, 121.8, 120.2, 115.4, 113.5, 62.0,
14.4.
MS (EI): m/z = 324 [M]+.
HRMS (ESI): m/z [M + H]+ for C18H13ClN2O2: 325.0744 found:
9/10-Methylbenzimidazo[1,2-a]quinoline-6-carbonitrile (3f)
Yellow solid; mp 183 °C.
1H NMR (500 MHz, DMSO-d6): d = 8.67–8.65 (m, 2 H), 8.45 (d,
J = 8.5 Hz, 0.5 H), 8.39 (s, 0.5 H), 8.09–8.05 (m, 1 H), 7.95–7.90
(m, 1 H), 7.81 (d, J = 8.5 Hz, 0.5 H), 7.70 (s, 0.5 H), 7.62–7.58 (m,
1 H), 7.38–7.30 (m, 1 H), 2.52 (s, 3 H).
325.0735.
Ethyl 3-Methoxybenzimidazo[1,2-a]quinoline-6-carboxylate
(3k)
13C NMR (125 MHz, DMSO-d6): d = 144.1, 143.9, 143.7, 141.7,
139.9, 139.7, 135.5, 135.4, 134.4, 133.3, 133.3, 133.2, 130.9, 130.8,
130.4, 128.3, 126.4, 124.9, 124.8, 121.0, 120.9, 119.6, 119.5, 115.7,
115.5, 115.4, 114.2, 114.0, 101.1, 101.0, 21.57, 21.14.
MS (EI): m/z = 257 [M]+.
HRMS (EI): m/z [M]+ for C17H11N3: 257.0953; found: 257.0964.
Yellow solid; mp 110 °C.
1H NMR (500 MHz, CDCl3): d = 8.50 (d, J = 9.0 Hz, 1 H), 8.35 (s,
1 H), 8.32 (d, J = 8.5 Hz, 1 H), 8.17 (d, J = 8.0 Hz, 1 H), 7.56–7.52
(m, 1 H), 7.51–7.47 (m, 1 H), 7.40 (q, J = 9.0 Hz, 1 H), 7.31 (d, J = 3
Hz, 1 H), 4.57 (q, J = 7.0 Hz, 2 H), 3.94 (s, 1 H), 1.51 (t, J = 7.0 Hz,
3 H).
Synthesis 2010, No. 16, 2794–2798 © Thieme Stuttgart · New York

2798
B.-W. Zhou et al.
PAPER
13C NMR (125 MHz, CDCl3): d = 163.9, 156.0, 144.7, 135.1, 131.2,
130.3, 124.5, 123.0, 122.8, 121.6, 120.5, 120.4, 116.4, 113.4, 112.1,
61.8, 55.7, 14.4.
by Chemistry Experiment Demonstration Center of Zhejiang Pro-
vince.
MS (EI): m/z = 320 [M]+.
HRMS (EI): m/z [M]+ for C19H16N2O3: 320.1161; found: 320.1177.
References
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Ethyl 3-Chlorobenzimidazo[1,2-a]quinoline-6-carboxylate (3l)
Yellow solid; mp 130 °C.
1H NMR (500 MHz, CDCl3): d = 8.48 (d, J = 9.0 Hz, 1 H), 8.29 (s,
1 H), 8.27 (d, J = 8.5 Hz, 1 H), 8.17 (d, J = 8.0 Hz, 1 H), 7.89 (d,
J = 2.5 Hz, 1 H), 7.75 (q, J = 9.0 Hz, 1 H), 7.58–7.54 (m, 1 H),
7.52–7.48 (m, 1 H), 4.57 (q, J = 7.0 Hz, 2 H), 1.50 (t, J = 7.0 Hz, 3
H).
13C NMR (125 MHz, CDCl3): d = 163.5, 144.9, 144.7, 135.0, 133.9,
131.7, 130.3, 129.9, 129.9, 124.9, 123.6, 123.0, 121.9, 121.4, 116.4,
113.5, 62.0, 14.3.
MS (EI): m/z = 324 [M]+.
HRMS (EI): m/z [M]+ for C18H13ClN2O2: 324.0666; found:
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324.0689.
Pyrido[3¢,2¢:4,5]imidazo[1,2-a]quinoline-6-carbonitrile (3m)
Yellow solid; mp 218 °C.
(4) Venkatesh, C.; Sundaram, G. S. M.; Ila, H.; Junjappa, H.
1H NMR (500 MHz, CDCl3): d = 9.97 (d, J = 8.5 Hz, 1 H), 8.69 (q,
J = 4.5 Hz, 1 H), 8.41 (q, J = 8.0 Hz, 1 H), 8.28 (s, 1 H), 7.98–7.90
(m, 2 H), 7.63–7.56 (m, 2 H).
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13C NMR (125 MHz, CDCl3): d = 145.6, 144.7, 144.3, 140.4, 136.7,
135.9, 133.7, 129.9, 128.6, 125.8, 121.1, 120.9, 118.1, 114.6, 102.9.
MS (EI): m/z = 244 [M]+.
HRMS (EI): m/z [M]+ for C15H8N4: 244.0749; found: 244.0760.
Benzimidazo[1,2-a]quinoline-6-carbonitrile (3n)
White solid; mp 160 °C.
(7) For selected examples on ligand-promoted Ullmann-type
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1450.
1H NMR (500 MHz, CDCl3): d = 7.94 (d, J = 16.5 Hz, 1 H), 7.68–
7.65 (m, 2 H), 7.52 (q, J = 7.5 Hz, 1 H), 7.46 (q, J = 8.0 Hz, 1 H),
7.28–7.25 (m, 2 H), 7.22–7.16 (m, 2 H), 7.09–7.05 (m, 1 H).
13C NMR (125 MHz, CDCl3): d = 150.8, 139.0, 135.5, 133.6, 133.2,
130.0, 127.7, 126.9, 124.5, 123.2, 119.8, 115.2.
MS (EI): m/z = 218 [M]+.
HRMS (EI): m/z [M]+ for C15H10N2: 218.0844; found: 218.0849.
Acknowledgment
We thank the National Natural Science Foundation of China (No.
20876148) as well as the Scientific Research Fund of Educational
Bureau of Zhejiang Province (20070304). This work was supported
(8) Büchi, J.; Zwicky, H.; Aebi, A. Arch. Pharm. (Weinheim,
Ger.) 1960, 293, 758.
Synthesis 2010, No. 16, 2794–2798 © Thieme Stuttgart · New York