Metal-Free Synthesis of 2-Substituted 3-(2-Hydroxyaryl)quinolines and 4-(2-Hydroxyaryl)acridines via Benzyne Chemistry

Article abstract of DOI:10.1021/acs.joc.7b02149

A metal-free approach for the synthesis of 3-aryl-2-substituted quinolines and 4-arylacridines has been developed via the 1,3-dipolar cycloaddition reactions of arynes with N-oxides. Reactions of various 2-substitued quinoline N-oxides with ortho-(trimethylsilyl)aryltriflates in the presence of KF gave 3-(2-hydroxyaryl)quinoline derivatives in good yields. Acridine N-oxides also reacted with arynes to furnish 4-(2-hydroxyaryl)acridines, albeit in moderate yields.

Full text of DOI:10.1021/acs.joc.7b02149

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Article
Metal-free synthesis of 2-substituted-3-(2-hydroxyaryl)quinolines
and 4-(2-hydroxyaryl)acridines via benzyne chemistry
Ankit Kumar Dhiman, Rakesh Kumar, Rakesh Kumar, and Upendra Sharma
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b02149 • Publication Date (Web): 07 Nov 2017
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The Journal of Organic Chemistry
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Metal-free synthesis of 2-substituted-3-(2-hydroxyaryl)quinolines and 4-
(2-hydroxyaryl)acridines via benzyne chemistry
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Ankit Kumar Dhiman,† Rakesh Kumar,†,‡ Rakesh Kumar,*,†,§ and Upendra Sharma*,†,‡
†Natural Product Chemistry and Process Development Division, CSIR-IHBT, Palampur, India
‡Academy of Scientific and Innovative Research, CSIR-IHBT, Palampur, India
TOC graphic
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ABSTRACT: A metal-free approach for the synthesis of 3-aryl-2-substituted quinolines and 4-
arylacridines has been developed via the 1,3-dipolar cycloaddition reactions of arynes with N-oxides.
Reactions of various 2-substitued quinoline N-oxides with ortho-(trimethylsilyl)aryltriflates in the pres-
ence of KF gave 3-(2-hydroxyaryl)quinoline derivatives in good yields. Acridine N-oxides also reacted
with arynes to furnish 4-(2-hydroxyaryl)acridines, albeit in moderate yields.
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1. INTRODUCTION
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Quinoline being important heterocycle is commonly encountered in several natural products,1 pharma-
ceutical agents2 and advanced functional materials.3 In pharmaceuticals, the substituted quinolines are
known to display a broad spectrum of biological activities.2,4 The remarkable antimalarial potential of
quinolines has been well recognized for centuries5 and these remain to be major targets as antimalarial
drugs in the prevailing situation of drug resistance.6
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Among various substituted quinolines, 2-substituted-3-arylquinolines are of significant biological im-
portance with antiproliferative,7 antibacterial,8 and antitumor activity9 and also act as selective cycloox-
ygenase-2 (COX-2),10 and PI3Kδ inhibitors (Figure 1).11 These compounds are also important materials
in molecular electronics e.g. iridium complex of 2,3-diphenylquinoline (Figure 1) is an efficient red
light emitting diode.12
H
CO2
N
H
CO2
N
Me
N
O
Me
R
N
Me
SO2
Antibacterial
MeHN
Selective COX-2 inhibitor
Antiproliferative
O
N
F
R
OR'
N
Me
N
N
N
2
N
NH
NC
Selective PI3Kd inhibitor
N
O
Ir
Me
O
NH2
NMe
Me
emitting diode
Antitumor
Red
light
Figure 1. Selected examples of important 2-substituted 3-arylquinolines
Arynes are versatile intermediates used in organic synthesis to access diverse building blocks13 as well
as natural products.14 Among the various reactions of arynes, 1,3-dipolar cycloadditions are of particular
interest and have been explored for a large variety of organic transformations.13,14
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Reactions of arynes with pyridine N-oxide have been reported to produce 2- and 3-(2-hydroxyaryl) pyr-
idines.15-17 The regioselectivity of reactions depended upon the reaction conditions as well as the aryne
source.15-17 In case of ortho-(trimethylsilyl)aryl triflates as the aryne sources, the product formation de-
pended upon the fluoride source and reaction solvent.16,17 Use of CsF in acetonitrile produced 3-(2-
hydroxyaryl)pyridines16 whereas, Bu4NF in CH2Cl2 afforded 2-(2-hydroxyaryl)pyridines (Scheme 1).17
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Scheme 1. Reactions of pyridine N-oxide with arynes
TMS
TBAF
N
CsF
+
OH
CH2Cl2
CH3CN
N
O
N
HO
OTf
17
Ref.
16
Ref.
We envisioned that cycloaddition reactions of arynes with 2-substituted quinolines which are rarely ex-
plored till date,18 would furnish the corresponding 2-substituted-3-(2-hydroxyaryl)quinolines (Scheme
2). In an earlier report, no reaction was observed between benzyne and 2-substituted quinoline N-
oxides.18 Herein, we report the synthesis of 2-substituted-3-(2-hydroxyaryl)quinolines via 1,3-dipolar
cycloaddition reactions of quinoline N-oxides with arynes. Reaction of acridine N-oxides with arynes
for the synthesis of 4-(2-hydroxyaryl)acridines are also explored.
Scheme 2. Reactions of quinoline N-oxide with arynes
KF
18-crown-6
CsF
N
N
N
O
R
+
OH
CH3CN
°
CH3CN
r.t.
N
R
HO
60 C
O
+
18
=
aryl,
Ref.
R
alkyl
aryne
precursor
=
mixture when R
H
R
work
This
= aryl
reaction
No
when
2. RESULTS AND DISCUSSIONS
For the optimization of best reaction conditions 2-phenylquinoline N-oxide (1a) was treated with
o-(trimethylsilyl)phenyltriflate (2a) in presence of fluoride source for 12 h (Table 1). Reactions using
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tetrabutylammonium fluoride (TBAF) in THF provided 77% isolated yield of
2-phenyl-3-(2-hydroxyphenyl)quinoline (3a) (entry 1). Minor side-product (4a), formed by reaction of
3a with excess benzyne was also observed. Use of THF-DCM mixture lowered the product yield to 61%
with a trace amount of 4a (entry 2). Use of CsF in THF failed to provide even traces of products (entry
3). However, switching the solvent to CH3CN resulted in 71% yield of the desired product along with
traces of 4a (entry 4). KF as F− source in CH3CN was unsuccessful (entry 5), however, to our delight,
2.0 equiv. of 18-crown-6 with KF as F− source in CH3CN afforded exclusively the desired product 3a in
84% yield (entry 6). Further, when reaction was carried out under reported conditions, lower yield of the
desired product was observed (entry 6 and 7).18
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Table 1. Optimization of reaction conditions
O
H
O
Ph
TMS
− source,
F
additive
rt, 12 h
solvent,
N
O
0.10
Ph
OTf
N
Ph
N
Ph
mmol
4a
mmol
2a,
3a, isolated
yields
0.15
1a,
entry
F− sourcea
nBu4NFb
nBu4NFb
CsF
additivec
solventd
conversion (%) yieldf (%)
3a:4ag
97:3
1
2
---
---
---
---
---
THF
>99
>99
0
77
61
DCM−THFe
THF
99:1
3
NA
NA
4
CsF
CH3CN
CH3CN
>99
0
71
98:2
5
KF
NA
84
NA
6
KF
18-crown-6 CH3CN
>99
>99
>99
100:0
75:25
18:82
7h
8i
CsF
CsF
---
---
CH3CN
CH3CN
45%
11%
a0.2 mmol (2.0 equiv). b1.0 M solution in THF. c0.20 mmol (2.0 equiv). d1.3 mL of solvent. eDCM-THF ratio 4:1. fyield of isolated prod-
uct. gcalculated from 1H NMR of crude reaction mixture. hreaction time 16h. iat 60 oC for 7h.
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With optimal reaction conditions in hand, the scope of reactions of substituted quinoline N-oxides with
arynes was studied (Table 2). First, 2-aryl quinoline N-oxides with a variety of aryl substituents were
reacted with 2a. Quinoline N-oxides with aryl group bearing para-electron donating -OMe as well as
electron withdrawing -NO2 provided moderate yields of the desired 3-arylated quinolines 3b and 3c,
respectively. Formation of minor products 4b (10%) and 4c (9%), was also observed. 2-Aryl quinoline
N-oxides with p-SCF3 and p-Br substituents also reacted successfully to give 70% and 65% yield of
products 3d and 3e, respectively. Presence of Br at meta- as well as sterically hindered ortho-positions
did not affect the reaction outcome and provided products 3f and 3g in 60% and 71% yields, respective-
ly. Formation of the minor product 4f was also observed in 8% yield in case of reaction with 1f. Steri-
cally challenging ortho-substituted 2-phenyl quinoline N-oxides (1h and 1i) afforded the desired prod-
ucts 3h and 3i in good yields. Further, 2-phenylquinoline N-oxides with various substituents in the
quinoline ring were reacted with benzyne precursor 2a. The methyl substitution on C-4 position provid-
ed good yield of the product 3j, however in the case of -NO2 group a lower yield of the desired product
3k was observed, possibly due to the poor solubility of the starting material. Various substituents at C-6
position of quinoline were also well tolerated providing the desired products in 45-73 % yields (3l-o). In
the case of C-7 derived quinoline, 4-chloro-7-trifluoromethylquinoline N-oxide, low yield of the desired
product (3p) was obtained. A sterically congested, 2-phenyl-8-methylquinoline-N-oxide, also reacted
efficiently to provide 3q in 48% yield along with a significant amount (18 %) of the side product (4q).
Similarly, heteroaryl substituents, benzothiazole, 2-bromopyridine and morpholine at C-2 position of
quinoline moiety were also compatible and furnished product (3r-t) in milder to good yields. The de-
sired products were also observed in case of benzo[f]quinoline (3u) albeit in low yield.
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Formation of side products 4b, 4c, 4f and 4q arouse our interest in the synthesis of such compounds,
selectively. In a model reaction, treatment of 2-phenylquinoline N-oxide (1a) with 4.0 equiv. of benzyne
precursor 2a and 5.0 equiv. of each KF and 18-crown-6 yielded 60% of product 4a along with formation
of only 20% of 3a.
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Table 2. Reactions of 2-arylquinolines with arynea
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7
8
O
H
O
KF
Ph
N
equiv)
(2.0
4
5
18-crown-6
TMS
OTf
6
R
7
equiv)
(2.0
CH3CN,
2-12 h
+
R
R
rt,
Ar
N
O
Ar
N
Ar
8
1
2a
3 isolated
4
isolated
,
,
yields
yields
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yield (%)
entry
1
1
Ar
R
H
H
H
H
H
H
H
H
H
time (h)
12h
1h
3
4
1a
1b
1c
1d
1e
1f
C6H5
3a, 84
3b, 50
3c, 65
3d, 70
3e, 65
3f, 60
3g, 71
3h, 70
3i, 56
3j, 74
3k, 12
3l, 73
3m, 51
3n, 72
3o, 45
3p, 20
3q, 48
3r, 73
-
2
p-OMeC6H5
p-NO2C6H5
p-SCF3C6H5
p-BrC6H5
m-BrC6H5
o-BrC6H5
o-MeC6H5
o-PhC6H5
C6H5
4b, 10
3
3h
4c, 9
4
2h
-
5
2h
-
6
2h
4f, 8
7
1g
1h
1i
3h
-
8
6h
-
9
3h
-
10
11
12
13
14
15
16
17
18
1j
4-Me
2h
-
1k
1l
C6H5
4-NO2
6-Me
4h
-
C6H5
3h
-
1m
1n
1o
1p
1q
1r
C6H5
6-iPr
5h
-
C6H5
6-F
3h
-
C6H5
6-CO2Me
4-Cl, 7-CF3
8-Me
5h
-
C6H5
3h
-
C6H5
3h
4q, 18
S
N
H
3h
-
Br
19
20
1s
1t
H
H
6h
3h
3s, 45
3t, 49
-
-
N
O
N
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21
1u
p-OMeC6H5
12h
3u, 45
-
1
2
5,6 =
3
4
aReagents and conditions: 1a (0.1−0.5 mmol), 2a (1.5 equiv), KF (2.0 equiv), 18-crown-6 (2.0 equiv).
5
6
7
8
9
Replacement of the aryl substituent by methyl, proved detrimental for the reactions leading to a signifi-
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cant decrease in the product yields (Scheme 3). Crude mixture of the reaction of 2-methylquinoline N-
1
oxide with 2a produced a complex H NMR which upon purification gave only 22% yield of the prod-
uct 3v. Similar results were obtained when the reaction was carried out under earlier reported reaction
conditions.18 Further methyl substitution at the C-4 and C-6 positions of the quinoline ring, significantly
improved the reaction outcome and resulted in 44% and 52% yields of the 2,4-dimethyl- and 2,6-
dimethyl-3-(2-hydroxyphenyl)quinolines, respectively (3w-x). Replacing 2-methyl with sterically chal-
lenging 2-iso-propyl (1y) and ethyl 2-hydroxypropanoate (1z), did not affect the outcome of the reaction
and provide desired products (3y-z) in acceptable yields (45-55%).
Scheme 3. Reactions of 2-methylquinoline N-oxides with arynea
H
O
4
KF
18-crown-6
equiv),
(2.0
(2.0
TMS
OTf
6
R
equiv)
R
2 h
CH CN
,rt,
3
N
O
alkyl
N
alkyl
=
=
3v
alkyl Me, R
22%
,
H,
1v-z
2a
=
=
3w
3x
alkyl Me, R 4-Me, 44%
,
=
=
alkyl Me, R 6-Me, 52%
,
,
i
=
=
H,
3y
3z
alkyl Pr, R
46%
=
=
H,
alkyl -CH
Et, R
2CH(OH)CO2
55%
,
aReagents and conditions: 1v-z (0.1-0.5 mmol), 2a (1.5 equiv), KF (2.0 equiv), 18-crown-6 (2.0 equiv).
The scope of reactions of 2-substituted quinoline N-oxides with different aryne precursors was next test-
ed (Scheme 4). 2-Phenylquinoline N-oxide (1a) was reacted with substituted arynes generated in situ
from the corresponding o-(trimethylsilyl)aryl triflates. Symmetrical, 4,5-dimethoxybenzyne precursor
(2b) gave 62% of the product 3za. Reaction of 3-methoxy benzyne derivative (2c) also afforded good
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yield of 3zb as a single isomer. Formation of a single regioisomer in the reactions of 3-methoxy ben-
zyne follows a general trend19 and has also been reported in reactions with pyridine N-oxide.16
1
2
3
4
5
6
7
8
9
Scheme 4. Scope of reactions of 2-phenylquinoline N-oxide with substituted arynesa
H
O
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5
R'
4
TMS
OTf
KF
18-crown-6
(2.0
equiv)
equiv),
(2.0
R'
3
CH CN
20
h
,rt,
3
N
Ph
N
O
Ph
=
=
3za
R'
R'
62%
,
77%b
,
=
=
2b,
4,5-di-OMe
R
R
4,5-di-OMe
3-OMe
1a
2c
,
3zb
3-OMe,
,
aReagents and conditions: 1a (0.1 mmol), 2 (1.5 equiv), KF (2.0 equiv), 18-crown-6 (2.0 equiv). bSingle isomer on the basis of 1H NMR of
crude mixture.
Further, when, 2-chloromethylquinoline N-oxide (5) was reacted with aryne precursor 2a using the
standard reaction conditions corresponding cyclic ether 6a was obtained as a single product in 25%
yield via the subsequent intramolecular SN2 reaction of the initially formed 2-chloromethyl-3-(2-
hydroxybenzene)quinoline intermediate (Scheme 5).
Scheme 5. Synthesis of a tetracyclic compound
TMS
KF
18-crown-6
(2.0
equiv)
equiv),
(2.0
12 h
CH CN
O
,rt,
3
N
O
N
OTf
equiv)
(1.5
Cl
6a
25%
,
5
Next, a one-pot protocol for the synthesis of 2-phenyl-3-(2-hydroxyphenyl)quinolines starting from
quinolines was explored. Quinoline N-oxide (7) was first reacted with commercially available aryl dia-
zonium tetrafluoroborates (1.5 equiv)20 in presence of KF (4.0 equiv) and 18-crown-6 (4.0 equiv) in
CH3CN for 30 minutes followed by the addition of benzyne precursor 2a (1.5 equiv) (Scheme 6). To our
delight, reaction worked well to furnish products 3b and 3c in 46% and 31% yields, respectively, start-
ing from 7. Although moderate yields of products were obtained, the one-pot strategy avoids an addi-
tional purification step and provides direct access to C-2, C-3 bis-functionalized quinolines.
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Scheme 6. One-pot synthesis of 2-aryl-3-(o-hydroxyaryl)quinolines
1
2
3
4
5
6
7
8
9
two step
One
pot
synthesis
H
O
Ar N2BF
KF
18-crown-6
equiv.)
equiv)
4 (1.5
(4.0
equiv)
min.
2a
(4.0
equiv)
(1.5
CH CN
30
rt, 5 h
,rt,
3
N
Ar
N
O
Ar
N
O
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=
=
3b
3c
Ar
R
4-OMePh,
46%
4-NO2Ph, 31%
,
,
7
Acridines constitute another important class of heterocycles that possess antimalarial activity,21 and are
commonly encountered in materials sciences and pharmaceuticals.22 We wondered whether acridine N-
oxides will undergo such reactions with arynes. To our surprise, when acridine N-oxide was reacted
with 2a, 4-(2-hydroxyphenyl)acridine (9a) was obtained in 53% yield (Table 3). The structure of 9a was
confirmed by NMR spectroscopy as well as X-ray crystallography. To test the generality of this reac-
tion, a series of substituted acridine N-oxides were reacted with arynes (Table 3). All substrate reacted
successfully and furnished 4-arylacridines 9a-g, albeit in low to moderate yields. To the best of our
knowledge, this is the first report for metal-free synthesis of C-4 aryl acridines using readily available
acridine N-oxides as starting materials.
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Table 3. Reactions of acridine N-oxides with arynes
1
2
3
4
5
6
7
8
9
R
R
8
KF
18-crown-6
1
equiv)
9
(2.0
TMS
OTf
equiv)
(2.0
R'
rt, 12h
CH3CN,
N
O
N
O
5
4
H
8
2
9
R'
isolated
yields
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
N
N
N
H
H
O
OMe
O
H
O
,
,
36%b
9b
9a
36%
Ph
9c
53%
,
OMe
OMe
OMe
Me
Cl
N
Ph
N
O
N
O
N
O
H
H
H
HO
OMe
,
9e
9d
33%
9f,
30%
39%
,
31%
9g,
aReagents and conditions: 8 (0.1-0.3 mmol), 2 (1.5 equiv), KF (2.0 equiv), 18-crown-6 (2.0 equiv). bSingle isomer on the basis of 1H NMR
of crude reaction mixture.
The reactions of pyridine-and quinoline N-oxides are proposed to proceed via pathway that involves the
formation of a five membered cycloadduct.15-18 In case of 2-substituted quinolines, the initially formed
cyclo-adduct (A) would rearrange to quinoid form (B). Intermediate B upon deprotonation by TfO- or
excess F− followed by cyclopropyl ring opening and re-aromatization would form 3-(2-
hydroxyaryl)quinolines (3) (Scheme 7). Reactions of acridine N-oxides with arynes are also proposed to
proceed through the formation of 5-membered cyclo-adduct A' (Scheme 7) via a [3+2] cycloaddition of
acridine N-oxide and aryne. Similar to the quinoline N-oxides, the rearrangement of cycloadduct A' to
intermediate B' followed by the deprotonation-re-aromatization would furnish 4-arylacridine product 9.
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Scheme 7. Proposed mechanism for the reactions of quinoline N-oxides and acridine N-oxides
with arynes
1
2
3
4
5
B
(OTf/F)
H
H
F
F
6
7
8
9
2a
3
9
R
N
R
N
N
R
O
A
O
R
O
B
≠
1
H
,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
H
2a
N
N
O
N
H
O
B
O
(OTf/F)
8a
B'
A'
3. CONCLUSIONS
In conclusion, a metal-free versatile and simple approach has been developed for the synthesis of
3-aryl-2-substituted quinolines and 4-arylacridines via the 1,3-dipolar cycloaddition reaction-
rearrangements of arynes with N-oxides. Reactions proceed at room temperature with moderate to good
yields of the desired products. One-pot two-step synthesis of 2,3-disubstituted quinolines was also be
achieved in moderate yields, albeit with moderate yields of products. This metal-free approach offers an
easy access to diverse 2,3-disubstituted quinolines for applications in pharmaceuticals and materials.
4. EXPERIMENTAL SECTION
4.1. General information
Unless otherwise stated, all reactions were carried out under air atmosphere in screw cap reaction vials.
All solvents were bought from Aldrich in sure-seal bottle and used as such. All chemicals were bought
from Sigma Aldrich, Alfa-aesar and TCI. Quinoline N-oxide23 and 2-arylquinolines20a were synthesized
by using literature report methods. For column chromatography, silica gel (230-400 mesh) from Merck
was used. A gradient elution using n-hexane and ethyl acetate was performed based on Merck alumini-
um TLC sheets (silica gel 60F254)
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4.2. Analytical information: Nuclear magnetic resonance spectra were recorded either on a Bruker-
1
2
3
1
Avance 600 or 300 MHz instrument. All H NMR experiments are reported in units, parts per million
4
5
6
(ppm) and were measured relative to the signals for residual chloroform (7.26), DMSO-d6 (2.50) and
7
8
13
acetone (2.05, 2.84) in the deuterated solvents. All C NMR spectra were reported in ppm relative to
9
1
deuterated chloroform (77.16) and acetone (29.84, 206.26) and all were obtained with H decoupling.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
High-resolution mass spectra (HRMS) were recorded on Waters ESI-TOF-MS. IR was analyzed by
Shimadzu IR Prestige-21with ZnSe Single reflection ATR accessory. The melting points were recorded
on a Bronsted Electro thermal 9100. Optimization studies were done by NMR and NMR yield were cal-
culated by using TCE as internal standard.
4.3. General Procedure for synthesis of 2-substituted-3-(o-hydroxyaryl)quinolines and 4-(o-
hydroxyaryl)acridines
To a solution of 2-substituted quinoline N-oxide (1) or acridine N-oxide (8) (1.0 molar equiv) in CH3CN
(1.3 mL per mmol) in a reaction vial equipped with magnetic stir bar, benzyne precursor, 2 (1.5 molar
equiv), 18-crown-6 (2.0 molar equiv) and KF (2.0 molar equiv) were added sequentially. Reaction mix-
ture was allowed to stir at room temperature until TLC showed disappearance of N-oxide. Reaction mix-
ture was diluted with water and transferred to separating funnel with ethyl acetate. Organic layer was
separated and aqueous layer was extracted three times with ethyl acetate. Combined organic layer was
washed with brine and then dried over anhydrous Na2SO4. Solvents were evaporated under reduced
pressure and the products were isolated by column chromatography using silica gel (mesh 230-400).
Eluting solvents for chromatography are indicated under the specific compound headings.
4.4 Characterization Data
2-(2-Phenylquinolin-3-yl)phenol (Table 1, entry 3a) 2-Phenylquinoline N-oxide 1a: 22 mg (0.10
mmol); benzyne precursor 2a: 44.8 mg (0.15 mmol), 18-crown-6: 52.8 mg (0.20 mmol), KF: 11.6 mg
(0.20 mmol), CH3CN: 1.3 mL. Column chromatography: eluting solvent 20% EtOAc in n-hexanes.
Yield: 25.0 mg (84%) of white solid, m.p. 216-218 °C.
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1H NMR (600 MHz, CDCl3): δ 8.22 (d, J = 6.6 Hz, 2H), 7.86 (d, J = 8.4 Hz, 1H), 7.76 – 7.78 (m, 1H),
7.57 – 7.60 (m, 1H), 7.49 – 7.51 (m, 2H), 7.25 – 7.29 (m, 3H), 7.20 – 7.23 (m, 1H), 7.13 (dd, J = 7.2,
1.2 Hz, 1H), 6.91 – 6.93 (m, 1H), 6.80 (d, J = 7.8 Hz, 1H), 4.92 (br s, 1H).
1
2
3
4
5
6
7
8
9
13C NMR (150 MHz, CDCl3): δ 158.9, 152.7, 147.9, 140.1, 139.0, 131.5, 130.2, 129.8, 129.69, 129.66,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
129.4(2C), 128.5, 128.2(2C), 127.6, 127.2, 127.1, 126.9, 121.1, 116.2.
IR (ZnSe): νmax (cm-1) 3055, 2922, 2852, 1589, 1487,1444, 1366, 1282, 1112, 969, 913, 829, 750, 696.
HRMS (ESI-TOF): m/z calcd for C21H16NO [M+H]+ 298.1226, found 298.1214.
2-(2-(4-Methoxyphenyl)quinolin-3-yl)phenol (Table 2, entry 3b) 2-(4-Methoxyphenyl)quinoline N-
oxide 1b: 126.0 mg (0.50 mmol); benzyne precursor 2a: 224.0 mg (0.75 mmol), 18-crown-6: 264.0 mg
(1.00 mmol), KF: 58.0 mg (1.00 mmol), CH3CN: 6.5 mL. Column chromatography: eluting solvent 5-
20% EtOAc in n-hexanes. Yield: 82.0 mg (50%) of white solid, m.p. 204-206 °C.
1H NMR (600 MHz, CDCl3): δ 8.18 (d, J = 8.4 Hz, 1H), 8.16 (s, 1H), 7.82 (d, J = 7.8 Hz, 1H), 7.73 –
7.76(m, 1H), 7.54 – 7.57 (m, 1H), 7.45 – 7.48 (m, 2H), 7.21 – 7.24 (m, 1H), 7.15 – 7.16 (m, 1H), 6.93 –
6.96 (m, 1H), 6.82 (dd, J = 8.4, 0.6 Hz, 1H), 6.77 – 6.80 (m, 2H), 5.05 (br s, 1H), 3.78 (s, 3H)
13C NMR (150 MHz, CDCl3): δ 160.1, 158.2, 152.7, 147.9, 139.1, 132.5, 131.5, 130.9 (2C), 130.1,
129.72, 129.65, 129.5, 127.6, 127.2, 127.0, 126.8, 121.2, 116.4, 113.7(2C), 55.4.
IR (ZnSe): νmax (cm-1) 3060, 2921, 2852, 1605, 1589, 1512, 1487, 1441, 1418, 1371, 1244, 1178, 1106,
1020, 970, 838, 793, 754, 691, 621.
HRMS (ESI-TOF): m/z calcd for C22H18NO2 [M+H]+ 328.1332, found 328.1314.
2-(4-methoxyphenyl)-3-(2-phenoxyphenyl)quinoline (Table 2, entry 4b) Yield of 4b: 20.6 mg
(10%) of colourless oil.
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1H NMR (600 MHz, CDCl3): δ 8.16 (d, J = 8.4 Hz, 1H), 8.14 (s, 1H), 7.82 (d, J = 8.4 Hz, 1H), 7.69 –
7.72 (m, 1H), 7.50 – 7.53(m, 1H), 7.43 – 7.45 (m, 3H), 7.24 – 7.25 (m, 1H), 7.13 – 7.16 (m, 3H), 6.96 –
6.99(m, 1H), 6.76 – 6.79(m, 2H), 6.71 (d, J = 8.4 Hz, 1H), 6.46 (d, J = 7.8 Hz, 2H), 3.80 (s, 3H).
1
2
3
4
5
6
7
8
9
13C NMR (150 MHz, CDCl3): δ 159.8, 158.8, 156.2, 154.7, 147.6, 138.3, 133.9, 132.1 (2C), 131.4,
131.1, 130.9, 129.6, 129.5(2C), 129.4, 129.2, 127.6, 127.0, 126.4, 123.5, 123.1, 119.3 (2C), 117.4,
113.5 (2C), 55.5.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
IR (ZnSe): νmax (cm-1): 3057, 2954, 2920, 2850, 1732, 1606, 1575, 1554, 1483, 1448, 1406, 1371,
1294, 1232, 1213, 1172, 1199, 1109, 1026, 792, 750, 688, 480.
HRMS (ESI-TOF): m/z calcd for C28H22NO2 [M+H]+ 404.1645 found 404.1634.
2-(2-(4-Nitrophenyl)quinolin-3-yl)phenol (Table 2, entry 3c) 2-(4-Nitrophenyl)quinoline N-oxide 1c:
133.0 mg (0.50 mmol); benzyne precursor 2a: 224.0 mg (0.75 mmol), 18-crown-6: 264.0 mg (1.00
mmol), KF: 58.0 mg (1.00 mmol), CH3CN: 6.5 mL. Column chromatography: eluting solvent 5-20%
EtOAc in n-hexanes. Yield: 111.0 mg (65%) of pale yellow solid, m.p. 246-248 °C.
1H NMR (600 MHz, DMSO-d6): δ 9.34 (s, 1H), 8.33 (s, 1H), 8.07 – 8.10(m, 3H), 8.04 (d, J = 7.8 Hz,
1H), 7.77 – 7.80 (m, 1H), 7.63 – 7.66(m, 3H), 7.22 – 7.24 (m, 1H), 7.14 – 7.17(m, 1H), 6.83 – 6.85 (m,
1H), 6.71 (d, J = 7.8 Hz, 1H).
13C NMR (150 MHz, DMSO-d6): δ 156.4, 154.1, 147.5, 146.8, 146.5, 138.4, 131.4, 131.1, 130.1 (2C),
130.0, 129.6, 128.8, 127.8, 127.3, 127.2, 126.0, 122.7 (2C), 119.4, 115.5.
IR (ZnSe): νmax (cm-1) 3423, 3347, 3064, 2923, 2852, 1724, 1592, 1515, 1485, 1458, 1345, 1277, 1217,
1177, 1137, 1107, 1014, 967, 853, 737, 700.
HRMS (ESI-TOF): m/z calcd for C21H15N2O3 [M+H]+ 343.1077 found 343.1065.
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2-(4-nitrophenyl)-3-(2-phenoxyphenyl)quinoline (Table 2, entry 4c) Yield of 4c: 19.0 mg (9%) of
1
2
3
pale yellow sticky solid.
4
5
6
7
8
1H NMR (600 MHz, CDCl3): δ 8.22 (s, 1H), 8.18 (d, J = 8.4 Hz, 1H), 8.09 (d, J = 8.4 Hz, 2H), 7.88 (d,
J = 7.8 Hz, 1H), 7.76 – 7.78 (m, 1H), 7.66 (d, J = 8.4 Hz, 2H), 7.59 – 7.62(m, 1H), 7.50 (dd, J = 7.2, 1.8
Hz, 1H), 7.28 – 7.31(m, 1H), 7.19 – 7.22 (m, 1H), 7.11 – 7.14 (m, 2H), 6.96 – 6.99 (m, 1H), 6.73 (d, J =
7.8 Hz, 1H), 6.41 (d, J = 7.2 Hz, 2H).
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
13C NMR (150 MHz, CDCl3): δ 156.7, 155.8, 154.1, 147.7, 147.53, 147.49, 138.8, 131.9, 130.8, 130.4
(2C), 130.3, 130.2, 129.9, 129.7, 129.6 (2C), 127.7, 127.6, 127.5, 123.7, 123.6, 123.2 (2C), 118.6 (2C),
117.8.
IR (ZnSe): νmax (cm-1) 3061, 2920, 2851, 1587, 1514, 1485, 1449, 1342, 1232, 1107, 850, 795, 748,
692, 621, 590.
HRMS (ESI-TOF): m/z calcd for C27H19N2O3 [M+H]+ 419.1390 found 419.1377.
2-(2-(4-((Trifluoromethyl)thio)phenyl)quinolin-3-yl)phenol
(Table
2,
entry
3d)
2-(4-
Nitrophenyl)quinoline N-oxide 1d: 96.0 mg (0.30 mmol); benzyne precursor 2a: 134.0 mg (0.45 mmol),
18-crown-6: 158.0 mg (0.60 mmol), KF: 35.0 mg (0.60 mmol), CH3CN: 3.9 mL. Column
chromatography: eluting solvent 20% EtOAc in n-hexanes. Yield: 83.6 mg (70%) of white solid, m.p.
165-167 °C.
1H NMR (600 MHz, CDCl3): δ 8.21 (s, 1H), 8.17 (d, J = 8.4 Hz, 1H), 7.85 (d, J = 7.8 Hz, 1H), 7.75 –
7.78 (m, 1H), 7.59 – 7.61 (m, 1H), 7.50 – 7.53 (m, 4H), 7.17 – 7.20 (m, 1H), 7.10 – 7.11 (m,1H), 6.89 –
6.92 (m, 1H), 6.71 (d, J = 7.8 Hz, 1H), 5.47 (br s, 1H).
13C NMR (150 MHz, CDCl3): δ 157.6, 152.7, 147.6, 142.9, 139.1, 135.7 (2C), 131.67 (q, JC-F = 307.5
Hz), 131.5, 130.5 (2C), 130.4, 130.1, 129.9, 129.5, 127.7 127.40, 127.37, 126.3, 124.4, 121.1, 116.1.
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IR (ZnSe): νmax (cm-1) 3460, 3061, 2921, 2852, 1719, 1573, 1486, 1443, 1403, 1370, 1282, 1237, 1114,
1
2
3
1074, 997, 920, 889, 747, 691.
4
5
6
7
HRMS (ESI-TOF): m/z calcd for C22H15F3NOS [M+H]+ 398.0821, found 398.0811.
8
9
2-(2-(4-Bromophenyl)quinolin-3-yl)phenol (Table 2, entry 3e) 2-(4-Bromophenyl)quinoline N-oxide
1e: 150.0 mg (0.50 mmol); benzyne precursor 2a: 224.0 mg (0.75 mmol), 18-crown-6: 264.0 mg (1.00
mmol), KF: 58.0 mg (1.00 mmol), CH3CN: 6.5 mL. Column chromatography: eluting solvent 20%
EtOAc in n-hexanes. Yield: 122.0 mg (65%) of pale yellow solid, m.p. 173-175 °C.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1H NMR (300 MHz, CDCl3): δ 8.18 (s, 1H), 8.16 (s, 1H), 7.83 (d, J = 8.1 Hz, 1H), 7.73 – 7.78 (m,
1H), 7.56 – 7.60 (m, 1H), 7.36 (s, 4H), 7.18 – 7.23 (m, 1H), 7.11 (d, J = 7.2 Hz, 1H), 6.90 – 6.95 (m,
1H), 6.76 (d, J = 7.8 Hz, 1H).
13C NMR (150 MHz, CDCl3): δ 157.8, 152.8, 147.8, 139.2, 139.1, 131.5, 131.2 (2C), 131.1 (2C),
130.3, 129.87, 129.85, 129.5, 127.6, 127.3, 127.2, 126.6, 123.0, 121.2, 116.3.
IR (ZnSe): νmax (cm-1) 3425, 3436, 3247, 3062, 2923, 2853, 1720, 1634, 1588, 1534, 1485, 1452, 1414,
1372, 1280, 1198, 1072, 1009, 791, 753, 592, 535, 482, 458.
HRMS (ESI-TOF): m/z calcd for C21H15BrNO [M+H]+ 376.0332, found 376.0316.
2-(2-(3-Bromophenyl)quinolin-3-yl)phenol (Table 2, entry 3f) 2-(3-Bromophenyl)quinoline N-oxide
1f: 90.0 mg (0.30 mmol); benzyne precursor 2a: 134.0 mg (0.75 mmol), 18-crown-6: 158.0 mg (0.60
mmol), KF: 35.0 mg (0.60 mmol), CH3CN: 3.9 mL. Column chromatography: eluting solvent 5-20%
EtOAc in n-hexanes. Yield: 68.0 mg (60%) of light red solid, m.p. 199-201 °C.
1H NMR (600 MHz, CDCl3): δ 8.21 (s, 1H), 8.20 (s, 1H), 7.87 (d, J = 7.8 Hz, 1H), 7.77 – 7.79 (m,
2H), 7.59 – 7.61 (m, 1H), 7.41 (d, J = 7.8 Hz, 1H), 7.32 (d, J = 7.2 Hz, 1H), 7.23-7.25 (m, 1H), 7.13 (d,
J = 7.8 Hz, 1H), 7.07 (t, J = 7.8 Hz, 1H), 6.94 – 6.96 (m, 1H), 6.80 (d, J = 7.8 Hz, 1H), 4.96 (br s, 1H)
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13C NMR (150 MHz, CDCl3): δ 157.3, 152.7, 147.8, 142.3, 139.0, 132.6, 131.5, 131.4, 130.3, 129.91,
1
2
3
129.85, 129.7, 129.4, 128.0, 127.6, 127.34, 127.32, 126.4, 122.3, 121.2, 116.1.
4
5
6
7
IR (ZnSe): νmax (cm-1) 3051, 2823, 2853, 1589, 1487, 1444, 1373, 1281, 1236, 1151, 1111, 1083, 1016,
8
9
969, 919, 844, 792, 750, 690, 602, 520.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
HRMS (ESI-TOF): m/z calcd for C21H14NaBrNO [M+Na]+ 398.0151, found 398.0139.
2-(3-bromophenyl)-3-(2-phenoxyphenyl)-quinoline (Table 2, entry 4f): Yield: 10.6 mg (8%) of yel-
lowish sticky solid.
1H NMR (600 MHz, CDCl3): δ 8.17 – 8.19 (m, 2H), 7.86 (d, J = 8.4 Hz, 1H), 7.71 – 7.75 (m, 2H), 7.57
(t, J = 7.2 Hz, 1H), 7.43 – 7.45 (m, 2H), 7.34 (d, J = 7.2 Hz, 1H), 7.27 – 7.28 (m, 1H), 7.16 – 7.19 (m,
3H), 7.08 (t, J = 7.8 Hz, 1H), 6.99 – 7.02 (m, J = 7.4 Hz, 1H), 6.71 (d, J = 7.8 Hz, 1H), 6.46 (d, J = 7.8
Hz, 2H).
13C NMR (150 MHz, CDCl3): δ 155.8, 154.5, 147.5, 143.2, 138.5, 132.8, 132.0, 131.03, 130.95, 130.6,
129.9, 129.7 (2C), 129.61, 129.56, 129.3, 128.1, 127.6, 127.4, 127.0, 123.7, 123.2, 122.3, 120.6, 119.2
(2C), 117.3.
IR (ZnSe): νmax (cm-1) 3059, 2922, 2850, 1587, 1575, 1554, 1485, 1469, 1446, 1367, 1230, 1211, 1199,
1161, 1116, 867, 748, 682, 601, 480.
HRMS (ESI-TOF): m/z calcd for C27H19BrNO [M+H]+ 452.0645, found 452.0634.
2-(2-(2-Bromophenyl)quinolin-3-yl)phenol (Table 2, entry 3g) 2-(2-Bromophenyl)quinoline N-oxide
1g: 125.0 mg (0.42 mmol); benzyne precursor 2a: 188.0 mg (0.63 mmol), 18-crown-6: 222.0 mg (0.84
mmol), KF: 49.0 mg (0.84 mmol), CH3CN: 5.5 mL. Column chromatography: eluting solvent 20%
EtOAc in n-hexanes. Yield: 112.3 mg (71%) of pale yellow solid, m.p. 217-219 °C.
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1H NMR (600 MHz, acetone-d6): δ 8.33 (s, 1H), 8.13 (s, 1H), 7.90 (d, J = 8.4 Hz, 1H), 7.86 (d, J = 7.8
Hz, 1H), 7.60 – 7.63 (m, 1H), 7.46 – 7.49 (m, 1H), 7.33 (d, J = 7.8 Hz, 1H), 7.27 – 7.28 (m, 1H), 7.08 –
7.11 (m, 1H), 7.00 – 7.02 (m, 1H), 6.96 – 6.97 (m, 1H), 6.89 – 6.92 (m, 1H), 6.64 (d, J = 8.4 Hz, 1H),
6.53 – 6.56 (m, 1H).
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13C NMR (150 MHz, acetone-d6): δ 160.0, 155.4, 147.7, 143.1, 138.7, 132.92, 132.84, 132.2(2C),
130.3, 130.01, 129.97, 129.9, 128.6, 128.4, 127.7, 127.3, 126.8, 123.3, 119.8, 116.3.
IR(ZnSe): νmax (cm-1) 3053, 1710, 1608, 1587, 1444, 1413, 1371, 1282, 1234, 1203, 1193, 1109, 1022,
970, 914, 750, 736.
HRMS (ESI-TOF): m/z calcd for C21H15BrNO [M+H]+ 376.0332, found 376.0323.
2-(2-(o-tolyl)quinolin-3-yl)phenol (Table 2, entry 3h) 2-(o-tolyl)quinoline N-oxide 1h: 94.0 mg (0.40
mmol); benzyne precursor 2a: 179.0 mg (0.60 mmol), 18-crown-6: 211.2 mg (0.80 mmol), KF: 46.4 mg
(0.80 mmol), CH3CN: 5.2 mL. Column chromatography: eluting solvent 7% EtOAc in n-hexanes.
Yield: 83.0 mg (70%) of white solid, m.p. 217-218 °C.
1H NMR (300 MHz, acetone-d6): δ 8.26 (s, 1H), 8.20 (s, 1H), 7.90 – 7.97(m, 2H), 7.65 – 7.70 (m, 1H),
7.50 – 7.54 (m, 1H), 6.88 – 7.09 (m, 5H), 6.61 – 6.71 (m, 2H), 2.11 (s, 3H).
13C NMR (75 MHz, acetone-d6): δ 161.2, 155.3, 147.9, 141.9, 138.7, 137.2, 133.2, 132.3, 130.6, 130.5,
130.1, 129.9, 129.7, 128.6, 128.2, 128.0, 127.6, 127.3, 125.3, 120.0, 116.3, 20.1.
IR (ZnSe): νmax (cm-1) 3059.10, 2789.07, 1554.63, 1487.12, 1444.68, 1371.39, 1284.59, 1201.65,
970.19, 732.95, 628.79, 480.28.
HRMS (ESI-TOF): m/z calcd for C22H18NO+ (M+H)+ 312.1383 found 312.1390.
2-(2-([1,1'-biphenyl]-2-yl)quinolin-3-yl)phenol (Table 2, entry 3i) 2-([1,1'-biphenyl]-2-yl)quinoline
N-oxide 1i: 89.2 mg (0.30 mmol); benzyne precursor 2a: 134.3 mg (0.45 mmol), 18-crown-6: 158.4 mg
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(0.60 mmol), KF: 34.8 mg (0.60 mmol), CH3CN: 3.9 mL. Column chromatography: eluting solvent 10-
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15% EtOAc in n-hexanes. Yield: 50.0 mg (56%) of brown solid, m.p. 162-164 °C.
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1H NMR (300 MHz, CDCl3) δ 8.27 (d, J = 8.4 Hz, 1H), 7.98 (s, 1H), 7.74 – 7.82 (m, 3H), 7.57 – 7.62
(m, 1H), 7.38 – 7.50 (m, 2H), 7.13 – 7.19 (m, 2H), 7.01 – 7.06 (m, 3H), 6.70 (d, J = 7.5 Hz, 2H), 6.58
(dd, J = 14.4, 7.5 Hz, 2H), 6.33 (d, J = 6.0 Hz, 1H).
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13C NMR (75 MHz, acetone-d6) δ 161.4, 155.2, 147.9, 142.2, 141.5, 141.2, 138.3, 133.5, 132.5,
132.2(2C), 130.2, 130.0, 129.97, 129.95, 129.4, 128.8, 128.5, 128.4 (2C), 128.1, 127.23, 127.17, 127.1,
127.0, 119.8, 115.9.
IR (ZnSe): νmax(cm-1) 3055.24, 2924.09, 2854.65, 1587.42, 1483.26, 1446.61, 1408.04, 1371.39,
1290.38, 1105.21, 1031.92, 968.27, 740.67, 671.23.
HRMS (ESI-TOF): m/z calcd for C27H20NO+ (M+H)+ 374.1539 found 374.1544.
2-(4-Methyl-2-phenylquinolin-3-yl)phenol (Table 2, entry 3j) 4-Methyl-2-phenylquinoline N-oxide
1j: 118.0 mg (0.50 mmol); benzyne precursor 2a: 224.0 mg (0.75 mmol), 18-crown-6: 264.0 mg (1.00
mmol), KF: 58.0 mg (1.00 mmol), CH3CN: 6.5 mL. Column chromatography: eluting solvent 20%
EtOAc in n-hexanes. Yield: 115.0 mg (74%) of white solid. m. p. 199-201 °C.
1H NMR (600 MHz, CDCl3): δ 8.21 (d, J = 8.4 Hz, 1H), 8.10 (d, J = 8.4 Hz, 1H), 7.74 – 7.77 (m, 1H),
7.60 – 7.63 (m, 1H), 7.38 (d, J = 6.0 Hz, 2H), 7.20 – 7.26 (m, 3H), 7.13 – 7.15 (m, 1H), 6.86 (d, J = 6.6
Hz, 1H), 6.79 (d, J = 6.6 Hz, 2H), 5.73 (br s, 1H), 2.54 (s, 3H)
13C NMR (150 MHz, CDCl3): δ 159.7, 153.5, 147.2, 144.9, 140.9, 131.7, 130.2, 129.8, 129.5,
129.3(2C), 128.8, 128.0, 127.8(2C), 127.2, 126.8, 125.7, 124.4, 120.6, 115.5, 16.0.
IR (ZnSe): νmax (cm-1) 3056, 2924, 1590, 1487, 1445, 1373, 1290, 1236, 1152, 1114, 1085, 1016, 970,
844, 793, 752, 603, 520.
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HRMS (ESI-TOF): m/z calcd for C22H18NO (M+H)+ 312.1383 found 312.1361.
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2-(4-Nitro-2-phenylquinolin-3-yl)phenol (Table 2, entry 3k) 4-Nitro-2-phenylquinoline N-oxide 1k:
54.0 mg (0.20 mmol); benzyne precursor 2a: 90.0 mg (0.30 mmol), 18-crown-6: 106.0 mg (0.40 mmol),
KF: 23.0 mg (0.40 mmol), CH3CN: 2.6 mL. Column chromatography: eluting solvent 20% EtOAc in n-
hexanes. Yield: 8.1 mg (12%) of pale yellow solid, m. p. 150-151 °C.
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1H NMR (600 MHz, CDCl3): δ 8.46 (dd, J = 8.4, 0.6 Hz, 1H), 8.31 (d, J = 8.4 Hz, 1H), 7.94 – 7.96 (m,
2H), 7.79 – 7.80 (m, 1H), 7.76 (d, J = 7.8 Hz, 1H), 7.68 – 7.72 (m, 2H), 7.63 – 7.64 (m, 2H), 7.59 – 7.62
(m, 1H), 7.49 – 7.51 (m, 1H), 7.28 – 7.30 (m, 1H).
13C NMR (150 MHz, CDCl3): δ 158.5, 156.2, 156.1, 147.3, 140.0, 130.0, 129.8, 129.5, 129.1 (2C),
128.9 (2C), 127.2, 126.8, 123.8, 123.1, 122.5, 120.9, 116.4, 114.7, 112.1.
IR (ZnSe): νmax (cm-1) 3049, 2956, 2920, 2850, 1726, 1579, 1556, 1535, 1508, 1492, 1458, 1444, 1438,
1361, 1192, 742, 700, 680.
HRMS (ESI-TOF): m/z calcd for C21H15N2O3 [M+H]+ 343.1077, found 343.1065.
2-(6-Methyl-2-phenylquinolin-3-yl)phenol (Table 2, entry 3l) 6-Methyl-2-phenylquinoline N-oxide
1l: 47.0 mg (0.20 mmol); benzyne precursor 2a: 90.0 mg (0.30 mmol), 18-crown-6: 106.0 mg (0.40
mmol), KF: 23.0 mg (0.40 mmol), CH3CN: 2.6 mL. Column chromatography: eluting solvent 20%
EtOAc in n-hexanes. Yield: 45.5 mg (73%) of white solid, m. p. 195-198 °C.
1H NMR (600 MHz, CDCl3): δ 8.10 (d, J = 7.8 Hz, 2H), 7.59 (d, J = 8.4 Hz, 2H), 7.47 – 7.48 (m, 2H),
7.23 – 7.28 (m, 3H), 7.18 – 7.21 (m, 1H), 7.10 – 7.11 (m, 1H), 6.89 – 6.91 (m, 1H), 6.79 (d, J = 8.4 Hz,
1H), 5.12 (br s, 1H), 2.57 (s, 3H).
13C NMR (150 MHz, CDCl3): δ 158.0, 152.8, 146.5, 140.1, 138.4, 137.0, 132.5, 131.5, 129.7, 129.6.,
129.5 (2C), 129.3, 128.4, 128.1 (2C), 127.2, 127.0, 126.4, 121.0, 116.2, 21.8.
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IR (ZnSe): νmax (cm-1) 3431, 3347, 3245, 3061, 2921, 2852, 1666, 1590, 1487, 1452, 1424, 1369, 1287,
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1198, 1024, 973, 890, 755, 725, 694, 632, 590, 573.
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HRMS (ESI-TOF): m/z calcd for C22H18NO [M+H]+ 312.1383, found 312.1364.
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2-(6-Isopropyl-2-phenylquinolin-3-yl)phenol (Table 2, entry 3m) 6-Isoporyl-2-phenylquinoline 1-
oxide 1m: 52.0 mg (0.20 mmol); benzyne precursor 2a: 90.0 mg (0.30 mmol), 18-crown-6: 106.0 mg
(0.40 mmol), KF: 23.0 mg (0.40 mmol), CH3CN: 2.6 ml. Column chromatography: eluting solvent 20%
EtOAc in n-hexanes. Yield: 34.5 mg (51%) of white solid, m. p. 68-70 °C.
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1H NMR (600 MHz, CDCl3): δ 8.14 (d, J = 6.6 Hz, 2H), 7.68 (dd, J = 9.0, 1.8 Hz, 1H), 7.64 (s, 1H),
7.46 – 7.48 (m, 2H), 7.23 – 7.29 (m, 3H), 7.20 (td, J = 7.8, 1.2 Hz, 1H), 7.09 – 7.11 (m,1H), 6.89 – 6.91
(m, 1H), 6.79 (d, J = 8.4 Hz, 1H), 3.11 – 3.16 (m, 1H), 1.37 (d, J = 6.6 Hz, 6H).
13C NMR (150 MHz, CDCl3): δ 158.1, 152.8, 147.8, 146.8, 140.2, 138.7, 131.5, 130.2, 129.7, 129.6,
129.47, 129.45 (2C), 128.4, 128.1 (2C), 127.2, 127.0, 123.6, 120.9, 116.2, 34.3, 24.0 (2C).
IR (ZnSe): νmax (cm-1) 3046, 2955, 2922, 2852, 1590, 1481, 1453, 1405, 1374, 1286, 1238, 1200, 1150,
1106, 1024, 972, 917, 834, 749, 692, 628, 588.
HRMS (ESI-TOF): m/z calcd for C24H22NO [M+H]+ 340.1696, found 340.1679.
2-(6-Fluoro-2-phenylquinolin-3-yl)phenol (Table 2, entry 3n) 6-Fluoro-2-phenylquinoline N-oxide
1n: 48.0 mg (0.20 mmol); benzyne precursor 2a: 90.0 mg (0.30 mmol), 18-crown-6: 106.0 mg (0.40
mmol), KF: 23.0 mg (0.40 mmol), CH3CN: 2.6 ml. Column chromatography: eluting solvent 10%
EtOAc in n-hexanes. Yield: 45.4 mg (72%) of white solid, m. p. 163-165 °C.
1H NMR (600 MHz, CDCl3): δ 8.14 – 8.16 (m, 1H), 8.12 (s, 1H), 7.48 – 7.51 (m, 1H), 7.42 – 7.46 (m,
3H), 7.26 – 7.28 (m, 1H), 7.22 – 7.24 (m, 2H), 7.14 – 7.16 (m, 1H), 7.09 – 7.10 (m, 1H), 6.87 – 6.90 (m,
1H), 6.68 (d, J = 7.8 Hz, 1H).
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13C NMR (150 MHz, CDCl3): δ 160.8 (d, J = 247.5 Hz), 158.4 (d, J = 3.0 Hz), 152.9, 144.7, 139.9,
138.4 (d, J = 6.0 Hz), 131.9 (d, J = 10.5 Hz), 131.5, 131.3, 129.7, 129.4, 128.5, 128.1, 127.8 (d, J = 10.5
Hz), 126.6, 120.9, 120.4, 120.2, 116.2, 110.58, 110.43.
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IR (ZnSe): νmax (cm-1) 3056, 2920, 2851, 1601, 1561, 1539, 1483, 1455, 1372, 1264, 1216, 1152, 1025,
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957, 916, 830, 752, 704, 588, 497.
HRMS (ESI-TOF): m/z calcd for C21H15FNO [M+H]+ 316.1132, found 316.1118.
Methyl 3-(2-hydroxyphenyl)-2-phenylquinoline-6-carboxylate (Table 2, entry 3o) 6-Fluoro-2-
phenylquinoline N-oxide 1o: 84.0 mg (0.30 mmol); benzyne precursor 2a: 134.0 mg (0.45 mmol), 18-
crown-6: 158.0 mg (0.60 mmol), KF: 35.0 mg (0.60 mmol), CH3CN: 3.9 mL. Column chromatography:
eluting solvent 20% EtOAc in n-hexanes. Yield: 48.0 mg (45%) of white solid, m. p. 192-195 °C.
1H NMR (600 MHz, acetone-d6): δ 8.71 (d, J = 1.8 Hz, 1H), 8.44 (s, 1H), 8.27 – 8.30 (m, 2H), 8.17 (d,
J = 8.4 Hz, 1H), 7.57 (d, J = 7.2 Hz, 2H), 7.24 – 7.30 (m, 3H), 7.19 – 7.22 (m, 2H), 6.85 – 6.89 (m, 2H),
3.98 (s, 3H).
13C NMR (150 MHz, CDCl3): δ 166.8, 161.1, 152.7, 149.5, 140.1, 139.9, 131.6, 131.1, 130.8, 129.9,
129.53, 129.46 (2C), 128.9, 128.4, 128.2 (2C), 126.6, 126.3, 121.2, 116.3, 52.6, 29.4.
IR (ZnSe): νmax (cm-1) 3319, 3059, 2957, 1711, 1686, 1624, 1439, 1402, 1344, 1276, 1190, 1096, 1024,
925, 849, 775, 750, 696, 584.
HRMS (ESI-TOF): m/z calcd for C23H18NO3 [M+H]+ 356.1281 found 356.1270.
2-(4-Chloro-2-phenyl-7-(trifluoromethyl)quinolin-3-yl)phenol (Table 2, entry 3p) 4-Chloro-2-
phenyl-7-(trifluoromethyl)quinoline N-oxide 1p: 120 mg (0.37 mmol); benzyne precursor 2a: 165.4 mg
(0.56 mmol), 18-crown-6: 195.0 mg (0.74 mmol), KF: 43.0 mg (0.74 mmol), CH3CN: 4.8 mL. Column
chromatography: eluting solvent 5% EtOAc in n-hexanes. Yield: 62.1 mg (20%) of white solid. m. p.
155-157 °C.
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1H NMR (600 MHz, CDCl3): δ 8.63 (s, 1H), 8.57 (d, J = 9.0 Hz, 1H), 7.95 – 7.97 (m, 2H), 7.87 (dd, J
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= 8.4, 1.2 Hz, 1H), 7.76 – 7.80 (m, 2H), 7.61 – 7.64 (m, 3H), 7.54 – 7.57 (m, 1H), 7.32 – 7.35 (m, 1H).
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13C NMR (150 MHz, CDCl3): δ 157.9, 157.5, 156.5, 146.1, 139.5, 131.5 (q, J = 33.0 Hz), 130.0, 129.1
(2C), 129.0 (2C), 128.0, 127.8 (q, J = 4.5 Hz), 124.2 (q, J = 271.5 Hz), 124.1, 122.8, 122.6, 122.5 (q, J
= 2.7 Hz), 122.2, 118.0, 116.3, 112.3.
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IR (ZnSe): νmax (cm-1) 3062, 2958, 2922, 2850, 1595, 1550, 1516, 1492, 1450, 1361, 1344, 1298, 1193,
1168, 1112, 1101, 750, 694.
HRMS (ESI-TOF): m/z calcd for C22H14ClF3NO [M+H]+ 400.0711 found 400.0701.
2-(8-Methyl-2-phenylquinolin-3-yl)phenol (Table 2, entry 3q) 8-Methyl-2-phenylquinoline N-oxide
1q: 48.0 mg (0.20 mmol); benzyne precursor 2a: 90.0 mg (0.30 mmol), 18-crown-6: 106.0 mg (0.40
mmol), KF: 23.0 mg (0.40 mmol), CH3CN: 2.6 mL. Column chromatography: eluting solvent 3-10%
EtOAc in n-hexanes. Yield: 30.1 mg (48%) of white solid; m. p. 72-75 °C.
1H NMR (600 MHz, CDCl3): δ 8.17 (s, 1H), 7.70 (d, J = 8.4 Hz, 1H), 7.58 – 7.62 (m, 3H), 7.46 – 7.48
(m, 1H), 7.27 – 7.31 (m, 3H), 7.23 – 7.25 (m, 1H), 7.17 (dd, J = 7.8, 1.2 Hz, 1H), 6.94 – 6.96 (m, 1H),
6.85 (d, J = 8.4 Hz, 1H), 2.89 (s, 3H).
13C NMR (150 MHz, CDCl3): δ 157.0, 152.7, 147.0, 140.5, 139.3, 137.8, 131.4, 130.1, 129.8 (2C),
129.6, 129.2, 128.5, 128.0 (2C), 127.2, 127.1, 126.9, 125.5, 121.1, 116.2,18.0.
IR (ZnSe): νmax (cm-1) 3426, 3350, 3242, 3115, 2926, 2854, 1663, 1534, 1464, 1265, 1182, 1080, 967,
894, 735, 537.
HRMS (ESI-TOF): m/z calcd for C22H18NO [M+H]+ 312.1383 found 312.1369.
8-Methyl-3-(2-phenoxyphenyl)-2-phenylquinoline (Table 2, entry 4q): Yield: 14.2 mg (18%) of col-
ourless semi solid.
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1H NMR (600 MHz, CDCl3): δ 8.14 (s, 1H), 7.69 (d, J = 7.8 Hz, 1H), 7.56-7.59 (m, 3H), 7.49 (dd, J =
7.2, 1.8 Hz, 1H), 7.42-7.44 (m, 1H), 7.30 – 7.33 (m, 1H), 7.23 – 7.27 (m, 3H), 7.13 – 7.17 (m, 3H), 6.97
– 7.00 (m, 1H), 6.63 – 6.65 (m, 1H), 6.39 – 6.40 (m, 2H), 2.87 (s, 3H, CH3).
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13C NMR (150 MHz, CDCl3): δ 157.4, 155.9, 155.0, 146.6, 141.7, 138.6, 137.7, 132.0, 131.3, 130.6,
129.9(2C), 129.6, 129.5 (2C), 129.1, 128.0, 127.9 (2C), 127.1, 126.4, 125.5, 123.6, 122.9, 119.7 (2C),
116.9, 18.02.
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IR (ZnSe): νmax (cm-1) 3055, 2916, 1595, 1573, 1485, 1444, 1406, 1369, 1234, 1215, 1195, 1157, 1070,
1022, 920, 867, 767, 748, 734, 601, 482.
HRMS (ESI-TOF): m/z calcd for C28H22NO [M+H]+ 388.1696 found 388.1688.
2-(2-(Benzo[d]thiazol-2-yl)quinolin-3-yl)phenol (Table 2, entry 3r) 2-(Benzo[d]thiazol-2-
yl)quinoline N-oxide 1r: 71.0 mg (0.25 mmol); benzyne precursor 2a: 111.0 mg (0.37 mmol), 18-
crown-6: 132.0 mg (0.50 mmol), KF: 29.0 mg (0.50 mmol), CH3CN: 3.2 mL. Column chromatography:
eluting solvent 10% EtOAc in n-hexanes. Yield: 64.1 mg (73%) of white solid; m. p. 190-192 °C.
1H NMR (600 MHz, CDCl3): δ 8.49 (s, 1H), 8.25 (d, J = 8.4 Hz, 1H), 8.21 (s, 1H), 7.93 – 7.96 (m,
2H), 7.89 (d, J = 7.8 Hz, 1H), 7.80 – 7.83 (m, 1H), 7.64 – 7.67 (m, 1H), 7.45 – 7.48 (m, 1H), 7.41 – 7.44
(m, 1H), 7.35 – 7.38 (m, 1H), 7.15 – 7.18 (m, 2H), 7.02 (td, J = 7.2, 1.2 Hz, 1H).
13C NMR (150 MHz, CDCl3): δ 170.4, 155.1, 152.9, 149.5, 147.1, 141.0, 136.1, 132.1, 131.5, 130.6,
130.4, 130.1, 129.7, 128.5, 128.4, 127.8, 126.5, 126.2, 123.7, 121.8, 121.6, 120.1.
IR (ZnSe): νmax (cm-1) 3282, 3059, 2956, 2922, 2852, 1750, 1587, 1485, 1452, 1371, 1259, 1029, 943,
748, 727, 700
HRMS (ESI-TOF): m/z calcd for C22H15N2OS [M+H]+ 355.0900 found 355.0889.
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2-(2-(2-bromopyridin-4-yl)quinolin-3-yl)phenol (Table 2, entry 3s) 2-(2-bromopyridin-4-
yl)quinoline N-oxide 1s: 60.0 mg (0.20 mmol); benzyne precursor 2a: 89.5 mg (0.30 mmol), 18-crown-
6: 105.6 mg (0.40 mmol), KF: 23.2 mg (0.40 mmol), CH3CN: 2.6 mL. Column chromatography: eluting
solvent 10-12% EtOAc in n-hexanes. Yield: 35.0 mg (45%) of brown solid, m.p. 182-183 °C.
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1H NMR (300 MHz, CDCl3) δ 8.21 (s, 1H), 8.15 (d, J = 8.4 Hz, 1H), 7.97 (d, J = 5.4 Hz, 1H), 7.88 (d,
J = 7.8 Hz, 1H), 7.75 – 7.81 (m, 2H), 7.59 – 7.64 (m, 1H), 7.27 – 7.33 (m, 2H), 7.25 (d, J = 1.5 Hz, 1H),
7.01 – 7.06 (m, 1H), 6.80 (dd, J = 8.1 Hz, J = 0.6 Hz, 1H).
13C NMR (75 MHz, CDCl3) δ 154.5, 153.0, 151.8, 148.7, 147.3, 141.4, 138.9, 131.2, 130.7, 130.2,
130.1, 129.5, 128.4, 127.8, 127.7, 127.6, 126.2, 122.6, 121.2, 116.7.
IR (ZnSe): νmax(cm-1) 3051.39, 1587.42, 1529.55, 1489.05, 1450.47, 1413.82, 1367.53, 1290.38,
1271.09, 1201.65, 1076.28, 908.47, 846.75, 750.31, 576.72.
HRMS (ESI-TOF): m/z calcd for C20H14BrN2O+ (M+H)+ 377.0284 found 377.0264.
2-(2-morpholinoquinolin-3-yl)phenol (Table 2, entry 3t) 2-morpholinoquinoline N-oxide 1t: 92.0 mg
(0.40 mmol); benzyne precursor 2a: 179.0 mg (0.60 mmol), 18-crown-6: 211.2 mg (0.80 mmol), KF:
46.4mg (0.80 mmol), CH3CN: 5.2 mL. Column chromatography: eluting solvent 6-10% EtOAc in hex-
anes. Yield: 60.0 mg (49%) of white solid, m.p. 118-119 °C.
1H NMR (300 MHz, CDCl3) δ 9.58 (br s, 1H), 8.12 (s, 1H), 7.99 (d, J = 8.4 Hz, 1H), 7.81 (d, J = 7.8
Hz, 1H), 7.67 – 7.72 (m, 1H), 7.47 – 7.52 (m, 2H), 7.34 – 7.39 (m, 1H), 7.06 – 7.11 (m, 2H), 3.86 (s,
4H), 3.32 (s, 4H).
13C NMR (75 MHz, CDCl3) δ 156.7, 154.7, 146.3, 141.6, 130.5, 130.1, 130.0, 128.1, 127.9, 127.7,
126.0, 126.3, 125.9, 121.5, 119.2, 66.6 (2C), 50.7 (2C).
IR (ZnSe): νmax (cm-1) 2968.45, 2918.30, 2877.79, 1564.27, 1485.19, 1448.54, 1359.82, 1296.16,
1219.01, 1143.79, 1068.56, 987.55, 756.10, 665.44.
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2-[3-(4-Methoxy-phenyl)-benzo[f]quinolin-2-yl]-phenol (Table 2, entry 3u): 2-[3-(4-Methoxy-
phenyl)-benzo[f]quinolin-2-yl]-phenol 1u: 54.0 mg (0.20 mmol); benzyne precursor 2a: 90.0 mg (0.30
mmol), 18-crown-6: 105.6 mg (0.40 mmol), KF: 23.2 mg (0.40 mmol), CH3CN: 2.6 mL. Column chro-
matography: eluting solvent 5% EtOAc in n-hexanes. Yield: 30.0 mg (45%) of brown solid; m. p. 72-75
°C.
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1H NMR (300 MHz, CDCl3): δ 9.43 (d, J = 6.9 Hz, 1H), 8.16 (d, J = 10.2 Hz, 1H), 7.89 – 7.94 (m,
1H), 7.83 (d, J = 8.7 Hz, 1H), 7.61 – 7.75 (m, 5H), 7.23 – 7.31 (m, 2H), 6.98 – 7.03 (m, 1H), 6.81 – 6.90
(m, 3H), 3.82 (s, 3H).
13C NMR (75 MHz, CDCl3): δ 160.2, 156.0, 152.6, 146.2, 139.2, 134.1, 132.7, 131.7, 131.4, 131.2
(2C), 129.7, 129.5, 128.5, 128.1, 128.0, 127.4, 127.20, 127.19, 125.01, 124.97 (2C), 121.4, 116.5, 113.7
(2C).
IR (ZnSe): νmax (cm-1) 3051, 1605, 1587, 1510, 1439, 1287, 1246, 1172, 1152, 1026, 1017, 924, 826,
802, 772.
HRMS (ESI-TOF): m/z calcd for C26H19NO2 [M+H]+ 378.1489 found 378.1471.
2-(2-Methylquinolin-3-yl)phenol (Scheme 3, entry 3v) 2-Methylquinoline N-oxide 1v: 50.0 mg (0.31
mmol); benzyne precursor 2a: 141.0 mg (0.47 mmol), 18-crown-6: 164.0 mg (0.62 mmol), KF: 36.0 mg
(0.62 mmol), CH3CN: 4.0 mL. Column chromatography: eluting solvent 10% EtOAc in n-hexanes.
Yield: 16.0 mg (22%) of off white solid, m. p. 190-192 °C.
1H NMR (600 MHz, CDCl3): δ 7.92 (d, J = 8.4 Hz, 1H), 7.90 (s, 1H), 7.61 – 7.64 (m, 1H), 7.58 (d, J =
7.8 Hz, 1H), 7.39 – 7.42 (m, 1H), 7.33 – 7.36 (m, 1H), 7.15 (dd, J = 7.8, 1.2 Hz, 1H), 7.08 (d, J = 7.8
Hz, 1H), 7.03 – 7.00 (m, 1H), 2.61 (s, 3H).
13C NMR (150 MHz, DMSO-d6): δ 158.1, 154.5, 146.4, 136.0, 132.9, 130.8, 129.2, 129.0, 127.9,
127.6, 126.55, 126.58, 125.7, 119.2, 115.5, 23.6.
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IR (ZnSe): νmax (cm-1) 3057, 2920, 2851, 1726, 1612, 1570, 1485, 1451, 1419, 1292, 1205, 1169, 983,
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804, 750, 665, 583.
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HRMS (ESI-TOF): m/z calcd for C16H14NO [M+H]+ 236.1070 found 236.1058.
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2-(2,4-Dimethylquinolin-3-yl)phenol (Scheme 3, entry 3w) 2,4-dimethylquinoline N-oxide 1w: 17.3
mg (0.10 mmol); benzyne precursor 2a: 45.0 mg (0.15 mmol), 18-crown-6: 53.0 mg (0.20 mmol), KF:
11.6 mg (0.20 mmol), CH3CN: 1.3 mL. Column chromatography: eluting solvent 10% EtOAc in n-
hexanes. Yield: 12.9 mg (44%) of dirty white solid, m.p. 181-183 °C.
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1H NMR (600 MHz, CDCl3): δ 7.85 (d, J = 8.4 Hz, 1H), 7.68 (d, J = 8.4 Hz, 1H), 7.56 (t, J = 7.2 Hz,
1H), 7.33 – 7.36 (m, 2H), 7.13 (d, J = 8.4 Hz, 1H), 6.96 – 7.01(m, 2H), 2.43 (s, 3H), 2.37 (s, 3H).
13C NMR (150 MHz, CDCl3): δ 158.8, 153.9, 146.2, 144.2, 130.7, 130.1, 129.8, 129.3, 128.3, 126.5,
126.0, 125.1, 124.4, 120.6, 117.0, 24.9, 16.1.
IR (ZnSe): νmax (cm-1) 3061, 2958, 2920, 2851, 1589, 1487, 1453, 1376, 1287, 1260, 1075, 1023, 794,
749, 692, 629, 589.
HRMS (ESI-TOF): m/z calcd for C17H16NO [M+H]+ 250.1226, found 250.1219.
2-(2,6-Dimethylquinolin-3-yl)phenol (Scheme 3, entry 3x) 2,4-Dimethylquinoline N-oxide 1x: 17.3
mg (0.10 mmol); benzyne precursor 2a: 45.0 mg (0.15 mmol), 18-crown-6: 53.0 mg (0.20 mmol), KF:
11.6 mg (0.20 mmol), CH3CN: 1.3 mL. Column chromatography: eluting solvent 10% EtOAc in n-
hexanes. Yield: 11.0 mg (52 %) of dirty white solid, m.p. 218-220 °C.
1H NMR (300 MHz, CD3OD) δ 7.95 (s, 1H), 7.87 (d, J = 8.7 Hz, 1H), 7.64 (s, 1H), 7.56 (dd, J = 8.4,
1.8 Hz, 1H), 7.27 (td, J = 7.8, 1.8 Hz, 1H), 7.15 (dd, J = 7.5, 1.5 Hz, 1H), 6.92 – 6.97 (m, 2H), 2.53 (s,
3H), 2.52 (s, 3H).
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13C NMR (75 MHz, CD3OD) δ 159.2, 155.9, 146.1, 138.0, 137.3, 134.9, 132.8, 132.0, 130.6, 128.6,
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IR (ZnSe): νmax (cm-1) 3426, 3349, 3243, 3064, 2922, 2852, 1725, 1657, 1534, 1452, 1377, 1285, 1202,
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HRMS (ESI-TOF): m/z calcd for C17H16NO [M+H]+ 250.1226, found 250.1220.
2-(2-isopropylquinolin-3-yl)phenol (Scheme 3, entry 3y) 2-isopropylquinoline N-oxide 1y: 56.1 mg
(0.30 mmol); benzyne precursor 2a: 125.3 mg (0.45 mmol), 18-crown-6: 158.4 mg (0.60 mmol), KF:
34.8 mg (0.60 mmol), CH3CN: 3.9 mL. Column chromatography: eluting solvent 8% EtOAc in n-
hexanes. Yield: 36.0 mg (45%) of brown solid, m.p. 163-164 °C.
1H NMR (300 MHz, acetone-d6) δ 8.32 (br s, 1H), 7.89 – 7.94 (m, 2H), 7.80 (d, J = 8.1 Hz, 1H), 7.59 –
7.64 (m, 1H), 7.40 – 7.46(m, 1H), 7.18 – 7.24 (m, 1H), 7.13 – 7.16 (m, 1H), 6.87 – 6.95 (m, 2H), 3.13 –
3.12 (m, 1H), 1.27 (d, J = 6.3 Hz, 3H), 1.03 (d, J = 6.3 Hz, 3H).
13C NMR (75 MHz, acetone-d6) δ 167.2, 155.6, 148.4, 137.5, 132.9, 132.1, 130.1, 129.7, 129.6, 128.4,
128.0, 127.8, 126.5, 120.6, 116.5, 33.4, 23.4, 22.0.
IR (ZnSe): νma x(cm-1) 2964.59, 2927.94, 1589.34, 1564.27, 1489.05, 1415.75, 1448.54, 1400.32,
1377.17, 1288.45, 1217.08, 1089.78, 981.77, 750.31, 655.80, 626.87.
HRMS (ESI-TOF): m/z calcd for C18H18NO+ (M+H)+ 264.1383 found 264.1384.
Ethyl 2-hydroxy-3-(3-(2-hydroxyphenyl)quinolin-2-yl)propanoate (Scheme 3, entry 3z) 2-(3-
ethoxy-2-hydroxy-3-oxopropyl)quinoline N-oxide 1z: 130.5mg (0.50 mmol); benzyne precursor 2a:
224.0 mg (0.75 mmol), 18-crown-6: 264.0 mg (1.00 mmol), KF: 58.0 mg (1.00 mmol), CH3CN: 3.9 mL.
Column chromatography: eluting solvent 12-15% EtOAc in n-hexanes. Yield: 93.0 mg (55%) of brown
solid, m.p. 144-145 °C.
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