Cu-catalyzed reduction of azaarenes and nitroaromatics with diboronic acid as reductant

Article abstract of DOI:10.1016/j.tet.2018.03.014

A ligand-free copper-catalyzed reduction of azaarenes with diboronic acid as reductant in an aprotic solvent under mild conditions has been developed. Most interestingly, the nitroazaarenes could be reduced exclusively to give the corresponding amines without touching the azaarene moieties. Furthermore, the reductive amination of aromatic nitro compounds and aromatic aldehydes has also been realized. A series of hydrogenated azaarenes and secondary amines were obtained with good functional group tolerance.

Full text of DOI:10.1016/j.tet.2018.03.014

Accepted Manuscript
Cu-catalyzed reduction of azaarenes and itroaromatics with diboronic acid as
reductant
Danwei Pi, Haifeng Zhou, Yanmei Zhou, Qixing Liu, Renke He, Guanshuo Shen,
Yasuhiro Uozumi
PII:
S0040-4020(18)30257-6
10.1016/j.tet.2018.03.014
TET 29354
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 28 December 2017
Revised Date: 26 February 2018
Accepted Date: 5 March 2018
Please cite this article as: Pi D, Zhou H, Zhou Y, Liu Q, He R, Shen G, Uozumi Y, Cu-catalyzed
reduction of azaarenes and itroaromatics with diboronic acid as reductant, Tetrahedron (2018), doi:
10.1016/j.tet.2018.03.014.
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ACCEPTED MANUSCRIPT
Graphical Abstract

ACCEPTED MANUSCRIPT
Cu-Catalyzed Reduction of Azaarenes and Nitroaromatics with
Diboronic Acid as Reductant
Danwei Pi,a Haifeng Zhou,*,a Yanmei Zhou,a Qixing Liu,a Renke He,a Guanshuo Shen, a,b and
Yasuhiro Uozumi*,a,b
a Research Center of Green Pharmaceutical Technology and Process, Hubei Key Laboratory of
Natural Products Research and Development, College of Biological and Pharmaceutical Sciences,
China Three Gorges University, Yichang 443002, China.
b Institute for Molecular Science, Myodaiji, Okazaki 444-8787, Japan.
Corresponding author:
E-mail: zhouhf@ctgu.edu.cn
E-mail:uo@ims.ac.jp
Abstract: A ligand-free copper-catalyzed reduction of azaarenes with diboronic acid as reductant
in an aprotic solvent under mild conditions has been developed. Most interestingly, the
nitroazaarenes could be reduced exclusively to give the corresponding amines without touching
the azaarene moieties. Furthermore, the reductive amination of aromatic nitro compounds and
aromatic aldehydes has also been realized. A series of hydrogenated azaarenes and secondary
amines were obtained with good functional group tolerance.
Keywords: Reduction; Homogeneous catalysis; Nitrogen heterocycles; Quinolines; Amination;
Aldehydes; Diboronic acid; Copper
1. Introduction
1,2,3,4-Tetrahydroquinolines and related N-heterocycles are important moieties in fine
chemicals, pharmaceuticals, agrochemicals, dyes, fragrances, and hydrogen-storage materials.1
The reduction of readily available quinolines using stoichiometric metal hydrides or reactive
metals as classic reductants is a straightforward method for preparing such compounds.2 In recent
decades, various catalytic hydrogenations and transfer hydrogenations under homogeneous or
heterogeneous conditions have also been developed.3–5 Aromatic amines are important
intermediates in the synthesis of many nitrogen-containing pharmaceuticals, agrochemicals,
bioactive compounds, dyes, and polymers.6 The reduction of nitro compounds is one of the
common and simple routes to prepare amines. Since the discovery of Béchamp reduction, a classic
process that generates much metallic waste,7 numerous efforts have been focused on exploring
new and efficient catalysts and reductants, as well as on developing simple and green procedures.8
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However, the reported methods have several drawbacks, such as a lack of chemoselectivity, the
need to handle flammable hydrogen gas, the use of relatively expensive metal catalysts, harsh
conditions. Given these facts, it is highly desirable to develop novel, efficient, and practical
methods for preparing 1,2,3,4-tetrahydroquinolines and related compounds.
Diboron reagents were initially used as borylation agents for preparing organoboron
compounds.9 In 2016, the diboronic acid [B2(OH)4]-mediated, Pd-catalyzed, transfer
hydrogenation of unsaturated carbon–carbon bonds with water as a hydrogen donor was
realized.10 Subsequently, the Cu–dipinacolborane (B2pin2)-catalyzed chemoselective reduction of
carbon–carbon double or triple bonds to C–C single bonds in α,β-unsaturated ketones was
developed.11 More recently, the reduction of aromatic nitro compounds to aromatic amines
mediated by diboron reagents has also been reported.12 Subsequently, Xuan and Song developed a
Pd/B2pin2-catalyzed reduction of N-heteroaromatics with water as a hydrogen donor.13 Moreover,
a B2(OH)4-promoted reduction of N-heteroaromatics with water as both solvent and hydrogen
donor under metal-free conditions has also achieved.14 In addition, several reductive tandem
reactions with diboron reagents have also been reported.15 Lately, we reported a palladium-
catalyzed chemoselective reduction and reductive amination of nitroarenes with water as a
hydrogen source mediated by diboronic acid.12b A one-pot synthesis of tetrahydroquinoxalines
from readily available 2-amino(nitro)anilines and 1,2-dicarbonyl compounds mediated by
diboronic acid with water as both a solvent and a hydrogen donor has also been reported by us.14b
However, the noble metal palladium and excess amount of diboronic acid (8 equiv) were
necessary in the above two cases. To continue our interest in using diboron reagents as a mediator
for transfer hydrogen, we developed a Cu-catalyzed reduction of azaarenes and nitro aromatic
compounds with B2(OH)4 as a reductant under mild conditions. Most interestingly, the
nitroazaarenes can be reduced exclusively to the corresponding amine, with the azaarene
remaining intact (Scheme 1).
R
? NO2
R
Cu(OAc)2 (5 mol %)
B2(OH)4 (3 equiv.)
N
H
R
N
MeCN, 40 oC
HN
R = NO2
ArCHO
Ar
N
Scheme 1.Cu-Catalyzed Chemoselective Reduction of Azaarenes and Nitro Groups
2. Results and discussion
Initially, we selected the reduction of quinoline (1a) as a model reaction to optimize the
reaction parameters. First, the reaction was performed with 3.0 equivalents of B2(OH)4 as
reductant in acetonitrile at 40 °C for 24 hours, but no reaction was observed (Table 1, entry 1).
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Table 1. Optimization of the Reaction Conditions a
Entry
1
2
3
4
5
6
7
8
Catalyst
–
Pd/C
Pd(OAc)2
Fe(OAc)2
Zn(OAc)2
AgOAc
Cu(OAc)2
Cu(OTf)2
CuF2
Reductant (equiv)
B2(OH)4 (3)
B2(OH)4 (3)
B2(OH)4 (3)
B2(OH)4 (3)
B2(OH)4 (3)
B2(OH)4 (3)
B2(OH)4 (3)
B2(OH)4 (3)
B2(OH)4 (3)
B2(OH)4 (3)
B2(OH)4 (3)
B2(OH)4 (3)
B2(OH)4 (3)
B2(OH)4 (3)
B2(OH)4 (2.5)
NaBH4 (3)
Solvent Time (h)
Yield (%)b
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
toluene
EtOAc
THF
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
8
0
27
32
0
0
0
98
71
9
33
29
75
67
61
92
0
9
10
11
12
13
14c
15
16
17
18
19
20
21
22
23
24
25
26
27
28
CuCl2
CuBr2
CuCl
CuI
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
B(OH)3 (3)
B2pin2 (3)
0
0
0
B2(cat)2 (3)
B2(OH)4 (3)
B2(OH)4 (3)
B2(OH)4 (3)
B2(OH)4 (3)
B2(OH)4 (3)
B2(OH)4 (3)
B2(OH)4 (3)
B2(OH)4 (3)
B2(OH)4 (3)
98
78
13
12
45
7
60
82
23
6
8
8
8
CH2Cl2
DMF
8
8
MeOH
H2O
8
8
aReaction conditions: quinoline (1a; 0.5 mmol), catalyst (5 mol %), reductant (3.0 equiv), solvent
b
c
(2 mL), 40 °C; Determined by GC analysis with an internal standard (mesitylene). 2 mol %
Cu(OAc)2 was used.
And then we tested various metal catalysts [Pd/C, Pd(OAc)2, Fe(OAc)2, Zn(OAc)2, AgOAc, and
Cu(OAc)2] (entries 2–7), and we found that Cu(OAc)2 gave 1,2,3,4-tetrahydroquinoline (2a) in
98% yield (entry 7). Other copper salts [Cu(OTf)2, CuF2, CuCl2, CuBr2, CuCl, and CuI] were also
screened, but relatively lower yields were obtained (entries 8–13). Next, we examined the effects
of the catalyst loading and the amount of reductant. The yield of 2a decreased to 61% when 2
mol % of Cu(OAc)2 was used (entry 14). When the amount of B2(OH)4 was reduced to 2.5
equivalents, a 92% yield of 2a was obtained (entry 15). Other boron reagents [NaBH4, B(OH)3,
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B2pin2, and B2(cat)2] were examined, but no reaction took place (entries 16–19). The yield of 2a
remained unchanged when the reaction time was reduced to 8 hours (entry 20). Other aprotic
solvents [toluene, EtOAc, tetrahydrofuran (THF), CH2Cl2, and N,N-dimethylformamide (DMF)]
were screened, but moderate yields were obtained in each case (entries 22–26). The reaction also
proceeded smoothly in methanol, giving an 82% yield (entry 27), whereas a lower yield was
obtained in water (entry 28). Finally, 5 mol % Cu(OAc)2, 3 equivalents of B2(OH)4, 2 mL of
MeCN, 40 °C, and 8 hours were selected as the optimal reaction conditions.
Scheme 1. Scope of Azaarenes.
Cu(OAc)2 (5 mol %)
B2(OH)4 (3 equiv.)
R
R
MeCN, 40 oC, 8 h
N
N
H
1a-v
2a-v
Me
Me
Me
N
H
N
Me
N
H
N
H
N
H
N
H
Me
H
Me
2e
2a
2b
: 92%
: 98%
2c
: 88%
2d
: 90%
2f
: 95%
: 97%
Br
MeO
Cl
N
N
N
H
Ph
N
H
Me
N
N
H
H
H
H
OMe
NO2
a
2h
: 92%
2g
: 96%
2i
: 91%
2l
: 84%
2k
2j
: 84%
: 0%
S
N
H
N
N
N
H
N
H
H
H
Me
Cl
OMe
F
a
a
a
a
a
2p
: 89%
2q
: 82%
2m
2n
: 92%
: 85%
2o
: 87%
H
N
H
N
N
H
N
H
N
H
Me
NH HN
N
H
Ph
a
a
a
2r
: 78%
2u
: 90%
2t
: 85%
2v: 93%
2s
: 72%
Reaction conditions: azaarene (0.5 mmol), Cu(OAc)2 (5 mol %), B2(OH)4 (3.0 equiv), MeCN (2
mL), 40 °C, 8 h. a80 °C, 12 h.
With the optimal reaction conditions in hand, we investigated the scope of azaarene (Scheme 2).
The reduction of electron-rich methyl-substituted quinolines 1b–g and methoxy-substituted
quinolines 1h–i proceeded smoothly to give the corresponding products 2b–i in 88–97% yield,
whereas electron-deficient quinolines gave relatively lower yields. For example, 6-chloro-1,2,3,4-
tetrahydroquinoline (2j) was isolated in 84% yield. None of the desired product was obtained from
8-nitroquinoline (1k). The 2-arylquinolines 1l–p also underwent this transformation, affording the
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corresponding products 2l–p in 84–92% yield at 80 °C for 12 hours. 2-(2-Thienyl)quinoline (1q)
was converted into the corresponding tetrahydroquinoline 2q in 82% yield. Polycyclic
heteroaromatics acridine (1r) and benzo[h]quinoline (1s) similarly gave the corresponding
products 2r and 2s in 78% and 72% yield, respectively. In addition, both the pyridine rings of
1,10-phenanthroline (1t) were reduced to give 1,2,3,4,7,8,9,10-octahydro-1,10-phenanthroline (2t)
in 85% yield. However, no reaction occurred when pyridine was used as a substrate. Furthermore,
the quinoxalines 1u and 1v also underwent the reduction to give the corresponding
tetrahydroquinoxalines 2u and 2v in 90% and 93% yield, respectively.
To our surprise, when we conducted the reduction of 8-nitroquinoline (1k) in the presence of
5 mol % of Cu(OAc)2 with three equivalents of B2(OH)4 as reductant in MeCN at 40 °C for 24
hours, the product 2k and 5 were not detected. Instead, the nitro group of 1k was reduced
exclusively to give quinolin-8-amine (4a) in 60% yield (Table 2, entry 1). The product 2k and 5
were still not observed even if raising the temperature and increasing the amount of B2(OH)4
(entries 2–5). Very interestingly, 1k could be reduced to compound 5 in 78% yield in the absence
of Cu(OAc)2, without detecting selective hydrogenated products 4a and 2k (entry 6).
Table 2. Chemoselective Reduction of 8-Nitroquinoline a
Entry
1
2
3
4
5
B2(OH)4 (equiv)
Temp (°C)
4a (%)
60
73
87
89
2k (%)
5 (%)
0
0
0
0
3
3
3
5
10
5
40
60
80
80
80
80
0
0
0
0
0
0
90
0
0
78
6b
aReaction conditions: 8-nitroquinoline (1k; 0.5 mmol), Cu(OAc)2 (5 mol %), B2(OH)4, MeCN (2
mL), 24 h; bIn the absence of Cu(OAc)2, water was used as solvent instead of MeCN.
As shown in Scheme 2, several control experiments were conducted. When 4a was used as a
substrate under the optimized reaction conditions, no reaction occurred and the starting material
remained intact. Moreover, when an equimolar mixture of quinoline (1a) and 8-nitroquinoline (1k)
was subjected to the reaction, product 4a was obtained in 83% yield, whereas 1,2,3,4-
tetrahydroquinoline (2a) was not detected. This showed that the nitro group was reduced
preferentially to the quinoline, and that nitro or amino compounds might poison Cu-catalyzed
quinoline reduction.
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Scheme 2. Control Experiments.
Reaction conditions: Cu(OAc)2 (5 mol %), B2(OH)4 (3 equiv), 80 °C, CH3CN (2 mL), 24 h.
To further demonstrate the chemoselective reduction of nitro groups in the presence of N-
heteroaromatics, we examined the reduction of the nitroquinolines 3b–d and 5-nitroisoquinoline
(3e) (Scheme 3). The nitro groups were reduced exclusively to give corresponding amines 4b–e in
73–90% yield. We then evaluated other nitroarenes. The nitrobenzenes 3f–h bearing a reducible
cyano group at various positions were selectively reduced to the corresponding amines 4f–h in
70–80% yield with the cyano group intact. The bromo(nitro)benzenes 3i and 3j were similarly
reduced to afford amines 4i and 4j, respectively, without debromination. Furthermore, the
nitrobenzenes 3k–p containing carbonyl, carboxy, ester, or amide groups were converted into the
corresponding amines 4k–p in 52–75% yield.
Scheme 3. Scope of Nitroaromatics
Reaction conditions: nitroarene (0.5 mmol), Cu(OAc)2 (5 mol %), B2(OH)4 (3.0 equiv), MeCN (2
mL), 80 °C, 24 h.
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Inspired by a reported preparation of N-alkylanilines via one-pot reduction of the corresponding
16
nitrobenzenes followed by reductive amination in the presence of Pd/B10H14 and our previous
work,12b,14b we attempted the reductive amination of aldehydes with nitroarenes in the presence of
the Cu(OAc)2/B2(OH)4 system (Scheme 4). When 8-nitroquinoline was treated with various
aromatic aldehydes 6a–f, the corresponding secondary amines 7a–f were obtained in 64–82%
yield. 2-Methyl-8-nitroquinoline, 2-nitrobenzonitrile, and 4-nitroacetophenone were also subjected
to this reductive amination with benzaldehyde (6a), giving the desired products 7g–i in 59–73%
yield.
Scheme 4. Scope of the Reductive Amination
Reaction conditions: nitroarene 3 (0.5 mmol), aldehyde 6 (0.6 mmol), Cu(OAc)2 (5 mol %),
B2(OH)4 (5 equiv), CH3CN (3.0 mL), 80 oC, 24 h.
In relation to the mechanism of the reduction of quinolines, we propose a plausible reaction
pathway shown in Scheme 5.13,14 Initially, transmetalation between Cu(OAc)2 and B2(OH)4 forms
the active catalytic species A in situ. Quinoline (1a) coordinates to A to give complex B, which
eliminates metaboric acid (O=BOH) to afford intermediate C. This isomerizes to intermediate D,
which, with the aid of B2(OH)4, is converted into enamine E with regeneration of the active
catalytic species A. The imine F is formed by isomerization of enamine E. The C=N bond of
imine F is reduced by a similar catalytic cycle to give intermediate I with regeneration of the
active catalytic species A. Finally, the tetrahydroquinoline (2a) is released through aqueous
workup.
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3. Conclusion
We have developed a novel, ligand-free, copper-catalyzed, chemoselective reduction of
azaarenes with diboronic acid as reductant in an aprotic solvent under mild conditions. It is
interesting to note that the nitro group of nitroazaarenes was reduced exclusively to afford various
amines. In addition, the reductive amination of aldehydes with nitroarenes to give secondary
amines in a one-pot process was also achieved.
Scheme 5. A Proposed Reaction Pathway for the Reduction of Quinoline
4. Experimental Section
4.1 General information
All reagents and solvents were purchased from commercial suppliers and used without further
purification. Gas chromatography was performed with a FULI GC9790II gas chromatograph
equipped with a 30 m capillary column. All products were isolated by column chromatography on
silica gel (300–400 mesh) with petroleum ether (PE; bp 60–90 °C) and EtOAc as eluents. All
1
compounds were characterized by means of H NMR (400 MHz), and 13C NMR (100 MHz)
spectroscopy with a Bruker 400 MHz instrument. Melting points were determined on an X-4
apparatus.
Typical Procedure for the synthesis of 1,2,3,4-Tetrahydroquinoline (2a)
A 20 mL Schlenk tube was charged with quinoline (1a; 65 mg, 0.5 mmol), Cu(OAc)2 (4.5 mg,
0.025 mmol), B2(OH)4 (135 mg, 1.5 mmol), and MeCN (2.0 mL). The mixture was stirred at
40 °C for 8 h until the reaction was completed (TLC), then cooled to room temperature and
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concentrated under reduced pressure. Water (10 mL) was added and the mixture was extracted
with EtOAc (3 × 10 mL). The organic phases were combined, dried over anhydrous Na2SO4,
filtered, and concentrated under reduced pressure. The residue was purified by column
chromatography with petroleum ether/ethyl acetate (8:1) as an eluent to give a brown liquid (2a:
65 mg, 98%yield).
Typical Procedure for the synthesis of 8-Aminoquinoline (4a)
A 20 mL Schlenk tube was charged with 8-nitroquinoline (1k; 87 mg, 0.5 mmol), Cu(OAc)2
(4.5 mg, 0.025 mmol), B2(OH)4 (135 mg, 1.5 mmol), and MeCN (2.0 mL). The mixture was
stirred at 80 °C for 24 h, then cooled to room temperature and concentrated under reduced
pressure. Similar workup to 2a gave a brown solid (4a: 63 mg, 87% yield).
Typical Procedure for the synthesis of N-Benzylquinolin-8-amine (7a)
A 20 mL Schlenk tube was charged with 8-nitroquinoline (1k; 87 mg, 0.5 mmol), benzaldehyde
(6a; 64 mg, 0.6 mmol), Cu(OAc)2 (4.5 mg, 0.025 mmol), B2(OH)4 (225 mg, 2.5 mmol), and
MeCN (3.0 mL). The mixture was stirred at 80 °C for 24 h until the reaction was completed
(TLC), then cooled to room temperature and concentrated under reduced pressure. Similar workup
to 2a gave a yellow solid (7a: 96 mg, 82% yield).
1
1,2,3,4-Tetrahydroquinoline (2a)4i: Brown liquid; H NMR (400 MHz, CDCl3): δ = 1.94–1.99
(m, 2H, CH2), 2.79 (t, J = 6.4 Hz, 2H, CH2), 3.32 (t, J = 5.6 Hz, 2H, CH2), 6.49 (d, J = 7.6 Hz, 1H,
Ar–H), 6.61–6.65 (m, 1H, Ar–H), 6.97–7.01(m, 2H, Ar–H) ppm; 13C NMR (100 MHz, CDCl3): δ
= 22.22, 27.02, 42.03, 114.25, 116.98, 121.50, 126.78, 129.58, 144.83 ppm.
2-Methyl-1,2,3,4-tetrahydroquinoline (2b)4i: Colorless liquid; 1H NMR (400 MHz, CDCl3): δ =
1.28 (d, J = 6.0 Hz, 3H, CH3), 1.65–1.72 (m, 1H), 1.97–2.03 (m, 1H), 2.77–2.95 (m, 2H, CH2),
3.44–3.49 (m, 1H, CH), 3.67 (s, br, 1H), 6.54 (d, J = 8.0 Hz, 1H, Ar–H), 6.68–6.72 (m, 1H, Ar–H),
7.03–7.07 (m, 2H, Ar–H) ppm; 13C NMR (100 MHz, CDCl3): δ = 22.75, 26.74, 30.25, 47.26,
114.15, 117.08, 121.20, 126.82, 129.40, 144.91 ppm.
1
3-Methyl-1,2,3,4-tetrahydroquinoline (2c)4i: Brown liquid; H NMR (400 MHz, CDCl3): δ =
1.12 (d, J = 6.4 Hz, 3H, CH3), 2.11–2.15 (m, 1H), 2.51 (dd, J1 = 16.0 Hz, J2 = 10.4 Hz, 1H), 2.83
(dd, J1 = 4.8 Hz, J2 = 2.0 Hz, 1H), 2.87 (dd, J1 = 4.8 Hz, J2 = 2.0 Hz, 1H), 2.96 (dd, J1 = 10.8 Hz,
J2 = 9.6 Hz, 1H), 3.31-3.35 (m, 1H), 6.55 (d, J = 8.0 Hz, 1H, Ar–H), 6.66–6.70 (m, 1H, Ar–H),
7.01–7.06 (m, 2H, Ar–H) ppm; 13C NMR (100 MHz, CDCl3): δ = 19.01, 27.24, 35.53, 48.90,
113.94, 116.98, 121.17, 126.75, 129.58, 144.34 ppm.
1
4-Methyl-1,2,3,4-tetrahydroquinoline (2d)4i: Brown liquid; H NMR (400 MHz, CDCl3): δ =
1.36 (d, J = 6.8 Hz, 3H, CH3), 1.73–1.77 (m, 1H), 2.02–2.07 (m, 1H), 2.96–2.99 (m, 1H, CH3),
3.31–3.41 (m, 2H, CH2), 6.54 (dd, J1 = 8.0 Hz, J2 = 1.2 Hz, 1H, Ar–H), 6.68–6.72 (m, 1H, Ar–H),
7.01–7.05 (m, 1H, Ar–H), 7.13 (d, J = 7.6 Hz, 1H, Ar–H) ppm; 13C NMR (100 MHz, CDCl3): δ =
22.74, 29.90, 30.27, 39.04, 114.22, 116.99, 126.65, 126.78, 128.51, 144.30 ppm.
1
8-Methyl-1,2,3,4-tetrahydroquinoline (2e)4i: Brown liquid; H NMR (400 MHz, CDCl3): δ =
2.00–2.06 (m, 2H), 2.17 (s, 3H, CH3), 2.88 (t, J = 6.4 Hz, 2H), 3.46 (t, J = 5.6 Hz, 2H), 6.65 (t, J =
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7.2 Hz, 1H), 6.95 (dd, J1 = 10.0 Hz, J2 = 8.0 Hz, 2H) ppm; 13C NMR (100 MHz, CDCl3): δ =
17.21, 22.23, 27.36, 42.41, 116.46, 120.92, 121.24, 127.44, 127.91, 142.76 ppm.
1
2,6-Dimethyl-1,2,3,4-tetrahydroquinoline (2f)4i: Yellow liquid; H NMR (400 MHz, CDCl3): δ
= 1.27 (d, J = 6.0 Hz, 3H, CH3), 1.62–1.68 (m, 1H), 1.96–2.01 (m, 1H), 2.28 (s, 3H, Ar–CH3),
2.74–2.89 (m, 2H), 3.39–3.45 (m, 2H), 6.48 (d, J = 8.4 Hz, 1H, Ar–H), 6.85–6.87 (m, 2H, Ar–H)
ppm; 13C NMR (100 MHz, CDCl3): δ = 20.49, 22.66, 26.65, 30.40, 47.37, 114.34, 121.31, 126.34,
127.27, 129.89, 142.48 ppm.
6-Bromo-2-methyl-1,2,3,4-tetrahydroquinoline (2g)4i: Colorless oil; 1H NMR (400 MHz,
CDCl3): δ = 1.24 (d, J = 6.0 Hz, 3H, CH3), 1.57–1.62 (m, 1H), 1.93–1.98 (m, 1H), 2.74–2.90 (m,
2H), 3.39–3.44 (m, 1H), 6.38 (d, J = 8.4 Hz, 1H, Ar–H), 7.06–7.12 (m, 2H, Ar–H) ppm; 13C NMR
(100 MHz, CDCl3): δ = 22.53, 26.47, 29.65, 47.12, 108.28, 115.42, 123.16, 129.35, 131.70,
143.80 ppm.
1
6-Methoxy-1,2,3,4-tetrahydroquinoline (2h)4j: Colorless oil; H NMR (400 MHz, CDCl3): δ =
1.90–1.96 (m, 2H, CH2), 2.74–2.77 (m, 2H, CH2), 3.24–3.27 (m, 2H, CH2), 3.73 (s, 3H, OCH3),
6.45 (d, J = 8.4 Hz, 1H, Ar–H), 6.56–6.61 (m, 2H, Ar–H) ppm; 13C NMR (100 MHz, CDCl3): δ =
22.47, 27.02, 42.38, 55.84, 112.91, 114.89, 115.63, 122.93, 138.90, 151.84 ppm.
1
8-Methoxy-1,2,3,4-tetrahydroquinoline (2i):18 Colorless oil; H NMR (400 MHz, CDCl3): δ =
1.98–2.04 (m, 2H, CH2), 2.83 (t, J = 6.4 Hz, 2H, CH2), 3.37–3.40 (m, 2H, CH2), 3.87 (s, 3H,
OCH3), 6.63–6.68 (m, 3H, Ar–H) ppm; 13C NMR (100 MHz, CDCl3): δ = 22.08, 26.67, 41.55,
55.43, 107.42, 115.94, 121.60, 121.73, 134.31, 146.41 ppm.
1
6-Chloro-1,2,3,4-tetrahydroquinoline (2j)4j: Brown liquid; H NMR (400 MHz, CDCl3): δ =
1.93–1.99 (m, 2H, CH2), 2.76 (t, J = 6.4 Hz, 2H, CH2), 3.32 (t, J = 5.6 Hz, 2H, CH2), 6.43 (d, J =
8.4 Hz, 1H, Ar–H), 6.93–6.96 (m, 2H, Ar–H) ppm; 13C NMR (100 MHz, CDCl3): δ = 21.74,
26.86, 41.88, 115.21, 121.35, 122.99, 126.53, 129.06, 143.12 ppm.
1
2-Phenyl-1,2,3,4-tetrahydroquinoline (2l)4i: Brown liquid; H NMR (400 MHz, CDCl3): δ =
2.09–2.15 (m, 1H), 2.21–2.25 (m, 1H), 2.82–2.88 (m, 1H), 2.99–3.03 (m, 1H), 4.13 (br, 1H), 4.53
(dd, J1 = 9.2 Hz, J2 = 3.2 Hz, 1H, CH2), 6.64 (d, J = 7.6 Hz, 1H, Ar–H), 6.75–6.79 (m, 1H, Ar–H),
7.11–7.14 (m, 2H, Ar–H), 7.40–7.52 (m, 5H, Ar–H) ppm; 13C NMR (100 MHz, CDCl3): δ = 26.48,
31.09, 56.33, 114.09, 117.25, 120.96, 126.66, 127.01, 127.55, 128.68, 129.41, 144.83, 144.92 ppm.
2-(p-Tolyl)-1,2,3,4-tetrahydroquinoline (2m)18: Yellow liquid; 1H NMR (400 MHz, CDCl3): δ =
2.04–2.10 (m, 1H), 2.12–2.17 (m, 1H), 2.43 (s, 3H, CH3), 2.79–2.84 (m, 1H), 2.96–3.00 (m, 1H),
4.47 (dd, J1 = 9.6 Hz, J2 = 3.2 Hz, 1H, CH), 6.58–6.61 (m, 1H, Ar–H), 6.70–6.74 (m, 1H, Ar–H),
7.06–7.10 (m, 2H, Ar–H), 7.24 (d, J = 8.0 Hz, 2H, Ar–H), 7.36 (d, J = 8.0 Hz, 2H, Ar–H) ppm;
13C NMR (100 MHz, CDCl3): δ = 21.16, 26.54, 31.08, 56.07, 114.00, 117.13, 120.93, 126.51,
126.92, 129.29, 129.33, 137.13, 141.89, 144.86 ppm.
2-(4-Methoxyphenyl)-1,2,3,4-tetrahydroquinoline (2n)17a: Pale yellow oil; 1H NMR (400 MHz,
CDCl3): δ = 2.02–2.04 (m, 1H), 2.10–2.13 (m, 1H), 2.77–2.82 (m, 1H), 2.93–2.97 (m, 1H), 3.86 (s,
3H, OCH3), 4.43 (dd, J1 = 9.2 Hz, J2 = 3.2 Hz, 1H, CH), 6.58 (d, J = 0.8 Hz, 1H, Ar–H), 6.67–
10

ACCEPTED MANUSCRIPT
6.71 (m, 1H, Ar–H), 6.92–6.95 (m, 2H, Ar–H), 7.03–7.06 (m, 2H, Ar–H), 7.34–7.37 (m, 2H, Ar–
H) ppm; 13C NMR (100 MHz, CDCl3): δ = 26.58, 31.12, 55.35, 55.75, 113.94, 113.98, 117.13,
120.90, 126.88, 127.65, 129.31, 136.91, 144.85, 158.98 ppm.
1
2-(4-Fluorophenyl)-1,2,3,4-tetrahydroquinoline (2o)17a: Colorless oil; H NMR (400 MHz,
CDCl3): δ = 1.99–2.06 (m, 1H), 2.11–2.17 (m, 1H), 2.75–2.82 (m, 1H), 2.94–3.02 (m, 1H), 4.07
(br, 1H), 4.48 (dd, J1 = 9.6 Hz, J2 = 3.2 Hz, 1H, CH), 6.60 (d, J = 8.0 Hz, 1H, Ar–H), 6.72 (t, J =
7.2 Hz, 1H, Ar–H), 7.05–7.11 (m, 4H, Ar–H), 7.39–7.41 (m, 2H, Ar–H) ppm; 13C NMR (100
MHz, CDCl3): δ = 26.34, 31.18, 55.64, 114.09, 115.27, 115.48, 117.39, 120.85, 126.98, 128.07,
128.15, 129.36, 140.53, 144.59, 160.93, 163.37 ppm.
1
2-(4-Chlorophenyl)-1,2,3,4-tetrahydroquinoline (2p)17a: Pale yellow oil; H NMR (400 MHz,
CDCl3): δ = 1.99–2.05 (m, 1H), 2.12–2.17 (m, 1H), 2.75–2.80 (m, 1H), 2.93–2.97 (m, 1H), 4.07
(br, 1H), 4.48 (dd, J1 = 9.2 Hz, J2 = 3.6 Hz, 1H, CH), 6.60 (d, J = 7.6 Hz, 1H, Ar–H), 6.70–6.74
(m, 1H, Ar–H), 7.05–7.09 (m, 2H, Ar–H), 7.30–7.50 (m, 4H, Ar–H) ppm; 13C NMR (100 MHz,
CDCl3): δ = 26.17, 31.02, 55.63, 144.01, 144.11, 117.45, 120.83, 126.58, 126.94, 127.01, 127.47,
127.94, 128.61, 128.73, 129.36, 133.05, 143.39, 144.45 ppm.
2-(Thiophen-2-yl)-1,2,3,4-tetrahydroquinoline (2q)17a: Viscous oil; 1H NMR (400 MHz,
CDCl3): δ = 2.07–2.12 (m, 1H), 2.19–2.22 (m, 1H), 2.78–2.84 (m, 1H), 2.93–2.97 (m, 1H), 4.10 (s,
1H), 4.63 (dd, J1 = 9.2 Hz, J2 = 3.2 Hz, 1H), 6.59 (d, J = 7.6 Hz, 1H, Ar–H), 6.70–6.74 (m, 1H,
Ar–H), 7.05–7.09 (m, 2H, Ar–H), 7.16–7.17 (m, 1H, Ar–H), 7.26–7.27 (m, 1H, Ar–H), 7.36–7.37
(m, 1H, Ar–H) ppm; 13C NMR (100 MHz, CDCl3): δ = 26.24, 30.28, 52.14, 114.15, 117.38,
120.81, 120.98, 126.14, 126.17, 126.95, 129.38, 144.44, 146.14 ppm.
1
9,10-dihydroacridine (2r)4i: Yellow solid, m.p.: 152–155 °C; H NMR (400 MHz, CDCl3): δ =
4.10 (s, 2H), 6.01 (br, 1H), 6.71 (dd, J1 = 7.6 Hz, J1 = 1.2 Hz, 2H), 6.88 (dt, J1 = 7.6 Hz, J2 = 1.2
Hz, 2H), 7.11–7.16 (m, 4H) ppm; 13C NMR (100 MHz, CDCl3): δ = 31.41, 113.45, 120.05, 120.65,
127.02, 128.62, 140.12 ppm.
1,2,3,4-Tetrahydrobenzo[h]quinoline (2s)4j: Yellow oil; 1H NMR (400 MHz, CDCl3): δ = 2.07–
2.12 (m, 2H), 2.98 (t, J = 6.0 Hz, 2H), 3.54 (t, J = 5.2 Hz, 2H), 7.17–7.25 (m, 2H), 7.44–7.46 (m,
2H), 7.73–7.76 (m, 1H), 7.79–7.81 (m, 1H) ppm; 13C NMR (100 MHz, CDCl3): δ = 22.16, 27.49,
42.46, 115.87, 116.98, 119.46, 123.27, 124.79, 124.97, 128.57, 128.63, 133.05, 139.02 ppm.
1,2,3,4,7,8,9,10-Octahydro-1,10-phenanthroline (2t)12b: Yellow solid, m.p.: 69–71 °C; 1H NMR
(400 MHz, CDCl3): δ = 1.90–1.95 (m, 4H), 2.76–2.79 (m, 4H), 3.34 (s, 4H), 6.50 (s, 2H, Ar–H)
ppm; 13C NMR (100 MHz, CDCl3): δ = 22.52, 26.93, 42.65, 119.19, 120.55, 132.86 ppm.
1
2-Methyl-1,2,3,4-tetrahydroquinoxaline (2u)13: Yellow solid, m.p.: 88–90 °C; H NMR (400
MHz, CDCl3): δ = 1.23 (d, J = 6.4 Hz, 3H, CH3), 3.09 (dd, J1 = 10.8 Hz, J2 = 8.4 Hz, 1 H), 3.36
(dd, J1 = 10.8 Hz, J2 = 2.8 Hz, 1H), 3.52–3.58 (m, 3H), 6.54–6.57 (m, 2H, Ar–H), 6.63–6.66 (m,
2H, Ar–H) ppm; 13C NMR (100 MHz, CDCl3): δ = 19.96, 45.74, 48.28, 114.48, 114.53, 118.72,
133.26, 133.63 ppm.
11

ACCEPTED MANUSCRIPT
2-Phenyl-1,2,3,4-tetrahydroquinoxaline (2v)14b: Brown liquid; 1H NMR (400 MHz, CDCl3): δ =
3.35–3.40 (m, 1H), 3.51 (dd, J1 = 8.4 Hz, J2 = 3.2 Hz, 1H), 4.53 (dd, J1 = 11.2 Hz, J2 = 3.2 Hz,
1H), 6.61–6.64 (m, 2H), 6.67–6.70 (m, 2H), 7.36–7.45 (m, 5H) ppm; 13C NMR (100 MHz,
CDCl3): δ = 49.16, 54.76, 114.48, 114.82, 118.82, 119.03, 127.01, 127.92, 127.94, 128.67, 132.71,
134.19, 141.84 ppm.
Quinolin-8-amine (4a)12b: Brown solid, m.p.: 62–65 °C; 1H NMR (400 MHz, CDCl3): δ = 5.03 (s,
br, 2H), 6.98 (dd, J1 = 7.6 Hz, J2 = 1.2 Hz, 1H), 7.20 (dd, J1 = 8.4 Hz, J2 = 1.2 Hz, 1H), 7.36–7.42
(m, 2H), 8.11 (dd, J1 = 8.4 Hz, J2 = 1.6 Hz, 1H), 8.81 (dd, J1 = 4.4 Hz, J2 = 2.0 Hz, 1H) ppm; 13
C
NMR (100 MHz, CDCl3): δ = 110.08, 116.09, 121.38, 127.40, 128.87, 136.04, 138.44, 143.95,
147.48 ppm.
1
1,2,3,4-Tetrahydroquinolin-8-amine (5)14a: Brown oil; H NMR (400 MHz, CDCl3): δ = 6.55
–
6.48 (m, 3H), 3.27 (t, J = 5.2 Hz, 2H), 2.93 (brs, 3H), 2.72 (t, J = 6.4 Hz, 2H), 1.89–1.83 (m, 2H)
ppm; 13C NMR (101 MHz, CDCl3): δ = 22.63, 27.26, 42.81, 114.31, 118.28, 121.37, 123.51,
134.09, 134.13 ppm.
Quinolin-5-amine (4b)12b: Brown solid, m.p.: 106–109 °C; 1H NMR (400 MHz, CDCl3): δ = 4.26
(s, br, 2H), 6.86 (dd, J1 = 7.2 Hz, J2 = 1.2 Hz, 1H), 7.39 (dd, J1 = 8.8 Hz, J2 = 4.4 Hz, 1H), 7.53–
7.62 (m, 2H), 8.22 (d, J = 8.4 Hz, 1H), 8.92 (dd, J1 = 4.4 Hz, J2 = 1.6 Hz, 1H) ppm; 13C NMR
(100 MHz, CDCl3): δ = 110.07, 118.73, 119.65, 120.22, 129.55, 130.05, 142.24, 149.11, 150.30
ppm.
2-Methylquinolin-8-amine (4c)12b: Brown solid, m.p.: 56–58 °C; 1H NMR (400 MHz, CDCl3): δ
= 2.75 (s, 3H), 5.00 (s, br, 2H), 6.95 (dd, J1 = 7.6 Hz, J2 = 1.2 Hz, 1H), 7.15 (dd, J1 = 8.4 Hz, J2 =
1.2 Hz, 1H), 7.27–7.32 (m, 2H), 7.99 (d, J = 8.4 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3): δ =
25.27, 102.89, 110.16, 115.93, 122.18, 126.33, 126.89, 136.11, 143.38, 156.20 ppm.
1
Quinolin-6-amine (4d)12a: Grey solid, m.p.: 117–119 °C; H NMR (400 MHz, CDCl3): δ = 4.00
(s, br, 2H), 6.94 (d, J = 9.2 Hz, 1H), 7.15-7.22 (m, 1H), 7.27-7.32 (m, 1H), 7.90–7.96 (m, 2H),
8.65-8.70 (m, 1H) ppm; 13C NMR (100 MHz, CDCl3): δ = 107.46, 121.43, 121.59, 129.77, 130.59,
133.82, 143.45, 144.60, 146.90 ppm.
1
Isoquinolin-5-amine (4e)12b: Brown solid, m.p.: 127–129 °C; H NMR (400 MHz, CDCl3): δ =
4.25 (s, br, 2H), 6.99 (t, J = 4.4 Hz, 1H), 7.45 (d, J = 4.8 Hz, 2H), 7.62 (d, J = 6.0 Hz, 1H), 8.53 (d,
J = 6.0 Hz, 1H), 9.23 (s, 1H) ppm; 13C NMR (100 MHz, CDCl3): δ = 113.14, 114.10, 118.06,
126.01, 127.82, 129.41, 141.28, 142.01, 152.97 ppm.
1
2-Aminobenzonitrile (4f)12b: colorless oil; H NMR (400 MHz, CDCl3): δ = 4.46 (s, br, 2H),
6.75–6.79 (m, 2H), 7.34–7.42 (m, 2H) ppm; 13C NMR (100 MHz, CDCl3): δ = 96.00, 115.20,
117.70, 118.02, 132.39, 134.06, 149.67 ppm.
1
3-Aminobenzonitrile (4g)12a: Yellow solid, m.p.: 50–52 °C; H NMR (400 MHz, CDCl3): δ =
3.91 (s, br, 2H), 6.89–6.94 (m, 2H), 7.04–7.07 (m, 1H), 7.26 (t, J = 8.0 Hz, 1H) ppm; 13C NMR
(100 MHz, CDCl3): δ = 112.96, 117.46, 118.89, 119.21, 122.05, 130.08, 146.98 ppm.
12

ACCEPTED MANUSCRIPT
1
4-Aminobenzonitrile (4h)12b: Yellow solid, m.p.: 83–85 °C; H NMR (400 MHz, CDCl3): δ =
4.20 (s, br, 2H), 6.68 (d, J = 8.8 Hz, 2H), 7.45 (dd, J1 = 8.4 Hz, J2 = 3.6 Hz, 2H) ppm; 13C
NMR(100 MHz, CDCl3): δ = 100.11, 114.46, 120.23, 133.85, 150.47 ppm.
3-Bromoaniline (4i)12b: White solid, m.p.: 29–31 °C; 1H NMR (400 MHz, CDCl3): δ = 3.75 (s, br,
2H), 6.61–6.64 (m, 1H), 6.87–6.92 (m, 2H), 7.04 (t, J = 8.0 Hz, 1H) ppm; 13C NMR (100 MHz,
CDCl3): δ = 113.65, 117.84, 121.39, 123.07, 130.64, 147.81 ppm.
1
2,5-Dibromoaniline (4j)12b: White solid, m.p.: 53–55 °C; H NMR (400 MHz, CDCl3): δ = 4.18
(s, br, 2H), 6.77 (dd, J1 = 8.4 Hz, J2 = 2.0 Hz, 1H), 6.94 (d, J = 2.0 Hz, 1H), 7.28 (d, J = 8.4 Hz,
1H) ppm; 13C NMR (100 MHz, CDCl3): δ = 107.77, 118.12, 121.75, 122.17, 133.64, 145.30 ppm.
1
1-(4-Aminophenyl)ethanone (4k)12b: Yellow solid, m.p.: 104–106 °C; H NMR (400 MHz,
CDCl3): δ = 2.54 (s, 3H), 4.18 (s, br, 2H), 6.69 (dd, J1 = 8.8 Hz, J2 = 1.6 Hz, 2H), 7.85 (dd, J1 =
8.4 Hz, J2 = 1.6 Hz, 2H) ppm; 13C NMR (100 MHz, CDCl3): δ = 26.14, 113.74, 127.87, 130.84,
151.14, 196.55 ppm.
1
(4-Aminophenyl)(phenyl)methanone (4l)12b: Yellow solid, m.p.: 122–124 °C; H NMR (400
MHz, CDCl3): δ = 4.19 (s, br, 2H), 6.70–6.73 (m, 2H), 7.47–7.51 (m, 2H), 7.56–7.60 (m, 1H),
7.75–7.77 (m, 4H) ppm; 13C NMR (100 MHz, CDCl3): δ = 113.66, 127.46, 128.11, 129.56, 131.45,
132.98, 138.88, 150.93, 195.35 ppm.
2-Aminobenzoic acid (4m)12b: White solid, m.p.: 178–180 °C; 1H NMR (400 MHz, CDCl3): δ =
6.72 (d, J = 6.8 Hz, 2H), 7.34–7.38 (m, 1H), 7.98 (d, J = 8.0 Hz, 1H) ppm; 13C NMR (100 MHz,
CDCl3): δ = 109.59, 116.50, 116.83, 132.17, 135.15, 151.14, 173.63 ppm.
1
Methyl-2-aminobenzoate (4n) 12b: Colorless oil; H NMR (400 MHz, CDCl3): δ = 3.91 (s, 3H),
5.76 (s, br, 2H), 6.66–6.71 (m, 2H), 7.28–7.33 (m, 1H), 7.90 (dd, J1 = 8.0 Hz, J2 = 1.6 Hz, 1H)
ppm; 13C NMR (100 MHz, CDCl3): δ = 51.57, 110.76, 116.31, 116.71, 131.25, 134.14, 150.46,
168.63 ppm.
1
2-Amino-N-benzylbenzamide (4o)12b: White solid, m.p.: 117–118 °C; H NMR (400 MHz,
CDCl3): δ = 4.65 (d, J = 5.6 Hz, 2H), 5.60 (s, br, 2H), 6.38 (s, br, 1H), 6.67 (t, J = 7.6 Hz, 1H),
6.73 (d, J = 8.4 Hz, 1H), 7.23–7.27 (m, 1H), 7.34–7.40 (m, 6H) ppm; 13C NMR (100 MHz,
CDCl3): δ = 43.76, 115.80, 116.64, 117.40, 127.11, 127.61, 127.85, 128.83, 132.45, 138.28,
148.87, 169.17 ppm.
1
N-(2-Aminophenyl)acetamide (4p)12b: Colorless oil; H NMR (400 MHz, CDCl3): δ = 2.18 (s,
3H), 3.91 (s, br, 2H), 6.80–6.83 (m, 2H), 7.07–7.11 (m, 1H), 7.17 (d, J = 7.6 Hz, 1H), 7.52 (s, br,
1H) ppm; 13C NMR (100 MHz, CDCl3): δ = 23.68, 118.16, 119.54, 124.24, 125.51, 127.36,
140.96, 169.06 ppm.
N-Benzylquinolin-8-amine (7a)12b: Yellow solid, m.p.: 40–42 °C; 1H NMR (400 MHz, CDCl3): δ
= 4.62 (d, J = 5.2 Hz, 2H), 6.66 (s, br, 1H), 6.70 (d, J = 7.6 Hz, 1H), 7.11 (d, J = 8.4 Hz, 1H),
7.30–7.44 (m, 5H), 7.49–7.51 (m, 2H), 8.12 (dd, J1 = 8.4 Hz, J2 = 1.6 Hz, 1H), 8.77 (dd, J1 = 4.4
Hz, J2 = 2.0 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3): δ = 47.73, 105.16, 114.19, 121.47,
127.17, 127.45, 127.80, 128.66, 136.07, 138.24, 139.25, 144.58, 146.97 ppm.
13

ACCEPTED MANUSCRIPT
1
N-(4-(Trifluoromethyl)benzyl)quinolin-8-amine (7b)12b: Yellow solid, m.p.: 68–70 °C; H
NMR (400 MHz, CDCl3): δ = 4.68 (d, J = 6.0 Hz, 2H), 6.60 (d, J = 7.6 Hz, 1H), 6.76 (s, br, 1H),
7.14 (dd, J1 = 8.4 Hz, J2 = 0.8 Hz, 1H), 7.36 (t, J = 8.0 Hz, 1H), 7.45 (dd, J1 = 8.4 Hz, J2 = 4.0 Hz,
1H), 7.57–7.65 (m, 4H), 8.13 (dd, J1 = 8.0 Hz, J2 = 1.6 Hz, 1H), 8.80 (dd, J1 = 4.0 Hz, J2 = 1.6 Hz,
1H) ppm; 13C NMR (100 MHz, CDCl3): δ = 47.26, 105.30, 114.70, 121.60, 122.91, 125.60 (q, JF
= 3.7 Hz) 127.55 (d, JF = 27.7 Hz), 128.67, 129.56, 136.16, 138.20, 143.57, 144.16, 147.14 ppm.
N-(2-(Trifluoromethyl)benzyl)quinolin-8-amine (7c)12b: Yellow solid, m.p.: 73–75 °C; 1H NMR
(400 MHz, CDCl3): δ = 4.85 (d, J = 6.0 Hz, 2H), 6.56 (dd, J1 = 7.6 Hz, J2 = 0.8 Hz, 1H), 6.78 (t, J
= 5.6 Hz, 1H), 7.12 (dd, J1 = 8.0 Hz, J2 = 0.8 Hz, 1H), 7.51-7.33 (m, 4H), 7.73 (dd, J1 = 16.4 Hz,
J2 = 7.6 Hz, 2H), 8.13 (dd, J1 = 8.0 Hz, J2 = 1.6 Hz, 1H), 8.80 (dd, J1 = 4.0 Hz, J2 = 1.6 Hz, 1H);
13C NMR (100 MHz, CDCl3) δ = 43.89 (d, JF = 3.1 Hz), 105.22, 114.57, 121.55, 123.31, 126.02
(t, JF = 5.9 Hz), 126.95, 127.71(d, JF = 8.0 Hz), 127.97, 128.23, 128.67, 132.19, 136.13, 137.95,
138.21, 144.10, 147.11.
N-(2-Fluorobenzyl)quinolin-8-amine (7d)12b: Yellow oil; 1H NMR (400 MHz, CDCl3): δ = 4.69
(d, J = 6.0 Hz, 2H), 6.65 (s, br, 1H), 6.71 (dd, J1 = 7.2 Hz, J2 = 0.4 Hz, 1H), 7.10–7.15 (m, 3H),
7.28–7.30 (m, 1H), 7.37–7.49 (m, 3H), 8.12 (dd, J1 = 8.4 Hz, J2 = 1.6 Hz, 1H), 8.8 (s, 1H); 13C
NMR (100 MHz, CDCl3): δ = 41.12 (d, JF = 4.7 Hz), 105.12, 114.43, 115.33 (d, JF = 21.1 Hz),
121.50, 124.22 (d, JF = 3.5 Hz), 126.12 (d, JF = 14.6 Hz), 127.77, 128.71 (d, JF = 8.0 Hz), 129.23
(d, JF = 4.4 Hz), 136.10, 138.26, 144.31, 147.05, 159.76, 162.21 ppm.
1
2-((Quinolin-8-ylamino)methyl)benzonitrile (7e)12b: Yellow solid, m.p.: 112–114 °C; H NMR
(400 MHz, CDCl3): δ = 4.86 (d, J = 6.4 Hz, 2H), 6.59–6.83 (m, 1H), 6.85 (s, br, 1H), 7.14 (dd, J1
= 8.0 Hz, J2 = 0.8 Hz, 1H), 7.34–7.41 (m, 2H), 7.45 (q, J = 4.4 Hz, 1H), 7.53–7.57 (m, 1H), 7.63–
7.65 (m, 1H), 7.74 (dd, J1 = 7.6 Hz, J2 = 0.8 Hz, 1H), 8.13 (dd, J1 = 8.4 Hz, J2 = 1.6 Hz, 1H), 8.80
(dd, J1 = 4.4 Hz, J2 = 2.0 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ = 45.77, 105.35, 111.23,
114.99, 117.51, 121.64, 127.59, 127.65, 127.83, 128.65, 133.04, 133.16, 136.16, 138.20, 143.33,
143.81, 147.22 ppm.
1
N-(4-Methoxybenzyl)quinolin-8-amine (7f)12b: Brown solid, m.p.: 71–73 °C; H NMR (400
MHz, CDCl3): δ = 3.85 (s, 3H), 4.53 (d, J = 5.2 Hz, 2H), 6.56 (s, br, 1H), 6.70 (d, J = 7.6 Hz, 1H),
6.92–6.95 (m, 2H), 7.10 (dd, J1 = 8.0 Hz, J2 = 0.8 Hz, 1H), 7.37–7.43 (m, 4H), 8.11 (dd, J1 = 8.4
Hz, J2 = 1.6 Hz, 1H), 8.76 (dd, J1 = 4.0 Hz, J2 = 1.6 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3): δ
= 47.20, 55.34, 105.09, 114.03, 114.08, 121.44, 127.80, 128.65, 128.75, 131.21, 136.05, 138.23,
144.61, 146.93, 158.8 ppm.
N-Benzyl-2-methylquinolin-8-amine (7g) 12b: Yellow solid, m.p.: 60–62 °C; 1H NMR (400 MHz,
CDCl3): δ = 2.74 (s, 3H), 4.61 (d, J = 4.8 Hz, 2H), 6.69 (s, br, 1H), 7.06 (d, J1 = 8.4 Hz, J2 = 1.2
Hz, 1H), 7.28–7.38 (m, 4H), 7.40–7.42 (m, 2H), 7.48–7.50 (m, 2H), 8.00 (d, J = 8.4 Hz, 1H) ppm;
13C NMR (100 MHz, CDCl3): δ = 25.22, 47.73, 114.05, 105.23, 122.18, 126.69, 127.06, 127.39,
128.60, 136.16, 137.50, 139.55, 144.13, 155.74 ppm.
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1
2-(Benzylamino)benzonitrile (7h)12b: Yellow solid, m.p.: 118–120 °C; H NMR (400 MHz,
CDCl3): δ = 4.48 (d, J = 5.6 Hz, 2H), 5.08 (s, br, 1H), 6.68 (d, J = 8.8 Hz, 1H), 6.73 (t, J = 7.6 Hz,
1H), 7.30–7.41 (m, 6H), 7.46 (dd, J1 = 7.6 Hz, J2 = 1.2 Hz, 1H) ppm; 13C NMR (100 MHz,
CDCl3): δ = 47.48, 95.90, 111.07, 116.90, 117.97, 127.21, 127.69, 128.91, 132.80, 134.34, 137.75,
150.09 ppm.
1-(4-(Benzylamino)phenyl)ethanone (7i)12b: Yellow solid, m.p.: 84–86 °C; 1H NMR (400 MHz,
CDCl3): δ = 2.53 (s, 3H), 4.45 (d, J = 5.6 Hz, 2H), 4.66 (s, br, 1H), 6.64 (dd, J1 = 7.2 Hz, J2 = 2.0
Hz, 2H), 7.30–7.42 (m, 5H), 7.86 (d, J1 = 6.8 Hz, J2 = 1.6 Hz, 2H) ppm; 13C NMR (100 MHz,
CDCl3): δ = 26.09, 47.63, 111.63, 127.41, 127.63, 128.61, 128.86, 130.85, 138.24, 151.95, 196.47
ppm.
Acknowledgement
We are grateful for financial support from the National Natural Science Foundation of China
(21202092) and for a Startup Foundation from the China Three Gorges University (KJ2012B080,
KJ2014H008, 2016PY076).
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