One-pot synthesis of N2-substituted 2-amino-4-aryl-5,6,7,8- tetrahydroquinoline-3-carbonitrile in basic ionic liquid [bmim]OH

Article abstract of DOI:10.1080/00397911.2010.516459

N2-Methyl-or aryl-substituted 2-amino-4-aryl-5,6,7,8-tetrahydroquinoline-3- carbonitriles were synthesized via a four-component, one-pot reaction of aromatic aldehyde, cyclohexanone, malononitrile, and amines in basic ionic liquid [bmim]OH with good to ex

Full text of DOI:10.1080/00397911.2010.516459

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One-Pot Synthesis of N2-
Substituted 2-Amino-4-aryl-5,6,7,8-
tetrahydroquinoline-3-carbonitrile in
Basic Ionic Liquid [bmim]OH
Yu Wan a b , Rui Yuan a , Fu-Ren Zhang a , Li-Ling Pang a , Rui Ma a
,
Cai-Hui Yue a , Wei Lin a , Wei Yin a , Rong-Cheng Bo a & Hui Wu a b
a School of Chemistry and Chemical Engineering, Xuzhou Normal
University, Xuzhou, P. R. China
b Key Laboratory of Biotechnology on Medical Plants of Jiangsu
Province, Jiangsu, P. R. China
Published online: 11 Jul 2011.
To cite this article: Yu Wan , Rui Yuan , Fu-Ren Zhang , Li-Ling Pang , Rui Ma , Cai-Hui Yue ,
Wei Lin , Wei Yin , Rong-Cheng Bo & Hui Wu (2011): One-Pot Synthesis of N2-Substituted 2-
Amino-4-aryl-5,6,7,8-tetrahydroquinoline-3-carbonitrile in Basic Ionic Liquid [bmim]OH, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
41:20, 2997-3015
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Synthetic Communications1, 41: 2997–3015, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.516459
ONE-POT SYNTHESIS OF N2-SUBSTITUTED
2-AMINO-4-ARYL-5,6,7,8-TETRAHYDROQUINOLINE-3-
CARBONITRILE IN BASIC IONIC LIQUID [bmim]OH
Yu Wan,1,2 Rui Yuan,1 Fu-Ren Zhang,1 Li-Ling Pang,1
Rui Ma,1 Cai-Hui Yue,1 Wei Lin,1 Wei Yin,1 Rong-Cheng Bo,1
and Hui Wu1,2
1School of Chemistry and Chemical Engineering, Xuzhou Normal University,
Xuzhou, P. R. China
2Key Laboratory of Biotechnology on Medical Plants of Jiangsu Province,
Jiangsu, P. R. China
GRAPHICAL ABSTRACT
Abstract N2-Methyl- or aryl-substituted 2-amino-4-aryl-5,6,7,8-tetrahydroquinoline-3-
carbonitriles were synthesized via a four-component, one-pot reaction of aromatic aldehyde,
cyclohexanone, malononitrile, and amines in basic ionic liquid [bmim]OH with good to
excellent yields. During this transformation, at least 11 bonds were cleaved and 7 new bonds
were constructed.
Keywords [bmim]OH; synthesis; tetrahydroquinoline
INTRODUCTION
In the field of organic synthesis, it would be very desirable to facilitate bond
formation of two or more bonds in one pot to achieve economically useful transfor-
mations, which should minimize the chemicals used and the waste produced, as well
as the reaction time. As a result, great attention has been paid to the development of
multicomponent reactions (MCRs).[1] A significant challenge with this process is that
all the reagents are added at the beginning and the same reaction conditions are
maintained throughout.
Received August 3, 2009.
Address correspondence to Hui Wu, School of Chemistry and Chemical Engineering, Xuzhou
Normal University, Xuzhou 221116, China. E-mail: wuhui72@yahoo.com.cn
2997

2998
Y. WAN ET AL.
Scheme 1. The framework with high bioactive.
Cyanopyridines, such as 2-amino-3-cyanopyridines, are versatile intermediates
for the synthesis of nitrogen heterocycles,[2–4] with different alkyl and aryl groups
that have been found to have antimicrobial,[5] antihypertensive,[6] cardiovascular,[7]
anti-inflammatory, analgesic, and antipyretic properties[8] as well as 1KK-b inhibitor
properties.[9] The preparation of 2-amino-3-cyanopyridine derivatives has been
reported in the literature from chalcones on treatment with ammonium acetate via
Michael-type condensation,[10] as well as via a one-pot coupling reaction of four
components[11] in conventional heating mode or under microwave irradiation and
other methods.[12,13] In these methods, catalysts and two active methylenes were
necessary. It is noticeable that high-steric-hindrance and low-activity ketones, such
as cyclohexanone, are rarely used as starting material to prepare polysubstituted pyr-
idines. Moreover, the reported methods for the preparation of framework (a)
(Scheme 1), which has a substituent group on N2, are relatively scarce. Tu and
coworkers[12b] had synthesized N2-substituted 2-amino-3-caynopyridine under
microwave irradiation, but only aryl can be introduced into the N2 position, and
highly active methylenes, 1,3-indanediones, were necessary. So, the synthesis of a
high bioactive framework (b)[14] (Scheme 1) from low-activity methylene is still a
challenge.
The use of room-temperature ionic liquids (RTILs) as catalyst and=or reaction
medium for green synthetic chemistry[15] is a fast-growing area. The acidic and neu-
tral ionic liquids have been successfully applied to many organic reactions.[16,17] In
basic ionic liquid, only [bmim]OH has been synthesized and used to promote organic
reactions,[18–20] but it has not been used to promote the synthesis of polysubstituted
quinoline derivatives.
Herein, we report a simple one-pot, four-component reaction to synthesize N2-
substituted-2-amino-3-cyano-4-aryl-5,6,7,8-tetrahydroquinoline derivatives in basic
ionic liquid [bmim]OH without any other catalysts (Scheme 2)
Scheme 2. The synthesis of N2-substituted-2-amino-3-cyano-4-aryl-5,6,7,8-tetrahydroquinoline derivatives.

2-AMINO-8-ARYL-TETRAHYDROQUINOLINE-3-CARBONITRILE
2999
RESULTS AND DISCUSSION
Initially, five ionic liquids were tested in the reaction of 4-methoxybenzalde-
hyde 1k, malononitrile 2, cyclohexanone 3, and methylamine 4a. As can be seen from
Table 1, when the reaction was carried out in [bpy]Br or [bmim]Br, no product was
detected at all (Table 1, entries 1 and 3). The best result was obtained in [bmim]OH
with 86% yield of the product, due to its strongest basicity, which means that the
main process of reaction is nucleophilic. Screening of the reaction time revealed that
the reaction performed in 4–6 h afforded the best results (Table 1, entries 11–17).
Moreover, increasing the reaction temperature from 50 ꢀC to 80 ꢀC gave enhanced
yields (Table 1, entries 17–21), while further increasing the reaction temperature to
90 ꢀC or 100 ꢀC did not lead to significant increase in yields (Table 1, entries 22
and 23).
Under the optimized conditions, the reactions of aromatic aldehydes 1, malo-
nonitrile 2, cyclohexanone 3, and methylamine (aq. 40%) 4a were investigated first
(Table 2). As can be seen from Table 2, the electronic effect and steric hindrance
Table 1. Optimizing reaction conditions based on control reactiona
Entry
Solvent
X (mol %)b
Time (h)
Temperature (ꢀC)
Yield (%)c
1
2
[bpy]Brd
[bpy]BF4
15
15
15
15
15
0
4
4
4
4
4
4
4
4
4
4
4
1
2
3
5
6
7
6
6
6
6
6
6
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
r.t.
50
60
70
90
100
Nrf
46
Nr
39
86
Nr
35
57
75
81
87
48
69
74
84
87
85
Nr
51
65
71
81
68
3
[bmim]Bre
[bmim]BF4
[bmim]OH
[bmim]OH
[bmim]OH
[bmim]OH
[bmim]OH
[bmim]OH
[bmim]OH
[bmim]OH
[bmim]OH
[bmim]OH
[bmim]OH
[bmim]OH
[bmim]OH
[bmim]OH
[bmim]OH
[bmim]OH
[bmim]OH
[bmim]OH
[bmim]OH
4
5
6
7
1
8
2
9
5
10
11
12
13
14
15
16
17
18
19
20
21
22
23
10
20
15
15
15
15
15
15
15
15
15
15
15
15
aReaction conditions: 4-methoxybenzaldehyde (1.0 mmol), malononitrile (1.0 mmol), cyclohexanone
(1.0 mmol), and methylamine (aq. 40%, 1.0 mmol).
bAmount of ionic liquid.
cIsolated yield.
dbpy ¼ 1-n-butylpridinum.
ebmim ¼ 1-n-butyl-3-methylimidazolium.
fNo reaction.

3000
Y. WAN ET AL.
Table 2. Synthesis of 5a in [bmim]OHa
Entry
Product
Ar
Time (h)
Yields (%)
Mp (ꢀC)
1
2
5aa
5ab
5ac
5ad
5ae
5af
5ag
5ah
5ai
C6H5
2-ClC6H4
6
6
6
6
6
5
5
5
5
6
6
6
6
6
83
77
67
79
70
77
79
76
80
71
87
85
83
86
172–174
172–173
184–186
219–211
174–175
180–182
218–220
227–229
224–226
204–206
178–180
195–197
196–198
179–181
3
4-ClC6H4
2-BrC6H4
4
5
4-BrC6H4
2,4-Cl2C6H3
4-CNC6H4
6
7
8
3-NO2C6H4
4-NO2C6H4
2-MeOC6H4
4-MeOC6H4
2,3-(MeO)2C6H3
3,4-(MeO)2C6H3
3,4,5-(MeO)3C6H2
9
10
11
12
13
14
5aj
5ak
5al
5am
5an
aReaction conditions: aromatic aldehyde (1.0 mmol), malononitrile (1.0 mmol), cyclohexanone
(1.0 mmol), methylamine (1.0 mmol), and ionic liquid (15 mol %), at 80 ꢀC.
of substitutes on aromatic aldehydes have little influence on the yields. Good yields
were obtained for all of the different substrates.
The encouraging results prompted us to test low-activity aromatic amines 4b
(Table 3). As can be seen from Table 3, although aromatic amines have a more bulky
steric effect than that of methylamine, they could still give good yields. This may due
to the stability of the intermediates B and C (Scheme 2). Aniline gave good yield
(81%, Table 3, entry 1). Electron-withdrawing groups of aniline such as -Cl, -Br,
Table 3. Synthesis of 5b in [bmim]OHa
Entry
Product
R
Time (h)
Yields (%)
Mp (ꢀC)
1
2
5baz
5bb
5bc
5bd
5be
5bf
C6H5
4-FC6H4
4
4
4
4
5
5
4
5
4
4
5
5
5
5
5
5
4
81
80
71
83
80
79
78
70
84
86
79
87
85
67
76
82
76
210–212
197–199
170–172
201–203
234–236
194–196
235–237
226–228
168–170
201–203
183–184
185–187
140–142
158–160
225–227
130–132
212–214
3
2-ClC6H4
3-ClC6H4
4
5
4-ClC6H4
3-BrC6H4
4-BrC6H4
6
7
5bg
5bh
5bi
8
4-NO2C6H4
3-MeC6H4
4-MeC6H4
9
10
11
12
13
14
15
16
17
5bj
5bk
5bl
3-MeOC6H4
4-MeOC6H4
2,3-(MeO)2C6H3
2-Me-3-ClC6H3
3-Cl-4-FC6H3
3,4-Me2C6H3
a-Naphthalene
5bm
5bn
5bo
5bp
5bq
aReaction conditions: 4-methoxybenzaldehyde (1.0 mmol), malononitrile (1.0 mmol), cyclohexanone
(1.0 mmol), amine (1.0 mmol), and ionic liquid (15 mol %), at 80 ꢀC.

2-AMINO-8-ARYL-TETRAHYDROQUINOLINE-3-CARBONITRILE
3001
Table 4. Synthesis of 5c in [bmim]OHa
Entry
Product
Ar
Time (h)
Yields (%)
Mp (ꢀC)
1
2
5ca
5cb
5cc
5cd
5ce
5cf
C6H5
2-ClC6H4
4
5
5
5
5
5
5
5
6
6
4
4
4
4
4
4
5
82
78
82
78
77
80
80
75
73
67
83
79
88
87
85
85
79
239–240
257–258
278–280
>300
3
4-ClC6H4
2-BrC6H4
4
5
3-BrC6H4
4-BrC6H4
231–232
255–256
225–227
240–241
230–232
>300
6
7
5cg
5ch
5ci
2,4-Cl2C6H3
4-CNC6H4
8
9
3-NO2C6H4
4-NO2C6H4
4-MeC6H4
10
11
12
13
14
15
16
17
5cj
5ck
5cl
248–249
216–218
226–228
229–230
258–260
207–209
248–250
2-MeOC6H4
4-MeOC6H4
2,3-(MeO)2C6H3
3,4-(MeO)2C6H3
3,4,5-(MeO)3C6H2
4-OHC6H4
5cm
5cn
5co
5cp
5cq
aReaction conditions: aldehyde (1.0 mmol), malononitrile (1.0 mmol), cyclohexanone (1.0 mmol),
NH4OAc (1.0 mmol), and ionic liquid (15 mol %), at rt.
Figure 1. X-ray crystal structure of 5ak.

3002
Y. WAN ET AL.
and -NO2 (Table 3, entries 2–8) gave slightly lower yields and took longer time than
electron-donating groups such as -Me and -OMe (Table 3, entries 10–12).
To compare this method with previous ones,[11–14] ammonium acetate was
tested subsequently (Table 4). Because ammonium acetate has a smaller steric effect
and greater activity than methylamine and aromatic amines, the reactions could be
carried out at room temperature. The results showed the generality of our method
for the preparation of N2-methyl- or aryl-substituted 2-amino-3-yano-4-aryl-
5,6,7,8-tetrahydroquinolines.
The structures of compound 5ak (Fig. 1), 5ba (Fig. 2) and 5ck (Fig. 3) were
determined by x-ray crystal structure analysis. The ethanol (95%)–dimethylforma-
midc (DMF) solution (10:1) of the products stood at room temperature for 5–7 days
to give single crystals suitable for X-ray diffraction analysis. The crystal data clearly
indicated that the structures of products conform to the speculated structures
completely.
The possible mechanism for the formation of 5 is shown in Scheme 3 based on
the work of Tu and coworkers.[12b] Clearly, [bmim]OH plays a crucial role in sup-
pressing other by-products. Because almost every step of the reaction is nucleophilic,
other ionic liquids show lower catalysis to the whole process because of their weaker
basicity, especially to the attack of intermediate A by 4. [bmim]OH can also promote
Figure 2. X-ray crystal structure of 5ba.

2-AMINO-8-ARYL-TETRAHYDROQUINOLINE-3-CARBONITRILE
3003
Figure 3. X-ray crystal structure of 5ck.
Scheme 3. Possible reaction mechanism.
Table 5. Yields for the reaction with recycled [bmim]OHa
Run
Isolated yields (%)
1
2
3
4
5
86
84
83
83
82
aReaction conditions: 4-methoxybenzaldehyde (1.0 mmol),
malononitrile (1.0 mmol), cyclohexanone (1.0 mmol),
methylamine (1.0 mmol), and ionic liquid (15 mol %), at 80 ꢀC.

3004
Y. WAN ET AL.
the stability of intermediates A, B, and C, for all of them bear basic functional
groups or anion ions.
We have recycled the ionic liquid, which worked well up to five cycles as a
reaction medium with slightly decrease in yields (Table 5).
EXPERIMENTAL
General Procedure
All reagents were purchased from commercial sources and used without further
purification. Thin-layer chromatographic (TLC) analysis was performed with
glass-backed plates precoated with silica gel and examined under ultraviolet light
(254 nm). NMR spectra were measured in CDCl3 with Me4Si as the internal stan-
dards on a Bruker Advance DPX-400 instrument at room temperature. Infrared
(IR) spectra were recorded on a Bruker Fourier transform (FT–IR) spectrometer;
absorbance is reported in cmꢁ1. The x-ray structure determinations were measured
on a Smartapex Bruke diffractometer. Mass spectra was determined by using a turn-
over frequency (TOF)–MS high–resolution mass spectrometer.
General Procedure for the Synthesis of Aimed Compounds in
Ionic Liquid
A mixture of aldehydes 1 (1.0 mmol), cyclohexanone 2 (1.0 mmol), malononi-
trile 3 (1.0 mmol), and amines 4 (1.0 mmol) was stirred in [bmim]OH (2 mL) at room
temperature or 80 ꢀC for 4–6 h. The reaction was monitored by TLC. The reaction
mixture was poured into water upon completion, and [bmim]OH was removed by
filtration. The product was purified by recrystallization with EtOH (95%). After
the extraction, [bmim]OH remaining in the conical flask was further washed with
ethyl acetate and dried at 90 ꢀC for 2 h under a high vacuum before the next run.
Data
5,6,7,8-Tetrahydro-2-(methylamino)-4-phenylquinoline-3-carbonitrile
1
(5aa). IR (KBr, n, cmꢁ1): 3374, 2930, 2860, 2212; H NMR (400 MHz, CDCl3) d:
1.64–1.67 (m, 2H, CH2), 1.81–1.84 (m, 2H, CH2), 2.31 (t, J ¼ 6.4 Hz, 2H, CH2),
2.85 (t, J ¼ 6.4 Hz, 2H, CH2), 3.06 (d, J ¼ 4.8 Hz, 3H, CH3), 5.05 (d, J ¼ 3.6 Hz,
1H, NH), 7.23–7.26 (m, 2H, ArH), 7.42–7.46 (m, 3H, ArH); 13C NMR (100 MHz,
CDCl3) d: 22.74, 23.05, 26.40, 28.38, 33.82, 89.94, 117.21, 118.86, 128.14, 128.62,
128.66, 136.54, 154.26, 157.05, 161.32. HRMS (ESI): m=z calcd. for C17H17N3,
263.1422; found, 264.1401 (M þ 1).
4-(2-Chlorophenyl)-5,6,7,8-tetrahydro-2-(methylamino)quinoline-3-
carbonitrile (5ab). IR (KBr, n, cmꢁ1): 3401, 2933, 2859, 2208; 1H NMR (400 MHz,
CDCl3) d: 1.66–1.70 (m, 2H, CH2), 1.81–1.84 (m, 2H, CH2), 2.12–2.26 (m, 2H, CH2),
2.84–2.88 (m, 2H, CH2), 3.07 (d, J ¼ 5.2 Hz, 3H, CH3), 5.07 (d, J ¼ 4.0 Hz, 1H, NH),
7.15–7.18 (m, 1H, ArH), 7.36–7.40 (m, 2H, ArH), 7.49–7.51 (m, 1H, ArH); 13C
NMR (100 MHz, CDCl3) d: 22.68, 22.78, 25.58, 28.39, 33.77, 89.85, 116.57,

2-AMINO-8-ARYL-TETRAHYDROQUINOLINE-3-CARBONITRILE
3005
119.36, 127.24, 129.61, 129.92, 130.15, 132.21, 135.51, 151.63, 158.94, 161.61. HRMS
(ESI): m=z calcd. for C17H16ClN3, 297.1033; found, 298.0989 (M þ 1).
4-(4-Chlorophenyl)-5,6,7,8-tetrahydro-2-(methylamino)quinoline-3-
carbonitrile (5ac). IR (KBr, n, cmꢁ1): 3402, 2937, 2861, 2210; 1H NMR (400 MHz,
CDCl3) d: 1.65–1.68 (m, 2H, CH2), 1.81–1.84 (m, 2H, CH2), 2.29 (t, J ¼ 6.0 Hz, 2H,
CH2), 2.85 (t, J ¼ 6.4 Hz, 2H, CH2), 3.07 (d, J ¼ 4.8 Hz, 3H, CH3), 5.04 (d, J ¼ 4.4 Hz,
1H, NH), 7.19 (d, J ¼ 8.4 Hz, 2H, ArH), 7.44 (d, J ¼ 8.4 Hz, 2H, ArH); 13C NMR
(100 MHz, CDCl3) d: 22.67, 23.00, 26.39, 28.37, 33.80, 89.68, 117.02, 118.72,
128.99, 129.63, 134.84, 134.89, 152.93, 157.04, 161.64. HRMS (ESI): m=z calcd.
for C17H16ClN3, 297.1033; found, 298.0997 (M þ 1).
4-(2-Bromophenyl)-5,6,7,8-tetrahydro-2-(methylamino)quinoline-3-
1
carbonitrile (5ad). IR (KBr, n, cmꢁ1): 3403, 3365, 2936, 2838, 2212; H NMR
(400 MHz, CDCl3): 1.65–1.72 (m, 2H, CH2), 1.82–1.88 (m, 2H, CH2), 2.23–2.26
(m, 1H, CH2), 2.30–2.35 (m, 1H, CH2), 2.86–2.89 (m, 2H, CH2), 3.08 (d, J ¼ 4.8 Hz,
3H, CH3), 5.10 (d, J ¼ 4.0 Hz, 1H, NH), 7.61 (d, J ¼ 8.0 Hz, 1H, ArH), 7.69 (t,
J ¼ 8.0 Hz, 1H, ArH), 8.14 (s, 1H, ArH), 8.31 (dd, J ¼ 0.8 Hz, 8.4 Hz, 1H, ArH);
13C NMR (100 MHz, CDCl3) d: 22.55, 22.91, 26.40, 28.39, 33.82, 89.31, 116.63,
118.43, 123.48, 123.69, 129.99, 134.43, 138.13, 148.29, 151.30, 157.03, 162.29. HRMS
(ESI): m=z calcd. for C17H16BrN3, 341.0528; found, 342.0502 (M þ 1).
4-(4-Bromophenyl)-5,6,7,8-tetrahydro-2-(methylamino)quinoline-3-car-
bonitrile (5ae). IR (KBr, n, cmꢁ1): 3405, 3369, 2939, 2839, 2214; 1H NMR
(400 MHz, CDCl3) d: 1.66–1.71 (m, 2H, CH2), 1.81–1.84 (m, 2H, CH2), 2.13–2.18
(m, 1H, CH2), 2.23–2.28 (m, 1H, CH2), 2.85–2.88 (m, 2H, CH2), 3.07 (d, J ¼ 4.8 Hz,
3H, CH3), 5.04 (d, J ¼ 3.6 Hz, 1H, NH), 7.15 (dd, J ¼ 1.6 Hz, 7.6 Hz, 1H, ArH),
7.27-7.31 (m, 1H, ArH), 7.42 (t, J ¼ 7.6 Hz, 1H, ArH), 7.68 (d, J ¼ 8.0 Hz, 1H,
ArH); 13C NMR (100MHz, CDCl3) d: 22.67, 22.79, 25.66, 28.37, 33.79, 89.75,
116.49, 119.15, 121.89, 127.83, 129.49, 130.22, 133.07, 137.61, 153.03, 156.89,
161.65. HRMS (ESI): m=z calcd. for C17H16BrN3, 341.0528; found, 342.0511 (M þ 1).
4-(2,4-Dichlorophenyl)-5,6,7,8-tetrahydro-2-(methylamino)quinoline-3-
carbonitrile (5af). IR (KBr, n, cmꢁ1): 3392, 2951, 2863, 2209; 1H NMR (400 MHz,
CDCl3) d: 1.68–1.71 (m, 2H, CH2), 1.82–1.84 (m, 2H, CH2), 2.20–2.23 (m, 2H, CH2),
2.85–2.87 (m, 2H, CH2), 3.07 (d, J ¼ 4.8 Hz, 3H, CH3), 5.05 (d, J ¼ 3.6 Hz, 1H, NH),
7.17 (s, 1H, ArH), 7.34–7.37 (m, 1H, ArH), 7.44 (d, J ¼ 8.8 Hz, 1H, ArH); 13C NMR
(100 MHz, CDCl3) d: 22.60, 22.73, 25.59, 28.39, 33.78, 89.46, 116.28, 119.02, 129.49,
130.24, 130.71, 131.12, 133.10, 136.95, 150.10, 156.91, 162.00. HRMS (ESI): m=z
calcd. for C17H15Cl2N3, 331.0643; found, 332.0616 (M þ 1).
4-(4-Cyanophenyl)-5,6,7,8-tetrahydro-2-(methylamino)quinoline-3-
carbonitrile (5ag). IR (KBr, n, cmꢁ1): 3364, 2943, 2840, 2222; 1H NMR (400 MHz,
CDCl3) d: 1.66–1.69 (m, 2H, CH2), 1.82–1.84 (m, 2H, CH2), 2.25 (t, J ¼ 6.0 Hz, 2H,
CH2), 2.86 (t, J ¼ 6.4 Hz, 2H, CH2), 3.07 (d, J ¼ 4.8 Hz, 3H, CH3), 5.08 (d, J ¼ 4.4 Hz,
1H, NH), 7.38 (d, J ¼ 8.4 Hz, 2H, ArH), 7.78 (d, J ¼ 8.0 Hz, 2H, ArH); 13C NMR
(100 MHz, CDCl3) d: 22.56, 22.89, 26.35, 28.38, 33.81, 89.01, 112.77, 116.64,
118.17, 118.34, 129.19, 132.53, 141.30, 151.94, 156.99, 162.14; HRMS (ESI): m=z
calcd. for C17H16N4, 288.1375; found, 289.1134 (M þ 1).

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Y. WAN ET AL.
5,6,7,8-Tetrahydro-2-(methylamino)-4-(3-nitrophenyl)quinoline-3-
carbonitrile (5ah). IR (KBr, n, cmꢁ1) 3394, 2953, 2891, 2207; 1H NMR (400 MHz,
CDCl3) d: 1.67–1.72 (m, 2H, CH2), 1.83–1.86 (m, 2H, CH2), 2.23–2.24 (m, 1H, CH2),
2.30–2.33 (m, 1H, CH2), 2.87–2.88 (m, 2H, CH2), 3.08 (d, J ¼ 4.8 Hz, 3H, CH3), 5.09
(d, J ¼ 4.8 Hz, 1H, NH), 7.60 (d, J ¼ 7.6 Hz, 1H, ArH), 7.68 (t, J ¼ 8.0 Hz, 1H, ArH),
8.14 (s, 1H, ArH), 8.31 (dd, J ¼ 0.8 Hz, 7.2 Hz, 1H, ArH); 13C NMR (100 MHz,
CDCl3) d: 22.55, 22.91, 26.40, 28.40, 33.82, 89.30, 116.63, 118.43, 123.47, 123.69,
129.99, 134.43, 138.13, 148.29, 151.30, 157.02, 162.28. HRMS (ESI): m=z calcd.
for C17H16N4O2, 308.1273; found, 309.1096 (M þ 1).
5,6,7,8-Tetrahydro-2-(methylamino)-4-(4-nitrophenyl)quinoline-3-
carbonitrile (5ai). IR (KBr, n, cmꢁ1): 3398, 2951, 2890, 2209; 1H NMR (400 MHz,
CDCl3) d: 1.65–1.68 (m, 2H, CH2), 1.81–1.84 (m, 2H, CH2), 2.29 (t, J ¼ 6.4 Hz, 2H,
CH2), 2.85 (t, J ¼ 6.4 Hz, 2H, CH2), 3.06 (d, J ¼ 4.8 Hz, 3H, CH3), 5.06 (d, J ¼ 4.0 Hz,
1H, NH), 7.12 (d, J ¼ 8.0 Hz, 2H, ArH), 7.60 (d, J ¼ 8.4 Hz, 2H, ArH); 13C NMR
(100 MHz, CDCl3) d: 22.67, 22.99, 26.39, 28.37, 33.80, 89.57, 117.00, 118.63,
123.06, 129.90, 131.93, 135.38, 152.90, 157.04, 161.66. HRMS (ESI): m=z calcd.
for C17H16N4O2, 308.1273; found, 309.1102 (M þ 1).
5,6,7,8-Tetrahydro-4-(2-methoxyphenyl)-2-(methylamino)quinoline-3-
carbonitrile (5aj). IR (KBr, n, cmꢁ1): 3408, 2935, 2834, 2203; 1H NMR (400 MHz,
CDCl3) d: 1.64–1.67 (m, 2H, CH2), 1.81–1.83 (m, 2H, CH2), 2.26 (t, J ¼ 6.4 Hz, 2H,
CH2), 2.83–2.87 (m, 2H, CH2), 3.05 (d, J ¼ 5.2 Hz, 3H, CH3), 3.79 (s, 3H, OCH3),
4.50 (d, J ¼ 4.0 Hz, 1H, NH), 6.98–7.09 (m, 3H, ArH), 7.37–7.42 (m, 1H, ArH);
13C NMR (100 MHz, CDCl3) d: 22.80, 22.90, 25.67, 28.38, 33.77, 55.59, 90.64,
111.26, 117.24, 119.93, 120.80, 125.31, 129.67, 130.30, 151.69, 155.98, 156.98,
160.82. HRMS (ESI): m=z calcd. for C18H19N3O, 293.1528; found, 294.1469
(M þ 1).
5,6,7,8-Tetrahydro-4-(4-methoxyphenyl)-2-(methylamino)quinoline-3-
carbonitrile (5ak). IR (KBr, n, cmꢁ1): 3458, 2936, 2831, 2205; 1H NMR
(400 MHz, CDCl3) d: 1.64–1.67 (m, 2H, CH2), 1.81–1.84 (m, 2H, CH2), 2.34 (t,
J ¼ 6.0 Hz, 2H, CH2), 2.85 (t, J ¼ 6.4 Hz, 2H, CH2), 3.06 (d, J ¼ 4.8 Hz, 3H, CH3),
3.85 (s, 3H, OCH3), 5.04 (d, J ¼ 6.4 Hz, 1H, NH), 6.98 (d, J ¼ 8.8 Hz, 2H, ArH),
7.18 (d, J ¼ 8.4 Hz, 2H, ArH); 13C NMR (100 MHz, CDCl3) d: 22.76, 23.11, 26.49,
28.38, 33.79, 55.29, 90.18, 114.01, 117.47, 119.18, 128.65, 129.59, 154.10, 157.12,
159.80, 161.17. HRMS (ESI): m=z calcd. for C18H19N3O, 293.1528; found,
294.1478 (M þ 1).
5,6,7,8-Tetrahydro-4-(2,3-dimethoxyphenyl)-2-(methylamino)quinoline-
3-carbonitrile (5al). IR (KBr, n, cmꢁ1): 3408, 2940, 2834, 2207; 1H NMR
(400 MHz, CDCl3) d: 1.67–1.68 (m, 2H, CH2), 1.81–1.83 (m, 2H, CH2), 2.36 (t,
J ¼ 6.4 Hz, 2H, CH2), 2.85 (t, J ¼ 6.4 Hz, 2H, CH2), 3.06 (s, 3H, CH3), 3.89 (s, 3H,
OCH3), 3.93 (s, 3H, OCH3), 5.05 (d, J ¼ 4.4 Hz, 1H, NH), 6.75 (s, 1H, ArH), 6.82
(dd, J ¼ 1.6 Hz, 8.0 Hz, 1H, ArH), 6.95 (d, J ¼ 8.0 Hz, 1H, ArH); 13C NMR
(100 MHz, CDCl3) d: 22.75, 23.11, 26.48, 28.37, 33.79, 55.89, 56.02, 90.13, 111.12,
115.51, 117.40, 119.08, 120.90, 128.89, 148.86, 149.25, 154.06, 157.10, 161.22. HRMS
(ESI): m=z calcd. for C19H21N3O2, 323.1634; found, 324.1457 (M þ 1).

2-AMINO-8-ARYL-TETRAHYDROQUINOLINE-3-CARBONITRILE
3007
5,6,7,8-Tetrahydro-4-(3,4-dimethoxyphenyl)-2-(methylamino)quinoline-
3-carbonitrile (5am). IR (KBr, n, cmꢁ1): 3408, 2938, 2894, 2211; 1H NMR
(400 MHz, CDCl3) d: 1.67–1.68 (m, 2H, CH2), 1.81–1.85 (m, 2H, CH2), 2.36 (t,
J ¼ 6.4 Hz, 2H, CH2), 2.86 (t, J ¼ 6.4 Hz, 2H, CH2), 3.06 (d, J ¼ 4.8 Hz, 3H, CH3),
3.89 (s, 3H, OCH3), 3.94 (s, 3H, OCH3), 5.05 (d, J ¼ 4.8 Hz, 1H, NH), 6.75 (s, 1H,
ArH), 6.83 (dd, J ¼ 2.0 Hz, 8.4 Hz, 1H, ArH), 6.95 (d, J ¼ 8.0 Hz, 1H, ArH); 13C
NMR (100 MHz, CDCl3) d: 22.75, 23.11, 26.49, 28.36, 33.79, 55.89, 56.03, 90.13,
111.12, 111.51, 117.40, 119.08, 120.90, 128.89, 148.86, 149.25, 154.05, 157.10,
161.23. HRMS (ESI): m=z calcd. for C19H21N3O2, 323.1634; found, 324.1498
(M þ 1).
5,6,7,8-Tetrahydro-4-(3,4,5-trimethoxyphenyl)-2-(methylamino)quinoline-
3-carbonitrile (5an). IR (KBr, n, cmꢁ1): 3407, 2934, 2891, 2210; 1H NMR
(400 MHz, CDCl3) d: 1.66–1.69 (m, 2H, CH2), 1.82–1.85 (m, 2H, CH2), 2.37 (t,
J ¼ 6.0 Hz, 2H, CH2), 2.85 (t, J ¼ 6.4 Hz, 2H, CH2), 3.06 (d, J ¼ 4.8 Hz, 3H, CH3),
3.86 (s, 6H, 2OCH3), 3.90 (s, 3H, OCH3), 5.07 (d, J ¼ 4.4 Hz, 1H, NH), 6.44 (s,
2H, ArH); 13C NMR (100 MHz, CDCl3) d: 22.72, 23.07, 26.39, 28.38, 33.80,
56.23, 60.96, 89.83, 105.44, 117.21, 118.89, 131.85, 138.08, 153.30, 154.14, 157.05,
161.37. HRMS (ESI): m=z calcd. for C20H23N3O3, 353.1739; found, 354.1725
(M þ 1).
5,6,7,8-Tetrahydro-4-(4-methoxyphenyl)-2-(phenylamino)quinoline-3-
carbonitrile (5ba). IR (KBr, n, cmꢁ1): 3338, 2937, 2838, 2217; 1H NMR
(400 MHz, CDCl3) d: 1.59–1.70 (m, 2H, CH2), 1.83–1.86 (m, 2H, CH2), 2.40 (t,
J ¼ 6.4 Hz, 2H, CH2), 2.92 (t, J ¼ 6.4 Hz, 2H, CH2), 3.86 (s, 3H, OCH3), 6.96 (s,
1H, NH), 7.00–7.05 (m, 3H, ArH), 7.21–7.24 (m, 2H, ArH), 7.34 (t, J ¼ 8.0 Hz,
2H, ArH), 7.69 (d, J ¼ 8.0 Hz, 2H, ArH); 13C NMR (100 MHz, CDCl3) d: 22.60,
22.95, 26.64, 33.68, 55.31, 91.94, 114.14, 116.88, 119.58, 121.84, 122.77, 128.25,
128.89, 129.61, 139.55, 153.57, 154.51, 159.99, 161.01. HRMS (ESI): m=z calcd.
for C23H21N3O, 355.1685; found, 356.1674 (M þ 1).
2-(4-Fluorophenylamino)-5,6,7,8-tetrahydro-4-(4-methoxyphenyl)quino-
line-3-carbonitrile (5bb). IR (KBr, n, cmꢁ1): 3420, 3341, 3252, 2947, 2868, 2213;
1H NMR (400 MHz, CDCl3) d: 1.67–1.70 (m, 2H, CH2), 1.83–1.86 (m, 2H, CH2),
2.40 (t, J ¼ 6.4 Hz, 2H, CH2), 2.89 (t, J ¼ 6.4 Hz, 2H, CH2), 3.87 (s, 3H, OCH3),
6.90 (s, 1H, NH), 7.00–7.05 (m, 4H, ArH), 7.22 (d, J ¼ 8.8 Hz, 2H, ArH),
7.60–7.63 (m, 2H, ArH); 13C NMR (100 MHz, CDCl3) d: 22.91, 23.27, 26.97,
34.00, 55.65, 92.07, 114.49, 115.67, 115.89, 117.19, 121.82, 121.89, 122.24, 128.52,
129.93, 135.80, 135.83, 153.93, 154.93, 157.77, 160.18, 160.35, 161.35. HRMS
(ESI): m=z calcd. for C23H20FN3O, 373.1590; found, 374.1563 (M þ 1).
2-(2-Chlorophenylamino)-5,6,7,8-tetrahydro-4-(4-methoxyphenyl)quino-
1
line-3-carbonitrile (5bc). IR (KBr, n, cmꢁ1): 3327, 2946, 2836, 2223; H NMR
(400 MHz, CDCl3) d: 1.70–1.72 (m, 2H, CH2), 1.85–1.87 (m, 2H, CH2), 2.42 (t,
J ¼ 6.4 Hz, 2H, CH2), 2.94 (t, J ¼ 6.4 Hz, 2H, CH2), 3.87 (s, 3H, OCH3), 7.01–7.03
(m, 3H, ArH), 7.22–7.26 (m, 3H, ArH), 7.40 (d, J ¼ 7.6 Hz, 1H, ArH), 7.67 (s, 1H,
NH), 8.69 (d, J ¼ 8.4 Hz, 1H, ArH); 13C NMR (100 MHz, CDCl3) d: 22.56, 22.90,
26.70, 33.64, 55.33, 93.16, 114.79, 116.30, 120.19, 122.64, 122.68, 122.72, 127.30,

3008
Y. WAN ET AL.
128.06, 129.12, 129.63, 136.35, 153.05, 154.66, 160.04, 160.75. HRMS (ESI): m=z
calcd. for C23H20ClN3O, 389.1295; found, 390.1281 (M þ 1).
2-(3-Chlorophenylamino)-5,6,7,8-tetrahydro-4-(4-methoxyphenyl)quino-
1
line-3-carbonitrile (5bd). IR (KBr, n, cmꢁ1): 3328, 2945, 2837, 2221; H NMR
(400 MHz, CDCl3) d: 1.68–1.71 (m, 2H, CH2), 1.85–1.87 (m, 2H, CH2), 2.21 (t,
J ¼ 6.4 Hz, 2H, CH2), 2.94 (t, J ¼ 6.4 Hz, 2H, CH2), 3.87 (s, 3H, OCH3), 6.97 (s,
1H, NH), 7.01 (d, J ¼ 8.8 Hz, 3H, ArH), 7.21–7.26 (m, 3H, ArH), 7.43 (d, J ¼ 8.4 Hz,
1H, ArH), 7.95 (s, 1H, ArH); 13C NMR (100 MHz, CDCl3) d: 22.54, 22.89, 26.88,
33.63, 55.33, 92.35, 114.19, 116.63, 117.40, 119.39, 122.53, 122.59, 128.04, 129.60,
129.80, 134.50, 140.76, 153.11, 154.62, 160.06, 161.06. HRMS (ESI): m=z calcd.
for C23H20ClN3O, 389.1295; found, 390.1278 (M þ 1).
2-(4-Chlorophenylamino)-5,6,7,8-tetrahydro-4-(4-methoxyphenyl)quino-
1
line-3-carbonitrile (5be). IR (KBr, n, cmꢁ1): 3336, 2937, 2838, 2224; H NMR
(400 MHz, CDCl3) d: 1.68–1.71 (m, 2H, CH2), 1.84–1.86 (m, 2H, CH2), 2.41 (t,
J ¼ 6.4 Hz, 2H, CH2), 2.91 (t, J ¼ 6.4 Hz, 2H, CH2), 3.87 (s, 3H, OCH3), 6.95 (s,
1H, NH), 7.01 (d, J ¼ 8.4 Hz, 2H, ArH), 7.22 (d, J ¼ 8.8 Hz, 2H, ArH), 7.23–7.30
(m, 2H, ArH), 7.64 (d, J ¼ 2.0 Hz, 2H, ArH); 13C NMR (100 MHz, CDCl3) d:
22.56, 22.90, 26.65, 33.65, 55.33, 92.13, 114.18, 116.73, 120.83, 122.25, 127.53,
128.09, 128.83, 129.59, 138.14, 153.27, 154.64, 160.05, 161.00. HRMS (ESI): m=z
calcd. for C23H20ClN3O, 389.1295; found, 390.1271 (M þ 1).
2-(3-Bromophenylamino)-5,6,7,8-tetrahydro-4-(4-methoxyphenyl)quino-
1
line-3-carbonitrile (5bf). IR (KBr, n, cmꢁ1): 3327, 2946, 2839, 2221; H NMR
(400 MHz, CDCl3) d: 1.68–1.71 (m, 2H, CH2), 1.85–1.88 (m, 2H, CH2), 2.41 (t,
J ¼ 6.4 Hz, 2H, CH2), 2.94 (t, J ¼ 6.4 Hz, 2H, CH2), 3.87 (s, 3H, OCH3), 6.95 (s,
1H, NH), 7.01 (d, J ¼ 8.4 Hz, 2H, ArH), 7.17–7.23 (m, 4H, ArH), 7.48–7.50 (m,
1H, ArH), 8.08 (s, 1H, ArH); 13C NMR (100 MHz, CDCl3) d: 22.54, 22.89, 26.67,
33.62, 55.33, 92.35, 114.19, 116.61, 117.88, 119.45, 122.27, 122.56, 125.51, 128.03,
129.60, 130.10, 140.88, 153.08, 154.61, 160.06, 161.05. HRMS (ESI): m=z calcd.
for C23H20BrN3O, 433.0790; found, 434.0771 (M þ 1).
2-(4-Bromophenylamino)-5,6,7,8-tetrahydro-4-(4-methoxyphenyl)quino-
1
line-3-carbonitrile (5bg). IR (KBr, n, cmꢁ1): 3336, 2935, 2837, 2223; H NMR
(400 MHz, CDCl3) d: 1.69–1.71 (m, 2H, CH2), 1.84–1.86 (m, 2H, CH2), 2.41 (t,
J ¼ 6.4 Hz, 2H, CH2), 2.91 (t, J ¼ 6.4 Hz, 2H, CH2), 3.87 (s, 3H, OCH3), 6.96 (s,
1H, NH), 7.01 (d, J ¼ 8.8 Hz, 2H, ArH), 7.02 (d, J ¼ 8.4 Hz, 2H, ArH), 7.43 (d,
J ¼ 8.8 Hz, 2H, ArH), 7.59 (d, J ¼ 8.8 Hz, 2H, ArH); 13C NMR (100 MHz, CDCl3)
d: 22.57, 22.91, 26.65, 33.67, 55.35, 92.15, 114.18, 116.75, 120.83, 122.25, 127.53,
128.11, 128.63, 129.59, 139.14, 149.93, 151.01, 160.20, 161.17. HRMS (ESI): m=z
calcd. for C23H20BrN3O, 433.0790; found, 434.0767 (M þ 1).
2-(3-Tolylamino)-5,6,7,8-tetrahydro-4-(4-methoxyphenyl)quinoline-3-
1
carbonitrile (5bh). IR (KBr, n, cmꢁ1): 3420, 3340, 3253, 2947, 2833, 2214; H
NMR (400 MHz, CDCl3) d: 1.68–1.71 (m, 2H, CH2), 1.84–1.86 (m, 2H, CH2),
2.36 (s, 3H, CH3), 2.40 (t, J ¼ 6.4 Hz, 2H, CH2), 2.92 (t, J ¼ 6.4 Hz, 2H, CH2),
3.87 (s, 3H, OCH3), 6.88 (d, J ¼ 7.6 Hz, 1H, NH), 6.91 (s, 1H, ArH), 7.01 (d,
J ¼ 8.8 Hz, 2H, ArH), 7.21–7.26 (m, 3H, ArH), 7.43 (s, 1H, ArH), 7.57 (d, J ¼ 8.4 Hz,

2-AMINO-8-ARYL-TETRAHYDROQUINOLINE-3-CARBONITRILE
3009
1H, ArH); 13C NMR (100 MHz, CDCl3) d: 21.62, 22.62, 22.97, 26.64, 33.67, 55.32,
91.91, 114.14, 116.77, 116.92, 120.27, 121.72, 123.65, 128.29, 128.75, 129.62, 128.68,
139.45, 153.65, 154.48, 159.98, 161.03. HRMS (ESI): m=z calcd. for C24H23N3O,
369.1841; found, 370.1821 (M þ 1).
2-(4-Tolylamino)-5,6,7,8-tetrahydro-4-(4-methoxyphenyl)quinoline-3-
carbonitrile (5bi). IR (KBr, n, cmꢁ1): 3341, 2941, 2849, 2222; 1H NMR (400 MHz,
CDCl3) d: 1.67–1.70 (m, 2H, CH2), 1.82–1.84 (m, 2H, CH2), 2.33 (s, 3H, CH3), 2.39
(t, J ¼ 6.4 Hz, 2H, CH2), 2.89 (t, J ¼ 6.4 Hz, 2H, CH2), 3.86 (s, 3H, OCH3), 6.90 (s,
1H, NH), 7.01 (d, J ¼ 8.8 Hz, 2H, ArH), 7.14 (d, J ¼ 8.0 Hz, 2H, ArH), 7.22 (d,
J ¼ 8.8 Hz, 2H, ArH), 7.54 (d, J ¼ 8.4 Hz, 2H, ArH); 13C NMR (100 MHz, CDCl3)
d: 18.43, 20.21, 20.57, 24.22, 31.26, 52.90, 89.23, 111.72, 114.56, 117.56, 119.08,
125.93, 126.98, 127.20, 130.02, 134.47, 151.36, 152.03, 157.55, 158.60. HRMS
(ESI): m=z calcd. for C24H23N3O, 369.1841; found, 370.1828 (M þ 1).
2-(4-Nitrophenylamino)-5,6,7,8-tetrahydro-4-(4-methoxyphenyl)quino-
1
line-3-carbonitrile (5bj). IR (KBr, n, cmꢁ1): 3331, 2934, 2833, 2220; H NMR
(400 MHz, CDCl3) d: 1.71–1.74 (m, 2H, CH2), 1.88–1.91 (m, 2H, CH2), 2.46 (t,
J ¼ 6.4 Hz, 2H, CH2), 2.98 (t, J ¼ 6.4 Hz, 2H, CH2), 3.88 (s, 3H, OCH3), 7.03 (d,
J ¼ 8.8 Hz, 2H, ArH), 7.23 (d, J ¼ 8.4 Hz, 2H, ArH), 7.35 (s, 1H, NH), 7.88 (d,
J ¼ 9.2 Hz, 2H, ArH), 8.22 (d, J ¼ 8.4 Hz, 2H, ArH); 13C NMR (100 MHz, CDCl3)
d: 22.16, 22.47, 26.49, 33.36, 55.07, 93.25, 114.00, 115.95, 117.79, 123.82, 124.95,
127.36, 129.29, 141.72, 145.37, 151.97, 154.62, 159.95, 160.86. HRMS (ESI): m=z
calcd. for C23H20N4O3, 400.1535; found, 401.1523 (M þ 1).
2-(3-Methoxyphenylamino)-5,6,7,8-tetrahydro-4-(4-methoxyphenyl)qui-
noline-3-carbonitrile (5bk). IR (KBr, n, cmꢁ1): 3420, 3341, 3253, 2947, 2833, 2214;
1H NMR (400 MHz, CDCl3) d: 1.68-1.71 (m, 2H, CH2), 1.84-1.87 (m, 2H, CH2),
2.40 (t, J ¼ 6.4 Hz, 2H, CH2), 2.93 (t, J ¼ 6.4 Hz, 2H, CH2), 3.83 (s, 3H, OCH3),
3.86 (s, 3H, OCH3), 6.61 (dd, J ¼ 2.0 Hz, 8.4 Hz, 1H, NH), 6.97-7.02 (m, 3H,
ArH), 7.11 (s, 1H, ArH), 7.20-7.26 (m, 3H, ArH), 7.56 (m, 1H, ArH); 13C NMR
(100 MHz, CDCl3) d: 22.59, 22.95, 26.64, 33.71, 55.26, 55.32, 92.08, 105.17,
108.51, 111.76, 114.15, 116.82, 121.93, 128.21, 129.54, 129.61, 140.80, 153.49,
154.53, 160.00, 160.13, 160.93. HRMS (ESI): m=z calcd. for C24H23N3O2,
385.1790; found, 386.1768 (M þ 1).
2-(4-Methoxyphenylamino)-5,6,7,8-tetrahydro-4-(4-methoxyphenyl)qui-
1
noline-3-carbonitrile (5bl). IR (KBr, n, cmꢁ1): 3346, 2947, 2833, 2211; H NMR
(400 MHz, CDCl3) d: 1.66–1.69 (m, 2H, CH2), 1.82–1.84 (m, 2H, CH2), 2.38 (t,
J ¼ 6.0 Hz, 2H, CH2), 2.87 (t, J ¼ 6.4 Hz, 2H, CH2), 3.81 (s, 3H, OCH3), 3.86 (s,
3H, OCH3), 6.82 (s, 1H, NH), 6.89 (d, J ¼ 9.2 Hz, 2H, ArH), 7.00 (d, J ¼ 8.8 Hz,
2H, ArH), 7.22 (d, J ¼ 8.8 Hz, 2H, ArH), 7.55 (d, J ¼ 8.8 Hz, 2H, ArH); 13C NMR
(100 MHz, CDCl3) d: 22.64, 23.00, 26.62, 33.71, 55.32, 55.56, 91.31, 114.12,
117.07, 121.29, 121.90, 128.38, 129.62, 129.53, 132.61, 154.00, 154.46, 155.63,
159.95, 161.08. HRMS (ESI): m=z calcd. for C24H23N3O2, 385.1790; found,
386.1775 (M þ 1).
2-(2,3-Dimethoxyphenylamino)-5,6,7,8-tetrahydro-4-(4-methoxyphenyl)-
quinoline-3-carbonitrile (5bm). IR (KBr, n, cmꢁ1): 3426, 3342, 3257, 2947, 2836,

3010
Y. WAN ET AL.
1
2215; H NMR (400 MHz, CDCl3) d: 1.66–1.68 (m, 2H, CH2), 1.79–1.81 (m, 2H,
CH2), 2.22 (s, 3H, OCH3), 2.33 (s, 3H, OCH3), 2.38 (t, J ¼ 6.4 Hz, 2H, CH2), 2.82
(t, J ¼ 6.4 Hz, 2H, CH2), 3.86 (s, 3H, OCH3), 6.77 (s, 1H, NH), 6.97–7.00 (m, 3H,
ArH), 7.12 (t, J ¼ 8.8 Hz, 1H, ArH), 7.23 (d, J ¼ 8.8 Hz, 2H, ArH), 7.55 (d,
J ¼ 8.0 Hz, 1H, ArH); 13C NMR (100 MHz, CDCl3) d: 13.98, 20.82, 22.64, 22.99,
26.65, 33.72, 55.32, 91.59, 114.14, 117.10, 120.69, 121.34, 125.59, 126.00, 128.43,
128.79, 129.65, 137.35, 154.36, 154.49, 159.95, 161.21. HRMS (ESI): m=z calcd.
for C25H25N3O3, 415.1896; found, 416.1887 (M þ 1).
2-(3,4-Dimethoxyphenylamino)-5,6,7,8-tetrahydro-4-(4-methoxyphenyl)-
quinoline-3-carbonitrile (5bn). IR (KBr, n, cmꢁ1): 3419, 3340, 3253, 2949, 2832,
1
2216; H NMR (400 MHz, CDCl3) d: 1.59–1.67 (m, 2H, CH2), 1.79–1.81 (m, 2H,
CH2), 2.38 (t, J ¼ 6.4 Hz, 2H, CH2), 2.82 (t, J ¼ 6.4 Hz, 2H, CH2), 3.81 (s, 3H,
OCH3), 3.83 (s, 3H, OCH3), 3.86 (s, 3H, OCH3), 6.77 (s, 1H, NH), 7.00–7.02 (m,
3H, ArH), 7.12 (m, 1H, ArH), 7.24 (d, J ¼ 8.0 Hz, 2H, ArH), 7.55 (d, J ¼ 8.0 Hz,
1H, ArH); 13C NMR (100 MHz, CDCl3) d 22.62, 22.98, 26.63, 33.70, 55.26, 55.32,
55.56, 91.57, 114.12, 117.08, 120.67, 121.32, 125.57, 125.98, 128.40, 128.76, 129.63,
137.33, 154.34, 154.46, 159.93, 161.19. HRMS (ESI): m=z calcd. for C25H25N3O3,
415.1896; found, 416.1881 (M þ 1).
2-(3-Chloro-2-methylphenylamino)-5,6,7,8-tetrahydro-4-(4-methoxyphe-
nyl)quinoline-3-carbonitrile (5bo). IR (KBr, n, cmꢁ1): 3420, 3341, 3252, 2947,
1
2833, 2213; H NMR (400 MHz, CDCl3) d: 1.67–1.69 (m, 2H, CH2), 1.81–1.84 (m,
2H, CH2), 2.38–2.42 (m, 5H, CH2þCH3), 2.84 (t, J ¼ 6.4 Hz, 2H, CH2), 3.87 (s,
3H, OCH3), 6.82 (s, 1H, NH), 7.01 (d, J ¼ 8.8 Hz, 2H, ArH), 7.14–7.17 (m, 2H,
ArH), 7.22–7.25 (m, 2H, ArH), 7.91-7.93 (m, 1H, ArH); 13C NMR (100 MHz,
CDCl3) d: 14.91, 22.58, 22.92, 26.67, 33.69, 55.34, 92.12, 114.19, 116.85, 120.70,
122.12, 124.79, 126.66, 127.84, 128.17, 129.63, 134.84, 138.92, 153.93, 154.48,
160.04, 161.16. HRMS (ESI): m=z calcd. for C24H22ClN3O, 403.1451; found,
404.1443 (M þ 1).
2-(3-Chloro-4-fluorophenylamino)-5,6,7,8-tetrahydro-4-(4-methoxyphe-
nyl)quinoline-3-carbonitrile (5bp). IR (KBr, n, cmꢁ1): 3350, 2955, 2838, 2208;
1H NMR (400 MHz, CDCl3) d: 1.70–1.71 (m, 2H, CH2), 1.85–1.86 (m, 2H, CH2),
2.41 (t, J ¼ 6.4 Hz, 2H, CH2), 2.92 (t, J ¼ 6.4 Hz, 2H, CH2), 3.87 (s, 3H, OCH3),
6.89 (s, 1H, NH), 7.01 (d, J ¼ 8.4 Hz, 2H, ArH), 7.07–7.09 (m, 1H, ArH), 7.22 (d,
J ¼ 8.4 Hz, 2H, ArH), 7.38–7.41 (m, 1H, ArH), 7.94–7.97 (m, 1H, ArH); 13C
NMR (100 MHz, CDCl3) d: 22.53, 22.89, 26.66, 33.62, 55.33, 92.09, 114.20,
116.31, 116.53, 116.63, 119.26, 119.33, 121.71, 122.52, 128.01, 129.53, 136.18,
153.15, 154.68, 160.08, 161.06. HRMS (ESI): m=z calcd. for C23H19ClFN3O,
407.1201; found, 408.1189 (M þ 1).
5,6,7,8-Tetrahydro-4-(4-methoxyphenyl)-2-(naphthalen-1-ylamino)
1
quinoline-3-carbonitrile (5bq). IR (KBr, n, cmꢁ1): 3337, 2938, 2840, 2218; H
NMR (400 MHz, CDCl3) d: 1.71–1.72 (m, 2H, CH2), 1.86–1.89 (m, 2H, CH2),
2.42 (t, J ¼ 5.6 Hz, 2H, CH2), 2.97 (t, J ¼ 6.4 Hz, 2H, CH2), 3.87 (s, 3H, OCH3),
7.02 (d, J ¼ 8.0 Hz, 2H, ArH), 7.13 (s, 1H, NH), 7.24 (d, J ¼ 8.4 Hz, 2H, ArH),
7.37 (t, J ¼ 7.2 Hz, 1H, ArH), 7.45 (t, J ¼ 7.2 Hz, 1H, ArH), 7.65 (d, J ¼ 8.8 Hz,
1H, ArH), 7.77–7.81 (m, 3H, ArH), 8.35 (s, 1H, ArH); 13C NMR (100 MHz, CDCl3)

2-AMINO-8-ARYL-TETRAHYDROQUINOLINE-3-CARBONITRILE
3011
d: 22.62, 22.96, 26.68, 33.71, 55.32, 92.17, 114.17, 115.42, 116.88, 120.71, 122.08,
124.32, 126.32, 127.37, 127.57, 128.22, 128.51, 129.63, 130.01, 134.14, 137.08,
153.59, 154.35, 160.02, 161.07. HRMS (ESI): m=z calcd. for C27H23N3O,
405.1841; found, 406.1826 (M þ 1).
2-Amino-5,6,7,8-tetrahydro-4-phenylquinoline-3-carbonitrile (5ca). IR
1
(KBr, n, cmꢁ1): 3417, 3310, 3164, 2930, 2213, 1646; H NMR (400 MHz, CDCl3)
d: 1.67–1.70 (m, 2H, CH2), 1.84–1.87 (m, 2H, CH2), 2.36 (t, J ¼ 6.4 Hz, 2H, CH2),
2.84 (t, J ¼ 6.4 Hz, 2H, CH2), 5.20 (s, 2H, NH2), 7.27 (dd, J ¼ 2.0 Hz, 8.4 Hz, 2H,
ArH), 7.44–7.52 (m, 3H, ArH). HRMS (ESI): m=z calcd. for C16H15N3, 249.1266;
found, 250.1249 (M þ 1).
2-Amino-4-(2-chlorophenyl)-5,6,7,8-tetrahydroquinoline-3-carbonitrile
(5cb). IR (KBr, n, cmꢁ1): 3425, 3303, 3163, 2935, 2214, 1643;1H NMR (400 MHz,
CDCl3) d: 1.59–1.62 (m, 2H, CH2), 1.71–1.75 (m, 2H, CH2), 2.01–2.12 (m, 2H, CH2),
2.71–2.74 (m, 2H, CH2), 6.67 (s, 2H, NH2), 7.32–7.34 (m, 1H, ArH), 7.49–7.51 (m,
2H, ArH), 7.63–7.65 (m, 1H, ArH). HRMS (ESI): m=z calcd. for C16H14ClN3,
283.0876; found, 284.0857 (M þ 1).
2-Amino-4-(4-chlorophenyl)-5,6,7,8-tetrahydroquinoline-3-carbonitrile
1
(5cc). IR (KBr, n, cmꢁ1): 3422, 3303, 3150, 2944, 2213, 1644; H NMR (400 MHz,
CDCl3) d: 1.66–1.70 (m, 2H, CH2), 1.83–1.86 (m, 2H, CH2), 2.34 (t, J ¼ 6.4 Hz, 2H,
CH2), 2.84 (t, J ¼ 6.4 Hz, 2H, CH2), 5.10 (s, 2H, NH2), 7.23 (d, J ¼ 8.0 Hz, 2H, ArH),
7.48 (d, J ¼ 8.4 Hz, 2H, ArH). HRMS (ESI): m=z calcd. for C16H14ClN3, 283.0876;
found, 284.0863 (M þ 1).
2-Amino-4-(2-bromophenyl)-5,6,7,8-tetrahydroquinoline-3-carbonitrile
1
(5cd). IR (KBr, n, cmꢁ1): 3424, 3300, 3143, 2942, 2213, 1644; H NMR (400 MHz,
CDCl3) d: 1.70–1.74 (m, 2H, CH2), 1.85–1.87 (m, 2H, CH2), 2.16–2.23 (m, 1H, CH2),
2.27–2.33 (m, 1H, CH2), 2.83–2.87 (m, 2H, CH2), 5.09 (s, 2H, NH2), 7.18 (dd,
J ¼ 1.6 Hz, 7.6 Hz, 1H, ArH), 7.34 (m, 1H, ArH), 7.45 (m, 1H, ArH), 7.72 (dd,
J ¼ 0.80 Hz, 7.6 Hz, 1H, ArH). HRMS (ESI): m=z calcd. for C16H14BrN3,
327.0371; found, 328.0359 (M þ 1).
2-Amino-4-(3-bromophenyl)-5,6,7,8-tetrahydroquinoline-3-carbonitrile
1
(5ce). IR (KBr, n, cmꢁ1): 3428, 3304, 3151, 2944, 2209, 1644; H NMR (400 MHz,
CDCl3) d: 1.67–1.73 (m, 2H, CH2), 1.84–1.87 (m, 2H, CH2), 2.30–2.36 (m, 2H, CH2),
2.83 (t, J ¼ 6.4 Hz, 2H, CH2), 5.13 (s, 2H, NH2), 7.21 (d, J ¼ 7.6 Hz, 1H, ArH),
7.36–7.42 (m, 2H, ArH), 7.60 (d, J ¼ 8.0 Hz, 1H, ArH). HRMS (ESI): m=z calcd.
for C16H14BrN3, 327.0371; found, 328.0351 (M þ 1).
2-Amino-4-(4-bromophenyl)-5,6,7,8-tetrahydroquinoline-3-carbonitrile
(5cf). IR (KBr, n, cmꢁ1): 3427, 3304, 3167, 2933, 2214, 1641;1H NMR (400 MHz,
CDCl3) d: 1.65–1.73 (m, 2H, CH2), 1.83–1.89 (m, 2H, CH2), 2.34 (t, J ¼ 6.0 Hz,
2H, CH2), 2.84 (t, J ¼ 6.0 Hz, 2H, CH2), 5.10 (s, 2H, NH2), 7.16 (d, J ¼ 8.4 Hz,
2H, ArH), 7.64 (d, J ¼ 8.4 Hz, 2H, ArH). HRMS (ESI): m=z calcd. for C16H14BrN3,
327.0371; found, 328.0360 (M þ 1).
2-Amino-4-(2,4-dichlorophenyl)-5,6,7,8-tetrahydroquinoline-3-carboni-
trile (5cg). IR (KBr, n, cmꢁ1): 3418, 3312, 3184, 2934, 2211, 1644;1H NMR

3012
Y. WAN ET AL.
(400 MHz, CDCl3) d: 1.71–1.74 (m, 2H, CH2), 1.85–1.88 (m, 2H, CH2), 2.26 (t,
J ¼ 6.0 Hz, 2H, CH2), 2.83–2.87 (m, 2H, CH2), 5.14 (s, 2H, NH2), 7.20 (d, J ¼ 2.4 Hz,
1H, ArH), 7.39 (dd, J ¼ 2.4 Hz, 8.8 Hz, 1H, ArH), 7.48 (d, J ¼ 8.4 Hz, 1H, ArH).
HRMS (ESI): m=z calcd. for C16H13Cl2N3, 317.0487; found, 318.0478 (M þ 1).
2-Amino-4-(4-cyanophenyl)-5,6,7,8-tetrahydroquinoline-3-carbonitrile
1
(5ch). IR (KBr, n, cmꢁ1): 3433, 3298, 3140, 2943, 2209, 1643; H NMR (400 MHz,
CDCl3) d: 1.69–1.73 (m, 2H, CH2), 1.85–1.88 (m, 2H, CH2), 2.97 (t, J ¼ 6.0 Hz, 2H,
CH2), 2.85 (t, J ¼ 6.4 Hz, 2H, CH2), 5.12 (s, 2H, NH2), 7.42 (d, J ¼ 8.4 Hz, 2H, ArH),
7.82 (d, J ¼ 8.0 Hz, 2H, ArH). HRMS (ESI): m=z calcd. for C17H14N4, 317.0487;
found, 318.0476 (M þ 1).
2-Amino-5,6,7,8-tetrahydro-4-(3-nitrophenyl)quinoline-3-carbonitrile
1
(5ci). IR (KBr, n, cmꢁ1): 3405, 3309, 3152, 2942, 2212, 1650; H NMR (400 MHz,
CDCl3) d: 1.70–1.75 (m, 2H, CH2), 1.85–1.91 (m, 2H, CH2), 2.28–2.30 (m, 1H, CH2),
2.35–2.38 (m, 1H, CH2), 2.85–2.89 (m, 2H, CH2), 5.18 (s, 2H, NH2), 7.64 (dd,
J ¼ 0.80 Hz, 7.6 Hz, 1H, ArH), 7.72 (t, J ¼ 7.6 Hz, 1H, ArH), 8.18 (s, 1H, ArH),
8.36 (dd, J ¼ 1.2 Hz, 7.2 Hz, 1H, ArH); HRMS (ESI): m=z calcd. for C16H14N4O2,
294.1117; found, 295.1109 (M þ 1).
2-Amino-5,6,7,8-tetrahydro-4-(4-nitrophenyl)quinoline-3-carbonitrile
1
(5cj). IR (KBr, n, cmꢁ1): 3417, 3305, 3140, 2945, 2214, 1646; H NMR (400 MHz,
CDCl3) d: 1.70–1.73 (m, 2H, CH2), 1.86–1.89 (m, 2H, CH2), 2.31 (t, J ¼ 6.4 Hz, 2H,
CH2), 2.88 (t, J ¼ 6.4 Hz, 2H, CH2), 5.11 (s, 2H, NH2), 7.48 (d, J ¼ 8.8 Hz, 2H, ArH),
8.38 (d, J ¼ 8.8 Hz, 2H, ArH). HRMS (ESI): m=z calcd. for C16H14N4O2, 294.1117;
found, 295.1104 (M þ 1).
2-Amino-5,6,7,8-tetrahydro-4-p-tolylquinoline-3-carbonitrile (5ck). IR
1
(KBr, n, cmꢁ1): 3433, 3301, 3148, 2936, 2209, 1643; H NMR (400 MHz, CDCl3)
d: 1.50-1.56 (m, 2H, CH2), 1.65–1.71 (m, 2H, CH2), 2.15 (t, J ¼ 6.0 Hz, 2H, CH2),
2.32 (s, 3H, CH3), 2.64 (t, J ¼ 6.4 Hz, 2H, CH2), 6.47 (s, 2H, NH2), 7.12 (d,
J ¼ 8.0 Hz, 2H, ArH), 7.25 (d, J ¼ 8.0 Hz, 2H, ArH). HRMS (ESI): m=z calcd. for
C17H17N3, 263.1422; found, 264.1410 (M þ 1).
2-Amino-5,6,7,8-tetrahydro-4-(2-methoxyphenyl)quinoline-3-carbonitrile
1
(5cl). IR (KBr, n, cmꢁ1): 3445, 3299, 3163, 2934, 2210, 1636; H NMR (400 MHz,
CDCl3) d: 1.68–1.72 (m, 2H, CH2), 1.83–1.88 (m, 2H, CH2), 2.31 (t, J ¼ 6.0 Hz, 2H,
CH2), 2.82–2.86 (m, 2H, CH2), 3.82 (s, 3H, OCH3), 5.05 (s, 2H, NH2), 7.02–7.12 (m,
3H, ArH), 7.42–7.46 (m, 1H, ArH). HRMS (ESI): m=z calcd. for C17H17N3O,
279.1372; found, 280.1359 (M þ 1).
2-Amino-5,6,7,8-tetrahydro-4-(4-methoxyphenyl)quinoline-3-carbonitrile
(5cm). IR (KBr, n, cmꢁ1): 3464, 3296, 3145, 2946, 2206, 1638; 1H NMR (400 MHz,
CDCl3) d: 1.62–1.67 (m, 2H, CH2), 1.79–1.84 (m, 2H, CH2), 2.34 (t, J ¼ 6.0 Hz, 2H,
CH2), 2.78 (t, J ¼ 6.4 Hz, 2H, CH2), 3.83 (s, 3H, OCH3), 5.00 (s, 2H, NH2), 6.96 (d,
J ¼ 8.8 Hz, 2H, ArH), 7.17 (d, J ¼ 8.4 Hz, 2H, ArH). HRMS (ESI): m=z calcd. for
C17H17N3O, 279.1372; found, 280.1361 (M þ 1).
2-Amino-5,6,7,8-tetrahydro-4-(2,3-dimethoxyphenyl)quinoline-3-
1
carbonitrile (5cn). IR (KBr, n, cmꢁ1): 3412, 3303, 3163, 2935, 2213, 1640; H

2-AMINO-8-ARYL-TETRAHYDROQUINOLINE-3-CARBONITRILE
3013
NMR (400 MHz, CDCl3) d: 1.63–1.71 (m, 2H, CH2), 1.83–1.86 (m, 2H, CH2),
2.18–2.25 (m, 1H, CH2), 2.35–2.41 (m, 1H, CH2), 2.81–2.85 (m, 2H, CH2), 3.73 (s,
3H, OCH3), 3.94 (s, 3H, OCH3), 5.04 (s, 2H, NH2), 6.70 (dd, J ¼ 1.2 Hz, 7.6 Hz,
1H, ArH), 7.02 (d, J ¼ 0.80 Hz, 1H, ArH), 7.17 (dd, J ¼ 8.0 Hz, 8.0 Hz, 1H, ArH).
HRMS (ESI): m=z calcd. for C18H19N3O2, 309.1477; found, 310.1456 (M þ 1).
2-Amino-5,6,7,8-tetrahydro-4-(3,4-dimethoxyphenyl)quinoline-3-
1
carbonitrile (5co). IR (KBr, n, cmꢁ1): 3413, 3148, 2911, 2210, 1649; H NMR
(400 MHz, CDCl3) d: 1.57–1.67 (m, 2H, CH2), 1.78–1.84 (m, 2H, CH2), 2.36 (t,
J ¼ 6.4 Hz, 2H, CH2), 2.77 (t, J ¼ 6.4 Hz, 2H, CH2), 3.87 (s, 3H, OCH3), 3.91 (s,
3H, OCH3), 4.97 (s, 2H, NH2), 6.73 (s, 1H, ArH), 6.79–6.82 (m, 1H, ArH), 6.93
(d, J ¼ 8.8 Hz, 1H, ArH). HRMS (ESI): m=z calcd. for C18H19N3O2, 309.1477;
found, 310.1454 (M þ 1).
2-Amino-5,6,7,8-tetrahydro-4-(3,4,5-trimethoxyphenyl)quinoline-3-car-
1
bonitrile (5cp). IR (KBr, n, cmꢁ1): 3437, 3305, 3167, 2929, 2211, 1640; H NMR
(400 MHz, CDCl3) d: 1.69–1.72 (m, 2H, CH2), 1.85–1.88 (m, 2H, CH2), 2.41 (t,
J ¼ 6.0 Hz, 2H, CH2), 2.83 (t, J ¼ 6.4 Hz, 2H, CH2), 3.89 (s, 6H, OCH3), 3.93 (s,
3H, OCH3), 5.09 (s, 2H, NH2), 6.47 (s, 2H, ArH). HRMS (ESI): m=z calcd. for
C19H21N3O3, 339.1583; found, 340.1576 (M þ 1).
2-Amino-5,6,7,8-tetrahydro-4-(4-hydroxyphenyl)quinoline-3-carboni-
1
trile (5cq). IR (KBr, n, cmꢁ1): 3442, 3310, 2934, 2209, 1646; H NMR (400 MHz,
CDCl3) d: 1.58–1.60 (m, 2H, CH2), 1.72–1.74 (m, 2H, CH2), 2.25 (t, J ¼ 6.0 Hz, 2H,
CH2), 2.69 (t, J ¼ 6.4 Hz, 2H, CH2), 6.47 (s, 2H, NH2), 6.86 (d, J ¼ 8.0 Hz, 2H, ArH),
7.10 (d, J ¼ 8.0 Hz, 2H, ArH), 9.73 (s, 1H, OH). HRMS (ESI): m=z calcd. for
C16H15N3O, 265.1215; found, 266.1407 (M þ 1).
X-ray crystal data for 5ak. Empirical formula, C18H19 N3O; crystal dimen-
˚
sion, 0.53 ꢂ 0.49 ꢂ 0.48 mm; triclinic; space group, Pꢁ1; a ¼ 7.0294 (15) A,
ꢀ
ꢀ
˚
˚
b ¼ 9.6048 (15) A, c ¼ 12.397 (2) A; a ¼ 81.064 (2) , b ¼ 86.281 (3) , c ¼ 72.817
3
3
ꢀ
˚
˚
(2) ; V ¼ 2789.8 (3) A ; Mr ¼ 293.36; Z ¼ 2; Dc ¼ 1.234 Mg=m ; k ¼ 0.71073 A;
m ¼ (Mo Ka) ¼ 0.079 mmꢁ1; F(000) ¼ 312; R1 ¼ 0.0534, wR2 ¼ 0.1342. Crystallo-
graphic data for the structure of 5ak reported in this article have been deposited with
the Cambridge Crystallographic Data Center as supplementary publication no.
CCDC-702027.
X-ray crystal data for 5ba. Empirical formula, C23H21N3O; crystal dimen-
˚
sion, 0.56 ꢂ 0.41 ꢂ 0.30 mm; triclinic; space group, Pꢁ1; a ¼ 9.7174 (11) A,
ꢀ
ꢀ
˚
˚
b ¼ 10.2425 (14) A, c ¼ 10.9758 (17) A; a ¼ 99.592 (2) , b ¼ 97.845 (2) (3) ,
c ¼ 116.399 (3)ꢀ; V ¼ 937.0 (2) A ; Mr ¼ 355.43; Z ¼ 2; Dc ¼ 1.260 Mg=m3;
3
˚
Ka) ¼ 0.079 mmꢁ1
;
F(000) ¼ 736;
R1 ¼ 0.1170,
˚
k ¼ 0.71073 A;
m ¼ (Mo
wR2 ¼ 0.1693. Crystallographic data for the structure of 5ba reported in this article
have been deposited with the Cambridge Crystallographic Data Center as sup-
plementary publication no. CCDC-702028.
X-ray crystal data for 5ck. Empirical formula, C15.50 H25N2; crystal dimen-
˚
sion, 0.58 ꢂ 0.36 ꢂ 0.35 mm; monoclinic; space group, P2(1)=c; a ¼ 9.0970 (14) A,
o
o
ꢀ
˚
˚
˚
b ¼ 18.471 (2) A, c ¼ 18.665 (2) A; a ¼ 90 , b ¼ 112.212 (2) , c ¼ 90 ; V ¼ 2903.6
(7) A ; Mr ¼ 239.38; Z ¼ 8; Dc ¼ 1.095 Mg=m3; k ¼ 0.71073 A; m ¼ (Mo
3
˚

3014
Y. WAN ET AL.
Ka) ¼ 0.064 mmꢁ1; F(000) ¼ 1056; R1 ¼ 0.0553, wR2 ¼ 0.1275. Crystallographic data
for the structure of 5ck reported in this article have been deposited with the
Cambridge Crystallographic Data Center as supplementary publication no. CCDC-
702029.
CONCLUSION
In summary, we have developed a useful method to construct N2-methyl- or
aryl-substituted 2-amino-3-cyano-4-aryl-5,6,7,8-tetrahydroquinolines from commer-
cially available starting materials in basic ionic liquid [bmim]OH. The notable fea-
tures of our method include the following: (1) During this transformation, at least
11 bonds were cleaved while 7 new bonds (two C-C single bonds, two C-C double
bonds, two C-N single bonds, and one C-N double bond) were constructed in one
pot. (2) This is a straightforward and effective pathway to afford N2-substituted
5,6,7,8-tetrahydroquinolines without any other catalysts. (3) To the best of our
knowledge, this is the first method using low-activity cyclohexanone as starting
material to synthesize the target molecule. Because of its numerous benefits, the pro-
tocol should be very useful in the synthesis of biologically active compounds. Future
effort to explore the bioactivity of products is currently under way.
ACKNOWLEDGMENTS
We are grateful to the National Natural Sciences Foundation of China (No.
20772103), Innovative Project in Xuzhou Normal University (Nos. 09YLB028 and
XSKY0907180), and the Qin Lan Project in Jiangsu Province (Nos. QL200607
and 08QLT001) for financial support.
REFERENCES
1. Orru, M. V. A.; Greef, M. Recent advances in solution-phase multicomponent method-
ology for the synthesis of heterocyclic compounds. Synthesis 2003, 1471–1499.
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