Copper(II)-Catalyzed Aerobic Oxidative Desulfitative 6π Electrocyclization: Efficient Synthesis of Diverse 4-Aminoquinolines

Article abstract of DOI:10.1002/adsc.201700410

The C?C bond formation via C?S bond activation (disclosed in 2000) has received increasing attention. However, stoichiometric amounts of exogenous thiophilic reagents are generally required as thiolate scavengers. Herein, a new model for the synthesis of 4-aminoquinolines, the copper(II)-catalyzed aerobic oxidative desulfitative 6π cyclization of the readily available N-arylimino ketene N,S-acetals is described. The reaction can proceed efficiently under mild conditions without any exogeneous thiolate scavengers (due to the formation of disulfide as the by-product) to afford diverse 4-aminoquinolines, a privileged structure motif displaying antimalarial activity, with a wide range of functional groups at the C-2 to C-8 positions. (Figure presented.).

Full text of DOI:10.1002/adsc.201700410

Title: Copper(II)-Catalyzed Aerobic Oxidative Desulfitative
6π Electrocyclization: Efficient Synthesis of Diverse 4-
Aminoquinolines
Authors: Lou Shi, Ling Pan, Yifei Li, and QUN LIU
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201700410
Link to VoR: http://dx.doi.org/10.1002/adsc.201700410

10.1002/adsc.201700410
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Copper(II)-Catalyzed Aerobic Oxidative Desulfitative
6Electrocyclization: Efficient Synthesis of Diverse 4-
Aminoquinolines
Lou Shi,a Ling Pan, a,b,* Yifei Li,a,b and Qun Liu a,b,*
a
Department of Chemistry, Northeast Normal University, Changchun 130024, China.
Tel (Fax) : +86-(0)431-8509-9759; e-mail: panl948@nenu.edu.cn; liuqun@nenu.edu.cn
Jilin Province Key Laboratory of Organic Functional Molecular Design & Synthesis, Faculty of Chemistry, Northeast
b
Normal University, Changchun 130024, China.
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.
Abstract. The C−C bond formation via C−S bond activation under mild reaction conditions without any exogenous
(disclosed in 2000) has received increasing attentions. thiolate scavengers (due to the formation of disulfide as the
However, stoichiometric amount of exogenous thiophilic by-product) to afford diverse 4-aminoquinolines,
a
reagents are generally required as thiolate scavengers. privileged structure motif displaying antimalarial activity,
Herein, a new model for the synthesis of 4-aminoquinolines, with a wide range of functional groups at C2−C8 positions.
Cu(II)-catalyzed aerobic oxidative desulfitative 6
cyclization of the readily available N-aryl-imino ketene N,S-
acetals is described. The reaction can proceed efficiently
Keywords: 6 cyclization; disulfide as by-product; 4-
aminoquinolines; heterocycles; imino ketene N,S-acetals
Introduction
In the rapidly growing area of transition-metal-
catalyzed C−C cross-coupling reactions, the C−S
bond activation for C−C bond formation,[1] especially
as represented by the Liebeskind−Srogl C−C cross-
coupling (L−S reaction) and its variants, has received
increasing attention and applied in many fields owing
to the expansion of both nucleophilic and
electrophilic sulfur-containing partners.[1-5] The L−S
reaction was disclosed in 2000 aimed at the synthesis
of ketones from Pd-catalyzed, Cu(I)-mediated C−C
cross-coupling of electrophilic thiol esters with
nucleophilic boronic acids under anaerobic, neutral
reaction conditions (Scheme 1a).[2a] In this early
version, at least a stoichiometric amount of Cu(I) salt,
as thiophilic soft Lewis acid, should be used to play
both roles as the co-catalyst to activate C−S bond and
the scavenger to trap the in-situ generated thiolate.[2a,6]
Later on, Cu(I) catalytic systems were studied in
details, for example, through modification of thiol
ester substrates to achieve efficient catalytic turnover
in a thiophilic environment (Scheme 1b and 1c).[2b,c]
Nowadays,
although
more
and
more
organometallics as nucleophiles and thioorganic
compounds as electrophiles have become promising
sources for L−S type reactions[1−5] and Cu(II) salt has
proven an efficient catalyst under aerobic
conditions,[4a] the reaction still faces the challenge
using a stoichiometric amount of Cu(I) salt and
boronic acid (Scheme 1a),[2a,5] boronic acids (Scheme
Scheme 1. Desulfitative C−C cross-coupling and related
reactions.
1
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10.1002/adsc.201700410
Advanced Synthesis & Catalysis
1b)[2b,4a] or esters,[3] the special N−O reactant
(Scheme 1c),[2c] or arynes (as nucleophilic partners,
Scheme 1d)[4b] as thiolate scavenger. In our recent
research, the L−S type reaction with ketene S,S-
acetals[7] as the thioorganic components[4] was
succeeded. However, a stoichiometric amount of
thiolate scavenger, such as, an arylboronic acid[4a] or
an aryne (Scheme 1d),[4b] was still necessary.
Over the last two decades, transition-metal-
catalyzed C−H bond activation for C−C bond
formation[8] has rapidly grown into an active area of
research for their atom- and step-economical
features.[9] Herein, we describe a new reaction model,
Cu(II)-catalyzed aerobic oxidative desulfitative
6cyclization for the construction of 4-
aminoquinolines. This reaction can proceed under
aerobic conditions to provide an alternative to dual
C−H/C−S activation for C−C bond formation process
without the requirement of expensive organometallic
reagents as thiolate scavengers (Scheme 1e). Based
on this new reaction, a simple and practical approach
to diverse 4-aminoquinolines, a privileged structure
motif displaying antimalarial activity,[10] with a wide
range of functional groups at C2−C8 positions, which
would otherwise be difficult to synthesize,[10,11] is
presented.
or withdrawing substitute on ortho-, meta- or para-
position of the phenyl ring are efficient nucleophiles
to give the desired N-aryl-imino ketene N,S-acetals 2
generally in good to high yields. Hopefully, 2l and 2t
can also be prepared in fair yields using 4-
(trifluoromethyl)aniline, bearing a strong electron-
withdrawing trifluoromethyl group, as the aryl amine
component. Clearly, the pseudo three-component
reaction provides a new and efficient access to -
imino ketene N,S-acetals in a single operation under
mild reaction conditions starting from readily
available starting materials.[7] In addition, the gram-
scale synthesis of 2a under identical conditions was
proven successful (7.86 g, 30 mmol of 1a to give 7.40
g of 2a, 67% yield).
Table 1. Preparation of N-aryl-imino ketene N,S-acetals.
Results and Discussion
As our continuing research on the C−S bond
activation for C−C bond formation reaction,[4] the
intramolecular version of the C−S activation for C−C
bond forming reaction was carried out at first using
N-aryl-imino ketene N,S-acetals 2 as the starting
materials. For the preparation of 2, catalyzed by
BF3·Et2O (30 mol%),[12] the model reaction (Table 1)
of the readily available ketene S,S-acetal 1a bearing
an acetyl and an ethoxyl carbonyl group, respectively,
at the terminal carbon[7a] was reacted with aniline (3
equiv) in toluene by adding aniline (toluene solution)
in 3 portions to the mixture of 1a and BF3·Et2O
within 1 h. As the result, ketene N,S-acetal 2a, as an
E/Z mixture,[7c,d] was obtained in 76% yield by
treating the reaction at 80 oC for 5 h. However, lower
yield of 2d (47%) was afforded from the reaction of
1a with 4-methoxyaniline under identical reaction
conditions, due to, probably, the reduced
nucleophilicity of 4-methoxyaniline by the formation
of complex between 4-methoxy moiety of 4-
methoxyaniline and BF3·Et2O. Hopefully, when a
super-acid catalyst, triflic acid (TfOH), was selected
to enhance the electrophilicity of dicarbonyl substrate
1a through protonation with carbonyl oxygen,[13] both
2a and 2d were obtained in high yields. Thus,
catalyzed by TfOH, a series of N-aryl-imino ketene
N,S-acetals 2a−2w were prepared from the pseudo
three-component reaction of selected aryl amines
with ketene S,S-acetals 1a and 1b, respectively (Table
1).
[a] 60% of TfOH was used.
-Oxo ketene N,S-acetals, which easily isomerizes
between (Z)- and (E)-configurations in both polar and
non-polar media under various conditions via an
imine intermediate,[7c,d] are versatile building blocks
in organic synthesis.[7c-e] This isomerization is
important for cyclization reactions due to the “equal
contribution”, for example the (Z)- and (E)-isomers
of ketene N,S-acetals 2 with dense reactive sites.[7c]
The above reaction (Table 1) showed that aniline
and aryl amines bearing either an electron-donating
2
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10.1002/adsc.201700410
Advanced Synthesis & Catalysis
Table 2. Optimization of Reaction Conditions for Synthesis of 4-Anilinoquinolines. [a]
Entry Catalyst [mol%]
Ligand [mol%]
Base [equiv]
Solvent
Temp [oC]
t [h]
3a [%]
1
2
3
4
5
6
7
8
Cu(OAc)2 (30%)
Cu(OAc)2 (30%)
-
CuCl2 (10%)
CuCl2 (10%)
CuBr2 (10%)
Cu2O (10%)
CuI (10%)
CuCl (10%)
AgOAc (10%)
ZnCl2 (10%)
CuCl2 (10%)
CuCl2 (10%)
CuCl2 (10%)
CuCl2 (10%)
CuCl2 (10%)
CuCl2 (10%)
-
-
-
-
DMF
DMF
DMF
130
130
130
80
60
80
80
80
60
80
80
80
80
80
80
80
80
5.5
2.3
10
12
12
21
28
14
7
30
30
16
30
23
30
30
12
30
49
9
K2CO3 (2.0)
K2CO3 (2.0)
K2CO3 (2.0)
K2CO3 (2.0)
K2CO3 (2.0)
K2CO3 (2.0)
K2CO3 (2.0)
K2CO3 (2.0)
K2CO3 (2.0)
K2CO3 (2.0)
K2CO3 (2.0)
K2CO3 (2.0)
K2CO3 (2.0)
K2CO3 (2.0)
K2CO3 (2.0)
K2CO3 (2.0)
Phen (10%)
Phen (10%)
Phen (10%)
Phen (10%)
Phen (10%)
Phen (10%)
Phen (10%)
Phen (10%)
Phen (10%)
Phen (10%)
Phen (10%)
Phen (10%)
Phen (10%)
Phen (10%)
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
DCE
83
67
82
86
83
82
trace
trace
78
65
57
54
20
17
9
10
11
12
13
14
15
16
17[b]
THF
dioxane
CHCl3
EtOH
toluene
[a] General reaction conditions: 2a (0.5 mmol), solvent 1 mL under aerobic conditions, and isolated yields of 3a.
[b] The reaction was conducted under nitrogen atmosphere.
Table 3. Preparation of 4-Aminoquinolines 3a−3w
[a] Reacted at 100 oC.
[b] Reacted at 110 oC.
3
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10.1002/adsc.201700410
Advanced Synthesis & Catalysis
With ready access to N,S-acetals 2 established, the
desulfitative cyclization of 2a (without separation of
the E- and Z-isomers) as a model to form the 4-
aminoquinoline compound, ethyl 2-methyl-4-
(phenylamino)quinoline-3-carboxylate 3a (Table 2),
was then examined. Under similar reaction conditions
as our previous aerobic, Cu-catalyzed desulfitative
C–C bond-forming reaction,[4a] catalyzed by
complex mixture instead of the desired 2a (Scheme
2a). In the case of the reaction of 4b[7c] with aniline,
the sequential deacylation/amination product 5 was
produced (Scheme 2b). These results tell that N-aryl-
imino ketene N,S-acetals 2a−2w should be formed
via N-imino ketene S,S-acetals 6 as intermediate
(Scheme 2c).
o
Cu(OAc)2 (mol 30%) in DMF at 130 C in the open
air for 5.5 h, 3a was obtained in 30% yield (Table 2,
entry 1). Pleasingly, the yield of 3a reached up to
50% by adding K2CO3 (2 equiv) to the above reaction
system (Table 2, entry 2). Whereas, in the absence of
Cu(OAc)2, the yield of 3a decreased to less than 10%
(Table 2, entry 3), indicating the role of both Cu(II)
catalyst and a base for the formation of 3.
Further optimization of reaction conditions showed
that, catalyzed by anhydrous CuCl2 (10 mol%), the
reaction of 2a proceeded efficiently in toluene in the
presence of 1,10-phenanthroline (Phen, 10 mol%)
o
and K2CO3 (2 equiv) in open air at 80 C for 12 h
(Table 2, entry 4). In this case, 3a was obtained in
83% yield. Whereas, lower yield of 3a was formed by
o
reducing the reaction temperature to 60 C (Table 2,
entry 5). Under similar reaction conditions as in
Table 2, entry 4, CuBr2, Cu2O (Table 2, entry 7), CuI
(Table 2, entry 8), and CuCl (Table 2, entry 9) were
efficient catalysts, respectively (Table 2, entries 6−9).
As a comparison, AgOAc and ZnCl2 were inefficient
catalysts (Table 2, entries 10 and 11); the solvents,
such as 1,2-dichloroethane (DCE), THF, dioxane, and
chloroform (Table 2, entries 12−15) gave lower
yields of 3a.
It was found that, running the reaction of 2a under
the identical conditions as in Table 2, entry 4 but in a
nitrogen atmosphere, 3a was given in low yield
(Table 2, entry 17). This result indicates that the
existence of molecular oxygen plays a crucial role for
desulfitative cyclization of 2 to give 3. Thus, under
the optimal conditions (Table 2, entry 4), a series of
4-anilinoquinolines 3 were prepared (Table 3).
Scheme 2. Proposed mechanism for formation of imino
ketene N,S-acetals 2a−2w.
Catalyzed either by BF3·Et2O or TfOH (Table 1),
the attempted isolation of 6a from the reaction of 1a
with aniline was failed. Alternatively, 4-
anilinoquinoline 3x, bearing an aryl group at C2, was
prepared in excellent yield with N-aryl-imino ketene
N,S-acetal 2x as substrate (Scheme 3a). In this case,
2x was synthesized by the reaction of -enamino
ester 7[16] with isothiocyanatobenzene. Similarly, 2y
and 2z were prepared and 4-anilinoquinoline 3y and
3z, bearing a (p-methoxyphenyl)amino and benzyl
amino group at C4, respectively, were also obtained.
The experimental results (Table 3) showed that, all
the N-aryl-imino ketene N,S-acetals 2a−2w (Table 1)
as substrates, including 2l and 2t bearing a strong
electron-withdrawing trifluoromethyl group,[14] can
give the desired 4-anilinoquinolines 3a−3w[15] in high
to excellent yields, though the nucleophilicity of the
4-(trifluoromethyl)aniline is reduced. In addition, the
desulfitative
cyclization
of
2
proceeds
chemoselectively, leaving ester (3a–l), acetyl (3m–t),
and, aryl halides, especially, the aryl bromide (3g and
3r) and aryl iodide (3h) functionalities intact. These
reactive functional groups can be utilized for further
modifications through Suzuki coupling and other
reactions. Furthermore, the gram-scale synthesis of
3a under identical conditions was proven successful
(7.40 g, 20.10 mmol of 2a to give 5.02 g of 3a, 81%
yield).
-Imino ketene N,S-acetals have rarely been
studied.[7c] It was found that, catalyzed either by
BF3·Et2O[12] or TfOH (Table 1), the reaction of -oxo
ketene N,S-acetal 4a[7c] with aniline afforded a
Scheme 3. Preparation of ketene N,S-acetals 2x−2z, 4-
aminoquinolines 3x−3z, and carbodiimide 10.
4
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10.1002/adsc.201700410
Advanced Synthesis & Catalysis
Conclusion
The successful synthesis of 4-aminoquinolines
3x−3z starting from -enamino ester 7 provides an
alternative route to 4-aminoquinolines and an
experimental evidence to support the formation of
2a−2w via N-imino ketene S,S-acetal intermediate 6
(Scheme 2c). Furthermore, N-imino ketene S,S-acetal
6x was prepared and subjected to the reaction
conditions for the synthesis of 4-aminoquinolines 3
(Scheme 3b). In this case, however, 4-ethylthio
quinoline 8 could not be obtained and 6x was
recovered in 83% yield. These results show that the
N,S-acetal moiety is crucial for the desulfitative
cyclization reaction. Indeed, carbodiimide 10 was
obtained from the Cu(II)-catalyzed elimination of
EtSH of carbamimidothioate 9 (Scheme 3c).
In conclusion, an extremely simple and efficient
pathway to construct substituted 4-anilinoquinolines
via
Cu(II)-catalyzed
desulfitative
6electrocyclization with disulfide as the by product
was developed. In this unprecedented reaction,
various imino ketene N,S-acetals, as starting materials,
can be prepared, generally, in good to high yields by
either the acid-catalyzed three-component reaction of
arylamines with acetyl ketene S,S-acetals or by the
reaction of -enamino esters with isothiocyanates
under mild reaction conditions. The Cu(II)-catalyzed
desulfitative cyclization of N-aryl-imino ketene N,S-
acetals can tolerate a wide range of reactive
functional groups and incorporate various functional
groups at C2−C8 positions of 4-anilinoquinolines as
products. Further works focused on expansion of this
new strategy are in progress.
In addition, running the reaction of 9 under the
identical conditions as in Table 2, entry 4 but in a
nitrogen atmosphere gave low yields of 10 (10%),
indicating that the existence of molecular oxygen in
air plays a crucial role for elimination of EtSH from 9
to afford 10. Based on above results (Table 2, 3 and
Scheme 3) and related reports,[4a,17,18] a mechanism for Experimental Section
the formation of 4-anilinoquinolines 3 was proposed
General procedure for the synthesis of 2 (taking 2a as an
(Scheme 4, with 3a as an example).
example).
To
the
solution
of
ethyl
2-
[bis(ethylthio)methylene]-3-oxobutanoate (131 mg, 0.50
mmol) and aniline (140 mg, 1.50 mmol) in toluene (1.0
mL) was added trifluoromethanesulfonic acid (13.3 L,
o
0.15 mmol), and stirred at 80 C. After the reaction was
finished as indicated by TLC (reaction time, 3.2 h),the
resulting mixture was allowed to cool to room temperature
and slowly poured into saturated aqueous NaCl (20 mL),
and extracted with dichloromethane (20 mL × 3). The
combined organic phase was dried over anhydrous
Na2SO4and concentrated in vacuo. The crude product was
purified by column chromatography on silica gel
(PE/EtOAc = 60:1) to afford 2a (134 mg, 73% yield) as
yellowish solid.
(3E)-Ethyl
2-(ethylthio(phenylamino)methylene)-3-
(phenylimino)butanoate(2a) [E/Z=1/4]: yield: 134 mg
(73%); yellowish solid; mp 45–46 oC; 1H NMR (500 MHz,
CDCl3) (Z-2a):= 10.85 (s, 1H), 7.27–7.21 (m, 4H), 7.13
(t, J = 7.5 Hz, 1H), 7.01 (t, J = 7.5 Hz, 1H), 6.89 (d, J = 7.5
Hz, 2H), 6.81 (d, J = 7.5 Hz, 2H), 4.23–4.15 (m, 2H),
3.13–3.00 (m, 2H), 1.93 (s, 3H), 1.38 (t, J = 7.5 Hz, 3H),
1.31 (t, J = 7.5 Hz, 3H). 1H NMR (500 MHz, CDCl3) (E-
2a): = 11.12 (s, 1H), 7.37–7.34 (m, 4H), 7.26–7.20 (m,
1H), 7.15–7.09 (m, 3H), 6.93 (d, J = 7.5 Hz, 2H), 4.26 (q,
J = 7.5 Hz, 2H), 2.75 (q, J = 7.5 Hz, 2H), 2.18 (s, 3H),
1.34 (t, J = 7.5 Hz, 3H), 1.18 (t, J = 7.5 Hz, 3H). 13C NMR
(125 MHz, CDCl3): = 167.7, 165.5, 157.8, 150.9, 138.4,
129.2, 129.0, 128.9, 128.4, 125.9, 125.6, 125.4, 125.2,
123.9, 123.2, 120.1, 119.3, 96.0, 59.7, 59.6, 27.0, 25.3,
17.9, 17.2, 14.4(2), 13.9. HR-MS (ESI): m/z = 369.1635,
calcd. for C21H25N2O2S (M+H)+: 369.1631.
Scheme 4. Proposed mechanism for formation of 4-
aminoquinolines 3.
According to the nature of the reversible
isomerization of ketene N,S-acetals,[7c,d] and
elimination of EtSH from 9 (Scheme 3c), a base-
promoted elimination of EtSH from imino ketene
N,S-acetal 2a would occur along with the generation
of ketenimine intermediate B and LCu(SEt)2 (L =
Phen).
electrocyclization[17] followed by aromatization to
give the thermodynamically favored 4-
Ketenimine
(B)
undergoes
6
(3E)-Ethyl 2-(ethylthio(p-tolylamino)methylene)-3-(p-
tolylimino)butanoate(2b) [E/Z=1:3]: yield: 164 mg
(83%); yellowish solid; mp 63–64 oC; 1H NMR (500 MHz,
CDCl3) (Z-2b): = 10.77 (s, 1H), 7.08 (d, J = 8.0 Hz, 2H),
7.03 (d, J = 8.0 Hz, 2H), 6.82 (d, J = 8.0 Hz, 2H), 6.69 (d,
J = 8.0 Hz, 2H), 4.22–4.15 (m, 2H), 3.12–2.98 (m, 2H),
2.30 (s, 3H), 2.29 (s, 3H), 1.90 (s, 3H), 1.37 (t, J = 7.5 Hz,
3H), 1.31 (t, J = 7.5 Hz, 3H). 1H NMR (500 MHz, CDCl3)
(E-2b): = 11.02 (s, 1H), 7.18–7.15 (m, 4H), 7.02–7.00 (m,
2H), 6.84–6.81 (m, 2H), 4.25 (q, J = 7.0 Hz, 2H), 2.74 (q,
J = 7.5 Hz, 2H), 2.35 (s, 3H), 2.34 (s, 3H), 2.14 (s, 3H),
1.34 (d, J = 7.0 Hz, 3H), 1.18 (t, J = 7.5 Hz, 3H). 13C NMR
(125 MHz, CDCl3): = 168.2, 167.8, 166.9, 165.1, 158.9,
158.1, 148.2, 148.0, 135.8, 135.7, 135.5, 133.4, 132.4,
129.7, 129.5, 129.0, 125.5, 125.2, 119.9, 119.2, 96.7, 95.5,
59.6, 59.5, 59.4, 26.9, 25.2, 21.0, 20.9, 20.8(2), 17.8, 17.1,
anilinoquinolines 3. At the same time, serving as a
crucial step forward, the eliminated EtSH is to be
oxidized by Cu(II) to form the disulfide,[18] (EtS)2, as
the by-product along with formation of a Cu(I)
species. In the presence of molecular oxygen as the
oxidant, catalytic system LCuIICl2 is to be regenerated
for the next cycle through oxidation of Cu(I) species
(Scheme 4). This mechanism can also be used to
explain the efficiency of Cu(I) salts as the catalysts
(Table 2, entries 8 and 9).
5
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10.1002/adsc.201700410
Advanced Synthesis & Catalysis
14.5, 14.4(2), 13.9. HR-MS (ESI): m/z = 397.1951, calcd.
(ESI): m/z = 437.0841, calcd. for C21H23Cl2N2O2S (M+H)+:
437.0852.
for C23H29N2O2S (M+H)+: 397.1944.
(3E)-Ethyl 2-(ethylthio(m-tolylamino)methylene)-3-(m-
tolylimino)butanoate(2c) [E/Z=1:4]: yield: 152 mg
(77%); yellow viscous liquid; 1H NMR (500 MHz, CDCl3)
(Z-2c): = 10.82 (s, 1H), 7.15–7.10 (m, 2H), 6.95 (d, J =
7.0 Hz, 1H), 6.81 (d, J = 7.5 Hz, 1H), 6.72–6.70 (m, 2H),
6.64 (s, 1H), 6.58 (d, J = 7.5 Hz, 1H), 4.40–4.05 (m, 2H),
2.99–3.12 (m, 2H), 2.28 (s, 3H), 2.27 (s, 3H), 1.96 (s, 3H),
1.37 (t, J = 7.5 Hz, 3H), 1.32 (t, J = 7.5 Hz, 3H). 1H NMR
(3E)-Ethyl
2-((4-bromophenylamino)(ethylthio)
methylene)-3-(4-bromophenylimino)butanoate(2g)
[E/Z=1:5]: yield: 194 mg (74%); yellowish solid; mp 78–
o
1
80 C; H NMR (500 MHz, CDCl3) (Z-2g): = 10.83 (s,
1H), 7.40 (d, J = 8.5 Hz, 2H), 7.34 (d, J = 8.0 Hz, 2H),
6.81 (d, J = 8.0 Hz, 2H), 6.67 (d, J = 8.5 Hz, 2H), 4.18 (q,
J = 7.0 Hz, 2H), 3.12–3.00 (m, 2H), 1.91 (s, 3H), 1.36 (t, J
1
= 7.5 Hz, 3H), 1.30 (t, J = 7.5 Hz, 3H). H NMR (500
(500 MHz, CDCl3) (E-2c): = 11.09 (s, 1H), 7.25–7.21 (m, MHz, CDCl3) (E-2g): = 11.07 (s, 1H), 7.48–7.45 (m, 4H),
2H), 7.02 (d, J = 7.5 Hz, 1H), 6.95–6.91 (m, 3H), 6.72–
6.70 (m, 2H), 4.28–4.12 (m, 2H), 2.74 (q, J = 7.5 Hz, 2H),
2.35 (s, 3H), 2.34 (s, 3H), 2.19 (s, 3H), 1.35 (t, J = 7.5 Hz,
3H), 1.18 (t, J = 7.5 Hz, 3H). 13C NMR (125 MHz,
CDCl3): = 168.0, 167.6, 166.6, 165.1, 158.5, 157.8,
150.9, 150.5, 139.0, 138.8, 138.6, 138.3, 137.8, 128.8,
128.7, 128.1, 126.5, 126.3, 125.9, 125.7, 124.6, 123.8,
122.3, 122.0, 120.7, 119.8, 116.7, 116.2, 97.0, 95.9, 59.5,
59.4, 26.9, 25.2, 21.4, 21.3, 21.2, 21.1, 17.8, 17.1, 14.4(2),
14.3, 13.8. HR-MS (ESI): m/z = 335.1766, calcd. for
C21H23N2O2 (M-SEt)+: 335.1754.
6.99 (d, J = 8.0 Hz, 2H), 6.82–6.79 (m, 2H), 4.25 (q, J =
7.0 Hz, 2H), 2.74 (q, J = 7.5 Hz, 2H), 2.14 (s, 3H), 1.33 (t,
J = 7.0 Hz, 3H), 1.18 (t, J = 7.5 Hz, 3H). 13C NMR (125
MHz, CDCl3): = 167.5, 166.3, 157.9, 157.3, 149.8, 149.3,
137.3, 132.3, 132.2, 132.1, 131.5, 126.8, 126.7, 121.8,
121.2, 119.1, 117.0, 116.2, 96.4, 59.9, 59.8, 27.1, 25.4,
17.8, 17.1, 14.4, 14.3, 13.8. HR-MS (ESI): m/z = 524.9831,
calcd. for C21H23Br2N2O2S (M+H) +: 524.9842.
(3E)-Ethyl 2-(ethylthio(4-iodophenylamino)methylene)-
3-(4-iodophenylimino)butanoate(2h) [E/Z=1:5]: yield:
o
1
205 mg (66%); yellowish solid; mp 90–91 C; H NMR
(500 MHz, CDCl3) (Z-2h): = 10.84 (s, 1H), 7.59 (d, J =
8.5 Hz, 2H), 7.53 (d, J = 8.5 Hz, 2H), 6.69 (d, J = 8.5 Hz,
2H), 6.55 (d, J = 8.5 Hz, 2H), 4.21–4.14 (m, 2H), 3.10–
2.98 (m, 2H), 1.92 (s, 3H), 1.36 (t, J = 7.5 Hz, 3H), 1.30 (t,
(3E)-Ethyl
2-(ethylthio(4-methoxyphenylamino)
methylene)-3-(4-methoxyphenylimino)butanoate(2d)
[E/Z=2:7]: yield: 165 mg (77%); yellow viscous liquid; 1H
NMR (400 MHz, CDCl3) (Z-2d): = 10.68 (s, 1H), 6.94–
6.72 (m, 8H), 4.30–4.13 (m, 2H), 3.77 (s, 3H), 3.76 (s, 3H), J = 7.0 Hz, 3H). 1H NMR (500 MHz, CDCl3) (E-2h): =
2.97–3.13 (m, 2H), 1.82 (s, 3H), 1.37 (t, J = 7.2 Hz, 3H),
1.30 (t, J = 7.2 Hz, 3H). 1H NMR (400 MHz, CDCl3) (E-
2d): = 10.92 (s, 1H), 7.06 (d, J = 8.8 Hz, 2H), 6.94–6.72
11.08 (s, 1H), 7.67–7.64 (m, 4H), 6.87 (d, J = 8.5 Hz, 2H),
6.69 (d, J = 8.5 Hz, 2H), 4.31–4.22 (m, 2H), 2.77–2.69 (m,
2H), 2.15 (s, 3H), 1.35–1.31 (m, 3H), 1.18 (t, J = 7.0 Hz,
(m, 6H), 3.80 (s, 3H), 3.79 (s, 3H), 2.75 (q, J = 7.5 Hz, 2H), 3H). 13C NMR (125 MHz, CDCl3): = 167.8, 167.4, 166.1,
2.09 (s, 3H), 1.36–1.34 (m, 3H), 1.19 (t, J = 7.5 Hz, 3H).
13C NMR (125 MHz, CDCl3): = 168.2, 167.9, 165.2,
159.4, 158.6, 157.9, 157.7, 156.3, 155.7, 152.7, 144.0,
143.8, 139.9, 131.2, 127.3, 127.0, 121.3, 120.6, 116.3,
114.7, 114.3, 114.2, 114.1, 113.7, 95.1, 59.5, 59.4, 55.6,
55.4, 55.3, 26.9, 25.2, 17.6, 17.0, 14.4, 13.9. HR-MS (ESI):
m/z = 429.1832, calcd. for C23H29N2O4S (M+H)+: 429.1843.
157.7, 157.0, 150.4, 138.2, 138.0, 137.9, 137.4, 137.3,
126.9, 126.7, 122.2, 121.5, 119.9, 96.4, 89.8, 86.9, 59.8,
27.1, 25.4, 17.8, 17.1, 14.4, 14.3, 13.8. HR-MS (ESI): m/z
+
= 642.9385, calcd. for C21H22I2N2NaO2S (M+Na)
642.9384.
:
(3E)-Ethyl
2-(ethylthio(3-methoxyphenylamino)
methylene)-3-(3-methoxyphenylimino)butanoate(2i)
(3E)-Ethyl
2-(ethylthio(4-fluorophenylamino)
[E/Z=1:4]: yield: 161 mg (75%); yellowish viscous liquid;
1H NMR (400 MHz, CDCl3) (Z-2i): = 10.84 (s, 1H),
7.18–7.11 (m, 2H), 6.73–6.63 (m, 1H), 6.57 (d, J = 8.8 Hz,
1H), 6.52 (d, J = 8.0 Hz, 1H), 6.47 (s, 1H), 6.40–6.37 (m,
2H), 4.20 (q, J = 7.2 Hz, 2H), 3.74 (s, 3H), 3.73 (s, 3H),
3.13–3.00 (m, 2H), 1.98 (s, 3H), 1.37 (t, J = 7.2 Hz, 3H),
1.32 (t, J = 7.2 Hz, 3H). 1H NMR (400 MHz, CDCl3) (E-
2i): = 11.09 (s, 1H), 7.30–7.24 (m, 2H), 6.77–6.67 (m,
4H), 6.57–6.52 (m, 1H), 6.48 (s, 1H), 4.26 (q, J = 7.2 Hz,
2H), 3.80 (s, 3H), 3.78 (s, 3H), 2.74 (q, J = 7.2 Hz, 2H),
2.20 (s, 3H), 1.35 (t, J = 7.2 Hz, 3H), 1.19 (t, J = 7.2 Hz,
3H). 13C NMR (125 MHz, CDCl3): = 167.9, 167.5, 166.9,
165.5, 160.1, 159.9, 159.7, 158.3, 157.6, 152.1, 151.6,
139.4, 129.7, 129.6, 129.5, 129.0, 117.5, 117.2, 112.4,
111.6, 111.3, 111.1, 110.9, 110.6, 109.0, 108.8, 105.6,
105.2, 97.2, 96.1, 59.6, 59.5, 55.2, 55.1, 55.0, 54.9, 26.9,
25.2, 17.8, 17.1, 14.3(2), 14.0, 13.8. HR-MS (ESI): m/z =
429.1837, calcd. for C23H29N2O4S (M+H) +: 429.1843.
methylene)-3-(4-fluorophenylimino)butanoate(2e)
[E/Z=1:5]: yield: 167 mg (86%); yellowish solid; mp 83–
o
1
84 C; H NMR (500 MHz, CDCl3) (Z-2e): = 10.76 (s,
1H), 6.99–6.92 (m, 4H), 6.90–6.88 (m, 2H), 6.78–6.75 (m,
2H), 4.20 (q, J = 7.5 Hz, 2H), 3.13–2.99 (m, 2H), 1.85 (s,
3H), 1.37 (t, J = 7.5 Hz, 3H), 1.30 (t, J = 7.5 Hz, 3H). 1H
NMR (500 MHz, CDCl3) (E-2e): = 11.01 (s, 1H), 7.12–
7.09 (m, 2H), 7.07–7.03 (m, 4H), 6.90–6.88 (m, 2H), 4.26
(q, J = 7.5 Hz, 2H), 2.76 (q, J = 7.5 Hz, 2H), 2.11 (s, 3H),
1.34 (t, J = 7.5 Hz, 3H), 1.19 (t, J = 7.5 Hz, 3H). 13C NMR
(125 MHz, CDCl3): = 167.8, 167.5, 166.1, 160.5 (d, J
=244.6 Hz), 160.7 (d, J =244.9 Hz), 160.5, 160.1, 158.6,
158.1, 157.9, 146.7 (d, J = 2.8 Hz), 146.4 (d, J = 2.8 Hz),
134.3 (d, J = 2.8 Hz), 134.2 (d, J = 2.8 Hz), 127.4 (d, J =
8.4 Hz), 127.2 (d, J = 8.4 Hz), 121.2 (d, J = 7.9 Hz), 120.6
(d, J = 7.9 Hz), 115.8 (d, J = 22.1 Hz), 115.0 (d, J = 22.1
Hz), 95.6(2), 59.5, 26.9, 25.2, 17.5, 16.8, 14.3(2), 14.2,
13.7. HR-MS (ESI): m/z
= 405.1428, calcd. for
C21H23F2N2O2S (M+H)+: 405.1443.
(3E)-Ethyl
2-((biphenyl-4-ylamino)(ethylthio)
methylene)-3-(biphenyl-4-ylimino)butanoate(2j)
(3E)-Ethyl
2-((4-chlorophenylamino)(ethylthio)
[E/Z=2:9]: yield: 182 mg (70%); yellowish solid; mp 46–
o
1
methylene)-3-(4-chlorophenylimino)butanoate(2f)
48 C; H NMR (500 MHz, CDCl3) (Z-2j):= 10.97 (s,
[E/Z=1:3]: yield: 164 mg (75%); white solid; mp 96–97 oC; 1H), 7.62–7.57 (m, 3H), 7.51 (d, J = 8.0 Hz, 4H), 7.47 (d,
1H NMR (500 MHz, CDCl3) (Z-2f): = 10.84 (s, 1H), 7.24
(d, J = 8.5 Hz, 2H), 7.20 (d, J = 8.5 Hz, 2H), 6.86 (d, J =
8.5 Hz, 2H), 6.73 (d, J = 8.5 Hz, 2H), 4.19 (q, J = 7.0 Hz,
2H), 3.16–2.94 (m, 2H), 1.91 (s, 3H), 1.36 (t, J = 7.0 Hz,
3H), 1.30 (t, J = 7.0 Hz, 3H). 1H NMR (500 MHz, CDCl3)
(E-2f): = 11.08 (s, 1H), 7.32 (d, J = 8.5 Hz, 4H), 7.05 (d,
J = 8.5 Hz, 2H), 6.86 (d, J = 8.5 Hz, 2H), 4.25 (q, J = 7.5
Hz, 2H), 2.75 (q, J = 7.5 Hz, 2H), 2.14 (s, 3H), 1.33 (t, J =
7.5 Hz, 3H), 1.18 (t, J = 7.5 Hz, 3H). 13C NMR (125 MHz,
CDCl3): = 167.9, 167.7, 167.4, 166.2, 157.9, 157.3,
149.3, 148.8, 136.8, 136.7, 131.4, 131.2, 129.2, 129.1,
129.0, 128.4, 128.3, 126.5, 126.3, 121.3, 120.7, 97.7, 96.2,
59.8, 59.7, 27.0, 25.3, 17.7, 17.0, 14.3, 14.2, 13.7. HR-MS
J = 8.5 Hz, 2H), 7.41–7.37 (m, 4H), 7.31–7.26 (m, 1H),
6.96 (d, J = 8.5 Hz, 2H), 6.91 (d, J = 8.5 Hz, 2H), 4.31–
4.20 (m, 2H), 3.27–2.95 (m, 2H), 2.02 (s, 3H), 1.40 (t, J =
7.5 Hz, 3H), 1.34 (t, J = 7.0 Hz, 3H). 1H NMR (500 MHz,
CDCl3) (E-2j):= 11.21 (s, 1H), 7.65–7.54 (m, 4H), 7.43–
7.37 (m, 4H), 7.34 (d, J = 7.5 Hz, 1H), 7.31–7.26 (m, 5H),
7.20–7.18 (m, 2H), 7.03 (d, J = 8.0 Hz, 2H), 4.37–4.14 (m,
2H), 2.78 (q, J = 7.5 Hz, 2H), 2.26 (s, 3H), 1.37 (d, J = 7.0
Hz, 3H), 1.21 (t, J = 7.5 Hz, 3H). 13C NMR (125 MHz,
CDCl3): = 168.1, 167.7, 167.0, 165.6, 158.3, 157.6,
150.1, 149.6, 140.8, 139.9, 138.6, 138.3, 137.5(2), 136.8,
135.9, 128.8, 128.7, 128.6, 127.7(2), 127.5, 127.3, 127.1,
126.8, 126.7(2), 126.6, 125.4, 125.1, 120.5, 119.8, 97.5,
96.2, 59.7, 59.6, 27.1, 25.4, 17.9, 17.3, 14.5, 14.4(2), 13.9.
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.201700410
Advanced Synthesis & Catalysis
HR-MS (ESI): m/z = 521.2245, calcd. for C33H33N2O2S
NMR (500 MHz, CDCl3) (Z-2o): = 13.18 (s, 1H), 6.91–
6.79 (m, 8H), 3.71 (s, 3H), 3.70 (s, 3H), 3.12–3.02 (m, 2H),
(M+H)+: 521.2257.
1
2.20 (s, 3H), 1.92 (s, 3H), 1.37 (t, J = 7.5 Hz, 3H). H
NMR (500 MHz, CDCl3) (E-2o): = 13.28 (s, 1H), 7.05 (d,
J = 8.5 Hz, 2H), 6.91–6.79 (m, 6H), 3.74 (s, 3H), 3.73 (s,
3H), 2.76–2.60 (m, 2H), 2.35 (s, 3H), 2.12 (s, 3H), 1.17 (t,
J = 7.5 Hz, 3H). 13C NMR (125 MHz, CDCl3): = 192.6,
192.4, 168.4, 165.9, 160.2, 160.1, 157.6, 157.5, 156.0,
155.6, 142.9, 142.4, 130.0, 126.5, 126.3, 121.5, 120.0,
113.9, 113.8, 113.4, 107.8, 106.3, 54.8(2), 54.7(2), 27.5,
27.2, 27.0, 24.8, 17.2, 16.5, 13.9, 13.5. HR-MS (ESI): m/z
= 399.1737, calcd. for C22H27N2O3S (M+H)+: 399.1737.
(3E)-Ethyl 2-(ethylthio(o-tolylamino)methylene)-3-(o-
tolylimino)butanoate(2k) [E/Z=1:1]: yield: 91 mg (46%);
1
yellowish viscous liquid; H NMR (400 MHz, CDCl3) (Z-
2k): = 10.64 (s, 1H), 7.25–7.07 (m, 4H), 7.04–7.00 (m,
2H), 6.76 (d, J = 8.0 Hz, 1H), 6.66 (d, J = 7.6 Hz, 1H),
4.21–4.13 (m, 2H), 3.16–3.05 (m, 2H), 2.25 (s, 6H), 1.99
(s, 3H), 1.39 (t, J = 7.2 Hz, 3H), 1.27 (t, J = 7.2 Hz, 3H).
1H NMR (400 MHz, CDCl3) (E-2k): = 10.95 (s, 1H),
7.25–7.07 (m, 6H), 6.94–6.88 (m, 2H), 4.26 (q, J = 6.8 Hz,
2H), 2.74 (q, J = 7.2 Hz, 2H), 2.31 (s, 3H), 2.10 (s, 3H),
1.73 (s, 3H), 1.34 (t, J = 6.8 Hz, 3H), 1.18 (t, J = 7.2 Hz,
3H). 13C NMR (125 MHz, CDCl3): = 168.1, 167.8, 166.9,
163.7, 159.0(2), 149.1, 148.2, 137.0, 136.9, 134.5, 134.0,
130.7, 130.5, 130.3, 129.9, 129.8, 127.4, 127.1, 126.7,
126.6, 126.5, 126.4, 126.2, 126.1, 125.5, 123.8, 123.3,
118.7, 118.2, 96.1, 94.7, 59.4, 59.3, 26.7, 24.9, 17.9(2),
17.4(2), 17.3, 16.8, 14.4, 14.3, 14.2(2). HR-MS (ESI): m/z
= 397.1937, calcd. for C23H29N2O2S (M+H)+: 397.1944.
(4E)-3-(Ethylthio(4-fluorophenylamino)methylene)-4-
(4-fluorophenylimino)pentan-2-one(2p) [E/Z=1:3]: yield:
o
1
125 mg (67%); white solid; mp 88–90 C; H NMR (400
MHz, CDCl3) (Z-2p): = 13.15 (s, 1H), 7.10–6.94 (m, 6H),
6.79–6.74 (m, 2H), 3.14–3.03 (m, 2H), 2.22 (s, 3H), 1.90
1
(s, 3H), 1.39 (t, J = 7.2 Hz, 3H). H NMR (400 MHz,
CDCl3) (E-2p): = 13.26 (s, 1H), 7.17–6.93 (m, 6H),
6.91–6.88 (m, 2H), 2.76–2.72 (m, 2H), 2.35 (s, 3H), 2.12
(s, 3H), 1.21 (t, J = 7.2 Hz, 3H). 13C NMR (125 MHz,
CDCl3): = 193.6, 193.5, 169.9, 168.0, 161.0 (d, J =246.3
Hz), 160.2, 160.1, 159.4 (d, J =241.3 Hz), 145.8 (d, J =2.5
Hz), 133.7 (d, J =2.5 Hz), 127.5 (d, J =8.8 Hz), 127.3 (d, J
=8.8 Hz), 121.9 (d, J =7.5 Hz), 120.6 (d, J =7.5 Hz), 116.3,
116.1(2), 116.0, 115.9, 115.8, 115.5, 115.3, 108.6, 106.9,
28.0, 27.8, 27.6, 25.5, 17.8, 17.0, 14.3, 13.8. HR-MS (ESI):
m/z = 397.1150, calcd. for C20H20F2N2NaOS (M+Na)+:
397.1157.
(3E)-Ethyl
2-(ethylthio(4-(trifluoromethyl)
phenylamino)methylene)-3-(4-(trifluoromethyl)
phenylimino)butanoate(2l) [E/Z=1:6]: yield: 86 mg
(34%); yellowish viscous liquid; 1H NMR (400 MHz,
CDCl3) (Z-2l): =11.06 (s, 1H), 7.57–7.50 (m, 4H), 7.02
(d, J = 8.4 Hz, 2H), 6.87 (d, J = 8.4 Hz, 2H), 4.22 (q, J =
7.2 Hz, 2H), 3.17–3.00 (m, 2H), 2.03 (s, 3H), 1.39 (t, J =
7.2 Hz, 3H), 1.34 (t, J = 7.2 Hz, 3H). 1H NMR (400 MHz,
CDCl3) (E-2l): =11.30 (s, 1H), 7.63 (d, J = 8.4 Hz, 2H),
7.57–7.55 (m, 2H), 7.22 (d, J = 8.0 Hz, 2H), 6.94 (d, J =
(4E)-3-((4-Chlorophenylamino)(ethylthio)methylene)-4-
8.0 Hz, 2H), 4.30–4.24 (m, 2H), 2.76–2.74 (m, 2H), 2.26 (s, (4-chlorophenylimino)pentan-2-one(2q)
[E/Z=1:3]:
o 1
3H), 1.39–1.33 (m, 3H), 1.23–1.20 (m, 3H). 13C NMR (125
MHz, CDCl3):  =167.4, 166.6, 156.6, 154.0, 141.5, 127.2
(q, J = 32.6 Hz), 126.3 (q, J = 3.9 Hz), 125.8 (q, J = 4.1
Hz), 124.2, 123.3, 122.8, 120.5, 120.1, 119.5, 97.6, 60.1,
26.4, 25.5, 18.0, 14.4, 13.7. 19F NMR (470 MHz, CDCl3):
= -63.8(2), -64.2, -64.3. HR-MS (ESI): m/z = 527.1196,
calcd. for C23H22F6N2NaO2S (M+Na)+: 527.1198.
yield: 134 mg (66%); white solid; mp 121–122 C; H
NMR (500 MHz, CDCl3) (Z-2q): = 13.23 (s, 1H), 7.29 (d,
J = 8.0 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 6.93 (d, J = 8.0
Hz, 2H), 6.72 (d, J = 8.0 Hz, 2H), 3.15–3.02 (m, 2H), 2.21
(s, 3H), 1.95 (s, 3H), 1.39 (t, J = 7.5 Hz, 3H). 1H NMR
(500 MHz, CDCl3) (E-2q): = 13.33 (s, 1H), 7.36–7.33 (m,
4H), 7.08 (d, J = 8.0 Hz, 2H), 6.87 (d, J = 8.0 Hz, 2H),
2.75–2.72 (m, 2H), 2.35 (s, 3H), 2.15 (s, 3H), 1.20 (t, J =
7.5 Hz, 3H). 13C NMR (125 MHz, CDCl3): = 193.7,
193.5, 169.8, 168.3, 159.5, 148.5, 148.3, 136.3, 136.2,
132.1, 131.9, 129.4, 129.2, 128.9, 128.8, 126.7, 126.6,
121.8, 120.5, 108.8, 107.2, 28.1, 27.8, 27.6, 25.5, 17.9,
17.0, 14.2, 13.7. HR-MS (ESI): m/z = 429.0566, calcd. for
C20H20Cl2N2NaOS (M+Na)+: 429.0566.
(4E)-3-(Ethylthio(phenylamino)methylene)-4-
(phenylimino)pentan-2-one(2m) [E/Z=1:3]: yield: 106
o
1
mg (63%); yellowish solid; mp 76–77 C; H NMR (500
MHz, CDCl3) (Z-2m): = 13.25 (s, 1H), 7.33–7.25 (m,
4H), 7.20 (t, J = 7.5 Hz, 1H), 7.04 (t, J = 7.5 Hz, 1H),
6.97(d, J = 7.5 Hz, 2H), 6.80 (m, J = 7.5 Hz, 2H), 3.21–
2.99 (m, 2H), 2.24 (s, 3H), 1.98 (s, 3H), 1.40 (t, J = 7.5 Hz,
1
3H). H NMR (500 MHz, CDCl3) (E-2m): = 13.38 (s,
(4E)-3-((4-Bromophenylamino)(ethylthio)methylene)-4-
1H), 7.41–7.38 (m, 4H), 7.27–7.25 (m, 1H), 7.16–7.13 (m,
3H), 6.94 (d, J = 7.0 Hz, 2H), 2.76–2.72 (m, 2H), 2.38 (s,
3H), 2.19 (s, 3H), 1.20 (t, J = 7.5 Hz, 3H). 13C NMR (125
(4-bromophenylimino)pentan-2-one(2r)
[E/Z=2:7]:
o 1
yield: 168 mg (68%); yellowish solid; mp 106–108 C; H
NMR (400 MHz, CDCl3) (Z-2r): = 13.24 (s, 1H), 7.42
MHz, CDCl3): = 193.3, 167.5, 160.0, 149.9, 137.8, 129.2, (d, J = 8.8 Hz, 2H), 7.36 (d, J = 8.8 Hz, 2H), 6.86 (d, J =
129.1(2), 128.7, 126.5, 126.3, 125.6, 125.4, 124.3, 123.6,
120.4, 119.1, 108.5, 107.2, 28.1, 27.8, 27.6, 25.5, 18.1,
17.1, 14.3, 13.8. HR-MS (ESI): m/z = 361.1345, calcd. for
C20H22N2NaOS (M+Na)+: 361.1345.
8.4 Hz, 2H), 6.67 (d, J = 8.4 Hz, 2H), 3.13–2.99 (m, 2H),
1
2.21 (s, 3H), 1.97 (s, 3H), 1.38 (t, J = 7.2 Hz, 3H). H
NMR (400 MHz, CDCl3) (E-2r): = 13.34 (s, 1H), 7.49–
7.46 (m, 4H), 7.01 (d, J = 8.4 Hz, 2H), 6.82 (d, J = 8.4 Hz,
2H), 2.74–2.71 (m, 2H), 2.35 (s, 3H), 2.15 (s, 3H), 1.19 (t,
J = 7.6 Hz, 3H). 13C NMR (125 MHz, CDCl3): = 193.4,
193.1, 169.5, 168.1, 159.1, 159.0, 148.7, 148.6, 136.5,
136.5, 132.1, 132.0, 131.9, 131.5, 126.7, 126.6, 122.0,
120.7, 119.6, 119.4, 117.0, 116.5, 108.6, 107.0, 27.9, 27.6,
27.4, 25.3, 17.7, 16.8, 14.1, 13.5. HR-MS (ESI): m/z =
516.9549, calcd. for C20H20Br2N2NaOS (M+Na)+:
516.9555.
(4E)-3-(Ethylthio(p-tolylamino)methylene)-4-(p-
tolylimino)pentan-2-one(2n) [E/Z=2:5]: yield: 121 mg
(66%); yellowish solid; mp 85–87 oC; 1H NMR (400 MHz,
CDCl3) (Z-2n): = 13.19 (s, 1H), 7.12 (d, J = 8.0 Hz, 2H),
7.06–7.38 (m, 2H), 6.88–6.86 (m, 2H), 6.70 (d, J = 8.0 Hz,
2H), 3.13–3.03 (m, 2H), 2.32 (s, 3H), 2.29 (s, 3H), 2.20 (s,
3H), 1.96 (s, 3H), 1.39 (t, J = 7.6 Hz, 3H). 1H NMR (400
MHz, CDCl3) (E-2n): = 13.31 (s, 1H), 7.20–7.17 (m, 4H),
7.07–7.02 (m, 2H), 6.87–6.83 (m, 2H), 2.75–2.71 (m, 2H),
2.37–2.33 (m, 9H), 2.15 (s, 3H), 1.19 (t, J = 7.6 Hz, 3H).
13C NMR (125 MHz, CDCl3): = 193.3, 193.1, 168.9,
166.9, 160.3, 147.6, 147.3, 136.3, 136.1, 135.2, 135.1,
133.7, 133.0, 129.8, 129.6(2), 129.2, 125.4, 125.3, 120.4,
119.0, 108.3, 107.0, 28.0, 27.7, 27.5, 25.3, 20.9(3), 20.8,
17.9, 17.0, 14.3, 13.8. HR-MS (ESI): m/z = 389.1644,
calcd. for C22H26N2NaOS (M+Na)+: 389.1658.
(4E)-3-((Biphenyl-4-ylamino)(ethylthio)methylene)-4-
(biphenyl-4-ylimino)pentan-2-one(2s) [E/Z=2:7]: yield:
o
1
152 mg (62%); yellowish solid; mp 124–125 C; H NMR
(500 MHz, CDCl3) (Z-2s): = 13.40 (s, 1H), 7.63–7.40 (m,
8H), 7.41–7.35 (m, 4H), 7.28 (t, J = 7.5 Hz, 2H), 6.99 (d, J
= 8.0 Hz, 2H), 6.91 (d, J =8.0 Hz, 2H), 3.17–3.05 (m, 2H),
1
2.30 (s, 3H), 2.05 (s, 3H), 1.43–1.39 (m, 3H). H NMR
(500 MHz, CDCl3) (E-2s): = 13.50 (s, 1H), 7.63–7.45 (m,
11H), 7.41–7.35 (m, 1H), 7.33–7.25 (m, 2H), 7.17 (d, J =
8.5 Hz, 2H), 7.06–7.03 (m, 2H), 2.77–7.73 (m, 2H), 2.42 (s,
3H), 2.24 (s, 3H), 1.18 (t, J = 7.5 Hz, 3H). 13C NMR (125
MHz, CDCl3): = 193.3, 193.1, 168.9, 167.4, 159.6, 149.2,
148.9, 140.4, 140.3, 139.6, 138.9, 138.7, 136.9, 136.7,
(4E)-3-(Ethylthio(4-methoxyphenylamino)methylene)-
4-(4-methoxyphenylimino)pentan-2-one(2o) [E/Z=1:3]:
o
1
yield: 151 mg (76%); yellowish solid; mp 120–121 C; H
7
This article is protected by copyright. All rights reserved.

10.1002/adsc.201700410
Advanced Synthesis & Catalysis
136.2, 128.6(2), 128.5, 127.6, 127.4, 127.2(2), 126.7(2),
126.6, 126.5, 125.4, 125.2, 120.9, 119.4, 108.7, 107.3, 28.0,
27.5, 25.4, 17.9, 17.0, 14.2, 13.7(2). HR-MS (ESI): m/z =
491.2157, calcd. for C32H31N2OS (M+H)+: 491.2152.
CDCl3): = 167.9, 167.7, 167.2, 166.4, 157.5, 157.0,
152.0, 151.5, 139.4, 134.6, 134.5, 134.3, 133.8, 130.0(2),
129.9, 129.4, 125.7, 125.6, 125.0, 124.9, 123.8, 123.0,
122.9, 120.2, 119.4, 117.9, 117.5, 98.0, 96.7, 59.7, 27.0,
25.3, 17.8, 17.0, 14.3, 14.2, 13.6. HR-MS (ESI): m/z =
459.0681, calcd. for C21H22Cl2N2NaO2S (M+Na)+:
459.0671.
(4E)-3-(Ethylthio(4-(trifluoromethyl)phenylamino)
methylene)-4-(4-(trifluoromethyl)phenylimino)pentan-
2-one(2t) [E/Z=1:4]: yield: 97 mg (41%); white solid; mp
109–110 oC; 1H NMR (400 MHz, CDCl3) (Z-2t): = 13.39
(s, 1H), 7.59 (d, J = 8.4 Hz, 2H), 7.53 (d, J = 8.4 Hz, 2H),
7.09 (d, J = 8.4 Hz, 2H), 6.85 (d, J = 8.4 Hz, 2H), 3.17–
3.04 (m, 2H), 2.26 (s, 3H), 2.06 (s, 3H), 1.41 (t, J = 7.2 Hz,
3H). 1H NMR (400 MHz, CDCl3) (E-2t): = 13.51 (s, 1H),
7.70–7.65 (m, 4H), 7.27–7.25 (m, 2H), 7.01 (d, J = 8.0 Hz,
2H), 2.80–2.70 (m, 2H), 2.40 (s, 3H), 2.26 (s, 3H), 1.23 (d,
J = 7.2 Hz, 3H). 13C NMR (125 MHz, CDCl3): = 193.9,
Synthesis of N-Aryl-Imino N,S-Acetals 2 under basic
conditions (taking 2a as an example). To the solution of
(Z)-ethyl 3-phenyl-3-(phenylamino)acrylate (134 mg, 0.50
mmol) in DMF (3 mL) was added NaH (26 mg, 1.1 mmol).
Then, phenyl isothiocyanate (81 mg, 0.6 mmol) was added
dropwise to the mixture and stirred for 20 min at room
temperature, followed by the addition of bromoethane (65
mg, 0.6 mmol). After the reaction was finished as indicated
169.0, 158.9, 153.0, 141.0, 128.0 (d, J = 32.6 Hz), 126.4 (q, by TLC (reaction time, 3.0 h), the resulting mixture was
J = 4.4 Hz), 126.0 (q, J = 3.9 Hz), 125.0, 120.4, 119.3,
108.0, 28.2, 28.0, 27.8, 25.7, 18.2, 17.2, 14.2, 13.6. 19F
NMR (470 MHz, CDCl3): = -63.9, -64.3, -64.4. HR-MS
(ESI): m/z = 497.1088, calcd. for C22H20F6N2NaOS
(M+Na)+: 497.1093.
poured into saturated aqueous NaCl (20 mL), and extracted
with diethyl ether (20 mL× 3). The combined organic
phase was dried with anhydrous Na2SO4, the solvent was
removed under reduced pressure, and the crude product
was purified by column chromatography on silica gel
(EtOAc/PE = 1: 60) to afford 2x (215 mg, 90%).
(3E)-Ethyl
2-(ethylthio(naphthalen-1-
ylamino)methylene)-3-(naphthalen-1-
Ethyl 3-(Ethylthio)-2-(phenyl(phenylimino)methyl)-3-
ylimino)butanoate(2u) [E/Z=2:5]: yield: 138 mg (59%);
(phenylamino)acrylate(2x) [E/Z=2:3]: yield: 215 mg
yellowish solid; mp 76–77 oC; 1H NMR (500 MHz, CDCl3) (90%); yellowish viscous liquid; H NMR (400 MHz,
1
(Z-2u): = 10.98 (s, 1H), 8.14 (d, J = 8.5 Hz, 1H), 7.81 (d,
J = 8.5 Hz, 1H), 7.74 (d, J = 8.0 Hz, 1H), 7.67–7.21 (m,
9H), 7.04 (d, J = 7.0 Hz, 1H), 6.86 (d, J = 7.0 Hz, 1H),
CDCl3) (Z-2x): = 11.11 (s, 1H), 7.50–6.40 (m, 15H),
4.33–4.26 (m, 2H), 2.95–2.82 (m, 2H), 1.37–1.31 (m, 3H),
1
1.19–1.10 (m, 3H). H NMR (400 MHz, CDCl3) (E-2x):
4.25–3.97 (m, 2H), 3.32–3.20 (m, 2H), 1.68 (s, 3H), 1.49 (t, = 11.30 (s, 1H), 7.50–6.40 (m, 15H), 4.33–4.26 (m, 2H),
1
J = 7.0 Hz, 3H), 1.17 (t, J = 7.0 Hz, 3H). H NMR (500
MHz, CDCl3) (E-2u): = 11.40 (s, 1H), 8.14 (d, J = 8.5
Hz, 1H), 8.09 (d, J = 8.5 Hz, 1H), 7.90–7.79 (m, 2H),
7.77–7.73 (m, 1H), 7.67–7.21 (m, 8H), 6.94 (d, J = 7.0 Hz,
1H), 4.41 (q, J = 7.0 Hz, 2H), 2.79 (q, J = 7.5 Hz, 2H),
2.19 (s, 3H), 1.49 (t, J = 7.0 Hz, 3H), 1.17 (t, J = 7.5 Hz,
2.83–2.76 (m, 2H), 1.37–1.31 (m, 3H), 1.19–1.10 (m, 3H).
13C NMR (125 MHz, CDCl3): = 168.4, 168.3, 165.4,
163.4, 159.0, 158.4, 150.3, 149.5, 139.1, 139.0, 133.1,
132.7, 129.2, 129.1(2), 128.6, 128.5, 128.2, 127.9, 127.5,
123.8, 123.5(2), 123.0, 122.9, 122.7, 120.9, 118.8, 99.5,
97.7, 60.0, 59.9, 26.9, 25.2, 14.2(2), 13.8, 13.7. HR-MS
3H). 13C NMR (125 MHz, CDCl3): = 168.4, 167.9, 165.7, (ESI): m/z = 431.1787, calcd. for C26H27N2O2S (M+H)+:
160.2, 159.9, 146.9, 146.6, 134.2(2), 134.1, 134.0, 130.3,
128.2, 128.0, 127.9, 127.7, 127.6, 127.2, 126.9, 126.7,
126.5, 126.2, 126.0, 125.7, 125.6(2), 125.2, 125.1, 124.8,
124.2, 124.1, 124.0, 123.9, 123.7, 123.3, 122.4, 122.2,
113.9, 97.0, 95.3, 59.9, 59.5, 27.0, 25.4, 17.8, 17.1, 14.5,
14.4, 14.3, 14.2. HR-MS (ESI): m/z = 491.1771, calcd. for
C29H28N2NaO2S (M+Na)+: 491.1764.
431.1788.
4-(4-Chlorophenylimino)-3-(ethylthio(4-methoxy
phenylamino)methylene)pentan-2-one(2y) [E/Z=1:3]:
o
1
yield: 147 mg (73%); yellowish solid; mp 86–87 C; H
NMR (500 MHz, CDCl3) (Z-2y): = 13.23 (s, 1H), 7.28 (d,
J = 8.5 Hz, 2H), 6.94–6.89 (m, 2H), 6.83–6.76 (m, 4H),
3.77 (s, 3H), 3.14–3.03 (m, 2H), 2.21 (s, 3H), 1.95 (s, 3H),
1.39 (t, J = 7.0 Hz, 3H). 1H NMR (500 MHz, CDCl3) (E-
2y):= 13.32 (s, 1H), 7.35 (d, J = 8.5 Hz, 2H), 7.08 (d, J =
8.0 Hz, 2H), 6.94–6.89 (m, 4H), 3.81 (s, 3H), 2.75–2.71 (m,
2H), 2.36 (s, 3H), 2.15 (s, 3H), 1.20 (t, J = 7.5 Hz, 3H). 13C
NMR (125 MHz, CDCl3): = 194.0, 193.9, 168.4, 166.0,
159.4, 156.5, 156.1, 143.2, 142.7, 136.4, 131.9, 131.7,
129.3, 129.2, 126.7, 126.5, 121.9, 120.5, 114.2, 113.9,
109.2, 107.8, 55.3, 28.0, 27.8, 27.5, 25.3, 17.7, 17.0, 14.3,
(4E)-3-(Ethylthio(naphthalen-1-ylamino)methylene)-4-
(naphthalen-1-ylimino)pentan-2-one(2v)
[E/Z=2:7]:
o
1
yield: 134 mg (61%); white solid; mp 45–46 C; H NMR
(500 MHz, CDCl3) (Z-2v): = 13.43 (s, 1H), 8.20 (d, J =
8.0 Hz, 1H), 7.83 (d, J = 8.5 Hz, 1H), 7.79 (d, J = 8.0 Hz,
1H), 7.71 (d, J = 8.0 Hz, 1H), 7.65 (t, J = 8.0 Hz, 1H),
7.49–7.39 (m, 5H), 7.36–7.33 (m, 2H), 7.11 (d, J = 7.5 Hz,
1H), 6.77 (d, J = 7.5 Hz, 1H), 3.38–3.22 (m, 2H), 2.31 (s,
3H), 1.69 (s, 3H), 1.51 (t, J = 7.5 Hz, 3H). 1H NMR (500
13.8. HR-MS (ESI): m/z
= 425.1054, calcd. for
MHz, CDCl3) (E-2v): = 13.77 (s, 1H), 8.06 (d, J = 8.0 Hz, C21H23ClN2NaO2S (M+Na)+: 425.1061.
1H), 7.94–7.89 (m, 2H), 7.87–7.82 (m, 2H), 7.67–7.63 (m,
1H), 7.60–7.53 (m, 2H), 7.50–7.38 (m, 5H), 7.04 (d, J =
Ethyl
2-((benzylamino)(ethylthio)methylene)-3-
7.0 Hz, 1H), 2.85–2.75 (m, 2H), 2.59 (s, 3H), 2.23 (s, 3H),
1.19 (t, J = 7.5 Hz, 3H). 13C NMR (125 MHz, CDCl3): =
193.9, 167.8, 162.4, 145.3, 134.2, 134.0, 133.9, 129.9,
128.3, 128.1, 127.9, 127.6, 127.2, 126.9, 126.7, 126.5,
126.2, 126.0, 125.6, 125.4, 125.1, 124.5, 124.0, 123.9,
123.5, 122.8, 122.5, 122.3, 114.5, 113.9, 106.7, 28.4, 27.6,
25.6, 17.9, 17.5, 14.3. HR-MS (ESI): m/z = 461.1657,
calcd. for C28H26N2NaOS (M+Na)+: 461.1658.
(phenylimino)butanoate(2z) [E/Z=1:4]: yield: 2.71 g
(71%); yellowish viscous liquid; 1H NMR (400 MHz,
CDCl3) (Z-2z): = 11.09 (s, 1H), 7.43–7.11 (m, 8H), 7.07
(d, J = 7.6 Hz, 2H), 4.74–4.46 (m, 2H), 4.29–4.04 (m, 2H),
3.07–2.97 (m, 2H), 1.93 (s, 3H), 1.39–1.24 (m, 3H), 1.19 (t,
J = 7.2 Hz, 3H). 1H NMR (400 MHz, CDCl3) (E-2z): =
11.10 (s, 1H), 7.43–7.11 (m, 8H), 7.10–7.05 (m, 2H),
4.74–4.46 (m, 2H), 4.29–4.04 (m, 2H), 2.83 (q, J = 7.2 Hz,
2H), 2.00 (s, 3H), 1.39–1.24 (m, 3H), 1.19 (t, J = 7.2 Hz,
3H). 13C NMR (150 MHz, CDCl3): = 168.3, 167.4, 164.1,
(4E)-3-((3-Chlorophenylamino)(ethylthio)methylene)-4-
(3-chlorophenylimino)pentan-2-one(2w) [E/Z=1:6]: yield: 163.8, 158.7, 158.1, 140.7, 139.7, 138.5, 138.4, 129.0(2),
131 mg (60%); yellow viscous liquid; 1H NMR (500 MHz,
CDCl3) (Z-2w): = 10.90 (s, 1H), 7.23–7.09 (m, 3H), 6.98
(d, J = 8.0 Hz, 1H), 6.94 (s, 1H), 6.86–6.76 (m, 2H), 6.66
(d, J = 8.0 Hz, 1H), 4.35–4.08 (m, 2H), 3.20–2.92 (m, 2H),
1.98 (s, 3H), 1.37 (t, J = 7.5 Hz, 3H), 1.32 (t, J = 7.5 Hz,
128.1, 128.0, 127.4, 126.4, 126.2, 125.6, 125.5, 125.2,
125.0, 97.9, 94.7, 59.4(2), 56.7, 56.3, 26.5, 24.4, 17.1, 17.0,
14.6, 14.4, 14.2, 14.1. HR-MS (ESI): m/z = 467.1769,
calcd. for C27H28N2NaO2S (M+Na)+: 467.1764.
1
2H). H NMR (500 MHz, CDCl3) (E-2w): = 11.14 (s,
(E)-Ethyl
3,3-bis(ethylthio)-2-(phenyl(phenylimino)
1H), 7.32–7.23 (m, 2H), 7.22–7.07 (m, 2H), 7.07 (d, J =
8.0 Hz, 1H), 7.00–6.98 (m, 2H), 6.94–6.91 (m, 1H), 4.35–
4.08 (m, 2H), 2.75 (q, J = 7.5 Hz, 2H), 2.18 (s, 3H), 1.38–
1.31 (m, 3H), 1.18 (t, J = 7.5 Hz, 3H). 13C NMR (125 MHz,
methyl)acrylate(6x): yield: 108 mg (54%); orange solid;
o
1
mp 53–54 C; H NMR (400 MHz, CDCl3):= 7.87 (d, J
= 7.6, 2H), 7.47–7.37 (m, 3H), 7.29–7.22 (m, 2H), 7.04 (t,
8
This article is protected by copyright. All rights reserved.

10.1002/adsc.201700410
Advanced Synthesis & Catalysis
J = 7.6 Hz, 1H), 6.99–6.93 (m, 2H), 4.08 (q, J = 7.2 Hz,
2H), 2.98–2.49 (m, 4H), 1.14–0.92 (m, 9H). 13C NMR (150
Ethyl
6-fluoro-4-(4-fluorophenylamino)-2-methyl
quinoline-3-carboxylate(3e): yield: 133 mg (78%); white
MHz, CDCl3): = 163.5, 163.4, 151.9, 150.7, 138.3, 131.8, solid; mp 98–99 oC; 1H NMR (500 MHz, CDCl3): = 8.57
130.4, 128.2, 128.1, 128.0, 123.8, 119.7, 60.8, 29.4, 29.3,
14.8, 14.6, 13.8. HR-MS (ESI): m/z = 422.1213, calcd. for
C22H25NNaO2S2 (M+Na)+: 422.1219.
(s, 1H), 7.92 (dd, J = 9.0, 5.5 Hz, 1H), 7.38 (ddd, J = 9.0,
8.0, 3.0 Hz, 1H), 7.24 (dd, J = 10.0, 3.0 Hz, 1H), 6.98–6.94
(m, 2H), 6.89–6.87 (m, 2H), 4.36 (q, J = 7.0 Hz, 2H), 2.80
(s, 3H), 1.40 (t, J = 7.0 Hz, 3H). 13C NMR (125 MHz,
CDCl3): = 168.7, 159.0 (d, J = 255.0 Hz), 159.0 (d, J =
251.3 Hz), 156.9 (d, J = 2.5 Hz), 148.7 (d, J = 5.0 Hz),
145.8, 139.1 (d, J = 2.5 Hz), 131.6 (d, J = 8.8 Hz), 121.1 (d,
J = 8.8 Hz), 120.7 (d, J = 25 Hz), 120.2 (d, J = 8.8 Hz),
116.1 (d, J = 22.5 Hz), 113.6, 109.2 (d, J = 25.0 Hz), 61.8,
26.3, 14.1. HR-MS (ESI): m/z = 343.1245, calcd. for
C19H17F2N2O2 (M+H)+: 343.1253.
General procedure for the synthesis of 3 (taking 3a as an
example). To the solution of 2a (184.0 mg, 0.5 mmol) in
toluene (1 mL) was added potassium carbonate (138.2 mg,
1 mmol), anhydrous cupric chloride (6.7 mg, 0.05 mmol),
o
and 1,10-phenanthroline (10 mol%)and stirred at 80 C.
After 2a was consumed as indicated by TLC (reaction time,
12.0 h), the mixture was poured into saturated aqueous
NaCl (30 mL), and extracted with dichloromethane (30 mL
× 3), the combined organic phase was dried over
anhydrous Na2SO4and concentrated in vacuo. The crude
product was purified by column chromatography on silica
gel (EtOAc/PE/TEA = 20: 120:1) to afford 3a (127 mg,
83%).
Ethyl
6-chloro-4-(4-chlorophenylamino)-2-methyl
quinoline-3-carboxylate(3f): yield: 123 mg (66%);
o
1
yellowish solid; mp 144–145 C; H NMR (500 MHz,
CDCl3): = 8.47 (s, 1H), 7.83 (d, J = 9.0 Hz, 1H), 7.63 (s,
1H), 7.55 (d, J = 9.0 Hz, 1H), 7.20 (d, J = 8.5 Hz, 2H),
6.81 (d, J = 8.5 Hz, 2H), 4.32 (q, J = 7.0 Hz, 2H), 2.77 (s,
3H), 1.37 (t, J = 7.0 Hz, 3H). 13C NMR (125 MHz, CDCl3):
= 168.4, 157.6, 147.0(2), 141.7, 131.6, 130.7(2), 129.2,
127.9, 123.8, 120.7, 114.8, 61.9, 26.1, 14.0. HR-MS (ESI):
m/z = 375.0655, calcd. for C19H17Cl2N2O2 (M+H)+:
375.0662.
Ethyl
2-methyl-4-(phenylamino)quinoline-3-
carboxylate(3a): yield: 127 mg (83%); yellowish solid;
o
1
mp 114–115 C; H NMR (500 MHz, CDCl3): = 8.66 (s,
1H), 7.93 (d, J = 8.5 Hz, 1H), 7.71 (d, J = 8.5 Hz, 1H),
7.61 (t, J = 7.0 Hz, 1H), 7.24–7.18 (m, 3H), 7.02 (t, J = 7.5
Hz, 1H), 6.91 (d, J = 7.5 Hz, 2H), 4.33 (q, J = 7.0 Hz, 2H),
2.83 (s, 3H), 1.38 (t, J = 7.0 Hz, 3H). 13C NMR (125 MHz,
CDCl3): = 168.7, 157.4, 148.6(2), 143.5, 130.6, 129.0,
128.9, 125.3, 124.5, 122.7, 119.9, 119.7, 113.3, 61.4, 26.3,
Ethyl
6-bromo-4-(4-bromophenylamino)-2-methyl
quinoline-3-carboxylate(3g): yield: 187 mg (81%);
o
1
yellowish solid; mp 124–125 C; H NMR (500 MHz,
CDCl3): = 8.43 (s, 1H), 7.83 (s, 1H), 7.75 (d, J = 9.0 Hz,
1H), 7.68 (d, J = 9.0 Hz, 1H), 7.34 (d, J = 8.5 Hz, 2H),
6.76 (d, J = 8.5 Hz, 2H), 4.29 (q, J = 7.0 Hz, 2H), 2.75 (s,
3H), 1.36 (t, J = 7.0 Hz, 3H). 13C NMR (125 MHz, CDCl3):
= 168.3, 157.7, 147.2, 146.6, 142.1, 134.2, 132.1, 130.8,
126.9, 121.3, 120.9, 118.8, 115.3, 114.9, 61.9, 26.1, 14.0.
HR-MS (ESI): m/z = 462.9640, calcd. for C19H17Br2N2O2
(M+H)+: 462.9651.
13.9. HR-MS (ESI): m/z
= 307.1449, calcd. for
C19H19N2O2 (M+H)+: 307.1441.
Ethyl
2,6-dimethyl-4-(p-tolylamino)quinoline-3-
carboxylate(3b): yield: 157 mg (94%); yellow solid; mp
o
1
89–90 C; H NMR (500 MHz, CDCl3): = 8.49 (s, 1H),
7.82 (d, J = 8.5 Hz, 1H), 7.49 (s, 1H), 7.42 (d, J = 8.5
Hz,1H), 7.02 (d, J = 8.0 Hz, 2H), 6.82 (d, J = 8.0 Hz, 2H),
4.26 (q, J = 7.0 Hz, 2H), 2.78 (s, 3H), 2.27 (s, 3H), 1.34 (t,
J = 7.0 Hz, 3H). 13C NMR (125 MHz, CDCl3): = 168.7,
156.2, 148.1, 146.9, 140.7, 134.0, 132.5, 132.2, 129.3,
128.4, 123.8, 120.1, 119.6, 112.7, 61.1, 25.7, 21.3, 20.5,
Ethyl 6-iodo-4-(4-iodophenylamino)-2-methylquinoline-
3-carboxylate(3h): yield: 201 mg (72%); white solid; mp
156–158 oC; 1H NMR (400 MHz, CDCl3): = 8.39 (s, 1H),
8.05 (s, 1H), 7.87 (d, J = 8.8 Hz, 1H), 7.64 (d, J = 8.8 Hz,
1H), 7.53 (d, J = 8.8 Hz, 2H), 6.64 (d, J = 8.8 Hz, 2H),
4.32 (q, J = 7.2 Hz, 2H), 2.77 (s, 3H), 1.37 (t, J = 7.2 Hz,
3H). 13C NMR (125 MHz, CDCl3): = 168.3, 158.1, 147.7,
146.6, 142.9, 139.6, 138.1, 133.9, 130.9, 121.8, 121.4,
114.9, 90.1, 85.6, 61.9, 26.3, 14.1. HR-MS (ESI): m/z =
558.9377, calcd. for C19H17I2N2O2 (M+H)+: 558.9374.
13.8. HR-MS (ESI): m/z
= 335.1744, calcd. for
C21H23N2O2 (M+H)+: 335.1754.
Ethyl 2,7-dimethyl-4-(m-tolylamino)quinoline-3-
carboxylate(3c) and ethyl 2,5-dimethyl-4-(m-
tolylamino)quinoline-3-carboxylate(3c’): yield: 144 mg
(86%); yellowish solid: mp 68–70 oC; 1H NMR (400 MHz,
CDCl3) (3c): = 8.69 (s, 1H), 7.71 (s, 1H), 7.60 (d, J = 8.8
Hz, 1H), 7.10 (t, J = 8.0 Hz, 1H), 7.44–7.00 (m, 1H), 6.83
(d, J = 7.6 Hz, 1H), 6.77 (s, 1H), 6.72–6.67 (m, 1H), 4.33
(q, J = 7.2 Hz, 2H), 2.81 (s, 3H), 2.47 (s, 3H), 2.26 (s, 3H),
1.39 (t, J = 7.2 Hz, 3H). 1H NMR (400 MHz, CDCl3) (3c’):
= 7.83 (d, J = 8.4 Hz, 1H), 7.79 (s, 1H), 7.54 (t, J = 8.4
Hz, 1H), 7.12–7.08 (m, 1H), 7.04–7.00 (m, 1H), 6.72–6.67
(m, 1H), 6.46 (s, 1H), 6.37 (d, J = 8.4 Hz, 1H), 4.25 (q, J =
Ethyl 7-methoxy-4-(3-methoxyphenylamino)-2-methyl
quinoline-3-carboxylate(3i) and ethyl 5-methoxy-4-(3-
methoxyphenylamino)-2-methylquinoline-3-
carboxylate(3i’): yield: 146 mg (80%); yellowish solid;
mp 83–85 oC; 1H NMR (400 MHz, CDCl3) (3i): = 8.83 (s,
1H), 7.63 (d, J = 9.2 Hz, 1H), 7.55–7.51 (m, 1H), 7.25 (s,
1H), 7.11 (t, J = 8.4 Hz, 1H), 6.85 (d, J = 9.2 Hz, 1H),
7.2 Hz, 2H), 2.76 (s, 3H), 2.55 (s, 3H), 2.20 (s, 3H), 1.29 (t, 6.51–6.47 (m, 1H), 6.45 (s, 1H), 4.35 (q, J = 7.2 Hz, 2H),
J = 7.2 Hz, 1H). 13C NMR (125 MHz, CDCl3): = 169.0,
168.5, 157.6, 156.2, 150.1, 149.1, 149.0, 147.9, 144.8,
143.6, 141.3, 139.1, 135.5, 130.4, 129.1, 129.0, 128.9,
128.1, 127.3, 126.6, 125.4, 123.6, 122.3, 122.3, 120.8,
118.7, 117.6, 117.5, 117.2, 113.6, 112.4, 61.5, 61.4, 26.6,
25.3, 23.2, 21.7, 21.4(2), 14.1, 13.9. HR-MS (ESI): m/z =
335.1744, calcd. for C21H23N2O2 (M+H)+: 335.1754.
3.91 (s, 3H), 3.69 (s, 3H), 2.82 (s, 3H), 1.39 (t, J = 7.2 Hz,
1
3H). H NMR (400 MHz, CDCl3) (3i’): = 9.50 (s, 1H),
7.56–7.50 (m, 1H), 7.20 (t, J = 8.0 Hz, 1H), 6.79 (d, J =
6.8 Hz, 1H), 6.72 (d, J = 7.6 Hz, 1H), 6.69 (s, 1H), 6.65 (d,
J = 8.0 Hz, 1H), 6.45 (s, 1H), 3.98 (s, 3H), 3.78 (s, 3H),
3.62 (q, J = 7.2 Hz, 2H), 2.63 (s, 3H), 1.11 (t, J = 7.2 Hz,
3H). 13C NMR (125 MHz, CDCl3): = 169.0, 168.2, 161.8,
160.4, 160.2, 158.4, 157.7, 157.0, 150.9, 149.2, 148.5,
145.0, 142.4, 129.9, 129.8(2), 127.2, 122.2, 117.3, 114.3,
114.2, 112.5, 111.6, 111.1, 110.4, 110.2, 108.4, 107.1,
105.8, 104.8, 61.5, 60.7, 56.4, 55.5, 55.2(2), 26.7, 24.6,
14.1, 13.8. HR-MS (ESI): m/z = 367.1658, calcd. for
C21H23N2O4 (M+H)+: 367.1652.
Ethyl 6-methoxy-4-(4-methoxyphenylamino)-2-methyl
quinoline-3-carboxylate(3d): yield: 183 mg (89%);
yellowish solid; mp 89–90 oC; 1H NMR (500 MHz,
CDCl3): = 8.75 (s, 1H), 7.80 (d, J = 9.0 Hz, 1H), 7.23 (d,
J = 9.0 Hz, 1H), 6.93–6.91 (m, 3H), 6.81 (d, J = 9.0 Hz,
2H), 4.34 (q, J = 7.5 Hz, 2H), 3.76 (s, 3H), 3.45 (s, 3H),
2.78 (s, 3H), 1.39 (t, J = 7.5 Hz, 3H). 13C NMR (125 MHz,
CDCl3): = 169.2, 155.9, 155.8, 155.1, 149.0, 144.6,
136.6, 130.3, 123.0, 122.9, 119.8, 114.3, 111.9, 104.2, 61.4,
55.5, 54.9, 26.3, 14.1. HR-MS (ESI): m/z = 367.1642,
calcd. for C21H23N2O4 (M+H)+: 367.1652.
Ethyl
4-(biphenyl-4-ylamino)-2-methyl-6-
phenylquinoline-3-carboxylate(3j): yield: 211 mg (92%);
o
1
yellowish solid; mp 132–133 C; H NMR (400 MHz,
CDCl3): = 9.05 (s, 1H), 7.98 (d, J = 8.4 Hz, 1H), 7.91–
7.86 (m, 2H), 7.58 (d, J = 7.6 Hz, 2H), 7.53 (d, J = 8.4 Hz,
2H), 7.44 (t, J = 7.6 Hz, 2H), 7.34 (t, J = 7.2 Hz, 1H),
9
This article is protected by copyright. All rights reserved.

10.1002/adsc.201700410
Advanced Synthesis & Catalysis
7.27–7.23 (m, 5H), 7.06 (d, J = 8.0 Hz, 2H), 4.38 (q, J =
7.2 Hz, 2H), 2.86 (s, 3H), 1.42 (t, J = 7.2 Hz, 3H). 13C
NMR (125 MHz, CDCl3): =168.8, 157.5, 149.1, 148.0,
142.7, 140.3, 139.8, 136.7, 136.1, 130.0, 129.3, 128.7,
128.6, 127.7, 127.2, 126.9(2), 126.5, 123.6, 121.0, 119.3,
112.5, 61.4, 26.5, 14.0. HR-MS (ESI): m/z = 459.2053,
calcd. for C31H27N2O2 (M+H)+: 459.2067.
HR-MS (ESI): m/z = 313.1143, calcd. for C18H15F2N2O
(M+H)+: 313.1147.
1-(6-Chloro-4-(4-chlorophenylamino)-2-methylquinolin
-3-yl)ethanone(3q): yield: 124 mg (72%); white solid; mp
171–172 oC; 1H NMR (400 MHz, CDCl3): = 7.90 (d, J =
8.8 Hz, 1H), 7.69 (s, 1H), 7.60 (d, J = 8.8 Hz, 1H), 7.28 (s,
1H), 7.19 (d, J = 8.8 Hz, 2H), 6.74 (d, J = 8.8 Hz, 2H),
2.70 (s, 3H), 2.48 (s, 3H). 13C NMR (125 MHz, CDCl3):
= 204.5, 155.5, 147.1, 142.7, 141.9, 131.6, 131.5, 130.9,
129.5, 127.5, 126.8, 123.1, 121.9, 119.4, 31.9, 24.9. HR-
MS (ESI): m/z = 345.0552, calcd. for C18H15Cl2N2O
(M+H)+: 345.0556.
Ethyl
2,8-dimethyl-4-(o-tolylamino)quinoline-3-
carboxylate(3k): yield: 149 mg (89%); yellowish solid;
o
1
mp 91–93 C; H NMR (400 MHz, CDCl3): = 8.40 (s,
1H), 7.47–7.43 (m, 2H), 7.21 (t, J = 4.8 Hz, 1H), 7.05 (t, J
= 7.6 Hz, 1H), 6.95–6.93 (m, 2H), 6.60 (t, J = 4.8 Hz, 1H),
4.30 (q, J = 7.2 Hz, 2H), 2.84 (s, 3H), 2.76 (s, 3H), 2.41 (s,
3H), 1.37 (t, J = 7.2 Hz, 3H). 13C NMR (125 MHz, CDCl3):
= 169.1, 156.2, 149.7, 147.7, 142.4, 136.9, 130.8, 130.6,
128.7, 126.3, 124.1, 123.2, 122.9, 120.0, 119.6, 112.8, 61.4,
26.9, 18.2, 18.1, 14.0. HR-MS (ESI): m/z = 335.1748,
calcd. for C21H23N2O2 (M+H)+: 335.1754.
1-(6-Bromo-4-(4-bromophenylamino)-2-methylquinolin
-3-yl)ethanone(3r): yield: 171 mg (79%); white solid; mp
177–178 oC; 1H NMR (400 MHz, CDCl3): = 7.87 (s, 1H),
7.84 (d, J = 8.8 Hz, 1H), 7.73 (d, J = 8.8 Hz, 1H), 7.34 (d,
J = 8.8 Hz, 2H), 7.21 (s, 1H), 6.69 (d, J = 8.8 Hz, 2H),
2.69 (s, 3H), 2.48 (s, 3H). 13C NMR (125 MHz, CDCl3):
= 204.5, 155.7, 147.3, 142.5, 142.4, 134.1, 132.4, 131.0,
126.9, 126.4, 122.4, 119.7(2), 114.9, 32.0, 24.9. HR-MS
(ESI): m/z = 432.9545, calcd. for C18H15Br2N2O (M+H)+:
432.9546.
Ethyl
2-methyl-6-(trifluoromethyl)-4-(4-
(trifluoromethyl)phenylamino)quinoline-3-carboxylate
(3l): yield: 166 mg (75%); white solid; mp 130–131 oC; 1H
NMR (400 MHz, CDCl3): = 8.66 (s, 1H), 8.06 (d, J = 8.8
Hz, 1H), 8.00 (s, 1H), 7.84 (d, J = 8.8 Hz, 1H), 7.50 (d, J =
8.4 Hz, 2H), 6.93 (d, J = 8.4 Hz, 2H), 4.37 (q, J = 7.2 Hz,
2H), 2.84 (s, 3H), 1.39 (t, J = 7.2 Hz, 3H). 13C NMR (125
MHz, CDCl3):  = 168.1, 160.0, 149.9, 147.9, 146.2, 130.5,
127.2 (q, J = 32.5 Hz), 126.7 (q, J = 2.6 Hz), 126.6 (q, J =
3.6 Hz), 123.1 (q, J = 4.5 Hz), 119.4, 118.7, 116.1, 62.2,
26.4, 14.0. 19F NMR (470 MHz, CDCl3):  = -64.0, -64.5.
HR-MS (ESI): m/z = 443.1178, calcd. for C21H17F6N2O2
(M+H)+: 443.1189.
1-(4-(Biphenyl-4-ylamino)-2-methyl-6-phenylquinolin-
3-yl)ethanone(3s): yield: 171 mg (80%); yellow solid; mp
1
188–190 oC; H NMR (500 MHz, CDCl3): = 8.02 (d, J =
9.0 Hz, 1H), 7.96–7.95 (m, 2H), 7.90 (d, J = 8.5 Hz, 1H),
7.56 (d, J = 7.0 Hz, 2H), 7.50 (d, J = 8.0 Hz, 2H), 7.43 (t, J
= 7.5 Hz, 2H), 7.36–7.24 (m, 6H), 6.98 (d, J = 8.0 Hz, 2H),
2.76 (s, 3H), 2.55 (s, 3H). 13C NMR (125 MHz, CDCl3):
= 204.8, 155.4, 148.1, 144.9, 142.9, 140.4, 140.0, 137.7,
135.7, 130.1, 129.5, 128.8(2), 128.0, 127.5, 127.2, 127.0,
126.6, 124.9, 122.8, 120.6, 119.8, 32.2, 25.4. HR-MS
(ESI): m/z = 429.1955, calcd. for C30H25N2O (M+H)+:
429.1961.
1-(2-Methyl-4-(phenylamino)quinolin-3-yl)ethanone
o
(3m): yield: 169 mg (71%); white solid; mp 137–138 C;
1H NMR (400 MHz, CDCl3):  = 7.95 (d, J = 8.4 Hz, 1H),
7.77 (d, J = 8.4 Hz, 1H), 7.64 (t, J = 6.8 Hz, 1H), 7.54 (s,
1H), 7.28 (t, J = 7.2 Hz, 1H), 7.21 (t, J = 7.6 Hz, 2H), 6.99
(t, J = 7.6 Hz, 1H), 6.84 (d, J = 7.6 Hz, 2H), 2.72 (s, 3H),
2.48 (s, 3H). 13C NMR (125 MHz, CDCl3):  = 204.9,
155.2, 148.6, 144.2, 143.6, 130.5, 129.3, 129.0, 125.2,
124.4, 122.3, 120.9, 118.6, 32.0, 25.0. HR-MS (ESI): m/z
= 277.1331, calcd. for C18H17N2O (M+H)+: 277.1335.
1-(2-Methyl-6-(trifluoromethyl)-4-(4-(trifluoromethyl)
phenylamino)quinolin-3-yl)ethanone(3t): yield: 144 mg
o
1
(70%); white solid; mp 192–193 C; H NMR (500 MHz,
CDCl3): = 8.09 (d, J = 9.0 Hz, 1H), 8.02 (s, 1H), 7.86 (d,
J = 9.0 Hz, 1H), 7.48 (d, J = 8.5 Hz, 2H), 7.45 (s, 1H),
6.85 (d, J = 8.5 Hz, 2H), 2.76 (s, 3H), 2.52 (s, 3H). 13
C
NMR (125 MHz, CDCl3):= 204.3, 157.7, 149.8, 146.3,
143.2, 130.6, 128.4, 127.8 (q, J = 32.5 Hz), 126.9 (q, J =
3.6 Hz), 126.5 (q, J = 3.3 Hz), 122.2 (q, J = 4.8 Hz), 120.7,
117.1, 31.9, 25.0. 19F NMR (470 MHz, CDCl3): = -63.9,
1-(2,6-Dimethyl-4-(p-tolylamino)quinolin-3-yl)ethanone
o
(3n): yield: 137 mg (90%); white solid; mp 136–137 C;
1H NMR (400 MHz, CDCl3): = 7.85 (d, J = 8.4 Hz, 1H),
7.56 (s, 1H), 7.48 (d, J = 8.4 Hz, 1H), 7.33 (s, 1H), 7.02 (d,
J = 8.0 Hz, 2H), 6.76 (d, J = 8.0 Hz, 2H), 2.67 (s, 3H),
2.42 (s, 3H), 2.36 (s, 3H), 2.28 (s, 3H). 13C NMR (125
MHz, CDCl3):  = 204.9, 154.3, 147.1, 144.1, 140.9, 135.1,
132.6, 132.0, 129.7, 128.8, 124.7, 122.8(2), 119.1, 31.9,
24.8, 21.7, 20.7. HR-MS (ESI): m/z = 305.1658, calcd. for
C20H21N2O (M+H)+: 305.1648.
-64.5. HR-MS (ESI): m/z
= 413.1078, calcd. for
C20H15F6N2O(M+H)+: 413.1083.
Ethyl
2-methyl-4-(naphthalen-1-ylamino)benzo[h]
quinoline-3-carboxylate(3u): yield: 201 mg (99%);
yellowish solid; mp 115–118 C; 1H NMR (400 MHz,
o
CDCl3): = 9.33 (d, J = 8.0 Hz, 1H), 9.08 (s, 1H), 8.37 (d,
J = 8.0 Hz, 1H), 7.88 (d, J = 8.0 Hz, 1H), 7.73–7.51 (m,
6H), 7.43 (d, J = 9.2 Hz, 1H), 7.32 (d, J = 9.2 Hz, 1H),
7.15 (t, J = 8.0 Hz, 1H), 6.67 (d, J = 7.6 Hz, 1H), 4.33 (q, J
= 7.2 Hz, 2H), 2.99 (s, 3H), 1.35 (t, J = 7.2 Hz, 3H). 13C
NMR (125 MHz, CDCl3): = 169.1, 157.0, 149.8, 147.3,
140.2, 134.4, 133.9, 131.2, 128.6, 128.4, 127.4, 126.9,
126.7, 126.5, 126.3, 125.6, 125.3, 125.2, 123.1, 122.3,
121.6, 117.0, 115.7, 114.8, 61.6, 26.9, 14.0. HR-MS (ESI):
m/z = 407.1744, calcd. for C27H23N2O2 (M+H)+ 407.1754.
1-(6-Methoxy-4-(4-methoxyphenylamino)-2-methyl
quinolin-3-yl)ethanone(3o): yield: 160 mg (95%); white
o
1
solid; mp 120–121 C; H NMR (400 MHz, CDCl3):  =
7.84 (s, 1H), 7.82 (d, J = 8.8 Hz, 1H), 7.25 (d, J = 8.8 Hz,
1H), 7.02 (s, 1H), 6.85 (d, J = 8.4 Hz, 2H), 6.78 (d, J = 8.4
Hz, 2H), 3.75 (s, 3H), 3.52 (s, 3H), 2.66 (s, 3H), 2.48 (s,
3H). 13C NMR (125 MHz, CDCl3):  = 205.0, 156.3, 155.5,
152.6, 144.6, 144.4, 136.5, 130.3, 123.6, 122.6, 121.8,
120.9, 114.4, 102.9, 55.4, 55.0, 32.0, 24.8. HR-MS (ESI):
m/z = 337.1548, calcd. for C20H21N2O3 (M+H)+: 337.1547.
1-(2-Methyl-4-(naphthalen-1-ylamino)benzo[h]quinolin
-3-yl)ethanone(3v): yield: 184 mg (98%); yellowish solid;
1
1-(6-Fluoro-4-(4-fluorophenylamino)-2-methylquinolin-
mp 184–185 oC; H NMR (400 MHz, CDCl3): = 9.27 (d,
3-yl)ethanone(3p): yield: 117 mg (75%); white solid; mp
J = 8.0 Hz, 1H), 8.25 (d, J = 9.2 Hz, 1H), 8.02 (s, 1H),
7.82 (d, J = 9.2 Hz, 1H), 7.66–7.41 (m, 7H), 7.30 (d, J =
9.2 Hz, 1H), 7.10 (t, J = 7.6 Hz, 1H), 6.58 (d, J = 7.6 Hz,
1H), 2.82 (s, 3H), 2.44 (s, 3H). 13C NMR (125 MHz,
CDCl3): = 205.0, 154.1, 147.0, 145.3, 140.2, 134.3,
133.7, 131.1, 128.5, 128.4, 127.4, 126.8, 126.6, 126.4,
126.2, 126.0, 125.6, 124.9, 122.7, 121.4, 121.2, 118.1,
114.5, 31.9, 25.5. HR-MS (ESI): m/z = 377.1638, calcd.
for C26H21N2O (M+H)+: 377.1648.
o
1
145–146 C; H NMR (500 MHz, CDCl3): = 7.94 (dd, J
= 9.0, 5.5 Hz, 1H), 7.52 (s, 1H), 7.40 (ddd, J = 9.0, 8.0, 3.0
Hz, 1H), 7.30 (dd, J = 9.0, 3.0 Hz, 1H), 6.96–6.92 (m, 2H),
6.83–6.79 (m, 2H), 2.69 (s, 3H), 2.50 (s, 3H). 13C NMR
(125 MHz, CDCl3): = 204.8, 159.5 (d, J = 245.9 Hz),
158.6 (d, J = 241.0 Hz), 154.5 (d, J = 2.6 Hz), 145.7, 144.1
(d, J = 5.0 Hz), 139.2 (d, J = 2.6 Hz), 131.6 (d, J = 8.8 Hz),
125.5, 121.4 (d, J = 9.3 Hz), 120.6 (d, J = 12.5 Hz), 120.4,
116.1 (d, J = 22.6 Hz), 108.1 (d, J = 23.8 Hz), 32.0, 24.8.
10
This article is protected by copyright. All rights reserved.

10.1002/adsc.201700410
Advanced Synthesis & Catalysis
Ethyl
7-chloro-4-(3-chlorophenylamino)-2-methyl
References
quinoline-3-carboxylate(3w): yield: 118 mg (63%);
yellowish solid; mp 108–109 C; 1H NMR (500 MHz,
o
[1] a) L. Wang, W. He, Z. Yu, Chem. Soc. Rev. 2013, 42,
599−621; b) S. G. Modha, V. P. Mehtaz, E. V. Van der
Eycken, Chem. Soc. Rev. 2013, 42, 5042−5055; c) H.
Prokopcova, C. O. Kappe, ACS Catal. 2014, 4,
280−288; d) H. Prokopcova, C. O. Kappe, Angew.
Chem. 2009, 121, 2312−2322; Angew. Chem. Int. Ed.
2009, 48, 2276−2286.
CDCl3): = 8.65 (s, 1H), 7.93 (s, 1H), 7.60 (d, J = 9.0 Hz,
1H), 7.18 (d, J = 9.0 Hz, 1H), 7.13 (t, J = 8.0 Hz, 1H), 6.98
(d, J = 8.0 Hz, 1H), 6.88 (s, 1H), 6.72 (d, J = 8.0 Hz, 1H),
4.37 (q, J = 7.5 Hz, 2H), 2.80 (s, 3H), 1.40 (t, J = 7.5 Hz,
3H). 13C NMR (125 MHz, CDCl3): = 168.4, 158.9, 149.3,
148.0, 144.7, 136.9, 135.0, 130.2, 128.2, 126.6, 125.9,
122.9, 119.6, 118.3, 117.7, 114.3, 61.9, 26.4, 14.0. HR-MS
(ESI): m/z = 375.0654, calcd. for C19H17Cl2N2O2 (M+H)+:
375.0662.
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Ethyl
2-phenyl-4-(phenylamino)quinoline-3-
carboxylate(3x): yield: 169 mg (92%); white solid; mp
141–142 oC; 1H NMR (400 MHz, CDCl3): = 8.65 (s, 1H),
8.09 (d, J = 8.4 Hz, 1H), 7.74 (d, J = 8.4 Hz, 1H), 7.66–
7.61 (m, 3H), 7.46–7.39 (m, 3H), 7.24–7.19 (m, 3H), 7.02
(t, J = 7.6 Hz, 1H), 6.94 (d, J = 7.6 Hz, 2H), 3.93 (q, J =
7.2 Hz, 2H), 0.73 (t, J = 7.2 Hz, 3H). 13C NMR (125 MHz,
CDCl3):= 169.3, 158.9, 148.9, 148.5, 143.5, 142.2,
130.8, 130.1, 129.1, 128.1, 128.0, 125.9, 124.9, 123.0,
120.2, 119.5, 113.7, 61.3, 13.0. HR-MS (ESI): m/z =
369.1607, calcd. for C24H20N2O2 (M+H)+: 369.1598.
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Ethyl
2-phenyl-4-(phenylamino)quinoline-3-
carboxylate(3x): yield: 169 mg (92%); white solid; mp
141–142 oC; 1H NMR (400 MHz, CDCl3): = 8.65 (s, 1H),
8.09 (d, J = 8.4 Hz, 1H), 7.74 (d, J = 8.4 Hz, 1H), 7.66–
7.61 (m, 3H), 7.46–7.39 (m, 3H), 7.24–7.19 (m, 3H), 7.02
(t, J = 7.6 Hz, 1H), 6.94 (d, J = 7.6 Hz, 2H), 3.93 (q, J =
7.2 Hz, 2H), 0.73 (t, J = 7.2 Hz, 3H). 13C NMR (125 MHz,
CDCl3): = 169.3, 158.9, 148.9, 148.5, 143.5, 142.2,
130.8, 130.1, 129.1, 128.1, 128.0, 125.9, 124.9, 123.0,
120.2, 119.5, 113.7, 61.3, 13.0. HR-MS (ESI): m/z =
369.1607, calcd. for C24H20N2O2 (M+H)+: 369.1598.
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1-(6-Chloro-4-(4-methoxyphenylamino)-2-methyl
quinolin-3-yl)ethanone(3y): yield: 161 mg (87%); white
o
1
solid; mp 165–166 C; H NMR (400 MHz, CDCl3): =
7.84 (d, J = 9.2 Hz, 1H), 7.76 (s, 1H), 7.75 (s, 1H), 7.52 (d,
J = 9.2 Hz, 1H), 6.88 (d, J = 9.2 Hz, 2H), 6.79 (d, J = 9.2
Hz, 2H), 3.77 (s, 3H), 2.65 (s, 3H), 2.42 (s, 3H). 13C NMR
(125 MHz, CDCl3): = 204.5, 156.1, 155.8, 146.9, 145.0,
135.7, 131.0, 130.6, 130.5, 123.1, 122.9, 122.3, 121.0,
114.6, 55.4, 31.9, 24.9. HR-MS (ESI): m/z = 341.1051,
calcd. for C19H18ClN2O2 (M+H)+: 341.1043.
Ethyl 4-(benzylamino)-2-methylquinoline-3-carboxylate
1
(3z): yield: 40 mg (25%); orange viscous liquid; H NMR
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= 8.4 Hz, 1H), 7.62 (t, J = 7.2 Hz, 1H), 7.39–7.30 (m, 6H),
6.87 (s, 1H), 4.67 (d, J = 5.4 Hz, 2H), 4.33 (q, J = 7.2 Hz,
2H), 2.72 (s, 3H), 1.35 (t, J = 7.2 Hz, 3H). 13C NMR (150
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129.0, 128.9, 127.8, 127.5, 124.4, 123.1, 118.7, 108.6, 61.3,
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C20H21N2O2 (M+H)+: 321.1598.
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N-((cyclohexylimino)methylene)aniline(10): yield: 69
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mg (69%); colorless liquid; H NMR (400 MHz, CDCl3) 
= 7.27 (t, J = 7.6 Hz, 2H), 7.13 – 7.04 (m, 3H), 3.46 (m,
1H), 2.14 – 1.90 (m, 2H), 1.81 – 1.71 (m, 2H), 1.62 – 1.41
(m, 3H), 1.40 – 1.18 (m, 3H). 13C NMR (150 MHz, CDCl3)
 = 140.9, 136.1, 129.2, 124.4, 123.3, 56.5, 34.9, 25.3, 24.3.
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Acknowledgements
Financial support of this research by the Natural Sciences
Foundation of Jilin Province (20170101181JC),the National
Natural Sciences Foundation of China (21572031, 21502016)
and the Specialized Research Fund for the Doctoral Program of
Higher Education (20130043120005) are greatly acknowledged.
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Advanced Synthesis & Catalysis
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Crystallographic
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Cu(II)-Catalyzed Desulfitative 6
Electrocyclization: Efficient Synthesis of Diverse
4-Aminoquinolines
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