Three-component green synthesis of N-arylquinoline derivatives in ionic liquid [Bmim+][BF4-]: reactions of arylaldehyde, 3-arylamino-5,5-dimethylcyclohex-2-enone, and active methylene compounds

Article abstract of DOI:10.1016/j.tet.2007.03.068

Three series of N-arylquinoline derivatives were synthesized by the three-component reactions of arylaldehyde, 3-arylamino-5,5-dimethylcyclohex-2-enone, and active methylene compounds including malononitrile, meldrum's acid, and 1,3-indenedione in ionic l

Full text of DOI:10.1016/j.tet.2007.03.068

Tetrahedron 63 (2007) 4439–4449
Three-component green synthesis of N-arylquinoline derivatives
in ionic liquid [BmimD][BF4L]: reactions of arylaldehyde,
3-arylamino-5,5-dimethylcyclohex-2-enone, and active
methylene compounds
a
b
a
a,b
Xiang-Shan Wang,a,b, Mei-Mei Zhang, Hong Jiang, Chang-Sheng Yao and Shu-Jiang Tu
*
aDepartment of Chemistry, Xuzhou Normal University, Xuzhou, Jiangsu 221116, PR China
bThe Key Laboratory of Biotechnology on Medical Plant, Xuzhou, Jiangsu 221116, PR China
Received 2 November 2006; revised 12 December 2006; accepted 13 March 2007
Available online 16 March 2007
Abstract—Three series of N-arylquinoline derivatives were synthesized by the three-component reactions of arylaldehyde, 3-arylamino-5,5-
dimethylcyclohex-2-enone, and active methylene compounds including malononitrile, meldrum’s acid, and 1,3-indenedione in ionic liquid
[bmim+][BFꢀ4 ] at 90 ꢁC.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
shown great promise as attractive alternatives to conven-
tional solvents.12 These materials are also widely used in
homogeneous catalysis,13 electrochemistry,14 photochemis-
try,15 and liquid crystals.16 The distinctive property of
room temperature ionic liquids is that they have essentially
no vapor pressure, which makes them optimal replacements
for the volatile organic solvents traditionally used as indus-
trial solvents. Another feature of ionic liquids is their ability
to be reused many times. Because of this advantage, ionic
liquids have made significant contributions to green chemis-
try and have been used widely as reaction medium in organic
chemistry.17 As a part of a program directed toward
the synthesis of new suitably functionalized heterocyclic
compounyds of potential biological activity in green
solvent,18 herein we report three series of N-arylquinoline
derivatives by three-component reactions of arylaldehyde,
3-arylamino-5,5-dimethylcyclohex-2-enone, and active
methylene compounds including malononitrile, meldrum’s
acid, and 1,3-indenedione in ionic liquid [bmim+][BF4ꢀ]
at 90 ꢁC.
Heteroaromatic rings containing nitrogen atoms often play
important roles as the scaffolds of bioactive substances.
Quinoline is one of the most popular N-heteroaromatic
compounds incorporated into the structures of many phar-
maceuticals. It is known that many quinoline containing
compounds exhibit a wide spectrum of pharmacological ac-
tivities, such as antiplasmodial,1 intrinsic,2 cytotoxic,3 func-
tional,4 antibacterial,5 antiproliferative,6 antimalarial,7 and
anticancer activities.8 Therefore, the synthesis of quinolines
has attracted much attention in organic synthesis. The clas-
sical methods for the synthesis of quinoline derivatives
include Skraup, Doebner–Von Miller, Conrad–Limbach,
Combes, and Pfitzinger quinoline syntheses.9 A number of
general synthetic methods have also been reported.10 How-
ever, they were either tedious or poor yields, while organic
solvents were used during all of the reactions. Furthermore,
it should be noted that there was no N-substitute in the
quinoline derivatives. To our best knowledge, only a few
studies11 concerning N-substituted quinolines were reported
in the literature, which were also synthesized in traditional
organic solvents.
2. Results and discussion
Room temperature ionic liquids (RTILs), especially those
based on the 1-N-alkyl-3-methyl imidazolium cation, have
In order to avoid the disadvantages such as volatility and
toxicity that many organic solvents inherently have, we em-
ployed RTILs into the three-component reaction as a green
medium. When the reaction of arylaldehyde 1, 3-arylamino-
5,5-dimethylcyclohex-2-enone 2, and mꢀalononitrile 3 was
performed in ionic liquid [bmim+][BF4 ] at 90 ꢁC, high
Keywords: N-Arylquinoline; Ionic liquid; Malononitrile; Meldrum’s acid;
1,3-Indenedione; Synthesis.
* Corresponding author. Tel.: +86 516 83500349; fax: +86 516 83403164;
e-mail: xswang1974@yahoo.com
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.03.068

4440
X.-S. Wang et al. / Tetrahedron 63 (2007) 4439–4449
Table 2. The reactions of arylaldehyde, 3-arylamino-5,5-dimethylcyclohex-
yields of 2-amino-1,4-diaryl-7,7-dimethyl-5-oxo-1,4,5,6,7,
8-hexahydroquinoline-3-carbonitriles
(Scheme 1).
2-enone, and malononitrile in ionic liquida
4
were obtained
Entry Ar
Ar0
Products Time (h) Yieldsb (%)
1
2
3
4
5
6
7
8
4-FC6H4
4-BrC6H4
3-NO2C6H4
3-NO2C6H4
4-FC6H4
C6H5
C6H5
C6H5
4a
4b
4c
6
7
5
5
6
7
6
5
5
6
5
4
6
6
94
95
96
93
94
95
94
98
99
96
96
98
94
96
Ar
O
O
CN
Ionic liquid
4-BrC6H4 4d
4-BrC6H4 4e
4-BrC6H4 4f
4-BrC6H4 4g
4-CH3C6H4 4h
4-CH3C6H4 4i
4-CH3C6H4 4j
4-CH3C6H4 4k
ArCHO
CH2(CN)2
+
Ar'
+
N
Ar'
4
NH2
N
H
4-BrC6H4
1
2
3,4-Cl2C6H3
3,4-Cl2C6H3
3-NO2C6H4
4-ClC6H4
3
Scheme 1.
9
10
11
12
13
14
2,4-Cl2C6H3
We began our study of the reaction showed in Scheme 1 by
optimizing the reaction conditions for the preparation of 4. A
summary of the optimization experiment is provided in
Table 1. The results showed that at room temperature, no re-
action took place (Table 1, entry 1). To our delight at 90 ꢁC
the reaction proceeded smoothly in high yield. To find the
optimum reaction time, the reaction was carried out in ionic
liquid [bmim+][BF4ꢀ] for 3, 6, or 9 h (Table 1, entries 3–5),
leading to 4a in 82%, 94%, and 94% yield, respectively.
Thus, the optimal reaction temperature and reaction time
is 90 ꢁC and 6 h, respectively. Moreover, different ionic liq-
uids were further investigated as shown in Table 1, we con-
cluded that the [bmim+][BFꢀ4 ] was the best ionic liquid for
this reaction. In addition to MeCN, MeOH and EtOH were
also tested as the reaction solvents. In these cases, product
4a was formed in slightly lower yield (Table 1, entries 11–
13). We also conducted the reaction under solvent-free con-
ditions; compound 4a was produced in 90% yield (Table 1,
entry 14).
4-Cl-2-NO2C6H3 4-CH3C6H4 4l
4-CH3C6H4
4-BrC6H4
4-CH3C6H4 4m
4-CH3C6H4 4n
Reaction condition: 10 mL [bmim+][BF4ꢀ], 1 mmol 1, 1 mmol 2, and
1 mmol 3.
Isolated yields.
a
b
dimethylcyclohex-2-enone, and 3 as model substrates proved
the successive reuse of the recovered ionic liquid. Even
in the fourth cycle the yield (92%) of product 4a is fairly
high.
In order to demonstrate the efficiency and the applicability
of the present method, we performed the reaction of a
variety of arylaldehydes 1 and 3-arylamino-5,5-dimethyl-
cyclohex-2-enones 2 with 3 at 90 ꢁC in ionic liquid
medium of [bmim+][BF4ꢀ]. As shown in Table 2, for series
of 1 and 2, either the aromatic ring containing electron-
withdrawing groups (such as halide, nitro) or electron-
donating groups (such as alkyl group), reacted well with
3 to give the corresponding products 4 in high yields
under the same reaction conditions. So we concluded
that no obvious effects from the electronic or nature of
the aromatic ring substituents were observed in the above
reactions.
After the reaction was completed (monitored by TLC), the
reaction mixtures were cooled to room temperature, the
solid was isolated by filtration, and the ionic liquid in filtrate
could be recovered easily by evaporation at 80 ꢁC in vacuum
for several hours. The recovered ionic liquid could be
used for the same reactions directly. Alternatively, the
ionic liquid was washed with ethyl acetate, followed by
evaporation at 80 ꢁC in vacuum for several hours, if it was
used for the other reaction with different substrates. Investi-
gations by using 4-fluorobenzaldehyde, 3-phenylamino-5,5-
As expected, when the methylene compound of malono-
nitrile was replaced by 1,3-indenedione 5, another series of
5,10-diaryl-7,8-dihydro-7,7-dimethyl-5H-indeno[1,2-b]-
quinolin-9,11(6H,10H)-dione derivatives 6 were obtained
under the same reaction conditions (Scheme 2). The results
are summarized in Table 3. The product of 6a was further
confirmed by X-ray diffraction analysis,19 and the crystal
structure is shown in Figure 1.
Table 1. Synthesis of 4a in ionic liquid at different reaction conditionsa
Entry
T (ꢁC)
Ionic liquidb
Time (h)
Yieldc (%)
1
2
3
4
5
6
7
8
rt
50
90
90
90
90
90
90
90
90
Reflux
Reflux
Reflux
90
[bmim+][BFꢀ4 ]
[bmim+][BFꢀ4 ]
[bmim+][BFꢀ4 ]
[bmimD][BFL4
[bmim+][BFꢀ4 ]
[emim+]Brꢀ
[pmim+]Brꢀ
[bmim+] Brꢀ
[emim+][BFꢀ4 ]
[pmim+][BFꢀ4 ]
CH3CN
6
6
3
6
9
6
6
6
6
0
78
82
94
94
86
87
90
90
91
90
87
89
90
]
Ar
O
O
O
O
O
Ionic liquid
ArCHO
+
Ar'
+
N
Ar'
6
N
H
9
1
2
5
10
11
12
13
14
6
10
11
8
Scheme 2.
CH3OH
EtOH
Solvent free
8
When the meldrum’s acid was selected as methylene
compound (Scheme 3), it was interesting that the desired
products 9 were not detected at all, while 4-aryl-7,7-
dimethyl-1-tolyl-3,4,7,8-tetrahydroquinoline-2,5(1H,6H)-
dione derivatives 8 were obtained in good yields via an
a
Reaction condition: 10 mL ionic liquid, 1 mmol 4-fluorobenzaldehyde,
1 mmol 3-phenylamino-5,5-dimethylcyclohex-2-enone, and 1 mmol 3.
bmim¼1-butyl-3-methylimidazolium; emim¼1-ethyl-3-methylimidazo-
lium; pmim¼1-methyl-3-propylimidazolium.
b
c
Isolated yields.

X.-S. Wang et al. / Tetrahedron 63 (2007) 4439–4449
4441
Table 3. The reactions of arylaldehyde, 3-arylamino-5,5-dimethylcyclohex-
Table 4. The reactions of arylaldehyde, 3-arylamino-5,5-dimethylcyclohex-
2-enone, and 1,3-indenedione in ionic liquida
2-enone, and meldrum’s acid in the ionic liquida
Entry Ar
Ar0
Products Time Yieldsb
Entry Ar
Time (h) Products Yieldsb (%)
(h)
(%)
1
2
3
4
5
6
2-ClC6H4
16
16
12
20
16
8a
8b
8c
8d
8e
8f
88
89
86
80
82
84
1
2
3
4
5
6
7
8
4-BrC6H4
4-BrC6H4
2-ClC6H4
4-ClC6H4
3,4-Cl2C6H3
4-BrC6H4
2,4-Cl2C6H3
4-NO2C6H4
4-CH3C6H4
4-BrC6H4
4-NO2C6H4
2,4-Cl2C6H3
3,4-(CH3O)2C6H3 2-Napthylphenyl 6m
2-ClC6H4
3-ClC6H4
4-OHC6H4
C6H5
4-BrC6H4
4-CH3C6H4
6a
6b
6c
6
7
5
6
6
6
6
5
7
6
5
6
8
5
7
8
95
95
96
91
92
90
93
93
90
93
92
94
93
92
91
91
2,4-Cl2C6H3
2-NO2C6H4
2-OCH3C6H4
2-FC6H4
1-Napthylphenyl 6d
1-Napthylphenyl 6e
1-Napthylphenyl 6f
1-Napthylphenyl 6g
1-Napthylphenyl 6h
2-Napthylphenyl 6i
2-Napthylphenyl 6j
2-Napthylphenyl 6k
2-Napthylphenyl 6l
2-NO2-4,5-OCH2OC6H4 12
Reaction condition: 10 mL [bmim+][BF4ꢀ], 1 mmol 1, 1 mmol 2, and
1 mmol 7.
Isolated yields.
a
b
9
10
11
12
13
14
15
16
Although the detailed mechanism of the above reaction
has not been clarified yet, the formation of 4-aryl-7,7-di-
methyl-1-tolyl-3,4,7,8-tetrahydroquinoline-2,5(1H,6H)-dione
derivatives 8 can be explained by the tentative mechanism
presented in Scheme 4. Importantly, meldrum’s acid readily
eliminated CO2 and acetone when heated.
2-Napthylphenyl 6n
2-Napthylphenyl 6o
2-Napthylphenyl 6p
Reaction condition: 10 mL [bmim+][BF4ꢀ], 1 mmol 1, 1 mmol 2, and
1 mmol 5.
Isolated yields.
a
b
O
O
O
O
O
IL
Ar CH
Ar CHO
+
O
O
O
O
O
O
Ar
O
O
O
O
Michael
Addition
O
CH
O
Ar
+
..
HN
O
N H
. .
Tol
Tol
O
O
Ar
N
O
Ar
-CO2
O
-CH3COCH3
N
O
OH
O
:
Tol
Tol
Scheme 4.
To verify the mechanism, we individually performed each
separate step. The Knoevenagel condensation product, 5-
(2-chlorobenzylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione
10 was obtained in 62% yield, when the 2-chlorobenzalde-
hyde (1, Ar¼2-ClC6H4) was treated with meldrum’s acid
in ionic liquid (Scheme 5). As expected, intermediate 10
smoothly reacted with 2 to give the corresponding quino-
line-2,5(1H,6H)-dione derivatives 8a (Scheme 5). This re-
sult suggests that a Knoevenagel condensation took place
during the reaction.
Figure 1. The structure of 6a showing 50% probability displacement
ellipsoids.
unexpected ring opening of meldrum’s acid reaction. How-
ever, only the aromatic rings with ortho-substituent
resulted in this reaction as summarized in Table 4.
O
O
Ar
N
O
O
O
O
O
Tol
9
O
Ionic liquid
ArCHO
+
+
Ar
NH
Tol
O
O
1
2
7
O
N
Tol
8
Scheme 3.

4442
X.-S. Wang et al. / Tetrahedron 63 (2007) 4439–4449
O
Cl
O
O
O
Cl
O
O
NH
Tol
IL 80 °C
CHO
Cl
O
O
O
O
IL
80 °C
CH
+
N
Tol
8a
O
10
7
Scheme 5.
3. Conclusion
1H NMR (DMSO-d6) d: 0.73 (s, 3H, CH3), 0.88 (s, 3H, CH3),
1.70 (d, J¼17.6 Hz, 1H, CH), 2.01 (d, J¼16.0 Hz, 1H, CH),
2.17–2.22 (m, 2H, 2CH), 4.48 (s, 1H, CH), 5.38 (s, 2H,
NH2), 7.15 (t, J¼8.8 Hz, 2H, ArH), 7.29–7.32 (m, 2H,
ArH), 7.41 (d, J¼6.8 Hz, 2H, ArH), 7.57–7.62 (m, 3H, ArH).
In conclusion, we found a green method for the syn-
theses of N-arylquinoline-3-carbonitrile derivatives, N-aryl-
indeno[1,2-b]quinolin-9,11(6H,10H)-dione derivatives, and
N-tolylquinoline-2,5(1H,6H)-dione derivatives by the three-
component reactions of arylaldehyde, 3-arylamino-5,
5-dimethylcyclohex-2-enone, and active methylene com-
pounds. The features of this procedure are mild reaction
conditions, high yields, operational simplicity, and the envi-
ronmentally friendly procedure. Meanwhile, [bmim+][BF4ꢀ]
could be reused for several rounds without significant loss
of activity.
LC–MS (ESI+, m/z): 797 [(2M+Na+), 5%], 386 [(Mꢀ1),
87%].
Anal. Calcd for C24H22FN3O: C 74.40, H 5.72, N 10.85;
found: C 74.28, H 5.77, N 10.93.
4.2.2. 2-Amino-4-(4-bromophenyl)-7,7-dimethyl-5-oxo-
1-phenyl-1,4,5,6,7,8-hexahydroquinoline-3-carbonitrile
4b. Pale yellow crystals, mp 275–277 ꢁC (lit.11b 270 ꢁC).
4. Experimental
4.1. General
IR (KBr, n, cmꢀ1): 3464, 3329, 3060, 2956, 2902, 2867,
2178, 1652, 1593, 1567, 1489, 1372, 1314, 1258, 1172,
1144, 1069, 1040, 1008, 840, 810, 757, 697.
Melting points were determined in open capillaries and are
uncorrected. IR spectra were recorded on a TENSOR 27
spectrometer in KBr. H NMR spectra were obtained from
solution in DMSO-d6 with Me4Si as internal standard using
an Inova-400 spectrometer. Elemental analyses were carried
out using Perkin–Elmer 240 II analyzer. ESI-MS was
performed using a FINNIGAN LCQ Advantage mass
spectrometer.
1H NMR (DMSO-d6) d: 0.73 (s, 3H, CH3), 0.88 (s, 3H, CH3),
1.70 (d, J¼17.6 Hz, 1H, CH), 2.01 (d, J¼16.0 Hz, 1H, CH),
2.19 (d, J¼16.8 Hz, 2H, 2CH), 4.46 (s, 1H, CH), 5.40 (s, 2H,
NH2), 7.24 (d, J¼8.0 Hz, 2H, ArH), 7.41 (d, J¼6.4 Hz,
2H, ArH), 7.53 (d, J¼8.0 Hz, 2H, ArH), 7.57–7.66 (m,
3H, ArH).
1
4.2.3. 2-Amino-7,7-dimethyl-4-(3-nitrophenyl)-5-oxo-1-
phenyl-1,4,5,6,7,8-hexahydroquinoline-3-carbonitrile
4c. Pale yellow crystals, mp 268–269 ꢁC.
4.2. General procedure for the syntheses of 2-amino-1,4-
diaryl-7,7-dimethyl-5-oxo-1,4,5,6,7,8-hexahydroquino-
line-3-carbonitrile 4
IR (KBr, n, cmꢀ1): 3465, 3329, 2960, 2871, 2179, 1651,
1618, 1592, 1523, 1417, 1374, 1349, 1257, 1146, 1072,
810, 734, 710, 693.
A dry 50 mL flask was charged with arylaldehyde
(1.0 mmol), malononitrile (1.0 mmol), 3-arylamino-5,5-
dimethylcyclohex-2-enone (1.0 mmol), and ionic liquid
[bmim+][BFꢀ4 ] (10 mL). The reaction mixture was
stirred at 90 ꢁC for 4–7 h, and then cooled to room
temperature. The generated yellow solid was filtered off,
and the ionic liquid in filtrate was then recovered for
reuse by evaporating at 80 ꢁC for several hours in vacuum.
The crude yellow products were washed with water and
purified by recrystallization from DMF and water,
followed by being dried at 80 ꢁC for several hours in vacuum
to give 4.
1H NMR (DMSO-d6) d: 0.72 (s, 3H, CH3), 0.89 (s, 3H, CH3),
1.73 (d, J¼17.6 Hz, 1H, CH), 2.02 (d, J¼16.0 Hz, 1H, CH),
2.22 (d, J¼16.0 Hz, 1H, CH), 2.24 (d, J¼17.6 Hz, 1H, CH),
4.65 (s, 1H, CH), 5.55 (s, 2H, NH2), 7.42 (d, J¼6.8 Hz, 2H,
ArH), 7.57–7.70 (m, 4H, ArH), 7.79 (d, J¼7.6 Hz, 1H, ArH),
8.09–8.11 (m, 2H, ArH).
Anal. Calcd for C24H22N4O3: C 69.55, H 5.35, N 13.52;
found: C 69.48, H 5.36, N 13.44.
4.2.1. 2-Amino-7,7-dimethyl-4-(4-fluorophenyl)-5-oxo-1-
phenyl-1,4,5,6,7,8-hexahydroquinoline-3-carbonitrile
4a. Pale yellow crystals, mp 263–265 ꢁC.
4.2.4. 2-Amino-1-(4-bromophenyl)-7,7-dimethyl-4-(3-
nitrophenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-
carbonitrile 4d. Pale yellow crystals, mp 271–274 ꢁC.
IR (KBr, n, cmꢀ1): 3454, 3339, 3053, 2959, 2958, 2888,
2177, 1651, 1639, 1592, 1558, 1504, 1489, 1417, 1371,
1340, 1257, 1216, 1153, 1046, 929, 849, 781, 764, 702.
IR (KBr, n, cmꢀ1): 3479, 3382, 2957, 2924, 2870, 2180,
1642, 1566, 1489, 1412, 1374, 1259, 1179, 1148, 1073,
1011, 895, 808, 746, 696.

X.-S. Wang et al. / Tetrahedron 63 (2007) 4439–4449
4443
1H NMR (DMSO-d6) d: 0.73 (s, 3H, CH3), 0.91 (s, 3H, CH3),
1.76 (d, J¼17.6 Hz, 1H, CH), 2.00 (d, J¼16.0 Hz, 1H, CH),
2.17 (d, J¼16.0 Hz, 1H, CH), 2.25 (d, J¼17.6 Hz, 1H, CH),
4.63 (s, 1H, CH), 5.72 (s, 2H, NH2), 7.38 (d, J¼8.4 Hz, 2H,
ArH), 7.64–7.69 (m, 1H, ArH), 7.79–7.81 (m, 3H, ArH),
8.07–8.11 (m, 2H, ArH).
Anal. Calcd for C24H20BrCl2N3O: C 55.73, H 3.90, N 8.12;
found: C 55.60, H 3.99, N 8.23.
4.2.8. 2-Amino-7,7-dimethyl-4-(3,4-dichlorophenyl)-
1-(4-methylphenyl)-5-oxo-1,4,5,6,7,8-hexahydroquino-
line-3-carbonitrile 4h. Pale yellow crystals, mp 270–
272 ꢁC.
Anal. Calcd for C24H21BrN4O3: C 58.43, H 4.29, N 11.36;
found: C 58.40, H 4.20, N 11.48.
IR (KBr, n, cmꢀ1): 3463, 3330, 3084, 3034, 2960, 2940,
2889, 2871, 2178, 1652, 1619, 1509, 1468, 1416, 1398,
1371, 1343, 1313, 1257, 1175, 1145, 1125, 1108, 1046,
1025, 880, 847, 812, 726, 671.
4.2.5. 2-Amino-1-(4-bromophenyl)-7,7-dimethyl-4-
(4-fluorophenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-
3-carbonitrile 4e. Pale yellow crystals, mp 253–255 ꢁC.
1H NMR (DMSO-d6) d: 0.74 (s, 3H, CH3), 0.88 (s, 3H, CH3),
1.74 (d, J¼17.6 Hz, 1H, CH), 2.02 (d, J¼16.0 Hz, 1H,
CH), 2.18 (d, J¼16.0 Hz, 1H, CH), 2.19 (d, J¼17.6 Hz,
1H, CH), 2.41 (s, 3H, CH3), 4.50 (s, 1H, CH), 5.43 (s, 2H,
NH2), 7.26–7.30 (m, 3H, ArH), 7.40 (d, J¼8.4 Hz, 2H,
ArH), 7.44 (d, J¼2.0 Hz, 1H, ArH), 7.61 (d, J¼8.4 Hz,
1H, ArH).
IR (KBr, n, cmꢀ1): 3467, 3331, 3066, 2967, 2951, 2868,
2181, 1654, 1620, 1601, 1505, 1486, 1415, 1373, 1256,
1219, 1153, 1070, 1011, 858, 811, 769, 739.
1H NMR (DMSO-d6) d: 0.73 (s, 3H, CH3), 0.89 (s, 3H,
CH3), 1.72 (d, J¼17.6 Hz, 1H, CH), 2.01 (d, J¼16.0 Hz,
1H, CH), 2.19 (d, J¼16.0 Hz, 1H, CH), 2.21 (d,
J¼17.6 Hz, 1H, CH), 4.46 (s, 1H, CH), 5.53 (s, 2H,
NH2), 7.12 (t, J¼8.8 Hz, 2H, ArH), 7.27–7.31 (m, 2H,
ArH), 7.37 (d, J¼8.4 Hz, 2H, ArH), 7.77 (d, J¼8.4 Hz,
2H, ArH).
Anal. Calcd for C25H23Cl2N3O: C 66.38, H 5.12, N 9.29;
found: C 66.44, H 5.10, N 9.12.
4.2.9. 2-Amino-7,7-dimethyl-1-(4-methylphenyl)-4-(3-
nitrophenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-
carbonitrile 4i. Pale yellow crystals, mp 281–283 ꢁC.
Anal. Calcd for C24H21BrFN3O: C 61.81, H 4.54, N 9.01;
found: C 61.90, H 4.58, N 8.97.
IR (KBr, n, cmꢀ1): 3483, 3383, 3032, 2960, 2927, 2870,
2179, 1643, 1612, 1564, 1529, 1510, 1412, 1375, 1348,
1302, 1259, 1146, 1043, 896, 809, 741, 698.
4.2.6. 2-Amino-1,4-di(4-bromophenyl)-7,7-dimethyl-5-
oxo-1,4,5,6,7,8-hexahydroquinoline-3-carbonitrile 4f.
Pale yellow crystals, mp 276–278 ꢁC.
1H NMR (DMSO-d6) d: 0.73 (s, 3H, CH3), 0.93 (s, 3H, CH3),
1.76 (d, J¼17.6 Hz, 1H, CH), 2.01 (d, J¼16.0 Hz, 1H, CH),
2.22 (d, J¼16.0 Hz, 1H, CH), 2.24 (d, J¼17.6 Hz, 1H, CH),
2.41 (s, 3H, CH3), 4.64 (s, 1H, CH), 5.51 (s, 2H, NH2), 7.29
(d, J¼7.6 Hz, 2H, ArH), 7.42 (d, J¼7.6 Hz, 2H, ArH), 7.65–
7.69 (m, 1H, ArH), 7.77 (d, J¼7.6 Hz, 1H, ArH), 8.08–8.10
(m, 2H, ArH).
IR (KBr, n, cmꢀ1): 3460, 3323, 3058, 2962, 2867, 2179,
1652, 1621, 1571, 1486, 1415, 1371, 1313, 1256, 1146,
1069, 1009, 858, 842, 803.
1H NMR (DMSO-d6) d: 0.73 (s, 3H, CH3), 0.89 (s, 3H, CH3),
1.72 (d, J¼17.6 Hz, 1H, CH), 1.99 (d, J¼16.0 Hz, 1H, CH),
2.19 (d, J¼16.0 Hz, 1H, CH), 2.21 (d, J¼17.6 Hz, 1H, CH),
4.44 (s, 1H, CH), 5.56 (s, 2H, NH2), 7.23 (t, J¼8.4 Hz, 2H,
ArH), 7.37 (t, J¼8.4 Hz, 2H, ArH), 7.51 (d, J¼8.4 Hz, 2H,
ArH), 7.77 (d, J¼8.4 Hz, 2H, ArH).
Anal. Calcd for C25H24N4O3: C 70.08, H 5.65, N 13.08;
found: C 70.25, H 5.60, N 13.00.
4.2.10. 2-Amino-4-(4-chlorophenyl)-7,7-dimethyl-1-
(4-methylphenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-
3-carbonitrile 4j. Pale yellow crystals, mp 260–262 ꢁC.
Anal. Calcd for C24H21Br2N3O: C 54.67, H 4.01, N 7.97;
found C 54.55, H 4.20, N 7.94.
4.2.7. 2-Amino-1-(4-bromophenyl)-4-(3,4-dichloro-
phenyl)-7,7-dimethyl-5-oxo-1,4,5,6,7,8-hexahydroquino-
line-3-carbonitrile 4g. Pale yellow crystals, mp 277–
279 ꢁC.
IR (KBr, n, cmꢀ1): 3441, 3306, 2959, 2927, 2870, 1651,
1621, 1557, 1510, 1469, 1442, 1408, 1373, 1258, 1243,
1152, 1110, 1034, 847, 820.
1H NMR (DMSO-d6) d: 0.73 (s, 3H, CH3), 0.89 (s, 3H, CH3),
1.73 (d, J¼17.6 Hz, 1H, CH), 2.00 (d, J¼16.0 Hz, 1H, CH),
2.19 (d, J¼16.08 Hz, 2H, 2CH), 2.41 (s, 3H, CH3), 4.47
(s, 1H, CH), 5.33 (s, 2H, NH2), 7.27–7.30 (m, 4H, ArH),
7.38–7.41 (m, 4H, ArH).
IR (KBr, n, cmꢀ1): 3464, 3334, 3059, 2957, 2888, 2870,
2178, 1650, 1620, 1570, 1487, 1466, 1398, 1371, 1256,
1147, 1071, 1044, 1022, 1010, 881, 850, 812.
1H NMR (DMSO-d6) d: 0.74 (s, 3H, CH3), 0.89 (s, 3H,
CH3), 1.75 (d, J¼17.2 Hz, 1H, CH), 2.02 (d, J¼16.0 Hz,
1H, CH), 2.19 (d, J¼16.4 Hz, 2H, 2CH), 4.49 (s, 1H, CH),
5.64 (s, 2H, NH2), 7.28 (dd, J¼8.4 Hz, J0¼2.0 Hz, 1H,
ArH), 7.37 (t, J¼8.4 Hz, 2H, ArH), 7.44 (d, J¼2.0 Hz, 1H,
ArH), 7.60 (d, J¼8.4 Hz, 1H, ArH), 7.78 (d, J¼8.4 Hz,
2H, ArH).
Anal. Calcd for C25H24ClN3O: C 71.85, H 5.79, N 10.05;
found: C 71.98, H 5.80, N 9.91.
4.2.11. 2-Amino-4-(2,4-dichlorophenyl)-7,7-dimethyl-1-
(4-methylphenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-
3-carbonitrile 4k. Pale yellow crystals, mp 267–269 ꢁC.

4444
X.-S. Wang et al. / Tetrahedron 63 (2007) 4439–4449
IR (KBr, n, cmꢀ1): 3470, 3339, 2965, 2929, 2871, 2174,
1651, 1626, 1584, 1557, 1466, 1419, 1371, 1316, 1260,
1245, 1203, 1154, 1101, 1042, 847, 807, 757, 738.
CH), 5.36 (s, 2H, NH2), 7.23 (d, J¼8.0 Hz, 2H, ArH), 7.28
(d, J¼8.0 Hz, 2H, ArH), 7.40 (d, J¼8.0 Hz, 2H, ArH),
7.52 (d, J¼8.0 Hz, 2H, ArH).
1H NMR (DMSO-d6) d: 0.80 (s, 3H, CH3), 0.89 (s, 3H, CH3),
1.78 (d, J¼17.6 Hz, 1H, CH), 1.96 (d, J¼16.0 Hz, 1H, CH),
2.17 (d, J¼16.4 Hz, 2H, 2CH), 2.41 (s, 3H, CH3), 4.98 (s,
1H, CH), 5.30 (s, 2H, NH2), 7.32 (d, J¼8.4 Hz, 2H, ArH),
7.37–7.42 (m, 4H, ArH), 7.53 (s, 1H, ArH).
Anal. Calcd for C25H24BrN3O: C 64.94, H 5.23, N 9.09;
found: C 64.90, H 5.28, N 9.22.
4.3. General procedure for the syntheses of 5,10-diaryl-
7,8-dihydro-7,7-dimethyl-5-phenyl-5H-indeno[1,2-b]-
quinolin-9,11(6H,10H)-dione 6
Anal. Calcd for C25H23Cl2N3O: C 66.38, H 5.12, N 9.29;
found: C 66.42, H 5.01, N 9.35.
A dry 50 mL flask was charged with arylaldehyde
(1.0 mmol), 1,3-indenedione (1.0 mmol), 3-arylamino-5,5-
dimethylcyclohex-2-enone (1.0 mmol), and ionic liquid
[bmim+][BFꢀ4 ] (10 mL). The reaction mixture was stirred
at 90 ꢁC for 5–8 h, and then cooled to room temperature.
The generated red solid was filtered off and the ionic liquid
in filtrate was then recovered for reuse by drying at 80 ꢁC for
several hours in vacuum. The crude red products were
washed with water and purified by recrystallization from
DMF and water, followed by being dried at 80 ꢁC for several
hours in vacuum to give 6.
4.2.12. 2-Amino-4-(4-chloro-2-nitrophenyl)-7,7-di-
methyl-1-(4-methylphenyl)-5-oxo-1,4,5,6,7,8-hexahydro-
quinoline-3-carbonitrile 4l. Pale yellow crystals, mp 274–
276 ꢁC.
IR (KBr, n, cmꢀ1): 3468, 3373, 2954, 2870, 2188, 1653,
1600, 1566, 1521, 1508, 1489, 1472, 1417, 1371, 1352,
1293, 1256, 837, 810, 756.
1H NMR (DMSO-d6) d: 0.71 (s, 3H, CH3), 0.86 (s, 3H, CH3),
1.78 (d, J¼17.2 Hz, 1H, CH), 1.93 (d, J¼16.0 Hz, 1H, CH),
2.09–2.14 (m, 2H, ArH), 2.42 (s, 3H, CH3), 5.20 (s, 1H, CH),
5.51 (s, 2H, NH2), 7.32 (d, J¼8.0 Hz, 2H, ArH), 7.44 (d,
J¼8.0 Hz, 2H, ArH), 7.52–7.54 (m, 2H, ArH), 7.87 (d,
J¼9.6 Hz, 1H, ArH).
4.3.1. 10-(4-Bromophenyl)-7,8-dihydro-7,7-dimethyl-5-
phenyl-5H-indeno[1,2-b]quinolin-9,11(6H,10H)-dione
(6a). Red crystals, mp 280–283 ꢁC.
IR (KBr, n, cmꢀ1): 3047, 2952, 2871, 1686, 1640, 1586,
1559, 1485, 1453, 1391, 1368, 1317, 1256, 1224, 1193,
1169, 1139, 1100, 1061, 1009, 938, 888, 845, 768, 734, 710.
Anal. Calcd for C25H23ClN4O3: C 64.86, H 5.01, N 12.10;
found: C 64.80, H 5.22, N 12.11.
1H NMR (DMSO-d6) d: 0.81 (s, 3H, CH3), 0.94 (s, 3H, CH3),
2.00 (d, J¼17.2 Hz, 1H, CH), 2.06 (d, J¼16.4 Hz, 1H, CH),
2.27 (d, J¼16.0 Hz, 1H, CH), 2.41 (d, J¼17.6 Hz, 1H, CH),
4.84 (s, 1H, CH), 5.10 (d, J¼7.2 Hz, 1H, ArH), 7.00 (t,
J¼7.6 Hz, 1H, ArH), 7.17–7.25 (m, 2H, ArH), 7.35 (d,
J¼8.0 Hz, 2H, ArH), 7.47 (d, J¼8.0 Hz, 2H, ArH), 7.71
(br, 5H, ArH).
4.2.13. 2-Amino-7,7-dimethyl-1,4-di(4-methylphenyl)-5-
oxo-1,4,5,6,7,8-hexahydroquinoline-3-carbonitrile 4m.
Pale yellow crystals, mp 252–254 ꢁC.
IR (KBr, n, cmꢀ1): 3459, 3331, 3032, 3007, 2954, 2866,
2179, 1655, 1620, 1557, 1509, 1413, 1372, 1257, 1146,
1042, 1017, 848, 797.
Anal. Calcd for C30H24BrNO2: C 70.59, H 4.74, N 2.74;
found: C 70.48, H 4.92, N 2.80.
1H NMR (DMSO-d6) d: 0.74 (s, 3H, CH3), 0.88 (s, 3H, CH3),
1.73 (d, J¼17.6 Hz, 1H, CH), 1.99 (d, J¼16.0 Hz, 1H, CH),
2.18 (d, J¼16.0 Hz, 1H, CH), 2.19 (d, J¼17.6 Hz, 1H, CH),
2.17 (s, 3H, CH3), 2.41 (s, 3H, CH3), 4.41 (s, 1H, CH), 5.24
(s, 2H, NH2), 7.12 (d, J¼8.0 Hz, 2H, ArH), 7.15 (d,
J¼8.0 Hz, 2H, ArH), 7.25 (d, J¼8.0 Hz, 2H, ArH), 7.39
(d, J¼8.0 Hz, 2H, ArH).
4.3.2. 5,10-Di(4-bromophenyl)-7,8-dihydro-7,7-di-
methyl-5H-indeno[1,2-b]quinolin-9,11(6H,10H)-dione
(6b). Red crystals, mp 271–273 ꢁC.
IR (KBr, n, cmꢀ1): 3089, 2959, 2883, 1692, 1645, 1608,
1590, 1559, 1487, 1455, 1395, 1365, 1301, 1254, 1223,
1191, 1169, 1141, 1100, 1070, 1010, 976, 888, 841, 791,
763, 705.
Anal. Calcd for C26H27N3O: C 78.56, H 6.85, N 10.57;
found: C 78.77, H 6.70, N 10.50.
4.2.14. 2-Amino-4-(bromophenyl)-7,7-dimethyl-
1-(4-methylphenyl)-5-oxo-1,4,5,6,7,8-hexahydroquino-
line-3-carbonitrile 4n. Pale yellow crystals, mp 261–
263 ꢁC.
1H NMR (DMSO-d6) d: 0.80 (s, 3H, CH3), 0.94 (s, 3H,
CH3), 1.98 (d, J¼17.6 Hz, 1H, CH), 2.05 (d, J¼16.0 Hz,
1H, CH), 2.26 (d, J¼16.0 Hz, 1H, CH), 2.38 (d,
J¼17.6 Hz, 1H, CH), 4.82 (s, 1H, CH), 5.26 (d, J¼7.6 Hz,
1H, ArH), 7.07–7.12 (m, 1H, ArH), 7.19–7.26 (m, 2H,
ArH), 7.34 (d, J¼8.0 Hz, 2H, ArH), 7.45 (d, J¼8.0 Hz,
2H, ArH), 7.72 (br, 2H, ArH), 7.90 (d, J¼8.4 Hz, 2H, ArH).
IR (KBr, n, cmꢀ1): 3460, 3320, 3055, 2950, 2866, 2180,
1653, 1619, 1569, 1509, 1483, 1413, 1371, 1257, 1173,
1145, 1041, 1007, 842, 805, 785.
LC–MS (ESI+, m/z): 1201 [(2M+Na+), 100%].
1H NMR (DMSO-d6) d: 0.73 (s, 3H, CH3), 0.88 (s, 3H, CH3),
1.74 (d, J¼17.6 Hz, 1H, CH), 2.01 (d, J¼16.0 Hz, 1H, CH),
2.17–2.21 (m, 2H, 2CH), 2.41 (s, 3H, CH3), 4.45 (s, 1H,
Anal. Calcd for C30H23Br2NO2: C 61.14, H 3.93, N 2.38;
found: C 61.00, H 3.98, N 2.49.

X.-S. Wang et al. / Tetrahedron 63 (2007) 4439–4449
4445
4.3.3. 10-(4-Chlorophenyl)-7,8-dihydro-7,7-dimethyl-5-
(4-methylphenyl)-5H-indeno[1,2-b]quinolin-9,11(6H,10H)-
dione (6c). Red crystals, mp 263–265 ꢁC.
IR (KBr, n, cmꢀ1):3054, 2964, 2871, 1687, 1653, 1633, 1588,
1560, 1541, 1521, 1455, 1391, 1362, 1261, 1225, 1191, 1167,
1125, 1103, 1067, 1009, 889, 863, 804, 784, 766, 729.
IR (KBr, n, cmꢀ1): 3059, 2957, 2933, 2857, 1673, 1644,
1637, 1590, 1558, 1511, 1456, 1439, 1365, 1321, 1301,
1223, 1189, 1170, 1140, 1110, 1058, 976, 888, 766, 756, 700.
1H NMR (DMSO-d6) d: 0.79 (s, 3H, CH3), 0.80 (s, 3H, CH3),
2.09 (d, J¼17.2 Hz, 1H, CH), 2.10 (d, J¼16.8 Hz, 1H,
CH), 2.21 (d, J¼16.8 Hz, 1H, CH), 2.24 (d, J¼17.2 Hz,
1H, CH), 4.67 (d, J¼7.6 Hz, 1H, ArH), 4.96 (s, 1H,
CH), 6.71–6.76 (m, 1H, ArH), 7.05–7.09 (m, 1H, ArH),
7.19 (d, J¼8.8 Hz, 1H, ArH), 7.42 (d, J¼8.4 Hz, 2H,
ArH), 7.49 (d, J¼8.4 Hz, 2H, ArH), 7.63–7.68 (m, 2H,
ArH), 7.79–7.85 (m, 2H, ArH), 8.03 (d, J¼7.2 Hz, 1H,
ArH), 8.20 (d, J¼8.0 Hz, 1H, ArH), 8.34 (d, J¼8.4 Hz,
1H, ArH).
1H NMR (DMSO-d6) d: 0.83 (s, 3H, CH3), 0.93 (s, 3H, CH3),
2.00 (d, J¼16.8 Hz, 2H, 2CH), 2.24 (d, J¼16.4 Hz, 1H, CH),
2.36 (d, J¼17.6 Hz, 1H, CH), 2.50 (s, 3H, CH3), 5.18 (d,
J¼7.6 Hz, 1H, ArH), 5.24 (s, 1H, CH), 6.98–7.03 (m, 1H,
ArH), 7.13–7.20 (m, 3H, ArH), 7.25–7.32 (m, 2H, ArH),
7.49–7.58 (m, 5H, ArH).
Anal. Calcd for C31H26ClNO2: C 77.57, H 5.46, N 2.92;
found: C 77.45, H 5.60, N 3.01.
Anal. Calcd for C34H26BrNO2: C 72.86, H 4.68, N 2.50;
found: C 72.80, H 4.52, N 2.54.
4.3.4. 10-(4-Chlorophenyl)-7,8-dihydro-7,7-dimethyl-5-
naphthalen-1-yl-5H-indeno[1,2-b]quinolin-9,11(6H,10H)-
dione (6d). Red crystals, mp 288–290 ꢁC.
4.3.7. 10-(2,4-Dichlorophenyl)-7,8-dihydro-7,7-dimethyl-
5-naphthalen-1-yl-5H-indeno[1,2-b]quinolin-9,11(6H,
10H)-dione (6g). Red crystals, mp 285–288 ꢁC.
IR (KBr, n, cmꢀ1): 3061, 2954, 2868, 1683, 1852, 1631,
1590, 1562, 1488, 1454, 1391, 1362, 1261, 1249, 1226,
1128, 1086, 1014, 1005, 889, 841, 785, 767, 732, 699.
IR (KBr, n, cmꢀ1):3058, 2954, 2867, 1692, 1650, 1633, 1587,
1560, 1507, 1466, 1391, 1364, 1259, 1226, 1192, 1171, 1133,
1103, 1047, 1004, 939, 891, 863, 782, 766, 732, 703.
1H NMR (DMSO-d6) d: 0.79 (s, 3H, CH3), 0.80 (s, 3H, CH3),
1.94 (d, J¼16.8 Hz, 1H, CH), 2.09 (d, J¼16.0 Hz, 1H, CH),
2.21 (d, J¼16.8 Hz, 1H, CH), 2.24 (d, J¼16.0 Hz, 1H, CH),
4.67 (d, J¼7.6 Hz, 1H, ArH), 4.97 (s, 1H, CH), 6.74 (t,
J¼7.6 Hz, 1H, ArH), 7.05–7.09 (m, 1H, ArH), 7.19 (d, J¼
6.8 Hz, 1H, ArH), 7.35 (d, J¼8.4 Hz, 2H, ArH), 7.48 (d,
J¼8.4 Hz, 2H, ArH), 7.64–7.69 (m, 2H, ArH), 7.79–7.85
(m, 2H, ArH), 8.03 (d, J¼7.2 Hz, 1H, ArH), 8.20 (d,
J¼8.4 Hz, 1H, ArH), 8.34 (d, J¼8.0 Hz, 1H, ArH).
1H NMR (DMSO-d6) d: 0.79 (s, 3H, CH3), 0.82 (s, 3H,
CH3), 2.01 (d, J¼17.2 Hz, 1H, CH), 2.04 (d, J¼16.4 Hz,
1H, CH), 2.22 (d, J¼16.4 Hz, 2H, 2CH), 4.66 (d,
J¼7.6 Hz, 1H, ArH), 5.36 (s, 1H, CH), 6.75 (t, J¼7.6 Hz,
1H, ArH), 7.06–7.10 (m, 1H, ArH), 7.17 (d, J¼6.8 Hz,
1H, ArH), 7.37 (dd, J¼8.4 Hz, J0¼2.0 Hz, 1H, ArH), 7.50
(d, J¼2.0 Hz, 1H, ArH), 7.63 (d, J¼8.4 Hz, 1H, ArH),
7.66–7.69 (m, 2H, ArH), 7.80–7.91 (m, 2H, ArH), 8.02 (d,
J¼6.8 Hz, 1H, ArH), 8.19–8.21 (m, 1H, ArH), 8.34 (d,
J¼8.4 Hz, 1H, ArH).
Anal. Calcd for C34H26ClNO2: C 79.14, H 5.08, N 2.71;
found: C 79.22, H 5.13, N 2.70.
Anal. Calcd for C34H25Cl2NO2: C 74.18, H 4.58, N 2.54;
found: C 74.10, H 4.70, N 2.55.
4.3.5. 10-(3,4-Dichlorophenyl)-7,8-dihydro-7,7-dimethyl-
5-naphthalen-1-yl-5H-indeno[1,2-b]quinolin-9,11(6H,10H)-
dione (6e). Red crystals, mp 284–286 ꢁC.
4.3.8. 7,8-Dihydro-7,7-dimethyl-5-naphthalen-1-yl-
10-(4-nitrophenyl)-5H-indeno[1,2-b]quinolin-9,11(6H,
10H)-dione (6h). Red crystals, mp 268–270 ꢁC.
IR (KBr, n, cmꢀ1): 3050, 2958, 2871, 1689, 1653, 1634,
1589, 1559, 1507, 1465, 1456, 1393, 1363, 1261, 1226,
1191, 1171, 1133, 1029, 1004, 891, 784, 766, 738, 699.
IR (KBr, n, cmꢀ1): 3059, 2958, 2929, 2869, 1694, 1673,
1634, 1589, 1562, 1514, 1455, 1390, 1363, 1261, 1227,
1193, 1171, 1134, 1006, 891, 829, 781, 761, 712, 702.
1H NMR (DMSO-d6) d: 0.80 (s, 3H, CH3), 0.91 (d,
J¼8.0 Hz, 3H, CH3), 2.00–2.14 (m, 2H, 2CH), 2.24 (d,
J¼16.0 Hz, 1H, CH), 2.26 (d, J¼17.2 Hz, 1H, CH), 4.68
(d, J¼7.6 Hz, 1H, ArH), 4.99 (s, 1H, CH), 6.73–6.77 (m,
1H, ArH), 7.08 (t, J¼7.2 Hz, 1H, ArH), 7.20 (d, J¼7.2 Hz,
1H, ArH), 7.47 (dd, J¼8.4 Hz, J0¼2.0 Hz, 1H, ArH), 7.56
(d, J¼8.4 Hz, 1H, ArH), 7.65–7.68 (m, 3H, ArH), 7.80–
7.85 (m, 2H, ArH), 8.06 (d, J¼7.6 Hz, 1H, ArH), 8.20 (d,
J¼7.6 Hz, 1H, ArH), 8.34 (d, J¼8.4 Hz, 1H, ArH).
1H NMR (DMSO-d6) d: 0.79 (s, 3H, CH3), 0.80 (s, 3H,
CH3), 1.96 (d, J¼17.2 Hz, 1H, CH), 2.10 (d, J¼16.4 Hz,
1H, CH), 2.25 (d, J¼16.4 Hz, 2H, 2CH), 4.69 (d,
J¼7.6 Hz, 1H, ArH), 5.12 (s, 1H, CH), 6.73–6.78 (m, 1H,
ArH), 7.06–7.10 (m, 1H, ArH), 7.20 (d, J¼6.8 Hz,
1H, ArH), 7.66–7.89 (m, 6H, ArH), 8.10 (d, J¼7.2 Hz,
1H, ArH), 8.17–8.30 (m, 3H, ArH), 8.35 (d, J¼8.4 Hz, 1H,
ArH).
Anal. Calcd for C34H25Cl2NO2: C 74.18, H 4.58, N 2.54;
found: C 74.02, H 4.66, N 2.60.
Anal. Calcd for C34H26N2O4: C 77.55, H 4.98, N 5.32; found
C 77.46, H 4.90, N 5.39.
4.3.6. 10-(4-Bromophenyl)-7,8-dihydro-7,7-dimethyl-
5-naphthalen-1-yl-5H-indeno[1,2-b]quinolin-9,11(6H,
10H)-dione (6f). Red crystals, mp 289–291 ꢁC.
4.3.9. 7,8-Dihydro-7,7-dimethyl-10-(4-methylphenyl)-5-
naphthalen-2-yl-5H-indeno[1,2-b]quinolin-9,11(6H,
10H)-dione (6i). Red crystals, mp 271–273 ꢁC.

4446
X.-S. Wang et al. / Tetrahedron 63 (2007) 4439–4449
IR (KBr, n, cmꢀ1): 3046, 2957, 2870, 1688, 1645, 1626,
1589, 1557, 1509, 1455, 1396, 1364, 1256, 1222, 1192,
1171, 1140, 1091, 1056, 872, 763.
1H NMR (DMSO-d6) d: 0.83 (d, J¼6.0 Hz, 3H, CH3), 0.90
(d, J¼9.2 Hz, 3H, CH3), 1.98–2.11 (m, 2H, 2CH), 2.26 (d,
J¼16.0 Hz, 1H, CH), 2.40–2.44 (m, 1H, CH), 5.01 (t,
J¼6.8 Hz, 1H, ArH), 5.27 (s, 1H, CH), 6.84–6.88 (m, 1H,
ArH), 7.12–7.16 (m, 1H, ArH), 7.21 (d, J¼7.2 Hz, 1H, ArH),
7.34–7.40 (m, 1H, ArH), 7.49 (dd, J¼6.0 Hz, J0¼2.0 Hz, 1H,
ArH), 7.58–7.61 (m, 1H, ArH), 7.71–7.87 (m, 3H, ArH),
8.06–8.19 (m, 2H, ArH), 8.23–8.38 (m, 2H, ArH).
1H NMR (DMSO-d6) d: 0.79 (s, 3H, CH3), 0.91 (s, 3H, CH3),
1.99 (d, J¼17.6 Hz, 1H, CH), 2.05 (d, J¼16.4 Hz, 1H, CH),
2.25 (s, 3H, CH3), 2.28 (d, J¼16.4 Hz, 1H, CH), 2.46 (d,
J¼17.6 Hz, 1H, CH), 4.86 (s, 1H, CH), 5.02 (d, J¼7.2 Hz,
1H, ArH), 6.83–6.87 (m, 1H, ArH), 7.11–7.14 (m, 3H,
ArH), 7.22 (d, J¼7.2 Hz, 1H, ArH), 7.32 (d, J¼7.2 Hz,
2H, ArH), 7.71–7.76 (m, 2H, ArH), 7.79 (d, J¼8.4 Hz,
1H, ArH), 8.19–8.35 (m, 4H, ArH).
Anal. Calcd for C34H25Cl2NO2: C 74.18, H 4.58, N 2.54;
found: C 74.29, H 4.60, N 2.48.
4.3.13. 7,8-Dihydro-7,7-dimethyl-10-(3,4-dimethoxyl-
phenyl)-5-naphthalen-2-yl-5H-indeno[1,2-b]quinolin-
9,11(6H,10H)-dione (6m). Red crystals, mp 251–254 ꢁC.
Anal. Calcd for C35H29NO2: C 84.82, H 5.90, N 2.83; found:
C 84.99, H 5.73, N 2.90.
4.3.10. 10-(4-Bromophenyl)-7,8-dihydro-7,7-dimethyl-
5-naphthalen-2-yl-5H-indeno[1,2-b]quinolin-9,11(6H,
10H)-dione (6j). Red crystals, mp 262–264 ꢁC.
IR (KBr, n, cmꢀ1): 3059, 2999, 2956, 2931, 2897, 2870,
2832, 1688, 1638, 1589, 1558, 1510, 1452, 1414, 1392,
1365, 1256, 1221, 1189, 1139, 1092, 1030, 871, 804, 765,
750, 717, 693.
IR (KBr, n, cmꢀ1): 3050, 2954, 1685, 1649, 1635, 1588,
1560, 1541, 1507, 1486, 1456, 1389, 1361, 1255, 1222,
1191, 1140, 762.
1H NMR (DMSO-d6) d: 0.84 (s, 3H, CH3), 0.92 (s, 3H, CH3),
2.01 (d, J¼17.2 Hz, 1H, CH), 2.08 (d, J¼16.0 Hz, 1H, CH),
2.31 (d, J¼16.0 Hz, 1H, CH), 2.51 (d, J¼17.2 Hz, 1H,
CH), 3.72 (s, 3H, CH3O), 3.79 (s, 3H, CH3O), 4.85 (s, 1H,
CH), 5.03 (d, J¼7.6 Hz, 1H, ArH), 6.83–6.97 (m, 4H,
ArH), 7.11–7.14 (m, 1H, ArH), 7.24 (d, J¼6.8 Hz, 1H,
ArH), 7.70–7.80 (m, 3H, ArH), 8.09–8.30 (m, 4H, ArH).
1H NMR (DMSO-d6) d: 0.79 (s, 3H, CH3), 0.91 (d,
J¼8.4 Hz, 3H, CH3), 1.97 (d, J¼16.8 Hz, 1H, CH), 2.07
(d, J¼16.4 Hz, 1H, CH), 2.29 (d, J¼16.0 Hz, 1H, CH),
2.45 (d, J¼17.6 Hz, 1H, CH), 4.88 (s, 1H, CH), 5.04 (d,
J¼7.2 Hz, 1H, ArH), 6.85–6.89 (m, 1H, ArH), 7.12–7.16
(m, 1H, ArH), 7.24 (d, J¼6.8 Hz, 1H, ArH), 7.38–7.42 (m,
2H, ArH), 7.48–7.52 (m, 2H, ArH), 7.70–7.87 (m, 3H,
ArH), 8.06–8.13 (m, 1H, ArH), 8.17 (d, J¼7.6 Hz, 1H,
ArH), 8.23–8.39 (m, 2H, ArH).
Anal. Calcd for C34H25Cl2NO2: C 74.18, H 4.58, N 2.54;
found: C 74.33, H 4.54, N 2.55.
4.3.14. 10-(2-Chlorophenyl)-7,8-dihydro-7,7-dimethyl-
5-naphthalen-2-yl-5H-indeno[1,2-b]quinolin-9,11(6H,
10H)-dione (6n). Red crystals, mp 286–288 ꢁC.
Anal. Calcd for C34H26BrNO2: C 72.86, H 4.68, N 2.50;
found: C 72.80, H 4.49, N 2.65.
IR (KBr, n, cmꢀ1): 3063, 2953, 1693, 1647, 1637, 1589,
1561, 1508, 1470, 1440, 1395, 1366, 1257, 1223, 1174,
1141, 1095, 1037, 874, 754, 736, 699.
4.3.11. 7,8-Dihydro-7,7-dimethyl-5-naphthalen-2-yl-10-
(4-nitrophenyl)-5H-indeno[1,2-b]quinolin-9,11(6H,10H)-
dione (6k). Red crystals, mp 231–233 ꢁC.
1H NMR (DMSO-d6) d: 0.82 (s, 3H, CH3), 0.90 (d,
J¼8.4 Hz, 3H, CH3), 1.95–2.10 (m, 2H, 2CH), 2.27 (d,
J¼16.4 Hz, 1H, CH), 2.42 (d, J¼17.2 Hz, 1H, CH), 5.00
(t, J¼7.2 Hz, 1H, ArH), 5.29 (s, 1H, CH), 6.86 (t,
J¼7.6 Hz, 1H, ArH), 7.11–7.21 (m, 3H, ArH), 7.28–7.36
(m, 2H, ArH), 7.55–7.59 (m, 1H, ArH), 7.70–7.84 (m, 3H,
ArH), 8.06–8.38 (m, 4H, ArH).
IR (KBr, n, cmꢀ1): 3050, 2958, 2867, 1688, 1647, 1636,
1591, 1562, 1519, 1456, 1392, 1362, 1255, 1223, 1193,
1171, 1092, 875, 764, 724.
1H NMR (DMSO-d6) d: 0.79 (s, 3H, CH3), 0.92 (d,
J¼9.2 Hz, 3H, CH3), 1.99–2.13 (m, 2H, 2CH), 2.30 (d,
J¼16.0 Hz, 1H, CH), 2.46 (d, J¼17.6 Hz, 1H, CH),
5.04 (s, 1H, CH), 5.06 (d, J¼8.0 Hz, 1H, ArH), 6.87–6.91
(m, 1H, ArH), 7.14–7.17 (m, 1H, ArH), 7.25 (d, J¼7.2 Hz,
1H, ArH), 7.72–7.95 (m, 5H, ArH), 8.06–8.12 (m, 1H,
ArH), 8.17–8.21 (m, 3H, ArH), 8.24–8.45 (m, 2H, ArH).
Anal. Calcd for C34H26ClNO2: C 79.14, H 5.08, N 2.71;
found: C 79.10, H 5.21, N 2.64.
4.3.15. 10-(3-Chlorophenyl)-7,8-dihydro-7,7-dimethyl-5-
naphthalen-2-yl-5H-indeno[1,2-b]quinolin-9,11(6H,
10H)-dione (6o). Red crystals, mp 227–229 ꢁC.
Anal. Calcd for C34H26N2O4: C 77.55, H 4.98, N 5.32;
found: C 77.40, H 4.92, N 5.51.
IR (KBr, n, cmꢀ1): 3050, 2951, 2882, 1684, 1647, 1636,
1591, 1559, 1508, 1472, 1457, 1395, 1365, 1257, 1222,
1192, 830, 734, 684.
4.3.12. 10-(2,4-Dichlorophenyl)-7,8-dihydro-7,7-di-
methyl-5-naphthalen-2-yl-5H-indeno[1,2-b]quinolin-
9,11(6H,10H)-dione (6l). Red crystals, mp 295–297 ꢁC.
1H NMR (DMSO-d6) d: 0.81 (s, 3H, CH3), 0.91 (d,
J¼6.4 Hz, 3H, CH3), 1.98–2.13 (m, 2H, 2CH), 2.29 (d,
J¼16.0 Hz, 1H, CH), 2.45 (d, J¼16.8 Hz, 1H, CH), 4.90
(s, 1H, CH), 5.03 (d, J¼6.8 Hz, 1H, ArH), 6.85–6.89 (m,
IR (KBr, n, cmꢀ1): 3058, 2952, 1682, 1637, 1591, 1558,
1508, 1468, 1396, 1365, 1255, 1222, 1191, 1174, 1142,
1097, 1059, 874, 846, 760.

X.-S. Wang et al. / Tetrahedron 63 (2007) 4439–4449
4447
1H, ArH), 7.13–7.17 (m, 1H, ArH), 7.25 (d, J¼6.8 Hz, 2H,
ArH), 7.35–7.43 (m, 3H, ArH), 7.69–7.86 (m, 3H, ArH),
8.06–8.39 (m, 4H, ArH).
IR (KBr, n, cmꢀ1): 2961, 2926, 2870, 1706, 1641, 1625,
1585, 1556, 1510, 1468, 1389, 1370, 1340, 1310, 1294,
1264, 1212, 1194, 1146, 1137, 1104, 1045, 984.
Anal. Calcd for C34H26ClNO2: C 79.14, H 5.08, N 2.71;
found: C 79.25, H 5.06, N 2.62.
1H NMR (DMSO-d6) d: 0.97 (s, 3H, CH3), 1.00 (s, 3H,
CH3), 2.00 (d, J¼17.6 Hz, 1H, CH), 2.16 (d, J¼16.0 Hz,
1H, CH), 2.30–2.37 (m, 5H, CH3+2CH), 2.59 (d,
J¼14.0 Hz, 1H, CH), 3.32 (dd, J¼14.0 Hz, J0¼7.6 Hz,
1H, CH), 4.56 (d, J¼7.6 Hz, 1H, CH), 7.16 (d, J¼
8.0 Hz, 2H, ArH), 7.26–7.32 (m, 3H, ArH), 7.43 (dd,
J¼8.4 Hz, J0¼2.0 Hz, 1H, ArH), 7.69 (d, J¼2.0 Hz, 1H,
ArH).
4.3.16. 7,7-Dimethyl-10-(4-hydroxylphenyl)-7,8-dihydro-
5-naphthalen-2-yl-5H-indeno[1,2-b]quinolin-9,11(6H,
10H)-dione (6p). Red crystals, mp >300 ꢁC.
IR (KBr, n, cmꢀ1): 3325, 3054, 2957, 2869, 1684, 1646,
1635, 1591, 1561, 1510, 1456, 1395, 1365, 1253, 1223,
1195, 1170, 1099, 874, 831, 763, 709.
LC–MS (ESI+, m/z): 879 [(2M+Na+), 68%].
1H NMR (DMSO-d6) d: 0.79 (s, 3H, CH3), 0.91 (s, 3H, CH3),
1.94 (d, J¼17.6 Hz, 1H, CH), 2.05 (d, J¼16.0 Hz, 1H, CH),
2.28 (d, J¼16.0 Hz, 1H, CH), 2.45 (d, J¼17.6 Hz, 1H, CH),
4.79 (s, 1H, CH), 5.01 (d, J¼6.8 Hz, 1H, ArH), 6.69 (d,
J¼7.2 Hz, 2H, ArH), 6.85 (t, J¼7.6 Hz, 1H, ArH), 7.12 (t,
J¼7.6 Hz, 1H, ArH), 7.21–7.23 (m, 3H, ArH), 7.69–7.79
(m, 3H, ArH), 8.07–8.34 (m, 4H, ArH), 9.24 (s, 1H, OH).
Anal. Calcd for C24H23Cl2NO2: C 67.29, H 5.41, N 3.27;
found: C 67.43, H 5.35, N 3.40.
4.4.3. 7,7-Dimethyl-4-(2-nitrophenyl)-1-tolyl-3,4,7,8-tet-
rahydroquinoline-2,5(1H,6H)-dione (8c). Pale yellow
crystals, mp 279–281 ꢁC.
IR (KBr, n, cmꢀ1): 3068, 3053, 2962, 2928, 2885, 1703,
1658, 1625, 1530, 1510, 1451, 1418, 1378, 1341, 1259,
1213, 1195, 1157, 1138, 982, 854, 788, 750, 695.
Anal. Calcd for C34H27NO3: C 82.07, H 5.47, N 2.81; found:
C 82.19, H 5.53, N 2.77.
4.4. General procedure for the syntheses of 4-aryl-7,7-
dimethyl-1-tolyl-3,4,7,8-tetrahydroquinoline-
2,5(1H,6H)-dione 8
1H NMR (DMSO-d6) d: 0.93 (s, 3H, CH3), 0.98 (s, 3H, CH3),
2.02 (d, J¼17.6 Hz, 1H, CH), 2.13 (d, J¼16.0 Hz, 1H, CH),
2.25 (d, J¼16.0 Hz, 1H, CH), 2.30 (d, J¼17.6 Hz, 1H, CH),
2.38 (s, 3H, CH3), 2.66 (d, J¼16.0 Hz, 1H, CH), 3.43
(dd, J¼16.0 Hz, J0¼8.4 Hz, 1H, CH), 4.64 (d, J¼8.4 Hz,
1H, CH), 7.18 (d, J¼8.0 Hz, 1H, CH), 7.26 (d, J¼8.0 Hz,
1H, CH), 7.31–7.36 (m, 2H, ArH), 7.45 (d, J¼8.0 Hz, 1H,
CH), 7.51–7.55 (m, 1H, ArH), 7.76–7.72 (m, 1H, ArH),
7.97 (d, J¼8.0 Hz, 1H, ArH).
A dry 50 mL flask was charged with arylaldehyde (1 mmol),
meldrum’s acid (1.0 mmol), 3-arylamino-5,5-dimethyl-
cyclohex-2-enone
(1.0 mmol),
and
ionic
liquid
[bmim+][BFꢀ4 ] (10 mL). The reaction mixture was stirred
at 90 ꢁC for 12–20 h, and then cooled to room temperature.
The generated yellow solid was filtered off and the ionic liq-
uid in filtrate was then recovered for reuse by drying at 80 ꢁC
for several hours in vacuum. The crude yellow products were
washed with water and purified by recrystallization from
DMF and water, followed by being dried at 80 ꢁC for several
hours in vacuum to give 8.
Anal. Calcd for C24H24N2O4: C 71.27, H 5.98, N 6.93;
found: C 71.50, H 5.89, N 6.84.
4.4.4. 7,7-Dimethyl-4-(2-methoxylphenyl)-1-tolyl-3,4,7,8-
tetrahydroquinoline-2,5(1H,6H)-dione (8d). Pale yellow
crystals, mp 201–203 ꢁC.
4.4.1. 4-(2-Chlorophenyl)-7,7-dimethyl-1-tolyl-3,4,7,8-
tetrahydroquinoline-2,5(1H,6H)-dione (8a). Colorless
crystals, mp 249–250 ꢁC.
IR (KBr, n, cmꢀ1): 3060, 3030, 3010, 2959, 2888, 2869,
1704, 1653, 1624, 1599, 1510, 1488, 1457, 1410, 1378,
1342, 1292, 1248, 1222, 1193, 1143, 1122, 1097, 1051,
1030, 958, 815, 756, 675.
IR (KBr, n, cmꢀ1): 2960, 2889, 2869, 1704, 1642, 1625,
1570, 1510, 1467, 1441, 1416, 1378, 1341, 1313, 1294,
1265, 1193, 1144, 1034, 815, 755.
1H NMR (DMSO-d6) d: 0.97 (s, 3H, CH3), 0.99 (s, 3H, CH3),
2.01 (d, J¼17.2 Hz, 1H, CH), 2.16 (d, J¼16.0 Hz, 1H,
CH), 2.28 (d, J¼17.2 Hz, 1H, CH), 2.31 (d, J¼16.0 Hz,
1H, CH), 2.36 (s, 3H, CH3), 2.62 (d, J¼15.6 Hz, 1H,
CH), 3.10 (dd, J¼15.6 Hz, J0¼8.0 Hz, 1H, CH), 3.85
(s, 3H, CH3), 4.51 (d, J¼8.0 Hz, 1H, CH), 6.89–6.93 (m,
1H, ArH), 7.01–7.14 (m, 4H, ArH), 7.22–7.30 (m, 3H,
ArH).
1H NMR (DMSO-d6) d: 0.98 (s, 3H, CH3), 1.01 (s, 3H, CH3),
2.02 (d, J¼17.6 Hz, 1H, CH), 2.17 (d, J¼16.0 Hz, 1H, CH),
2.31–2.37 (m, 5H, CH3+2CH), 2.61 (d, J¼16.0 Hz, 1H,
CH), 3.28 (dd, J¼16.0 Hz, J0¼8.0 Hz, 1H, CH), 4.60 (d,
J¼8.0 Hz, 1H, CH), 7.14–7.17 (m, 2H, ArH), 7.26–7.37
(m, 5H, ArH), 7.51 (d, J¼7.6 Hz, 1H, ArH).
Anal. Calcd for C24H24ClNO2: C 73.18, H 6.14, N 3.56;
found: C 73.29, H 6.08, N 3.55.
Anal. Calcd for C25H27NO3: C 77.09, H 6.99, N 3.60; found:
C 76.87, H 7.15, N 3.62.
4.4.2. 4-(2,4-Dichlorophenyl)-7,7-dimethyl-1-tolyl-
3,4,7,8-tetrahydroquinoline-2,5(1H,6H)-dione (8b). Col-
orless crystals, mp 251–253 ꢁC.
4.4.5. 7,7-Dimethyl-4-(2-fluorophenyl)-1-tolyl-3,4,7,8-
tetrahydroquinoline-2,5(1H,6H)-dione (8e). Pale yellow
crystals, mp 183–185 ꢁC.

4448
X.-S. Wang et al. / Tetrahedron 63 (2007) 4439–4449
IR (KBr, n, cmꢀ1): 3068, 3053, 2960, 2891, 2870, 1203,
1654, 1525, 1583, 1511, 1485, 1455, 1419, 1379, 1344,
1313, 1294, 1262, 1219, 1175, 1140, 1089, 960, 816, 760.
4.6. Supplementary material
Crystallographic data for the structure of 6a reported in this
paper have been deposited at the Cambridge Crystallo-
graphic Data Centre as supplementary publication with
no. CCDC-608551. Copies of available material can be
obtained, free of charge, on application to the Director,
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax:
+44(0) 1223-336033 or e-mail: deposit@ccdc.cam.ac.uk).
1H NMR (DMSO-d6) d: 0.94 (s, 3H, CH3), 0.98 (s, 3H,
CH3), 2.02 (d, J¼17.6 Hz, 1H, CH), 2.16 (d, J¼16.0 Hz,
1H, CH), 2.24–2.32 (m, 2H, ArH), 2.38 (s, 3H, CH3), 2.57
(d, J¼16.0 Hz, 1H, CH), 3.26 (dd, J¼16.0 Hz, J0¼8.0 Hz,
1H, CH), 4.51 (d, J¼8.4 Hz, 1H, CH), 7.06–7.31 (m, 8H,
ArH).
Anal. Calcd for C24H24FNO2: C 76.37, H 6.41, N 3.71;
found: C 76.30, H 6.28, N 3.70.
Acknowledgements
We are grateful to the Natural Science Foundation
(06AXL10) of Xuzhou Normal University and Natural
Science Foundation (no. 04KJB150139) of the Education
Committee of Jiangsu Province for financial support.
4.4.6. 7,7-Dimethyl-4-(2-nitro-4,5-methylenedioxyl-
phenyl)-1-tolyl-3,4,7,8-tetrahydroquinoline-2,5(1H,6H)-
dione (8f). Yellow crystals, mp 218–220 ꢁC.
IR (KBr, n, cmꢀ1): 3082, 3063, 3032, 2956, 2923, 2894,
2869, 1706, 1655, 1627, 1521, 1483, 1417, 1385, 1366,
1343, 1328, 1291, 1260, 1216, 1174, 1150, 1118, 924,
881, 815, 757, 691.
References and notes
1. Beagley, P.; Blackie, M. A. L.; Chibale, K.; Clarkson, C.;
Meijboom, R.; Moss, J. R.; Smith, P.; Su, H. Dalton Trans.
2003, 3046–3051.
2. Sawada, Y.; Kayakiri, H.; Abe, Y.; Mizutani, T.; Inamura, N.;
Asano, M.; Hatori, C.; Aramori, I.; Oku, T.; Tanaka, H.
J. Med. Chem. 2004, 47, 2853–2863.
3. Ma, Z.; Hano, Y.; Nomura, T.; Chen, Y. Bioorg. Med. Chem.
Lett. 2004, 14, 1193–1196.
4. Denton, T. T.; Zhang, X.; Cashman, J. R. J. Med. Chem. 2005,
48, 224–239.
1H NMR (DMSO-d6) d: 0.92 (s, 3H, CH3), 0.96 (s, 3H, CH3),
1.92 (d, J¼17.2 Hz, 1H, CH), 2.08 (d, J¼16.0 Hz, 1H, CH),
2.32 (d, J¼16.0 Hz, 1H, CH), 2.36 (s, 3H, CH3), 2.39 (d,
J¼17.2 Hz, 1H, CH), 2.62 (d, J¼16.4 Hz, 1H, CH), 3.39
(dd, J¼16.4 Hz, J0¼8.4 Hz, 1H, CH), 4.69 (d, J¼8.4 Hz,
1H, CH), 6.20 (d, J¼4.8 Hz, 2H, CH2), 6.84 (s, 1H, ArH),
7.13–7.17 (m, 2H, ArH), 7.30–7.35 (m, 2H, ArH), 7.62 (s,
1H, ArH).
Anal. Calcd for C25H24N2O6: C 66.95, H 5.39, N 6.25;
found: C 66.75, H 5.50, N 6.36.
5. Fokialakis, N.; Magiatis, P.; Chinou, L.; Mitaku, S.; Tillequin,
F. Chem. Pharm. Bull. 2002, 50, 413–414.
6. Fossa, P.; Mosti, L.; Menozzi, G.; Marzano, C.; Baccichetti, F.;
Bordin, F. Bioorg. Med. Chem. 2002, 10, 743–751.
7. Ryckebusch, A.; Derprez-Poulain, R.; Maes, L.; Debreu-
Fontaine, M. A.; Mouray, E.; Grellier, P.; Sergheraert, C.
J. Med. Chem. 2003, 46, 542–557.
8. Morgan, L. R.; Jursic, B. S.; Hooper, C. L.; Neumann, D. M.;
Thangaraj, K.; Leblanc, B. Bioorg. Med. Chem. Lett. 2002,
12, 3407–3411.
9. (a) Skraup, H. Chem. Ber. 1880, 13, 2086–2087; (b) Mansake,
R. H.; Kulka, M. Org. React. 1953, 7, 59–61; (c) Doebner, O.;
Miller, V. W. Chem. Ber. 1881, 14, 2812–2813; (d) Conrad, M.;
Limbach, L. Chem. Ber. 1887, 20, 944–945; (e) Combes, A.
Compt. Rend. 1888, 106, 142–143; (f) Pfitzinger, W. J. Prakt.
Chem. 1886, 33, 100.
10. (a) Demeunynck, M.; Moucheron, C.; Mesmaeker, A. K.-D.
Tetrahedron Lett. 2002, 43, 261–264; (b) Baraznenok, I. L.;
Nenajdenko, V. G.; Balenkova, E. S. Eur. J. Org. Chem.
1999, 937–941; (c) Ali, M. M.; Tasneem, K. C.; Rajanna,
P. K.; Prakash, S. Synlett 2001, 251–253; (d) Palacios, F.;
Ochoa de Retana, A. M.; Oyarzabal, J. Tetrahedron 1999, 55,
5947–5964; (e) Charpentier, P.; Lobregat, V.; Levacher, V.;
Dupas, G.; Queguiner, G.; Bourguignon, J. Tetrahedron Lett.
1998, 39, 4013–4016; (f) Cho, C. S.; Kim, B. T.; Kim, T. J.;
Shim, S. C. Chem. Commun. 2001, 2576–2577; (g)
Uchiyama, K.; Hayashi, Y.; Narasaka, K. Synlett 1997, 445–
447; (h) Crousse, B.; Begue, J.-P.; Bonnet-Delpon, D. J. Org.
Chem. 2000, 65, 5009–5013; (i) Hsiao, Y.; Rivera, N. R.;
Yasuda, N.; Hughes, D. L.; Reider, P. J. Org. Lett. 2001, 3,
1101–1104.
4.5. General procedure for the synthesis of 5-(2-chloro-
benzylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione 10
A mixture of 2-chlorobenzaldehyde (0.42 g, 3.0 mmol) and
meldrum’s acid (7ꢀ; 0.43 g, 3.0 mmol) in the ionic liquid me-
dium [bmim+][BF4 ] (5 mL) was stirred at 60 ꢁC for 8 h until
the reaction was complete (monitored by TLC). The mixture
was then cooled to room temperature, and the yellow solid
was collected by filtration. The filtrate of the ionic liquid
[bmim+][BFꢀ4 ] was then recovered for reuse by drying at
80 ꢁC for several hours in vacuum. The crude yellow product
was washed with EtOH; this gave 5-(2-chlorobenzylidene)-
2,2-dimethyl-1,3-dioxane-4,6-dione 10. A mixture of this
intermediate (0.27 g, 1.0 mmol) and 5,5-dimethyl-3-(4-
methylanilinꢀo)cyclohex-2-enone (0.23 g, 1.0 mmol) in
[bmim+][BF4 ] (5 mL) was stirred at 90 ꢁC for 5 h to com-
plete the reaction (monitored by TLC). The mixture was
then cooled to room temperature, the yellow solid was col-
lected by filtration, and the filtrate of the ionic liquid
[bmim+][BFꢀ4 ] was then recovered for reuse by drying at
80 ꢁC for several hours in vacuum. The crude yellow product
was washed with H2O, purified by recrystallization from
DMF–H2O, and dried at 80 ꢁC for several hours in vacuum,
this gave 8a in 92% yield.
4.5.1. 5-(2-Chlorobenzylidene)-2,2-dimethyl-1,3-diox-
ane-4,6-dione 10. White powder, mp 133ꢀ134 ꢁC (lit.20
133 ꢁC).

X.-S. Wang et al. / Tetrahedron 63 (2007) 4439–4449
4449
11. (a) Abdel-Gawad, S. M.; El-Gaby, M. S. A.; Heiba, H. I.; Aly,
H. M.; Ghorab, M. M. J. Am. Chem. Soc. 2005, 52, 1227–1236;
(b) Hammouda, M.; Mashaly, M. M.; Afsah, E. M. Pharmazie
1994, 49, 365–366; (c) Assy, M. G.; Abd-Ell Motti, F. M.
Egypt. J. Chem. 1996, 39, 581–586; (d) Assy, M. G.; Abd-Ell
Motti, F. M. Indian J. Chem., Sect. B 1996, 35, 608–610;
(e) Assy, M. G.; Fikry, R. M.; Aouf, N. H. J. Indian Chem.
Soc. 1997, 74, 152–153.
12. (a) Welton, T. Chem. Rev. 1999, 99, 2071–2084; (b) Wasser-
scheid, P.; Keim, W. Angew. Chem., Int. Ed. 2000, 42, 3772–
3789; (c) Dupont, J.; De Souza, R. F.; Suarez, P. A. Z. Chem.
Rev. 2002, 102, 3667–3692.
Yadav, J. S.; Reddy, B. V. S.; Basak, A. K.; Narsaiah, A. V.
Tetrahedron Lett. 2003, 44, 1047–1050; (e) Su, C.; Chen,
Z. C.; Zheng, Q. G. Synthesis 2003, 555–559; (f) Hakkou,
H.; Jacques, J.; Eynde, V.; Hamelin, J.; Bazureau, J. P.
Synthesis 2004, 1793–1798.
18. (a) Wang, X. S.; Zhang, M. M.; Zeng, Z. S.; Shi, D. Q.; Tu, S. J.;
Wei, X. Y.; Zong, Z. M. Tetrahedron Lett. 2005, 46, 7169–
7173; (b) Wang, X. S.; Zhang, M. M.; Zeng, Z. S.; Shi,
D. Q.; Tu, S. J.; Wei, X. Y.; Zong, Z. M. Chem. Lett. 2005,
34, 1316–1317; (c) Wang, X. S.; Zhang, M. M.; Zeng, Z. S.;
Shi, D. Q.; Tu, S. J.; Wei, X. Y.; Zong, Z. M. Synthesis 2006,
24, 4187–4199; (d) Wang, X. S.; Zhang, M. M.; Zeng, Z. S.;
Shi, D. Q.; Tu, S. J.; Wei, X. Y.; Zong, Z. M. J. Heterocycl.
Chem. 2006, 43, 989–995; (e) Wang, X. S.; Zhang, M. M.;
Shi, D. Q.; Tu, S. J.; Wei, X. Y.; Zong, Z. M. J. Heterocycl.
Chem. 2007, 44, 441–447.
€
ꢀ
ꢀ
13. Skoda-Foldes, R.; Takacs, E.; Horvath, J.; Tuba, Z.; Kollar, L.
Green Chem. 2003, 5, 643–645.
14. Hussey, C. L. Chemistry of Nonaqueous Solutions; Mamantov,
G., Popov, A. I., Eds.; VCH: Weinheim, Germany, 1994; p 227.
15. (a) Gordon, C. M.; McLean, A. J. Chem. Commun. 2000, 1395–
1396; (b) Karmakar, R.; Samanta, A. J. Phys. Chem. A 2003,
107, 7340–7346.
16. (a) Abdallah, D. J.; Robertson, A.; Hsu, H.-F.; Weiss, R. G.
J. Am. Chem. Soc. 2000, 122, 3053–3062; (b) Bradley, A. E.;
Hardacre, C.; Holbrey, J. D.; Johnston, S.; McMath, S. E. J.;
Nieuwenhuyzen, M. Chem. Mater. 2002, 14, 629–635; (c)
Bowlas, C. J.; Bruce, D. W.; Seddon, K. R. Chem. Commun.
1996, 1625–1626.
17. (a) Silverira Neto, B. A.; Ebeling, G.; Goncalves, R. S.; Gozzo,
F. C.; Eberlin, M. N.; Dupont, J. Synthesis 2004, 1155–1158;
(b) Yeung, K. S.; Farkas, M. E.; Qiu, Z.; Yang, Z.
Tetrahedron Lett. 2002, 43, 5793–5795; (c) Fraga-Dubreuil,
J.; Bazureau, J. P. Tetrahedron 2003, 59, 6121–6130; (d)
19. Crystal data for 6a: C30H24BrNO2; M¼510.41, red block
crystals, 0.34ꢂ0.21ꢂ0.04 mm, tetragonal, space group
˚
P21/n, a¼10.9821(11), b¼17.5795(18), c¼12.2340(13) A,
b¼91.645(3)ꢁ, V¼2360.9(4)3, Z¼4, Dc¼1.436 g cmꢀ3
.
F(000)¼1048, m(Mo Ka)¼1.770 mmꢀ1. Intensity data were
collected on Rigaku Mercury diffractometer with graphite
˚
monochromated Mo Ka radiation (l¼0.71070 A) using u
scan mode with 3.33ꢁ<q<25.35ꢁ. Unique reflections of 4307
were measured and 3385 reflections with I>2s(I) were used
in the refinement. Structure was solved by direct methods and
expanded using Fourier techniques. The final cycle of full-
matrix least squares technique to R¼0.0679 and wR¼0.0920.
20. Deshmukh, M. N.; Burud, R.; Baldino, C.; Chan, P. C. M.; Liu,
J. Synth. Commun. 2003, 33, 3299–3303.