Preparation of 2-arylquinolines from β-arylpropionitriles with aryllithiums and NIS through iminyl radical-mediated cyclization

Article abstract of DOI:10.1039/c9ob00944b

Treatment of β-arylpropionitriles with aryllithiums, followed by the reaction with water and then with NIS under irradiation with a tungsten lamp gave 2-arylquinolines in good to moderate yields. The present reaction proceeds through the formation of N-iodoimines from imines with NIS, the generation of imino-nitrogen-centered radicals, and their cyclization onto the aromatic rings of the imines to form 2-aryl-3,4-dihydroquinolines. Finally, the oxidation of 2-aryl-3,4-dihydroquinolines with NIS proceeds smoothly to generate 2-arylquinolines.

Full text of DOI:10.1039/c9ob00944b

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ISSN 1477-0520
COMMUNICATION
Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
benzene
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DOI: 10.1039/C9OB00944B
Journal Name
ARTICLE
Preparation of 2-Arylquinolines from -Arylpropionitriles
with Aryllithiums and NIS through Iminyl Radical-Mediated
Cyclization
Received 00th January 20xx,
Accepted 00th January 20xx
Hiroki Naruto,a Hideo Togo*a
DOI: 10.1039/x0xx00000x
Abstract text goes here. Treatment of -arylpropionitriles with aryllithiums, followed by the reaction with water and
then NIS under irradiation with a tungsten lamp gave 2-arylquinolines in good to moderate yields. The present
reaction proceeds through the formation of N-iodoimines from imines with NIS, the generation of imino-nitrogen-
centered radicals, and their cyclization onto the aromatic rings of the imines to form 2-aryl-3,4-dihydroquinolines.
Finally, the oxidation of 2-aryl-3,4-dihydroquinolines with NIS proceeds smoothly to generate 2-arylquinolines.
www.rsc.org/
diketones.
Introduction
However, much more simpler and efficient synthetic methods have
The quinoline skeleton is one of the most important units because
it bears potent biological activities, such as antimalarial, antibiotic,
anticancer, anti-inflammatory, and anti-HIV activities, in
been required due to the importance of quinolines.1 Recent reports
for the preparation of quinoline units with transition metals are as
follows:2 the preparations of 2-aminoquinolines with N-acyl-o-
alkynylanilines and isocyanides in the presence of Pd(OAc)2;2a 2,4-
substituted quinolines with (Z)-N-arylbenzimidoyl chlorides and
tert-butyl 1-(aryl)propyn-2-yl carbonates in the presence of CuI;2b
2-aminoquinolines with -(2-aminophenyl)--ynones and
ynamides in the presence of IPrAuCl and AgSbF6;2c 2-
arylquinolines with -arylethanols and o-aminobenzyl alcohols in
the presence of Cu2L6 (L = 4,6-dimethylpyrimidine-2-thione);2d 2-
aryl-3-tosylquinolines with anthranils and tosylhydrazones in the
presence of Cu(OAc)2 and AgOTf;2e quinolines with anilines and
allyl alcohols in the presence of [RuCl2(p-cym)]2, Cu(OAc)2, and
AgSbF6;2f 2,3,4-trisubstituted quinolines with N-aryl amides and
1,2-diarylethynes in the presence of [Cp*CoCl2]2 and AgNTf2;2g
2,4-disubstituted quinolines with -(o-aminophenyl)benzyl
alcohols and secondary alcohols in the presence of Mn(I)•PNP
pincer complex;2h 2,4-diarylquinolines with N-benzylanilines and
pharmaceuticals.1
For example, quinine has antimalarial,
analgesic, and anti-inflammatory activities, and amodiaquine,
chloroquine, and primaquine have antimalarial properties,1a~1e as
shown in Fig. 1. Today, there are many established methods for
the preparation of quinoline skeletons, including the Skraup
quinoline synthesis with anilines and acrolein, the Robinson-
Foulds quinoline synthesis with N-acyl o-vinylanilines, the
Friedländer quinoline synthesis with o-aminobenzaldehydes and
ketones, and the Combes quinoline synthesis with anilines and 1,3-
Cl
N
HO
HN
N
NEt2
O
N
Cl
styrene
in
the
presence
of
tris(4-
3-
Quinine
Amodiaquine
bromophenyl)aminiumhexachloroantimonate
(TBPA+•);2i
arylquinolines with anilines and -(aryl)acetaldehydes in the
presence of CuBr and CF3SO3H;2j and 2,3,4-trisubstituted
quinolines with diaryliodonium salts, nitriles, and alkynes in the
presence of Cu(OTf)2.2k In addition, as recent reports for the
preparation of quinoline units without transition metals, the
following examples are enumerated: the preparations of 4-aryl-3-
tosylquinolines with N-(arylpropargyl)anilines and toluenesulfinic
O
N
NH
N
HN
NH2
2
Cl
Chloroquine
N
Primaquine
Fig. 1 Typical Quinolines Bearing Antimalarials
acid
(difluoromethyl)quinolines with o-cyanoanilines and methyl 4,4-
difluorobut-2-ynoate;3b
2-arenesulfonylquinolines with o-
under
LED
irradiation;3a
4-amino-2-
a. Graduate School of Science, Chiba University
Yayoi-cho 1-33, Inage-ku, Chiba 263-8522, Japan
alkynylisocyanobenzenes and arenesulfinate;3c 2,4-disubstituted
quinolines with acetophenones, anilines, and -(aryl)acetaldehydes
in the presence of molecular iodine in DMSO;3d 2,3,4-
† Footnotes relating to the title and/or authors should appear here.
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
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trisubstituted quinolines with arylisothiocyanates, alkynes and
CF3SO3Me;3e and trisubstituted quinolines with o-ethynylaryl
isocyanides and (PhTe)2 or (PhSe)2 under irradiation with a Hg
lamp.3f On the other hand, synthetic studies of imino-carbon-
centered radicals and imino-nitrogen-centered radicals for the
preparation of nitrogen-containing heterocycles,4 especially
phenanthridines from 2-isocyanobiaryls via imino-carbon-centered
radicals, have become popular recently. However, most of those
studies have focused on imino-carbon-centered radicals (imidoyl
radicals) formed by the addition of radical species to isonitriles,
and synthetic studies of imino-nitrogen-centered radicals (iminyl
radicals) for the preparation of nitrogen-containing heterocycles
are quite limited.5 Recent reports for the construction of nitrogen-
containing heterocycles using imino-nitrogen-centered radicals
phenylpropionitrile 1a even if the reaction was carriVeidewoAurtticaletO-n1li0ne
DOI: 10.1039/C9OB00944B
°C. For the recovery of -phenylpropionitrile 1a, the reaction
mixture after the 1st reaction step was quenched with D2O (2.0 mL)
(2nd step), and the obtained mixture containing imine Ia-A was
treated with NIS under the same procedure and conditions to give
2-phenylquinoline 2a-A in 65
% yield, together with -
phenylpropionitrile--d1 1a in 26% yield (entry 6). The 1st
reaction step with PhLi was further studied to reduce the amount of
-proton abstraction from -phenylpropionitrile 1a by PhLi, by
changing the reaction temperature, the amount of PhLi, the
dropwise addition time of PhLi, and the reaction time. However,
the yield of 2-phenylquinoline 2a-A was not improved. Thus, to
obtain 2-phenylquinoline 2a-A efficiently, the reaction of -
phenylpropionitrile 1a with PhLi (A, 3.0 equiv.) at -10 °C for 0.5 h
(1st step) was the best (entry 5). As a gram-scale experiment, -
phenylpropionitrile 1a (8.0 mmol) was treated under the same
procedure and conditions as those of entry 5 to give 2-
phenylquinoline 2a-A in 63% yield (entry 7). Then, the solvent in
the 3rd reaction step was changed from DCE to THF, MeOH, and
CH3CN, and it was found that DCE was the best choice (entries 5,
and 9~11). When the reaction of imine Ia-A with NIS in the 3rd
reaction step was carried out at 70 °C for 3 h instead the irradiation
with a tungsten lamp, the yield of 2-phenylquinoline 2a was
(iminyl radicals) are as follows:6 the construction of
a
phenanthridine core with N-aryl acrylamides bearing a cyano
group and CF3SO2Cl in the presence of Ru(phen)3Cl2 under
irradiation with blue LED;6a a phenanthridine core with N-aryl
acrylamides bearing a cyano group and BrCH2CN in the presence
of fac-Ir(ppy)3 under irradiation with a blue LED;6b quinoline and
phenanthridine cores with aromatic aldehydes and O-aroyl
hydroxylamines in the presence of fac-Ir(ppy)3 under irradiation
with white LED;6c quinoline and phenanthridine cores with O-aroyl
compounds of aryl ketone oximes in the presence of fac-Ir(ppy)3
decreased (entries
5
and 12).
When 1,3-diiodo-5,5-
under
irradiation
with
white
LED;6d
and
3-
dimethylhydantoin (DIH, 1.1 equiv.) was used instead of NIS (2.1
equiv.) in the 3rd reaction step, the yield of 2-phenylquinoline 2a-A
was 64%, and that of -phenylpropionitrile 1a was 33% under the
same procedure and conditions (entry 13). When I2 (2.1 equiv.)
and K2CO3 (1.5 equiv.) were used instead of NIS in the 3rd reaction
step under the same procedure and conditions, 2-phenylquinoline
(methoxycarbonyl)quinolines with 3-arylallyl azides bearing a
methoxycarbonyl group at 2-position with NBS under irradiation
with a fluorescent lamp.6e
As part of our synthetic studies of iminyl radicals formed from N-
iodo imines
for
construction
of
nitrogen-containing
2a-A was not obtained at all (entry 14).
When N-
heteroaromatics, such as phenanthridines,7 here we would like to
report a simple preparation of 2-arylquinolines from the reaction of
-arylpropionitriles and aryllithiums, followed by the reaction with
N-iodosuccinimide (NIS) under irradiation with a tungsten lamp.
bromosuccinimide (NBS, 2.1 equiv.) and N-chlorosuccinimide
(NCS, 2.1 equiv.) were used instead of NIS in the 3rd reaction step
under the same procedure and conditions, 2-phenylquinoline 2a-A
was obtained in 14% and 0% yields, together with the isolation of
1,3-diphenyl-1-propanone, a hydrolyzed ketone of imine Ia-A, in
61% and 68% yields, respectively (entries 15, 16). Thus, NBS
shows poor reactivity and NCS did not work at all in the formation
of 2-phenylquinoline 2a-A from imine Ia-A. When the 3rd
reaction step in entry 5 was carried out in the presence of 2,6-di-
tert-butyl-4-methylphenol (BHT, 1.5 equiv.) and 2,2,6,6-
tetramethylpiperidine 1-oxyl radical (TEMPO, 1.5 equiv.) under
the same procedure and conditions, 2-phenylquinoline 2a-A was
not obtained at all in both reactions, and 1,3-diphenyl-1-
propanone, a hydrolyzed ketone of the imine, was obtained in 41
% and 27% yields, respectively (entries 17, 18). Thus, those
results indicate that the formation of 2-phenylquinoline 2a-A from
imine Ia-A is a radical-mediated reaction. In addition, when PhLi
prepared from the reaction of bromobenzene (3.0 equiv.) and n-
BuLi (3.1 equiv.), instead of commercially available PhLi (3.0
equiv.) was used under the same procedure and conditions as those
of entry 5, the yield of 2-phenylquinoline 2a-A was markedly
decreased to 13% (entry 19).
Results and Discussion
First, to understand the cyclization ability of an iminyl radical onto
an aromatic ring and the optimal reaction conditions, -
phenylpropionitrile 1a (3.0 mmol) was treated with PhLi (A, 1.3
equiv., 1.8 equiv., 2.5 equiv., and 3.0 equiv.) in THF (5.0 mL) at 0
°C for 1 h (1st step), and then with water (5.0 mL) (2nd step) to
form imine Ia-A. Then, imine Ia-A was treated with N-
iodosuccinimide (NIS, 2.1 equiv.) in 1,2-dichloroethane (DCE, 6.0
mL) under irradiation with a tungsten lamp (300 W) in the range of
30 °C~40 °C (3rd step) to give 2-phenylquinoline 2a-A in 38%,
51%, 58%, and 59% yields together with the recovery of -
phenylpropionitrile 1a, respectively, as shown in Table 1 (entries
1~4). When the reaction of -phenylpropionitrile 1a with PhLi
(3.0 equiv.) was carried out at -10 °C for 0.5 h (1st step), and
obtained imine 1a-A was treated with NIS under the same
procedure and conditions, 2-phenylquinoline 2a-A was obtained in
65% yield, together with -phenylpropionitrile 1a in 33% yield
(entry 5). The reason why -phenylpropionitrile 1a was recovered
partly is that PhLi not only added mainly to the nitrile group of -
phenylpropionitrile 1a, but also abstracted an -proton of -
This is mainly due to the reaction of the carbanion derived from
the -proton abstraction of -phenylpropionitrile 1a by n-BuLi,
with formed 1-bromobutane.
2 | J. Name., 2012, 00, 1-3
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Table 1. Optimization of Reaction Conditions
Scheme 1. Transformation of b-Arylpropionitriles 1 to 2-Arylquinolines 2.
View Article Online
DOI: 10.1039/C9OB00944B
1) ArLi (3.0 equiv.), THF (5.0 mL),
CN
1) PhLi (A, X equiv.)
-10 °C, 30 min. (1st step)
R2
R2
THF (5.0 mL)
Temp., Time
R1
NH
Ph
N
2
2) H2O (5.0 mL)
2) H2O (5.0 mL) (2nd step)
CN
(3.0 mmol)
1
3) NIS (2.1 equiv.), DCE (6.0 mL)
(1st step)
(2nd step)
W-hn, 30~40 °C, 3 h (3rd step)
(3.0 mmol)
ArLi (A~K)
1a
Ia-A
A: Ar = phenyl
B: Ar = o-methylphenyl C: Ar = m-methylphenyl
3) W-hn
D: Ar = p-methylphenyl E: Ar = p-methoxyphenyl F: Ar = p-chlorophenyl
G: Ar = p-bromophenyl H: Ar = p-(trifluoromethyl)phenyl
NIS (2.1 equiv.)
N
Ph
Solvent (6.0 mL)
30~40 °C, 3 h
(3rd step)
I: Ar = 2-naphthyl
J: Ar = benzofuran-2-yl
2a-A
Products, Yields
Me
Me
N
Me
N
N
Me
2b-C
66%
2b-A
70%
2b-B
47%
E n t r y X (equiv.) Temp Time (h) Reagent
(ºC)
Solvent
Yield (%)
Me
2a-A
Me
Me
Me
N
N
N
1
1.3
1.8
2.5
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
0
1
NIS
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
THF
38(49)a
51(43)a
58(31)a
59(40)a
65(33)a
65(26)c
63
Me
OMe
Cl
2b-D
65%
2b-E
61%
2b-F
67%
2
0
1
NIS
Me
N
Me
Et
Me
Et
3
0
1
NIS
N
N
4
0
1
NIS
Br
CF3
2b-G
62%
2b-H
2b-I
65%
56%a
5
–10
–10
–10
–10
–10
–10
–10
–10
–10
–10
–10
–10
–10
–10
–10
–10
0.5
0.5
0.5
1
NIS
Me
6b
7d
8
NIS
O
N
N
N
NIS
Me
2c-A
66%
2b-J
2c-B
63%
62%b
NIS
55
Et
Et
Et
Et
Et
Et
Et
9
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
NIS
12
N
N
N
2c-C
73%
2c-D
78%
2c-E
71%
10
11
12e
13f
14g
15
16
17i
18j
19k
20l
NIS
MeOH
MeCN
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
6
Me
Br
OMe
CF3
Me
NIS
25
N
N
N
NIS
41
2c-H
2c-F
67%
2c-G
68%
Cl
62%a
DIH
I2, K2CO3
NBS
NCS
NIS
64(33)a
0
i
Et
iPr
i
Pr
O
N
N
N
14 (61)h
0 (68)h
0 (41)h
0 (27)h
13
2c-I
73%
2c-J
2d-A
55%
66%b
iPr
Pr
i
N
N
N
2d-D
56%
2d-F
59%
2d-C
74%
Me
Cl
NIS
Me
Pr
iPr
Bn
Bn
NIS
N
N
N
NIS
16
2d-I
57%
2d-G
54%
2e-A
62%
Br
a Yield of recovered 1a. b After 1st reaction step, D2O (2.0 mL) was added.
c Yield of -phenylpropionitrile--d1. d Reaction was carried out with 1a
(8.0 mmol) and irradiation time at 3rd reaction step was 6 h. e Reaction
was carried out at 70 ºC for 3 h instead of irradiation with a tungsten lamp.
f Instead of NIS, DIH (1.1 equiv.) was used. g Instead of NIS, I2 (2.1 equiv.)
Bn
Bn
Bn
Bn
N
N
N
Me
Me
Br
2e-C
77%
2e-D
74%
and K2CO3 (1.5 equiv.) were used. h Yield of 1,3-diphenyl-1-propanone.
i
2e-B
Me
Bn
73%
In 3rd reaction step, BHT (1.5 equiv.) was added. j In 3rd reaction step,
TEMPO (1.5 equiv.) was added. k Instead of PhLi (3.0 equiv.), PhLi
prepared from bromobenzene (3.0 equiv.) and n-BuLi (3.1 equiv.) was
used. l In 1st reaction step, 1-bromobutane (3.0 equiv.) was added.
N
N
N
2e-E
66%
OCH3
Cl
2e-F
66%
2e-G
61%
This journal is © The Royal Society of Chemistry 20xx
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Journal Name
methylphenyl, p-methoxyphenyl, p-chlorophenyl, p-bromophenyl,
Bn
Bn
Bn
View Article Online
DOI: 10.1039/C9OB00944B
p-(trifluoromethyl)phenyl, 2-naphthyl, and benzofuran-2-yl groups
O
N
N
N
at 2-position were also obtained in good to moderate yields,
2e-H
2e-I
70%
2e-J
CF3
Me
65%a
70%b
respectively, as shown in Scheme 1.
When other -
-methyl--(o-
Me
arylpropionitriles,
such
as
1f,
Me
Me
Me
methylphenyl)propionitrile
methylphenyl)propionitrile
-methyl--(p-
-(p-chlorophenyl)--
methylpropionitrile 1h, and -dimethyl--phenylpropionitrile 1i,
were treated with phenyllithium (A) under the same procedure and
conditions, 3-methyl-2-phenylquinoline derivatives 2f-A~2i-A
were obtained in good to moderate yields, respectively, as shown
in Scheme 1.
N
N
Cl
N
1g,
2f-A
2g-A
68%
2h-A
62%
46%c,d
Me
Me
N
2i-A
40%
a 1st reaction step was conducted for 90 min.
b 1st reaction step was conducted at 0 °C .
c
In 3rd reaction step, NIS (3.0 equiv.) was used.
d 3rd reaction step was stirred for 5 h.
Scheme 2. Orientation for Radical Cyclization onto Aromatic Ring
1) PhLi (3.0 equiv.)
THF (5.0 mL)
-10 °C, 30 min.
(1st step)
Practically, when the reaction in entry 5 was carried out in the
presence of 1-bromobutane (3.0 equiv.) in the 1st reaction step
under the same procedure and conditions, the yield of 2-
phenylquinoline 2a-A was considerably decreased to 16% (entry
20). Thus, when -arylpropionitriles 1, which have two -
hydrogen atoms, are treated with ArLi prepared from the reactions
of ArBr with n-BuLi, we cannot expect good yields due to the
reactions of the carbanions derived from -arylpropionitriles 1,
with formed 1-bromobutane.
CN
Me
Cl
Me
Cl
N
H
2) H2O (5.0 mL)
(2nd step)
Ph
1j (1.0 mmol)
Ij-A
Cl
Me
3) NIS (2.1 equiv.)
DCE (6.0 mL)
+
W-hv, 30~40 °C, 3 h
(3rd step)
Me
N
Cl
N
2j'-A
2j-A
60% (2j-A : 2j'-A = 78:22)
Finally, instead of a tungsten lamp (300 W), when the reaction of
the 3rd step in entry 5 was carried out under irradiation with a LED
lamp (60 W) at room temperature and a high-pressure mercury
lamp (400 W) at the range of 35 °C~40 °C under the same
procedure and conditions, the yield of 2-phenylquinoline 2a-A was
slightly decreased to 51% and 41%, together with -
phenylpropionitrile 1a in 27% and 31% yields, respectively.
To understand the orientation for the radical cyclization of an
imino-nitrogen-centered radical onto an aromatic ring, -(p-
chlorobenzyl)--(p-methylbenzyl)acetonitrile 1j was treated with
PhLi (A, 3.0 equiv.) in THF (5.0 mL) at -10 °C for 0.5 h, and then
with water (5.0 mL) to form the corresponding phenylimine Ij-A.
Then, phenylimine Ij-A was treated with NIS (2.1 equiv.) in DCE
(6.0 mL) under irradiation with a tungsten lamp in the range of 30
°C~40 °C to give 3-(p-chlorobenzyl)-7-methyl-2-phenylquinoline
2j-A and 7-chloro-3-(p-methylbenzyl)-2-phenylquinoline 2j’-A in
60% yield (78:22), as shown in Scheme 2. Thus, this result
indicates that the imino-nitrogen-centered radical has an
electrophilic character.
Then, as our next strategy, we used -alkyl--arylpropionitriles 1
as substrates to reduce the amount of -proton abstraction of -
arylpropionitriles 1 by n-BuLi. Based on the above results, -
methyl--phenylpropionitrile 1b (3.0 mmol) was treated with
aryllithiums B~J (3.0 equiv.) prepared from aryl bromides and n-
BuLi in THF (5.0 mL) at -10 °C for 0.5 h (1st step), and then with
water (5.0 mL) to form the corresponding arylimines I (2nd step).
Then, arylimines I were treated with N-iodosuccinimide (NIS, 2.1
equiv.) in 1,2-dichloroethane (DCE, 6.0 mL) under irradiation with
a tungsten lamp (300 W) in the range of 30 °C~40 °C for 3 h (3rd
step) to give 2-aryl-3-methylquinolines 2b-B~2b-J bearing o-
Based on the obtained results, a possible reaction mechanism for
the formation of 2-arylquinolines from -arylpropionitriles is
shown in Scheme 3. Arylimine I formed from the reaction of -
arylpropionitrile with aryllithium reacts with NIS to form N-iodo
arylimine II. Under irradiation with a tungsten lamp, homolytic
bond cleavage of the N-I bond in N-iodo arylimine II occurs to
methylphenyl,
methoxyphenyl,
m-methylphenyl,
p-chlorophenyl,
p-methylphenyl,
p-bromophenyl,
p-
p-
form imino-nitrogen-centered radical III.
Reactive imino-
(trifluoromethyl)phenyl, 2-naphthyl, and benzofuran-2-yl groups at
2-position in good to moderate yields, respectively, as shown in
Scheme 1. When -substituted -phenylpropionitriles 1c, 1d, and
1e bearing ethyl, isopropyl, and benzyl groups at -position were
treated with aryllithiums A~J under the same procedure and
nitrogen-centered radical III cyclizes onto the aromatic ring of the
-arylethyl group in radical III to form adduct intermediate IV that
is smoothly oxidized to 2-aryl-3,4-dihydroquinoline V by NIS.
Once 2-aryl-3,4-dihydroquinoline V is formed, it is further
oxidized to 2-arylquinoline 2 by NIS through the intermediates VI
and VII. Practically, the formation of 2-arylquinoline in the
presence of BHT, a hydrogen atom donor, and TEMPO, a radical
trapping reagent, is completely inhibited. Moreover, as the formed
conditions,
2-aryl-3-ethylquinolines
2c-A~2c-J,
2-aryl-3-
isopropylquinolines 2d-A~2d-I, and 2-aryl-3-benzylquinolines 2e-
A~2e-J bearing phenyl, o-methylphenyl, m-methylphenyl, p-
4 | J. Name., 2012, 00, 1-3
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Organic & Biomolecular Chemistry
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Journal Name
ARTICLE
imino-nitrogen-centered radical has an electrophilic character, it
cyclizes onto the electron-rich aromatic ring of aryl -
arylethylimine I to form 2-arylquinoline 2. It is known that
homolytic bond cleavage of the N-I bond in N-iodosulfonamides
under irradiation with a tungsten lamp occurs smoothly to form
nitrogen-containing heterocyclic compounds with sulfonamides,
(diacetoxyiodo)benzene (DIB), and iodine.8 In contrast, homolytic
bond cleavage of N-Br and N-Cl does not occur smoothly under
the present reaction conditions.
(deuterochloroform at 77.0 ppm). Characteristic pVeiaewksArtiincle tOhneline
DOI: 10.1039/C9OB00944B
infrared (IR) spectra were recorded in wave number, cm . High-
-1
resolution mass spectra were measured with Thermo Fisher
Scientific Exactive Orbitrap mass spectrometers. Melting points
were uncorrected. Thin-layer chromatography (TLC) was
performed using 0.25 mm silica gel plates (60F-254). The
products were purified by column chromatography on neutral
silica gel 60N (63–210 mesh).
Typical Procedure for Preparation of -Arylpropionitriles 1:
Lithium diisopropylamide (LDA, 75.6 mmol, 1.08 M in hexane, 70.0
mL) was added dropwise to a solution of propionitrile (75.6 mmol,
4.32 g) in THF (70.0 mL) at −78 °C under argon atmosphere. After 5
min., benzyl bromide (84.0mmol, 9.98 mL) was added to the
Scheme 3. Plausible Reaction Mechanism
R1
R1
Ar
R1
Ar
Li
H2O
R2
R2
R2
N
Li
N
H
N
°
Ar
I
1
mixture. The obtained mixture was stirred at –78 C for 1 h and at
NIS
room temperature for 90 min under argon atmosphere. Then, aq.
NH4Cl solution (50 mL) was added to the reaction mixture and the
product was extracted with CHCl3 (50 mL × 3). The organic layer
was purified by silica-gel column chromatography (eluent: n-
hexane:EtOAc = 9:1) to give -methyl--phenylpropionitrile 1b
(5.20 g 47%). Other -arylpropionitriles 1 were prepared by the
same procedure and conditions in the range of 51%~58% yields. -
Phenylpropionitrile 1a is commercially available.
W-hn
R1
Ar
R1
Ar
R1
Ar
R2
R2
R2
N
N
N
I
IV
III
II
I
R1
Ar
R2
1/2 I2
N
2
HI
O
N
-Methyl--phenylpropionitrile (1b): clorless oil; IR (neat): 3030,
HI
1
2239 cm-1; H-NMR (400 MHz, CDCl3): δ = 1.33 (d, 3H, J = 6.8
R1
H
O
Hz), 2.80-2.99 (m, 3H), 7.23 (d, 2H, J = 7.4 Hz), 7.28 (t, 1H, J = 7.3
Hz), 7.34 (t, 2H, J = 7.1 Hz); 13C-NMR (100 MHz, CDCl3): δ =
17.5, 27.4, 39.9, 122.5, 127.1, 128.6, 129.0, 136.8; HRMS (APCI):
Calcd for C10H12N [M+H]+ = 146.0965, Found = 146.0964.
R1
Ar
H
R1
NIS
R2
R2
R2
N
Ar
N
N
Ar
I
V
I
VI
VII
Conclusions
-Ethyl--phenylpropionitrile (1c): corless oil; IR (neat): 3030,
1
2238 cm-1; H-NMR (400 MHz, CDCl3): δ = 1.12 (t, 3H, J = 7.3
Irradiation treatment of imines formed from the reactions of -
Hz), 1.59-1.72 (m, 2H), 2.68-2.76 (m, 1H), 2.86 (dd, 1H, J = 6.3,
13.8 Hz), 2.94 (dd, 1H, J = 8.4, 13.7 Hz) 7.23-7.26 (m, 2H), 7.26-
7.29 (m, 1H), 7.34 (t, 2H, J = 7.2 Hz); 13C-NMR (100 MHz, CDCl3):
δ =11.5, 25.0, 35.4, 38.0, 121.6, 127.1, 128.6, 128.9, 137.0; HRMS
(APCI): Calcd for C11H14N [M+H]+ = 160.1123, Found = 160.1121.
arylpropionitriles with aryllithiums, and then with water and
NIS, with a tungsten lamp gave the corresponding 2-
arylquinolines in good to moderate yields. The key points of
the present reactions are as follows. NIS plays the role of an
iodination reagent of the formed imines, and homolytic bond
cleavage of the formed N-I bond occurs to generate an iminyl
radical, i.e., an imino-nitrogen-centered radical. The iminyl
radical cyclizes onto the aromatic ring derived from
arylpropionitrile to form 2-aryl-3,4-dihydroquinoline, which is
smoothly oxidized to 2-arylquinoline by NIS. This is a novel
method for the preparation of 2-arylquinolines from
-Isopropyl--phenylpropionitrile (1d): colorless oil; IR (neat):
1
3031, 2236cm-1; H-NMR (400 MHz, CDCl3): δ =1.11 (d, 3H, J =
-
6.7 Hz), 1.13 (d, 3H, J = 6.7 Hz), 1.87 (sext, 1H, J = 6.7 Hz), 2.65-
2.71 (m, 1H), 2.81-2.94 (m, 2H), 7.22-7.27 (m, 3H), 7.34 (t, 2H, J =
7.4 Hz); 13C-NMR (100 MHz, CDCl3): δ = 11.5, 25.0, 35.4, 38.0,
121.6, 127.1, 128.6, 128.9, 137.0; HRMS (APCI): Calcd for
C12H16N [M+H]+ = 174.1279, Found = 174.1277.
-
arylpropionitriles, and would be useful for the preparation of
quinoline derivatives under transition-metal-free conditions.
-Benzyl--phenylpropionitrile (1e): white solid; mp: 89-90 °C;
IR (neat): 3062, 3028, 2240 cm-1; H-NMR (400 MHz, CDCl3): δ =
1
Experimental Section
General: H NMR spectra were measured on 400 MHz and 500
2.93 (d, 4H, J = 7.0 Hz), 3.03 (quin, 1H, J = 7.5 Hz), 7.24-7.27 (m,
4H), 7.27-7.30 (m, 2H), 7.35 (t, 4H, J = 7.2 Hz); 13C-NMR (100
MHz, CDCl3): δ = 35.8, 37.9, 121.2, 127.3, 128.7, 129.0, 136.7;
HRMS (APCI): Calcd for C16H16N [M+H]+ = 222.1278, Found =
222.1277.
1
MHz spectrometers. Chemical shifts were recorded as follows:
chemical shift in ppm from internal tetramethylsilane on the 
scale, multiplicity (s = singlet; d = doublet; t = triplet; q = quartet;
m = multiplet; br = broad), coupling constant (Hz), integration,
and assignment. 13C NMR spectra were measured on 125 MHz
spectrometers. Chemical shifts were recorded in ppm from the
solvent resonance employed as the internal standard
-(p-Chlorobenzyl)--(p-methylbenzyl)acetonitrile (1j): white
1
solid; mp: 86 °C; yellow oil; IR (neat): 3053, 2242 cm-1; H-NMR
(400 MHz, CDCl3): δ = 2.34 (s, 3H), 2.81-2.89 (m, 4H), 2.93-3.01
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ARTICLE
(m, 1H), 7.11-7.21 (m, 6H), 7.31 (d, 2H, J = 8.4 Hz); 13C-NMR (100 (eluent: n-hexane:EtOAc
Journal Name
=
9:1) to give 3V-miewetAhrtyicll-e2O-n(4lin’e-
DOI: 10.1039/C9OB00944B
MHz, CDCl3): δ = 21.1, 35.9, 37.1, 37.5, 121.1, 128.9 (2C),129.5, methylphenyl)quinoline 2b-D (453.6 mg, 65%).
130.4, 133.2, 133.4, 135.2, 137.0; HRMS (APCI): Calcd for
C17H17NCl [M+H]+ = 270.1046, Found = 270.1044.
3-Methyl-2-(2’-methylphenyl)quinoline (2b-B): Yield: 328.3 mg
1
(47%); yellow oil; IR (neat): 3058, 1599, 1555 cm-1; H-NMR (400
MHz, CDCl3): δ = 2.10 (s, 3H), 2.25 (s, 3H), 7.23-7.33 (m, 4H), 7.54
(t, 1H, J = 8.2 Hz), 7.67 (t, 1H, J = 8.4 Hz) 7.81 (d, 1H, J = 7.0 Hz),
8.03 (s, 1H), 8.12 (d, 1H, J = 7.9 Hz); 13C-NMR (100 MHz, CDCl3):
δ =19.4, 19.6, 125.8, 126.3, 126.7, 127.6, 128.1 (2C), 128.6, 129.2,
129.8, 130.2, 135.3, 136.0, 140.3, 146.4, 161.4; HRMS (ESI): Calcd
for C17H16N [M+H]+ = 234.1277, Found = 234.1272.
Typical Procedure for Transformation of -Arylpropionitriles 1
to 2-Arylquinolines 2 (1): To a solution of -phenylpropionitrile 1a
(3.0 mmol, 393.54 mg) in THF (5.0 mL) was added PhLi (9.0 mmol,
°
1.1 M in cyclohexane and diethyl ether, 8.5 mL) at -10 C. The
°
obtained mixture was stirred for 30 min at –10 C under an argon
atmosphere. Then, H2O (5.0 mL) was added to the mixture, and the
product was extracted with CHCl3 (15 mL × 3) quickly. The organic
layer was dried over Na2SO4, and the solvent was removed under
reduced pressure. To the residue in 1,2-dichloroethane (6.0 mL) was
added NIS (6.3 mmol, 1.417 g) at room temperature, and the
obtained mixture was stirred under irradiation with a tungsten lamp
(300 W) for 3 h in the range of 30 °C~40 °C. Then, sat. Na2SO3
aqueous solution (15 mL) was added to the reaction mixture, and the
product was extracted with CHCl3 (15 mL × 3). The organic layer
was purified by silica-gel column chromatography (eluent: n-
hexane:EtOAc = 9:1) to give 2-phenylquinoline 2a-A (399.6 mg
65%).
3-Methyl-2-(3’-methylphenyl)quinoline (2b-C): Yield: 464.8 mg
1
(66%); yellow oil; IR (neat): 3058, 1598, 1557 cm-1; H-NMR (400
MHz, CDCl3): δ = 2.44 (s, 3H), 2.46 (s, 3H), 7.22-7.24 (m, 1H),
7.36-7.41 (m, 3H), 7.52 (t, 1H, J = 7.5 Hz), 7.66 (t, 1H, J = 7.6 Hz)
7.78 (d, 1H, J = 7.9 Hz), 8.02 (s, 1H), 8.13 (d, 1H, J = 8.5 Hz); 13C-
NMR (100 MHz, CDCl3): δ = 20.6, 21.5, 125.8, 126.3, 126.6, 127.5,
128.0, 128.6, 128.8, 129.2 (2C), 129.4, 136.6, 138.0, 140.7, 146.5,
160.7; HRMS (ESI): Calcd for C17H16N [M+H]+ = 234.1277, Found
= 234.1273.
3-Methyl-2-(4’-methylphenyl)quinoline (2b-D): Yield: 453.6 mg
1
(65%); yellow oil; IR (neat): 3057, 1598, 1557 cm-1; H-NMR (400
2-Phenylquinoline (2a-A): Yield: 399.6 mg (65%); white solid; mp:
MHz, CDCl3): δ = 2.43 (s, 3H), 2.48 (s, 3H), 7.30 (d, 2H, J = 7.7
Hz), 7.49-7.53 (m, 3H), 7.65 (td, 1H, J = 7.7, 1.6 Hz) 7.77 (d, 1H, J
= 8.2 Hz), 8.01 (s, 1H), 8.11 (d, 1H, J = 8.4 Hz); 13C-NMR (100
MHz, CDCl3): δ = 20.6, 21.2, 126.1, 126.5, 127.3, 128.5, 128.7,
128.8, 129.1 (2C), 136.5, 137.8 (2C), 146.5, 160.4; HRMS (ESI):
Calcd for C17H16N [M+H]+ = 234.1277, Found = 234.1274.
1
83-85 °C; IR (neat): 3057, 1597, 1556 cm-1; H-NMR (400 MHz,
CDCl3): δ = 7.47 (tt, 1H, J = 7.2, 2.1 Hz ), 7.52-7.56 (m, 3H), 7.74
(td, 1H, J = 7.8, 1.5 Hz), 7.84 (d, 1H, J = 8.0 Hz), 7.89 (d, 1H, J =
8.5 Hz), 8.16-8.19 (m, 3H), 8.24 (d, 1H, J = 8.5 Hz); 13C-NMR (100
MHz, CDCl3): δ = 119.0, 126.3, 127.1, 127.4, 127.5, 128.8, 129.3,
129.6, 129.7, 136.8, 139.7, 148.2, 157.4; HRMS (ESI): Calcd for
C15H12N [M+H]+ = 206.0964, Found = 206.0959.
2-(4’-Methoxyphenyl)-3-methylquinoline (2b-E): Yield: 454.0 mg
(61%); white solid; mp: 74-75 °C; IR (neat): 3044, 1606, 1514, 1031
3-Methyl-2-phenylquinoline (2b-A): Yield: 462.5 mg (70%);
1
cm-1; H-NMR (400 MHz, CDCl3): δ = 2.50 (s, 3H), 3.88 (s, 3H),
1
yellow oil; IR (neat): 3058, 1598, 1557 cm-1; H-NMR (400 MHz,
7.02 (d, 2H, J = 8.6 Hz), 7.50 (t, 1H, J = 8.2 Hz), 7.57 (d, 2H, J = 8.6
Hz), 7.65 (t, 1H, J = 8.4 Hz), 7.77 (d, 1H, J = 8.2 Hz), 8.00 (s, 1H),
8.11 (d, 1H, J = 8.4 Hz); 13C-NMR (100 MHz, CDCl3): δ = 20.8,
55.3, 113.7, 126.2, 126.6, 127.4, 128.6, 129.2 (2C), 130.3, 133.4,
136.7, 146.6, 159.6, 160.1; HRMS (ESI): Calcd for C17H16ON
[M+H]+ = 250.1226, Found = 250.1226.
CDCl3): δ = 2.47 (s, 3H), 7.44-7.54 (m, 4H), 7.60 (d, 2H, J = 8.0
Hz), 7.67 (t, 1H, J = 7.8 Hz), 7.79 (d, 1H, J = 8.5 Hz), 8.03 (s, 1H),
8.13 (d, 1H, J = 8.5 Hz); 13C-NMR (100 MHz, CDCl3): δ = 20.6,
126.4, 126.7, 127.5, 128.1, 128.3, 128.7, 128.8, 129.2, 129.3, 136.7,
140.8, 146.6, 160.5; HRMS (ESI): Calcd for C16H14N [M+H]+ =
220.1117, Found = 220.1121.
2-(4’-Chlorophenyl)-3-methylquinoline (2b-F): Yield: 512.3 mg
(67%); white solid; mp: 87-89 °C; IR (neat): 3053, 1596, 1555 cm-1;
1H-NMR (400 MHz, CDCl3): δ = 2.47 (s, 3H), 7.47 (d, 2H, J = 8.6
Hz), 7.51-7.57 (m, 3H), 7.68 (t, 1H, J = 8.2 Hz), 7.79 (d, 1H, J = 7.9
Hz), 8.04 (s, 1H), 8.11 (d, 1H, J = 8.4 Hz); 13C-NMR (100 MHz,
CDCl3): δ = 20.6, 126.6, 126.7, 127.6, 128.5, 128.9, 129.0, 129.2,
130.3, 134.3, 137.0, 139.2, 146.6, 159.2; HRMS (ESI): Calcd for
C16H13NCl [M+H]+ = 254.0731, Found = 254.0733.
Typical Procedure for Transformation of -Arylpropionitriles 1
to 2-Arylquinolines 2 (2): n-BuLi (9.0 mmol, 1.5 M in hexane, 5.73
mL) was added dropwise to a solution of p-bromotoluene (9.3 mmol,
1.590 g) in THF (5.0 mL) at −50 °C under an argon atmosphere.
After 30 min, a solution of -methyl--phenylpropionitrile 1b (3.0
mmol, 435.62 mg) in THF (2.0 mL) was added to the mixture at -10
°C. The obtained mixture was stirred for 30 min at –10 °C under an
argon atmosphere. Then, H2O (5.0 mL) was added to the mixture,
and the imine was extracted with CHCl3 (15 mL × 3) quickly. The
organic layer was dried over Na2SO4, and removal of the solvent
under reduced pressure gave the imine. To the residual imine in 1,2-
dichloroethane (6.0 mL) was added NIS (6.3 mmol, 1.417 g) at room
temperature, and the mixture was stirred under irradiation with a
tungsten lamp (300 W) for 3 h in the range of 30~40 °C. Sat.
Na2SO3 aqueous solution (15 mL) was added to the reaction mixture,
and the obtained mixture was extracted with CHCl3 (15 mL × 3).
The organic layer was purified by silica-gel column chromatography
2-(4’-Bromophenyl)-3-methylquinoline (2b-G): Yield: 556.4 mg
(62%); white solid; mp: 99-100 °C; IR (neat): 3048, 1598, 1555 cm-
1; 1H-NMR (400 MHz, CDCl3): δ = 2.47 (s, 3H), 7.49 (d, 2H, J = 8.5
Hz), 7.53 (t, 1H, J = 7.9 Hz), 7.63 (d, 2H, J = 8.5 Hz), 7.67 (t, 1H, J
= 8.3 Hz), 7.79 (d, 1H, J = 7.9 Hz), 8.03 (s, 1H), 8.10 (d, 1H, J = 8.3
Hz); 13C-NMR (100 MHz, CDCl3): δ = 20.5, 122.6, 126.6, 126.7,
127.6, 128.9 (2C), 129.2, 130.6, 131.4, 137.0, 139.7, 146.6, 159.2;
6 | J. Name., 2012, 00, 1-3
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Organic & Biomolecular Chemistry
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ARTICLE
HRMS (ESI): Calcd for C16H13NBr [M+H]+ = 298.0226, Found = J = 7.5 Hz), 7.24-7.26 (m, 1H), 7.31-7.38 (m, 3H), 7.52 (t, 1H, J =
View Article Online
DOI: 10.1039/C9OB00944B
298.0224.
7.6 Hz), 7.66 (t, 1H, J = 7.6 Hz), 7.81 (d, 1H, J = 8.0 Hz), 8.05 (s,
1H), 8.13 (d, 1H, J = 8.2 Hz); 13C-NMR (100 MHz, CDCl3): δ =
14.7, 21.5, 25.9, 125.6, 126.2, 126.8, 127.6, 128.0, 128.7 (2C),
129.2, 129.3, 134.7, 135.3, 137.9, 140.8, 146.2, 160.8; HRMS (ESI):
Calcd for C18H18N [M+H]+ = 248.1434, Found = 248.1432.
3-Methyl-2-[4’-(trifluoromethyl)phenyl]quinoline (2b-H): Yield:
478.4 mg (56%); white solid; mp: 129-130 °C; IR (neat): 3021,
2927, 1694, 1652 cm-1; H-NMR (400 MHz, CDCl3): δ = 2.47 (s,
1
3H), 7.55 (t, 1H, J = 7.6, 1.1 Hz), 7.68 (d, 1H, J = 7.6 Hz), 7.75-7.82
(m, 4H), 7.81 (dd, 1H, J = 8.2, 1.3 Hz), 8.06 (s, 1H), 8.11 (d, 1H, J = 3-Ethyl-2-(4’-methylphenyl)quinoline (2c-D): Yield: 580.3 mg
1
8.4 Hz); 13C-NMR (100 MHz, CDCl3): δ = 20.3, 124.2 (q, JC-F
=
(78%); yellow oil; IR (neat): 2968, 1597, 1557 cm-1; H-NMR (400
272.3 Hz) 125.3 (d, JC-F = 3.8 Hz), 125.5, 126.8 (2C), 127.7, 128.8, MHz, CDCl3): δ = 1.20 (t, 3H, J = 7.5 Hz), 2.43 (s, 3H), 2.81 (q, 2H,
129.0, 129.3, 130.2 (q, JC-F = 32.4 Hz), 137.0, 144.4, 146.6, 158.9; J = 7.5 Hz), 7.29 (d, 2H, J = 7.7 Hz), 7.48 (d, 2H, J = 8.2 Hz), 7.51
HRMS (ESI): Calcd for C17H13NF3 [M+H]+ = 288.0995, Found = (t, 1H, J = 7.5 Hz), 7.66 (td, 1H, J = 7.7, 1.4 Hz), 7.81 (dd, 1H, J =
288.0992.
7.9, 1.1 Hz), 8.04 (s, 1H), 8.12 (d, 1H, J = 8.4 Hz); 13C-NMR (100
MHz, CDCl3): δ = 14.7, 21.3, 26.0, 126.2, 126.8, 127.6, 128.6 (2C),
128.9, 129.2, 134.7 135.3, 137.7, 138.0, 146.3, 160.6; HRMS (ESI):
Calcd for C18H18N [M+H]+ = 248.1434, Found = 248.1436.
3-Methyl-2-(naphthalene-2’-yl)quinoline (2b-I): Yield: 526.8 mg
(65%); white solid; mp: 98-99 °C; IR (neat): 3057, 3017, 1591, 1553
1
cm-1; H-NMR (400 MHz, CDCl3): δ = 2.51 (s, 3H), 7.51-7.55 (m,
3H), 7.68 (t, 1H, J = 7.0 Hz), 7.72 (dd, 1H, J = 8.4, 1.6 Hz), 7.80 (d, 3-Ethyl-2-(4’-methoxyphenyl)quinoline (2c-E): Yield: 563.3 mg
1H, J = 8.2 Hz), 7.90-7.93 (m, 2H), 7.96 (d, 1H, J = 8.4 Hz), 8.06 (s, (71%); yellow oil; IR (neat): 2966, 1576, 1557, 1033 cm-1; 1H-NMR
1H), 8.07 (s, 1H), 8.15 (d, 1H, J = 8.4 Hz); 13C-NMR (100 MHz, (400 MHz, CDCl3): δ = 1.21 (t, 3H, J = 7.5 Hz), 2.83 (q, 2H, J = 6.8
CDCl3): δ = 20.6, 126.2, 126.3, 126.4, 126.6, 126.7, 127.5, 127.7, Hz), 3.88 (s, 3H), 7.02 (dt, 2H, J = 8.6, 2.0 Hz), 7.49-7.53 (m, 3H),
127.9, 128.1, 128.4, 128.8, 129.2, 129.3, 133.0, 133.1, 136.7, 138.3, 7.66 (td, 1H, J = 7.7, 1.4 Hz), 7.80 (dd, 1H, J = 8.2, 1.4 Hz), 8.03 (s,
146.6, 160.4; HRMS (ESI): Calcd for C20H16N [M+H]+ = 270.1277, 1H), 8.11 (d, 1H, J = 7.5 Hz); 13C-NMR (100 MHz, CDCl3): δ =
Found = 270.1277.
14.7, 26.0, 55.3, 113.7, 126.1, 126.8, 127.5, 128.6, 129.1, 130.0,
133.4, 134.8, 135.3, 146.3, 159.5, 160.2; HRMS (ESI): Calcd for
C18H18ON [M+H]+ = 264.1383, Found = 264.1379.
2-(Benzofuran-2’-yl)-3-methylquinoline (2b-J): Yield: 480.8 mg
(62%); yellow solid; mp: 79-81 °C; IR (neat): 3131, 3023, 1595,
1
1543 cm-1; H-NMR (400 MHz, CDCl3): δ = 2.82 (s, 3H), 7.29 (td, 3-Ethyl-2-(4’-chlorophenyl)quinoline (2c-F): Yield: 536.6 mg
1H, J = 7.7, 0.9 Hz), 7.38 (td, 1H, J = 7.7, 1.4 Hz), 7.48 (d, 1H, J = (67%); white solid; mp: 48-49 °C; IR (neat): 2970, 1599, 1558 cm-1;
0.9 Hz), 7.53 (dd, 1H, J = 7.4, 1.1 Hz), 7.64-7.71 (m, 3H), 7.77 (d, 1H-NMR (400 MHz, CDCl3): δ = 1.20 (t, 3H, J = 7.5 Hz), 2.79 (q,
1H, J = 8.2 Hz), 8.04 (s, 1H), 8.18 (d, 1H, J = 8.6 Hz); 13C-NMR 2H, J = 7.5 Hz), 7.45-7.50 (m, 4H), 7.54 (td, 1H, J = 7.5, 1.1 Hz),
(100 MHz, CDCl3): δ = 21.3, 108.6, 111.8, 121.6, 123.0, 125.2, 7.68 (td, 1H, J = 7.7, 1.6 Hz), 7.82 (d, 1H, J = 8.2 Hz), 8.06 (s, 1H),
126.6, 126.9, 127.5, 128.4, 129.0, 129.1, 129.3, 137.7, 146.5, 148.9, 8.10 (d, 1H, J = 8.4 Hz); 13C-NMR (100 MHz, CDCl3): δ = 14.7,
155.1, 155.2; HRMS (ESI): Calcd for C18H14ON [M+H]+
260.1070, Found = 260.1071.
=
25.9, 126.5, 126.9, 127.7, 128.5, 128.9, 129.2, 130.2, 134.2, 135.0,
135.1, 139.3, 146.3, 159.3; HRMS (ESI): Calcd for C17H15NCl
[M+H]+ = 268.0888, Found = 268.0883.
3-Ethyl-2-phenylquinoline (2c-A): Yield: 460.6 mg (66%); white
solid; mp:59-61 °C; IR (neat): 2964, 1597, 1558 cm-1; 1H-NMR (400 3-Ethyl-2-(4’-bromophenyl)quinoline (2c-G): Yield: 634.1 mg
MHz, CDCl3): δ = 1.20 (t, 3H, J = 7.5 Hz), 2.80 (q, 2H, J = 7.6 Hz), (68%); white solid; mp: 57-58 °C; IR (neat): 3346, 2970, 1600, 1486
7.42-7.51 (m, 3H), 7.53-7.56 (m, 3H), 7.67 (td, 1H, J = 7.6 Hz), 7.82 cm-1; 1H-NMR (400 MHz, CDCl3): δ = 1.20 (t, 3H, J = 7.5 Hz), 2.79
(dd, 1H, J = 8.4, 1.4 Hz), 8.06 (s, 1H), 8.13 (d, 1H, J = 7.9 Hz); 13C- (q, 2H, J = 7.5 Hz), 7.44 (dt, 2H, J = 8.6, 2.1 Hz), 7.54 (td, 1H, J =
NMR (100 MHz, CDCl3): δ = 14.7, 26.0, 126.3, 126.9, 127.7, 128.0, 7.4, 1.1 Hz), 7.63 (dt, 2H, J = 8.4, 2.2 Hz), 7.68 (td, 1H, J = 7.7, 1.4
128.2, 128.7 (2C), 129.2, 134.8, 135.2, 140.9, 146.3, 160.6; HRMS Hz), 7.82 (d, 1H, J = 7.0 Hz), 8.06 (s, 1H), 8.10 (d, 1H, J = 8.6 Hz);
(ESI): Calcd for C17H16N [M+H]+ = 234.1277, Found = 234.1277.
13C-NMR (100 MHz, CDCl3): δ = 14.7, 25.9, 122.4, 126.6, 126.9,
127.7, 129.0, 129.2, 130.5, 131.4, 135.0, 135.1, 139.8, 146.3, 159.3;
HRMS (ESI): Calcd for C17H15NBr [M+H]+ = 312.0382, Found =
312.0379.
3-Ethyl-2-(2’-methylphenyl)quinoline (2c-B): Yield: 469.0 mg
1
(63%); yellow oil; IR (neat): 2967, 1596, 1558 cm-1; H-NMR (400
MHz, CDCl3): δ = 1.16 (t, 3H, J = 7.5 Hz), 2.09 (s, 3H), 2.49-2.61
(m, 2H), 7.29-7.33 (m, 4H), 7.54 (t, 1H, J = 8.2 Hz), 7.67 (td, 1H, J 3-Ethyl-2-[4’-(trifluoromethyl)phenyl]quinoline (2c-H): Yield:
= 7.6, 1.6 Hz), 7.83 (d, 1H, J = 7.9 Hz), 8.06 (s, 1H), 8.12 (d, 1H, J = 561.3 mg (62%); white solid; mp: 94-95 °C; IR (neat): 2968, 1589,
1
8.4 Hz); 13C-NMR (100 MHz, CDCl3): δ = 14.2, 19.5, 25.5, 125.6, 1553 cm-1; H-NMR (400 MHz, CDCl3): δ = 1.21 (t, 3H, J = 7.5
126.3, 126.9, 127.7, 128.0, 128.3, 128.6, 129.1, 130.2, 134.3 135.5, Hz), 2.79 (q, 2H, J = 7.5 Hz), 7.56 (t, 1H, J = 7.9, Hz), 7.67-7.72 (m,
135.7, 140.1, 146.2, 161.1; HRMS (ESI): Calcd for C18H18N [M+H]+ 3H), 7.76 (d, 2H, J = 8.4 Hz), 7.84 (d, 1H, J = 8.4 Hz), 8.10 (s, 1H),
= 248.1434, Found = 248.1431.
8.11 (d, 1H, J = 9.5 Hz); 13C-NMR (100 MHz, CDCl3): δ = 14.7,
25.8, 124.2 (q, JC-F = 271.8 Hz), 125.3 (d, JC-F = 3.8 Hz), 126.8,
127.0, 127.9, 129.1, 129.2 (2C), 130.2 (q, JC-F = 32.4 Hz), 134.9,
135.2, 144.5, 146.3, 159.0; HRMS (ESI): Calcd for C18H15NF3
[M+H]+ = 302.1151, Found = 302.1148.
3-Ethyl-2-(3’-methylphenyl)quinoline (2c-C): Yield: 543.2 mg
(73%); yellow oil; IR (neat): 2967, 1596, 1557 cm-1; H-NMR (400
MHz, CDCl3): δ = 1.20 (t, 3H, J = 7.5 Hz), 2.43 (s, 3H), 2.79 (q, 2H,
1
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Organic & Biomolecular Chemistry
Page 8 of 11
ARTICLE
Journal Name
3-Ethyl-2-(naphthalene-2’-yl)quinoline (2c-I): Yield: 623.1 mg 1H, J = 7.6, 1.5 Hz), 7.83 (d, 1H, J = 8.2 Hz), 8.10 (Vdie,w1AHrt,icJle =On8lin.4e
13
(73%); yellow oil; IR (neat): cm-1; 3055, 2965, 1595, 1557 cm-1; 1H- Hz), 8.13 (s, 1H); C-NMR (100 MHz, CDCl3): δ = 24.1, 29.3,
DOI: 10.1039/C9OB00944B
NMR (400 MHz, CDCl3): δ = 1.20 (t, 3H, J = 7.5 Hz), 2.86 (q, 2H, J 126.5, 127.1, 127.9, 128.5, 129.0, 129.2, 130.2, 133.0, 134.1, 139.4,
= 8.2 Hz), 7.52-7.53 (m, 3H), 7.69 (td, 2H, J = 8.4, 1.8 Hz), 7.85 (d, 140.2, 146.1, 159.1; HRMS (ESI): Calcd for C18H17NCl [M+H]+ =
1H, J = 6.8 Hz), 7.91 (d, 1H, J = 6.1 Hz), 7.92 (d, 1H, J = 6.1 Hz), 282.1044, Found = 282.1042.
7.96 (d, 1H, J = 8.4 Hz), 8.04 (s, 1H), 8.10 (s, 1H), 8.15 (d, 1H, J =
8.4 Hz); 13C-NMR (100 MHz, CDCl3): δ =14.7, 26.1, 126.2, 126.3,
126.4, 126.6, 126.9, 127.7 (2C), 127.9, 128.0, 128.3, 128.8, 129.3,
133.0, 133.2, 135.0, 135.5, 138.4, 146.4, 160.5; HRMS (ESI): Calcd
for C21H18N [M+H]+ = 284.1434, Found = 284.1430.
3-Isopropyl-2-(4’-bromophenyl)quinoline (2d-G): Yield: 529.5
mg (54%); white solid; mp: 94-96 °C; IR (neat): 2962, 1595, 1553
1
cm-1; H-NMR (400 MHz, CDCl3): δ = 1.25 (d, 6H, J = 6.8 Hz),
3.21 (sep, 1H, J = 6.8 Hz), 7.41 (d, 2H, J = 8.6 Hz), 7.54 (td, 1H, J =
6.8 Hz), 7.63 (d, 2H, J = 6.5 Hz), 7.69 (td, 1H, J = 7.7, 1.6 Hz), 7.83
2-(Benzofuran-2’-yl)-3-ethylquinoline (2c-J): Yield: 542.0 mg (d, 1H, J = 8.2 Hz), 8.09 (d, 1H, J = 8.4 Hz), 8.13 (s, 1H); 13C-NMR
(66%); yellow solid; mp: 92-93 °C; IR (neat): 3124, 3063, 2964, (100 MHz, CDCl3): δ = 24.1, 29.2, 122.3, 126.5, 127.1, 127.8, 129.0,
1
1594, 1543 cm-1; H-NMR (400 MHz, CDCl3): δ = 1.39 (t, 3H, J = 129.2, 130.5, 131.4, 133.0, 139.8, 140.1, 146.1, 159.0; HRMS (ESI):
7.5 Hz), 3.21 (q, 2H, J = 7.5 Hz), 7.28 (td, 1H, J = 7.6, 0.9 Hz), 7.36 Calcd for C18H17NBr [M+H]+ = 326.0539, Found = 326.0534.
(t, 1H, J = 7.7 Hz), 7.45 (s, 1H), 7.53 (td, 1H, J = 7.6, 1.1 Hz), 7.62
3-Isopropyl-2-(naphthalene-2’-yl)quinoline (2d-I): Yield: 506.8
(dd, 1H, J = 8.2, 0.7 Hz), 7.67-7.71 (m, 2H), 7.79 (d, 1H, J = 8.2
Hz), 8.08 (s, 1H), 8.16 (d, 1H, J = 8.6 Hz); 13C-NMR (100 MHz,
CDCl3): δ = 14.7, 26.4, 108.2, 111.7, 121.6, 123.1, 125.1, 126.9
(2C), 127.8, 128.4, 129.1, 129.3, 135.3, 135.9, 146.4, 148.9, 155.2,
155.5; HRMS (ESI): Calcd for C19H16ON [M+H]+ = 274.1226,
Found = 274.1224.
1
mg (57%); yellow oil; IR (neat): 3055, 2961, 1596, 1556 cm-1; H-
NMR (400 MHz, CDCl3): δ = 1.26 (d, 6H, J = 7.0 Hz), 3.32 (sep,
1H, J = 7.0 Hz), 7.52-7.57 (m, 3H), 7.64 (dd, 1H, J = 8.4, 1.8 Hz),
7.69 (td, 1H, J = 7.7, 1.5 Hz), 7.86 (d, 1H, J = 8.2 Hz), 7.91-7.93 (m,
2H), 7.96 (d, 1H, J = 8.6 Hz), 8.01 (s, 1H), 8.14 (d, 1H, J = 8.4 Hz),
8.17 (s, 1H); 13C-NMR (100 MHz, CDCl3): δ = 24.1, 29.3, 126.2,
3-Isopropyl-2-phenylquinoline (2d-A): Yield: 410.3 mg (55%); 126.4, 126.7 (2C), 127.1, 127.7, 127.9 (2C), 128.3, 128.9, 129.2,
white solid; mp: 69-70 °C; IR (neat): 3046, 2960, 1596, 1558 cm-1; 132.8, 132.9, 133.2 (2C), 138.4, 140.5, 146.2, 160.3; HRMS (ESI):
1H-NMR (400 MHz, CDCl3): δ = 1.25 (d, 6H, J = 6.7 Hz), 3.25 (sep, Calcd for C22H20N [M+H]+ = 298.1590, Found = 298.1588.
1H, J = 6.7 Hz), 7.44-7.55 (m, 6H), 7.67 (td, 1H, J = 7.6, 1.4 Hz),
7.83 (d, 1H, J = 8.1 Hz), 8.11 (d, 1H, J = 8.1 Hz), 8.13, (s, 1H); 13C-
NMR (100 MHz, CDCl3): δ = 24.1, 29.2, 126.3, 127.0, 127.8, 127.9,
128.2, 128.7, 128.8, 129.2, 132.7, 140.3, 140.9, 146.1, 160.4; HRMS
(ESI): Calcd for C18H18N [M+H]+ = 248.1434, Found = 248.1430.
3-Benzyl-2-phenylquinoline (2e-A): Yield: 551.2 mg (62%); white
1
solid; mp: 93-94 °C; IR (neat): 2990, 1596, 1553 cm-1; H-NMR
(400 MHz, CDCl3): δ = 4.13 (s, 2H), 7.00 (d, 2H, J = 6.8 Hz), 7.17-
7.24 (m, 3H), 7.41-7.54 (m, 6H), 7.68 (td, 1H, J = 7.6 Hz), 7.76 (d,
1H, J = 8.2 Hz), 7.93 (s, 1H), 8.14 (d, 1H, J = 8.4 Hz); 13C-NMR
3-Isopropyl-2-(3’-methylphenyl)quinoline (2d-C): Yield: 580.2 (100 MHz, CDCl3): δ = 39.1, 126.2, 126.5, 127.1, 127.5, 128.1,
mg (74%); white solid; mp: 88-90 °C; IR (neat): 2957, 1591, 1558 128.3, 128.5, 128.8, 129.0, 129.1, 129.3, 132.5, 137.0, 140.0, 140.6,
1
cm-1; H-NMR (400 MHz, CDCl3): δ = 1.25 (d, 6H, J = 6.8 Hz), 146.6, 160.7; HRMS (ESI): Calcd for C22H18N [M+H]+ = 296.1434,
2.44 (s, 3H), 3.24 (sep, 1H, J = 6.8 Hz), 7.24-7.38 (m, 4H), 7.52 (td, Found = 296.1431.
1H, J = 7.5, 1.1 Hz), 7.66 (td, 1H, J = 7.7, 1.4 Hz), 7.82 (d, 1H, J =
8.2 Hz), 8.11 (d, 1H, J = 4.1 Hz), 8.13 (s, 1H); 13C-NMR (100 MHz,
CDCl3): δ = 21.5, 24.1, 29.2, 125.7, 126.2, 127.0, 127.7, 128.0,
128.7 (2C), 129.2, 129.4, 132.6, 137.9, 140.4, 140.9, 146.1, 160.6;
HRMS (ESI): Calcd for C19H20N [M+H]+ = 262.1590, Found =
262.1586.
3-Benzyl-2-(2’-methylphenyl)quinoline (2e-B): Yield: 677.6 mg
(73%); yellow oil; mp: 147-148 °C; IR (neat): 3027, 2950, 1596,
1
1562 cm-1; H-NMR (400 MHz, CDCl3): δ = 1.94 (s, 3H), 3.91 (s,
2H), 6.89-6.92 (m, 2H), 7.14-7.25 (m, 6H), 7.32 (t, 1H, J = 7.0 Hz)
7.53 (td, 1H, J = 7.6, 1.1 Hz), 7.68 (td, 1H, J = 7.7, 1.4 Hz), 7.78 (d,
1H, J = 8.2 Hz) 7.95 (s, 1H), 8.12 (d, 1H, J = 8.4 Hz); 13C-NMR
3-Isopropyl-2-(4’-methylphenyl)quinoline (2d-D): Yield: 440.7 (100 MHz, CDCl3): δ = 19.3, 39.0, 125.7, 126.2, 126.4, 127.1, 127.5,
mg (56%); white solid; mp: 80 °C; IR (neat): 2954, 1596, 1553 cm-1; 128.2, 128.3, 128.4, 129.0, 129.1, 129.2, 130.3, 133.3, 135.8, 136.2,
1H-NMR (400 MHz, CDCl3): δ = 1.25 (d, 6H, J = 6.8 Hz), 2.44 (s, 139.2, 139.8, 146.5, 161.2; HRMS (ESI): Calcd for C23H20N [M+H]+
3H), 3.28 (sep, 1H, J = 6.8 Hz), 7.29 (d, 2H, J = 7.9 Hz), 7.42 (d, = 310.1590, Found = 310.1588.
2H, J = 7.9 Hz), 7.52 (td, 1H, J = 7.6, 1.1 Hz), 7.65 (td, 1H, J = 7.7,
3-Benzyl-2-(3’-methylphenyl)quinoline (2e-C): Yield: 716.7 mg
(77%); white solid; mp: 87-88 °C; IR (neat):2983, 1594, 1555 cm-1;
1H-NMR (400 MHz, CDCl3): δ = 2.37 (s, 3H), 4.11 (s, 2H), 7.00-
7.02 (m, 2H), 7.17-7.257 (m, 6H), 7.30 (t, 1H, J = 7.5 Hz) 7.51 (td,
1H, J = 7.6, 1.3 Hz), 7.67 (td, 1H, J = 7.7, 1.4 Hz), 7.75 (d, 1H, J =
8.2 Hz) 7.91 (s, 1H), 8.14 (d, 1H, J = 8.6 Hz); 13C-NMR (100 MHz,
1.4 Hz), 7.82 (d, 1H, J = 7.0 Hz), 8.10 (d, 1H, J = 7.0 Hz), 8.12 (s,
1H); 13C-NMR (100 MHz, CDCl3): δ = 21.3, 24.1, 29.2, 126.1,
127.0, 127.7, 128.6, 128.7, 128.9, 129.2, 132.6, 137.7, 138.0, 140.4,
146.1, 160.4; HRMS (ESI): Calcd for C19H20N [M+H]+ = 262.1590,
Found = 262.1587.
3-Isopropyl-2-(4’-chlorophenyl)quinoline (2d-F): Yield: 501.3 mg CDCl3): δ = 21.4, 39.1, 125.7, 126.2, 126.4, 127.1, 127.4, 128.0,
(59%); white solid; mp: 94 °C; IR (neat): 2954, 1598, 1555 cm-1; 1H- 128.4, 128.9, 129.0 (2C), 129.2, 129.5, 132.5, 136.8, 137.9, 140.0
NMR (400 MHz, CDCl3): δ = 1.25 (d, 6H, J = 7.0 Hz), 3.21 (sep, (2C), 146.5, 160.9; HRMS (ESI): Calcd for C23H20N [M+H]+ =
1H, J = 6.8 Hz), 7.47-7.48 (m, 4H), 7.54 (t, 1H, J = 6.8 Hz), 7.68 (td, 310.1590, Found = 310.1587.
8 | J. Name., 2012, 00, 1-3
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Organic & Biomolecular Chemistry
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Journal Name
ARTICLE
3-Benzyl-2-(4’-methylphenyl)quinoline (2e-D): Yield: 680.4 mg (m, 3H), 7.98 (s, 1H), 8.16 (d, 1H, J = 8.4 Hz); 13C-NMR (100 MHz,
View Article Online
DOI: 10.1039/C9OB00944B
1
(74%); yellow oil; IR (neat): 3026, 1594, 1558 cm-1; H-NMR (400 CDCl3): δ = 39.4, 126.4, 126.5, 126.6, 126.7, 126.9, 127.4, 127.7,
MHz, CDCl3): δ = 2.42 (s, 3H), 4.14 (s, 2H), 7.03 (d, 2H, J = 7.0 127.9, 128.2, 128.5, 128.6, 128.7, 129.2, 129.4, 129.5, 132.8, 133.2,
Hz), 7.18-7.28 (m, 5H), 7.40 (d, 2H, J = 8.1 Hz), 7.50 (t, 1H, J = 7.0 133.3, 137.4, 138.2, 140.2, 146.9, 160.8; HRMS (ESI): Calcd for
Hz), 7.67 (td, 1H, J = 7.6, 1.4 Hz), 7.73 (d, 1H, J = 8.1 Hz) 7.89 (s, C26H20N [M+H]+ = 346.1590, Found = 346.1588.
1H), 8.13 (d, 1H, J = 8.5 Hz); 13C-NMR (100 MHz, CDCl3): δ =
2-(Benzofuran-2’-yl)-3-benzylquinoline (2e-J): Yield: 704.4 mg
21.3, 39.0, 126.2, 126.3, 127.0, 127.4, 128.5, 128.8 (2C), 128.9,
129.0, 129.2, 132.5, 136.9, 137.7, 137.9, 140.1, 146.6, 160.7; HRMS
(ESI): Calcd for C23H20N [M+H]+ = 310.1590, Found = 310.1588.
(70%); white solid; mp: 135 °C; IR (neat): 3136, 3019, 1590, 1556
1
cm-1; H-NMR (400 MHz, CDCl3): δ = 4.57 (s, 2H), 7.19-7.25 (m,
3H), 7.27-7.30 (m, 3H), 7.36 (td, 1H, J = 8.4, 1.4 Hz), 7.39 (s, 1H),
3-Benzyl-2-(4’-methoxyphenyl)quinoline (2e-E): Yield: 645.3 mg 7.52 (t, 1H, J = 7.0 Hz), 7.59 (d, 1H, J = 8.2 Hz), 7.67 (d, 1H, J = 7.7
(66%); white solid; mp: 107-108 °C; IR (neat): 2987, 1606, 1486, Hz), 7.69-7.73 (m, 2H), 7.90 (s, 1H), 8.18 (dd, 1H, J = 8.4, 0.9 Hz);
1
1028 cm-1; H-NMR (400 MHz, CDCl3): δ = 3.86 (s, 3H), 4.16 (s, 13C-NMR (100 MHz, CDCl3): δ = 39.1, 108.4, 111.6, 121.6, 123.1,
2H), 6.97 (dd, 2H, J = 6.7, 2.2 Hz), 7.03 (d, 2H, J = 6.8 Hz), 7.18- 125.1, 126.3, 126.9, 127.0, 127.5, 128.3, 128.6, 129.0, 129.3, 129.4,
7.27 (m, 3H), 7.45 (dd, 2H, J = 6.7, 2.3 Hz), 7.49 (td, 1H, J = 7.6, 129.5, 132.1 138.0 (2C), 139.6, 146.6, 155.1; HRMS (ESI): Calcd
1.1 Hz), 7.67 (td, 1H, J = 7.7, 1.4 Hz), 7.73 (d, 1H, J = 8.2 Hz), 7.90 for C24H18ON [M+H]+ = 336.1383, Found = 336.1379.
(s, 1H), 8.12 (d, 1H, J = 8.4 Hz); 13C-NMR (100 MHz, CDCl3): δ =
3,5-Dimethyl-2-phenylquinoline (2f-A): Yield: 324.8 mg (46%);
39.1, 55.3, 113.7, 126.2 (2C), 127.0, 127.3, 128.4, 128.9, 129.0,
129.2, 130.2, 132.5, 133.1, 137.0, 140.1, 146.6, 159.6, 160.7; HRMS
(ESI): Calcd for C23H20ON [M+H]+ =326.1539, Found = 326.1535.
1
white solid; yellow oil; IR (neat): 2919, 1598, 1569 cm-1; H-NMR
(400 MHz, CDCl3): δ = 2.51 (s, 3H), 2.81 (s, 3H), 7.38-7.52 (m,
5H), 7.61 (d, 1H, J = 7.9 Hz), 7.68-7.71 (m, 2H), 7.98 (s, 1H); 13C-
3-Benzyl-2-(4’-chlorophenyl)quinoline (2e-F): Yield: 653.1 mg NMR (100 MHz, CDCl3): δ = 17.9, 20.7, 124.6, 126.0, 127.3, 128.0
(66%); white solid; mp: 89-91 °C; IR (neat): 3021, 1597, 1555 cm-1; (2C), 128.5, 128.6, 129.3, 137.0, 137.2, 141.2, 145.7, 158.6; HRMS
1H-NMR (400 MHz, CDCl3): δ = 4.12 (s, 2H), 6.99 (d, 2H, J = 6.6 (ESI): Calcd for C17H16N [M+H]+ = 234.1277, Found = 234.1275.
Hz), 7.20-7.27 (m, 3H), 7.40-7.41 (m, 4H), 7.54 (td, 1H, J = 7.6, 1.1
3,7-Dimethyl-2-phenylquinoline (2g-A): Yield: 476.7 mg (68%);
Hz), 7.70 (td, 1H, J = 7.7, 1.4 Hz), 7.77 (d, 1H, J = 8.2 Hz) 7.96 (s,
1H), 8.12 (d, 1H, J = 8.4 Hz); 13C-NMR (100 MHz, CDCl3): δ =
39.0, 126.3, 126.7, 127.1, 127.5, 128.4, 128.5, 128.8, 129.2, 129.3,
130.2, 132.1, 134.3, 137.3, 139.0, 139.6, 146.6, 159.4; HRMS (ESI):
Calcd for C22H17NCl [M+H]+ = 330.1044, Found = 330.1042.
1
yellow oil; IR (neat): 3024, 2952, 1600, 1560 cm-1; H-NMR (400
MHz, CDCl3): δ = 2.45 (s, 3H), 2.54 (s, 3H), 7.40-7.51 (m, 4H), 7.54
(s, 1H), 7.59 (d, 2H, J = 6.7 Hz), 7.93 (s, 1H), 8.01 (d, 1H, J = 8.8
Hz); 13C-NMR (100 MHz, CDCl3): δ = 20.6, 21.6, 125.5, 127.5,
128.0, 128.2, 128.8, 128.9, 129.0, 131.0, 136.0, 136.1, 140.9, 145.1,
3-Benzyl-2-(4’-bromophenyl)quinoline (2e-G): Yield: 688.3 mg 159.5; HRMS (ESI): Calcd for C17H16N [M+H]+ = 234.1277, Found
(61%); white solid; mp: 103-104 °C; IR (neat): 3028, 1597, 1551 = 234.1273.
cm-1; 1H-NMR (400 MHz, CDCl3): δ = 4.12 (s, 2H), 6.99 (d, 2H, J =
7-Chloro-3-methyl-2-phenylquinoline (2h-A): Yield: 474.2 mg
6.6 Hz), 7.18-7.27 (m, 3H), 7.35 (d, 2H, J = 8.6 Hz), 7.51-7.58 (m,
3H), 7.70 (td, 1H, J = 7.7, 1.4 Hz), 7.77 (d, 1H, J = 8.2 Hz) 7.95 (s,
1H), 8.12 (d, 1H, J = 8.8 Hz); 13C-NMR (100 MHz, CDCl3): δ =
39.0, 122.6, 126.3, 126.7, 127.1, 127.5, 128.5, 128.8, 129.2, 129.3,
130.5, 131.4, 132.1, 137.3, 139.5, 139.6, 146.6, 159.4; HRMS (ESI):
Calcd for C22H17NBr [M+H]+ = 374.0539, Found = 374.0537.
1
(62%); yellow oil; IR (neat): 2985, 1592, 1553 cm-1; H-NMR (400
MHz, CDCl3): δ = 2.47 (s, 3H), 7.43-7.52 (m, 3H), 7.57-7.61 (m,
3H), 7.76 (s, 1H), 7.94 (s, 1H), 8.05 (d, 1H, J = 9.1 Hz); 13C-NMR
(100 MHz, CDCl3): δ = 20.6, 125.3, 128.1, 128.3 (2C), 128.7, 129.6,
130.3, 130.9, 132.0, 135.7, 140.4, 144.9, 160.7; HRMS (ESI): Calcd
for C16H13NCl [M+H]+ = 254.0731, Found = 254.0727.
3-Benzyl-2-[4’-(trifluoromethyl)phenyl]quinoline (2e-H): Yield:
3,4-Dimethyl-2-phenylquinoline (2i-A): Yield: 280.7 mg (40%);
white solid; mp: 59-61 °C; IR (neat): 3060, 2988, 1575, 1494 cm-1;
1H-NMR (400 MHz, CDCl3): δ = 2.39 (s, 3H), 2.70 (s, 3H), 7.40-
7.50 (m, 3H), 7.53-7.57 (m, 3H), 7.65 (td, 1H, J = 7.7, 1.4 Hz), 8.04
(d, 1H, J = 8.4 Hz), 8.11 (d, 1H, J = 7.5 Hz); 13C-NMR (100 MHz,
CDCl3): δ = 14.7, 17.4, 123.2, 126.0, 126.9, 127.0, 127.8 (2C),
128.1, 128.8, 130.0, 141.7, 142.1, 145.8, 160.4; HRMS (ESI): Calcd
for C17H16ON [M+H]+ = 234.1277, Found = 234.1276.
707.5 mg (65%); white solid; mp: 105-106 °C; IR (neat): 3028,
1
2954, 1598, 1553 cm-1; H-NMR (400 MHz, CDCl3): δ = 4.11 (s,
2H), 6.97 (d, 2H, J = 6.6 Hz), 7.19-7.24 (m, 3H), 7.54-7.58 (m, 3H),
7.69 (d, 2H, J = 8.2 Hz), 7.72 (t, 1H, J = 7.6 Hz), 7.80 (d, 1H, J = 8.2
Hz), 7.99 (s, 1H), 8.13 (d, 1H, J = 8.2 Hz); 13C-NMR (100 MHz,
CDCl3): δ = 39.0, 124.1 (q, JC-F = 272.5 Hz), 125.2 (d, JC-F = 3.8
Hz), 126.4, 126.9, 127.1, 127.6, 128.5, 128.8, 129.2 (2C), 129.4,
130.2 (q, JC-F = 32.5 Hz), 132.0, 137.4, 139.5, 144.1, 146.6, 159.2;
HRMS (ESI): Calcd for C23H17NF3 [M+H]+ = 364.1308, Found =
364.1305.
3-(4’-Chlorobenzyl)-7-methyl-2-phenylquinoline (2j-A): Yield:
161.6 mg (47%); white solid; mp: 95-98 °C; NOE (3.9%) between H
atom at 8-position and CH3 group at 7-position in quinoline core was
3-Benzyl-2-(naphthalene-2’-yl)quinoline (2e-I): Yield: 724.4 mg
(70%); white solid; mp: 118 °C; IR (neat): 3048, 3019, 1594, 1551
cm-1; 1H-NMR (400 MHz, CDCl3): δ = 4.18 (s, 2H), 7.02 (d, 2H, J =
6.6 Hz), 7.19-7.24 (m, 3H), 7.49-7.56 (m, 3H), 7.63 (dd, 1H, J = 8.3,
1.6 Hz), 7.70 (td, 1H, J = 7.7, 1.4 Hz), 7.78-7.83 (m, 2H), 7.88-7.94
1
observed. IR (neat): 3026, 2968, 1596, 1558 cm-1; H-NMR (400
MHz, CDCl3): δ = 2.54 (s, 3H), 4.08 (s, 2H), 6.89 (d, 2H, J = 8.3
Hz), 7.19 (d, 2H, J = 8.3 Hz), 7.42-7.45 (m, 5H), 7.52-7.54 (m, 2H)
7.81 (s, 1H), 8.02 (d, 1H, J = 8.2 Hz); 13C-NMR (100 MHz, CDCl3):
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 9
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Organic & Biomolecular Chemistry
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ARTICLE
Journal Name
(k) Y. Wang, C. Chen, J. Peng, and M. Li, Angew. Chem. Int.
δ = 21.6, 38.5, 125.9, 127.4, 128.1, 128.3, 128.5, 128.8, 128.9,
130.2, 131.6, 131.8, 132.0, 136.3, 136.5, 138.5, 140.5, 145.3, 159.6;
HRMS (ESI): Calcd for C23H19N [M+H]+ = 344.1201, Found =
344.1197.
View Article Online
Ed. 2013, 52, 5323-5327.
DOI: 10.1039/C9OB00944B
(3) Without transition metals: (a) Y. Zhang, W. Chen, X. Jia, L.
Wang, and P. Li, Chem. Commun. 2019, 55, 2785-2788. (b) Z.
Fan, S. Yang, X. Peng, C. Zhang, J. Han, J. Chen, H. Deng, M.
Shao, H. Zhang, and W. Cao, Tetrahedron 2019, 75, 868-873.
(c) O. Khaikate, J. Meesin, M. Pohmakotr, V. Reutrakul, P.
Leowanawat, D. Soorukram, and C. Kuhakarn, Org. Biomol.
Chem. 2018, 16, 8553-8558. (d) X. Geng, X. Wu, P. Zhao, J.
Zhang, Y. Wu, and A. Wu, Org. Lett. 2017, 19, 4179-4182. (e)
P. Zhao, X. Yan, H. Yin, and C. Xi, Org. Lett. 2014, 16, 1120-
1123. (f) T. Mitamura, K. Iwata, and A. Ogawa, Org. Lett.
2009, 11, 3422-3424.
(4) Reviews: (a) L. Tumir, M. R. Stojkovic, and M. I.
Piantanida, Beilstein J. Org. Chem. 2014, 10, 2930-2954. (b)
B. Zhang and A. Studer, Chem. Soc. Rev. 2015, 44, 3505-
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Spagnolo, Curr. Org. Chem. 2007, 11, 1366-1384.
7-Chloro-3-(4’-methylbenzyl)-2-phenylquinoline (2j’-A): Yield:
45.6mg (13%); white solid; mp: 135 °C; IR (neat): 3048, 3019,
1594, 1509 cm-1; 1H-NMR (400 MHz, CDCl3): δ = 2.32 (s, 3H), 4.08
(s, 2H), 6.89 (d, 2H, J = 7.9 Hz), 7.06 (d, 2H, J = 7.9 Hz), 7.44-7.51
(m, 5H), 7.60 (dd, 1H, J = 9.1, 2.1 Hz), 7.73 (s, 1H), 7.80 (s, 1H),
8.06 (d, 1H, J = 8.8 Hz); 13C-NMR (100 MHz, CDCl3): δ = 21.0,
38.6, 125.7, 128.1, 128.4, 128.8, 128.9, 129.3, 130.0, 130.9, 132.1,
133.9, 135.9 (2C), 136.0, 136.4, 140.2, 144.9, 160.9; HRMS (ESI):
Calcd for C23H19N [M+H]+ = 344.1201, Found = 344.1196.
ORCID
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Hideo Togo: 0000-0002-3633-7292
Supporting Information
1H-NMR and 13C-NMR charts of all quinolone derivatives 2.
Acknowledgements
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Biomol. Chem. 2018, 16, 414-423. (b) Y. Yu, Z. Cai, W.
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Financial support in the form of a Grant-in–Aid for Scientific
Research (No. 18K05118) from the Ministry of Education,
Culture, Sports, Science, and Technology in Japan is gratefully
acknowledged.
Notes and references
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10 | J. Name., 2012, 00, 1-3
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Organic & Biomolecular Chemistry
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DOI: 10.1039/C9OB00944B
Table of contents
1) OB-ART-04-2019-000944.text.pdf: Manuscript
2) OB-ART-04-2019-000944CorrespondingLetter.docx:
Corresponding Letter
3) OB-ART-04-2019-000944SI.pdf:
Supporting information
1H-NMR and 13C-NMR charts of all quinoline derivatives
4) OB-ART-04-2019-000944.GA: Graphic Abstract
5) Table of Content Entry