Pd-Catalyzed Tandem Reaction of 2-Aminostyryl Nitriles with Arylboronic Acids: Synthesis of 2-Arylquinolines

Article abstract of DOI:10.1021/acs.joc.9b01875

A novel palladium-catalyzed protocol for the synthesis of 2-arylquinolines via tandem reaction of 2-aminostyryl nitriles with arylboronic acids has been developed with good functional group tolerance. The presented approach offers a new synthetic pathway toward the core structures of 2-arylquinolines compared to classical condensation reaction of (E)-2-aminostyryl aryl ketones. Moreover, the present synthetic route could be readily scaled up to gram quantity without difficulty. Preliminary mechanistic experiments showed that this transformation involves a nucleophilic addition of aryl palladium species to the nitrile to generate an aryl ketone intermediate followed by an intramolecular cyclization and dehydration to quinoline ring.

Full text of DOI:10.1021/acs.joc.9b01875

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Article
Pd-Catalyzed Tandem Reaction of 2-Aminostyryl Nitriles
with Arylboronic Acids: Synthesis of 2-Arylquinolines
Tong Xu, Yinlin Shao, Ling Dai, Shulin Yu, Tianxing Cheng, and Jiuxi Chen
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b01875 • Publication Date (Web): 24 Sep 2019
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Pd-Catalyzed Tandem Reaction of 2-Aminostyryl Nitriles with
Arylboronic Acids: Synthesis of 2-Arylquinolines
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Tong Xu, Yinlin Shao,* Ling Dai, Shulin Yu, Tianxing Cheng and Jiuxi Chen*
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College of Chemistry & Materials Engineering, Wenzhou University, Wenzhou 325035, China.
E-mail: shaoyl@wzu.edu.cn; jiuxichen@wzu.edu.cn
R2
N
R2
R1
Pd
CN
+
Ar
Ar
B(OH)2
Ar
R1
NH2
37 examples
Ar
up to 90% yield
ABSTRACT: A novel palladium-catalyzed protocol for the synthesis of
2-arylquinolines via tandem reaction of 2-aminostyryl nitriles with arylboronic acids
has been developed with good functional group tolerance. The presented approach
offers a new synthetic pathway toward the core structures of 2-arylquinolines
compared with classical condensation reaction of (E)-2-aminostyryl aryl ketones.
Moreover, the present synthetic route could be readily scaled up to gram quantity
without difficulty. Preliminary mechanistic experiments showed that this
transformation involves a nucleophilic addition of aryl pallidium species to the nitrile
to generate an aryl ketone intermediate followed by an intramolecular cyclization and
dehydration to quinoline ring.
_______________________________________________________________________________
INTRODUCTION
Heteroaromatic units are important structural features in bioactive small molecules,1
and quinolines are among the most highly represented heterocycles in
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pharmaceuticals and agrochemicals. In fact, the quinolines ring ranks 22rd among the
351 ring systems found in marketed drugs.2 Among the various quinoline derivatives
developed, 2-substituted quinolines are particularly important, as they are not only
associated with a wide range of biological properties such as antimalarial and
antitumor activity3 but are also used as key building in the preparation of functional
materials with improved physical properties.4 The importance of 2-substituted
quinolines as synthetic targets has stimulated the development of numerous useful
methods.5 Traditionally, quinolines are synthesized through condensation of anilines
with suitable coupling reagent in the presence of acid or base promoter, viz. Knorr,
Friedländer, Skraup reaction and etc.6 Recently, these methods were replaced by
transition-metal-catalyzed annulation of aniline derivatives and have proved to be an
efficient strategy for quinoline synthesis.7
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Among possible approaches, the dehydrative cyclization of 2-aminostyryl ketone
derivatives is an attractive strategy for the construction of 2-substituted quinolines.
However, the amino group cannot approach the carbonyl group to undergo the
condensation reaction because of the steric configuration (Scheme 1a). A careful
literature screening reveals that there are many successful strategies involving the
change of unreactive (E)-2-aminostyryl ketones into the unstable but reactive
(Z)-configuration intermediate to undergo dehydrative cyclization reaction by using
either photoisomerization,8a-b catalytic TBAI,8c simple benzylamine,8d stoichiometric
amount of I2,8e PhSeCl in the presence of a base,8f or a strong acid under reflux
conditions.8g It should be pointed out that for the synthesis of 2-arylquinolines used
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not only dehydrative cyclization of 2-aminostryl ketones but also other methods. For
example, Mamedov group reported аn efficient sodium dithionite (Na2S2O4)-mediated
method for construction of 2-arylquinolines via in situ Meinwald
rearrangement/intramolecular reductive cyclization of o-nitrobenzalacetophenone
oxides (Scheme 1b).9 This practical approach is of excellent functional group
compatibility with as high as 98% yield under mild reaction conditions from easily
available reagents. Despite these contributions, new approaches for accessing this
type of reaction still holds its relevance for broader substrates scope and simple
operation.
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Scheme 1. New Strategy for the Synthesis of 2-Arylquinolines
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a) Synthesis of quinolines via dehydrative cyclization of 2-aminostyryl ketone
O
direct intramolecular
dehydrative cyclization
R1
R
R
X
ref. 8
N
R1
NH2
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configurational
change
dehydrative
cyclization
√
R1
R
O
NH2
b) An efficient sodium dithionite-mediated method for construction of 2-arylquinolines
O
O
R
OH
Ar
Na2S2O4
R
Ar
up to 98% yield
N
NO2
Ref. 9
c) Transitional-metal-catalyzed addition of organoboron reagents to nitriles
[M]
O
N
[M]
hydrolysis
RCN
+
ArB(OH)2
R
Ar
R
Ar
d) This work: Pd-catalyzed tandem reaction of 2-aminostyryl nitriles with ArB(OH)2
R2
R2
R1
Ar
Pd
CN
+
ArB(OH)2
R
R
R1
NH2
N
Transition-metal-catalyzed transformation of nitriles is a useful method to
construct carbon–carbon and carbon–heteroatom bonds for organic chemistry research
and the fine chemical industry.10 To date, a number of transition-metal-catalyzed
systems for the carbopalladation of nitriles to ketones and derivatives with
organoboron reagents (Scheme 1c),11 sodium aryl sulfinates or arylsulfinic acids,12
aryl halides,13 benzoic acids,14 and arylhydrazines15 as coupling partners have been
presented. Compared to the addition reaction of organometallic reagents such as
organolithium or organomagnesium to nitriles,16 abovementioned carbopalladation
reagents are highly regarded due to their advantages of stability to air and moisture as
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well as good functional group tolerance. Inspired by hereinbefore work, as a part of
our research program aimed at transition-metal-catalyzed synthesis of N-containing
heterocycles with organoboron reagents and nitriles,17 we envisioned that
palladium-catalyzed carbopalladation of 2-aminostyryl nitrile derivatives would
afford 2-aminostyryl ketone derivatives easily, which might further prompt an
intramolecular nucleophilic attack onto this in situ formed carbonyl group by -NH2
with the aid of lewis acid and/or acid medium, providing the desire 2-arylquinoline
skeletons (Scheme 1d). Compared with direct cyclization protocol of 2-aminostyryl
ketone derivatives for the construction of 2-arylquinolines, this would be an attractive
synthetic strategy in research, since it provides easy and rapid access to large libraries
of organic compounds with diverse substitution patterns. To the best of our
knowledge, an efficient one-step synthesis of substituted 2-arylquinoline skeletons via
tandem addition/cyclization of organoboron to 2-aminostyryl nitrile derivatives has
not been well documented in literature.
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RESULTS AND DISCUSSION
At the outset of our studies, the reaction between (E)-3-(2-aminophenyl)acrylonitrile
(1a) and phenylboronic acid (2a) was chosen to explore the optimal conditions. The
reaction in the presence of Pd(OAc)2 (5 mol%), 2,2'-bipyridine (L1) (10 mol%) and
trifluoroacetic acid (TFA) (2 equiv) was performed in THF (2mL) at 70 oC for 24 h in
the air, affording the target structure 2-phenylquinoline (3a) in 15% yield (Table 1,
entry 1). An investigation of the solvent effect revealed that toluene was optimal to
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give a best 21% yield, and the use of THF, DMF, DMSO, EtOH and water led to
lower yields (Table 1, entries 1-6). Among the various additives which we screened,
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p-toluenesulfonic acid monohydrate (TsOH ∙ H2O) was most effective and give the
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highest yield of 44% (Table 1, entries 7-11). The yield decreased to 28% when only
1.0 equiv of TsOH∙H2O was used, while this transformation could not be proceeded
further when a higher amount of TsOH ∙ H2O was used (Table 1, entry 11). Other
bidentate nitrogen ligands such as 5,5'-dimethyl-2,2'-bipyridine (L2),
6,6'-dimethyl-2,2'-bipyridine (L3) and 4,7-diphenyl-1,10-phenanthroline (L4) were
less effective than 2,2'-bipyridine (L1) due to the electronic effect or steric effect
(Table 1, entries 12-14). A series of Pd catalysts were then screened with
Pd(CF3COO)2 giving the best 57% yield (Table 1, entries 15-17). However, this
reaction did not work while Pd(0) such as Pd(PPh3)4 was used (Table 1, entry 17). To
further improve the reaction efficiency, we examined the reaction temperature and
o
found that the yield improved to 69% when the temperature was increased to 90 C,
o
but the yield remained unchanged when the temperature was raised to 110 C (Table
1, entries 18-19). Prolonging the reaction time to 36 h led to a significant
improvement in yield (Table 1, entries 20-21). At last, the amount of phenylboronic
acid (2a) was tested and found that the yield decreased to 63% when only 1 equiv of
2a was used and the yield remained unchanged for excess phenylboronic acid (Table
1, entry 22). The reaction did not work well if either Pd catalyst, ligand or TsOH∙H2O
was absent (Table 1, entries 23-25). Therefore, the optimal reaction conditions can be
summarized as follows: 0.3 mmol (E)-3-(2-aminophenyl)acrylonitrile and 0.6 mmol
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phenylboronic acid in toluene (2 mL) with Pd(CF3COO)2 catalyst (5 mol %), TsOH∙
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H2O (2 equiv), 2,2'-bipyridine (10 mol%), at 90 °C for 36 h under air atmosphere.
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Table 1. Optimization of Reaction Conditionsa
NH2
catalyst (5 mol%), ligand (10 mol %)
+
PhB(OH)2
N
solvent (2 mL), additive
CN
1a
2a
3a
Ph
Ph
N
N
N
N
N
N
N
N
L1
Pd Source Ligand
L2
L3
L4
Temp(oC)
Yield(%)b
Additive
Solvent
Time
Entry
70
70
70
70
70
70
70
70
70
70
70
70
70
70
70
70
70
90
110
90
90
90
90
90
90
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L2
L3
L4
L1
L1
L1
L1
L1
L1
L1
L1
L1
-
1
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
THF
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
36
48
36
36
36
36
15
TFA
2
DMF
<10
ND
TFA
3
DMSO
EtOH
TFA
4
trace
21
TFA
5
toluene
H2O
TFA
6
trace
16
TFA
7
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
CH3SO3H
CH3CO2H
H2SO4
8
trace
<10
23
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
CSA
44 (46c, 28d)
TsOH•H2O
TsOH•H2O
TsOH•H2O
TsOH•H2O
TsOH•H2O
TsOH•H2O
TsOH•H2O
TsOH•H2O
TsOH•H2O
TsOH•H2O
TsOH•H2O
TsOH•H2O
TsOH•H2O
TsOH•H2O
-
36
16
13
Pd(CF3CO2)2
PdCl2
57
47
Pd(PPh3)4
Pd(CF3CO2)2
Pd(CF3CO2)2
Pd(CF3CO2)2
Pd(CF3CO2)2
Pd(CF3CO2)2
-
trace
69
70
80
79
63e (80f)
N.R.
trace
10
Pd(CF3CO2)2
Pd(CF3CO2)2
L1
a
1a
2a
(0.6 mmol), Pd Source (5 mol %), Ligand (10 mol %), Solvent (2.0
Conditions:
(0.3 mmol),
mL), additive (2 equiv), 70 oC, 24 h, air. b isolated yields, c TsOH•H2O (3 equiv), d TsOH•H2O (1
equiv), e 1 equiv of , 3 equiv of
f
2a
2a
.
Having identified effective conditions for the tandem addition/cyclization of
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organoboron to 2-aminostyryl nitrile derivatives for the construction of
2-arylquinoline skeletons, we studied the scope of phenylboronic acid first, and the
results are shown in Table 2. The reaction was found to work well with a variety of
arylboronic acids. The reactivities of para-, meta-, and ortho-tolylboronic acids were
evaluated, and the results demonstrated that the steric effect of the substituent had an
obvious impact on the reaction. For example, treatment of 1a with para- and
meta-tolylboronic acids provided 86% and 82% yields of 3b and 3c, respectively
(Table 2, entries 1-2), while the ortho-tolylboronic acid afforded the desired product
3d with a diminished yield of 73% (Table 2, entry 3). 3,5-Dimethyl phenylboronic
acid afforded the desire 3e in comparable 84% yield while bulky 2,6-dimethyl
phenylboronic acid was unsuitable in this transformation (Table 2, entries 4-5).
Interestingly, arylboronic acids bearing methoxy substituents at 4-positions provided
the corresponding product 3g in lower yield compared with other moieties bearing
electron-donating groups, affording significant amount of byproduct such as 2-amino
quinoline18 and 4,4'-dimethoxy-1,1'-biphenyl. Functional groups, such as naphthyl
and biphenyl were also tolerated with observed yields ranging from 69% to 85%
(Table 2, entries 7-9). To our delight, the method tolerates the entire range of halogen
substituents and strong electron-withdrawing substituent (e.g. p-CF3 and m-NO2),
although the yields of cyclized products 3l-3s were lower than those of
electron-sufficient substrates, which makes this method particularly appealing,
enabling further access to more complex compounds in combination with
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cross-coupling transformations (Table 2, entries 11 − 18). However,
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p-nitrophenylboronic acids was unefficient substrate under current conditions (Table
2, entry 19). Additionally, thiophen-3-ylboronic acid was also successfully
transformed to target quinoline 3u when subjected to the reaction condition with 29%
yield (Table 2, entry 20). However, the reaction failed to deliver the desired product
when methylboronic acid or (E)-styrylboronic acid was used as the substrate (Table 2,
entries 21-22). In order to support the role of o-amino group, the reaction with
cinnamonitrile (1x) under the same procedure and conditions was carried out.
However, the desire product 3a was not observed (Table 2, entry 23).
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Table 2. Reaction of Various Arylboronic Acids with (E)-3-(2-Aminophenyl)-
Acrylonitrile a
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Pd(CF3COO)2 (5 mol%)
CN
bpy (10 mol%)
ArB(OH)2
+
toluene, TsOH H2O
90 oC, 36 h, air
N
Ar
NH2
1a
7
2
3
8
9
1)
2)
3)
4)
8)
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N
N
N
N
3b,
3c,
3d,
3e,
86%
82%
33%
73%
84%
82%
5)
9)
6)
7)
N
N
N
N
OMe
3f,
3g,
3h,
3i,
0%
85%
10)
11)
12)
16)
N
F
N
N
N
Ph
F
3j,
3k,
3l,
3m,
69%
60%
40%
75%
68%
23%
66%
63%
61%
13)
17)
14)
15)
19)
F
N
N
N
N
Cl
Br
I
3n,
3o,
3p,
3q,
69%
N
20)
18)
22)
NO2
N
N
S
N
CF3
3u,
29%
3r,
3s,
3t,
trace
NO2
21)
23)
CN
N
Ph
N
1x
3w,
0%
3v,
0%
a
1a
2a
(0.6 mmol), Pd(CF3COO)2 (5 mol%), bpy (10 mol%), toluene (2.0 mL), TsOH•H2O (2
Conditions:
(0.3 mmol),
equiv), 90 oC, 36 h, air, isolated yield.
Encouraged by these results, we next assessed the reaction of various substituted
(E)-3-(2-aminophenyl)acrylonitriles with arylboronic acids under our optimal
conditions (Table 3). The influence of substitutions on the aniline ring was first
investigated. The electronic effect of the substituents affected the yields of this
transformation to some extent. For example, when substrates bearing a para-methyl
and methoxy group on the phenyl ring were examined, 3y and 3z were obtained in a
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lower yield of 73% and 44%, respectively (Table 3, entries 1-2).
Electron-withdrawing groups, such as fluoro, chloro, bromo, trifluoromethyl on the
phenyl ring at the para or meta-position, were well tolerated in this transformation
affording the desire 2-arylquinolines in a higher yield, ranging from 74% to 90%
(Table 3, entries 3-8). The para-substituent positions at the phenyl moiety of
arylboronic acids were also examined, and the results demonstrated that the electronic
properties of the substituents affected the yields of the reaction to some extent. In
general, the arylboronic acids bearing an electron-withdrawing substituent (e.g. F)
produced a slightly lower yield of cyclization products than those analogues bearing
an electron-donating substituent except the methoxyl-substituted 2-arylquinolines
(Table 3, entries 9-14). Next, we further examined variation of the alkenyl in the
styrene motif of (2-aminophenyl)acrylonitriles. Alkyl groups such as methyl, ethyl
and isopropyl containing substrates at the vinyl attached to the phenyl ring side were
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made, affording 3zm-3zo in 43−89% yield, respectively (Table 3, entries 15−17).
Alkenyl group such as butenyl at the same position was unsuitable in this cyclization
process (Table 3, entry 18). Phenyl group was also tolerated, affording the desired
product 3zq in 49% yield (Table 3, entry 19). However, phenyl containing substrate at
the vinyl attached to the cyano group could not go through such transformation (Table
3, entry 20).
Table 3. Reaction of Various (E)-3-(2-Aminophenyl)acrylonitriles with
Arylboronic Acids a
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3
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7
8
R2
R2
N
Pd(CF3COO)2 (5 mol%)
R1
Ar
CN
bpy (10 mol%)
R
R1
NH2
1
+
R
ArB(OH)2
toluene, TsOH H2O
90 oC, 36 h, air
2
3
9
1)
5)
2)
3)
4)
O
Cl
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N
Cl
N
N
N
3y,
3z,
3za,
3zb,
86%
73%
44%
84%
6)
7)
F3C
8)
Br
F
F
N
N
N
N
3zc,
3zd,
3ze,
3zf,
90%
80%
74%
62%
81%
81%
9)
Br
10)
11)
Cl
12)
Cl
Br
N
N
N
N
CH3
OCH3
F
3zg,
3zh,
3zi,
3zj,
34%
66%
77%
13)
Cl
14)
Cl
15)
16)
N
N
N
N
F
3zm,
89%
3zk,
3zl,
3zn,
68%
77%
17)
18)
19)
20)
N
N
N
N
3zo,
3zp,
3zq,
3zr,
43%
complex
49 %
N.R.
a
1
2
Conditions: (0.3 mmol), (0.6 mmol), Pd(CF3COO)2 (5 mol%), bpy (10 mol%), toluene (2.0 mL), TsOH•H2O (2 equiv),
90 oC, 36 h, air, isolated yield.
The efficiency of this catalytic system was further demonstrated by running the
transformation on a laboratory preparative scale. For example, the tandem reaction of
(E)-3-(2-aminophenyl)but-2-enenitrile with phenylboronic acid was performed on a
gram scale (6.33 mmol), and 3zm was obtained in 85% isolated yield (Scheme 2).
Scheme 2. A Gram-Scale Transformation
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5
CN
standard conditions
B(OH)2
+
6
7
8
N
NH2
1.0 g
85% yield
3zm
, 1.174 g
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To clarify the mechanism, we investigated the reactions shown in Scheme 3. As
expected, the reactions of (E)-3-(2-aminophenyl)-1-phenylprop-2-en-1-one (4a) under
standard conditions without of phenylboronic acids afforded the product
2-phenylquinoline
(3a)
in
80%
yield,
indicating
that
the
(E)-3-(2-aminophenyl)-1-phenylprop-2-en-1-one (4a) could be achieved from the
reaction of 1a with 2a in advance in this reaction (Scheme 3a). The cyclization
reaction of 4a could also proceeded to give the desired product 3a in similar 77%
yield
without
acid
(Scheme
3b),
while
the
reaction
of
(E)-3-(2-aminophenyl)acrylonitrile (1a) and phenylboronic acid (2a) under standard
conditions without acid can only afford 3a in 10% yield (Table 1, entry 25).
(E)-3-(2-aminophenyl)-1-phenylprop-2-en-1-one (4a) could also smoothly
transformed into the desire cyclized product 3a in 74% yield with p-toluenesulfonic
acid monohydrate (Scheme 3c), indicating that the acid is essential for the formation
of intermediate 4a, but not crucial for further cyclization. No formation of the
desired product 3a was observed in the absence of palladium catalyst and acid
(Scheme 3d).
Scheme 3. Control Experiments
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O
Pd(CF3COO)2 (5 mol%)
bpy (10 mol%)
5
6
7
8
(a)
(b)
(c)
N
toluene, TsOH H2O
90 oC, 36 h, air
NH2
4a
3a
, 80%
9
Pd(CF3COO)2 (5 mol%)
bpy (10 mol%)
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O
O
O
toluene, 90 oC, 36 h, air
N
NH2
4a
3a
, 77%
TsOH H2O
toluene, 90 oC, 36 h, air
N
NH2
4a
3a
, 74%
90 oC, 36 h, air
(d)
X
N
toluene
NH2
4a
3a
On the basis of the above mentioned results and relevant reports in the literature,
a possible reaction mechanism for the formation of 2-aryl quinazolines is illustrated in
Scheme 4. The reaction proceeds by forming palladium-aryl species A generated from
the transmetalation process derived from the Pd(II) catalyst and arylboronic acid.
Thereafter, nitrile 1a coordination to Pd[Ar] affords the intermediate B, which
undergoes an intramolecular insertion of the nitrile group to yield the corresponding
ketimine palladium complex C. Further the above complex C afforded the ketone
intermediate D, and thus regenerates the Pd(II) catalyst. The ketone intermediate D
undergoes C=C bond E/Z configurational tautomerization to afford E with the aid of
acid and/or Pd(II) species, which is followed by intramolecular condensation to yield
the corresponding desired product 3.
Scheme 4 Proposed mechanism.
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CN
Ar[Pd]
ArB(OH)2
A
2
NH2
1a
7
8
9
N
[Pd]
Ar
O
Y
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O
[Pd]
NH2
Ar
Ar
B
NH2
NH2
D
[Pd]
Ar
N
H3O+
Y
O
NH2
c-c bond rotation
/isomerization
- H2O
Ar
C
O
NH2
Ar
N
Ar
NH2
Y
3
Y = H+ or [Pd]
E
CONCLUSIONS
In summary, we have developed a new approach for the synthesis of 2-arylquinolines
by the Pd-catalyzed tandem reaction of 2-aminostyryl nitriles with arylboronic acids.
This protocol provides an alternative synthetic pathway to access 2-arylquinolines
compared with classical condensation reaction of (E)-2-aminostyryl ketones. Further
efforts to extend this catalytic system to the preparation of other useful heterocyclic
compounds are currently underway in our laboratories.
EXPERIMENTAL SECTION
General Methods. Melting points are uncorrected. 1H NMR and 13C NMR spectra
were measured on a 500 MHz spectrometer (1H at 500 MHz, 13C at 125 MHz), using
CDCl3 and d6-DMSO as the solvent at room temperature. Chemical shifts are given δ
relative to TMS, and the coupling constants J are given in hertz. High-resolution mass
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spectra were recorded on an ESI-Q-TOF mass spectrometer. Substrates
6
7
(E)-3-(2-aminophenyl)acrylonitriles
(1a-1zr)
and
8
9
(E)-3-(2-aminophenyl)-1-phenylprop-2-en-1-one (4a) were prepared by the modified
literature methods.19 Other commercially obtained reagents were used without further
purification. Column chromatography was performed using EM silica gel 60
(300−400 mesh).
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General procedure for the Synthesis of 2-Aryl Quinolines.
In a 25 mL sealed tube, (E)-3-(2-aminophenyl)acrylonitrile (1) (0.3 mmol, 43.3
mg), arylboronic acid (2) (0.6 mmol, 73.2 mg), palladium(II)trifluoroacetate (0.015
mmol, 5.0 mg), 2,2'-bipyridine (0.03 mmol, 4.7 mg) and p-toluenesulfonic acid (0.6
mmol, 142.7 mg) were dissolved in toluene (2.0 mL). The reaction mixture was then
heated at 90 °C (oil bath) with vigorous stirring for 36 hours. After the reaction
equilibrium, the mixture was poured into ethyl acetate, which was washed with
saturated NaHCO3 (2 × 10 mL) and then brine (1 × 10 mL). After the aqueous layer
was extracted with ethyl acetate, the combined organic layers were dried over
anhydrous Na2SO4 and evaporated under vacuum. The filtrate was concentrated in
vacuo and purified by a silica gel packed flash chromatography column with
petroleum ether/ethyl acetate (10:1) as the eluent to afford the desired products.
(E)-3-(2-Aminophenyl)acrylonitrile (1a): Yellow solid (432.2 mg, 60%), mp
131-132 oC. 1H NMR (500 MHz, CDCl3) δ 7.53 (d, J = 16.5 Hz, 1H), 7.28 (d, J = 8.0
Hz, 1H), 7.21 (dd, J1 = 7.5 Hz, J2 = 7.0 Hz, 1H), 6.79 (dd, J1 = 7.5 Hz, J2 = 7.0 Hz,
1H), 6.72 (d, J = 8.0 Hz, 1H), 5.80 (d, J = 16.5 Hz, 1H), 3.28 (brs, 2H); 13C{1H}
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NMR (125 MHz, CDCl3) δ 146.3, 145.1, 132.2, 127.3, 119.6, 119.3, 118.6, 117.2,
96.0. Spectroscopic data for the title compound were consistent with those reported in
the literature.19a
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(E)-3-(2-Amino-5-methylphenyl)acrylonitrile (1y): Yellow solid (355.7 mg, 45%),
o
1
mp 116-118 C. H NMR (500 MHz, CDCl3) δ 7.51 (d, J = 21.0 Hz, 1H), 7.08 (s,
1H), 7.03 (d, J = 10.0 Hz, 1H), 6.64 (d, J = 10.0 Hz, 1H), 5.78 (d, J = 21.0 Hz, 1H),
3.79 (brs, 2H), 2.24 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 146.4, 142.9, 133.2,
128.6, 127.3, 119.6, 118.8, 117.5, 95.5, 20.3. Spectroscopic data for the title
compound were consistent with those reported in the literature.20a
(E)-3-(2-Amino-5-methoxyphenyl)acrylonitrile (1z): Yellow solid (278.5 mg,
32%), mp 111-112 oC. 1H NMR (500 MHz, CDCl3) δ 7.52 (d, J = 20.5 Hz, 1H), 6.86
(dd, J1 = 3.5 Hz, J2 = 11.0 Hz, 1H), 6.80 (d, J = 3.5 Hz, 1H), 6.69 (d, J = 11.0 Hz,
1H), 5.80 (d, J = 20.5 Hz Hz, 1H), 3.76 (m, 3H), 3.63 (brs, 2H); 13C{1H} NMR (125
MHz, CDCl3) δ 153.2, 146.1, 139.2, 120.6, 119.4, 119.0, 118.5, 111.0, 96.2, 55.8.
HRMS (ESI) calcd for C10H11N2O [M + H]+: 175.0866, found 175.0867.
(E)-3-(2-Amino-4-chlorophenyl)acrylonitrile (1za): Yellow solid (462.9 mg,
o
1
52%), mp 146-148 C. H NMR (500 MHz, DMSO-d6) δ 7.75 (d, J = 20.5 Hz, 1H),
7.43 (d, J = 10.5 Hz, 1H), 6.72 (d, J = 2.5 Hz, 1H), 6.54 (dd, J1 = 2.5 Hz, J2 = 10.5
Hz, 1H), 6.16 (d, J = 20.5 Hz, 1H), 6.03 (s, 2H); 13C{1H} NMR (125 MHz,
DMSO-d6) δ 149.5, 145.6, 136.9, 128.6, 120.0, 116.4, 116.2, 115.6, 94.2. HRMS (ESI)
calcd for C9H8ClN2 [M + H]+: 179.0371, found 179.0370.
(E)-3-(2-Amino-5-chlorophenyl)acrylonitrile (1zb): Yellow solid (498.5 mg,
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o
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56%), mp 132-133 C. H NMR (500 MHz, DMSO-d6) δ 7.71 (d, J = 20.5 Hz, 1H),
7.44 (d, J = 2.5 Hz, 1H), 7.08 (dd, J1 = 3.0 Hz, J2 = 11.0 Hz, 1H), 6.64 (d, J = 11.0
Hz, 1H), 6.23 (d, J = 20.5 Hz, 1H), 5.88 (s, 2H). 13C{1H} NMR (125 MHz,
DMSO-d6) δ 146.7, 145.0, 131.5, 125.3, 119.7, 119.4, 118.0, 113.5, 94.6.
Spectroscopic data for the title compound were consistent with those reported in the
literature.20a
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
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58
59
60
(E)-3-(2-Amino-4-fluorophenyl)acrylonitrile (1zc): Yellow solid (388.9 mg,
o
1
48%), mp 69-70 C. H NMR (500 MHz, DMSO-d6) δ 7.70 (d, J = 20.5 Hz, 1H),
7.44-7.40 (m, 1H), 6.39-6.36 (m, 1H), 6.32-6.27 (m, 1H), 6.05 (d, J = 20.5 Hz, 1H),
6.01 (s, 2H);13C{1H} NMR (125 MHz, CDCl3) δ 165.3 (d, J = 250.1 Hz), 147.0 (d, J
= 11.6 Hz), 145.2, 129.4 (d, J = 10.6 Hz), 118.5, 115.8, 106.8 (d, J = 22.6 Hz), 103.4
(d, J = 24.7 Hz), 95.6. HRMS (ESI) calcd for C9H8FN2 [M + H]+: 163.0666, found
163.0669.
(E)-3-(2-Amino-5-bromophenyl)acrylonitrile (1zd): Yellow solid (477.3 mg,
o
1
43%), mp 128-130 C. H NMR (500 MHz, DMSO-d6) δ 7.75-7.69 (m, 1H),
7.59-7.57 (m, 1H), 7.23-7.21 (m, 1H), 6.64-6.60 (m, 1H), 6.29-6.22 (m, 1H), 5.95 (s,
2H); 13C{1H} NMR (125 MHz, DMSO-d6) δ 147.0, 144.9, 134.2, 128.2, 119.4, 118.7,
118.4, 107.0, 94.6. Spectroscopic data for the title compound were consistent with
those reported in the literature.20a
(E)-3-(2-Amino-5-(trifluoromethyl)phenyl)acrylonitrile (1ze): Yellow solid
(562.0 mg, 53%), mp 117-118 oC. 1H NMR (500 MHz, CDCl3) δ 7.49 (d, J = 20.5 Hz,
2H), 7.43 (d, J = 10.5 Hz, 1H), 6.77 (d, J = 10.5 Hz, 1H), 5.87 (d, J = 20.5 Hz, 1H),
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4.24 (brs, 2H); 13C{1H} NMR (125 MHz, CDCl3) 147.7, 145.1, 128.7 (q, J = 3.8 Hz),
125.2 (t, J = 270.0 Hz), 124.7 (q, J = 3.8 Hz), 121.1 (q, J = 32.5 Hz), 118.6, 118.0,
116.7, 97.9. HRMS (ESI) calcd for C10H8F3N2 [M + H]+: 213.0634, found 213.0634.
(E)-3-(2-Amino-5-fluorophenyl)acrylonitrile (1zf): Yellow solid (534.8 mg,
10
11
12
13
14
15
16
17
18
19
20
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47
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49
50
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57
58
59
60
o
1
66%), mp 130-131 C. H NMR (500 MHz, DMSO-d6) δ 7.73 (dd, J1 = 2.0 Hz, J2 =
20.0 Hz, 1H), 7.27-7.24 (m, 1H), 6.98-6.93 (m, 1H), 6.65-6.62 (m, 1H), 6.19 (d, J =
13
20.0 Hz, 1H), 5.62 (s, 2H); C{1H} NMR (125 MHz, CDCl3) δ 156.4 (d, J = 238.4
Hz), 145.1 (d, J = 2.4 Hz), 141.4 (d, J = 1.8 Hz), 120.4 (d, J = 7.2 Hz), 119.3 (d, J =
23.1 Hz), 118.6 (d, J = 7.6 Hz), 118.1, 112.7 (d, J = 23.0 Hz), 97.3. Spectroscopic
data for the title compound were consistent with those reported in the literature.20a
(E)-3-(2-Aminophenyl)but-2-enenitrile (1zm): Yellow solid (395.2 mg, 50%),
o
1
mp 64-66 C. H NMR (500 MHz, CDCl3) δ 7.17-7.13 (m, 1H), 7.03-7.01 (m, 1H),
6.80-6.76 (m, 1H), 6.73-6.71 (m, 1H), 5.55-5.54 (m, 1H), 3.79 (brs, 2H), 2.43-2.42
(m,3H); 13C{1H} NMR (125 MHz, CDCl3) δ 160.8, 142.8, 130.1, 127.9, 125.6, 118.7,
116.9, 116.5, 98.8, 22.0. Spectroscopic data for the title compound were consistent
with those reported in the literature.19b
1
(E)-3-(2-Aminophenyl)pent-2-enenitrile (1zn): Yellow oil (309.8 mg, 36%). H
NMR (500 MHz, CDCl3) δ 7.17-7.13 (m, 1H), 6.97-6.95 (m, 1H), 6.79-6.75 (m, 1H),
6.73-6.71 (m, 1H), 5.44 (s, 1H), 3.79 (brs, 2H), 2.83 (q, J = 9.5 Hz, 2H), 1.07 (t, J =
13
9.5 Hz, 3H); C{1H} NMR (125 MHz, CDCl3) δ 166.9, 143.1, 129.9, 128.2, 124.3,
118.5, 116.6, 116.3, 98.2, 28.9, 12.7. HRMS (ESI) calcd for C11H13N2 [M + H]+:
173.1073, found 173.1081.
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(E)-3-(2-Aminophenyl)-4-methylpent-2-enenitrile (1zo): Yellow solid (316.4
6
7
o
1
mg, 34%), mp 159-160 C. H NMR (500 MHz, CDCl3) δ 7.16-7.11 (m, 1H),
8
9
6.87-6.85 (m, 1H), 6.76-6.70 (m, 2H), 5.31 (s, 1H), 3.66 (brs, 2H), 3.40-3.30 (m, 1H),
10
11
12
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47
48
49
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51
52
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57
58
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60
13
1.20-1.19 (m, 6H); C{1H} NMR (125 MHz, CDCl3) δ 170.8, 143.1, 129.4, 128.3,
123.6, 117.6, 116.2, 115.8, 98.7, 35.4, 20.9. HRMS (ESI) calcd for C12H15N2 [M +
H]+: 187.1235, found 187.1239.
(E)-3-(2-Aminophenyl)hepta-2,6-dienenitrile (1zp): Yellow oil (297.2 mg, 30%).
1H NMR (500 MHz, CDCl3) δ 7.17-7.13 (m, 1H), 6.97-6.95 (m, 1H), 6.79-6.75 (m,
1H), 6.71 (d, J = 9.5 Hz, 1H), 5.85-5.75 (m, 1H), 5.51 (s, 1H), 5.03-4.99 (m, 2H),
3.73 (brs, 2H), 2.94 (t, J = 9.5 Hz, 2H), 2.22-2.17 (m, 2H); 13C{1H} NMR (125 MHz,
CDCl3) δ 164.3, 143.3, 136.7, 130.0, 128.1, 124.0, 118.4, 116.8, 116.4, 116.2, 99.4,
34.9, 31.9. HRMS (ESI) calcd for C13H15N2 [M + H]+: 199.1230, found 199.1230.
(E)-3-(2-Aminophenyl)-3-phenylacrylonitrile (1zq) (473.2 mg, 46%): Yellow
o
1
solid, mp 100-102 C. H NMR (500 MHz, CDCl3) δ 7.58-7.56 (m, 2H), 7.48-7.42
(m, 3H), 7.23-7.21 (m, 1H), 7.10-7.08 (m, 1H), 6.82 (dd, J1 = 9.5 Hz, J2 = 9.0 Hz,
1H), 6.71 (d, J = 9.5 Hz, 1H), 5.67 (s, 1H), 3.73 (brs, 2H); 13C{1H} NMR (125 MHz,
CDCl3) δ 161.5, 144.3, 136.4, 131.0, 130.7, 130.6, 129.0, 128.7, 124.8, 118.6, 117.7,
116.5, 97.0. HRMS (ESI) calcd for C15H13N2 [M + H]+: 221.1073, found 221.1074.
(E)-3-(2-Aminophenyl)-2-phenylacrylonitrile (1zr): Yellow solid (506.2 mg,
o
1
46%), mp 152-153 C. H NMR (500 MHz, CDCl3) δ 7.79 (s, 1H), 7.70 (d, J = 10.5
Hz, 1H), 7.65 (d, J = 10.5 Hz, 1H), 7.59-7.49 (m, 5H), 7.46-7.42 (m, 1H), 7.30-7.27
(m, 1H), 5.06 (brs, 2H); 13C{1H} NMR (125 MHz, CDCl3) δ 155.2, 147.0, 137.5,
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137.2, 129.6, 129.1, 128.9, 128.2, 127.5, 125.5, 125.0, 124.2, 122.8. HRMS (ESI)
calcd for C15H13N2 [M + H]+: 221.1073, found 221.1074.
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(E)-3-(2-Aminophenyl)-1-phenylprop-2-en-1-one (4a): Yellow solid (446.2 mg,
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40%), mp 109-110 C. H NMR (500 MHz, CDCl3) δ 8.04-7.99 (m, 3H), 7.60-7.56
(m, 1H), 7.54-7.47 (m, 4H), 7.22-7.18 (m, 1H), 6.80 (dd, J1 = 9.5 Hz, J2 = 9.0 Hz,
1H), 6.73 (d, J =10.5 Hz, 1H), 4.12 (brs, 2H); 13C{1H}190.3, 146.3, 140.2, 138.3,
132.8, 131.7, 128.6, 128.5, 128.1, 121.7, 120.2, 118.9, 116.8. Spectroscopic data for
the title compound were consistent with those reported in the literature.9d
2-Phenylquinoline (3a): Yellow solid (49.2 mg, 80%), mp 81-82 oC. 1H NMR (500
MHz, CDCl3) δ 8.24-8.17 (m, 4H), 7.89 (d, J = 10.0 Hz, 1H), 7.84 (d, J = 10.0 Hz,
1H), 7.76-7.72 (m, 1H), 7.56-7.52 (m, 3H), 7.49-7.46 (m, 1H); C{1H} NMR (125
13
MHz, CDCl3) δ 157.4, 148.3, 139.6, 136.8, 129.7, 129.6, 129.4, 128.8, 127.6, 127.4,
127.2, 126.3, 119.0. Spectroscopic data for the title compound were consistent with
those reported in the literature.9d
2-(p-Tolyl)quinoline (3b): White solid (56.5 mg, 86%), mp 80-82 oC. 1H NMR (500
MHz, CDCl3) δ 8.19-8.07 (m, 4H), 7.87-7.81 (m, 2H), 7.72-7.71 (m, 1H), 7.51-7.48
(m, 1H), 7.34-7.33 (m, 2H), 2.43 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 157.3,
148.2, 139.5, 136.8, 136.7, 129.7, 129.6, 129.5, 127.4, 127.1, 126.1, 118.9, 21.3.
Spectroscopic data for the title compound were consistent with those reported in the
literature.7a
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2-(m-Tolyl)quinoline (3c): Yellow oil (53.9 mg, 82%). H NMR (500 MHz,
CDCl3) δ 8.22-8.19 (m, 2H), 8.03 (s, 1H), 7.94 (d, J = 9.5 Hz, 1H), 7.86 (d, J = 9.5
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Hz,1H), 7.83-7.81 (m, 1H), 7.76-7.72 (m, 1H), 7.55-7.51 (m, 1H), 7.43 (dd, J1 = 9.5
Hz, J2 = 9.5 Hz, 1H), 7.30 (d, J = 9.5 Hz, 1H), 2.50(s, 3H); 13C{1H} NMR (125 MHz,
CDCl3) δ 157.6, 148.3, 139.7, 138.5, 136.7, 130.2, 129.7, 129.6, 128.8, 128.3, 127.5,
127.2, 126.2, 124.8, 119.2, 21.6. Spectroscopic data for the title compound were
consistent with those reported in the literature.7a
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2-(o-Tolyl)quinoline (3d): Yellow oil (48.0 mg, 73%). 1H NMR (500 MHz, CDCl3)
δ 8.22-8.19 (m, 2H), 7.88-7.86 (m, 1H), 7.78-7.73 (m, 1H), 7.59-7.51 (m, 3H),
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7.39-7.32 (m, 3H), 2.44 (s, 3H); C{1H} NMR (125 MHz, CDCl3) δ 160.3, 147.9,
140.8, 136.1, 136.0, 130.9, 129.7, 129.6, 129.5, 128.5, 127.5, 126.8, 126.4, 126.0,
122.4, 20.4. Spectroscopic data for the title compound were consistent with those
reported in the literature.7b
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2-(3,5-Dimethylphenyl)quinoline (3e): White oil (58.8 mg, 84%). H NMR (500
MHz, CDCl3) δ 8.20 (dd, J1 = 7.5 Hz, J2 = 7.0 Hz, 2H), 7.86 (d, J = 8.5 Hz, 1H),
7.83-7.81 (m, 1H), 7.78 (s, 2H), 7.75-7.72 (m, 1H), 7.54-7.51 (m, 1H), 7.12 (s, 1H),
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2.45 (s, 6H); C{1H} NMR (125 MHz, CDCl3) δ 157.8, 148.3, 139.7, 138.4, 136.6,
131.1, 129.7, 129.6, 127.5, 127.2, 126.2, 125.5, 119.3, 21.5. Spectroscopic data for
the title compound were consistent with those reported in the literature.7a
o
2-(4-Methoxyphenyl)quinoline (3g): White solid (23.3 mg, 33%), mp 123-124 C.
1H NMR (500 MHz, CDCl3) δ 8.21-8.14 (m, 4H), 7.85-7.80 (m, 2H), 7.72 (ddd, J1 =
9.8 Hz, J2 = 9.5 Hz, J3 = 0.5 Hz, 1H), 7.51 (ddd, J1 = 9.3 Hz, J2 = 9.3 Hz, J3 = 0.5 Hz,
1H), 7.05 (d, J = 11.0 Hz, 2H), 3.89 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ
160.9, 156.9, 148.3, 136.6, 132.2, 129.6, 129.5, 128.9, 127.4, 126.9, 125.9, 118.5,
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114.3, 55.4. Spectroscopic data for the title compound were consistent with those
reported in the literature.7a
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2-(Naphthalen-1-yl)quinoline (3h): Yellow oil (65.1 mg, 85%). H NMR (500
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MHz, CDCl3) δ 8.28-8.27 (m, 2H), 8.16 (d, J = 8.5 Hz, 1H), 7.96 (dd, J1 = 8.5 Hz, J2
= 8.0 Hz, 2H), 7.91 (d, J = 8.0 Hz, 1H), 7.81-7.78 (m, 1H), 7.75-7.74 (m, 1H), 7.71
(d, J = 8.0 Hz, 1H), 7.63-7.59 (m, 2H), 7.55-7.47 (m, 2H); 13C{1H} NMR (125 MHz,
CDCl3) δ 159.4, 148.1, 138.7, 136.3, 134.1, 131.3, 129.8, 129.7, 129.2, 128.4, 127.8,
127.6, 127.0, 126.6, 126.5, 126.0, 125.7, 125.4, 123.3. Spectroscopic data for the title
compound were consistent with those reported in the literature.8c
o
2-(Naphthalen-2-yl)quinoline (3i): Yellow solid (62.8 mg, 82%), mp 161-163 C.
1H NMR (500 MHz, CDCl3) δ 8.64 (s, 1H), 8.38 (d, J = 8.5 Hz, 1H), 8.30-8.26 (m,
2H), 8.04-8.03 (m, 1H), 8.02-8.00 (m, 2H), 7.91-7.90 (m, 1H), 7.85 (d, J = 8.5 Hz,
1H), 7.78-7.76 (m, 1H), 7.57-7.53 (m, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ
157.1, 148.1, 137.1, 136.6, 133.9, 133.5, 129.9, 129.5, 128.9, 128.6, 127.7, 127.5,
127.4, 127.2, 126.8, 126.5, 126.4, 125.1, 119.2. Spectroscopic data for the title
compound were consistent with those reported in the literature.9c
2-([1,1'-Biphenyl]-4-yl)quinoline (3j): White solid (58.2 mg, 69%), mp 176-177
oC. 1H NMR (500 MHz, CDCl3) δ 8.27 (d, J = 8.0 Hz, 4H), 7.94 (d, J = 8.0 Hz, 1H),
7.86 (d, J = 8.0 Hz, 1H), 7.79-7.75 (m, 3H), 7.69 (d, J = 7.5 Hz, 2H), 7.56 (dd, J1 =
7.5 Hz, J2 = 7.0 Hz, 1H), 7.49 (dd, J1 = 7.5 Hz, J2 = 7.5 Hz, 2H), 7.39 (dd, J1 = 7.5
Hz, J2 = 7.0 Hz, 1H); 13C{1H} NMR (125 MHz, CDCl3) δ 156.8, 142.4, 140.6, 137.3,
130.0, 129.4, 128.9, 128.2, 127.7, 127.6, 127.5, 127.3, 127.2, 126.5, 119.0.
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Spectroscopic data for the title compound were consistent with those reported in the
literature.9c
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2-(4-(Tert-butyl)phenyl)quinoline (3k): White solid (58.8 mg, 75%), mp 69-71 C.
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1H NMR (500 MHz, CDCl3) δ 8.21-8.19 (m, 2H), 8.12 (d, J = 8.5 Hz, 2H), 7.87 (d, J
= 8.5 Hz, 1H), 7.82 (d, J = 8.5 Hz, 1H), 7.75-7.71 (m, 1H), 7.57 (d, J = 8.5 Hz, 2H),
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7.54-7.50 (m, 1H), 1.40 (s, 9H); C{1H} NMR (125 MHz, CDCl3) δ 157.4, 152.6,
148.4, 136.9, 136.7, 129.7, 129.6, 127.4, 127.3, 127.1, 126.1, 125.8, 118.9, 34.8, 31.3.
Spectroscopic data for the title compound were consistent with those reported in the
literature.7a
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2-(4-Fluorophenyl)quinoline (3l):Yellow solid (44.2 mg, 66%), mp 82-84 C. H
NMR (500 MHz, CDCl3) δ 8.21 (d, J = 10.5 Hz, 1H), 8.18-8.14 (m, 3H), 7.82 (d, J =
10.5 Hz, 2H), 7.76-7.72 (m, 1H), 7.55-7.52 (m, 1H), 7.23-7.19 (m, 2H); 13C NMR
(125 MHz, CDCl3) δ 164.0 (d, J = 249.6 Hz), 156.4, 146.6, 136.0, 135.3 (d, J = 2.8
Hz), 132.0, 131.2, 130.7, 129.4 (d, J = 8.5 Hz), 127.6, 126.2, 119.4, 115.9 (d, J = 21.7
Hz). Spectroscopic data for the title compound were consistent with those reported in
the literature.7a
2-(3-Fluorophenyl)quinoline (3m): Yellow solid (40.8 mg, 61%), mp 40-42 oC. 1H
NMR (500 MHz, CDCl3) δ 8.24 (d, J = 11.0 Hz, 1H), 8.19 (d, J = 11.0 Hz, 1H),
7.94-7.92 (m, 2H), 7.86-7.83 (m, 2H), 7.77-7.73 (m, 1H), 7.57-7.46 (m, 2H),
7.19-7.14 (m, 1H); 13C{1H} NMR (125 MHz, CDCl3) δ 163.4 (d, J = 245.7 Hz), 155.8
(d, J = 2.5 Hz), 148.2, 142.0, 141.9, 137.0, 130.3 (d, J = 8.1 Hz), 129.8 (d, J = 14.7
Hz), 127.5, 127.4, 126.6, 123.1 (d, J = 2.7 Hz), 118.7, 116.2 (d, J = 21.4 Hz), 114.5
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(d, J = 22.8 Hz). Spectroscopic data for the title compound were consistent with those
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2-(2-Fluorophenyl)quinoline (3n): Yellow solid (40.2 mg, 60%), mp 77-82 C. H
NMR (500 MHz, CDCl3) δ 8.21 (dd, J1 = 10.5 Hz, J2 = 10.0 Hz, 2H), 8.13-8.08 (m,
1H), 7.90-7.84 (m, 2H), 7.77-7.73 (m, 1H), 7.56 (dd, J1 = 10.0 Hz, J2 = 8.5 Hz, 1H),
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7.47-7.41 (m, 1H), 7.35-7.31 (m, 1H), 7.24-7.19 (m, 1H); C{1H} NMR (125 MHz,
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CDCl3) δ 159.8 (d, J = 249.8 Hz), 153.0, 152.9, 147.3, 135.2, 130.5 (d, J = 3.0 Hz),
129.8 (d, J = 8.5 Hz), 128.6 (d, J = 8.6 Hz), 126.9 (d, J = 12.0 Hz), 126.4, 126.2,
125.6, 123.7 (d, J = 3.5 Hz), 121.4 (d, J = 8.1 Hz), 115.2 (d, J = 22.8 Hz).
Spectroscopic data for the title compound were consistent with those reported in the
literature.7b
2-(4-Chlorophenyl)quinoline (3o): White solid (48.9 mg, 68%), mp 111-113 oC. 1H
NMR (500 MHz, CDCl3) δ 8.25-8.18 (m, 2H), 8.13 (d, J = 7.5 Hz, 2H), 7.85-7.84 (m,
2H), 7.76-7.73 (m, 1H), 7.56-7.53 (m, 1H), 7.50 (d, J = 7.5 Hz, 2H); C{1H} NMR
13
(125 MHz, CDCl3) δ 156.0, 148.1, 137.9, 137.1, 135.7, 129.9, 129.6, 129.0, 128.9,
127.5, 127.2, 126.6, 118.6. Spectroscopic data for the title compound were consistent
with those reported in the literature.7b
2-(4-Bromophenyl)quinoline (3p):Yellow solid (53.7 mg, 63%), mp 117-118 oC. 1H
NMR (500 MHz, CDCl3) δ 8.24 (d, J = 7.5 Hz, 1H), 8.18 (d, J = 7.5 Hz, 1H), 8.06 (d,
J = 7.5 Hz, 2H), 7.85-7.83 (m, 2H), 7.76-7.73 (m, 1H), 7.66 (d, J = 7.5 Hz, 2H),
7.56-7.53 (m, 1H); C{1H} NMR (125 MHz, CDCl3) δ 156.0, 148.1, 138.4, 137.1,
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132.0, 129.9, 129.6, 129.2, 127.5, 127.3, 126.6, 124.0, 118.5. Spectroscopic data for
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2-(4-Iodophenyl)quinoline (3q): White solid (68.6 mg, 69%), mp 140-141 C. H
NMR (500 MHz, CDCl3) δ 8.25-8.20 (m, 2H), 7.93-7.92 (m, 2H), 7.88-7.83 (m, 4H),
7.76-7.74 (m, 1H), 7.57-7.54 (m, 1H); 13C{1H} NMR (125 MHz, CDCl3) δ 156.1,
147.9, 147.8, 138.0, 137.3, 130.0, 129.5, 129.3, 127.5, 127.3, 126.7, 118.5, 96.1.
Spectroscopic data for the title compound were consistent with those reported in the
literature.9b
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2-(4-(Trifluoromethyl)phenyl)quinoline (3r): White solid (32.8 mg, 40%), mp
124-125 oC. 1H NMR (500 MHz, CDCl3) δ 8.29 (d, J = 8.0 Hz, 3H), 8.23 (d, J = 8.0
Hz, 1H), 7.90 (d, J = 8.0 Hz, 1H), 7.87 (d, J = 8.0 Hz, 1H), 7.79 (d, J = 8.0 Hz, 2H),
7.78-7.76 (m, 1H), 7.58 (dd, J1 = 8.0 Hz, J2 = 8.0 Hz, 1H); 13C{1H} NMR (125 MHz,
CDCl3) δ 156.9, 148.3, 142.1, 140.6, 138.5, 136.8, 129.7, 128.0 (d, J = 214.6 Hz),
128.0, 127.6 (d, J = 15.3 Hz), 127.5, 127.3, 126.3, 118.9. Spectroscopic data for the
title compound were consistent with those reported in the literature.7a
o
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2-(3-Nitrophenyl)quinoline (3s): White solid (17.3 mg, 23%), mp 121-123 C. H
NMR (500 MHz, CDCl3) δ 9.04 (s, 1H), 8.55 (d, J = 9.5 Hz, 1H), 8.32-8.29 (m, 2H),
8.20 (d, J = 11.0 Hz, 1H), 7.93 (d, J = 11.0 Hz, 1H), 7.87 (d, J = 10.0 Hz, 1H),
7.80-7.76 (m, 1H), 7.72-7.68 (m, 1H), 7.61-7.57 (m, 1H); C{1H} NMR (125 MHz,
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CDCl3) δ 154.4, 148.9, 148.2, 141.3, 137.4, 133.3, 130.2, 129.9, 129.8, 127.6, 127.1,
123.9, 122.4, 118.3. Spectroscopic data for the title compound were consistent with
those reported in the literature.7b
1
2-(Thiophen-3-yl)quinoline (3u): Yellow oil (18.4 mg, 29%). H NMR (500 MHz,
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CDCl3) δ 8.18-8.16 (m, 1H), 8.14 (d, J = 10.5 Hz, 1H), 8.07-8.06 (m, 1H), 7.89-7.88
(m, 1H), 7.79 (d, J = 10.5 Hz, 2H), 7.71 (d, J = 10.5 Hz, 1H), 7.51 (d, J = 10.5 Hz,
1H), 7.46-7.44 (m, 1H); 13C{1H} NMR (125 MHz, CDCl3) δ 153.2, 136.8, 129.8,
129.4, 127.5, 127.1, 126.9, 126.4, 126.2, 124.9, 124.8, 119.1. Spectroscopic data for
the title compound were consistent with those reported in the literature.7b
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6-Methyl-2-phenylquinoline (3y): White solid (48.0 mg, 73%), mp 98-100 C. H
NMR (500 MHz, CDCl3) δ 8.18-8.16 (m, 2H), 8.10 (d, J = 11.0 Hz, 2H), 7.82 (d, J =
11.0 Hz, 1H), 7.57-7.52 (m, 4H), 7.48-7.45 (m, 1H), 2.55 (s, 3H); 13C{1H} NMR (125
MHz, CDCl3) δ 156.5, 146.8, 139.8, 136.2, 136.1, 132.0, 129.4, 129.2, 128.8, 127.5,
127.2, 126.3, 119.0, 21.6. Spectroscopic data for the title compound were consistent
with those reported in the literature.6d
1
6-Methoxy-2-phenylquinoline (3z): Yellow oil (31.0 mg, 44%). H NMR (500
MHz, CDCl3) δ 8.15-8.14 (m, 1H), 8.13 (s, 1H), 8.11 (d, J = 6.0 Hz, 1H), 8.08 (d, J =
6.0 Hz, 1H), 7.83 (d, J = 11.5 Hz, 1H), 7.52 (dd, J1 = 9.5 Hz, J2 = 9.0 Hz, 2H), 7.45
(d, J = 9.5 Hz, 1H), 7.39 (dd, J1 = 3.5 Hz, J2= 11.5 Hz, 1H), 7.08 (d, J = 3.5 Hz, 1H),
3.94 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 157.8, 155.0, 144.4, 139.8, 135.5,
131.2, 128.9, 128.8, 128.2, 127.3, 122.3, 119.2, 105.1, 55.5. Spectroscopic data for
the title compound were consistent with those reported in the literature.7a
7-Chloro-2-phenylquinoline (3za): White solid (60.2 mg, 84%), mp 113-114 oC. 1H
NMR (500 MHz, CDCl3) δ 8.21-8.15 (m, 4H), 7.89-7.87 (m, 1H), 7.77-7.75 (m, 1H),
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7.56-7.48 (m, 4H); C{1H} NMR (125 MHz, CDCl3) δ 158.2, 148.5, 139.0, 136.7,
135.6, 129.7, 128.9, 128.7, 128.6, 127.6, 127.4, 125.5, 119.2. Spectroscopic data for
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6-Chloro-2-phenylquinoline (3zb): White solid (61.7 mg, 86%), mp 106-107 C.
11H NMR (500 MHz, CDCl3) δ 8.16-8.11 (m, 4H), 7.89 (d, J = 9.0 Hz, 1H), 7.84-7.80
(m, 1H), 7.66 (d, J = 9.0 Hz, 1H), 7.55-7.52 (m, 2H), 7.49-7.47 (m, 1H);13C{1H}
NMR (125 MHz, CDCl3) δ 157.5, 146.6, 139.2, 135.8, 132.0, 131.3, 130.6, 129.6,
128.9, 127.7, 127.5, 126.1, 119.8. Spectroscopic data for the title compound were
consistent with those reported in the literature.7a
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7-Fluoro-2-phenylquinoline (3zc): White solid (53.5 mg, 80%), mp 88-89 C. H
NMR (500 MHz, CDCl3) δ 8.22 (d, J = 8.0 Hz, 1H), 8.16 (d, J = 7.5 Hz, 2H),
7.86-7.80 (m, 3H), 7.56-7.53 (m, 2H), 7.50-7.47 (m, 1H), 7.34-7.30 (m, 1H);
13C{1H} NMR (125 MHz, CDCl3) δ 163.3 (d, J = 249.6 Hz), 158.3, 149.3 (d, J = 12.9
Hz), 139.3, 136.6, 129.6, 129.4 (d, J = 10.0 Hz), 128.9, 127.6, 124.2, 118.3 (d, J = 2.5
Hz), 116.7 (d, J = 25.5 Hz), 113.3 (d, J = 20.2 Hz). Spectroscopic data for the title
compound were consistent with those reported in the literature.20e
6-Bromo-2-phenylquinoline (3zd): White solid (62.8 mg, 74%), mp 116-118 oC. 1H
NMR (500 MHz, CDCl3) δ 8.15 (d, J = 8.0 Hz, 2H), 8.10-8.09 (m, 1H), 8.04 (d, J =
8.0 Hz, 1H), 7.96 (s, 1H), 7.88-7.86 (m, 1H), 7.79-7.77 (m, 1H), 7.55-7.52 (m, 2H),
7.50-7.47 (m, 1H); C{1H} NMR (125 MHz, CDCl3) δ 157.6, 146.8, 139.1, 135.8,
13
133.1, 131.4, 129.6, 129.5, 128.9, 128.2, 127.5, 120.0, 119.7. Spectroscopic data for
the title compound were consistent with those reported in the literature.7a
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2-Phenyl-6-(trifluoromethyl)quinoline (3ze): Yellow oil (66.4 mg, 81%). H NMR
(500 MHz, CDCl3) δ 8.26 (d, J = 10.0 Hz, 2H), 8.20-8.17 (m, 2H), 8.12 (s, 1H), 7.94
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(d, J = 10.0 Hz, 1H), 7.90-7.88 ( m, 1H), 7.58-7.51 (m, 3H); 13C{1H} NMR (125
MHz, CDCl3) δ 159.3, 149.3, 138.9, 137.4, 130.9, 130.0, 129.0, 128.2, 127.9, 127.7,
126.1, 125.4 (q, J = 3.8 Hz), 125.3 (q, J = 3.8 Hz), 123.1, 120.0. Spectroscopic data
for the title compound were consistent with those reported in the literature.7a
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6-Fluoro-2-phenylquinoline (3zf): White solid (60.2 mg, 90%), mp 94-95 C. H
NMR (500 MHz, CDCl3) δ 8.21-8.19 (m, 2H), 8.17-8.15 (m, 2H), 7.91 (d, J = 10.5
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Hz, 1H), 7.56-7.44 (m, 5H); C{1H} NMR (125 MHz, CDCl3) δ 160.4 (d, J = 248.0
Hz), 156.7 (d, J = 2.8 Hz), 145.3, 139.2, 136.2 (d, J = 5.2 Hz), 132.1 (d, J = 9.1 Hz),
129.5, 128.9, 127.7 (d, J = 10.0 Hz), 127.5, 119.9 (d, J = 25.7 Hz), 119.7, 110.5 (d, J
= 21.7 Hz). Spectroscopic data for the title compound were consistent with those
reported in the literature.7a
6-Bromo-2-(p-tolyl)quinoline (3zg): Yellow solid (58.8 mg, 66%), mp 171-173 oC.
1H NMR (500 MHz, CDCl3) δ 8.09 (d, J = 8.5 Hz, 1H), 8.07-8.02 (m, 3H), 7.96 (s,
1H), 7.87 (d, J = 8.5 Hz, 1H), 7.77 (d, J = 8.5 Hz, 1H), 7.33 (d, J = 8.5 Hz, 2H), 2.44
(s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 157.6, 146.8, 139.8, 136.3, 135.7, 133.0,
131.3, 129.6, 129.5, 128.2, 127.4, 119.8, 119.6, 21.3. HRMS (ESI) calcd for
C16H13BrN [M + H]+: 298.0226, found 298.0230.
6-Bromo-2-(4-fluorophenyl)quinoline (3zh):Yellow solid (56.0 mg, 62%), mp
o
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162-163 C. H NMR (500 MHz, CDCl3) δ 8.18-8.14 (m, 3H), 8.08-8.07 (m, 1H),
8.00 (s, 1H), 7.86 (d, J = 9.0 Hz, 1H), 7.81-7.79 (m, 1H), 7.22 (dd, J1 = 9.0 Hz, J2 =
8.5 Hz, 2H);13C{1H} NMR (125 MHz, CDCl3) δ 164.0 (d, J = 249.8 Hz), 156.5,
146.8, 135.9, 135.3 (d, J = 3.0 Hz),133.3, 131.3, 129.5, 129.4 (d, J = 8.5 Hz), 128.2,
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