AgSCF3/Na2S2O8-Promoted Trifluoromethylthiolation/Cyclization of o-Propargyl Arylazides/ o-Alkynyl Benzylazides: Synthesis of SCF3-Substituted Quinolines and Isoquinolines

Article abstract of DOI:10.1021/acs.joc.9b00181

A AgSCF₃/Na₂S₂O₈-promoted trifluoromethylthiolation/cascade cyclization of o-propargyl arylazides (or o-alkynyl benzylazides) triggered by a carbon-carbon triple bond is reported. This strategy provides the synthesis of valuable SCF₃-substituted quinoline and isoquinoline systems via the construction of one C(sp²)-SCF₃ bond and one C-N bond within one process.

Full text of DOI:10.1021/acs.joc.9b00181

Subscriber access provided by WEBSTER UNIV
Article
AgSCF3/Na2S2O8 Promoted Trifluoromethylthiolation-
Cyclization of o-Propargyl Arylazides/o-Alkynyl Benzylazides:
Synthesis of SCF3-Substituted Quinolines and Isoquinolines
Yi-Feng Qiu, Yue-Jie Niu, Xi Wei, Bao-Qian Cao, Xi-Cun Wang, and Zheng-Jun Quan
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b00181 • Publication Date (Web): 05 Mar 2019
Downloaded from http://pubs.acs.org on March 5, 2019
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a service to the research community to expedite the dissemination
of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in
full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully
peer reviewed, but should not be considered the official version of record. They are citable by the
Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore,
the “Just Accepted” Web site may not include all articles that will be published in the journal. After
a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web
site and published as an ASAP article. Note that technical editing may introduce minor changes
to the manuscript text and/or graphics which could affect content, and all legal disclaimers and
ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or
consequences arising from the use of information contained in these “Just Accepted” manuscripts.
is published by the American Chemical Society. 1155 Sixteenth Street N.W.,
Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the
course of their duties.

Page 1 of 38
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
AgSCF3/Na2S2O8 Promoted Trifluoromethylthiolation-Cyclization of o-Propargyl
Arylazides/o-Alkynyl Benzylazides: Synthesis of SCF3-Substituted Quinolines and
Isoquinolines
9
Yi-Feng Qiu†,∥ Yue-Jie Niu,†,∥ Xi Wei,† Bao-Qian Cao,† Xi-Cun Wang,*,† Zheng-Jun Quan*,†,‡
†College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou, Gansu
730070, P. R. China
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
‡Gansu International Scientific and Technological Cooperation Base of Water-Retention Chemical
Functional Materials, Lanzhou, 730070, P. R. China
ABSTRACT: A AgSCF3/Na2S2O8 promoted trifluoromethylthiolation/cascade cyclization of o-
propargyl arylazides (or o-alkynyl benzylazides) triggered by a carbon–carbon triple bond is
reported. This strategy provides the synthesis of valuable SCF3-substituted quinoline and
isoquinoline systems via the construction s of one C(sp2)–SCF3 bond and one C–N bond within one
process.
4Å MS (25 mg)
HMPA (0.5 equiv)
Na2S2O8 (3.0 equiv)
SCF3
+
SCF
Ag
3 (1.5 equiv)
N
N3
MeCN, Ar
80 oC, 6 h
44 wokrable examples
Broad substrate scope
Yield up to 89%
■ INTRODUCTION
Owing to the fulfilling bioactivities of fluorine-containing compounds, organofluorine chemistry
research has achieved increasing and diversifying applications in drug development, pesticide
chemistry, and material technology.1 The trifluoromethylthio group (SCF3) has held a remarkable
position for its high metabolic stability, electronegativity and lipophilicity with great acceleration
in absorption rate and membrane permeability in bioavailability.2 Due to the complicated operations,
highly toxic reagents, and poor selectivity in the traditional synthetic methods of
trifluoromethylthiolation,3 adequate evolutions are acquired in the exploitation of varieties of new
reagents.4 With the persistent efforts of Billard,5 Shen,6 and Qing2e,2f,7 et al., various electrophilic
trifluoromethylthiolation reagents8 have been exploited. Nevertheless, limited efforts were devoted
to an efficient construction of a cyclic system during the direct trifluoromethylthiolation process. In
a subsequent study, AgSCF3 has presented as a significant straightforward reagent9 for
trifluoromethylthiolation-cyclization reaction in a radical10 or anion pathway.11 In 2014, the Wang
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 38
1
2
3
4
5
6
7
8
9
group first demonstrated the synthesis of SCF3-containing oxindoles through Ag-promoted
aryltrifluoromethylthiolation/cyclization of alkenes including a unique SCF3 radical pathway
(Scheme 1a).10a Qing reported a copper-mediated trifluoromethylthiolation/cyclization of 2,3-
allenoic acids in the past year (Scheme 1b).7e Soon afterwards, the Wu group presented a facile
assembly of trifluoromethylthio-substituted isoquinolines in the presence of silver(I) salt and
base.11b For the addition of radical onto triple bonds with more difficulties, Liang and co-workers
disclosed the first AgSCF3-promoted trifluoromethylthiolation/cyclization of 1,6-enynes including
a radical course, generating a polycyclic fluorene cyclic system efficiently (Scheme 1d).10f Soon
afterwards, a variety of trifluoromethylthio-substituted spiro[4,5]trienones were synthesized by Liu
and co-workers from activated alkynes through a trifluoromethylthiolation/dearomatization process
(Scheme 1e).10h Still, the development of a direct construction of most common heterocyclic
scaffold with the simultaneous incorporation of a trifluoromethylthio group is driven by an
increasing desire in organofluorine chemistry.
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
Quinoline and isoquinoline have become identified as numerous pharmacological, toxicological,
or physiological activities in synthetic chemistry and pharmaceutical analysis.12 Such compounds
are also significant scaffold structure and precious intermediates found in various ligands, natural
products and pharmaceutically active molecules.13 The efficient construction for quinoline and
isoquinoline has been a hot and classical concern in organic methodology research.13 As is well
known, radical cascaded cyclization strategy has become an ingenious approach for constructing
heterocyclic molecules for combining multi-step reactions into one synthetic operation.14 Given our
present interest in fluorine-10f,11d or sulfur-containing15 groups incorporation, and the persistent
anticipation towards new routes to the crucial scaffold for bioactive molecules,11d,16 we designed a
AgSCF3/Na2S2O8 promoted cascade cyclization of o-propargyl arylazides (or o-alkynyl
benzylazides). In this paper, a series of trifluoromethylthio-substituted quinolines and isoquinolines
system were constructed within a single step via direct trifluoromethylthiolation-cyclization
reaction (Scheme 1f).
Scheme 1. Previous Works on Direct Trifluoromethylthiolation-Cyclization Strategies and
Our New Anticipation towards Trifluoromethylthio-substituted Quinolines and Isoquinolines
ACS Paragon Plus Environment

Page 3 of 38
The Journal of Organic Chemistry
1
2
3
Trifluoromethylthiolation-cyclization triggered by a C-C double bond
4
5
6
7
8
9
(a) Synthesis of 2-indolones (Wang's work)
K2S2O8 (3 equiv)
SCF3
HMPA (0.5 equiv)
+
Ag
SCF
3
O
MeCN
N
O
N
75 oC, 12 h
(b) Synthesis of 2-furanones (Qing's work)
CuCN (20 mol %)
Na2S2O8 (2 equiv)
SCF3
COOH
+
Ag
SCF
3
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
MeCN/HOAc (4:1)
70 oC, 3 h
O
O
O
(c) Synthesis of isoquinolines (Wu's work)
OH
N
AgOTf (10 mol %)
K3PO4 (4.5 equiv)
p-MeOC6H4SO2Cl (1.5 equiv)
SCF3
+
Ag
SCF
3
DMA, 25 o
C
O
Trifluoromethylthiolation-cyclization triggered by a C-C triple bond
(d) Synthesis of fluorenes (Liang's work)
K2S2O8 (3 equiv)
HMPA (0.5 equiv)
2,2':6',2''-terpyridine (10 mol %)
X
+
Ag
SCF
3
MeCN/DMF (1:1)
80 oC, 12 h
X = NTs, C(COOMe)2, Y = CH2
X = O, Y = carbonyl group
X
Y
Y
SCF3
(e) Synthesis of spiro[4,5]trienones compounds (Liu and Liang's work)
O
K2S2O8 (3 equiv)
TBHP (5 equiv)
HMPA (0.5 equiv)
N
SCF3
+
Ag
SCF
3
MeCN
80 oC, 12 h
O
N
O
this work
(f) Synthesis of quinolines and isoquinolines (
N3
)
SCF3
N
N
2-
N3
SCF
Ag
3/S2O8
SCF3
SCF3
■ RESULTS AND DISCUSSION
Our initial attempt to obtain trifluoromethylthio-substituted quinoline 2aa began by using starting
material 1aa (0.2 mmol), AgSCF3 (1.5 equiv), and K2S2O8 (3.0 equiv) in the presence of HMPA
(50 mol %) in acetonitrile under argon at 80 °C for 6 h. Delightedly, the expected product 2aa was
obtained in a yield of 55% with over 25% of 1aa recovered simultaneously (Table 1, entry 1).
Prolonging the reaction time gave a slightly lower yield of 52% for product 2aa (entry 2). The
survey on solvents indicated that MeCN was the best choice (entries 3–5). And the screen of
oxidants gave a higher yield of 63% with the addition of 3.0 equiv of Na2S2O8 (entries 6–10). The
replacement of HMPA or a higher temperature was unable to give a better result (entries 11–12).
Subsequently, the addition of 4Å molecular sieve (25 mg) proved to be highly efficient as 83% of
product 2aa was isolated and no 1aa remained unreacted (entries 13–18). The control experiments
presented that argon and base were necessary (entries 19–20).
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 38
1
2
3
4
Table 1. Reaction Conditions Optimization a
5
6
7
8
SCF3
conditions
+
SCF
Ag
3 (1.5 equiv)
N
N3
1aa
2aa
9
entry solvent
oxidant (equiv)
K2S2O8 (3.0)
Na2S2O8 (3.0)
K2S2O8 (3.0)
K2S2O8 (3.0)
additive (20 mol %)
yield (%)b
55
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
1c
2d
3
MeCN
MeCN
DMF
52
23
4
DMSO
39
5
dioxane K2S2O8 (3.0)
trace
63
6
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
Na2S2O8 (3.0)
(NH4)2S2O8 (3.0)
oxone (3.0)
7
47
8
trace
0
9
PhI(OAc)2 (3.0)
Na2S2O8 (2.5)
Na2S2O8 (3.0)
Na2S2O8 (3.0)
Na2S2O8 (3.0)
Na2S2O8 (3.0)
Na2S2O8 (3.0)
Na2S2O8 (3.0)
Na2S2O8 (3.0)
Na2S2O8 (3.0)
Na2S2O8 (3.0)
Na2S2O8 (3.0)
10
11e
12f
13
14
15
16
17
18
19g
20h
47
33
43
1,10-phen
38
2,2':6',2''-terpyridine
TBAI
33
68
SDS
44
13X M.S. (25 mg)
4Å M.S. (25 mg)
4Å M.S. (25 mg)
4Å M.S. (25 mg)
74
83
29
39
aUnless otherwise noted, the reactions were conducted with 1aa (0.2 mmol), AgSCF3 (1.5 equiv),
oxidant (3.0 equiv), HMPA (0.5 equiv), and additive (20 mol %) or molecular sieve (25 mg) in
anhydrous solvent (2 mL) under an argon atmosphere at 80 °C for 6 h. bIsolated products yields are
given. cOver 25% of 1aa was recovered. dThis reaction was performed for 10 h with over 25% of
e
f
1aa recovered. DBU (0.5 equiv) was used instead of HMPA. This reaction was performed at
g
h
100 °C. Without HMPA. This reaction was performed under an air atmosphere. SDS = Sodium
dodecyl sulfate.
ACS Paragon Plus Environment

Page 5 of 38
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
To investigate the scope of this trifluoromethylthiolation-cyclization transformation, various
substituted o-propargyl arylazides were synthesized. The corresponding trifluoromethylthio-
substituted quinolines (2aa–2ax and 2ba–2bg) could be isolated smoothly (Scheme 2). Both
electron-rich (1aa–1af) and -insufficient (1ag–1al) groups of R1 on the para-position of phenyl
group showed good compatibility with this transformation.
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
The substrate with a large long-chain/branched alkyl group (n-pentyl/t-Bu group) or a strong
electron-withdrawing group (CF3 or CN) were tolerated generating the corresponding products in
47% to 84% yields (2ae, 2af, 2ak and 2al). The substrates with a meta- (1am and 1an) or ortho-
(1ao and 1ar) substituent group worked smoothly as well. The ortho-position steric effect exerted
little influence on this transformation. The developed reaction conditions could also be applied to
multisubstituted substrates (2as–2aw). Notably, the substrate with an electron-withdrawing (nitro
group, 1aw) or a heterocyclic group (2-thienyl group, 1ax) proceeded smoothly in this
transformation as well. Subsequently, several substrates contained distinct substituents of R2 (1ba–
1bg) were prepared to explore the reaction scope. In general, substituents for various electronic
effects showed good compatibilities in this reaction system. Product 2be contained an ortho-methyl
group was identified in a trace yield for ortho-substituent steric effect. When the methyl group was
replaced by a chlorine atom, the corresponding product 2bf was isolated in 84% yield. The
substrates contained a strong electron-donating group (1bg) was tolerated and gave the
corresponding trifluoromethylthio-substituted quinoline product 2bg in 67% yield. The construction
of product 2aa was confirmed by X-ray crystal structure analysis (see the Supporting Information
(SI)).
Scheme 2. Synthesis of Trifluoromethylthio-substituted Quinolines 2a and 2ba
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 38
1
2
3
4
5
6
7
8
SCF
Ag
3 (1.5 equiv)
SCF3
Na2S2O8 (3.0 equiv)
HMPA (0.5 equiv)
4Å MS (25 mg)
R2
R2
N3
R1
N
R1
MeCN, Ar
80 oC, 6 h
1a 1b
2a 2b
(
(
)
)
9
, R1 = H, 83%
, R1 = Ph, 62%
SCF3
2aa
2ag
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
SCF3
, R1 = OMe, 76%
, R1 = Me, 72%
, R1 = Et, 65%
, R1 = F, 74%
2ab
2ac
2ad
2ae
2af
2ah
2ai
R1
, R1 = Cl, 62%
, R1 = Ac, 86%
N
N
2aj
, R1 = n-pentyl, 47%
, R1 = CF3, 72%
, R1 = Me, 74%
, R1 = Cl, 89%
2ak
2al
2am
2an
R1
, R1 = t-Bu, 66%
, R1 = CN, 84%
SCF3
SCF3
R1
SCF3
, R1 = Me, 86%
, R1 = OMe, 73%
, R1 = F, 63%
2ao
N
N
2ap
2aq
2ar
N
N
R1
R1
, R1 = Br, 76%
R1
, R1 = Me, 74%
, R1 = Cl, 64%
, R1 = Me, 66%
, R1 = Cl, 57%
2as
2at
2au
2av
SCF3
SCF3
SCF3
SCF3
NO2
R2
N
N
N
S
MeO
, R2 = OMe, 52%
, R2 = Br, 60%
2bb
2bc
2aw
2ax
2ba
, 54%
, 49%
, 79%
SCF3
SCF3
SCF3
O
N
O
Cl
N
N
R2
OMe
, R2 = Me, trace
, R2 = Cl, 84%
2be
2bf
2bd
, 73%
2bg
, 67%
aUnless otherwise noted, all reactions were performed with 1a/1b (0.2 mmol), AgSCF3 (1.5 equiv),
Na2S2O8 (3.0 equiv), HMPA (0.5 equiv), and 4Å molecular sieve (25 mg) in anhydrous MeCN (2
mL) at 80 °C under an argon atmosphere for 6 h. Isolated products yields are given.
Stimulated by the above result, a series of o-alkynyl benzylazides were synthesized to explore
the reaction scope further. Satisfactorily, as presented in Scheme 3, our expected
trifluoromethylthio-substituted isoquinolines (2ca–2cn) were isolated in moderate to good yields by
prolonging the reaction time to 12 h. In this portion, more by-products came under observation by
TLC analyses, which might be due to the insufficiently selective addition of SCF3 radical onto the
carbon–carbon triple bond of the substrate. Generally, this transformation has the similar electronic
and steric effects with o-propargyl arylazide substrates. Remarkably, the substrate with a
heterocyclic group (2-thienyl, 1cn) or a multiple-ring group (1-naphthyl group, 1cm) also worked
smoothly. The substrate with an alkyl (1co) was unable to afford the respect product. The
construction of 2ca was identified by X-ray crystal structure analysis as well (see the SI).
Scheme 3. Synthesis of Trifluoromethylthio-substituted Isoquinolines 2ca
ACS Paragon Plus Environment

Page 7 of 38
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
SCF
Ag
3 (1.5 equiv)
SCF3
Na2S2O8 (3.0 equiv)
HMPA (0.5 equiv)
4Å MS (25 mg)
N3
R2
R1
R2
R1
R
N
MeCN, Ar
80 oC, 12 h
1c
2c
SCF3
SCF3
2ca
2cb
2cc
2cd
2ce
, R = H, 68%
SCF3
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
, R = OMe, 46%
, R = Et, 53%
, R = Br, 73%
, R = CN, 48%
Cl
N
N
N
2cf
2cg
, 68%
, 81%
SCF3
SCF3
SCF3
SCF3
Cl
N
N
R2
N
N
, R2 = Me, 78%
, R2 = Cl, 57%
F
S
2ci
2cj
2ch
2ck
2cl
, 62%
, 54%
, 73%
SCF3
SCF3
SCF3
N
N
N
2cm
2cn
2co
, trace
, 67%
, 28%
aUnless otherwise noted, all reactions were performed with 1c (0.2 mmol), AgSCF3 (1.5 equiv),
Na2S2O8 (3.0 equiv), HMPA (0.5 equiv), and 4Å molecular sieve (25 mg) in anhydrous MeCN (2
mL) at 80 °C under an argon atmosphere for 12 h. Isolated products yields are given.
Some necessary inhibition experiments were conducted carefully in order to explore the reaction
mechanism (Scheme 4). The reaction was completely inhibited with the addition of BHT (2,6-di-
tert-butyl-4-methylphenol) or TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl), which verified our
hypothesis that this transformation went through a radical process. Silver salts also proved to have
significant effect in the reaction system, since other SCF3 sources (CuSCF3 or NMe4SCF3) failed to
give the corresponding products.
Scheme 4. Exploration Experiments for Mechanism
Radical Trapping Experiments
SCF
Ag
3 (1.5 equiv)
SCF3
Na2S2O8 (3.0 equiv)
HMPA (0.5 equiv)
4Å MS (25 mg)
+
TEMPO (1.5 equiv)
(1)
(2)
N
N3
1aa
MeCN, Ar
80 oC, 6 h
a
2aa
, 0%
SCF
Ag
3 (1.5 equiv)
SCF3
Na2S2O8 (3.0 equiv)
HMPA (0.5 equiv)
4Å MS (25 mg)
+
BHT (1.5 equiv)
N
N3
1aa
MeCN, Ar
80 oC, 6 h
a
2aa
, 0%
Control Experiments
Na2S2O8 (3.0 equiv)
HMPA (0.5 equiv)
4Å MS (25 mg)
SCF3
CuSCF3 (1.5 equiv)
or
NMe4SCF3 (1.5 equiv)
+
(3)
N
N3
MeCN, Ar
80 oC, 6 h
1aa
2aa
, trace
aOver 80% of substrate 1aa was recovered.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 38
1
2
3
4
5
6
7
8
9
According to the precedent literature10 and the above control experiments, a plausible mechanism
is depicted in Scheme 5. The oxidation of AgSCF3 by Na2S2O8 gives the SCF3· radical, which is
added to the carbon-carbon triple bond of substrate 1 to give intermediate A. Intermediate A goes
through the subsequent 6-endo-dig cyclization process to generate radical anion intermediate B,
which then releases a molar of nitrogen to give nitrogen radical intermediate C. An 1,3-radical
migration of intermediate C affords carbon radical intermediate D, which undergoes another SET
process from intermediate D to Ag(II) species to generate product 2.
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
Scheme 5. Plausible Reaction Mechanism
SCF3
SCF3
cyclization
N3
N
N
N
N
SCF3
N
SCF
Ag
3
N
SET
1aa
A
B
2-
2-
SO
4
S2O8
SO4
+
Ag(I)
SET
-N2
2-
S2O8
H
SCF3
SCF3
1,3-radical
migration
SCF3
-H+
Ag(II)
2aa
N
N
N
E
D
C
To sum up, we presented a AgSCF3/Na2S2O8-promoted cascade cyclization of o-propargyl
arylazides (o-alkynyl benzylazides) to synthesize a series of trifluoromethylthio-substituted
quinoline (isoquinoline) derivatives. This transformation occurred smoothly in moderate to
excellent yields with one C(sp2)–N bond and C(sp2)–SCF3 bond concurrently constructed.
According to the control experiment, a radical pathway triggered by a carbon–carbon triple was
involved in this reaction process. So, some particular functional groups (nitro, cyan, and
trifluoromethyl groups) could be applied and were unaffected by strong electronic effect.
■ EXPERIMENTAL SECTION
General Experimental Information. Silica gel (200-300 mesh) was used in column
1
chromatography. H NMR spectra were recorded on 400 or 600 MHz in CDCl3 or d-acetone and
chemical shifts (ppm) were recorded with tetramethylsilane (TMS) as the internal reference standard.
13C{1H} NMR spectra were recorded on 100 or 150 MHz in CDCl3 or d-acetone, 19F spectra were
recorded on 376 MHz in CDCl3 (CFCl3 as outside standard and low field is positive). Multiplicities
are given as: s (singlet), d (doublet), t (triplet), dd (doublet of doublets), dq (doublet of quartets), q
ACS Paragon Plus Environment

Page 9 of 38
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
(quartet) or m (multiplet). IR spectra were recorded on a FT-IR spectrometer and only major peaks
are reported in cm-1. HR-MS was obtained using a Q-Orbitrap (for compounds 1) or Q-TOF (for
compounds 2) instrument equipped with ESI source. The copies of 1H NMR, 13C{1H} NMR, and
19F NMR spectra of all compounds are provided in the Supporting Information. Room temperature
is 23–25 °C. THF was distilled immediately before use from Na/benzophenone. Acetonitrile was
distilled from CaH2 and stored in a dryer before use. Other commercially available reagents and
solvents were used directly.
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
General Procedures for Preparation of Starting Materials. For the synthesis of 1aa (This
procedure could not be used for the synthesis of substrate 1aj, 1al, 1aw and 1ax. Please see Scheme
S1 in the Supporting Information): NaN3 (6.5 g, 100 mmol, 2.0 equiv) was added into a stirred
solution of 2-nitrobenzaldehyde A (7.56 g, 50 mmol) in HMPA (150 mL). The reaction mixture was
allowed to stir at 50 °C for 72 h. After completion of the reaction determined by TLC, the reaction
mixture was quenched by addition of an aqueous saturated solution of NH4Cl (150 mL) and
extracted with methyl tert-butyl ether (3×150 mL). The organic layers were combined to be washed
with brine and dried over Na2SO4 for 20 min. Then the solution would be concentrated under
reduced pressure. The obtained residue would be further purified by flash column chromatography
(silica gel, petroleum ether/ethyl acetate, 500:1) to give 2-azidobenzaldehyde B (96%, 7.06 g, 48
mmol).
n-BuLi (2.5 M, 5.8 mL, 1.2 equiv) was added dropwise via a syringe to a stirred solution of
phenylacetylene (1.71 g, 12 mmol, 1.4 equiv) in dry THF (30 mL) under argon at -78 °C. The
reaction mixture was allowed to stir for 10 min. Then, the solution of 2-azidobenzaldehyde B (1.47
g, 10 mmol) in THF was added at -78 °C. The reaction mixture was allowed to stir for 10 min at
room temperature (Note: prolonging the reaction time would lead to an obvious yield decrease for
this reaction). After the completion of the reaction determined by TLC, the reaction mixture was
quenched by an aqueous saturated solution of NH4Cl (30 mL) and extracted with ethyl acetate (2×50
mL). The organic layers were combined to be washed with brine and dried over Na2SO4 for 20 min.
Then the solution would be concentrated under reduced pressure. The obtained residue would be
further purified by flash column chromatography (silica gel, petroleum ether/ethyl acetate, 4:1) to
give 1-(2-azidophenyl)-3-phenylprop-2-yn-1-ol C (79%, 2.36 g, 9.48 mmol).
Triethylsilane (872 mg, 7.5 mmol, 1.5 equiv) and 2,2,2-trifluoroacetic acid (855 mg, 7.5 mmol,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 38
1
2
3
4
5
6
7
8
9
1.5 equiv) were sequentially added to a stirred solution of 1-(2-azidophenyl)-3-phenylprop-2-yn-1-
ol C (1.25 g, 5 mmol) in dichloromethane (30 mL) at 0 °C. The mixture was allowed to stir over
night at room temperature. After the completion of the reaction determined by TLC, the reaction
mixture was quenched an aqueous saturated solution of NaHCO3 (30 mL) and extracted with
dichloromethane (2×50 mL). The organic layers were combined to be washed with brine and dried
over Na2SO4 for 20 min. Then the solution would be concentrated under reduced pressure. The
obtained residue would be further purified by flash column chromatography (silica gel, petroleum
ether/ethyl acetate, 50:1) to give 1-azido-2-(3-phenylprop-2-yn-1-yl)benzene 1aa (70%, 816.6 mg,
3.5 mmol).
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
For the synthesis of 1aw (This procedure was also used for the synthesis of substrate 1aj, 1al and
1ax. Please see Scheme S2 in the Supporting Information): Ethynylmagnesium bromide (0.5 mol/L
in THF, 45 mL, 1.5 equiv) was added dropwise into a stirred solution of 2-azidobenzaldehyde B
(2.21 g, 15 mmol) in THF (35 mL) under argon. The mixture was allowed to stir at room temperature
for 4 h. After the completion of the reaction determined by TLC, the reaction mixture was quenched
by addition of an aqueous saturated solution of NH4Cl (35 mL) and extracted with ethyl acetate
(2×70 mL). The organic layers were combined to be washed with brine and dried over Na2SO4 for
20 min. Then the solution would be concentrated under reduced pressure. The resulting material 1-
(2-azidophenyl)prop-2-yn-1-ol D (95%, 2.47 g, 14.3 mmol) was directly used for the next step
without further purification.
Pd(PPh3)2Cl2 (56.2 mg, 0.08 mmol, 1 mol %) and CuI (30.5 mg, 0.16 mmol, 2 mol %) were
sequentially added to a stirred solution of 1-(2-azidophenyl)prop-2-yn-1-ol D (1.39 g, 8 mmol) in
triethylamine (40 mL) under argon at room temperature. The mixture was allowed to stir for 10 min.
Then 2-iodo-1-methoxy-4-nitrobenzene (2.68 g, 9.6 mmol, 1.2 equiv) was added. The mixture was
allowed to stir overnight. An aqueous saturated solution of NH4Cl (40 mL) was poured into the
resulting mixture and the mixture was extracted with ethyl acetate (2×50 mL). The organic layers
were combined to be washed with brine and dried over Na2SO4 for 20 min. Then the solution would
be concentrated under reduced pressure. The obtained residue would be further purified by flash
column chromatography (silica gel, petroleum ether/ethyl acetate, 2:1) to give 1-(2-azidophenyl)-3-
(2-methoxy-5-nitrophenyl)prop-2-yn-1-ol E (95%, 2.46 g, 7.6 mmol).
Substrate 2-(3-(2-azidophenyl)prop-1-yn-1-yl)-1-methoxy-4-nitroben zene 1aw (68%) was
ACS Paragon Plus Environment

Page 11 of 38
The Journal of Organic Chemistry
1
2
3
4
synthesized via the similar preparation procedure of substrate 1aa.
5
6
7
8
For the synthesis of 1ca (Please see Scheme S3 in the Supporting Information): Pd(PPh3)2Cl2
(210.6 mg, 0.3 mmol, 1 mol %) and CuI (114.3 mg, 0. 6 mmol, 2 mol %) were sequentially added
to a stirred solution of phenylacetylene (3.68 g, 36 mmol, 1.2 equiv) in triethylamine (100 mL)
under argon at room temperature. The mixture was allowed to stir for 10 min. Then (2-
iodophenyl)methanol F (7.02 g, 30 mmol) was added. The mixture was allowed to stir overnight.
An aqueous saturated solution of NH4Cl (80 mL) was poured into the resulting mixture and the
mixture was extracted with ethyl acetate (2×150 mL). The organic layers were combined to be
washed with brine and dried over Na2SO4 for 20 min. Then the solution would be concentrated
under reduced pressure. The obtained residue would be further purified by flash column
chromatography (silica gel, petroleum ether/ethyl acetate/triethylamine, 100:25:1) to give (2-
(phenylethynyl)phenyl)methanol G (99%, 6.19 g, 29.7 mmol).
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
DBU (1.98 g, 13 mmol, 1.3 equiv) and diphenyl phosphoryl azide (1.65 g, 6 mmol, 1.2 equiv)
were sequentially added portion-wise to a solution of (2-(phenylethynyl)phenyl)methanol G (1.05
g, 5 mmol) in toluene (25 mL) at room temperature. The mixture was allowed to stir overnight.
After the completion of the reaction determined by TLC analysis, the reaction mixture was
extracted with ethyl acetate (2×30 mL). The organic layers were combined to be washed with brine
and dried over Na2SO4 for 20 min. Then the solution would be concentrated under reduced pressure.
The obtained residue would be further purified by flash column chromatography (silica gel,
petroleum ether/ethyl acetate, 10:1) to give 1-(azidomethyl)-2-(phenylethynyl)benzene 1ca (83 %,
4.2 mmol, 0.97 g).
General Procedure for the Synthesis of Products. For the synthesis of 2aa (Please see
Scheme S4 in the Supporting Information): Na2S2O8 (142.9 mg, 0.6 mmol, 3.0 equiv), AgSCF3
(62.7 mg, 0.3 mmol, 1.5 equiv) and 4Å molecular sieve (25 mg) were sequentially added an oven-
dried tube charged with 1-azido-2-(3-phenylprop-2-yn-1-yl) benzene (1aa; 46.7 mg, 0.2 mmol).
The tube was evacuated and backfilled with argon (repeated three times). And then, HMPA (17.4
μL, 0.5 eq) and anhydrous MeCN (2 mL) were added via syringe. The resulting mixture was
allowed to stir at 80 °C for 6 h, and then extracted with ethyl ether (2×20 mL), washed with a
saturated aqueous solution of saturated brine, dried over Na2SO4, and evaporated under reduced
pressure. The residue was further purified by chromatography on silica gel (petroleum ether/ethyl
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 38
1
2
3
4
5
6
acetate/triethylamine, 100:30:1) to afford the product 2-phenyl-3-((trifluoromethyl)thio)quinoline
(2aa) in 83% yield.
7
8
9
Scale-up experiment. When the reaction system was scaled up to gram scale (1.0 g of 1aa was
added) under the optimal conditions, the corresponding product 2aa was isolated in 67% (0.88 g).
for 12h.
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
1
1-azido-2-(3-(4-methoxyphenyl)prop-2-yn-1-yl)benzene (1ab): yellow oil; 0.87 g; 66%; H
NMR (400 MHz, CDCl3) δ ppm 7.60 (d, J = 6.8 Hz, 1H), 7.39−7.37 (m, 2H), 7.29 (t, J = 7.6 Hz,
1H), 7.15−7.12 (m, 2H), 6.83−6.81 (m, 2H), 3.78 (s, 3H), 3.72 (s, 2H); 13C{1H} NMR (100 MHz,
CDCl3) δ ppm 159.2, 137.5, 133.0, 129.6, 128.2, 128.0, 124.9, 117.8, 115.6, 113.8, 85.0, 82.8, 55.2,
21.2. HRMS (ESI/Q-Orbitrap) m/z: [M + H]+ Calcd for C16H14N3O 264.1131; Found 264.1131 (0
ppm).
1-azido-2-(3-(p-tolyl)prop-2-yn-1-yl)benzene (1ac): yellow oil; 0.73 g; 59%; 1H NMR (400 MHz,
CDCl3) δ ppm 7.62−7.60 (m, 1H), 7.34 (d, J = 8.0 Hz, 2H), 7.30 (t, J = 7.6 Hz, 1H), 7.16−7.13 (m,
2H), 7.10 (d, J = 8.0 Hz, 2H), 3.73 (s, 2H), 2.34 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ ppm
137.9, 137.6, 131.5, 129.7, 129.0, 128.1, 128.0, 124.9, 120.4, 117.9, 85.8, 83.1, 21.4, 21.2. HRMS
(ESI/Q-Orbitrap) m/z: [M + H]+ Calcd for C16H14N3 248.1182; Found 248.1182 (0 ppm).
1
1-azido-2-(3-(4-ethylphenyl)prop-2-yn-1-yl)benzene (1ad): yellow oil; 0.67 g; 51%; H NMR
(400 MHz, CDCl3) δ ppm 7.62 (d, J = 7.6 Hz, 1H), 7.37 (d, J = 8.0 Hz, 2H), 7.32−7.28 (m, 1H),
7.15 (dd, J = 8.8 Hz 4.0 Hz, 4H), 3.73 (s, 2H), 2.63 (q, J = 7.6 Hz, 2H), 1.22 (t, J = 7.6 Hz, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ ppm 144.2, 137.6, 131.6, 129.6, 128.1, 128.0, 127.8, 124.9,
120.7, 117.8, 85.8, 83.1, 76.9, 28.8, 21.2, 15.4. HRMS (ESI/Q-Orbitrap) m/z: [M + H]+ Calcd for
C17H16N3 262.1339; Found 262.1340 (0.4 ppm).
1-azido-2-(3-(4-pentylphenyl)prop-2-yn-1-yl)benzene (1ae): yellow oil; 0.65 g; 43%; 1H NMR
(400 MHz, CDCl3) δ ppm 7.60 (dd, J = 7.6 Hz 0.8 Hz, 1H), 7.36 (s, J = 8.0 Hz, 2H), 7.27 (t, J = 7.6
Hz, 1H), 7.14−7.08 (m, 4H), 3.72 (s, 2H), 3.58−3.55 (m, 2H), 1.62−1.55 (m, 2H), 1.34−1.26 (m,
4H), 0.91−0.86 (m, 3H);13C{1H} NMR (100 MHz, CDCl3) δ ppm 142.9, 137.5, 131.5, 129.6, 128.3,
128.1, 128.0, 124.8, 120.6, 117.7, 85.8, 83.2, 35.8, 31.4, 30.9, 22.5, 21.2, 14.0. HRMS (ESI/Q-
Orbitrap) m/z: [M + H]+ Calcd for C20H22N3 304.1808; Found 304.1808 (0 ppm).
1
4-(3-(2-azidophenyl)prop-1-yn-1-yl)-1,1'-biphenyl (1ag): yellow solid; 0.90 g; 58%; H NMR
(400 MHz, CDCl3) δ ppm 7.61 (d, J = 7.2 Hz, 1H), 7.55 (d, J = 7.2 Hz, 2H), 7.51 (s, 4H), 7.40 (t, J
ACS Paragon Plus Environment

Page 13 of 38
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
= 7.6 Hz, 2H), 7.33−7.26 (m, 2H), 7.15−7.10 (m, 2H), 3.74 (s, 2H); 13C{1H} NMR (100 MHz,
CDCl3) δ ppm 140.5, 140.3, 137.6, 132.0, 129.6, 128.8, 128.1, 127.9, 127.5, 126.9, 126.9, 124.9,
122.4, 117.8, 87.3, 82.9, 21.2. HRMS (ESI/Q-Orbitrap) m/z: [M + H]+ Calcd for C21H16N3 310.1339;
Found 310.1340 (0.3 ppm).
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
1-azido-2-(3-(4-fluorophenyl)prop-2-yn-1-yl)benzene (1ah): yellow oil; 0.97 g; 77%; 1H NMR
(400 MHz, CDCl3) δ ppm 7.58−7.56 (m, 1H), 7.44−7.39 (m, 2H), 7.30 (dt, J = 8.0 Hz 1.2 Hz, 1H),
7.16−7.12 (m, 2H), 7.01−6.96 (m, 2H), 3.71 (s, 2H);13C{1H} NMR (100 MHz, CDCl3) δ ppm 162.2
(d, 1J = 247 Hz, 1C), 137.6, 133.4 (d, 3J = 8 Hz, 1C), 129.6, 128.1, 127.9, 124.9, 119.6 (d, 4J = 4
Hz, 1C), 117.9, 115.4 (d, 2J = 22 Hz, 1C), 86.3 (d, 5J = 1 Hz, 1C), 81.8, 21.1; 19F NMR (376 MHz,
CDCl3) δ ppm -112.03 (s, 1F). HRMS (ESI/Q-Orbitrap) m/z: [M + H]+ Calcd for C15H11FN3
252.0932; Found 252.0932 (0 ppm).
1-(4-(3-(2-azidophenyl)prop-1-yn-1-yl)phenyl)ethan-1-one (1aj): yellow solid; 1.05 g; 76%; 1H
NMR (400 MHz, CDCl3) δ ppm 7.87 (d, J = 8.4 Hz, 2H), 7.56 (d, J = 7.2 Hz, 1H), 7.51 (d, J = 8.0
Hz, 2H), 7.31 (t, J = 7.6 Hz, 1H), 7.14 (t, J = 8.4 Hz, 2H), 3.75 (s, 2H), 2.57 (s, 3H); 13C{1H} NMR
(100 MHz, CDCl3) δ ppm 197.2, 137.6, 135.9, 131.7, 129.5, 128.4, 128.2, 128.1, 127.3, 124.9, 117.9,
90.4, 82.2, 26.5, 21.2. HRMS (ESI/Q-Orbitrap) m/z: [M + H]+ Calcd for C17H14N3O 276.1131;
Found 276.1133 (0.7 ppm).
1-azido-2-(3-(4-(trifluoromethyl)phenyl)prop-2-yn-1-yl)benzene (1ak): yellow solid; 1.07 g;
71%; 1H NMR (400 MHz, CDCl3) δ ppm 7.56−7.52 (m, 5H), 7.30 (t, J = 7.6 Hz, 1H), 7.14 (t, J =
7.6 Hz, 2H), 3.74 (s, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ ppm 137.7, 131.9, 129.6 (q, J = 32
Hz, 1C), 129.6, 128.3, 127.4, 127.4, 127.4, 125.3, 125.1 (q, J = 4 Hz, 1C), 124.9, 122.6, 117.9, 89.5,
81.7, 21.2; 19F NMR (376 MHz, CDCl3) δ ppm -63.14 (s, 3F). HRMS (ESI/Q-Orbitrap) m/z: [M +
H]+ Calcd for C16H11F3N3 302.0900; Found 302.0898 (0.7 ppm).
4-(3-(2-azidophenyl)prop-1-yn-1-yl)benzonitrile (1al): yellow solid; 0.68 g; 53%; 1H NMR (400
MHz, CDCl3) δ ppm 7.57 (d, J = 8.4 Hz, 2H), 7.53−7.50 (m, 3H), 7.33 (t, J = 7.2 Hz, 1H), 7.17−7.14
(m, 2H), 3.76 (s, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ ppm 137.7, 132.1, 131.9, 129.5, 128.5,
128.4, 127.1, 124.9, 118.5, 118.0, 111.2, 91.8, 81.4, 21.2. HRMS (ESI/Q-Orbitrap) m/z: [M + H]+
Calcd for C16H11N4 259.0978; Found 259.0978 (0 ppm).
1-azido-2-(3-(3-chlorophenyl)prop-2-yn-1-yl)benzene (1an): yellow oil; 0.84 g; 63%; 1H NMR
(400 MHz, CDCl3) δ ppm 7.54 (d, J = 7.6 Hz, 1H), 7.41 (d, J = 0.8 Hz, 1H), 7.31−7.23 (m, 3H),
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 38
1
2
3
4
5
6
7
8
7.20−7.10 (m, 3H), 3.71 (s, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ ppm 137.6, 134.0, 131.5,
129.7, 129.5, 129.4, 128.1, 128.1, 127.5, 125.2, 124.9, 117.8, 88.1, 81.6, 21.1. HRMS (ESI/Q-
Orbitrap) m/z: [M + H]+ Calcd for C15H11ClN3 268.0636; Found 268.0635 (0.4 ppm).
9
1-azido-2-(3-(o-tolyl)prop-2-yn-1-yl)benzene (1ao): yellow oil; 0.89 g; 72%; 1H NMR (400 MHz,
CDCl3) δ ppm 7.63 (d, J = 7.2 Hz, 1H), 7.42 (d, J = 7.6 Hz, 1H), 7.31 (t, J = 7.2 Hz, 1H), 7.19−7.11
(m, 5H), 3.79 (s, 2H), 2.44 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ ppm 140.1, 137.6, 132.0,
129.6, 129.3, 128.2, 128.1, 127.8, 125.5, 124.9, 123.3, 117.9, 90.5, 81.9, 21.4, 20.8. HRMS (ESI/Q-
Orbitrap) m/z: [M + H]+ Calcd for C16H14N3 248.1182; Found 248.1182 (0 ppm).
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
1
1-azido-2-(3-(2-methoxyphenyl)prop-2-yn-1-yl)benzene (1ap): yellow oil; 0.84 g; 64%; H
NMR (400 MHz, CDCl3) δ ppm 7.71 (d, J = 7.6 Hz, 1H), 7.43 (dd, J = 7.6 Hz 1.6 Hz, 1H), 7.31−7.24
(m, 2H), 7.15 (t, J = 7.6 Hz, 2H), 6.89 (dd, J = 13.6 Hz 7.6 Hz, 2H), 3.89 (s, 3H), 3.81 (s, 2H);
13C{1H} NMR (100 MHz, CDCl3) δ ppm 160.0, 137.5, 133.6, 129.7, 129.3, 128.1, 127.9, 124.9,
120.4, 117.7, 112.6, 110.5, 90.7, 79.4, 55.8, 21.5. HRMS (ESI/Q-Orbitrap) m/z: [M + H]+ Calcd for
C16H14N3O 264.1131; Found 264.1132 (0.4 ppm).
1-azido-2-(3-(2-fluorophenyl)prop-2-yn-1-yl)benzene (1aq): yellow oil; 0.85 g; 68%; 1H NMR
(400 MHz, CDCl3) δ ppm 7.63 (d, J = 7.6 Hz, 1H), 7.44 (dt, J = 7.6 Hz 1.6 Hz, 1H), 7.33−7.24 (m,
2H), 7.18−7.14 (m, 2H), 7.09−7.04 (m, 2H), 3.79 (s, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ ppm
162.9 (d, 1J = 249 Hz, 1C), 137.6, 133.6 (d, 3J = 2 Hz, 1C), 129.6, 129.5 (d, 3J = 8 Hz, 1C), 128.1,
127.6, 125.0, 123.8 (d, 4J = 4 Hz, 1C), 117.8, 115.4 (d, 2J = 21 Hz, 1C), 112.0 (d, 2J = 15 Hz, 1C) ,
92.1 (d, 5J = 247 Hz, 3C), 76.4, 21.4; 19F NMR (376 MHz, CDCl3) δ ppm -111.00 (s, 1F). HRMS
(ESI/Q-Orbitrap) m/z: [M + H]+ Calcd for C15H11FN3 252.0932; Found 252.0932 (0 ppm).
1-azido-2-(3-(2-bromophenyl)prop-2-yn-1-yl)benzene (1ar): yellow oil; 1.09 g; 70%; 1H NMR
(400 MHz, CDCl3) δ ppm 7.71 (d, J = 7.6 Hz, 1H), 7.55 (d, J = 8.0 Hz, 1H), 7.47−7.45 (m, 1H),
7.29 (t, J = 7.6 Hz, 1H), 7.22 (t, J = 7.6 Hz, 1H), 7.16−7.10 (m, 3H), 3.79 (s, 2H); 13C{1H} NMR
(100 MHz, CDCl3) δ ppm 137.5, 133.4, 132.3, 129.7, 129.0, 128.1, 127.5, 126.9, 125.6, 125.5, 124.9,
117.8, 91.6, 81.7, 21.4. HRMS (ESI/Q-Orbitrap) m/z: [M + H]+ Calcd for C15H11BrN3 312.0131;
Found 312.0129 (0.6 ppm).
1
1-(3-(2-azidophenyl)prop-1-yn-1-yl)-3,5-dimethylbenzene (1as): yellow oil; 0.73 g; 56%; H
NMR (400 MHz, CDCl3) δ ppm 7.59 (d, J = 8.0 Hz, 1H), 7.25 (t, J = 7.6 Hz, 1H), 7.10 (dd, J = 16.0
Hz 8.0 Hz, 4H), 6.89 (s, 1H), 3.70 (s, 2H), 2.25 (s, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ ppm
ACS Paragon Plus Environment

Page 15 of 38
The Journal of Organic Chemistry
1
2
3
4
5
6
137.7, 137.5, 129.7, 129.5, 129.3, 128.0, 127.9, 124.8, 123.1, 117.7, 85.7, 83.3, 21.1, 21.0. HRMS
(ESI/Q-Orbitrap) m/z: [M + H]+ Calcd for C17H16N3 262.1339; Found 262.1340 (0.4 ppm).
7
8
1
1-(3-(2-azidophenyl)prop-1-yn-1-yl)-3,5-dichlorobenzene (1at): yellow solid; 1.09 g; 72%; H
9
NMR (400 MHz, CDCl3) δ ppm 7.50 (d, J = 7.6 Hz, 1H), 7.35−7.23 (m, 4H), 7.16−7.13 (m, 2H),
3.71 (s, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ ppm 137.7, 134.7, 129.8, 129.5, 128.3, 128.2,
127.2, 126.3, 124.9, 117.9, 89.6, 80.4, 21.1. HRMS (ESI/Q-Orbitrap) m/z: [M + H]+ Calcd for
C15H10Cl2N3 302.0246; Found 302.0245 (0.3 ppm).
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
1
4-(3-(2-azidophenyl)prop-1-yn-1-yl)-1,2-dimethylbenzene (1au): yellow oil; 0.88 g; 67%; H
NMR (400 MHz, CDCl3) δ ppm 7.60 (d, J = 7.6 Hz, 1H), 7.29−7.23 (m, 2H), 7.20−7.09 (m, 1H),
7.03 (d, J = 7.6 Hz, 2H), 3.71 (s, 1H), 2.22 (s, 3H), 2.20 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3)
δ ppm 137.5, 136.6, 136.5, 132.7, 129.6, 129.5, 129.0, 128.2, 128.0, 124.8, 120.7, 117.7, 85.5, 83.2,
21.2, 19.6, 19.5. HRMS (ESI/Q-Orbitrap) m/z: [M + H]+ Calcd for C17H16N3 262.1339; Found
262.1338 (0.4 ppm).
4-(3-(2-azidophenyl)prop-1-yn-1-yl)-2-chloro-1-methylbenzene (1av): yellow solid; 0.83 g;
59%; 1H NMR (400 MHz, CDCl3) δ ppm 7.54 (d, J = 7.6 Hz, 1H), 7.40 (s, 1H), 7.26 (t, J = 7.6 Hz,
1H), 7.20 (d, J = 8.0 Hz, 1H), 7.10 (dd, J = 16.8 Hz 8.0 Hz, 3H), 3.69 (s, 2H), 2.31 (s, 3H); 13C{1H}
NMR (100 MHz, CDCl3) δ ppm 137.5, 136.0, 134.0, 131.9, 130.6, 129.7, 129.5, 128.1, 127.7, 124.8,
122.5, 117.8, 87.1, 81.7, 21.1, 19.9. HRMS (ESI/Q-Orbitrap) m/z: [M + H]+ Calcd for C16H13ClN3
282.0793; Found 282.0793 (0 ppm).
2-(3-(2-azidophenyl)prop-1-yn-1-yl)-1-methoxy-4-nitrobenzene (1aw): yellow solid; 1.22 g;
79%; 1H NMR (400 MHz, CDCl3) δ ppm 8.28 (d, J = 2.8 Hz, 1H), 8.16 (dd, J = 9.2 Hz 6.8 Hz, 1H),
7.63 (d, J = 7.2 Hz, 1H), 7.32 (t, J = 7.6 Hz, 1H), 7.17 (t, J = 8.4 Hz, 2H), 6.92 (d, J = 9.2 Hz, 1H),
3.98 (s, 1H), 3.80 (s, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ ppm 164.6, 140.9, 137.6, 129.6,
129.0, 128.2, 127.3, 125.2, 124.9, 117.9, 113.8, 110.1, 93.0, 77.0, 56.5, 21.4. HRMS (ESI/Q-
Orbitrap) m/z: [M + H]+ Calcd for C16H13N4O3 309.0982; Found 309.0981 (0.3 ppm).
2-(3-(2-azidophenyl)prop-1-yn-1-yl)thiophene (1ax): light red oil; 0.49 g; 41%; 1H NMR (400
MHz, CDCl3) δ ppm 7.53 (d, J = 7.2 Hz, 1H), 7.26 (t, J = 7.6 Hz, 1H), 7.15 (d, J = 4.8 Hz, 2H),
7.10 (dd, J = 12.4 Hz 8.4 Hz, 2H), 6.92−6.90 (m, 1H), 3.72 (s, 2H); 13C{1H} NMR (100 MHz,
CDCl3) δ ppm 137.5, 131.4, 129.6, 128.1, 127.5, 126.7, 126.3, 124.8, 123.5, 117.8, 90.7, 76.1, 21.4.
HRMS (ESI/Q-Orbitrap) m/z: [M + H]+ Calcd for C13H10N3S 240.0590; Found 240.0585 (2.1 ppm).
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 38
1
2
3
4
5
6
7
8
9
1-azido-3-methyl-2-(3-(m-tolyl)prop-2-yn-1-yl)benzene (1ba): yellow oil; 0.95 g; 73%; 1H NMR
(400 MHz, CDCl3) δ ppm 7.16−7.07 (m, 4H), 7.00 (d, J = 7.6 Hz, 1H), 6.96−6.92 (m, 2H), 3.68 (s,
2H), 2.41 (s, 3H), 2.23 (s, 3H);13C{1H} NMR (100 MHz, CDCl3) δ ppm 138.8, 137.8, 137.6, 132.1,
128.6, 128.5, 127.9, 127.7, 126.9, 126.7, 123.4, 115.8, 86.4, 80.4, 21.0, 19.5, 17.8. HRMS (ESI/Q-
Orbitrap) m/z: [M + H]+ Calcd for C17H16N3 262.1339; Found 262.1339 (0 ppm).
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
2-azido-4-methoxy-1-(3-phenylprop-2-yn-1-yl)benzene (1bb): yellow oil; 0.74 g; 56%; 1H NMR
(400 MHz, CDCl3) δ ppm 7.48−7.42 (m, 3H), 7.27 (t, J = 2.8 Hz, 3H), 6.69−6.67 (m, 2H), 3.79 (m,
3H), 3.66 (s, 2H);13C{1H} NMR (100 MHz, CDCl3) δ ppm 159.5, 138.3, 131.6, 130.4, 128.2, 127.8,
123.6, 120.2, 110.1, 104.0, 87.1, 82.6, 55.4, 20.4. HRMS (ESI/Q-Orbitrap) m/z: [M + H]+ Calcd for
C16H14N3O 264.1131; Found 264.1129 (0.8 ppm).
1
2-azido-4-bromo-1-(3-phenylprop-2-yn-1-yl)benzene (1bc): yellow oil; 1.05 g; 67%; H NMR
(400 MHz, CDCl3) δ ppm 7.55 (d, J = 8.4 Hz, 1H), 7.43 (t, J = 1.6 Hz, 2H), 7.29−7.27 (m, 3H),
6.82−6.71 (m, 1H), 6.70 (s, 1H), 3.67 (s, 2H);13C{1H} NMR (100 MHz, CDCl3) δ ppm 139.9, 138.9,
131.6, 130.7, 128.2, 127.9, 124.6, 123.3, 115.2, 108.5, 86.2, 83.2, 20.7. HRMS (ESI/Q-Orbitrap)
m/z: [M + H]+ Calcd for C15H11BrN3 312.0131; Found 312.0131 (0 ppm).
2-azido-4-chloro-1-(3-(4-methoxyphenyl)prop-2-yn-1-yl)benzene (1bd): yellow solid; 0.80 g;
54%; 1H NMR (400 MHz, CDCl3) δ ppm 7.54 (d, J = 8.4 Hz, 1H), 7.35 (d, J = 8.4 Hz, 2H), 6.79
(d, J = 8.0 Hz, 3H), 6.66 (s, 1H), 3.74 (s, 3H), 3.63 (s, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ
ppm 159.2, 139.7, 138.8, 132.8, 130.6, 124.8, 115.4, 115.1, 113.7, 108.4, 84.5, 83.0, 55.0, 20.7.
HRMS (ESI/Q-Orbitrap) m/z: [M + H]+ Calcd for C16H13ClN3O 298.0742; Found 298.0742 (0 ppm).
2-azido-1-methyl-3-(3-(m-tolyl)prop-2-yn-1-yl)benzene (1be): yellow oil; 0.76 g; 58%; 1H NMR
(400 MHz, CDCl3) δ ppm 7.40 (d, J = 6.8 Hz, 1H), 7.25 (d, J = 9.6 Hz, 2H), 7.15 (t, J = 7.6 Hz,
1H), 7.10−7.04 (m, 3H), 3.81 (s, 2H), 2.40 (s, 3H), 2.28 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3)
δ ppm 137.8, 136.2, 132.5, 132.2, 130.8, 130.0, 128.7, 128.7, 128.1, 127.3, 126.0, 123.3, 86.4, 83.0,
22.4, 21.1, 17.9. HRMS (ESI/Q-Orbitrap) m/z: [M + H]+ Calcd for C17H16N3 262.1339; Found
262.1339 (0 ppm).
2-azido-1-chloro-3-(3-(m-tolyl)prop-2-yn-1-yl)benzene (1bf): yellow oil; 0.87 g; 62%; 1H NMR
(400 MHz, CDCl3) δ ppm 7.47 (d, J = 7.6 Hz, 1H), 7.26−7.23 (m, 3H), 7.17 (t, J = 7.6 Hz, 1H),
7.07 (t, J = 8.0 Hz, 2H), 3.79 (m, 2H), 2.30 (s, 3H);13C{1H} NMR (100 MHz, CDCl3) δ ppm 137.9,
134.2, 132.4, 132.2, 129.4, 129.1, 128.8, 128.6, 128.1, 127.8, 126.3, 123.0, 85.6, 83.5, 22.6, 21.2.
ACS Paragon Plus Environment

Page 17 of 38
The Journal of Organic Chemistry
1
2
3
4
HRMS (ESI/Q-Orbitrap) m/z: [M + H]+ Calcd for C16H13ClN3 282.0793; Found 282.0792 (0.4 ppm).
5
6
1
5-azido-6-(3-phenylprop-2-yn-1-yl)benzo[d][1,3]dioxole (1bg): yellow solid; 0.73 g; 53%; H
7
8
9
NMR (400 MHz, CDCl3) δ ppm 7.43 (t, J = 3.6 Hz, 2H), 7.28 (d, J = 2.4 Hz, 3H), 7.07 (s, 1H), 6.64
(s, 1H), 5.94 (s, 2H), 3.65 (s, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ ppm 147.3, 144.9, 131.6,
130.3, 128.2, 127.9, 123.4, 121.0, 109.4, 101.6, 99.1, 86.8, 82.8, 20.9. HRMS (ESI/Q-Orbitrap) m/z:
[M + H]+ Calcd for C16H12N3O2 278.0924; Found 278.0922 (0.7 ppm).
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
1
1-(azidomethyl)-2-((4-ethylphenyl)ethynyl)benzene (1cc): light yellow oil; 1.08 g; 83%; H
NMR (400 MHz, CDCl3) δ ppm 7.55−7.53 (m, 1H), 7.46 (d, J = 8.0 Hz, 2H), 7.35 (d, J = 7.2 Hz,
1H), 7.32−7.25 (m, 2H), 7.16 (d, J = 8.0 Hz, 2H), 4.57 (m, 2H), 2.63 (q, J = 7.6 Hz, 2H), 1.22 (t, J
= 7.6 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ ppm 145.0, 137.0, 132.3, 131.5, 128.4, 128.4,
128.1, 127.9, 123.0, 119.9, 94.8, 85.9, 53.2, 28.8, 15.3. HRMS (ESI/Q-Orbitrap) m/z: [M + H]+
Calcd for C17H16N3 262.1339; Found 262.1339 (0 ppm).
1
1-(azidomethyl)-2-((4-bromophenyl)ethynyl)benzene (1cd): light yellow oil; 1.19 g; 76%; H
NMR (400 MHz, CDCl3) δ ppm 7.54 (d, J = 7.2 Hz, 1H), 7.46 (d, J = 8.4 Hz, 2H), 7.38−7.28 (m,
5H), 4.55 (s, 2H);13C{1H} NMR (100 MHz, CDCl3) δ ppm 137.1, 132.9, 132.4, 131.6, 128.9, 128.5,
128.2, 122.8, 122.4, 121.7, 93.3, 87.7, 53.2. HRMS (ESI/Q-Orbitrap) m/z: [M + H]+ Calcd for
C15H11BrN3 312.0131; Found 312.0129 (0.6 ppm).
1
4-((2-(azidomethyl)phenyl)ethynyl)benzonitrile (1ce): light yellow oil; 0.94 g; 73%; H NMR
(400 MHz, CDCl3) δ ppm 7.64−7.58 (m, 5H), 7.41 (d, J = 4.0 Hz, 2H), 7.38−7.33 (m, 1H), 4.58 (m,
2H); 13C{1H} NMR (100 MHz, CDCl3) δ ppm 137.3, 132.6, 131.9, 131.9, 129.5, 128.7, 128.3,
127.5, 121.7, 118.3, 111.7, 92.5, 90.7, 53.1. HRMS (ESI/Q-Orbitrap) m/z: [M + H]+ Calcd for
C16H11N4 259.0978; Found 259.0978 (0 ppm).
1
2-(azidomethyl)-4-methyl-1-(phenylethynyl)benzene (1ci): light yellow oil; 1.06 g; 86%; H
NMR (400 MHz, CDCl3) δ ppm 7.53−7.52 (m, 2H), 7.45 (d, J = 7.6 Hz, 1H), 7.32 (d, J = 3.2 Hz,
3H), 7.17 (s, 1H), 7.10 (d, J = 7.6 Hz, 1H), 4.54 (s, 2H), 2.35 (s, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ ppm 138.9, 136.9, 132.2, 131.4, 129.2, 128.9, 128.3, 128.3, 123.0, 119.7, 93.7, 86.7, 53.2,
21.4. HRMS (ESI/Q-Orbitrap) m/z: [M + H]+ Calcd for C16H14N3 248.1182; Found 248.1183 (0.4
ppm).
1
2-(azidomethyl)-1-fluoro-3-(phenylethynyl)benzene (1ck): light yellow oil; 0.93 g; 74%; H
NMR (400 MHz, CDCl3) δ ppm 7.56−7.54 (m, 2H), 7.38−7.35 (m, 4H), 7.28 (dt, J = 8.0 Hz 5.6 Hz,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 38
1
2
3
4
5
6
7
8
9
1H), 7.08 (t, J = 8.8 Hz, 1H), 4.61 (s, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ ppm 161.19 (d, 1J
= 247 Hz, 1C), 131.6, 130.0 (d, 3J = 9 Hz, 1C), 128.9, 128.4, 128.2 (d, 4J = 3 Hz, 1C), 125.8 (d, 3J
= 5 Hz, 1C), 124.2 (d, 2J = 17 Hz, 1C), 122.3, 115.9 (d, 2J = 22 Hz, 1C), 94.9, 85.6 (d, 5J = 4 Hz,
1C), 46.3 (d, 3J = 3 Hz, 1C); 19F NMR (376 MHz, CDCl3) δ ppm -116.21 (t, J = 7.1 Hz, 1F). HRMS
(ESI/Q-Orbitrap) m/z: [M + H]+ Calcd for C15H11FN3 252.0932; Found 252.0929 (1.2 ppm).
1-((2-(azidomethyl)phenyl)ethynyl)-3,5-dimethylbenzene (1cl): light yellow oil; 1.14 g; 87%; 1H
NMR (400 MHz, CDCl3) δ ppm 7.55−7.53 (m, 1H), 7.37−7.26 (m, 3H), 7.17 (s, 2H), 6.96 (s, 1H),
4.58 (s, 2H), 2.30 (s, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ ppm 137.9, 137.0, 132.3, 130.5,
129.2, 128.5, 128.4, 128.1, 122.9, 122.4, 95.0, 85.8, 53.2, 21.0. HRMS (ESI/Q-Orbitrap) m/z: [M +
H]+ Calcd for C17H16N3 262.1339; Found 262.1338 (0.4 ppm).
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
1
2-phenyl-3-((trifluoromethyl)thio)quinoline (2aa): white solid; 50.7 mg; 83%; H NMR (400
MHz, CDCl3) δ ppm 8.66 (s, 1H), 8.19 (d, J = 8.0 Hz, 1H), 7.90 (d, J = 7.2 Hz, 1H), 7.84−7.81 (m,
1H), 7.62 (d, J = 6.0 Hz, 3H), 7.50 (d, J = 4.4 Hz, 3H); 13C{1H} NMR (150 MHz, CDCl3) δ ppm
161.9, 148.1 ,145.9, 139.3, 131.7, 129.6, 129.6, 129.2 (q, J = 308 Hz, 1C, SCF3), 128.8, 128.1,
127.6, 127.6, 127.1, 118.0 (J = 2 Hz, 1C, C-SCF3, quartet peak should be obtained, however, doublet
peak was observed due to the low resolution of NMR machine); 19F NMR (376 MHz, CDCl3) δ ppm
-42.43 (s, 3F). IR (neat, cm-1): 3060, 2925, 1772, 1614, 1576, 1549, 1481, 1443, 1400, 1369, 1114,
962, 918, 866, 790, 758, 723, 699, 604; HRMS (ESI/Q-TOF) m/z: [M + Na]+ Calcd for
C16H10F3NNaS 328.0378; Found 328.0384 (1.8 ppm).
2-(4-methoxyphenyl)-3-((trifluoromethyl)thio)quinoline (2ab): yellow solid; 51.0 mg; 76%; 1H
NMR (400 MHz, CDCl3) δ ppm 8.62 (s, 1H), 8.18−8.13 (m, 2H), 7.87 (d, J = 8.4 Hz, 1H), 7.84−7.79
(m, 1H), 7.62−7.59 (m, 2H), 7.06−7.02 (m, 2H), 3.88 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ
ppm 160.2, 148.1, 145.8, 136.6, 131.6, 131.2, 129.5, 129.2 (q, J = 308 Hz, 1C, SCF3), 127.6, 126.9,
125.9, 118.0 (J = 1 Hz, 1C, C-SCF3, quartet peak should be obtained, however, doublet peak was
observed due to the low resolution of NMR machine), 114.2, 113.6, 55.3; 19F NMR (376 MHz,
CDCl3) δ ppm -42.46 (s, 3F). IR (neat, cm-1): 2959, 2926, 2596, 1605, 1548, 1508, 1452, 1370,
1290, 1250, 1177, 1114, 1028, 964, 920, 833, 788, 758, 615; HRMS (ESI/Q-TOF) m/z: [M + H]+
Calcd for C17H13F3NOS 336.0664; Found 336.067 (3.6 ppm).
2-(p-tolyl)-3-((trifluoromethyl)thio)quinoline (2ac): yellow solid; 46.0 mg; 72%; 1H NMR (400
MHz, CDCl3) δ ppm 8.62 (s, 1H), 8.17 (d, J = 8.4 Hz, 1H), 7.86 (d, J = 8.0 Hz, 1H), 7.82−7.78 (m,
ACS Paragon Plus Environment

Page 19 of 38
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
1H), 7.59 (t, J = 7.6 Hz, 1H), 7.53 (d, J = 8.0 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 2.43 (s, 3H); 13C{1H}
NMR (100 MHz, CDCl3) δ ppm 161.8, 148.1, 145.6, 138.8, 136.5, 131.6, 129.5, 129.5, 129.2 (q, J
= 307 Hz, 1C, SCF3), 128.8, 127.6, 127.4, 126.9, 124.8, 118.0 (J = 2 Hz, 1C, C-SCF3, quartet peak
should be obtained, however, doublet peak was observed due to the low resolution of NMR
machine), 21.3; 19F NMR (376 MHz, CDCl3) δ ppm -42.39 (s, 3F). IR (neat, cm-1): 3738, 1844,
1613, 1479, 1399, 1370, 1184, 1128, 966, 824, 786, 754, 608; HRMS (ESI/Q-TOF) m/z: [M + H]+
Calcd for C17H13F3NS 320.0715; Found 320.0722 (2.2 ppm).
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
1
2-(4-ethylphenyl)-3-((trifluoromethyl)thio)quinoline (2ad): yellow solid; 43.3 mg; 65%; H
NMR (400 MHz, CDCl3) δ ppm 8.60 (s, 1H), 8.17 (d, J = 8.8 Hz, 1H), 7.82 (d, J = 8.0 Hz, 1H),
7.76 (t, J = 8.8 Hz, 1H), 7.55 (t, J = 8.0 Hz, 3H), 7.32 (d, J = 8.0 Hz, 2H), 2.72 (q, J = 7.6 Hz, 2H),
1.28 (d, J = 7.6 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ ppm 161.7, 148.0, 145.5, 145.0,
136.7, 131.5, 129.6, 129.5, 129.2 (q, J = 308 Hz, 1C, SCF3), 127.6, 127.5, 127.3, 126.9, 117.9 (J =
2 Hz, 1C, C-SCF3, quartet peak should be obtained, however, doublet peak was observed due to the
low resolution of NMR machine), 28.7, 15.4; 19F NMR (376 MHz, CDCl3) δ ppm -42.32 (s, 3F). IR
(neat, cm-1): 3039, 2932, 2872, 1913, 1717, 1689, 1614, 1575, 1549, 1484, 1458, 1401, 1369, 1294,
1155, 1108, 1021, 970, 916, 869, 836, 792, 759, 619; HRMS (ESI/Q-TOF) m/z: [M + H]+ Calcd for
C18H15F3NS 334.0872; Found 334.0876 (1.2 ppm).
1
2-(4-pentylphenyl)-3-((trifluoromethyl)thio)quinoline (2ae): yellow solid; 35.3 mg; 47%; H
NMR (400 MHz, CDCl3) δ ppm 8.63 (s, 1H), 8.18 (d, J = 8.4 Hz, 1H), 7.88 (d, J = 8.0 Hz, 1H),
7.83−7.79 (m, 1H), 7.63−7.59 (m, 1H), 7.54 (d, J = 8.4 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 2.69 (t, J
= 8.0 Hz, 2H), 1.71−1.64 (m, 2H), 1.37−1.34 (m, 4H), 0.93−0.88 (m, 3H); 13C{1H} NMR (100
MHz, CDCl3) δ ppm 161.9, 148.1, 145.5, 143.8, 136.6, 131.6, 129.5, 129.2 (q, J = 308 Hz, 1C,
SCF3), 128.2, 127.6, 127.4, 127.0, 118.1 (J = 2 Hz, 1C, C-SCF3, quartet peak should be obtained,
however, doublet peak was observed due to the low resolution of NMR machine), 35.8, 31.5, 31.0,
22.6, 14.0; 19F NMR (376 MHz, CDCl3) δ ppm -42.38 (s, 3F). IR (neat, cm-1): 3059, 2924, 1740,
1616, 1554, 1481, 1433, 1399, 1370, 1109, 1027, 973, 920, 864, 792, 757; HRMS (ESI/Q-TOF)
m/z: [M + H]+ Calcd for C21H21F3NS 376.1341; Found 376.1349 (2.1 ppm).
2-(4-(tert-butyl)phenyl)-3-((trifluoromethyl)thio)quinoline (2af): light yellow solid; 47.7 mg;
66%; 1H NMR (400 MHz, CDCl3) δ ppm 8.63 (s, 1H), 8.17 (d, J = 8.4 Hz, 1H), 7.87 (d, J = 8.0 Hz,
1H), 7.83−7.78 (m, 1H), 7.59 (dd, J = 13.6 Hz 8.0 Hz, 3H), 7.52 (d, J = 8.4 Hz, 2H), 1.38 (s, 9H);
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 20 of 38
1
2
3
4
5
6
7
8
9
13C{1H} NMR (100 MHz, CDCl3) δ ppm 161.7, 151.9, 148.1, 145.4, 136.4, 131.6, 129.5, 129.3,
129.2 (q, J = 307 Hz, 1C, SCF3), 127.6, 127.4, 127.0, 125.6, 125.1, 118.0 (q, J = 2 Hz, 1C, SCF3),
34.7, 31.3; 19F NMR (376 MHz, CDCl3) δ ppm -42.30 (s, 3F). IR (neat, cm-1): 3053, 2963, 1786,
1664, 1611, 1550, 1479, 1400, 1368, 1268, 1115, 1019, 970, 836, 790, 756, 610; HRMS (ESI/Q-
TOF) m/z: [M + H]+ Calcd for C20H19F3NS 362.1185; Found 362.1193 (2.2 ppm).
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
2-([1,1'-biphenyl]-4-yl)-3-((trifluoromethyl)thio)quinoline (2ag): yellow solid; 47.3 mg; 62%;
1H NMR (400 MHz, CDCl3) δ ppm 8.66 (s, 1H), 8.20 (d, J = 8.4 Hz, 1H), 7.89 (d, J = 8.0 Hz, 1H),
7.85−7.81 (m, 1H), 7.73 (m, 4H), 7.67 (d, J = 7.2 Hz, 2H), 7.62 (t, J = 8.0 Hz, 1H), 7.47 (t, J = 7.6
Hz, 2H), 7.37 (t, J = 7.6 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ ppm 161.5, 148.1, 146.0,
141.7, 140.6, 138.2, 131.8, 130.1, 129.5, 129.2 (q, J = 307 Hz, 1C, SCF3), 128.8, 127.6, 127.5,
127.2, 127.0, 126.9, 117.8 (J = 2 Hz, 1C, C-SCF3, quartet peak should be obtained, however, doublet
peak was observed due to the low resolution of NMR machine); 19F NMR (376 MHz, CDCl3) δ ppm
-42.33 (s, 3F). IR (neat, cm-1): 3057, 2852, 1923, 1611, 1481, 1398, 1201, 1146, 1126, 1101, 966,
910, 846, 762, 733, 692; HRMS (ESI/Q-TOF) m/z: [M + H]+ Calcd for C22H15F3NS 382.0872;
Found 382.0881 (2.4 ppm).
1
2-(4-fluorophenyl)-3-((trifluoromethyl)thio)quinoline (2ah): yellow solid; 47.8 mg; 74%; H
NMR (400 MHz, CDCl3) δ ppm 8.66 (s, 1H), 8.17 (d, J = 8.4 Hz, 1H), 7.90 (d, J = 8.0 Hz, 1H),
7.86−7.82 (m, 1H), 7.63 (dd, J = 8.8 Hz 5.6 Hz, 3H), 7.19 (t, J = 8.8 Hz, 2H); 13C{1H} NMR (100
MHz, CDCl3) δ ppm 163.2 (d, 1J = 247 Hz, 1C), 160.9, 148.1, 146.4, 135.4 (d, 4J = 3 Hz, 1C), 131.9,
131.7 (d, 3J = 8 Hz, 1C), 129.5, 129.1 (q, J = 308 Hz, 1C, SCF3), 127.6 (d, 2J = 13 Hz, 1C), 127.1,
117.7 (J = 2 Hz, 1C, C-SCF3, quartet peak should be obtained, however, doublet peak was observed
due to the low resolution of NMR machine), 115.2, 115.0; 19F NMR (376 MHz, CDCl3) δ ppm -
42.52 (s, 3F), -112.86—112.94 (m, 1F). IR (neat, cm-1): 3624, 3057, 2925, 1780, 1601, 1549, 1513,
1482, 1404, 1369, 1229, 1155, 1115, 970, 841, 787, 759, 607; HRMS (ESI/Q-TOF) m/z: [M + Na]+
Calcd for C16H9F4NNaS 346.0284; Found 346.0287 (0.9 ppm).
1
2-(4-chlorophenyl)-3-((trifluoromethyl)thio)quinoline (2ai): yellow solid; 42.1 mg; 62%; H
NMR (400 MHz, CDCl3) δ ppm 8.66 (s, 1H), 8.17 (d, J = 8.4 Hz, 1H), 7.89 (d, J = 8.0 Hz, 1H),
7.83 (t, J = 7.6 Hz, 1H), 7.65−7.58 (m, 3H), 7.48 (d, J = 7.6 Hz, 2H); 13C{1H} NMR (100 MHz,
CDCl3) δ ppm 160.8, 148.1, 146.5, 137.7, 135.1, 132.0, 131.1, 129.5, 129.0 (q, J = 308 Hz, 1C,
SCF3), 128.3, 127.8, 127.7, 127.1, 117.5 (J = 2 Hz, 1C, C-SCF3, quartet peak should be obtained,
ACS Paragon Plus Environment

Page 21 of 38
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
however, doublet peak was observed due to the low resolution of NMR machine); 19F NMR (376
MHz, CDCl3) δ ppm -42.49 (s, 3F). IR (neat, cm-1): 3059, 2924, 1785, 1484, 1402, 1298, 1115,
1015, 968, 833, 787, 755; HRMS (ESI/Q-TOF) m/z: [M + Na]+ Calcd for C16H9ClF3NNaS 361.9989;
Found 361.9995 (1.7 ppm).
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
1-(4-(3-((trifluoromethyl)thio)quinolin-2-yl)phenyl)ethan-1-one (2aj): yellow solid; 59.8 mg;
86%; 1H NMR (400 MHz, acetone) δ ppm 8.99 (s, 1H), 8.17 (dd, J = 13.2 Hz 8.8 Hz, 4H), 7.99−7.95
(m, 1H), 7.87 (d, J = 8.4 Hz, 1H), 7.78 (t, J = 7.6 Hz, 1H), 2.69 (s, 3H); 13C{1H} NMR (100 MHz,
acetone) δ ppm 197.7, 162.0, 149.3, 148.2, 144.9, 138.3, 133.2, 131.2, 130.5 (J = 307 Hz, 1C, C-
SCF3, quartet peak should be obtained, however, due to the poor solubility of this compound in each
solvent, the insufficient acquisition time lead to doublet peak presented in 13C{1H} NMR spectrum),
130.4, 129.1, 129.0, 128.6, 128.3, 117.9 (J = 1 Hz, 1C, C-SCF3, quartet peak should be obtained,
however, doublet peak was observed due to the low resolution of NMR machine), 26.9; 19F NMR
(376 MHz, CDCl3) δ ppm -43.92 (s, 3F). IR (neat, cm-1): 3049, 2918, 2777, 1819, 1672, 1608, 1485,
1398, 1359, 1270, 1150, 1110, 960, 834, 794, 760, 732, 654, 610; HRMS (ESI/Q-TOF) m/z: [M +
Na]+ Calcd for C18H12F3NNaOS 370.0484; Found 370.0492 (2.2 ppm).
2-(4-(trifluoromethyl)phenyl)-3-((trifluoromethyl)thio)quinoline (2ak): yellow solid; 53.8 mg;
72%; 1H NMR (400 MHz, CDCl3) δ ppm 8.70 (s, 1H), 8.19 (d, J = 8.4 Hz, 1H), 7.93 (d, J = 8.4 Hz,
1H), 7.88−7.84 (m, 1H), 7.77 (s, 4H), 7.67 (t, J = 7.6 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3)
δ ppm 160.7, 148.2, 146.9, 142.8, 132.2, 130.8 (q, J = 33 Hz, 1C, C-CF3), 130.2, 129.6, 129.0 (q, J
= 308 Hz, 1C, SCF3), 128.0, 127.7, 127.3, 125.1 (q, J = 4 Hz, 1C, C-C-CF3), 124.1 (q, J = 271 Hz,
1C, CF3), 117.3 (J = 3 Hz, 1C, C-SCF3, quartet peak should be obtained, however, doublet peak
was observed due to the low resolution of NMR machine); 19F NMR (376 MHz, CDCl3) δ ppm -
42.54 (s, 3F). IR (neat, cm-1): 2645, 1617, 1485, 1406, 1330, 1154, 1121, 1020, 972, 847, 792, 760,
619; HRMS (ESI/Q-TOF) m/z: [M + Na]+ Calcd for C17H9F6NNaS 396.0252; Found 396.0259 (1.8
ppm).
4-(3-((trifluoromethyl)thio)quinolin-2-yl)benzonitrile (2al): dark yellow solid; 55.5 mg; 84%;
1H NMR (400 MHz, CDCl3) δ ppm 8.72 (s, 1H), 8.19 (d, J = 8.4 Hz, 1H), 7.95 (d, J = 8.0 Hz, 1H),
7.89 (t, J = 7.6 Hz, 1H), 7.79 (dd, J = 12.4 Hz 8.4 Hz, 4H), 7.70 (t, J = 7.6 Hz, 1H); 13C{1H} NMR
(100 MHz, CDCl3) δ ppm 160.0, 148.1, 147.2, 143.6, 132.3, 131.8, 130.5, 129.5, 128.9 (q, J = 308
Hz, 1C, SCF3), 128.2, 127.8, 127.3, 118.5, 116.9 (J = 2 Hz, 1C, C-SCF3, quartet peak should be
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 22 of 38
1
2
3
4
5
6
7
8
9
obtained, however, doublet peak was observed due to the low resolution of NMR machine), 112.5;
19F NMR (376 MHz, CDCl3) δ ppm -42.54 (s, 3F). IR (neat, cm-1): 3057, 2708, 1817, 1612, 1483,
1371, 1329, 1114, 970, 844, 790, 755; HRMS (ESI/Q-TOF) m/z: [M + Na]+ Calcd for
C17H9F3N2NaS 353.0331; Found 353.0341 (2.8 ppm).
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
1
2-(m-tolyl)-3-((trifluoromethyl)thio)quinoline (2am): yellow liquid; 47.3 mg; 74%; H NMR
(400 MHz, CDCl3) δ ppm 8.63 (s, 1H), 8.19 (d, J = 8.4 Hz, 1H), 7.88 (d, J = 8.0 Hz, 1H), 7.83−7.79
(m, 1H), 7.61 (t, J = 7.6 Hz, 1H), 7.43 (s, 1H), 7.39−7.36 (m, 2H), 7.29 (d, J = 7.2 Hz, 1H), 2.44 (s,
3H); 13C{1H} NMR (100 MHz, CDCl3) δ ppm 162.0, 147.9, 145.4, 139.2, 137.9, 131.6, 130.1,
129.6, 129.5, 129.2 (q, J = 308 Hz, 1C, SCF3), 127.9, 127.6, 127.5, 127.0, 126.7, 118.1 (J = 2 Hz,
1C, C-SCF3, quartet peak should be obtained, however, doublet peak was observed due to the low
resolution of NMR machine), 21.5; 19F NMR (376 MHz, CDCl3) δ ppm -42.34 (s, 3F). IR (neat, cm-
1): 3055, 2924, 1614, 1577, 1550, 1483, 1451, 1399, 1370, 1118, 978, 917, 837, 781, 755, 728, 700;
HRMS (ESI/Q-TOF) m/z: [M + H]+ Calcd for C17H13F3NS 320.0715; Found 320.0721 (1.9 ppm).
2-(3-chlorophenyl)-3-((trifluoromethyl)thio)quinoline (2an): light yellow solid; 60.5 mg; 89%;
1H NMR (400 MHz, CDCl3) δ ppm 8.67 (s, 1H), 8.18 (d, J = 8.4 Hz, 1H), 7.91 (d, J = 8.4 Hz, 1H),
7.95 (d, J = 7.6 Hz, 1H), 7.66 (d, J = 12.4 Hz, 2H), 7.51 (d, J = 7.2 Hz, 1H), 7.47−7.41 (m, 2H);
13C{1H} NMR (100 MHz, CDCl3) δ ppm 160.5, 148.1, 146.5, 141.0, 134.1, 132.0, 129.8, 129.6,
129.3, 129.0 (q, J = 308 Hz, 1C, SCF3), 129.0, 127.9, 127.9, 127.7, 127.2, 117.5 (J = 2 Hz, 1C, C-
SCF3, quartet peak should be obtained, however, doublet peak was observed due to the low
resolution of NMR machine); 19F NMR (376 MHz, CDCl3) δ ppm -42.44 (s, 3F). IR (neat, cm-1):
3422, 3063, 2926, 2855, 1942, 1784, 1616, 1574, 1482, 1370, 1302, 1258, 1107, 981, 891, 783,
756, 727, 692; HRMS (ESI/Q-TOF) m/z: [M + Na]+ Calcd for C16H9ClF3NNaS 361.9989; Found
361.9999 (2.8 ppm).
2-(o-tolyl)-3-((trifluoromethyl)thio)quinoline (2ao): yellow liquid; 54.9 mg; 86%; 1H NMR (400
MHz, CDCl3) δ ppm 8.63 (s, 1H), 8.19 (d, J = 8.0 Hz, 1H), 7.90 (d, J = 8.0 Hz, 1H), 7.82 (t, J = 7.6
Hz, 1H), 7.63 (t, J = 7.2 Hz, 1H), 7.39−7.36 (m, 1H), 7.32−7.24 (m, 3H), 2.14 (s, 3H); 13C{1H}
NMR (100 MHz, CDCl3) δ ppm 162.2, 147.8, 144.4, 138.9, 135.8, 131.6, 130.2, 129.4, 129.2 (q, J
= 308 Hz, 1C, SCF3), 129.1, 128.8, 127.6, 127.5, 127.1, 125.6, 119.3 (C-SCF3, quartet peak should
be obtained, however, single peak was observed due to the low resolution of NMR machine), 19.5;
19F NMR (376 MHz, CDCl3) δ ppm -41.97 (s, 3F). IR (neat, cm-1): 3703, 3403, 3060, 2926, 1842,
ACS Paragon Plus Environment

Page 23 of 38
The Journal of Organic Chemistry
1
2
3
4
5
6
1614, 1577, 1484, 1454, 1399, 1370, 1296, 1109, 970, 864, 758; HRMS (ESI/Q-TOF) m/z: [M +
H]+ Calcd for C17H13F3NS 320.0715; Found 320.0724 (2.8 ppm).
7
8
9
2-(2-methoxyphenyl)-3-((trifluoromethyl)thio)quinoline (2ap): yellow solid; 49.0 mg; 73%; 1H
NMR (400 MHz, CDCl3) δ ppm 8.59 (s, 1H), 8.19 (d, J = 8.4 Hz, 1H), 7.87 (d, J = 8.4 Hz, 1H),
7.81−7.76 (m, 1H), 7.59 (t, J = 7.6 Hz, 1H), 7.52 (dd, J = 7.6 Hz 1.6 Hz, 1H), 7.48−7.44 (m, 1H),
7.15−7.12 (m, 1H), 6.97 (d, J = 8.4 Hz, 1H), 3.76 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ ppm
160.3, 156.5, 148.4, 144.4, 131.2, 130.6, 130.5, 129.6 (q, J = 307 Hz, 1C, SCF3), 129.5, 128.8,
127.7, 127.3, 127.1, 121.1, 120.2 (J = 2 Hz, 1C, C-SCF3, quartet peak should be obtained, however,
doublet peak was observed due to the low resolution of NMR machine), 110.3, 55.2; 19F NMR (376
MHz, CDCl3) δ ppm -42.67 (s, 3F). IR (neat, cm-1): 3412, 3060, 2936, 2838, 1785, 1603, 1552,
1490, 1463, 1437, 1398, 1370, 1292, 1256, 1110, 1024, 973, 921, 754; HRMS (ESI/Q-TOF) m/z:
[M + H]+ Calcd for C17H13F3NOS 336.0664; Found 336.0671 (2.1 ppm).
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
1
2-(2-fluorophenyl)-3-((trifluoromethyl)thio)quinoline (2aq): yellow liquid; 40.7 mg; 63%; H
NMR (400 MHz, CDCl3) δ ppm 8.67 (s, 1H), 8.20 (d, J = 8.4 Hz, 1H), 7.92 (d, J = 8.4 Hz, 1H),
7.86−7.82 (m, 1H), 7.67−7.63 (m, 1H), 7.58 (t, J = 7.6 Hz, 1H), 7.48 (dd, J = 13.6 Hz 7.6 Hz, 1H),
7.32 (t, J = 7.6 Hz, 1H), 7.18 (t, J = 9.2 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ ppm 159.7
(d, 1J = 308 Hz, 1C), 158.1, 148.4, 146.1, 131.9, 131.2 (d, 3J = 3 Hz, 1C), 131.1 (d, 3J = 9 Hz, 1C),
129.6, 129.2 (q, J = 307 Hz, 1C, SCF3), 127.9, 127.8, 127.6 (d, 2J = 15 Hz, 1C), 127.3, 124.4 (d, 4J
= 3 Hz, 1C), 119.0 (J = 2 Hz, 1C, C-SCF3, quartet peak should be obtained, however, doublet peak
was observed due to the low resolution of NMR machine), 115.4 (d, 2J = 22 Hz, 1C); 19F NMR (376
MHz, CDCl3) δ ppm -42.85 (d, J = 3 Hz, 3F), -115.31 (d, J = 3 Hz, 1F). IR (neat, cm-1): 3680, 3063,
2926, 1798, 1617, 1580, 1554, 1486, 1454, 1400, 1371, 1287, 1249, 1213, 1159, 1108, 975, 862,
822, 788, 758; HRMS (ESI/Q-TOF) m/z: [M + Na]+ Calcd for C16H9F4NNaS 346.0284; Found
346.0294 (2.9 ppm).
1
2-(2-bromophenyl)-3-((trifluoromethyl)thio)quinoline (2ar): yellow solid; 58.4 mg; 76%; H
NMR (400 MHz, CDCl3) δ ppm 8.67 (s, 1H), 8.21−8.19 (m, 1H), 7.93 (t, J = 8.0 Hz, 1H), 7.87−7.82
(m, 1H), 7.68−7.64 (m, 2H), 7.51−7.45 (m, 2H); 7.36−7.32 (m, 1H); 13C{1H} NMR (100 MHz,
CDCl3) δ ppm 161.7, 148.0, 146.0, 140.4, 131.8, 130.9, 130.2, 129.6, 129.2 (q, J = 308 Hz, 1C,
SCF3), 127.9, 127.8, 127.5, 127.4, 123.0, 119.0 (J = 2 Hz, 1C, C-SCF3, quartet peak should be
obtained, however, doublet peak was observed due to the low resolution of NMR machine); 19F
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 24 of 38
1
2
3
4
5
6
7
8
NMR (376 MHz, CDCl3) δ ppm -42.46 (s, 3F). IR (neat, cm-1): 3059, 2926, 1618, 1572, 1554, 1481,
1433, 1399, 1370, 1284, 1108, 1026, 973, 922, 864, 792, 757; HRMS (ESI/Q-TOF) m/z: [M + Na]+
Calcd for C16H9BrF3NNaS 405.9483; Found 405.9489 (1.5 ppm).
9
2-(3,5-dimethylphenyl)-3-((trifluoromethyl)thio)quinoline (2as): yellow solid; 49.3 mg; 74%;
1H NMR (400 MHz, CDCl3) δ ppm 8.62 (s, 1H), 8.18 (d, J = 8.4 Hz, 1H), 7.87 (d, J = 8.4 Hz, 1H),
7.83−7.79 (m, 1H), 7.63−7.59 (m, 1H), 7.19 (s, 2H), 7.11 (s, 1H), 2.40 (s, 6H); 13C{1H} NMR (100
MHz, CDCl3) δ ppm 162.1, 147.9, 145.0, 139.2, 137.6, 131.5, 130.5, 129.5, 129.2 (q, J = 308 Hz,
1C, SCF3), 127.6, 127.4, 127.2, 127.0, 118.3 (J = 2 Hz, 1C, C-SCF3, quartet peak should be obtained,
however, doublet peak was observed due to the low resolution of NMR machine), 21.4; 19F NMR
(376 MHz, CDCl3) δ ppm -42.27 (s, 3F). IR (neat, cm-1): 3153, 2921, 1715, 1603, 1481, 1451, 1399,
1371, 1297, 1205, 1157, 1107, 1013, 976, 915, 854, 789, 756, 732, 699; HRMS (ESI/Q-TOF) m/z:
[M + H]+ Calcd for C18H15F3NS 334.0872; Found 334.0879 (2.1 ppm).
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
2-(3,5-dichlorophenyl)-3-((trifluoromethyl)thio)quinoline (2at): yellow liquid; 47.9 mg; 64%;
1H NMR (400 MHz, CDCl3) δ ppm 8.69 (s, 1H), 8.18 (d, J = 8.4 Hz, 1H), 7.93−7.86 (m, 2H), 7.68
(t, J = 7.6 Hz, 1H), 7.53 (d, J = 1.6 Hz, 2H), 7.48 (s, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ ppm
159.2, 148.0, 147.0, 142.0, 134.7, 132.3, 129.6, 128.9, 128.9 (q, J = 308 Hz, 1C, SCF3), 128.3,
128.2, 127.7, 127.3, 117.1 (J = 1 Hz, 1C, C-SCF3, quartet peak should be obtained, however, doublet
peak was observed due to the low resolution of NMR machine); 19F NMR (376 MHz, CDCl3) δ ppm
-42.35 (s, 3F). IR (neat, cm-1): 2959, 2869, 1857, 1558, 1483, 1408, 1369, 1262, 1119, 963, 852,
806, 785, 754, 728, 685; HRMS (ESI/Q-TOF) m/z: [M + Na]+ Calcd for C16H8Cl2F3NNaS 395.9599;
Found 395.9609 (2.5 ppm).
2-(3,4-dimethylphenyl)-3-((trifluoromethyl)thio)quinoline (2au): yellow solid; 44.0 mg; 66%;
1H NMR (400 MHz, CDCl3) δ ppm 8.62 (s, 1H), 8.17 (d, J = 8.4 Hz, 1H), 7.87 (d, J = 8.4 Hz, 1H),
7.82−7.79 (m, 1H), 7.60 (t, J = 7.6 Hz, 1H), 7.40 (s, 1H), 7.33 (d, J = 7.6 Hz, 1H), 7.25 (d, J = 7.2
Hz, 1H), 2.35 (s, 3H), 2.34 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ ppm 161.9, 148.0, 145.2,
137.5, 136.9, 136.5, 131.5, 130.6, 129.5, 129.3, 129.2 (q, J = 308 Hz, 1C, SCF3), 127.6, 127.3,
127.0, 126.9 118.2 (q, J = 2 Hz, 1C, C-SCF3), 19.9, 19.7; 19F NMR (376 MHz, CDCl3) δ ppm -
42.31 (s, 3F). IR (neat, cm-1): 2923, 1714, 1616, 1576, 1550, 1481, 1450, 1402, 1370, 1263, 1107,
1003, 979, 824, 787, 754, 617; HRMS (ESI/Q-TOF) m/z: [M + Na]+ Calcd for C18H14F3NNaS
356.0691; Found 356.0700 (2.5 ppm).
ACS Paragon Plus Environment

Page 25 of 38
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
2-(3-chloro-4-methylphenyl)-3-((trifluoromethyl)thio)quinoline (2av): yellow solid; 40.3 mg;
57%; 1H NMR (400 MHz, CDCl3) δ ppm 8.65 (s, 1H), 8.17 (d, J = 8.4 Hz, 1H), 7.89 (d, J = 8.4 Hz,
1H), 7.83 (t, J = 8.0 Hz, 1H), 7.63 (t, J = 7.6 Hz, 2H), 7.43 (d, J = 7.6 Hz, 1H), 7.35 (d, J = 8.0 Hz,
1H), 2.46 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ ppm 160.4, 148.1, 146.3, 138.4, 136.8,
134.2, 131.9, 130.5, 130.2, 129.5, 129.1 (q, J = 308 Hz, 1C, SCF3), 127.9, 127.7, 127.6, 127.1,
117.6 (J = 1 Hz, 1C, C-SCF3, quartet peak should be obtained, however, doublet peak was observed
due to the low resolution of NMR machine), 20.0; 19F NMR (376 MHz, CDCl3) δ ppm -42.42 (s,
3F). IR (neat, cm-1): 3060, 2959, 2926, 1765, 1616, 1577, 1549, 1482, 1447, 1400, 1370, 1256,
1107, 978, 901, 826, 788, 754, 698, 620; HRMS (ESI/Q-TOF) m/z: [M + H]+ Calcd for
C17H12ClF3NS 354.0326; Found 354.0337 (3.1 ppm).
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
2-(2-methoxy-5-nitrophenyl)-3-((trifluoromethyl)thio)quinoline (2aw): yellow solid; 41.1 mg;
54%; 1H NMR (400 MHz, CDCl3) δ ppm 8.66 (s, 1H), 8.45−8.39 (m, 2H), 8.19 (d, J = 8.4 Hz, 1H),
7.95 (d, J = 8.0 Hz, 1H), 7.87 (dd, J = 8.4 Hz 7.6 Hz, 1H), 7.69 (t, J = 7.6 Hz, 1H), 7.08 (d, J = 9.2
Hz, 1H), 3.90 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ ppm 161.5, 158.0, 148.4, 145.6, 141.7,
131.9, 130.0, 129.5, 129.2 (J = 307 Hz, 1C, SCF3), 128.0, 127.8, 127.4, 126.7, 126.7, 120.9 (J = 1
Hz, 1C, C-SCF3, quartet peak should be obtained, however, doublet peak was observed due to the
low resolution of NMR machine), 110.5, 56.2; 19F NMR (376 MHz, CDCl3) δ ppm -42.74 (s, 3F).
IR (neat, cm-1): 2926, 2850, 1732, 1613, 1587, 1521, 1490, 1462, 1428, 1343, 1270, 1109, 1070,
1020, 988, 909, 865, 825, 794, 754, 734, 637; HRMS (ESI/Q-TOF) m/z: [M + Na]+ Calcd for
C17H11F3N2O3NaS 403.0335; Found 403.0346 (2.7 ppm).
2-(thiophen-2-yl)-3-((trifluoromethyl)thio)quinoline (2ax): dark yellow solid; 30.5 mg; 49%;
1H NMR (400 MHz, CDCl3) δ ppm 8.57 (s, 1H), 8.14−8.09 (m, 2H), 7.81−7.77 (m, 2H), 7.57−7.51
(m, 2H), 7.16 (dd, J = 5.2 Hz 4.0 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ ppm 154.0, 148.2,
148.2, 142.9, 132.0, 130.5, 129.6, 129.3 (q, J = 308 Hz, 1C, SCF3), 129.2, 127.7, 127.5, 127.4,
126.5, 115.6 (q, J = 2 Hz, 1C, C-SCF3); 19F NMR (376 MHz, CDCl3) δ ppm -42.55 (s, 3F). IR (neat,
cm-1): 3069, 2924, 1616, 1574, 1547, 1482, 1424, 1372, 1310, 1243, 1106, 851, 783, 752, 708;
HRMS (ESI/Q-TOF) m/z: [M + Na]+ Calcd for C14H8F3NNaS2 333.9942; Found 333.9948 (1.8
ppm).
Characterization Data of 2ba−2bd and 2bf−2bg
5-methyl-2-(m-tolyl)-3-((trifluoromethyl)thio)quinoline (2ba): yellow solid; 52.7 mg; 79%; 1H
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 26 of 38
1
2
3
4
5
6
7
8
NMR (400 MHz, CDCl3) δ ppm 8.79 (s, 1H), 8.02 (d, J = 8.4 Hz, 1H), 7.69−7.65 (m, 1H), 7.45 (s,
1H), 7.41−7.35 (m, 3H), 7.28 (d, J = 7.6 Hz, 1H), 2.72 (s, 3H), 2.44 (s, 3H); 13C{1H} NMR (100
MHz, CDCl3) δ ppm 161.6, 148.4, 142.5, 139.2, 137.8, 134.7, 131.4, 130.1, 129.5, 129.2 (q, J = 308
9
Hz, 1C, SCF3), 127.8, 127.8, 127.7, 126.7, 126.5, 117.4 (q, J = 1 Hz, 1C, C-SCF3), 21.4, 18.4; 19
F
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
NMR (376 MHz, CDCl3) δ ppm -42.49 (s, 3F). IR (neat, cm-1): 3036, 2949, 2924, 1945, 1582, 1555,
1468, 1379, 1285, 1110, 1062, 986, 916, 810, 793, 758, 727, 697, 640; HRMS (ESI/Q-TOF) m/z:
[M + H]+ Calcd for C18H15F3NS 334.0872; Found 334.0875 (0.9 ppm).
7-methoxy-2-phenyl-3-((trifluoromethyl)thio)quinoline (2bb): yellow solid; 34.9 mg; 52%; 1H
NMR (400 MHz, CDCl3) δ ppm 8.54 (s, 1H), 7.76 (d, J = 8.8 Hz, 1H), 7.61 (d, J = 6.4 Hz, 2H),
7.51−7.48 (m, 4H), 7.28−7.25 (m, 1H), 3.95 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ ppm
162.7, 162.6, 150.2, 146.0, 139.6, 129.6, 129.2 (q, J = 308 Hz, 1C, SCF3), 128.7, 128.7, 128.0,
122.4, 121.0, 114.7 (J = 2 Hz, 1C, C-SCF3, quartet peak should be obtained, however, doublet peak
was observed due to the low resolution of NMR machine), 107.3, 55.7; 19F NMR (376 MHz, CDCl3)
δ ppm -42.92 (s, 3F). IR (neat, cm-1): 3011, 2959, 2934, 2855, 1712, 1621, 1486, 1448, 1400, 1379,
1329, 1284, 1219, 1158, 1107, 1027, 974, 920, 851, 817, 752, 698, 640; HRMS (ESI/Q-TOF) m/z:
[M + Na]+ Calcd for C17H12F3NONaS 358.0484; Found 358.0487 (0.8 ppm).
1
7-bromo-2-phenyl-3-((trifluoromethyl)thio)quinoline (2bc): yellow solid; 46.1 mg; 60%; H
NMR (400 MHz, CDCl3) δ ppm 8.59 (s, 1H), 7.87−7.82 (m, 2H), 7.62−7.60 (m, 2H), 7.50 (dd, J =
5.2 Hz 2.0 Hz, 3H), 7.25 (dd, J = 6.8 Hz 2.4 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ ppm
163.1, 148.8, 145.7, 144.1, 139.1, 129.5, 129.4, 129.1 (q, J = 308 Hz, 1C, SCF3), 129.0, 128.1,
124.6, 120.9, 117.1 (J = 1 Hz, 1C, C-SCF3, quartet peak should be obtained, however, doublet peak
was observed due to the low resolution of NMR machine), 117.0; 19F NMR (376 MHz, CDCl3) δ
ppm -42.52 (s, 3F). IR (neat, cm-1): 3060, 2925, 1615, 1580, 1483, 1430, 1375, 1332, 1287, 1251,
1105, 974, 865, 814, 758, 698; HRMS (ESI/Q-TOF) m/z: [M + H]+ Calcd for C16H10BrF3NS
383.9664; Found 383.9672 (2.1 ppm).
7-chloro-2-(4-methoxyphenyl)-3-((trifluoromethyl)thio)quinoline (2bd): yellow solid; 54.0 mg;
73%; 1H NMR (400 MHz, CDCl3) δ ppm 8.56 (s, 1H), 7.85−7.80 (m, 2H), 7.60 (d, J = 8.4 Hz, 2H),
7.23 (dd, J = 8.8 Hz 2.4 Hz, 1H), 7.03 (d, J = 8.4 Hz, 2H), 3.89 (s, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ ppm 162.5, 160.3, 148.9, 145.6, 143.9, 131.5, 131.2, 129.4, 129.2 (q, J = 309 Hz, 1C,
SCF3), 124.4, 120.7, 117.1 (J = 1 Hz, 1C, C-SCF3, quartet peak should be obtained, however,
ACS Paragon Plus Environment

Page 27 of 38
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
doublet peak was observed due to the low resolution of NMR machine), 117.0, 113.6, 55.3; 19F
NMR (376 MHz, CDCl3) δ ppm -42.56 (s, 3F). IR (neat, cm-1): 2926, 2842, 1609, 1577, 1514, 1484,
1419, 1375, 1329, 1293, 1251, 1155, 1106, 1032, 972, 835, 779; HRMS (ESI/Q-TOF) m/z: [M +
H]+ Calcd for C17H12ClF3NOS 370.0275; Found 370.0284 (2.4 ppm).
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
1
8-chloro-2-(m-tolyl)-3-((trifluoromethyl)thio)quinoline (2bf): yellow solid; 59.4 mg; 84%; H
NMR (400 MHz, CDCl3) δ ppm 8.63 (s, 1H), 7.91 (dd, J = 7.6 Hz 1.2 Hz, 1H), 7.81−7.79 (m, 1H),
7.54−7.47 (m, 3H), 7.39 (t, J = 7.6 Hz, 1H), 7.30 (d, J = 7.2 Hz, 1H), 2.46 (s, 3H); 13C{1H} NMR
(100 MHz, CDCl3) δ ppm 162.0, 145.1, 144.2, 138.7, 137.8, 133.9, 131.5, 130.6, 130.0, 129.1 (q, J
= 308 Hz, 1C, SCF3), 128.1, 127.9, 127.4, 127.1, 126.6, 119.5 (q, J = 2 Hz, 1C, C-SCF3), 21.5; 19F
NMR (376 MHz, CDCl3) δ ppm -42.11 (s, 3F). IR (neat, cm-1): 3051, 2924, 2513, 1703, 1541, 1460,
1400, 1364, 1263, 1110, 1011, 764, 700; HRMS (ESI/Q-TOF) m/z: [M + Na]+ Calcd for
C17H11ClF3NNaS 376.0145; Found 376.0154 (2.4 ppm).
6-phenyl-7-((trifluoromethyl)thio)-[1,3]dioxolo[4,5-g]quinoline (2bg): white solid; 46.8 mg;
67%; 1H NMR (400 MHz, CDCl3) δ ppm 8.41 (s, 1H), 7.59 (d, J = 6.4 Hz, 2H), 7.50−7.44 (m, 4H),
7.10 (s, 1H), 6.15 (s, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ ppm 160.3, 152.6, 148.7, 147.1,
144.5, 139.5, 129.7, 129.2 (q, J = 308 Hz, 1C, SCF3), 128.6, 128.0, 124.4, 115.5 (J = 2 Hz, 1C, C-
SCF3, quartet peak should be obtained, however, doublet peak was observed due to the low
resolution of NMR machine), 105.9, 102.3, 102.2; 19F NMR (376 MHz, CDCl3) δ ppm -42.75 (s,
3F). IR (neat, cm-1): 3061, 2912, 2783, 1953, 1882, 1641, 1614, 1573, 1461, 1418, 1381, 1321,
1265, 1229, 1160, 1105, 1037, 976, 939, 856, 783, 758, 699, 612; HRMS (ESI/Q-TOF) m/z: [M +
Na]+ Calcd for C17H10F3NO2NaS 372.0277; Found 372.0286 (2.4 ppm).
3-phenyl-4-((trifluoromethyl)thio)isoquinoline (2ca): white solid; 41.5 mg; 68%; 1H NMR (400
MHz, CDCl3) δ ppm 8.65 (s, 1H), 8.19 (d, J = 8.4 Hz, 1H), 7.89 (d, J = 7.6 Hz, 1H), 7.82 (d, J = 7.6
Hz, 1H), 7.62 (s, 3H), 7.50 (d, J = 4.8 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ ppm 161.9,
148.1, 145.9, 139.3, 131.7, 129.6, 129.6, 129.2 (q, J = 308 Hz, 1C, SCF3), 128.8, 128.1, 127.6,
127.6, 127.1, 117.9 (J = 2 Hz, 1C, C-SCF3, quartet peak should be obtained, however, doublet peak
was observed due to the low resolution of NMR machine); 19F NMR (376 MHz, CDCl3) δ ppm -
42.42 (s, 3F). IR (neat, cm-1): 3053, 2925, 2865, 1616, 1497, 1450, 1321, 1239, 1171, 1120, 1103,
1035, 1022, 954, 847, 754, 728, 714, 699, 654; HRMS (ESI/Q-TOF) m/z: [M + H]+ Calcd for
C16H11F3NS 306.0559; Found 306.0566 (2.3 ppm).
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 28 of 38
1
2
3
4
5
6
7
8
9
3-(4-methoxyphenyl)-4-((trifluoromethyl)thio)isoquinoline (2cb): white solid; 30.8 mg; 46%;
1H NMR (400 MHz, CDCl3) δ ppm 9.38 (s, 1H), 8.61 (d, J = 8.4 Hz, 1H), 8.04 (d, J = 8.0 Hz, 1H),
7.90−7.86 (m, 1H), 7.69 (t, J = 7.6 Hz, 1H), 7.59 (d, J = 8.8 Hz, 2H), 7.02 (d, J = 4.4 Hz, 2H), 3.88
(s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ ppm 160.6, 159.8, 154.8, 139.4, 132.6, 132.1, 131.7,
129.3 (q, J = 310 Hz, 1C, SCF3), 128.0, 127.9, 127.7, 125.8, 114.2 (J = 2 Hz, 1C, C-SCF3, quartet
peak should be obtained, however, doublet peak was observed due to the low resolution of NMR
machine), 113.3, 55.3; 19F NMR (376 MHz, CDCl3) δ ppm -41.52 (s, 3F). IR (neat, cm-1): 3005,
2957, 2928, 1886, 1725, 1609, 1575, 1552, 1514, 1439, 1414, 1344, 1291, 1249, 1128, 1102, 1032,
974, 834, 793, 757, 693, 637; HRMS (ESI/Q-TOF) m/z: [M + H]+ Calcd for C17H13F3NOS 336.0664;
Found 336.0672 (2.4 ppm).
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
1
3-(4-ethylphenyl)-4-((trifluoromethyl)thio)isoquinoline (2cc): yellow solid; 35.3 mg; 53%; H
NMR (400 MHz, CDCl3) δ ppm 9.39 (s, 1H), 8.61 (d, J = 8.4 Hz, 1H), 8.05 (d, J = 8.4 Hz, 1H),
7.90−7.86 (m, 1H), 7.11−7.67 (m, 1H), 7.54 (d, J = 8.0 Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H), 2.74 (q,
J = 7.6 Hz, 2H), 1.30 (t, J = 7.6 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ ppm 161.1, 154.8,
144.5, 139.3, 137.6, 132.1, 130.2, 129.2 (q, J = 309 Hz, 1C, SCF3), 128.0, 128.0, 127.7, 127.4,
125.8, 114.4 (J = 2 Hz, 1C, C-SCF3, quartet peak should be obtained, however, doublet peak was
observed due to the low resolution of NMR machine), 28.7, 15.4; 19F NMR (376 MHz, CDCl3) δ
ppm -41.41 (s, 3F). IR (neat, cm-1): 3027, 2965, 2931, 1712, 1616, 1552, 1441, 1412, 1247, 1129,
1102, 1023, 974, 834, 757; HRMS (ESI/Q-TOF) m/z: [M + Na]+ Calcd for C18H14F3NNaS 356.0691;
Found 356.0697 (1.7 ppm).
3-(4-bromophenyl)-4-((trifluoromethyl)thio)isoquinoline (2cd): white solid; 56.1 mg; 73%; 1H
NMR (400 MHz, CDCl3) δ ppm 9.40 (s, 1H), 8.61 (d, J = 8.4 Hz, 1H), 8.07 (d, J = 8.4 Hz, 1H),
7.91 (t, J = 7.6 Hz, 1H), 7.29 (t, J = 7.6 Hz, 1H), 7.62 (d, J = 8.0 Hz, 2H), 7.50 (d, J = 8.0 Hz, 2H);
13C{1H} NMR (100 MHz, CDCl3) δ ppm 159.7, 155.0, 139.1, 139.1, 132.4, 131.9, 131.0, 129.1 (q,
J = 309 Hz, 1C, SCF3), 128.2, 128.1, 128.1, 125.8, 122.9, 114.8 (J = 1 Hz, 1C, C-SCF3, quartet
peak should be obtained, however, doublet peak was observed due to the low resolution of NMR
machine); 19F NMR (376 MHz, CDCl3) δ ppm -41.39 (s, 3F). IR (neat, cm-1): 2924, 1618, 1572,
1489, 1440, 1375, 1246, 1131, 1102, 1011, 977, 862, 827, 791, 757; HRMS (ESI/Q-TOF) m/z: [M
+ Na]+ Calcd for C16H9BrF3NNaS 405.9483; Found 405.9494 (2.7 ppm).
4-(4-((trifluoromethyl)thio)isoquinolin-3-yl)benzonitrile (2ce): yellow solid; 31.7 mg; 48%; 1H
ACS Paragon Plus Environment

Page 29 of 38
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
NMR (400 MHz, CDCl3) δ ppm 9.44 (s, 1H), 8.64 (d, J = 8.4 Hz, 1H), 8.12 (d, J = 8.0 Hz, 1H),
7.96 (t, J = 7.6 Hz, 1H), 7.79 (d, J = 7.6 Hz, 3H), 7.74 (d, J = 8.0 Hz, 2H); 13C{1H} NMR (100
MHz, CDCl3) δ ppm 158.8, 155.3, 144.6, 139.0, 132.7, 131.7, 131.0, 128.9 (q, J = 310 Hz, 1C,
SCF3), 128.6, 128.4, 128.2, 125.7, 118.7, 115.2 (J = 2 Hz, 1C, C-SCF3, quartet peak should be
obtained, however, doublet peak was observed due to the low resolution of NMR machine), 112.1;
19F NMR (376 MHz, CDCl3) δ ppm -41.35 (s, 3F). IR (neat, cm-1): 3408, 3064, 2925, 2854, 1923,
1725, 1617, 1554, 1441, 1410, 1376, 1294, 1248, 1131, 1101, 1022, 976, 911, 839, 793, 758, 734;
HRMS (ESI/Q-TOF) m/z: [M + H]+ Calcd for C17H10F3N2S 331.0511; Found 331.0522 (3.2 ppm).
3-(3-chlorophenyl)-4-((trifluoromethyl)thio)isoquinoline (2cf): yellow solid; 55.0 mg; 81%; 1H
NMR (400 MHz, CDCl3) δ ppm 9.40 (s, 1H), 8.62 (d, J = 8.4 Hz, 1H), 8.07 (d, J = 8.0 Hz, 1H),
7.93−7.90 (m, 1H), 7.74 (t, J = 7.6 Hz, 1H), 7.62 (s, 1H), 7.51−7.49 (m, 1H), 7.42 (dd, J = 14.0 Hz
7.6Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ ppm 159.4, 155.0, 141.8, 139.1, 133.8, 132.4,
130.3, 129.1, 129.1 (q, J = 310 Hz, 1C, SCF3), 128.5, 128.4, 128.3, 128.2, 128.1, 125.8, 115.0 (C-
SCF3, quartet peak should be obtained, however, single peak was observed due to the low resolution
of NMR machine); 19F NMR (376 MHz, CDCl3) δ ppm -41.32 (s, 3F). IR (neat, cm-1): 3067, 2926,
2854, 1942, 1616, 1553, 1486, 1439, 1411, 1376, 1342, 1248, 1211, 1131, 1102, 978, 883, 760,
708, 689; HRMS (ESI/Q-TOF) m/z: [M + Na]+ Calcd for C16H9ClF3NNaS 361.9989; Found
361.9997 (2.2 ppm).
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
1
3-(o-tolyl)-4-((trifluoromethyl)thio)isoquinoline (2cg): yellow solid; 43.4 mg; 68%; H NMR
(400 MHz, CDCl3) δ ppm 9.42 (s, 1H), 8.60 (d, J = 8.4 Hz, 1H), 8.07 (d, J = 8.0 Hz, 1H), 7.90 (t, J
= 8.0 Hz, 1H), 7.20 (t, J = 7.6 Hz, 1H), 7.38−7.24 (m, 4H), 2.12 (m, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ ppm 161.5, 154.9, 139.8, 138.9, 135.9, 132.2, 130.0, 129.8, 129.2 (q, J = 309 Hz, 1C,
SCF3), 128.4, 128.1, 128.1, 127.9, 125.6, 125.2, 115.8 (J = 1 Hz, 1C, C-SCF3, quartet peak should
be obtained, however, doublet peak was observed due to the low resolution of NMR machine), 19.6;
19F NMR (376 MHz, CDCl3) δ ppm -40.81 (s, 3F). IR (neat, cm-1): 3063, 3024, 2957, 2926, 1728,
1618, 1555, 1485, 1444, 1413, 1376, 1290, 1248, 1130, 1102, 1044, 976, 938, 868, 758, 728; HRMS
(ESI/Q-TOF) m/z: [M + H]+ Calcd for C17H13F3NS 320.0715; Found 320.0721 (1.9 ppm).
6-chloro-3-phenyl-4-((trifluoromethyl)thio)isoquinoline (2ch): yellow solid; 36.7 mg; 54%; 1H
NMR (400 MHz, CDCl3) δ ppm 9.38 (s, 1H), 8.61 (s, 1H), 8.01 (d, J = 8.8 Hz, 1H), 7.66 (d, J = 8.4
Hz, 1H), 7.59 (d, J = 7.2 Hz, 2H), 7.50−7.45 (m, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ ppm
ACS Paragon Plus Environment