Indium(III) chloride catalyzed one-pot multicomponent synthesis of chromenone- and quinolone-annulated imidazole derivatives

Article abstract of DOI:10.1055/s-0033-1339547

A one-pot multicomponent strategy for the synthesis of chromenone- and quinolone-annulated imidazole derivatives from easily available starting materials has been achieved via an indium(III) chloride catalyzed domino reaction. The protocol is simple, step-economic, and less hazardous, and also provides good yields of the products. Georg Thieme Verlag Stuttgart, New York.

Full text of DOI:10.1055/s-0033-1339547

PAPER
▌2983
paper
Indium(III) Chloride Catalyzed One-Pot Multicomponent Synthesis of
Chromenone- and Quinolone-Annulated Imidazole Derivatives
One-Pot Multicomponent Synthesis of Annulated Imidazole Derivatives
K. C. Majumdar,* Debankan Ghosh, Sudipta Ponra
Department of Chemistry, University of Kalyani, Kalyani 741235, W.B., India
Fax +91(33)25828282; E-mail: kcm@klyuniv.ac.in
Received: 08.05.2013; Accepted after revision: 16.07.2013
7H-imidazo[4,5-f]quinolin-7-one derivatives by a simple,
step-economic, and less hazardous methodology is still
important and requires further investigation.
Abstract: A one-pot multicomponent strategy for the synthesis of
chromenone- and quinolone-annulated imidazole derivatives from
easily available starting materials has been achieved via an indi-
um(III) chloride catalyzed domino reaction. The protocol is simple,
step-economic, and less hazardous, and also provides good yields of
the products.
Multicomponent reactions (MCR) play an important role
in synthetic and medicinal chemistry and have been uti-
lized to access bioactive compounds.15 Their ability to
generate complex molecular scaffolds from simple pre-
cursors in a single step makes them a powerful synthetic
tool for organic synthesis. Multicomponent reactions are
advantageous compared to linear stepwise synthesis as
they reduce reaction times and provide high atom econo-
my and selectivity.16
Recently Lee et al.17 reported a copper-catalyzed three-
component reaction of a 2-haloaniline, an aldehyde, and
sodium azide for the construction of a fused imidazole
ring. Our interest in the synthesis of potential bioactive
heterocycles by metal catalysis and multicomponent
strategy18 prompted us to undertake a study of the synthe-
sis of chromeno[5,6-d]imidazol-7(3H)-one, and 3,6-di-
hydro-7H-imidazo[4,5-f]quinolin-7-one derivatives by
the metal-catalyzed multicomponent reaction approach;
herein, we report our results (Scheme 1).
Key words: multicomponent reaction, indium(III) chloride, imid-
azole, aromatic aldehyde, sodium azide
Among various five-membered nitrogen heterocycles,
imidazole derivatives have gained a distinctive place in
the field of medicinal chemistry. The insertion of the im-
idazole nucleus is a vital synthetic strategy in drug design
for its well-known biological properties, which includes
antibacterial,1 antifungal,2 analgesic,3 anti-inflammatory,4
anticancer,5 antiviral,6 and antidepressant7 properties.
Furthermore, some compounds bearing a chromenone-
annulated imidazole core are effective as a phosphodi-
esterese inhibitor,8 CNS depressant,9 and also inhibit car-
cinoma in mammals.10 Many compounds of industrial and
technological importance contain the imidazole nucleus,
and it can also be found in various compounds that are
used in photography and electronics.11
R
Br
Furthermore, chromenones and quinolone subunits are the
parent component of a large number of bioactive natural
products, and their derivatives show extensive biological
activity.12 Chromeno[5,6-d]imidazol-7(3H)-one and 3,6-
dihydro-7H-imidazo[4,5-f]quinolin-7-one cores posses an
imidazole nucleus fused to a chromenone and quinolone
molecule respectively at their 5,6-position. This new class
of compounds and their derivatives may be of interest to
pharmacologists and medicinal chemists. Close ana-
logues, chromeno[4,3-d]imidazol-4(3H)-one derivatives,
were synthesized by Trimarco et al.13 via a multistep syn-
thesis, but chromeno[5,6-d]imidazol-7(3H)-one and 3,6-
dihydro-7H-imidazo[4,5-f]quinolin-7-one are still less in-
vestigated and to the best of our knowledge so far there is
only one report14 of chromeno[5,6-d]imidazol-7(3H)-one
derivatives by the reaction of 5,6-diamino-2H-chromen-
2-one, benzoic acid, and polyphosphoric acid under reflux
conditions; the methodology suffers from the requirement
for strongly acidic conditions. Hence the synthesis of
chromeno[5,6-d]imidazol-7(3H)-one and 3,6-dihydro-
N
NH2
NH
X = O, NMe,
+ RCHO
NaN3
+
NEt
O
X
R = aryl
O
X
1
2
3
Scheme 1 Reagents and conditions: InCl3 (10 mol%), DMSO, 130
°C, 8 h.
As a model reaction, 6-amino-5-bromo-2H-chromen-2-
one (1a), 4-methoxybenzaldehyde (2a), and sodium azide
(3) were reacted in dimethyl sulfoxide using copper(I) io-
dide (10 mol%) as the catalyst at 130 °C for eight hours.
A new product was obtained in low yield (47%) (Table 1,
entry 1). The spectral analysis of the compound confirmed
the formation of the desired product 4a. As this type of re-
action may be improved by introduction of a ligand, we
examined the use of ligands such as N,N,N′,N′-tetrameth-
ylethylenediamine, N,N′-dimethylethylenediamine, and
L-proline in this reaction, however their use did not im-
prove the yield of product 4a (entries 2–4). Copper(II)
was also inefficient in enhancing the yield of the reaction
(entry 5). We next considered the use of indium(III) chlo-
ride as it is known for its relatively low toxicity and excel-
lent tolerance to oxygen- and nitrogen-containing
SYNTHESIS 2013, 45, 2983–2988
Advanced online publication: 13.08.2013
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0033-1339547; Art ID: SS-2013-Z0345-OP
© Georg Thieme Verlag Stuttgart · New York

2984
K. C. Majumdar et al.
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Table 1 Optimization of the Reaction Conditionsa
xylene and toluene were ineffective (entries 12 and 13).
Other Lewis acid catalysts [Yb(OTf)2, AlCl3, FeCl3,
AgSbF6] were also found to be ineffective (entries 14–
17). This reaction failed completely without a catalyst
(entry 18).
OMe
Br
NH2
+
CHO
+
NaN3
N
O
O
MeO
Thus, the optimized reaction conditions are 10 mol% in-
dium(III) chloride in dimethyl sulfoxide at 130 °C for
eight hours. The scope of this protocol was extended to
different aromatic and heteroaromatic aldehydes and oth-
er heterocyclic systems.
1a
2a
3
NH
4
O
O
Entry
Catalyst (mol%)
Solvent
Temp (°C) Yieldb (%)
The results showed that the precursors 1a–c successfully
gave the desired chromeno[5,6-d]imidazol-7(3H)-one and
3,6-dihydro-7H-imidazo[4,5-f]quinolin-7-one derivatives
in very good yields (68–82%). The structures of the prod-
ucts 4a–m were determined from their spectral and ana-
lytical data. 1H NMR of the product 4a showed a
characteristic peak for the NH proton at δ = 13.26 as well
as at 13.21. Moreover, it also showed two pairs of dou-
blets, one pair at δ = 6.61 (J = 9.6 Hz) and 6.53 (J = 9.6
Hz), and another at 7.84 (J = 8.8Hz) and 7.72 (J = 8.4Hz).
The pair of singlets and both the pairs of doublets and also
their coupling constants indicate that the compound 4a
might exist in two tautomeric forms 4a and 4a′ (Figure 1).
These structures were fully optimized by the Gaussian 03
program using the DFT method (using B3LYP level and
6-31G as basis set). The calculations show that the tauto-
mer 4a (–621199.57 kcal/mol) is more stable than the tau-
tomer 4a′ (–621197.22 kcal/mol), thus it predominates.
1
2c
3d
4e
5
CuI (10)
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
130
130
130
130
130
130
150
120
130
130
130
130
reflux
130
130
130C
130
130
47
49
45
39
36
78
75
52
72
69
53
0
CuI (10)
CuI (10)
CuI (10)
Cu(OAc)2 (10)
InCl3 (10)
InCl3 (10)
InCl3 (10)
InCl3 (5)
6f
7
8
9
10
11
12
13
14
15
16
17
18
InCl3 (20)
InCl3 (10)
InCl3 (10)
InCl3 (10)
Yb(OTf)2 (10)
AlCl3 (10)
FeCl3 (10)
AgSbF6 (10)
–
xylene
toluene
DMSO
DMSO
DMSO
DMSO
DMSO
0
OMe
O
OMe
trace
0
H
N
N
O
NH
N
O
O
0
4a
4a′
0
Figure 1 Two probable tautomers 4a and 4a′
0
a Reaction conditions: 6-amino-5-bromo-2H-chromen-2-one (1a, 1.0
mmol), 4-methoxybenzaldehyde (2a, 1.5 mmol), NaN3 (3, 2.0 mmol),
catalyst, solvent (5 mL), 8 h.
The other compounds 4d,h,i,l,m show both tautomers in
1
their H NMR spectra. The remaining compounds in
b Isolated yields.
1
Table 2 show only the major tautomer in their H NMR
c TMEDA (10 mol%) was used as a ligand.
d DMEDA (10 mol%) was used as a ligand.
spectra.
e
L-proline (10 mol%) was used as a ligand.
Aldehydes containing electron-donating groups furnished
the corresponding imidazole derivatives in very good
yields. Furfuraldehyde (2e) also gave the desired products
in good yields. Aromatic aldehydes with electron-with-
drawing groups, such as nitro or fluoro, yielded insepara-
ble complex mixtures. The reaction was found to be
totally ineffective for aliphatic aldehydes.
f Optimized reaction condition.
substrates and functional groups.19 When indium(III)
chloride was employed as the catalyst in dimethyl sulfox-
ide at 130 °C, a satisfactory result was obtained without
the use of a ligand (78%; entry 6). The yield of the product
was not improved by increasing or decreasing the reaction
temperature (entries 7 and 8). We also found that the yield
of the reaction also did not improved by increasing or de-
creasing the catalyst loading (entries 9 and 10). We also
examined the used of different solvents, such as N,N-di-
methylformamide, xylene, and toluene; N,N-dimethylform-
amide was moderately effective (entry 11) but nonpolar
A plausible rationalization for the formation of the prod-
uct 4 is depicted in Scheme 2. At first the condensation of
the substrates 1 and aldehydes 2 generate an imine. The
initially formed imine can follow either path a or path b.
In path a, indium may co-ordinate with the imine bond A
followed by azide insertion to give intermediate C. This
may then undergo cyclization to form intermediate E that
readily generates the product 4 by aromatization.17 Alter-
Synthesis 2013, 45, 2983–2988
© Georg Thieme Verlag Stuttgart · New York

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One-Pot Multicomponent Synthesis of Annulated Imidazole Derivatives
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Table 2 Synthesis of Various Chromeno[5,6-d]imidazol-7(3H)-one and 3,6-Dihydro-7H-Imidazo[4,5-f]quinolin-7-one Derivativesa
Ar
Ar
Br
N
HN
NH2
NH
N
+
+
ArCHO
+
NaN3
O
X
X
O
X
O
(minor)
1a X = O
1b X = NMe
1c X = NEt
2a–f
3
4a–m (major)
Entry
Precursor
Aldehyde
Product
Yieldb (%)
1
2
1a
1a
1a
1a
1a
1a
1b
1b
1c
1c
1c
1c
1c
2a, Ar = 4-MeOC6H4
2b, Ar = Ph
4a
4b
4c
4d
4e
4f
78
76
74
81
75
71
70
74
80
77
73
82
74
3
2c, Ar = 4-MeC6H4
2d, Ar = 4-EtOC6H4
2e, Ar = 2-furyl
4
5
6
2f, Ar = 2-MeO-5-ClC6H3
2b, Ar = Ph
7
4g
4h
4i
8
2d, Ar = 4-EtOC6H4
2a, Ar = 4-MeOC6H4
2b, Ar = Ph
9
10
11
12
13
4j
2c, Ar = 4-MeC6H4
2d, Ar = 4-EtOC6H4
2e, Ar = 2-furyl
4k
4l
4m
a Reaction conditions: 1a–c (1.0 mmol), aldehyde (1.5 mmol), NaN3 (2.0 mmol), InCl3 (0.1 mmol), DMSO (5 mL), 130 °C, 8 h.
b Isolated yield.
natively in path b, indium may coordinate with both the In summary, we have developed an efficient protocol for
imine and the halogen B facilitating the replacement of the synthesis of chromeno[5,6-d]imidazol-7(3H)-one and
halogen20 by the azide forming the intermediate D. This 3,6-dihydro-7H-imidazo[4,5-f]quinolin-7-one derivatives
may then undergo cyclization forming the common inter- in good yields. The advantages of this methodology are its
mediates E that afford the products 4.
simplicity and step economy, and it affords the products
Br
In(III)
Br
Br
NH2
ArCHO
path a
Ar
O
Ar
ArCHO
path b
O
N
X
In(III)
N
X
O
X
1
B
A
N3
– Br
N
N3
N
N
N
(III)In
N
Ar
N
N
Ar
In(III)
Ar
O
O
H
N
X
O
N
X
N
X
C
E
D
Ar
N
O
NH
X
4
Scheme 2 Plausible mechanistic pathway for the formation of 4
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 2983–2988

2986
K. C. Majumdar et al.
PAPER
13C NMR (100 MHz, DMSO-d6): δ = 160.4, 150.3, 140.1, 139.6,
135.1, 131.6, 129.6, 128.7, 126.9, 126.5, 115.2, 110.9, 21.0.
MS: m/z = 277.03 [M + H]+.
in good yields. The synthesized compounds as well as the
synthetic method could be useful to the pharmacologists
and the medicinal chemists.
Anal. Calcd for C17H12N2O2: C, 73.90; H, 4.38; N, 10.14. Found: C,
74.09; H, 4.31; N, 10.08.
Melting ranges were determined in open capillaries and are uncor-
rected. IR spectra were recorded on a Perkin-Elmer L 120-000A
spectrophotometer on KBr disks. 1H and 13C NMR spectra were re-
corded on a Bruker DPX-400 spectrometer in DMSO-d6 with TMS
as internal standard. CHN was recorded on 2400 series II CHN an-
alyzer Perkin Elmer. MS were recorded on a Q-TOF micro instru-
ment at the Indian Institute of Chemical Biology, Kolkata. Silica gel
[(60–120, 230–400 mesh), Rankem, India] was used for chromato-
graphic separation. Silica gel G, GF-254 [CDH, (India)] was used
for TLC. Petroleum ether refers to the fraction boiling between 60
°C and 80 °C.
2-(4-Ethoxyphenyl)chromeno[5,6-d]imidazol-7(3H)-one (4d)
Following the typical procedure using 1a (0.24 g) gave 4d (0.248 g,
81%) as a pale yellow solid; mp 236–238 °C.
IR (KBr): 3221, 1706, 1608, 1255, 778 cm–1.
1H NMR (400 MHz, DMSO-d6): δ = [13.23 (br s), 13.18 (br s) (1
H)], 8.53 (d, J = 9.2 Hz, 1 H), 8.14 (d, J = 8.4 Hz, 2 H), [7.85 (d,
J = 8.4 Hz), 7.72 (d, J = 8.8 Hz) (1 H)], 7.23 (d, J = 8.4 Hz, 1 H),
7.12 (d, J = 8.4 Hz, 2 H), [6.61 (d, J = 9.6 Hz), 6.53 (d, J = 9.6 Hz)
(1 H)], 4.12 (q, J = 6.8 Hz, 2 H), 1.37 (t, J = 6.8 Hz, 3 H).
13C NMR (100 MHz, DMSO-d6): δ = 160.8, 160.1, 152.2, 140.9,
134.5, 133.7, 129.4, 128.7, 128.1, 120.2, 114.9, 111.4, 109.3, 63.4,
14.6.
2-(4-Methoxyphenyl)chromeno[5,6-d]imidazol-7(3H)-one (4a);
Typical Procedure
6-Amino-5-bromo-2H-chromen-2-one (1a, 0.24 g, 1 mmol), 4-meth-
oxybenzaldehyde (2a, 0.204 g, 1.5 mmol), and NaN3 (3, 0.195 g, 2.0
mmol) were mixed in DMSO (5 mL). To the mixture was added
InCl3 (0.022 g, 0.1 mmol), and it was then heated with stirring at
130 °C for 8 h. After completion of the reaction (TLC monitoring),
the mixture was cooled and diluted with EtOAc (50 mL), washed
with H2O (2 × 20 mL) and brine (20 mL), and dried (Na2SO4). The
solvent was removed under reduced pressure. The resulting crude
product was then purified by column chromatography (silica gel,
60–120 mesh, hexane–EtOAc, 1:1) to give 4a (0.228 g, 0.78 mmol,
78%) as a light yellow solid; mp 264–266 °C.
MS: m/z = 307.13 [M + H]+.
Anal. Calcd for C18H14N2O3: C, 70.58; H, 4.61; N, 9.15. Found: C,
70.74; H, 4.52; N, 9.03.
2-(Furan-2-yl)chromeno[5,6-d]imidazol-7(3H)-one (4e)
Following the typical procedure using 1a (0.24 g) gave 4e (0.189 g,
75%) as a brown solid; mp >300 °C.
IR (KBr): 3193, 1679, 1602, 1265, 780 cm–1.
1H NMR (400 MHz, DMSO-d6): δ = 13.42 (br s, 1 H), 8.51 (d,
J = 9.2 Hz, 1 H), 7.98 (s, 1 H), 7.74 (br s, 1 H), 7.24 (d, J = 8.8 Hz,
2 H), 6.76 (s, 1 H), 6.54 (d, J = 9.2 Hz, 1 H).
IR (KBr): 3261, 1720, 1607, 1247, 772 cm–1.
1H NMR (400 MHz, DMSO-d6): δ = [13.26 (br s), 13.21 (br s) (1
H)], 8.54 (d, J = 9.6 Hz, 1 H), 8.15 (d, J = 8.4 Hz, 2 H), [7.85 (d,
J = 8.8 Hz), 7.72 (d, J = 8.4 Hz) (1 H)], 7.24 (d, J = 8.4 Hz, 1 H),
7.14 (d, J = 8.4 Hz, 2 H), [6.61 (d, J = 9.6 Hz), 6.53 (d, J = 9.6 Hz)
(1 H)], 3.85 (s, 3 H).
MS: m/z = 253.07 [M + H]+.
Anal. Calcd for C14H8N2O3: C, 66.67; H, 3.20; N, 11.11. Found: C,
66.43; H, 3.23; N, 11.17.
2-(5-Chloro-2-methoxyphenyl)chromeno[5,6-d]imidazol-
7(3H)-one (4f)
Following the typical procedure using 1a (0.24 g) gave 4f (0.232 g,
71%) as a light reddish solid; mp >300 °C.
13C NMR (100 MHz, DMSO-d6): δ = 160.9, 160.6, 153.3, 150.0,
140.0, 139.6, 131.0, 128.2, 121.9, 115.1, 114.7, 114.4, 110.6, 109.3,
55.3.
HRMS: m/z [M + Na]+ calcd for C17H12N2O3: 315.0746; found:
315.0749.
IR (KBr): 32345, 1714, 1604, 1278, 772 cm–1.
1H NMR (400 MHz, DMSO-d6): δ = 12.60 (br s, 1 H), 8.59 (d,
J = 9.6 Hz, 1 H), 8.38 (d, J = 2.8 Hz, 1 H), 7.85 (d, J = 8.8 Hz, 1 H),
7.57 (dd, J = 8.8, 2.8 Hz, 1 H), 7.31 (t, J = 8.8 Hz, 2 H), 6.55 (d,
J = 9.6 Hz, 1 H), 4.06 (s, 3 H).
2-Phenylchromeno[5,6-d]imidazol-7(3H)-one (4b)
Following the typical procedure using 1a (0.24 g) gave 4b (0.20 g,
76%) as a pale yellow solid; mp >300 °C.
IR (KBr): 3245, 1683, 1605, 1287, 774 cm–1.
13C NMR (100 MHz, DMSO-d6): δ = 160.6, 155.6, 150.2, 149.2,
139.6, 138.8, 131.1, 131.0, 128.7, 124.8, 116.0, 115.3, 114.4, 111.4,
109.3, 56.4.
1H NMR (400 MHz, DMSO-d6): δ = 13.38 (br s, 1 H), 8.56 (d,
J = 9.6 Hz, 1 H), 8.21 (d, J = 7.6 Hz, 2 H), 7.81 (br s, 1 H), 7.62–
7.52 (m, 3 H), 7.28 (d, J = 8.8 Hz, 1 H), 6.58 (d, J = 8.8 Hz, 1 H).
MS: m/z = 327.05 [M + H]+, 329.06 [M + H + 2]+.
13C NMR (100 MHz, DMSO-d6): δ = 160.1, 150.3, 139.5, 131.7,
131.6, 130.3, 129.6, 129.1, 129.0, 126.6, 115.3, 111.2, 105.3, 99.5.
Anal. Calcd for C17H11ClN2O3: C, 62.49; H, 3.39; N, 8.57. Found:
C, 62.22; H, 3.44; N, 8.69.
MS: m/z = 263.05 [M + H]+.
6-Methyl-2-phenyl-3,6-dihydro-7H-imidazo[4,5-f]quinolin-7-
one (4g)
Following the typical procedure using 1b ( 0.253 g) gave 4g (0.193
g, 70%) as a light yellow solid; mp >300 °C.
Anal. Calcd for C16H10N2O2: C, 73.27; H, 3.84; N, 10.68. Found: C,
73.41; H, 3.88; N, 10.57.
2-p-Tolylchromeno[5,6-d]imidazol-7(3H)-one (4c)
Following the typical procedure using 1a (0.24 g) gave 4c (0.205 g,
74%) as a light yellow solid; mp 280–282 °C.
IR (KBr): 3456, 1727, 1608, 1290, 780 cm–1.
1H NMR (400 MHz, DMSO-d6): δ = 13.30 (br s, 1 H), 8.55 (d,
J = 9.6 Hz, 1 H), 8.10 (d, J = 8.0 Hz, 2 H), 7.78 (br s, 1 H), 7.40 (d,
J = 8.0 Hz, 2 H), 7.25 (d, J = 8.8 Hz, 1 H), 6.57 (d, J = 9.2 Hz, 1 H),
2.40 (s, 3 H).
IR (KBr): 3113, 1636, 1595, 1287, 779 cm–1.
1H NMR (400 MHz, DMSO-d6): δ = 13.23 (br s, 1 H), 8.51 (d,
J = 9.6 Hz, 1 H), 8.22 (d, J = 7.6 Hz, 2 H), 7.82 (br s, 1 H), 7.59 (t,
J = 7.2 Hz, 2 H), 7.52 (t, J = 7.2 Hz, 1 H), 7.43 (d, J = 9.2 Hz, 1 H),
6.75 (br s, 1 H), 3.72 (s, 3 H).
MS: m/z = 276.06 [M + H]+.
Anal. Calcd for C17H13N3O: C, 74.17; H, 4.76; N, 15.26. Found: C,
74.28; H, 4.80; N, 15.17.
Synthesis 2013, 45, 2983–2988
© Georg Thieme Verlag Stuttgart · New York

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One-Pot Multicomponent Synthesis of Annulated Imidazole Derivatives
2987
2-(4-Ethoxyphenyl)-6-methyl-3,6-dihydro-7H-imidazo[4,5-
f]quinolin-7-one (4h)
Following the typical procedure using 1b (0.253 g) gave 4h (0.236
g, 74%) as a pale yellow solid; mp >300 °C.
2-(4-Ethoxyphenyl)-6-ethyl-3,6-dihydro-7H-imidazo[4,5-
f]quinolin-7-one (4l)
Following the typical procedure using 1c (0.267 g) gave 4l (0.273
g, 82%) as a light yellow solid; mp 288–290 °C.
IR (KBr): 3224, 1645, 1597, 1247, 778 cm–1.
IR (KBr): 3123, 1643, 1602, 1260, 786 cm–1.
1H NMR (400 MHz, DMSO-d6): δ = [13.08 (br s), 13.04 (br s) (1
H)], 8.47 (d, J = 9.2 Hz, 1 H), 8.13 (d, J = 7.6 Hz, 2 H), [7.87 (d,
J = 8.8 Hz), 7.74 (d, J = 8.8 Hz) (1 H)], 7.38 (d, J = 8.8 Hz, 1 H),
7.11–7.09 (m, 2 H), [6.74 (d, J = 9.2 Hz), 6.68 (d, J = 9.2 Hz) (1
H)], 4.11 (q, J = 6.8 Hz, 2 H), 3.69 (s, 3 H), 1.35 (t, J = 6.8 Hz, 3 H).
1H NMR (400 MHz, DMSO-d6): δ = [13.07 (br s), 13.03 (br s) (1
H)], 8.48 (d, J = 9.6 Hz, 1 H), 8.14 (d, J = 7.6 Hz, 2 H), [7.88 (d,
J = 8.4 Hz), 7.75 (d, J = 8.8 Hz) (1 H)], 7.43 (d, J = 9.2 Hz, 1 H),
7.12 (d, J = 7.6 Hz, 2 H), [6.74 (d, J = 9.2 Hz), 6.68 (d, J = 9.2 Hz)
(1 H)], 4.36 (q, J = 6.4 Hz, 2 H), 4.13 (q, J = 6.8 Hz, 2 H), 1.37 (t,
J = 6.8 Hz, 3 H), 1.26 (t, J = 6.4 Hz, 3 H).
13C NMR (100 MHz, DMSO-d6): δ = 161.2, 160.5, 152.7, 141.4,
139.0, 135.3, 134.2, 129.8, 128.6, 122.7, 122.4, 120.7, 120.5, 115.4,
111.8, 109.8, 63.8, 37.7, 15.1, 13.4.
MS: m/z = 320.14 [M + H]+.
Anal. Calcd for C19H17N3O2: C, 71.46; H, 5.37; N, 13.16. Found: C,
71.28; H, 5.40; N, 13.27.
MS: m/z = 334.09 [M + H]+.
6-Ethyl-2-(4-methoxyphenyl)-3,6-dihydro-7H-imidazo[4,5-
f]quinolin-7-one (4i)
Following the typical procedure using 1c (0.267 g) gave 4i (0.255
g, 80%) as a light brown solid; mp >300 °C.
Anal. Calcd for C20H19N3O2: C, 72.05; H, 5.74; N, 12.60. Found: C,
71.92; H, 5.81; N, 12.69.
IR (KBr): 3084, 1643, 1601, 1256, 786 cm–1.
6-Ethyl-2-(furan-2-yl)-3,6-dihydro-7H-imidazo[4,5-f]quinolin-
7-one (4m)
Following the typical procedure using 1c (0.267 g) gave 4m (0.207
g, 74%) as a deep yellow solid; mp 290–292 °C.
1H NMR (400 MHz, DMSO-d6): δ = [13.07 (br s), 13.03 (br s) (1
H)], 8.49 (d, J = 9.6 Hz, 1 H), 8.18–8.14 (m, 2 H), [7.88 (d, J = 9.2
Hz), 7.76 (d, J = 9.2 Hz) (1 H)], 7.43 (dd, J = 8.8, 4.4 Hz, 1 H), 7.14
(dd, J = 8.0, 4.0 Hz, 2 H), [6.74 (d, J = 9.6 Hz), 6.68 (d, J = 9.6 Hz)
(1 H)], 4.37 (q, J = 6.8 Hz, 2 H), 3.86 (s, 3 H), 1.27 (t, J = 6.8 Hz, 3
H).
13C NMR (100 MHz, DMSO-d6): δ = 160.7, 160.5, 152.2, 140.8,
134.8, 133.6, 129.3, 128.1, 128.0, 122.4, 120.2, 120.0, 114.4, 111.3,
109.3, 55.4, 37.4, 12.9.
IR (KBr): 3117, 1647, 1598, 1236, 785 cm–1.
1H NMR (400 MHz, DMSO-d6): δ = [13.44 (br s), 13.21 (br s) (1
H)], [8.48 (d, J = 9.6 Hz), 8.42 (d, J = 9.6 Hz) (1 H)], 7.95 (br s, 1
H), [7.85 (d, J = 9.2 Hz), 7.73 (d, J = 8.8 Hz) (1 H)], 7.45 (t, J = 8.8
Hz, 1 H), [7.23 (d, J = 3.6 Hz), 7.18 (d, J = 3.6 Hz) (1 H)], 6.74 (br
s, 1 H), [6.70 (d, J = 9.6 Hz), 6.66 (d, J = 9.2 Hz) (1 H)], 4.34 (q,
J = 6.4 Hz, 2 H), 1.24 (t, J = 6.4 Hz, 3 H).
MS: m/z = 320.05 [M + H]+.
MS: m/z = 280.03 [M + H]+.
Anal. Calcd for C19H17N3O2: C, 71.46; H, 5.37; N, 13.16. Found: C,
71.59; H, 5.31; N, 13.12.
Anal. Calcd for C16H13N3O2: C, 68.81; H, 4.69; N, 15.05. Found: C,
68.98; H, 4.65; N, 14.97.
6-Ethyl-2-phenyl-3,6-dihydro-7H-imidazo[4,5-f]quinolin-7-one
(4j)
Following the typical procedure using 1c (0.267 g) gave 4j (0.233
g, 77%) as a light yellow solid; mp >300 °C.
IR (KBr): 3109, 1648, 1598, 1250, 782 cm–1.
1H NMR (400 MHz, DMSO-d6): δ = 13.23 (br s, 1 H), 8.51 (d,
J = 9.6 Hz, 1 H), 8.22 (d, J = 8.0 Hz, 2 H), 7.90 (br s, 1 H), 7.59 (t,
J = 7.2 Hz, 2 H), 7.53 (d, J = 7.2 Hz, 1 H), 7.48 (d, J = 9.2 Hz, 1 H),
6.73 (d, J = 8.0 Hz, 1 H), 4.38 (q, J = 6.8 Hz, 2 H), 1.27 (t, J = 6.8
Hz, 3 H).
Acknowledgement
We thank the DST (New Delhi), UGC (New Delhi) and CSIR (New
Delhi) for financial assistance. One of us (K.C.M.) is thankful to
UGC, (New Delhi) for a UGC Emeritus Fellowship, and two of us
(D.G.) and (S.P.) are grateful to CSIR, (New Delhi) for their re-
search fellowships. We also thank the DST (New Delhi) for provi-
ding Bruker NMR spectrometer (400 MHz) and Perkin-Elmer CHN
analyzer, UV-VIS spectrometer and Perkin-Elmer FT-IR under
FIST program.
MS: m/z = 290.10 [M + H]+.
Anal. Calcd for C18H15N3O: C, 74.72; H, 5.23; N, 14.52. Found: C,
74.94; H, 5.19; N, 14.44.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnoIufproi
m
tgioSrantnugIifoop
r
itmnatr
6-Ethyl-2-p-tolyl-3,6-dihydro-7H-imidazo[4,5-f]quinolin-7-one
(4k)
Following the typical procedure using 1c (0.267 g) gave 4k (0.221
g, 73%) as a yellow solid; mp >300 °C.
References
IR (KBr): 3115, 1644, 1599, 1285, 787 cm–1.
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Synthesis 2013, 45, 2983–2988

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