An Improved Environmentally Friendly Approach to 4-Nitro-, 4-Sulfonyl-, and 4-Aminoquinolines and 4-Quinolones through Conjugate Addition of Nucleophiles to β-(2-Aminophenyl)-α,β-ynones

Article abstract of DOI:10.1055/s-0036-1588147

Sequential addition/annulation reactions of sulfinate and nitrite anions to β-(2-aminophenyl)-α,β-ynones led to valuable 4-sulfonylquinolines and 4-nitroquinolines. The latter proved to be versatile precursors of N-unsubstituted 4-aminoquinolines and 4-quinolones. Reaction of β-(2-aminophenyl)-α,β-ynones with DMF/NaOH resulted in the formation of 4-(dimethylamino)quinolines. The use of an alternative CO-free procedure for the preparation of substrates β-(2-aminophenyl)-α,β-ynones allowed extension of the methodology to the synthesis of 4-substituted 2-alkylquinolines.

Full text of DOI:10.1055/s-0036-1588147

SYNTHESIS
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1
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7
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1
0
X
© Georg Thieme Verlag Stuttgart · New York
2017, 49, A–L
paper
A
N. D. Rode et al.
Paper
Synthesis
An Improved Environmentally Friendly Approach to 4-Nitro-,
4-Sulfonyl-, and 4-Aminoquinolines and 4-Quinolones through
Conjugate Addition of Nucleophiles to β-(2-Aminophenyl)-α,β-
ynones
Navnath D. Rodea
Antonio Arcadia
Marco Chiarinib
Fabio Marinelli*a
O
RCHO
NO2
I
OH
R
R
a) Sonogashira
b) MnO2
NaNO2, NH4Cl
DMF, 60 °C
+
R = (hetero)aryl,
dienyl, alkyl
NH2
N
R
NH2
53–84% (13 examples)
DMF/H2O
NaOH
60 °C
NaSO2Tol
NH4Cl, DMF
80 °C
+
HCOO–NH4
H3O+
50 °C
a Dipartimento di Scienze Fisiche e Chimiche, Università
di L’Aquila, Via Vetoio, 67010 Coppito (AQ), Italy
b Facoltà di Bioscienze e Tecnologie Agroalimentari e
Ambientali, Università di Teramo, via R. Balzarini, 1,
64100 Teramo (Te), Italy
Pd/C
Me2N
SO2Tol
H2N
O
fabio.marinelli@univaq.it
N
R
N
R
N
R
N
R
H
43–76% (3 examples) 54–92% (16 examples) 66–90% (3 examples)
58–93% (3 examples)
Received: 13.01.2017
Accepted after revision: 27.01.2017
Published online: 22.02.2017
the 4-position of the quinoline ring. Nevertheless, some
limitations of this procedure should be highlighted. For ex-
ample, direct conjugate addition of hydroxide ion or ammo-
nia to 2 was quite difficult (vide infra). Moreover, the start-
ing ynones 2 were obtained through Pd-catalyzed carbon-
ylative coupling of 2-ethynylaniline with aryl iodides or
vinyl triflates. This route requires the reactions to be car-
ried out under CO atmosphere, and restricts the nature of
the substituent R to aryl and vinyl groups; consequently,
our ynone-based approach to quinolines has not yet been
applied to the preparation of 2-alkylquinolines.
DOI: 10.1055/s-0036-1588147; Art ID: ss-2017-t0026-op
Abstract Sequential addition/annulation reactions of sulfinate and ni-
trite anions to β-(2-aminophenyl)-α,β-ynones led to valuable 4-sulfo-
nylquinolines and 4-nitroquinolines. The latter proved to be versatile
precursors of N-unsubstituted 4-aminoquinolines and 4-quinolones.
Reaction of β-(2-aminophenyl)-α,β-ynones with DMF/NaOH resulted in
the formation of 4-(dimethylamino)quinolines. The use of an alterna-
tive CO-free procedure for the preparation of substrates β-(2-amino-
phenyl)-α,β-ynones allowed extension of the methodology to the syn-
thesis of 4-substituted 2-alkylquinolines.
O
Key words nitroquinolines, tosylquinolines, aminoquinolines, quino-
lones, ynones
RX, CO
Pd cat.
R
Quinoline is one of the most important heterocyclic sys-
tem, with widespread inclusion in a variety of naturally oc-
curring compounds,1 and many quinoline derivatives have
found application in therapy, for example as antimalarial2
and anticancer agents.3 Quinoline-based frameworks also
are key intermediates in assembling new materials with in-
teresting electronic properties.4 We have thoroughly exam-
ined the use of β-(2-aminophenyl)-α,β-ynones 2 as build-
ing blocks for the synthesis of quinolines by means of a gen-
eral strategy based on the conversion of the alkyne triple
bond into a cis-alkene moiety, which subsequently under-
goes sequential cyclocondensation.5 Among the different
methodologies we have developed for this transforma-
tion,6,7 conjugate addition of nucleophiles to 2 followed by
sequential cycloamination of C=O has emerged as a
straightforward and efficient route to 2,4-disubstituted
quinolines (Scheme 1).8 Halo-, alkoxy-, arylthio-, amino-,
and EWG-containing alkyl substituents were introduced at
NH2
NH2
2
1
NuH
Nu
Nu
N
O
R
– H2O
NH2
R
3
Nu = I, Br, OR', SR', NHR, CR'2EWG
R = aryl, heteroaryl, vinyl
X = I, OTf
Scheme 1 Previously developed synthesis of quinolines through con-
jugate addition of nucleophiles to β-(2-aminophenyl)-α,β-ynones 2
As part of our ongoing interest towards the develop-
ment of sustainable synthetic procedures for the synthesis
of heterocycles,9 we planned further investigation to over-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

B
N. D. Rode et al.
Paper
Synthesis
come the above limitations and to extend the scope of the
sequential conjugate addition to ynones 2 followed by an-
nulation, including different nucleophiles of practical im-
portance. Although the carbonylative coupling reaction al-
lows ready access to 2, we decided to test also an alternative
procedure, involving Sonogashira coupling of 2-iodoaniline
4 (or its substituted analogues) with terminal propargylic
alcohols 5 followed by oxidation of the resulting products 6.
Some examples of this approach to 2 (R = Ph, Me, i-Pr)
through oxidation of 6 with MnO210 or Cr(VI)11 were previ-
ously reported. Thus, ynones 2a–i (bearing alkyl, as well as
aryl, dienyl, and heteroaryl groups) were prepared by oxi-
dation of 6 with MnO2 (Table 1). Ynones 2j–q were instead
prepared using previously described carbonylative coupling
(Figure 1).
O
R
–
Y
NH2
TolSO2
–
NO2
NO2
2
SO2Tol
Y
N
R
Y
N
R
8
7
Scheme 2 Conjugate addition of nitrite and sulfinate anion to 2/cy-
clization
4-Nitroquinolines are useful intermediates. They have
found application of as direct precursors of fluorinated im-
aging agents for detecting neurological disorders12 and for
the synthesis of a trifluoromethylated analogue of ICI
D8331.13
Table 1 Synthesis of Ynones 2a–i
OH
Interestingly, 4-aminoquinolines14 and 4-unsubstituted
quinolines15 can also be obtained by selective reduction of
4-nitroquinolines. To the best of our knowledge, prepara-
tion of 4-nitroquinolines from acyclic precursors has not
been previously reported: the introduction of the 4-nitro
group is usually achieved by electrophilic nitration of the
quinoline ring, and requires its preliminary activation as
the N-oxide. One example of displacement of 4-chloroquin-
oline derivative by nitrite anion has also been described.16
Both these procedures rely on synthetic elaboration of a
preformed quinoline derivative.
4-(Arylsulfonyl)quinoline derivatives showed interest-
ing pharmacological properties as serotonin 5-HT6 receptor
antagonists.17 They also are useful intermediates, since the
good leaving ability of ArSO2 group facilitates SNAr reac-
tions.18,20a This characteristic has been employed, for exam-
ple, in the last step of a large-scale convergent synthesis of
the macrocyclic HCV protease inhibitor BI 201302 recently
published from a Boehringer-Ingelheim research group.19
Tosylation of a suitable 4-quinolone, followed by nucleop-
hilic displacement of OTs with sulfinate anion, was used in
this case to prepare the target sulfonylquinoline derivative.
4-Sulfonylquinolines were otherwise prepared through re-
action of nitroarenes with allyl tolyl sulfones20 and reaction
of indol-3-yl methyl sulfone with nitrobenzene.21 Oxidation
of 7-chloro-4-(p-tolylthio)quinoline to the corresponding
sulfonyl derivative was also described.22
R
OH
5
PdCl2(PPh3)2
CuI
I
R
i-Pr2NH
MnO2
2a–i
Y
NH2
THF, r.t.
60–97%
NH2
6a–i
Y
CHCl3, 60 °C
49–81%
4
R
Y
4
5
6
Yield
(%)
2
Yield
(%)
Ph
Et
H
H
H
H
H
H
H
Cl
F
4a
4a
4a
4a
4a
4a
4a
4b
4c
5a
5b
5c
5d
5e
5f
6a
99
2a
2b
2c
2d
2e
2f
52
6b
6c
6d
6e
6f
96
81
83
60
97
87
95
95
81
70
49
58
63
69
84
72
n-C5H11
c-Hex
C4H9(CH=CH)2
2-furyl
2-BrC6H4
Ph
5g
5a
5a
6g
6h
6i
2g
2h
2i
Ph
Then, we attempted the extension of the scope of our
conjugate addition–cyclization methodology to include ni-
trite and arylsulfinate anions as nucleophiles, with the aim
of obtaining interesting 4-nitroquinoline and 4-sulfonyl-
quinoline derivatives 7 and 8, respectively (Scheme 2).
1-naphthyl
2j
Therefore, new efficient approaches to these significant
quinoline derivatives should be beneficial. Herein we report
the results of our study.
We started the investigation by exploring the reaction
of the nitrite anion with ynones 2. Conjugate addition of
NO2– to enones has been described;23 no examples of simi-
lar reactions with ynones have been reported so far. Thus,
O
2k 3-MeC6H4
2l 4-MeOC6H4
2m 4-ClC6H4
3-MeO2CC6H4
2o 4-AcC6H4
R
2n
NH2
2p 3-F3CC6H4
2-thienyl
2q
Figure 1 Ynones 2j–q
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

C
N. D. Rode et al.
Paper
Synthesis
reaction between 2a and NaNO2 was selected as a model
system, and the results obtained under different conditions
are summarized in Table 2.
Table 3 Sequential Conjugate Addition of Nitrite to 2/Cyclizationa
O
NO2
N
NaNO2
NH4Cl
R
When the reaction of 2a with 2 equiv of sodium nitrite
was carried out in DMF at 60 °C in the presence of 2 equiva-
lents of TsOH (this additive was an efficient proton source
for the reaction of 2 with NaI),24 the corresponding quino-
line 7a was obtained only in poor yield (entry 1); worse re-
sults were observed by using water as additive and in ab-
sence of any additive (entries 2–4). Ammonium chloride in
DMF was a more suitable additive, giving 7a in satisfactory
yield (entries 5–8), and the best result was observed at
60 °C (entry 7). Other solvents were less effective than DMF
(entries 9–11).
DMF
60 °C
46–84%
Y
R
Y
NH2
2
7
Entry
2
R
Y
7
Yieldb (%)
1
2
2a
2c
2f
Ph
H
H
H
H
Cl
H
H
H
H
H
H
H
H
7a
71
n-C5H11
2-furyl
7c
7f
22 (63c)
46 (70d)
84
3
4
2g
2h
2j
2-BrC6H4
Ph
7g
7h
7j
5
72
Table 2 Optimization of the Conjugate Addition of NaNO2 to 2aa
6
1-naphthyl
3-MeC6H4
4-MeOC6H4
4-ClC6H4
68
7
2k
2l
7k
7l
62
O
NO2
8
69
Ph
NaNO2
9
2m
2n
2o
2p
2q
7m
7n
7o
7p
7q
65
additive
solvent
10
11
12
13
3-MeO2CC6H4
4-AcC6H4
53
N
Ph
NH2
2a
78
7a
3-F3CC6H4
2-thienyl
60
Entry
Solvent
Additive
Temp
(°C)
Time
(h)
Yielda,b
(%) of 7a
68
a Reaction conditions: molar ratio 2/NaNO2/NH4Cl = 1:2:2, 60 °C, 2 h (un-
less otherwise stated).
1
2
DMF
DMF
DMF
EtOH
DMF
DMF
DMF
DMF
EtOH
MeCN
THF
TsOH
H2O
60
60
1
10
10
5
24
6
b Yield of isolated product.
c Carried out at 40 °C for 6 h.
d Carried out at 40 °C for 3 h.
3
none
100
80
9
4
none
10
43
52
71
55
28
23
29
5
NH4Cl
NH4Cl
NH4Cl
NH4Cl
NH4Cl
NH4Cl
NH4Cl
100
80
2
dure was less general in the case of R = alkyl. For example
ynone 2c, bearing an n-pentyl substituent, afforded quino-
line 7c in good yield at 40 °C; however, under the same re-
action conditions, a cyclohexyl substituent gave worse re-
sults (ynone 2d was consumed, but we were not able to iso-
late the expected 2-cyclohexyl-4-nitroquinoline from the
complex reaction mixture obtained).
6
2
7
60
2
8
r.t.
60
24
10
10
24
9
10
11
60
60
a Reaction conditions: 2a (0.25 mmol), additive (2 equiv), NaNO2 (2 equiv),
Next, we extended the procedure to the synthesis of 4-
sulfonylquinoline derivatives 8.
solvent (1 mL).
b Yield of isolated product.
As reported in Table 4, the reaction afforded satisfactory
results not only with aryl/heteroaryl substituents, but also
with alkyl substituents in the starting ynones (entries 2–4).
A dienyl group was also introduced successfully (entry 5).
Although primary amines reacted efficiently with
ynones 2 to give N-substituted 4-aminoquinolines,8b we
failed to obtain 4-aminoquinolines 9 (bearing an unsubsti-
tuted NH2 group) through conjugate addition of NH3 to 2
using similar conditions. As an example, 9a was detected in
trace amounts when 2a was reacted with 2 equivalents of 2
M NH3 in methanol in a screw cap-sealed tube (toluene,
110 °C, 16 h). Selective Pd/C catalyzed reduction of 7 with
ammonium formate allowed a convenient preparation of
products 9 (Scheme 3).25
The optimized conditions of entry 7 were used to ex-
plore the substrate scope of this sequential conjugate addi-
tion of the nitrite anion/cyclization (Table 3).
Ynones 2 bearing aryl moieties containing both elec-
tron-donating and electron-withdrawing substituents were
converted into the corresponding 2-aryl-4-nitroquinolines
in moderate to good yields, and a Cl substituent at the quin-
oline 7-position was also allowed (entry 5). Heteroaryl
groups were also successfully introduced in the target
products (entries 3 and 13). In some instances, depending
on the nature of the R group, the reaction afforded better
results at 40 °C (entries 2 and 3). The scope of the proce-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

D
N. D. Rode et al.
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Synthesis
Table 4 Sequential Conjugate Addition of Sulfinate to 2/Cyclizationa
NO2
N
O
1 M H2SO4
CF3COOH
50 °C, 4 h
R
N
H
R
7
10
O
R
10
Yield (%)
O
S
N
O
TolSO2Na
NH4Cl
R
Ph
4-ClC6H4
2-thienyl
10a
10m
10q
93
58
78
DMF
80 °C
Y
R
Y
NH2
66–92%
Scheme 4 Hydrolysis of 7 to give 4-quinolones 10
2
8
Entry
2
R
Y
8
Yieldb (%)
Surprisingly, an attempt to carry out the addition of
NaOH to 2a using DMF/H2O (80:20) in place of MeCN re-
sulted in the isolation of 4-(dimethylamino)quinoline 11a
in 71% yield after 1 hour at 60 °C. When the experiment
was repeated omitting NaOH, under otherwise identical
conditions, only starting material was detected in the reac-
tion mixture, without formation of 11a. Prolonging the re-
action time to 8 hours afforded similar results. These obser-
vations support the idea that, under the present reaction
conditions, DMF does not act as a nucleophile.26 Likely, its
base-promoted hydrolysis generates dimethylamine, whose
reaction with 2a affords 11a (the reaction of ynones 2 with
secondary amines to give 11 has been reported8b,27). The
use of DMF in place of dimethylamine to give 11 was briefly
explored (Scheme 5).
1
2
2a
2b
2c
2d
2e
2f
Ph
H
8a
8b
8c
8d
8e
8f
83
54
86
66c
72c
86
70
83
88
89
87
91
75
83
92
78
Et
H
H
H
H
H
H
F
3
n-C5H11
c-Hex
4
5
(E,E)-octa-1,3-dienyl
2-furyl
6
7
2g
2i
2-BrC6H4
8g
8i
8
Ph
9
2j
1-naphthyl
3-MeC6H4
4-MeOC6H4
4-ClC6H4
H
H
H
H
H
H
H
H
8j
10
11
12
13
14
15
16
2k
2l
8k
8l
2m
2n
2o
2p
2q
8m
8n
8o
8p
8q
3-MeO2CC6H4
4-AcC6H4
3-F3CC6H4
2-thienyl
O
N
R
5% NaOH
DMF
60 °C
N
R
NH2
a Reaction conditions: molar ratio 2/ArSO2Na/NH4Cl = 1:2:2, 80 °C, 2 h (un-
less otherwise stated).
2
11
b Yield of isolated product.
c Carried out at 50 °C for 1 h.
R
11
Yield (%)
Ph
11a
11c
11l
71
43
76
n-C5H11
4-MeOC6H4
NO2
N
NH2
N
HCOONH4
Pd/C
Scheme 5 Reaction of 2 with DMF/NaOH to give 4-(dimethylami-
no)quinolines 11
MeOH
40 °C, 1 h
R
R
7
9
R
9
Yield (%)
In summary, we have developed a practical route to 4-
nitroquinolines 7 and 4-sulfonylquinolines 8 through the
reaction of β-(2-aminophenyl)-α,β-ynones 2 with nitrite
and sulfinate anions in the presence of cheap ammonium
chloride as a proton source. The 4-nitroquinoline deriva-
tives obtained proved to be versatile precursors of interest-
ing 2-aryl-4-quinolones28 and N-unsubstituted 4-amino-
quinolines.29 DMF/NaOH was demonstrated to be an alter-
native to the use of dimethylamine for the synthesis of 4-
(dimethylamino)quinolines. The preparation of starting
ynones using an alternative environmentally friendly CO-
free procedure allowed the introduction of alkyl groups (as
well as other useful substituents) in the 2-position of the
quinoline ring, due to the wide availability of terminal
alkynes 5.
Ph
9a
9f
89
66
90
2-furyl
4-AcC6H4
9o
Scheme 3 Reduction of 7 to give 4-aminoquinolines 9
Also conjugate addition of hydroxide ion to 2 to give 4-
quinolone derivatives was unsuccessful: we observed a
sluggish reaction when 2a was treated with 2 equivalents
of 5% NaOH in MeCN at 60 °C (after 24 h, TLC analysis
showed only partial conversion of the starting ynone, with
little formation of 2-phenyl-4-quinolone 10a). Hydrolysis
of 4-nitroquinolines13 allowed a simple alternative route to
10 (Scheme 4).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

E
N. D. Rode et al.
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Synthesis
Unless otherwise stated, all starting materials, catalysts, and solvents
were commercially available and were used as purchased. Reaction
products were purified by flash chromatography on silica gel eluting
with n-hexane/EtOAc mixtures. 2-iodoanilines 4a–c and terminal
alkynes 5a–c are commercially available; terminal alkynes 5d,30 5e,31
5f,32 and 5g33 are known compounds. Propargylic alcohol 6a10b and
ynones 2a,10b 2j,8a 2l,8a 2m,8a 2p,8a and 2o24 are known compounds.
Ynones 2k, 2n and 2q were prepared according to the literature.6b
Quinolines 7a,34 9a,35 10a,28d 10m,28c 10q,28d 11a,26 and 11l26 are
known compounds and were identified by comparison of their physi-
cal and spectral data with those reported in the cited references.
Melting points were obtained using a Büchi 500 apparatus and are
uncorrected. IR spectra (KBr pellets or neat on NaCl plates) were re-
3-(2-Aminophenyl)-1-(2-bromophenyl)prop-2-yn-1-ol (6g); Typi-
cal Procedure for the Sonogashira Coupling of 2-Iodoaniline with
Alkynes 5a–g
To a solution of 2-iodoaniline (1.000 g, 4.57 mmol) in THF (15 mL)
and i-Pr2NH (3.20 mL, 22.83 mmol) were added 1-bromo-2-ethynyl-
benzene 5g (1.16 g, 5.48 mmol), PdCl2(PPh3)2 (0.048 g, 0.068 mmol,
1.5 mol%), and CuI (0.026 g, 0.136 mmol, 3 mol%). The mixture was
stirred at r.t. under N2 for 2 h. After completion of the reaction, the
mixture was extracted with NH4Cl (0.5 M) and EtOAc (3 ×). The com-
bined organic phases were dried (Na2SO4) and evaporated. The resi-
due was purified by column chromatography (petroleum ether/EtOAc,
80:20) to give 6g as a brown oil; yield: 1.205 g (87%).
IR (neat): 3404, 3283, 3009, 2175, 1618, 1589, 1431, 1025, 755 cm–1
.
1
corded on a Perkin-Elmer Spectrum Two FT-IR spectrophotometer.
1H NMR (400 MHz, CDCl3): δ = 7.82 (dd, J = 1.9, 7.8 Hz, 1 H), 7.58 (dd,
J = 1.6, 8.0 Hz, 1 H), 7.35–7.39 (m, 1 H), 7.29 (dd, J = 1.6, 7.9 Hz, 1 H),
7.18–7.22 (m, 1 H), 7.10–7.14 (m, 1 H), 6.65–6.79 (m, 2 H), 6.03 (s, 1
H), 4.20 (br s, 2 H, NH2).
13C NMR (100.6 MHz, CDCl3): δ = 148.09, 139.70, 133.11, 132.31,
130.23, 130.08, 129.93, 128.48, 127.99, 122.54, 117.92, 114.45,
106.95, 93.14, 83.52, 64.81.
H NMR spectra were recorded at 400 MHz on a Bruker Avance III
spectrometer referenced to TMS (δ = 0) in CDCl3. 13C NMR spectra
were obtained using the same instrument at 100.6 MHz and were cal-
ibrated with CDCl3 (δ = 77.03). HRMS spectra were recorded using a
MALDI-TOF spectrometer: AB SCIEX TOF/TOF 5800 System.
3-(2-Aminophenyl)-1-(m-tolyl)prop-2-yn-1-one (2k)
Yellow solid; yield: 0.518 g (58%); mp 119–120 °C.
HRMS MALDI-TOF: m/z [M + H]+ calcd for C15H13BrNO: 302.0181;
found: 302.0180.
IR (KBr): 3404, 3312, 2171, 1642, 1623, 1597, 1456, 1154, 738 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.00–8.04 (m, 2 H), 7.48 (dd, J = 1.6, 6.7
Hz, 1 H), 7.38–7.45 (m, 2 H), 7.23–7.28 (m, 1 H), 6.71–6.76 (m, 2 H),
4.52 (s, 2 H, NH2), 2.45 (s, 3 H).
1-(2-Aminophenyl)pent-1-yn-3-ol (6b)
Brown oil; yield: 0.780 g (96%).
13C NMR (100.6 MHz, CDCl3): δ = 178.02, 150.40, 138.53, 137.07,
134.83, 133.77, 132.59, 129.72, 128.54, 126.99, 117.97, 114.71,
103.94, 93.45, 90.97, 21.35.
HRMS MALDI-TOF: m/z [M + H]+ calcd for C16H14NO: 236.1075; found:
236.1077.
IR (neat): 3474, 3371, 2972, 2930, 2220, 1618, 1494, 1456, 1315,
1012, 746 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.24–7.26 (m, 1 H), 7.08–7.13 (m, 1 H),
6.65–6.69 (m, 2 H), 4.58 (t, J = 6.3 Hz, 1 H), 4.20 (br s, 2 H, NH2), 1.78–
1.86 (m, 2 H), 1.06 (t, J = 7.4 Hz, 3 H).
13C NMR (100.6 MHz, CDCl3): δ = 147.81, 132.24, 129.73, 117.95,
114.42, 107.45, 95.55, 81.45, 64.24, 31.07, 9.60.
Methyl 3-[3-(2-Aminophenyl)prop-2-ynoyl]benzoate (2n)
Yellow solid; yield: 0.826 g (82%); mp 156–158 °C.
HRMS MALDI-TOF: m/z [M + H]+ calcd for C11H14NO: 176.1075; found:
176.1072.
IR (KBr): 3408, 3317, 2175, 1726, 1618, 1434, 1199, 713 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.88–8.89 (m, 1 H), 8.37–8.39 (m, 1 H),
8.28–8.30 (m, 1 H), 7.61 (t, J = 7.9 Hz, 1 H), 7.51 (dd, J = 1.7, 7.9 Hz, 1
H), 7.25–7.30 (m, 1 H), 6.73–6.77 (m, 2 H), 4.57 (br s, 2 H, NH2), 3.98
(s, 3 H).
13C NMR (100.6 MHz, CDCl3): δ = 176.75, 166.12, 150.64, 137.23,
134.59, 134.04, 133.19, 132.96, 130.84, 130.81, 128.93, 118.05,
114.79, 103.48, 93.21, 92.40, 52.49.
1-(2-Aminophenyl)oct-1-yn-3-ol (6c)
Brown oil; yield: 0.810 g (81%).
IR (neat): 3474, 3366, 2930, 2856, 2220, 1618, 1494, 1456, 1315,
1016, 746 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.25 (dd, J = 1.7, 8.1 Hz, 1 H), 7.08–7.12
(m, 1 H), 6.65–6.69 (m, 2 H), 4.62 (t, J = 6.6 Hz, 2 H), 4.20 (br s, 1 H,
NH2), 1.74–1.84 (m, 2 H), 1.47–1.54 (m, 2 H), 1.28–1.35 (m, 4 H), 0.90
(t, J = 6.7 Hz, 3 H).
HRMS MALDI-TOF: m/z [M + H]+ calcd for C17H14NO3: 280.0974;
found: 280.0973.
13C NMR (100.6 MHz, CDCl3): δ = 147.79, 132.21, 129.70, 117.94,
114.42, 107.48, 95.86, 81.33, 63.02, 37.98, 31.45, 25.00, 22.56, 14.00.
3-(2-Aminophenyl)-1-(thiophen-2-yl)prop-2-yn-1-one (2q)
Brown solid; yield: 1.57 g (92%); mp 131–132 °C.
HRMS MALDI-TOF: m/z [M + H]+ calcd for C14H20NO: 218.1545; found:
218.1545.
IR (KBr): 3400, 3321, 2179, 1635, 1589, 1411, 1290, 717 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.99 (dd, J = 1.3, 2.6 Hz, 1 H), 7.76 (dd,
J = 1.7, 7.9 Hz, 1 H), 7.72 (dd, J = 1.3, 3.6 Hz, 1 H), 7.24–7.28 (m, 1 H),
7.19 (dd, J = 1.3, 3.6 Hz, 1 H), 6.71–6.75 (m, 2 H), 4.50 (br s, 2 H, NH2).
3-(2-Aminophenyl)-1-cyclohexylprop-2-yn-1-ol (6d)
Brown solid; yield: 0.553 g (83%); mp 104–106 °C.
IR (KBr): 3382, 3295, 2845, 2177, 1624, 1495, 1295, 1025, 747 cm–1
13C NMR (100.6 MHz, CDCl3): δ = 169.52, 150.36, 144.98, 134.91,
.
1H NMR (400 MHz, CDCl3): δ = 7.26–7.28 (m, 1 H), 7.09–7.14 (m, 1 H),
6.66–6.70 (m, 2 H), 4.43 (d, J = 6.1 Hz, 1 H), 4.19 (br s, 2 H, NH2), 1.91–
1.95 (m, 1 H), 1.78–1.81 (m, 2 H), 1.62–1.72 (m, 2 H), 1.11–1.30 (m, 6
H).
134.58, 133.80, 132.70, 128.41, 118.02, 114.73, 103.85, 92.87, 89.89.
HRMS MALDI-TOF: m/z [M + H]+ calcd for C13H10NOS: 228.0483;
found: 228.0480.
13C NMR (100.6 MHz, CDCl3): 147.83, 132.30, 129.72, 117.93, 114.37,
107.49, 94.70, 82.29, 67.83, 44.30, 28.76, 28.29, 26.40, 25.92, 25.89.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

F
N. D. Rode et al.
Paper
Synthesis
HRMS MALDI-TOF: m/z [M + H]+ calcd for C15H20NO: 230.1545; found:
β-(2-Aminophenyl)-α,β-ynones 2a–i; General Procedure
230.1542.
This transformation was carried out according to ref. 10a. Propargylic
alcohol 6 (4–10 mmol) was dissolved in CHCl3 (10–25 mL) and acti-
vated MnO2 (5 equiv) was added. The heterogeneous mixture was re-
fluxed for 3–5 h; the reaction progress was monitored by TLC. When
the conversion of starting material was complete, the crude mixture
was filtered through a short pad of Celite using EtOAc as eluent. The
solvent was removed under reduced pressure and the residue was pu-
rified by column chromatography (silica gel, petroleum ether/EtOAc
mixtures).
(4E,6E)-1-(2-Aminophenyl)undeca-4,6-dien-1-yn-3-ol (6e)
Brown oil; yield: 0.418 g (60%).
IR (neat): 3368, 3024, 2926, 2218, 1613, 1455, 1316, 1158, 748 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.27 (dd, J = 8.2, 1.9 Hz, 1 H), 7.09–7.13
(m, 1 H), 7.65–7.69 (m, 2 H), 7.42 (dd, J = 15.50, 10.2 Hz, 1 H), 6.03–
6.09 (m, 1 H), 5.73–5.81 (m, 2 H), 5.16 (d, J = 6.1 Hz, 1 H), 4.17 (br s, 2
H, NH2), 2.10 (q, J = 6.9 Hz, 2 H), 1.28–1.39 (m, 4 H), 0.89 (t, J = 7.1 Hz,
3 H).
13C NMR (100.6 MHz, CDCl3): 147.93, 137.46, 132.67, 132.28, 129.88,
128.86, 128.77, 117.91, 114.43, 107.19, 93.69, 82.71, 63.33, 32.36,
31.24, 22.21, 13.92.
1-(2-Aminophenyl)pent-1-yn-3-one (2b)
Brown oil; yield: 0.630 g (81%).
IR (neat): 3470, 3366, 2980, 2935, 2175, 1660, 1622, 1490, 1460,
1315, 1116, 1045, 755 cm–1
.
HRMS MALDI-TOF: m/z [M + H]+ calcd for C17H22NO: 256.1701; found:
256.1700.
1H NMR (400 MHz, CDCl3): δ = 7.33–7.36 (m, 1 H), 7.19–7.23 (m, 1 H),
6.65–6.71 (m, 2 H), 4.47 (br s, 2 H, NH2), 2.69 (q, J = 7.3 Hz, 2 H), 1.21
(t, J = 7.3 Hz, 3 H).
13C NMR (100.6 MHz, CDCl3): δ = 188.28, 150.21, 133.74, 132.47,
117.73, 144.56, 103.43, 93.91, 88.81, 38.60, 8.24.
3-(2-Aminophenyl)-1-(furan-2-yl)prop-2-yn-1-ol (6f)
Brown solid; yield: 1.90 g (97%); mp 123–124 °C.
IR (KBr): 3408, 2922, 2191, 2171, 1647, 1618, 1386, 1265, 1069 cm–1
1H NMR (400 MHz, CDCl3): δ = 7.43 (dd, J = 1.0, 1.9 Hz, 1 H), 7.29 (dd,
J = 1.5, 8.2 Hz, 1 H), 7.11–7.15 (m, 1 H), 6.66–6.70 (m, 2 H), 6.50 (d,
J = 3.3 Hz, 1 H), 6.37 (dd, J = 1.8, 3.3 Hz, 1 H), 5.72 (s, 1 H), 4.25 (br s, 2
H, NH2).
13C NMR (100.6 MHz, CDCl3): δ = 153.00, 148.21, 143.05, 132.34,
130.20, 117.93, 114.48, 110.52, 107.87, 106.73, 91.68, 82.69, 58.75.
HRMS MALDI-TOF: m/z [M + H]+ calcd for C13H12NO2: 214.0868;
found: 214.0870.
.
HRMS MALDI-TOF: m/z [M + H]+ calcd for C11H12NO: 174.0919; found:
174.0920.
1-(2-Aminophenyl)oct-1-yn-3-one (2c)
Brown solid; yield: 0.556 g (70%); mp 52–53 °C.
IR (KBr): 3453, 3341, 2933, 2867, 2177, 1645, 1458, 1325, 1258, 1075,
755 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.36 (d, J = 8.2 Hz, 1 H), 7.20–7.24 (m, 1
H), 6.67–6.71 (m, 2 H), 4.45 (br s, 2 H, NH2), 2.66 (t, J = 7.9 Hz, 2 H),
1.71–1.78 (m, 2 H), 1.33–1.36 (m, 4 H), 0.91 (t, J = 7.9 Hz, 3 H).
13C NMR (100.6 MHz, CDCl3): δ = 187.98, 150.20, 133.82, 132.51,
117.85, 114.58, 103.60, 94.23, 88.61, 45.39, 31.15, 24.05, 22.38, 13.87.
3-(2-Amino-4-chlorophenyl)-1-phenylprop-2-yn-1-ol (6h)
Brown solid; yield: 1.10 g (95%); mp 82–83 °C.
IR (KBr): 3386, 3307, 3066, 2829, 2210, 1603, 1487, 1420, 1266, 1046,
HRMS MALDI-TOF: m/z [M + H]+ calcd for C14H18NO: 216.1388; found:
216.1389.
809 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.56 (d, J = 8.1 Hz, 2 H), 7.30–7.39 (m, 3
H), 7.16 (d, J = 8.8 Hz, 1 H), 6.61–6.63 (m, 2 H), 5.67 (s, 1 H), 4.27 (br s,
2 H, NH2).
13C NMR (100.6 MHz, CDCl3): δ = 148.96, 140.63, 135.56, 133.20,
128.72, 128.47, 126.61, 118.07, 114.18, 105.60, 95.09, 82.36, 65.04.
3-(2-Aminophenyl)-1-cyclohexylprop-2-yn-1-one (2d)
Yellow solid; yield: 0.217 g (49%);36 mp 92–93 °C.
IR (KBr): 3451, 3348, 2922, 2847, 2181, 1639, 1490, 1258, 1002 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.35–7.38 (m, 1 H), 7.20–7.24 (m, 1 H),
6.67–6.71 (m, 2 H), 4.44 (br s, 2 H, NH2), 2.47–5.54 (m, 1 H), 2.04–2.08
(m, 2 H), 1.79–1.84 (m, 2 H), 1.66–1.71 (m, 1 H), 1.46–1.55 (m, 2 H),
1.21–1.39 (m, 3 H).
13C NMR (100.6 MHz, CDCl3): δ = 191.24, 150.15, 133.83, 132.43,
117.85, 114.58, 103.81, 93.56, 89.39, 52.17, 28.52, 25.80, 25.42.
HRMS MALDI-TOF: m/z [M + H]+ calcd for C15H13ClNO: 258.0686;
found: 258.0686.
3-(2-Amino-4-fluorophenyl)-1-phenylprop-2-yn-1-ol (6i)
Brown oil; yield: 0.290 g (95%).
IR (neat): 3370, 3066, 2879, 2218, 1624, 1503, 1445, 1283, 1171,
HRMS MALDI-TOF: m/z [M + H]+ calcd for C15H18NO: 228.1388; found:
228.1386.
1013, 846, 697 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.55–7.57 (m, 2 H), 7.30–7.39 (m, 3 H),
7.21 (dd, J = 1.9, 8.1 Hz, 1 H), 6.31–6.38 (m, 2 H), 5.67 (s, 1 H), 4.31 (br
s, 2 H, NH2).
13C NMR (100.6 MHz, CDCl3): δ = 163.84 (d, JC-F = 247 Hz), 149.83 (d,
JC-F = 12 Hz), 140.71, 133.86 (d, JC-F = 10.7 Hz), 128.70, 128.43, 126.61,
105.19 (d, JC-F = 22.7 Hz), 103.18, 101.19 (d, JC-F = 25.7 Hz), 94.00,
82.49, 65.05.
(4E,6E)-1-(2-Aminophenyl)undeca-4,6-dien-1-yn-3-one (2e)
Brown solid; yield: 0.210 g (58%); mp 66–67 °C.
IR (KBr): 3329, 2959, 2922, 2166, 1635, 1618, 1577, 1319, 1178, 991,
750 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.45–7.52 (m, 1 H), 7.38–7.40 (m, 1 H),
7.19–7.24 (m, 1 H), 6.68–6.72 (m, 2 H), 6.28–6.35 (m, 2 H), 6.23 (d,
J = 15.3 Hz, 1 H), 4.47 (br s, 2 H, NH2), 2.20–2.25 (m, 2 H), 1.31–1.49
(m, 4 H), 0.92 (t, J = 7.4 Hz, 3 H).
HRMS MALDI-TOF: m/z [M + H]+ calcd for C15H13FNO: 242.0981;
found: 242.0981.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

G
N. D. Rode et al.
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Synthesis
13C NMR (100.6 MHz, CDCl3): δ = 178.21, 150.10, 148.43, 147.72,
133.48, 132.22, 130.00, 128.67, 117.83, 114.64, 104.06, 92.95, 88.92,
32.96, 30.71, 22.23, 13.83.
HRMS MALDI-TOF: m/z [M + H]+ calcd for C17H20NO: 254.1545; found:
254.1545.
4-Nitro-2-phenylquinoline (7a); Typical Procedure for 2-Substi-
tuted 4-Nitroquinolines 7a–q
To a mixture of 3-(2-aminophenyl)-1-phenylprop-2-yn-1-one (2a,
0.200 g, 0.90 mmol), NaNO2 (0.125 g, 1.80 mmol), and NH4Cl (0.097 g,
1.80 mmol) was added DMF (3 mL). The mixture was stirred at 60 °C
for 2 h, then extracted with water and EtOAc (3 ×). The combined or-
ganic phase was dried (Na2SO4) and concentrated under reduced
pressure. The residue was purified by column chromatography (pe-
troleum ether/EtOAc 90:10) to give 7a; yield: 160 mg (71%)
3-(2-Aminophenyl)-1-(furan-2-yl)prop-2-yn-1-one (2f)
Yellow solid; yield: 0.828 g (63%); mp 109–111 °C.
IR (KBr): 3395, 3317, 2183, 1618, 1456, 1394, 1004, 742 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.67–7.68 (m, 1 H), 7.39–7.43 (m, 2 H),
7.22–7.27 (m, 1 H), 6.69–6.75 (m, 2 H), 6.59–6.61 (m, 1 H), 4.61 (s, 2
H, NH2).
13C NMR (100.6 MHz, CDCl3): δ = 164.76, 153.30, 150.64, 147.70,
133.66, 132.77, 119.87, 117.86, 114.85, 112.73, 103.37, 92.67, 90.75.
4-Nitro-2-pentylquinoline (7c)
Brown liquid; yield: 36 mg (63%).
IR (neat): 3408, 2955, 2930, 2860, 1622, 1535, 1353, 767 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.35–8.38 (m, 1 H), 8.16–8.18 (m, 1 H),
7.80–7.84 (m, 2 H), 7.67–7.71 (m, 1 H), 3.05–3.09 (m, 2 H), 1.83–1.90
(m, 2 H), 1.38–1.43 (m, 4 H), 0.92 (t, J = 7.1 Hz, 3 H).
13C NMR (100.6 MHz, CDCl3): δ = 163.28, 152.76, 150.01, 130.80,
129.62, 128.76, 122.58, 117.22, 115.32, 39.11, 31.57, 29.24, 22.50,
13.97.
HRMS MALDI-TOF: m/z [M + H]+ calcd for C13H10NO2: 212.0712;
found: 212.0715.
3-(2-Aminophenyl)-1-(2-bromophenyl)prop-2-yn-1-one (2g)
Yellow solid; yield: 0.818 g (69%); mp 108–109 °C.
HRMS MALDI-TOF: m/z [M + K]+ calcd for C14H16KN2O2: 283.0849;
found: 283.0850.
IR (KBr): 3401, 3221, 2167, 1637, 1610, 1315, 1007, 730 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.01 (dd, J = 1.8, 7.9 Hz, 1 H), 7.70 (dd,
J = 1.4, 7.9 Hz, 1 H), 7.36–7.47 (m, 3 H), 7.23–7.27 (m, 1 H), 6.69–6.73
(m, 2 H), 4.51 (br s, 2 H, NH2).
13C NMR (100.6 MHz, CDCl3): δ = 177.49, 150.65, 138.16, 134.79,
134.00, 133.15, 132.98, 132.29, 127.47, 120.96, 118.00, 114.68,
103.59, 94.68, 92.82.
2-(Furan-2-yl)-4-nitroquinoline (7f)
Yellow solid; yield: 56 mg (70%); mp 103–105 °C.
IR (KBr): 3425, 3138, 1611, 1588, 1525, 1348, 1088, 1020, 761 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.34–8.36 (m, 1 H), 8.33 (s, 1 H), 8.20–
8.23 (m, 1 H), 7.83 (ddd, J = 8.5, 7.10, 1.4 Hz, 1 H), 7.67–7.71 (m, 2 H),
7.34 (dd, J = 3.5, 0.8 Hz, 1 H), 6.64 (dd, J = 3.6, 1.8 Hz, 1 H).
13C NMR (100.6 MHz, CDCl3): δ = 152.26, 150.27, 148.91, 145.10,
145.09, 131.28, 129.98, 129.10, 122.74, 117.47, 112.78, 111.87,
111.72.
HRMS MALDI-TOF: m/z [M + H]+ calcd for C15H11BrNO: 300.0024;
found: 300.0024.
3-(2-Amino-4-chlorophenyl)-1-phenylprop-2-yn-1-one (2h)
Yellow solid; yield: 0.753 g (84%); mp 137–138 °C.
HRMS MALDI-TOF: m/z [M + K]+ calcd for C13H8KN2O3: 279.0172;
found: 279.0170.
IR (KBr): 3391, 3317, 3200, 2183, 1647, 1598, 1257, 1008, 692 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.17–8.20 (m, 2 H), 7.61–7.65 (m, 1 H),
7.49–7.54 (m, 2 H), 7.39 (d, J = 8.3 Hz, 1 H), 6.74 (d, J = 1.9 Hz, 1 H),
6.69–6.71 (m, 1 H), 4.63 (br s, 2 H, NH2).
13C NMR (100.6 MHz, CDCl3): δ = 177.66, 151.16, 138.64, 136.84,
134.74, 134.11, 129.45, 128.70, 118.37, 114.46, 102.35, 93.85, 90.03.
2-(2-Bromophenyl)-4-nitroquinoline (7g)
Pale yellow solid; yield: 48 mg (84%); mp 146–147 °C.
IR (KBr): 3420, 3066, 1603, 1528, 1366, 1341, 1237, 1025, 749 cm–1
1H NMR (400 MHz, CDCl3): δ = 8.48 (d, J = 7.3 Hz, 1 H). 8.30–8.33 (m, 2
H), 7.87–7.92 (m, 1 H), 7.78–7.82 (m, 1 H), 7.69–7.76 (m, 2 H), 7.48–
7.52 (m, 1 H), 7.37 (ddd, J = 7.9, 1.9 Hz, 1 H).
.
HRMS MALDI-TOF: m/z [M + H]+ calcd for C15H11ClNO: 256.0529;
found: 256.0530.
13C NMR (100.6 MHz, CDCl3): δ = 117.1, 117.7, 121.76, 122.76, 128.01,
129.94, 130.42, 130.98, 131.14, 131.65, 133.61, 139.68, 150.08,
152.08, 158.5.
HRMS MALDI-TOF: m/z [M + K]+ calcd for C15H9BrKN2O2: 366.9484;
found: 366.9484.
3-(2-Amino-4-fluorophenyl)-1-phenylprop-2-yn-1-one (2i)
Yellow solid; yield: 205 mg (72%); mp 158–160 °C.
IR (KBr): 3400, 3321, 2183, 1639, 1568, 1452, 1282, 1012, 725 cm–1
1H NMR (400 MHz, CDCl3): δ = 8.19 (d, J = 7.3 Hz, 2 H), 7.63 (t, J = 7.4
.
Hz, 1 H), 7.45–7.54 (m, 3 H), 6.42–6.48 (m, 2 H), 4.67 (br s, 2 H, NH).
1
13C NMR (100.6 MHz, CDCl3): δ = 177.73, 165.68 (d, JC-F = 252 Hz),
7-Chloro-4-nitro-2-phenylquinoline (7h)
3
3
152.39 (d, JC-F = 13 Hz), 136.95, 135.90 (d, JC-F = 11 Hz), 134.05,
Yellow solid; yield: 40 mg (72%); mp 220–222 °C.
IR (KBr): 3429, 3051, 1617, 1488, 1530, 1354, 1081, 911, 820 cm–1
1H NMR (400 MHz, CDCl3): δ = 8.33–8.36 (m, 2 H), 8.22–8.23 (m, 1 H),
8.14–8.16 (m, 2 H), 7.61–7.64 (m, 1 H), 7.51–7.56 (m, 3 H).
13C NMR (100.6 MHz, CDCl3): δ = 158.27, 153.03, 150.62, 137.36,
137.02, 130.88, 130.17, 129.21, 129.18, 127.43, 124.14, 115.99,
113.16,
2
2
129.44, 128.69, 105.96 (d, JC-F = 23.8 Hz), 101.32 (d, JC-F = 24.7 Hz),
.
100.12 (d, 4JC-F = 2.3 Hz), 93.41, 90.44.
HRMS MALDI-TOF: m/z [M + H]+ calcd for C15H11FNO: 240.0825;
found: 240.0824.
HRMS MALDI-TOF: m/z [M + K]+ calcd for C15H9ClKN2O2: 322.9990;
found: 322.9991.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

H
N. D. Rode et al.
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Synthesis
2-(Naphthalen-1-yl)-4-nitroquinoline (7j)
1H NMR (400 MHz, CDCl3): δ = 8.84–8.85 (m, 1 H), 8.42–8.47 (m, 3 H),
8.31–8.33 (m, 1 H), 8.19–8.21 (m, 1 H), 7.89 (ddd, J = 8.5, 7.10, 1.4 Hz,
1 H), 7.74–7.78 (m, 1 H), 7.66 (t, J = 8.3 Hz, 1 H), 4.00 (s, 3 H).
13C NMR (100.6 MHz, CDCl3): δ = 166.64, 156.04, 150.38, 137.94,
131.76, 131.46, 131.33, 131.20, 130.51, 129.73, 129.38, 128.49,
122.73, 117.76, 112.93, 52.45.
Pale yellow solid; yield: 37 mg (68%); mp 131–132 °C.
IR (KBr): 3412, 3088, 3042, 1604, 1521, 1336, 1236, 1143, 900, 766
cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.49–8.51 (m, 1 H), 8.34–8.37 (m, 1 H),
8.27 (s, 1 H), 8.14–8.17 (m, 1 H), 7.90–8.03 (m, 3 H), 7.76–7.83 (m, 2
H), 7.63 (t, J = 8.1 Hz, 1 H), 7.51–7.58 (m, 2 H).
13C NMR (100.6 MHz, CDCl3): δ = 117.24, 117.49, 122.73, 124.97,
125.40, 126.41, 127.30, 128.36, 128.72, 129.71, 131.28, 130.46,
130.85, 131.26, 134.11, 136.63, 150.30, 152.85, 159.45.
HRMS MALDI-TOF: m/z [M + K]+ calcd for C17H12KN2O4: 347.0434;
found: 347.0434.
1-[4-(4-Nitroquinolin-2-yl)phenyl]ethan-1-one (7o)
White solid; yield: 43 mg (78%); mp 184–185 °C.
IR (KBr): 3425, 3084, 1680, 1574, 1532, 1423, 1356, 1265, 767 cm–1
HRMS MALDI-TOF: m/z [M + K]+ calcd for C19H12KN2O2: 339.0536;
found: 339.0535.
.
1H NMR (400 MHz, CDCl3): δ = 8.43–8.46 (m, 2 H), 8.31–8.33 (m, 3 H),
8.13–8.15 (d, J = 8.5 Hz, 2 H), 7.90 (ddd, J = 8.5, 7.10, 1.4 Hz, 1 H), 7.78
(ddd, J = 8.5, 7.10, 1.4 Hz, 1 H), 2.69 (s, 3 H).
4-Nitro-2-(m-tolyl)quinoline (7k)
Pale yellow solid; yield: 35 mg (62%); mp 92–93 °C.
13C NMR (100.6 MHz, CDCl3): δ = 197.56, 155.82, 153.47, 150.44,
141.57, 138.32, 131.40, 130.62, 129.97, 129.09, 127.66, 122.76,
177.67, 113.10, 29.73, 26.84.
HRMS MALDI-TOF: m/z [M + K]+ calcd for C17H12KN2O3: 331.0485;
found: 331.0487.
IR (KBr): 3425, 3088, 2922, 1602, 1527, 1370, 1309, 1153, 891, 768
cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.37–8.41 (m, 2 H), 8.28 (d, J = 8.3 Hz, 1
H), 8.02 (s, 1 H), 7.96 (d, J = 8.3 Hz, 1 H), 7.84 (t, J = 8.3 Hz, 1 H), 7.71 (t,
J = 8.3 Hz, 1 H), 7.44 (t, J = 8.0 Hz, 1 H), 7.33 (d, J = 8.0 Hz, 1 H), 2.49 (s,
3 H).
4-Nitro-2-[3-(trifluoromethyl)phenyl]quinoline (7p)
Yellow solid; yield: 33 mg (60%); mp 126–128 °C.
13C NMR (100.6 MHz, CDCl3): δ = 157.38, 153.27, 150.34, 138.94,
137.56, 131.30, 131.04, 130.69, 130.38, 129.25, 129.05, 128.06,
124.61, 124.28, 122.65, 117.55, 113.18, 21.56.
IR (KBr): 3420, 3080, 2852, 1605, 1520, 1405, 1324, 1234, 1117, 931,
771 cm–1
.
HRMS MALDI-TOF: m/z [M + K]+ calcd for C16H12KN2O2: 303.0536;
1H NMR (400 MHz, CDCl3): δ = 8.51–8.52 (m, 1 H), 8.30–8.44 (m, 4 H),
7.89 (ddd, J = 8.4, 7.00, 1.4 Hz, 1 H), 7.74–7.79 (m, 2 H), 7.67–7.71 (m,
1 H).
found: 303.0536.
2-(4-Methoxyphenyl)-4-nitroquinoline (7l)
13C NMR (100.6 MHz, CDCl3): δ = 155.40, 153.55, 150.38, 138.33,
Yellow solid; yield: 38 mg (69%); mp 104–105 °C.
2
4
131.77 (q, JC-F = 33.00 Hz), 131.44, 130.55, 130.52 (q, JC-F = 1.4 Hz),
IR (KBr): 3429, 3096, 2968, 2835, 2366, 1606, 1522, 1357, 1249, 1176,
3
3
1034, 766 cm–1
.
129.93, 129.68, 127.03 (q, JC-F = 3.8 Hz), 124.37 (q, JC-F = 3.8 Hz),
124.00 (q, 1JC-F = 273 Hz), 122.74, 117.83, 112.70,
1H NMR (400 MHz, CDCl3): δ = 8.37–8.39 (m, 1 H), 8.36 (s, 1 H), 8.23–
8.25 (m, 1 H), 8.18 (d, J = 8.2 Hz, 2 H), 7.83 (ddd, J = 8.4, 7.00, 1.4 Hz, 1
H), 7.68 (ddd, J = 8.4, 6.95, 1.4 Hz, 1 H), 7.08 (d, J = 8.2 Hz, 2 H), 3.90 (s,
3 H).
HRMS MALDI-TOF: m/z [M + K]+ calcd for C16H9F3KN2O2: 357.0253;
found: 357.0253.
4-Nitro-2-(thiophen-2-yl)quinoline (7q)
13C NMR (100.6 MHz, CDCl3): δ = 161.78, 156.78, 153.34, 150.40,
Yellow solid; yield: 38 mg (68%); mp 114–116 °C.
131.01, 130.21, 128.94, 128.87, 122.66, 117.29, 114.58, 112.62, 55.50.
IR (KBr): 3416, 2925, 1606, 1522, 1425, 1356, 1239, 1067, 771 cm–1
.
HRMS MALDI-TOF: m/z [M + K]+ calcd for C16H12KN2O3: 319.0485;
1H NMR (400 MHz, CDCl3): δ = 8.31–8.33 (m, 1 H), 8.24 (s, 1 H), 8.14–
8.17 (m, 1 H), 7.74–7.81 (m, 2 H), 7.65 (ddd, J = 8.5, 6.9, 1.3 Hz, 1 H),
7.52 (dd, J = 1.3, 4.9 Hz, 1 H), 7.16 (dd, J = 3.8, 4.9 Hz, 1 H).
found: 319.0485.
2-(4-Chlorophenyl)-4-nitroquinoline (7m)
13C NMR (100.6 MHz, CDCl3): δ = 153.03, 152.22, 150.12, 143.38,
131.20, 130.15, 129.86, 128.96, 128.43, 127.21, 122.68, 117.46,
111.99.
HRMS MALDI-TOF: m/z [M + K]+ calcd for C13H8KN2O2S: 294.9944;
found: 294.9940.
Yellow solid; yield: 36 mg (65%); mp 182–183 °C.
IR (KBr): 3416, 2925, 1591, 1520, 1486, 1368, 1091, 1011, 765 cm–1
1H NMR (400 MHz, CDCl3): δ = 8.38–8.43 (m, 2 H), 8.26–8.29 (m, 1 H),
8.16 (d, J = 8.7 Hz, 2 H), 7.85–7.89 (m, 1 H), 7.74 (ddd, J = 8.4, 6.9, 1.4
Hz, 1 H), 7.53 (d, J = 8.7 Hz, 2 H).
.
13C NMR (100.6 MHz, CDCl3): δ = 1.55.89, 150.38, 136.93, 136.03,
131.29, 130.42, 129.59, 129.42, 129.41, 128.72, 128.71, 122.73,
117.66, 112.68,
HRMS MALDI-TOF: m/z [M + Na]+ calcd for C15H9ClN2NaO2: 307.0250;
found: 307.0248.
2-Phenyl-4-tosylquinoline (8a); Typical Procedure for 2-Substitut-
ed 4-Tosylquinolines 8a–q
To a mixture of 3-(2-aminophenyl)-1-phenylprop-2-yn-1-one (2a,
0.200 g, 0.90 mmol), sodium p-toluenesulfinate (0.323 g, 1.80 mmol),
and NH4Cl (0.097 g, 1.80 mmol) was added DMF (3 mL). The mixture
was stirred at 80 °C for 2 h, then extracted with water and EtOAc (3 ×).
The combined organic phases were dried (Na2SO4) and concentrated
under reduced pressure. The residue was purified by column chroma-
tography (petroleum ether/EtOAc 90:10) to give 8a as a brown solid;
yield: 269 mg (83%); mp 171–173 °C.
Methyl 3-(4-Nitroquinolin-2-yl)benzoate (7n)
Yellow solid; yield: 29 mg (53%); mp 140–142 °C.
IR (KBr): 3426, 3083, 2958, 1726, 1526, 1437, 1283, 1236, 1108 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

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N. D. Rode et al.
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Synthesis
IR (KBr): 3441, 3059, 1579, 1490, 1446, 1315, 1145, 1087, 815, 749
cm–1
1H NMR (400 MHz, CDCl3): δ = 8.71 (s, 1 H), 8.60–8.62 (m, 1 H), 8.22–
8.26 (m, 3 H), 7.91 (d, J = 8.3 Hz, 2 H), 7.75 ddd, J = 8.4, 7.9, 1.4 Hz, 1
H), 7.52–7.62 (m, 4 H), 7.30 (d, J = 8.2 Hz, 2 H), 2.38 (s, 3 H).
13C NMR (100.6 MHz, CDCl3): δ = 156.78, 149.63, 145.86, 145.01,
138.15, 137.50, 130.82, 130.49, 130.27, 130.08, 129.11, 128.27,
127.95, 127.60, 124.10, 121.08, 119.27, 21.62.
IR (KBr): 3383, 3018, 2964, 2403, 1581, 1411, 1328, 1220, 1145 cm–1
.
.
1H NMR (400 MHz, CDCl3): δ = 8.49–8.52 (m, 1 H), 8.32 (s, 1 H), 8.05–
8.07 (m, 1 H), 7.88 (d, J = 8.1 Hz, 2 H), 7.68 (ddd, J = 8.1, 7.20, 1.5 Hz, 1
H), 7.51 (ddd, J = 8.4, 7.1, 1.4 Hz, 1 H), 7.43 (dd, J = 9.8, 15.9 Hz, 1 H),
7.29 (d, J = 8.1 Hz, 2 H), 6.76 (d, J = 15.9 Hz, 1 H), 6.32–6.38 (m, 1 H),
6.10–6.17 (m, 1 H), 2.37 (s, 3 H), 2.22 (q, J = 5.6 Hz, 2 H), 1.33–1.49 (m,
4 H), 0.93 (t, J = 6.8 Hz, 3 H).
13C NMR (100.6 MHz, CDCl3): δ = 156.10, 149.57, 145.03, 144.91,
141.56, 137.22, 130.36, 130.15, 130.02, 129.80, 128.97, 127.88,
127.70, 124.08, 120.83, 119.74, 32.77, 31.18, 22.27, 21.59, 13.91.
HRMS MALDI-TOF: m/z [M + K]+ calcd for C22H17KNO2S: 398.0617;
found: 398.0620.
HRMS MALDI-TOF: m/z [M + K]+ calcd for C24H25KNO2S: 430.1243;
found: 430.1241.
2-Ethyl-4-tosylquinoline (8b)
Brown solid; yield: 48 mg (54%); mp 126–127 °C.
IR (KBr): 3432, 2971, 2925, 1594, 1494, 1321, 1146, 1084, 760 cm–1
2-(Furan-2-yl)-4-tosylquinoline (8f)
.
Brown solid; yield: 71 mg (86%); mp 182–184 °C.
1H NMR (400 MHz, CDCl3): δ = 8.54–8.57 (m, 1 H), 8.09–8.11 (m, 2 H),
7.88 (d, J = 8.3 Hz, 2 H), 7.71 (ddd, J = 8.5, 7.10, 1.3 Hz, 1 H), 7.56 (ddd,
J = 8.5, 7.10, 1.3 Hz, 1 H), 7.30 (d, J = 8.3 Hz, 2 H), 3.11 (q, J = 7.6 Hz, 2
H), 2.38 (s, 3 H), 1.44 (t, J = 7.6 Hz, 3 H).
13C NMR (100.6 MHz, CDCl3): δ = 163.59, 149.26, 145.25, 144.93,
137.52, 130.18, 130.03, 129.96, 127.88, 127.69, 124.06, 121.22,
120.70, 32.34, 21.60, 13.56.
IR (KBr): 3424, 3137, 1589, 1496, 1317, 1161, 1141, 1084, 814, 660
cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.62 (s, 1 H), 8.55–8.58 (m, 1 H), 8.16
(d, J = 8.4 Hz, 1 H), 7.91 (d, J = 8.1 Hz, 2 H), 7.67–7.74 (m, 2 H), 7.55
(ddd, J = 8.4, 7.10, 1.4 Hz, 1 H), 7.26–7.33 (m, 3 H), 6.62–6.64 (m, 1 H),
2.38 (s, 3 H).
13C NMR (100.6 MHz, CDCl3): δ = 152.68, 149.48, 148.53, 145.82,
145.05, 144.96, 137.43, 130.65, 130.38, 130.08, 128.06, 127.98,
124.21, 120.95, 118.16, 112.65, 111.60, 21.61.
HRMS MALDI-TOF: m/z [M + K]+ calcd for C18H17KNO2S: 350.0617;
found: 350.0619.
HRMS MALDI-TOF: m/z [M + Na]+ calcd for C20H15NNaO3S: 372.0670;
found: 372.0670.
2-Pentyl-4-tosylquinoline (8c)
Yellow solid; yield: 28 mg (86%); mp 103–104 °C.
IR (KBr): 3441, 3072, 2976, 1638, 1510, 1597, 1383, 1310, 848, 761
2-(2-Bromophenyl)-4-tosylquinoline (8g)
cm–1
.
Brown solid; yield: 51 mg (70%); mp 172–174 °C.
1H NMR (400 MHz, CDCl3): δ = 8.56 (d, J = 8.5 Hz, 1 H), 8.08–8.11 (m, 2
H), 7.87 (d, J = 8.3 Hz, 2 H), 7.71 (t, J = 8.5 Hz, 1 H), 7.55 (t, J = 8.5 Hz, 1
H), 7.29 (d, J = 8.3 Hz, 2 H), 3.06 (t, J = 7.7 Hz, 2 H), 2.37 (s, 3 H), 1.82–
1.90 (m, 2 H), 1.36–1.43 (m, 4 H), 0.92 (t, J = 7.6 Hz, 3 H).
13C NMR (100.6 MHz, CDCl3): δ = 162.81, 149.29, 142.10, 144.90,
137.57, 130.15, 130.02, 129.97, 127.87, 127.85, 124.05, 121.62,
120.67, 39.26, 31.62, 29.33, 22.50, 21.58, 13.99.
IR (KBr): 3424, 3066, 2913, 1593, 1495, 1399, 1323, 1145, 1087, 810,
769 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.71–7.74 (m, 1 H), 8.51 (m, 1 H), 8.22–
8.25 (m, 1 H), 7.94 (d, J = 8.3 Hz, 2 H), 7.79 (ddd, J = 8.4, 7.10, 1.5 Hz, 1
H), 7.66–7.74 (m, 3 H), 7.49 (ddd, J = 7.6, 7.1, 1.2 Hz, 1 H), 7.31–7.37
(m, 3 H), 2.39 (s, 3 H).
13C NMR (100.6 MHz, CDCl3): δ = 158.12, 149.29, 145.13, 144.80,
140.20, 137.30, 133.49, 131.67, 130.77, 130.52, 130.12, 128.84,
128.14, 127.99, 124.22, 123.12, 121.86, 121.08, 21.64.
HRMS MALDI-TOF: m/z [M + K]+ calcd for C21H23KNO2S: 392.1087;
found: 392.1087.
HRMS MALDI-TOF: m/z [M + K]+ calcd for C22H16BrKNO2S: 475.9722;
found: 475.9723.
2-Cyclohexyl-4-tosylquinoline (8d)
Pale yellow solid; yield: 53 mg (66%); mp 188–190 °C.
IR (KBr): 3425, 3067, 2923, 2848, 2175, 1596, 1494, 1446, 1317, 1143,
7-Fluoro-2-phenyl-4-tosylquinoline (8i)
1087, 810, 767 cm–1
.
Yellow solid; yield: 65 mg (83%); mp 203–204 °C.
1H NMR (400 MHz, CDCl3): δ = 8.53–8.55 (m, 1 H), 8.14 (s, 1 H), 8.09–
8.11 (m, 1 H), 7.87 (d, J = 8.1 Hz, 2 H), 7.70 (ddd, J = 8.4, 7.20, 1.4 Hz, 1
H), 7.54 (ddd, J = 8.4, 7.20, 1.4 Hz, 1 H), 7.28 (d, J = 8.1 Hz, 2 H), 2.97–
3.04 (m, 1 H), 2.37 (s, 3 H), 2.04–2.07 (m, 2 H), 1.90–1.95 (m, 2 H),
1.64–1.84 (m, 4 H), 1.43–1.53 (m, 2 H).
13C NMR (100.6 MHz, CDCl3): δ = 166.47, 149.18, 145.16, 144.84,
137.64, 130.12, 130.05, 130.02, 127.84, 127.61, 124.01, 120.86,
120.31, 47.45, 32.56, 26.38, 25.92, 21.59.
IR (KBr): 3430, 3084, 1618, 1587, 1508, 1453, 1325, 1150, 1082, 846,
680 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.63–8.67 (m, 2 H), 8.22–8.24 (dd,
J = 1.8, 8.3 Hz, 2 H), 7.90 (d, J = 8.4 Hz, 2 H), 7.84 (dd, J = 9.6, 2.7 Hz, 1
H), 7.51–7.59 (m, 3 H), 7.36–7.41 (m, 1 H), 7.32 (d, J = 8.4 Hz, 2 H),
2.39 (s, 3 H).
13C NMR (100.6 MHz, CDCl3): δ = 163.35 (d, JC-F = 253 Hz), 157.97,
1
2
151.01 (d, JC-F = 13 Hz), 146.16, 146.15, 145.25, 137.75, 137.25,
HRMS MALDI-TOF: m/z [M + K]+ calcd for C22H23KNO2S: 404.1087;
found: 404.1090.
3
130.58, 130.18, 129.15, 127.92, 127.65, 126.40 (d, JC-F = 9.6 Hz),
3
4
2
118.50 (d, JC-F = 2.4 Hz), 118.02 (d, JC-F = 1.2 Hz), 114.42 (d, JC-
F = 20.1 Hz), 21.64.
HRMS MALDI-TOF: m/z [M + K]+ calcd for C22H16FKNO2S: 416.0523;
found: 416.0523.
2-[(1E,3E)-Octa-1,3-dienyl]-4-tosylquinoline (8e)
Brown solid; yield: 82 mg (72%); mp 76–78 °C.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

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N. D. Rode et al.
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Synthesis
2-(Naphthalen-1-yl)-4-tosylquinoline (8j)
Methyl 3-(4-Tosylquinolin-2-yl)benzoate (8n)
Brown solid; yield: 66 mg (88%); mp 206–207 °C.
IR (KBr): 3424, 3054, 1585, 1493, 1318, 1138, 1085, 969, 784, 768 cm–1
1H NMR (400 MHz, CDCl3): δ = 8.74–8.76 (m, 1 H), 8.50 (s, 1 H), 8.27–
8.30 (m, 1 H), 8.13–8.16 (m, 1 H), 7.93–8.01 (m, 4 H), 7.77–7.83 (m, 2
H), 7.69 (ddd, J = 8.5, 6.9, 1.3 Hz, 1 H), 7.63 (dd, J = 8.1, 1.2 Hz, 1 H),
7.51–5.57 (m, 2 H), 7.31–7.33 (m, 2 H), 2.38 (s, 3 H).
13C NMR (100.6 MHz, CDCl3): δ = 158.99, 149.47, 145.65, 145.14,
137.38, 137.09, 134.09, 130.94, 130.82, 130.63, 130.15, 130.05,
128.64, 128.38, 128.08, 127.14, 126.30, 125.40, 125.14, 124.22,
123.32, 120.92, 21.64.
White solid; yield: 62 mg (75%); mp 125–126 °C.
.
IR (KBr): 3424, 3075, 2954, 1931, 1716, 1579, 1494, 1399, 1294, 1151,
815, 770 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.9 (t, J = 1.9 Hz, 1 H), 8.75 (s, 1 H),
8.61–8.63 (m, 1 H), 8.46–8.49 (m, 1 H), 8.19–8.27 (m, 2 H), 7.92 (d,
J = 8.2 Hz, 2 H), 7.78 ddd (J = 8.4, 7.10, 1.5 Hz, 1 H), 7.60–7.68 (m, 2 H),
7.32 (d, J = 8.2 Hz, 2 H), 4.01 (s, 3 H), 2.39 (s, 3 H).
13C NMR (100.6 MHz, CDCl3): δ = 166.73, 155.66, 149.61, 146.16,
145.11, 138.50, 137.44, 131.93, 131.23, 131.17, 130.90, 130.66,
130.12, 127.27, 124.12, 121.26, 118.99, 52.38, 21.63.
HRMS MALDI-TOF: m/z [M + K]+ calcd for C26H19KNO2S: 448.0774;
HRMS MALDI-TOF: m/z [M + K]+ calcd for C24H19KNO4S: 456.0672;
found: 448.0775.
found: 456.0672.
2-(m-Tolyl)-4-tosylquinoline (8k)
1-[4-(4-Tosylquinolin-2-yl)phenyl]ethan-1-one (8o)
White solid; yield: 58 mg (83%); mp 203–204 °C.
White solid; yield: 71 mg (89%); mp 130–131 °C.
IR (KBr): 3424, 3046, 2917, 1593, 1580, 1322, 1145, 1085, 761 cm–1
.
IR (KBr): 3332, 3050, 2929, 1682, 1586, 1493, 1420, 1325, 1151, 1086,
841, 765 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.70 (s, 1 H), 8.59–8.61 (m, 1 H), 8.21–
8.24 (m, 1 H), 8.01–8.07 (m, 2 H), 7.91 (d, J = 8.3 Hz, 2 H), 7.74 (ddd,
J = 8.4, 7.1, 1.4 Hz, 1 H), 7.58 (ddd, J = 8.4, 7.1, 1.4 Hz, 1 H), 7.45 (t,
J = 7.8 Hz, 1 H), 7.28–7.35 (m, 3 H), 2.50 (s, 3 H), 2.37 (s, 3 H).
13C NMR (100.6 MHz, CDCl3): δ = 156.98, 149.62, 145.75, 144.98,
138.86, 138.11, 137.56, 131.07, 130.78, 130.44, 130.06, 129.01,
128.21, 128.20, 127.93, 124.77, 124.08, 121.05, 119.42, 21.60, 21.56.
1H NMR (400 MHz, CDCl3): δ = 8.73 (s, 1 H), 8.61–8.64 (m, 1 H), 8.35
(d, J = 8.1 Hz, 2 H), 8.23–8.26 (m, 1 H), 8.14 (d, J = 8.1 Hz, 2 H), 7.92 (d,
J = 8.1 Hz, 2 H), 7.78 (ddd, J = 8.5, 7.10, 1.5 Hz, 1 H), 7.64 (ddd, J = 8.3,
7.10, 1.6 Hz, 1 H), 7.32 (d, J = 8.1 Hz, 2 H), 2.69 (s, 3 H), 2.39 (s, 3 H).
13C NMR (100.6 MHz, CDCl3): δ = 197.65, 155.39, 149.64, 146.21,
145.17, 142.15, 138.11, 137.38, 131.00, 130.75, 130.14, 129.02,
128.84, 127.98, 127.76, 124.16, 121.38, 119.13, 26.83, 21.63.
HRMS MALDI-TOF: m/z [M + K]+ calcd for C23H19KNO2S: 412.0774;
found: 412.0776.
HRMS MALDI-TOF: m/z [M + K]+ calcd for C24H19KNO3S: 440.0723;
found: 440.0724.
2-(4-Methoxyphenyl)-4-tosylquinoline (8l)
4-Tosyl-2-[3-(trifluoromethyl)phenyl]quinoline (8p)
White solid; yield: 67 mg (87%); mp 151–152 °C.
Yellow solid; yield: 68 mg (92%); mp 158–159 °C.
IR (KBr): 3428, 3071, 1594, 1434, 1321, 1237, 1150, 860, 766 cm–1
.
IR (KBr): 3424, 2996, 2929, 2834, 1606, 1589, 1495, 1400, 1322, 1252,
1150, 1085, 831, 760 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.66 (s, 1 H), 8.55–8.58 (m, 1 H), 8.16–
8.24 (m, 3 H), 7.90 (d, J = 8.2 Hz, 2 H), 7.72 (ddd, J = 8.4, 7.10, 1.5 Hz, 1
H), 7.55 (ddd, J = 8.4, 7.10, 1.5 Hz, 1 H), 7.28–7.31 (m, 2 H), 7.08 (d,
J = 8.6 Hz, 2 H), 3.91 (s, 3 H), 2.37 (s, 3 H).
1H NMR (400 MHz, CDCl3): δ = 8.71 (s, 1 H), 8.61–8.64 (m, 1 H), 8.54
(s, 1 H), 8.42 (d, J = 7.9 Hz, 1 H), 8.24–8.27 (m, 1 H,), 7.92 (d, J = 8.3 Hz,
2 H), 7.79 (ddd, J = 8.5, 7.1, 1.4 Hz, 2 H), 7.70 (t, J = 7.9 Hz, 1 H), 7.64
(ddd, J = 8.4, 7.1, 1.4 Hz, 1 H), 7.32 (d, J = 8.3 Hz, 2 H), 2.39 (s, 3 H).
13C NMR (100.6 MHz, CDCl3): δ = 161.59, 158.31, 149.65, 145.92,
144.93, 137.59, 130.72, 130.57, 130.38, 130.05, 129.05, 127.91,
127.80, 124.07, 120.73, 118.87, 114.50, 55.48, 21.61.
HRMS MALDI-TOF: m/z [M + K]+ calcd for C23H19KNO3S: 428.0723;
found: 428.0720.
13C NMR (100.6 MHz, CDCl3): δ = 155.05, 149.62, 146.39, 145.20,
2
138.91, 137.38, 131.63 (q, JC-F = 32.6 Hz), 130.96, 130.81, 130.71 (q,
4JC-F = 1.3 Hz), 130.16, 129.60, 128.82, 128.00, 126.78 (q, 3JC-F = 3.7 Hz),
1
3
124.06 (q, JC-F = 273 Hz), 124.48 (q, JC-F = 3.7 Hz), 124.17, 121.38,
118.77, 21.64.
HRMS MALDI-TOF: m/z [M + K]+ calcd for C23H16F3KNO2S: 466.0491;
found: 466.0492.
2-(4-Chlorophenyl)-4-tosylquinoline (8m)
White solid; yield: 68 mg (91%); mp 187–188 °C.
IR (KBr): 3432, 3066, 1591, 1416, 1324, 1144, 1088, 836, 754 cm–1
2-(Thiophen-2-yl)-4-tosylquinoline (8q)
.
Brown solid; yield: 62 mg (78%); mp 191–192 °C.
1H NMR (400 MHz, CDCl3): δ = 8.66 (s, 1 H), 8.59–8.91 (m, 1 H), 8.18–
8.22 (m, 3 H), 7.90 (d, J = 8.4 Hz, 2 H), 7.76 (t, J = 8.1 Hz, 1 H), 7.60
(ddd, J = 8.5, 7.10, 1.4 Hz, 1 H), 7.54 (d, J = 8.4 Hz, 2 H), 7.31 (d, J = 8.1
Hz, 2 H), 2.38 (s, 3 H).
13C NMR (100.6 MHz, CDCl3): δ = 155.49, 149.62, 146.12, 145.11,
137.48, 136.65, 136.56, 130.82, 130.66, 130.13, 129.33, 128.88,
128.49, 127.97, 124.15, 121.18, 118.81, 21.64.
IR (KBr): 3424, 3099, 3071, 1585, 1424, 1317, 1141, 1085, 816, 712
cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.58 (s, 1 H), 8.51–8.54 (m, 1 H), 8.11–
8.13 (m, 1 H), 7.90 (d, J = 8.3 Hz, 2 H), 7.85–7.86 (m, 1 H), 7.70 (ddd,
J = 8.4, 7.10, 1.4 Hz, 1 H), 7.51–7.56 (m, 2 H), 7.30 (d, J = 8.3 Hz, 2 H),
7.18–7.21 (m, 1 H), 2.38 (s, 3 H).
13C NMR (100.6 MHz, CDCl3): 151.94, 149.42, 145.65, 145.07, 144.05,
137.38, 130.62, 130.27, 130.08, 129.92, 128.43, 127.93, 127.23,
124.14, 120.96, 118.18, 21.62.
HRMS MALDI-TOF: m/z [M + K]+ calcd for C22H16ClKNO2S: 432.0227;
found: 432.0226.
HRMS MALDI-TOF: m/z [M + K]+ calcd for C20H15KNO2S2: 404.0181;
found: 404.0179.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

K
N. D. Rode et al.
Paper
Synthesis
4-Amino-2-phenylquinoline (9a); Typical Procedure for the Syn-
thesis of 4-Aminoquinolines 9
1H NMR (400 MHz, CDCl3): δ = 7.97–8.02 (m, 2 H), 7.60 (t, J = 7.8 Hz, 1
H), 7.40 (t, J = 7.8 Hz, 1 H), 6.67 (s, 1 H), 3.02 (s, 6 H), 2.87 (t, J = 8.0 Hz,
2 H), 1.78–1.84 (m, 2 H), 1.35–1.45 (m, 4 H), 0.91 (t, J = 7.1 Hz, 3 H).
13C NMR (100.6 MHz, CDCl3): δ = 163.29, 157.71, 149.44, 129.24,
128.74, 124.19, 123.90, 121.72, 107.39, 43.95, 39.75, 31.93, 29.99,
22.63, 14.09.
A mixture of 2-phenyl-4-nitroquinoline (7a, 50 mg, 0.20 mmol), Pd/C
(10 mg), and ammonium formate (63 mg, 1.0 mmol) in MeOH (2.5
mL) was stirred at r.t. for 4 h. Pd/C was filtered off through a short
path of silica gel. The filtrate was extracted with water and EtOAc (3
×). Evaporation of solvent followed by column chromatography (pe-
troleum ether/EtOAc, 60:40) afforded 9a; yield: 39 mg (89%).
HRMS MALDI-TOF: m/z [M + H]+ calcd for C16H23N2: 243.1861; found:
243.1861.
2-(Furan-2-yl)quinolin-4-amine (9f)
Brown solid; yield: 28 mg (66%); mp 92–94 °C.
Acknowledgment
IR (KBr): 3478, 3299, 3058, 1645, 1595, 1516, 1216, 1013, 896, 751
cm–1
.
This work was supported by the University of L’Aquila (Italy).
1H NMR (400 MHz, CDCl3): δ = 8.03–8.05 (m, 1 H), 7.70–7.73 (m, 1 H),
7.64 (ddd, J = 8.4, 6.9, 1.5 Hz, 1 H), 7.57 (dd, J = 0.9, 1.8 Hz, 1 H), 7.38–
7.42 (m, 1 H), 7.14 (dd, J = 0.8, 3.4 Hz, 1 H), 7.06 (s, 1 H), 6.55 (dd,
J = 1.7, 3.4 Hz, 1 H), 4.79 (s, 2 H, NH2).
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0036-1588147.
13C NMR (100.6 MHz, CDCl3): δ = 154.01, 149.97, 149.52, 148.94,
S
u
p
p
ortiInfogrmoaitn
S
u
p
p
o
nrtogI
f
rmoaitn
143.54, 129.84, 129.77, 124.81, 120.01, 118.08, 112.02, 109.03, 99.57.
HRMS MALDI-TOF: m/z [M + H]+ calcd for C13H11N2O: 211.0871;
found: 211.0869.
References
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Yellow solid; yield: 22 mg (90%); mp 199–200 °C.
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.
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2.64 (s, 3 H).
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143.74, 137.12, 130.32, 128.62, 127.71, 125.14, 120.51, 117.61,
101.49, 26.66
HRMS MALDI-TOF: m/z [M + H]+ calcd for C17H15N2O: 263.1184;
found: 263.1184.
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1204, 1054, 851, 767 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

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Synthesis
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L