A clean synthesis of 1,4-diarylquinoline derivatives catalyzed by TEBAC in aqueous media

Article abstract of DOI:10.1002/jccs.200700149

A series of 1,4-diarylquinoline derivatives were synthesized by the reaction of arylmethylidene-malononitriles or 2-cyano-3-aryl-1-acrylate and 3-arylamino-5,5-dimethylcyclohex-2-enone in aqueous media at 100 °C catalyzed by TEBAC. Meanwhile, the water me

Full text of DOI:10.1002/jccs.200700149

Journal of the Chinese Chemical Society, 2007, 54, 1033-1039
1033
A Clean Synthesis of 1,4-Diarylquinoline Derivatives Catalyzed by TEBAC
in Aqueous Media
a,b
a
b
Xiang-Shan Wang * (
Da-Qing Shi
Department of Chemistry, Xuzhou Normal University, Xuzhou Jiangsu 221116, P. R. China
The Key Laboratory for Biotechnology on Medical Plants of Jiangsu Province, 221116, P. R. China
), Mei-Mei Zhang (
), Hong Jiang (
),
a,b
a,b
(
) and Shu-Jiang Tu
(
)
a
b
A series of 1,4-diarylquinoline derivatives were synthesized by the reaction of arylmethylidene-
malononitriles or 2-cyano-3-aryl-1-acrylate and 3-arylamino-5,5-dimethylcyclohex-2-enone in aqueous
media at 100 °C catalyzed by TEBAC. Meanwhile, the water medium was chosen as green solvent.
Keywords: Quinoline; TEBAC; Aqueous media; Synthesis.
Most chemical reactions of organic substances con-
ducted in the laboratory as well as in industry need organic
solvents as reaction media, although water is safe, benign,
environmentally friendly and cheap compared with organic
solvents. In the 1980s, Breslow discovered that a Diels-
Alder reaction performed in water can be subject to huge
Scheme I
O
Ar
O
R
R
TEBAC
Ar CH
C
+
H O
2
N
NH2
CN
N Ar'
H
Ar'
1
2
3
1
accelerations. The observation led to increased interest
1
,4-diarylquinolines 3a. A summary of the optimization
from synthetic organic chemists to organic reactions in wa-
ter. In the past ten years, water used as medium has been re-
ported for a large number of organic reactions, such as Claisen
experiment is provided in Table 1. It turned out that at room
temperature, no reaction took place even when the amount
of catalyst (TEBAC) was increased to 20 mol% (Table 1,
entries 1 and 2). The catalyst plays a crucial role in the suc-
cess of the reaction in terms of the rate and the yields. From
Table 1, we can see using just 10 mol% TEBAC at reflux in
water is sufficient to make the reaction happen. More cata-
lyst does not result in a greater improvement of this reac-
tion. To find the optimum reaction time, the reaction was
carried out in the presence of a certain amount of TEBAC
(here we used 10 mol%) for 8, 10, or 12 hours, leading to 3a
in 72%, 93% and 93% yield, respectively. Thus, the opti-
mal reaction times and catalyst amount is 10 hours and 10
2
3
rearrangement, Diels-Alder reactions, Reformatsky reac-
5
4
tions and many other reactions.
Quinoline derivatives are a class of important com-
6
pounds, which are widely ascribed to have antitumor, anti-
7
8
9
bacterial, anti-plasmodial, antimalarial and anticancer
1
activities. The traditional methods available for the syn-
0
thesis of quinolines are either in organic solvents or ordi-
11
nary 4-arylquinolines. Because of the toxic and volatile
nature of many organic solvents, we investigated the syn-
thesis of these potential active compounds mentioned above
under environmentally friendly conditions. Particularly,
we focused our attention on the use of water as reaction me-
dium. Here we would like to report the synthesis of 1,4-di-
arylquinoline derivatives by the reaction of arylmethyl-
idenemalononitriles or 2-cyano-3-aryl-1-acrylate and 3-
arylamino-5,5-dimethyl cyclohex-2-enone in aqueous me-
dia at 100 °C catalyzed by TEBAC.
mol% TEBAC, respectively. In addition, CH
3 2 3
(CH )15NMe Br
3
2 3
and CH (CH )11SO Na were also tested as catalysts. In
these cases, product 3a was formed in slightly lower yields
(Table 1, entries 9-10). Moreover the catalyst of TEBAC
together with water can be reused for the synthesis of 3a
without significant loss of activity; perhaps the product in
the reused TEBAC and water has saturated, which made
the yield slightly higher in the second and third runs. The
We began our study of the reaction shown in Scheme I
by optimizing the reaction conditions for the preparation of
*
Corresponding author. E-mail: x_s.wang@yahoo.com.cn or xswang1974@yahoo.com

1
034 J. Chin. Chem. Soc., Vol. 54, No. 4, 2007
Wang et al.
a
Table 1. Synthesis of 3a in water under different reaction conditions
b
Time/h Yield /(%)
Entry
Temperature/°C Amount/mol%
Catalyst
1
2
3
4
5
6
7
8
9
r.t.
r.t.
10
20
10
10
10
10
5
TEBAC
TEBAC
10
10
10
8
0
0
50
TEBAC
52
72
93
93
83
92
91
89
100
100
100
100
100
100
100
TEBAC
TEBAC
10
12
10
10
10
10
TEBAC
TEBAC
20
10
10
TEBAC
CH (CH ) NMe Br
3
2 15
3
1
a
0
CH (CH ) SO Na
3 2 11 3
Reaction condition: 10 mL water, 2 mmol 1a and 2 mmol 2a.
Isolated yields.
b
a
Table 2. Reuse of the catalyst for synthesis of 3a
in Table 3. All of 1 and 2 gave expected products in high
yields, either bearing electron-withdrawing groups (such
as halide, nitro) or electron-donating groups (such as alkyl
group, alkoxyl group) under the same reaction conditions.
So we concluded that no obvious effects from the elec-
tronic or nature of the aromatic ring substituents were ob-
served in the above reactions.
Round
1
2
3
4
b
Yield
93
94
94
92
a
Reaction condition: 10 mL water, 2 mmol 1a and 2 mmol 2a.
Isolated yields.
b
1
results are summarized in Table 2.
Products 3 were completely characterized by IR, H
In order to apply this reaction to a library synthesis,
various kinds of 3-arylamino-5,5-dimethylcyclohex-2-enone
NMR and elemental analyses. The analyses were in agree-
ment with their structures. The melting points of the known
compounds were in accordance with those in the literature.
In order to further confirm the structure, the X-ray diffrac-
1
and arylmethylidenemalononitriles or 2-cyano-3-aryl-
1
-acrylate 2 were subjected to give the corresponding 1,4-
1
2
diarylquinolines 3, and representative examples are shown
tion analysis of the product 3g was carried out. As ex-
Table 3. The reaction times and yields of the products 3
Entry
Ar
Ar’
R
Time (h)
Yields (%)
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
a
b
c
d
e
f
4-ClC H
6
C H
6
CN
10
14
12
10
10
14
8
93
89
89
90
94
88
93
97
93
90
98
87
79
81
82
83
80
81
81
4
5
3-ClC H
6
4-FC H
4
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
4
6
3,4-(CH ) C H
3
4-ClC H
6 4
2
6
3
2,4-Cl C H
2
4-BrC H
6
6
3
4
4
4
3-NO C H
2
4-BrC H
6
6
4
4-CH C H
3
4-BrC H
6
6
4
g
h
i
2-ClC H
6
4-CH C H
3 6
4
4
4
4
4
4
4
4
4
4
4
4
4-FC H
6
4-CH C H
3 6
8
4
3-ClC H
6
4-CH C H
3 6
8
4
j
4-CH OC H
3
4-CH C H
3 6
10
8
6
4
k
l
4-NO C H
2
4-CH C H
3 6
6
4
3-ClC H
6
4-CH C H
3
CO Et
2
16
16
17
16
18
17
20
18
4
4
4
6
m
n
o
p
q
r
s
2-ClC H
6
4-CH C H
6
CO Et
2
3
4-ClC H
6
4-CH C H
3
CO Et
2
6
2,4-Cl C H
2
4-CH C H
6
CO Et
2
6
3
3
3-NO C H
6
4-CH C H
6
CO Et
2
2
4
3
3-NO C H
6
4-CH C H
6
CO Me
2
2
4
3
4-ClC H
6
C H
6
CO Et
2
4
5
3-NO C H
2
4-FC H
6
CO Et
2
6
4
4

Synthesis of Quinoline Derivatives in Aqueous Media
J. Chin. Chem. Soc., Vol. 54, No. 4, 2007 1035
pected, the structure we obtained was 2-amino-7,7-di-
methyl-4-(2-chlorophenyl)-1-(4-methylphenyl)-5-oxo-
3 3
CH ), 0.89 (s, 3H, CH ), 1.76 (d, J = 17.2 Hz, 1H, CH), 1.96
(d, J = 16.0 Hz, 1H, CH), 2.18 (d, J = 16.0 Hz, 1H, CH),
2.20 (d, J = 17.2 Hz, 1H, CH), 5.02 (s, 1H, CH), 5.28 (s, 2H,
1
,4,5,6,7,8-hexahydroquinolin-3-carbonitrile, which is
shown in Fig. 1.
NH
.45 (d, J = 7.2 Hz, 2H, ArH), 7.58-7.63 (m, 3H, ArH); C
NMR (DMSO-d ): 26.7, 29.3, 32.1, 33.9, 41.3, 49.4, 110.9,
121.2, 127.8, 128.0, 129.5, 129.9, 130.1, 130.2, 130.4,
31.7, 136.2, 144.0, 151.3, 151.4, 194.8; IR (KBr), n: 3470,
2
), 7.19-7.23 (m, 1H, ArH), 7.32-7.39 (m, 3H, ArH),
1
3
7
6
EXPERIMENTAL
1
Melting points were determined in open capillaries
3340, 3063, 2956, 2898, 2867, 2178, 1651, 1619, 1592,
1567, 1488, 1469, 1446, 1415, 1374, 1297, 1261, 1145,
1034, 826, 747, 703.
and are uncorrected. IR spectra were recorded on a TEN-
1
SOR 27 spectrometer in KBr. H NMR spectra were ob-
tained from solution in DMSO-d
6
with Me
4
Si as internal
Anal. Calcd for C24
3
H22ClN O: C 71.37, H 5.49, N
standard using an Inova-400 spectrometer. Elemental anal-
yses were carried out using a Perkin-Elmer 240 analyzer.
10.40; found C 71.38, H 5.58, N 10.52.
2-Amino-4-(3-chlorophenyl)-1-7,7-dimethyl-(4-fluoro-
Typical experimental procedure
phenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinolin-3-carbo-
A 50 mL flask was charged with arylmethylidene-
malononitriles or 2-cyano-3-aryl-1-acrylate 1 (2 mmol),
nitrile 3b
1
Mp 276-278 °C; H NMR (DMSO-d
6
): d 0.75 (s, 3H,
3
-arylamino-5,5-dimethylcyclohex-2-enone 2 (2 mmol),
3 3
CH ), 0.90 (s, 3H, CH ), 1.73 (d, J = 17.6 Hz, 1H, CH), 2.02
TEBAC (0.2 mmol) and water (10 mL). The mixture was
stirred at refluxing temperature for 8~20 h, and then cooled
to room temperature. The generated solid was filtered off
and washed with water. The crude product was purified by
recrystallization from DMF and water to give 3.
(d, J = 16.0 Hz, 1H, CH), 2.19 (d, J = 16.0 Hz, 1H, CH),
2.20 (d, J = 17.6 Hz, 1H, CH), 4.47 (s, 1H, CH), 5.57 (s, 2H,
1
3
NH
NMR (DMSO-d
117.2, 117.4, 121.5, 125.8, 126.5, 126.9, 130.6, 132.41,
32.44, 133.0, 149.1, 150.8, 151.6, 161.3, 163.7, 195.1; IR
2
), 7.25-7.28 (m, 3H, ArH), 7.36-7.44 (m, 2H, ArH); C
6
): 26.4, 29.2, 32.1, 36.6, 41.2, 49.4, 111.3,
1
2
-Amino-4-(4-chlorophenyl)-7,7-dimethyl-5-oxo-1-
(KBr), n: 3464, 3331, 3070, 2966, 2873, 2180, 1654, 1620,
1591, 1569, 1507, 1416, 1372, 1306, 1256, 1226, 1179,
1151, 1090, 1046, 879, 851, 786, 711, 698.
phenyl-1,4,5,6,7,8-hexahydroquinolin-3-carbonitrile 3a
1
6
Mp 258-260 °C; H NMR (DMSO-d ): d 0.80 (s, 3H,
Anal. Calcd for C24
3
H21ClFN O: C 68.32, H 5.02, N
9
.96; found C 68.30, H 5.27, N 9.90.
2
7
-Amino-1-(4-chlorophenyl)-4-(3,4-dimethylphenyl)-
,7-dimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinolin-3-
carbonitrile 3c
Mp 264-266 °C; H NMR (DMSO-d
), 0.89 (s, 3H, CH ), 1.72 (d, J = 17.6 Hz, 1H, CH), 1.98
d, J = 16.0 Hz, 1H, CH), 2.17-2.24 (m, 8H, 2CH + 2CH ),
.35 (s, 1H, CH), 5.42 (s, 2H, NH ), 6.92 (d, J = 7.6 Hz, 1H,
ArH), 6.99 (s, 1H, ArH), 7.07 (d, J = 7.6 Hz, 1H, ArH), 7.39
1
6
): d 0.75 (s, 3H,
CH
3
3
(
3
4
2
1
3
(
d, J = 8.4 Hz, 2H, ArH), 7.64 (d, J = 8.4 Hz, 2H, ArH); C
NMR (DMSO-d ): 19.2, 19.9, 26.3, 29.4, 32.1, 36.1, 41.1,
9.5, 112.2, 121.7, 124.3, 128.2, 129.7, 130.4, 132.1, 134.2,
34.4, 135.4, 135.9, 144.2, 150.0, 151.1, 195.0; IR (KBr),
6
4
1
n: 3460, 3332, 2963, 2936, 2871, 2179, 1654, 1590, 1571,
1
1
521, 1490, 1456, 1416, 1371, 1313, 1255, 1151, 1091,
042, 1013, 851, 813, 813, 770.
Fig. 1. The crystal structure of compound 3g.

1
036 J. Chin. Chem. Soc., Vol. 54, No. 4, 2007
Wang et al.
Anal. Calcd for C26
H
26ClN
3
O: C 72.29, H 6.07, N
2-Amino-4-(2-chlorophenyl)-7,7-dimethyl-1-(4-methyl-
phenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinolin-3-carbo-
9
.73; found C 72. 20, H 6.20, N 9.80.
nitrile 3g
1
Mp 254-256 °C; H NMR (DMSO-d
2
7
-Amino-1-(4-bromophenyl)-4-(2,4-dichlorophenyl)-
,7-dimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinolin-3-
6
): d 0.81 (s, 3H,
CH
(d, J = 16.0 Hz, 1H, CH), 2.18 (d, J = 16.0 Hz, 1H, CH),
2.20 (d, J = 17.6 Hz, 1H, CH), 2.42 (s, 3H, CH ), 5.01 (s,
1H, CH), 5.23 (s, 2H, NH ), 7.18-7.22 (m, 1H, ArH), 7.31-
3 3
), 0.89 (s, 3H, CH ), 1.79 (d, J = 17.6 Hz, 1H, CH), 1.96
carbonitrile 3d
Mp 276-278 °C; H NMR (DMSO-d
), 0.90 (s, 3H, CH ), 1.77 (d, J = 17.2 Hz, 1H, CH), 1.95
d, J = 16.0 Hz, 1H, CH), 2.17 (d, J = 16.0 Hz, 1H, CH),
.18 (d, J = 17.2 Hz, 1H, CH), 4.97 (s, 1H, CH), 5.52 (s, 2H,
NH ), 7.39-7.43 (m, 4H, ArH), 7.52 (s, 1H, ArH), 7.78 (d, J
8.4 Hz, 2H, ArH); IR (KBr), n: 3474, 3330, 3100, 2957,
1
6
): d 0.80 (s, 3H,
3
CH
3
3
2
(
7.42 (m, 7H, ArH); IR (KBr), n: 3441, 3306, 3068, 2959,
2928, 2871, 2176, 1651, 1621, 1557, 1510, 1469, 1442,
1408, 1316, 1258, 1243, 1152, 1110, 1034, 1022, 942, 847,
820, 761, 707, 674.
2
2
=
2
1
7
871, 2173, 1644, 1583, 1560, 1487, 1470, 1420, 1314,
290, 1254, 1206, 1171, 1141, 1099, 1042, 1011, 847, 809,
59, 739.
3
Anal. Calcd for C25H24ClN O: C 71.85, H 5.79, N
10.05; found C 71.90, H 5.83, N 9.90.
Anal. Calcd for C24
H
20BrCl
2
N
3
O: C 55.73, H 3.90, N
2-Amino-7,7-dimethyl-4-(4-fluorophenyl)-1-(4-methyl-
phenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinolin-3-carbo-
8
.12; found C 55.62, H 4.07, N 8.20.
nitrile 3h
1
Mp 240-242 °C; H NMR (DMSO-d
2
-Amino-1-(4-bromophenyl)-7,7-dimethyl-4-(3-nitro-
6
): d 0.72 (s, 3H,
phenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinolin-3-carbo-
CH
(d, J = 16.0 Hz, 1H, CH), 2.19 (d, J = 16.0 Hz, 2H, 2CH),
2.40 (s, 3H, CH ), 4.46 (s, 1H, CH), 5.31 (s, 2H, NH ), 7.14
3 3
), 0.87 (s, 3H, CH ), 1.72 (d, J = 17.6 Hz, 1H, CH), 1.99
nitrile 3e
1
Mp 271-274 °C; H NMR (DMSO-d
6
): d 0.72 (s, 3H,
3
2
CH
d, J = 16.0 Hz, 1H, CH), 2.18 (d, J = 16.0 Hz, 1H, CH),
.20 (d, J = 17.6 Hz, 1H, CH), 4.45 (s, 1H, CH), 5.54 (s, 2H,
NH ), 7.28 (d, J = 8.4 Hz, 2H, ArH), 7.36-7.38 (m, 4H,
ArH), 7.77 (d, J = 8.4 Hz, 2H, ArH); IR (KBr), n: 3462,
3
), 0.89 (s, 3H, CH
3
), 1.71 (d, J = 17.6 Hz, 1H, CH), 1.99
(t, J = 8.8 Hz, 2H, ArH), 7.27-7.31 (m, 4H, ArH), 7.40 (d, J
= 8.0 Hz, 2H, ArH); IR (KBr), n: 3467, 3335, 3062, 3030,
2954, 2904, 2863, 2179, 1653, 1618, 1601, 1570, 1507, 1448,
1414, 1387, 1313, 1258, 1218, 1154, 1044, 856, 811, 786.
(
2
2
3
Anal. Calcd for C25H24FN O: C 74.79, H 6.03, N
3
1
1
326, 3059, 2964, 2953, 2867, 2179, 1653, 1621, 1570,
487, 1414, 1372, 1312, 1256, 1173, 1147, 1087, 1069,
042, 1011, 940, 858, 844, 804, 768, 738.
10.47; found C 74.70, H 6.13, N 10.52.
2-Amino-4-(3-chlorophenyl)-7,7-dimethyl-1-(4-methyl-
phenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinolin-3-carbo-
4 3
Anal. Calcd for C24H21BrN O : C 58.43, H 4.29, N
11.36; found C 58.30, H 4.33, N 11.39.
nitrile 3i
1
Mp 233-234 °C; H NMR (DMSO-d
6
): d 0.74 (s, 3H,
2
-Amino-1-(4-bromophenyl)-7,7-dimethyl-4-(4-methyl-
CH
(d, J = 16.0 Hz, 1H, CH), 2.20 (d, J = 16.8 Hz, 2H, 2CH),
2.41 (s, 3H, CH ), 4.48 (s, 1H, CH), 5.40 (s, 2H, NH ),
3 3
), 0.89 (s, 3H, CH ), 1.75 (d, J = 17.6 Hz, 1H, CH), 2.02
phenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinolin-3-carbo-
nitrile 3f
3
2
1
Mp 258-261 °C; H NMR (DMSO-d
6
): d 0.74 (s, 3H,
7.24-7.28 (m, 5H, ArH), 7.34-7.42 (m, 3H, ArH); IR (KBr),
n: 3464, 3335, 3035, 2961, 2929, 2871, 2179, 1654, 1619,
1568, 1509, 1470, 1416, 1389, 1372, 1307, 1256, 1174,
1145, 1107, 1045, 877, 782, 710.
CH
d, J = 16.0 Hz, 1H, CH), 2.16-2.27 (m, 5H, 2CH + CH
.40 (s, 1H, CH), 5.46 (s, 2H, NH ), 7.12 (d, J = 8.4 Hz, 2H,
3
), 0.90 (s, 3H, CH
3
), 1.71 (d, J = 18.0 Hz, 1H, CH), 1.99
(
3
),
4
2
ArH), 7.15 (d, J = 8.4 Hz, 2H, ArH), 7.34 (d, J = 8.4 Hz, 2H,
ArH), 7.77 (d, J = 8.4 Hz, 2H, ArH); IR (KBr), n: 3458,
3
Anal. Calcd for C25H24ClN O: C 71.85, H 5.79, N
10.05; found C 71.70, H 5.88, N 10.12.
3
1
7
329, 3031, 2962, 2951, 2180, 1655, 1621, 1574, 1486,
414, 1372, 1256, 1179, 1150, 1070, 1043, 1010, 848, 807,
67.
2-Amino-7,7-dimethyl-4-(4-methoxylphenyl)-1-(4-meth-
ylphenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinolin-3-carbo-
nitrile 3j
Anal. Calcd for C25
3
H23BrN O: C 64.94, H 5.23, N
1
Mp 239-241 °C; H NMR (DMSO-d ): d 0.73 (s, 3H,
9
.09; found C 64.81, H 5.40, N 9.15.
6

Synthesis of Quinoline Derivatives in Aqueous Media
J. Chin. Chem. Soc., Vol. 54, No. 4, 2007 1037
CH
3
), 0.88 (s, 3H, CH
3
), 1.71 (d, J = 17.6 Hz, 1H, CH), 1.99
Ethyl 2-amino-4-(2-chlorophenyl)-7,7-dimethyl-1-(4-
methylphenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinolin-3-
(
d, J = 16.0 Hz, 1H, CH), 2.18 (d, J = 16.0 Hz, 1H, CH),
2
3
8
8
.19 (d, J = 17.6 Hz, 1H, CH), 2.41 (s, 3H, CH
3
), 3.73 (s,
carbonylate 3m
1
H, CH O), 4.40 (s, 1H, CH), 5.25 (s, 2H, NH ), 6.88 (d, J =
3
2
Mp 237-239 °C; H NMR (DMSO-d
6
): d 0.69 (s, 3H,
), 1.66
d, J = 17.2 Hz, 1H, CH), 1.90 (d, J = 16.0 Hz, 1H, CH),
.14 (d, J = 16.0 Hz, 1H, CH), 2.17 (d, J = 17.2 Hz, 1H,
CH), 2.43 (s, 3H, CH ), 3.91 (q, J = 7.2 Hz, 2H, CH ), 5.20
s, 1H, CH), 6.70 (s, 2H, NH ), 7.08-7.11 (m, 1H, ArH),
.22-7.26 (m, 2H, ArH), 7.33 (d, J = 8.4 Hz, 2H, ArH),
.8 Hz, 1H, ArH), 7.18 (d, J = 8.4 Hz, 2H, ArH), 7.26 (d, J =
.8 Hz, 2H, ArH), 7.40 (d, J = 8.4 Hz, 2H, ArH); IR (KBr),
3 3 3
CH ), 0.86 (s, 3H, CH ), 1.16 (t, J = 7.2 Hz, 3H, CH
(
2
n: 3468, 3337, 3055, 2957, 2930, 2869, 2838, 2176, 1655,
1
1
620, 1583, 1565, 1559, 1463, 1448, 1410, 1373, 1300,
257, 1213, 1151, 1030, 844, 813, 796, 741, 670.
3
2
(
2
7
7
2
1
1
3
1
8
27 3
Anal. Calcd for C26H N O: C 75.52, H 6.58, N
1
3
6
.43-7.48 (m, 3H, ArH); C NMR (DMSO-d ): 14.6, 21.0,
1
0.16; found C 75.69, H 6.60, N 10.07.
6.1, 29.5, 31.9, 33.8, 41.4, 49.6, 78.0, 112.6, 126.6, 127.2,
29.3, 130.0, 130.1, 131.0, 132.3, 132.4, 133.5, 139.5,
45.2, 150.6, 153.1, 169.2, 194.7; IR (KBr), n: 3470, 3245,
061, 2957, 2902, 2868, 1661, 1632, 1589, 1501, 1439,
371, 1311, 1271, 1250, 1207, 1171, 1144, 1088, 1047,
46, 795, 753, 724.
2
-Amino-7,7-dimethyl-1-(4-methylphenyl)-4-(4-nitro-
phenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinolin-3-carbo-
nitrile 3k
1
Mp 260-262 °C; H NMR (DMSO-d
6
): d 0.73 (s, 3H,
CH
3
), 0.89 (s, 3H, CH
3
), 1.76 (d, J = 17.6 Hz, 1H, CH), 2.00
Anal. Calcd for C27
2 3
H29ClN O : C 69.74, H 6.29, N
(
d, J = 16.0 Hz, 1H, CH), 2.18-2.23 (m, 2H, 2CH), 2.42 (s,
6
.02; found C 69.62, H 6.40, N 6.18.
3
8
8
3 2
H, CH ), 4.61 (s, 1H, CH), 5.47 (s, 2H, NH ), 7.33 (d, J =
.0 Hz, 1H, ArH), 7.41 (d, J = 8.4 Hz, 2H, ArH), 7.55 (d, J =
.4 Hz, 2H, ArH), 8.22 (d, J = 8.8 Hz, 2H, ArH); IR (KBr),
Ethyl 2-amino-4-(4-chlorophenyl)-7,7-dimethyl-1-(4-
methylphenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinolin-3-
n: 3460, 3322, 2958, 2870, 2184, 1642, 1620, 1567, 1512,
carbonylate 3n
1
7
413, 1372, 1343, 1257, 1146, 1108, 1043, 1021, 871, 827,
54, 669.
1
Mp 198-200 °C; H NMR (DMSO-d
6
): d 0.67 (s, 3H,
), 1.67
d, J = 17.6 Hz, 1H, CH), 1.96 (d, J = 16.0 Hz, 1H, CH),
.18 (d, J = 16.0 Hz, 1H, CH), 2.20 (d, J = 17.6 Hz, 1H,
CH), 2.42 (s, 3H, CH ), 3.95 (q, J = 6.8 Hz, 2H, CH ), 4.90
s, 1H, CH), 6.74 (s, 2H, NH ), 7.29-7.31 (m, 6H, ArH),
3 3 3
CH ), 0.87 (s, 3H, CH ), 1.12 (t, J = 6.8 Hz, 3H, CH
Anal. Calcd for C25
24 4 3
H N O : C 70.08, H 5.65, N
(
1
3.08; found C 70.01, H 5.73, N 13.18.
2
3
2
Ethyl 2-amino-4-(3-chlorophenyl)-7,7-dimethyl-1-(4-
methylphenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinolin-3-
(
2
1
3
7
2
1
1
2
6
.43 (d, J = 8.0 Hz, 2H, ArH); C NMR (DMSO-d ): 14.6,
carbonylate 3l
1.0, 26.1, 29.5, 32.1, 33.6, 41.1, 49.6, 78.7, 113.7, 127.9,
28.9, 129.4, 129.9, 130.1, 131.0, 133.5, 139.5, 147.3,
50.4, 153.0, 168.8, 195.0; IR (KBr), n: 3470, 3247, 3050,
958, 1666, 1637, 1500, 1372, 1309, 1270, 1251, 1171,
1
Mp 219-221 °C; H NMR (DMSO-d
6
): d 0.68 (s, 3H,
), 1.67
d, J = 17.6 Hz, 1H, CH), 1.98 (d, J = 16.0 Hz, 1H, CH),
.19 (d, J = 16.0 Hz, 1H, CH), 2.23 (d, J = 17.6 Hz, 1H,
CH), 2.42 (s, 3H, CH ), 3.97 (q, J = 7.2 Hz, 2H, CH ), 4.89
s, 1H, CH), 6.52 (s, 2H, NH ), 7.17 (d, J = 8.0 Hz, 1H,
ArH), 7.23-7.33 (m, 5H, ArH), 7.44 (d, J = 8.0 Hz, 2H,
3 3 3
CH ), 0.88 (s, 3H, CH ), 1.13 (t, J = 7.2 Hz, 3H, CH
(
2
1
149, 1087, 1049, 1015, 839, 815.
Anal. Calcd for C27
.02; found C 69.68, H 6.39, N 6.01.
3
2
H
2 3
29ClN O : C 69.74, H 6.29, N
(
2
6
1
ArH); C NMR (DMSO-d
3
6
): 14.6, 21.0, 26.1, 29.5, 32.1,
Ethyl 2-amino-4-(2,4-chlorophenyl)-7,7-dimethyl-1-(4-
methylphenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinolin-3-
3
1
1
1
1
4.1, 41.1, 49.5, 78.6, 113.4, 125.6, 125.9, 127.6, 129.7,
29.76, 129.82, 130.1, 131.1, 132.3, 133.5, 139.6, 150.7,
53.0, 168.8, 195.0; IR (KBr), n: 3466, 3268, 3052, 2960,
659, 1632, 1589, 1495, 1373, 1311, 1271, 1250, 1207,
173, 1094, 1049, 771, 712, 684.
carbonylate 3o
1
Mp 220-222 °C; H NMR (DMSO-d
6
): d 0.68 (s, 3H,
), 1.64
d, J = 17.2 Hz, 1H, CH), 1.89 (d, J = 16.0 Hz, 1H, CH),
.15 (d, J = 16.0 Hz, 1H, CH), 2.16 (d, J = 17.2 Hz, 1H,
CH), 2.41 (s, 3H, CH ), 3.90 (q, J = 7.2 Hz, 2H, CH ), 5.15
3 3 3
CH ), 0.84 (s, 3H, CH ), 1.05 (t, J = 7.2 Hz, 3H, CH
(
Anal. Calcd for C27
2 3
H29ClN O : C 69.74, H 6.29, N
2
6
.02; found C 69.60, H 6.50, N 6.10.
3
2

1
038 J. Chin. Chem. Soc., Vol. 54, No. 4, 2007
Wang et al.
(
s, 1H, CH), 6.70 (s, 2H, NH
2
), 7.30-7.34 (m, 3H, ArH),
2.19 (d, J = 16.0 Hz, 1H, CH), 2.22 (d, J = 17.6 Hz, 1H,
7
.36 (d, J = 2.0 Hz, 1H, ArH), 7.42-7.46 (m, 3H, ArH); IR
CH), 3.95 (q, J = 6.8 Hz, 2H, CH
2
), 4.90 (s, 1H, CH), 6.73
(
KBr), n: 3469, 3250, 2958, 1658, 1632, 1558, 1490, 1371,
(s, 2H, NH ), 7.30 (s, 4H, ArH), 7.42 (d, J = 6.8 Hz, 2H,
2
1
7
310, 1271, 1249, 1208, 1174, 1150, 1095, 1044, 845, 819,
98, 756.
ArH), 7.59-7.65 (m, 3H, ArH); IR (KBr), n: 3384, 3270,
2962, 1652, 1640, 1591, 1488, 1411, 1373, 1306, 1269,
1247, 1209, 1170, 1148, 1119, 1083, 1040, 1012, 846, 784,
755, 704.
Anal. Calcd for C27
2 2 3
H28Cl N O : C 64.93, H 5.65, N
5
.61; found C 64.88, H 5.70, N 5.73.
Anal. Calcd for C26
2 3
H27ClN O : C 69.25, H 6.03, N
Ethyl 2-amino-7,7-dimethyl-1-(4-methylphenyl)-4-(3-
nitrophenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinolin-3-
6.21; found C 69.10, H 6.21, N 6.25.
carbonylate 3p
Ethyl 2-amino-4-(3-chlorophenyl)-7,7-dimethyl-1-(4-
fluorophenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinolin-3-
1
Mp 236-237 °C; H NMR (DMSO-d
6
): d 0.67 (s, 3H,
), 1.71
d, J = 17.2 Hz, 1H, CH), 1.97 (d, J = 16.0 Hz, 1H, CH),
.19-2.28 (m, 2H, 2CH), 2.43 (s, 3H, CH ), 3.96 (q, J = 7.2
Hz, 2H, CH ), 5.01(s, 1H, CH), 6.80 (s, 2H, NH ), 7.33 (d, J
8.0 Hz, 2H, ArH), 7.46 (d, J = 8.0 Hz, 2H, ArH), 7.57-
.60 (m, 1H, ArH), 7.75 (d, J = 7.6 Hz, 1H, ArH), 8.00 (dd,
CH
3
), 0.89 (s, 3H, CH
3
), 1.12 (t, J = 7.2 Hz, 3H, CH
3
carbonylate 3s
1
Mp 226-228 °C; H NMR (DMSO-d
(
6
): d 0.67 (s, 3H,
), 1.69
2
3
CH
3
), 0.89 (s, 3H, CH
3
), 1.12 (t, J = 6.8 Hz, 3H, CH
3
2
2
(d, J = 17.2 Hz, 1H, CH), 1.97 (d, J = 16.0 Hz, 1H, CH),
2.21 (d, J = 16.0 Hz, 1H, CH), 2.26 (d, J = 17.2 Hz, 1H,
=
7
CH), 3.95 (q, J = 6.8 Hz, 2H, CH
2
), 5.00 (s, 1H, CH), 6.92
J = 8.0 Hz, J¢ = 1.6 Hz, 1H, ArH), 8.12 (d, J = 1.6 Hz, 1H,
ArH); IR (KBr), n: 3444, 3286, 2961, 1661, 1632, 1529,
(s, 2H, NH ), 7.48-7.52 (m, 4H, ArH), 7.58 (t, J = 8.0 Hz,
2
1H, ArH), 7.75 (d, J = 7.6 Hz, 1H, ArH), 8.00 (dd, J = 8.0
Hz, J¢ = 1.6 Hz, 1H, ArH), 8.11 (d, J = 1.6 Hz, 1H, ArH); IR
(KBr), n: 3465, 3275, 2957, 1667, 1627, 1508, 1373, 1349,
1327, 1303, 1271, 1244, 1211, 1177, 1156, 1090, 1045,
927, 897, 861, 782, 728, 700.
1
9
493, 1373, 1348, 1309, 1270, 1206, 1176, 1095, 1042,
00, 821, 794, 744, 722, 702.
Anal. Calcd for C27
29 3 5
H N O : C 68.19, H 6.15, N 8.84;
found C 68.25, H 6.29, N 8.95.
Anal. Calcd for C26
2 3
H26ClFN O : C 66.59, H 5.59, N
Methyl 2-amino-7,7-dimethyl-1-(4-methylphenyl)-4-(3-
nitrophenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinolin-3-
5.97; found C 66.70, H 5.72, N 6.10.
In conclusion, we found a novel method available for
the synthesis of 1,4-diarylquinoline derivatives in aqueous
media catalyzed by TEBAC in high yields. Meanwhile, the
aqueous medium chosen was a green solvent which could
be reused for several rounds without significant loss of ac-
tivity.
carbonylate 3q
1
Mp 256-258 °C; H NMR (DMSO-d
6
): d 0.66 (s, 3H,
CH
3
), 0.87 (s, 3H, CH
3
), 1.67 (d, J = 17.2 Hz, 1H, CH), 1.98
(
d, J = 16.0 Hz, 1H, CH), 2.20-2.28 (m, 2H, 2CH), 2.42 (s,
3
H, CH
3
), 3.54 (s, 3H, CH
3
), 5.03 (s, 1H, CH), 6.84 (s, 2H,
NH
2
), 7.31 (d, J = 8.0 Hz, 2H, ArH), 7.45 (d, J = 8.0 Hz, 1H,
ArH), 7.56-7.60 (m, 1H, ArH), 7.74 (d, J = 8.0 Hz, 1H,
ArH), 8.00 (dd, J = 8.4 Hz, J¢ = 1.6 Hz, 1H, ArH), 8.10 (d, J
ACKNOWLEDGEMENTS
=
1.6 Hz, 1H, ArH); IR (KBr), n: 3456, 3272, 2954, 1687,
1
1
7
663, 1634, 1523, 1496, 1435, 1371, 1347, 1324, 1270,
252, 1210, 1175, 1149, 1082, 923, 825, 806, 780, 747,
25, 701.
We are grateful to the Natural Science Foundation
(No. 04KJB150139) of the Education Committee of Jiang-
su Province for financial support.
Anal. Calcd for C26
27 3 5
H N O : C 67.66, H 5.90, N 9.10;
found C 67.54, H 6.09, N 9.22.
Received September 4, 2006.
Ethyl 2-amino-4-(4-chlorophenyl)-7,7-dimethyl-5-oxo-
1
-phenyl-1,4,5,6,7,8-hexahydroquinolin-3-carbonylate 3r
1
Mp 204-206 °C; H NMR (DMSO-d
6
): d 0.66 (s, 3H,
), 1.62
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