Copper-Mediated Trifluoromethylthiolation of Heteroaryl Bromides

Article abstract of DOI:10.1002/adsc.201500575

An efficient protocol for the copper-mediated trifluoromethylthiolation of heteroaryl bromides has been achieved using the copper complex (bpy)Cu(SCF₃) as trifluoromethylthiolating reagent. This procedure provides a straightforward synthetic method for heteroaryl trifluoromethyl sulfides from readily available, simple starting materials. The reaction demonstrates a broad substrate scope and tolerates a wide array of functional groups, including nitrile, ester, chloro, nitro, or methoxy substituents.

Full text of DOI:10.1002/adsc.201500575

FULL PAPERS
DOI: 10.1002/adsc.201500575
Copper-Mediated Trifluoromethylthiolation of Heteroaryl
Bromides
a
a,
Mengjia Zhang and Zhiqiang Weng *
a
State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fujian
350108, Peopleꢀs Republic of China
Fax: (+86)-591-2286-6121; e-mail: zweng@fzu.edu.cn
Received: June 14, 2015; Revised: October 18, 2015; Published online: January 18, 2016
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201500575.
Abstract: An efficient protocol for the copper-medi- tion demonstrates a broad substrate scope and toler-
ated trifluoromethylthiolation of heteroaryl bro- ates a wide array of functional groups, including ni-
mides has been achieved using the copper complex trile, ester, chloro, nitro, or methoxy substituents.
(
bpy)Cu(SCF ) as trifluoromethylthiolating reagent.
3
This procedure provides a straightforward synthetic
method for heteroaryl trifluoromethyl sulfides from Keywords: copper; CÀS bond formation; heteroaryl
readily available, simple starting materials. The reac- bromides; thioethers; trifluoromethylthiolation
Introduction
philic reactions of trifluoromethylthiolate with aryl
[9]
halides or diazonium salts. Although these methods
Compounds containing the (trifluoromethyl)thio constitute important processes in both academia and
group (SCF ) are extremely useful scaffolds in the industry, some of them suffer from limitations of
3
pharmaceutical, agricultural, and advanced materials a combination of high temperatures, unstable re-
industries, mainly due to the high electron-withdraw- agents, and narrow substrate scopes.
ing effect and useful lipophilicity (p =1.44) of the
In recent years, transition metal-catalyzed or -medi-
R
[
1]
[10]
SCF group. For example, these compounds can be ated trifluoromethylthiolation
has emerged as
3
[
2]
[3]
found in insecticides as well as anti-inflammatory,
and anticoccidial agents (Scheme 1). The develop- a single step with readily available aryl halides, ar-
a powerful strategy for the preparation of ArSCF in
3
[
4]
[11]
[12]
[13]
ment of efficient procedures for the introduction of ylboronic acids,
arenediazonium salts,
Although the synthesis of aryl trifluoro-
methyl sulfides has been comprehensively explored,
Most commonly, aryl trifluoromethyl sulfides versatile methods for the formation of heteroaryl tri-
and
[14]
a SCF group into organic compounds is therefore of arenes.
3
[
5]
considerable interest.
[15]
(
ArSCF ) are prepared by means of either nucleophil- fluoromethyl sulfides are not so broadly developed.
3
[6]
[7]
[8]
ic, electrophilic, or radical trifluoromethylation
The transition metal-mediated trifluoromethylthio-
of aryl sulfides, disulfides, or thiocyanates, or nucleo- lation of heteroaryl bromides is of significance to the
pharmaceutical and agrochemical industry because of
the comparatively lower cost of heteroaryl bromides
and the ubiquity of heterocyclic motifs in active phar-
[16]
maceutical ingredients. However, the use of these
substrates has been problematic due to the potential
coordination of the product and/or substrate to the
metal center resulting in the formation of inactive
metal complexes. Therefore, novel reagents and reac-
tions to synthesize heteroaryl trifluoromethyl sulfides
are of value.
The use of copper reagents for the synthesis of or-
Scheme 1. Examples of CF S-containing-containing bioac- ganofluorine compounds has attracted much interest
3
tive molecules.
due to their good reactivity, low toxicity, and good re-
3
86
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FULL PAPERS
Copper-Mediated Trifluoromethylthiolation of Heteroaryl Bromides
[
17]
giospecificity.
Recently, we invented a copper re- due to its relatively weak coordination ability with
agent (bpy)Cu(SCF ) (1; bpy=2,2’-bipyridine) for the the copper reagent and a higher boiling point.
3
nucleophilic trifluoromethylthiolation of aryl iodides
Using the optimized conditions, the scope and gen-
[
18]
and activated aryl bromides.
While this reaction erality of this methodology was further investigated
provides an efficient approach for the synthesis of with 1 and a variety of bromopyridines (Table 2). The
aryl trifluoromethyl thioethers, with the increasing reactions between 2-bromopyridines 2a–i and 1 gave
use of heteroarenes in medicinal and agrochemistry, the corresponding trifluoromethylthiolated products
we were prompted to investigate the development of 3a–i in good to excellent yields (Table 2, entries 1–9).
methodologies for the synthesis of heteroaryl trifluor- For example, 2-bromopyridines 2c–f having electron-
omethyl thioethers from heteroaryl bromides.
withdrawing groups, such as 6-cyano, 6-ester, and 5-
nitro, exhibited good reactivity, producing 3c–f in 85–
9
9% yields (Table 2, entries 3–6). Many potentially re-
Results and Discussion
active functional groups, such as nitrile, ester, and
nitro were well tolerated. 2-Bromopyridines possess-
Initially, the reaction was carried out under similar ing electron-donating groups are also good substrates.
conditions as those we had developed previously for 2-Bromo-5-methoxypyridine (2g) and 2-bromo-6-(4-
the trifluoromethylthiolation of 2-bromo-3-methylpyr- methoxyphenyl)pyridine (2h) afforded the corre-
[
18]
idine, namely in CH CN at 1108C for 15 h. The re- sponding products 3g and 3h in 72% and 84% yields,
3
action of 2-bromopyridine 2a with 1.2 equiv. of 1 af- respectively (Table 2, entries 7 and 8). Notably, the
forded the corresponding product 2-(trifluorome- chloride function in 2i was well tolerated, and this
thylthio)pyridine 3a in a moderate yield (64%; substrate reacted smoothly to afford the desired prod-
Table 1, entry 1). To improve the reaction efficiency, uct 3i in 92% yield (Table 2, entry 9).
further screening of the reaction parameters was per-
formed.
In a similar manner, unactivated 3-bromopyri-
dines 2j–o and 4-bromopyridines 2p–s reacted with
[20]
Given that the solvent can have a marked influence 1 to afford the corresponding products 3j–s in moder-
[
19]
on the trifluoromethylthiolation reaction, we under- ate yields (Table 2, entries 10–19). The reaction is also
took a rapid screening of the solvents (Table 1, en- compatible with a variety of functional groups, such
tries 2–8). Other solvents, such as DMF, NMP, tolu- as nitrile, ester, nitro, chloro, methoxy, or thiophene
ene, and THF gave lower reactivity (Table 1, entries 2, substituents.
and 4–6), whereas DMSO provided less interesting re-
To extend the scope of this reaction, we next exam-
sults (Table 1, entry 3). Switching to an ethereal sol- ined the trifluoromethylthiolation of other brominat-
vent such as diglyme led to a significant increased ed nitrogen-containing heterocycles (Table 3). The
yield (84%; Table 1, entry 7). Further screening stud- fused heterocycles 3- and 8-bromoquinoline 4a and
ies revealed that dioxane is the most suitable solvent 4b, gave the corresponding products 5a and 5b in
at 1108C for 15 h (90%; Table 1, entry 8), presumably 45% and 31% yields (Table 3, entries 1 and 2). When
heterocycles with more than one nitrogen atom, such
as 2-bromoquinoxaline 4c and 2-bromopyrimidine 4d
were used as substrates, 5c and 5d were obtained in
Table 1. Optimization of the trifluoromethylthiolation of 2-
bromopyridine.
[
a]
87% and 92% yields, respectively (Table 3, entries 3
and 4). In addition, 5-bromopyrimidine 4e and 5-
bromo-2-methoxypyrimidine 4f yielded products 5e
and 5f in lower yields (19% and 38%, respectively;
Table 3, entries 5 and 6). Moreover, when 6-bromo-
imidazo[1,2-a]pyrazine 4g was subjected to the reac-
tion conditions, the corresponding product 5g was ob-
tained in 54% yield (Table 3, entry 7). 6-Bromoimida-
zo[1,2-a]pyridine 4h also reacted with 1 to provide the
desired product 5h in 25% yield (Table 3, entry 8).
These optimized conditions were also applicable to
five-membered heteroaryl bromides. 2-Bromo-1-
methyl-1H-benzo[d]imidazole 4i was reactive and re-
sulted in the formation of the desired product 5i in
[
b]
Entry
Solvent
Temp. [8C]
Time [h]
Yield [%]
1
2
3
4
5
6
7
8
CH CN
DMF
DMSO
NMP
toluene
THF
110
110
110
110
110
80
15
15
15
15
15
15
15
15
64
52
5
28
50
39
84
90
3
diglyme
dioxane
110
110
7
5% isolated yield (Table 3, entry 9). Moreover, 2-
bromo-5-methylthiazole 4j, 2-bromobenzo[d]thiazole
k, and 2-bromo-6-methoxybenzo[d]thiazole 4l par-
[a]
Reaction conditions: 1 (0.060 mmol), 2a (0.050 mmol),
4
solvent (1.5 mL), N2.
[b]
19
The yield was determined by F NMR spectroscopy with ticipated in the reaction with 1 to give trifluorome-
PhOCF as internal standard.
thylthiolated products 5j–l in 80%, 92%, and 81%
3
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Mengjia Zhang and Zhiqiang Weng
FULL PAPERS
[
a]
Table 2. Trifluoromethylthiolation of bromopyridines by (bpy)Cu(SCF ) 1.
3
[
[
[
[
a]
b]
c]
d]
Reaction conditions: 1 (0.36 mmol, 1.2 equiv.), 2 (0.30 mmol), dioxane (3.0 mL), N2.
Isolated yield.
19
The yield was determined by F NMR spectroscopy with PhOCF as internal standard.
3
2.4 equiv. of 1 were used.
yields (Table 3, entries 10–12). The oxazole substrate benzofuran 4n and 3-bromobenzo[b]thiophene 4p,
1
9
4
m was an efficient partner, providing the product 5m which both gave <10% yields ( F NMR) of products
in 84% yield (Table 3, entry 13). Some observed limi- (Table 3, entries 14 and 16). Furthermore, the
tations to the reaction included the use of 3-bromo- trifluoromethylthiolation reaction with 2-ester substi-
3
88
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Copper-Mediated Trifluoromethylthiolation of Heteroaryl Bromides
[
a]
Table 3. Trifluoromethylthiolation of heteroaryl bromides by (bpy)Cu(SCF ) 1.
3
[
[
[
[
a]
b]
c]
d]
Reaction conditions: 1 (0.36 mmol, 1.2 equiv.), 2 (0.30 mmol), dioxane (3.0 mL), N2.
Isolated yield.
19
The yield was determined by F NMR spectroscopy with PhOCF as internal standard.
3
2.4 equiv. of 1 were used.
tuted 3-bromothiophene 4o was also proved challeng- 3f (0.93 g) and 5l (0.84 g) were isolated in 85% and
ing to afford the corresponding product 5o only in 83% in gram amounts, respectively (Scheme 2).
1
7% yield (Table 3, entry 15).
In order to demonstrate the scalability and practic- pyridine utilizing the general procedure. As shown in
Finally, we investigated the reactivity of dibromo-
ability of this protocol, the trifluoromethylthiolation Scheme 3, treatment of 2,3-dibromopyridine 6 with
was performed on a 4.5 mmol and 6.1 mmol scale 3.0 equiv. of 1 afforded the desired 3-bromo-2-[(tri-
with
6-bromo-2-methyl-3-nitropyridine
2f fluoromethyl)thio]pyridine
7
and bis-trifluorome-
(
Scheme 2a) and 2-bromo-6-methoxybenzo[d]thiazole thylthiolated product 8 in a ratio of 79:21.
4l (Scheme 2b). The trifluoromethylthiolated products
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Mengjia Zhang and Zhiqiang Weng
FULL PAPERS
[
21]
[22]
[23]
eroaryl bromides 2h, and 2o–s,
4i,
4m,
and (bpy)-
[
18]
Cu(SCF3) were prepared according to the published pro-
cedures. All other reagents were obtained from commercial
sources and used without further purification. The H,
and C{1H} NMR spectra were obtained at 293 K on
a Bruker Advance 400 spectrometer, and chemical shifts
were recorded relative to the solvent resonance. F NMR
1
19
F
1
3
19
chemical shifts were determined relative to CFCl as exter-
3
nal standard and low field is positive. GC-MS measurements
were conducted on a Shimadzu QP2010SE. HR-MS were
obtained on a Waters GCT-TOF at the Shanghai Institute of
Organic Chemistry.
General Procedure for Trifluoromethylthiolation of
Heteroaryl bromides with (bpy)Cu(SCF3)
Heteroaryl bromide
2
(0.30 mmol), [(bpy)Cu(SCF )]
3
1
(114 mg, 0.36 mmol, 1.2 equiv.), and dioxane (3.0 mL)
were added to a reaction tube with a Teflon screw cap
equipped with a stir bar. The mixture was stirred at 1108C
for 15 h. The reaction mixture was filtered through a pad of
celite. To the filtrate was added water (10 mL) at 08C. The
Scheme 2. Scalability of the trifluoromethylthiolation reac-
tion.
resulting mixture was extracted with Et O (3”15 mL), and
2
the combined organic layer was washed with water, and
then dried over MgSO . The solvent was removed by rotary
4
evaporation in an ice bath and the resulting product was pu-
rified by column chromatography on silica gel with pentane/
Et O.
2
[
18]
2
-(Trifluoromethylthio)pyridine
(3a):
Quantitative
1
9
F NMR analysis of the reaction mixture indicated that 3a
1
was produced in 90% yield. H NMR (400 MHz, CDCl ):
3
Scheme 3. Regioselective trifluoromethylthiolation.
d=8.64 (d, J=4.5 Hz, 1H), 7.75 (t, J=7.7 Hz, 1H), 7.61 (d,
1
9
J=7.9 Hz, 1H), 7.39–7.30 (m, 1H); F NMR (376 MHz,
1
3
CDCl ): d=À40.2 (s, 3F): C NMR (101 MHz, CDCl ): d=
3
3
1
50.7 (s), 137.7 (s), 129.4 (q, J=308.0 Hz), 129.3 (s), 128.3
Conclusions
+ +
(
s), 128.2 (s); GC-MS: m/z=179 (M ), 110 (M ÀCF ).
3
2
-Methyl-6-[(trifluoromethyl)thio]pyridine (3b): Quantita-
19
In conclusion, we have developed an efficient access
to heteroaryl trifluoromethyl sulfides. The reaction of 3b was produced in 92% yield. Obtained as a yellow liquid.
tive F NMR analysis of the reaction mixture indicated that
1
(
bpy)Cu(SCF ) 1 with bromopyridines, bromoquino- R (diethyl ether/n-pentane 1:10)=0.63. H NMR (400 MHz,
3
f
lines, bromoquinoxalines, bromopyrimidines, bromoi- CDCl ): d=7.61 (t, J=7.7 Hz, 1H), 7.42 (d, J=7.7 Hz, 1H),
3
19
7
.17 (d, J=7.7 Hz, 1H), 2.58 (s, 3H): F NMR (376 MHz,
midazo[1,2-a]pyrazines, bromoimidazole, bromooxa-
zole, and bromobenzo[d]thiazole affords the corre-
sponding heteroaryl trifluoromethyl sulfides in moder-
ate to excellent yields. This methodology tolerates dif-
ferent substituents on the heteroaryl bromides, such
as nitrile, ester, chloro, nitro, or methoxy moieties.
13
CDCl ): d=À40.4 (s, 3F); C NMR (101 MHz, CDCl ): d=
3
3
1
3
60.1 (s), 148.3 (q, J=2.6 Hz), 137.7 (s), 129.5 (q, J=
08.2 Hz), 125.3 (q, J=1.8 Hz), 123.6 (s), 24.3 (s); IR (KBr):
n=2928, 1584, 1560, 1443, 1130, 1096, 907, 861, 784, 730,
À1
+
6
(
78, 544, 468, 428 cm ; GC-MS: m/z=193 (M ), 124
+
M ÀCF ); HR-MS (EI): m/z=193.0172, calcd. for
3
C H NSF : 193.0173.
7
6
3
6-[(Trifluoromethyl)thio]picolinonitrile (3c): Obtained as
a yellow liquid in 94% yield (58 mg). R (diethyl ether/n-
Experimental Section
f
1
pentane 1:2)=0.40. H NMR (400 MHz, CDCl ): d=7.93–
3
7
1
.88 (m, 1H), 7.76 (d, J=7.7 Hz, 1H), 7.71 (d, J=7.7 Hz,
General Information
1
9
H); F NMR (376 MHz, CDCl ): d=À39.6 (s, 3F);
3
1
3
All manipulations were carried out under an inert atmos-
phere using a nitrogen-filled glovebox or standard Schlenk
techniques. All glassware was oven or flame dried immedi-
ately prior to use. Solvents were freshly dried and degassed
according to the procedures in Purification of Laboratory
Chemicals prior to use. Deuterated solvents were purchased
from Cambridge Isotope Laboratories, Inc., and were de-
gassed and stored over activated 4 Š molecular sieves. Het-
C NMR (101 MHz, CDCl ): d=152.6 (q, J=2.8 Hz), 138.6
3
(s), 134.4 (s), 129.5 (q, J=2.2 Hz), 128.7 (q, J=309.1 Hz),
127.2 (s), 116.1 (s); IR(KBr): n=2923, 1573, 1433, 1142,
1096, 904, 800, 728, 649, 479 cm ; GC-MS: m/z=203
À1
+
+
(M ÀH), 134 (M ÀCF ); HR-MS (EI): m/z=203.9967,
3
calcd. for C H N SF : 203.9969.
7
3
2
3
Methyl 6-[(trifluoromethyl)thio]picolinate (3d): Obtained
as a yellow liquid in 87% yield (61 mg). R (diethyl ether/n-
f
3
90
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Copper-Mediated Trifluoromethylthiolation of Heteroaryl Bromides
1
pentane 1:3)=0.50. H NMR (400 MHz, CDCl ): d=8.11 (d,
2.2 Hz), 148.0 (s), 137.2 (s), 131.1 (q, J=2.3 Hz), 128.6 (q,
J=308.9 Hz), 123.3 (s); IR (KBr): n=1563, 1394, 1261,
3
J=7.7 Hz, 1H), 7.89 (t, J=7.8 Hz, 1H), 7.76 (d, J=7.9 Hz,
1
9
À1
+
1
3
H), 3.98 (s, 3H); F NMR (376 MHz, CDCl ): d=À40.1 (s,
1098, 903, 726, 650, 479 cm ; GC-MS: m/z=212 (M ÀH),
3
13
+
F); C NMR (101 MHz, CDCl ): d=164.6 (s), 150.2 (q,
143 (M ÀCF ); HR-MS (EI): m/z=212.9619, calcd. for
3
3
J=2.9 Hz), 148.9 (s), 138.7 (s), 130.5 (q, J=2.0 Hz), 129.2
C H NSClF : 212.9627.
6
3
3
(
1
q, J=308.6 Hz), 124.9 (s), 53.1 (s); IR (KBr): n=2958,
5-[(Trifluoromethyl)thio]nicotinonitrile (3j): Obtained as
À1
729, 1431, 1311, 1132, 1093, 799, 727, 650 cm ; GC-MS:
an orange liquid in 54% yield (33 mg). R (diethyl ether/n-
f
+
+
1
m/z=236 (M ÀH), 167 (M ÀCF ); HR-MS (EI): m/z=
pentane 1:4)=0.58. H NMR (400 MHz, CDCl ): d=9.04 (s,
1H), 9.00 (s, 1H), 8.29 (s, 1H); F NMR (376 MHz,
3
3
1
9
2
37.0067, calcd. ForC H NO SF : 237.0071.
8
6
2
3
13
5-Nitro-2-[(trifluoromethyl)thio]pyridine (3e): Obtained
CDCl ): d=À41.6 (s, 3F); C NMR (101 MHz, CDCl ): d=
3
3
as an orange liquid in 99% yield (66 mg). R (diethyl ether/
n-pentane 1:10)=0.50. H NMR (400 MHz, CDCl ): d=9.38
158.5 (s), 153.9 (s), 146.1 (s), 128.8 (q, J=309.5 Hz), 123.1
(q, J=2.2 Hz), 115.0 (s), 111.2 (s); IR (KBr): n=2283, 1415,
f
1
3
À1
(d, J=2.7 Hz, 1H), 8.50 (dd, J=8.7, 2.7 Hz, 1H), 7.65 (d,
1316, 1115, 1097, 1024, 905, 728, 695, 672, 489, 451 cm ;
19
+
+
J=8.7 Hz, 1H); F NMR (376 MHz, CDCl ): d=À39.7 (s,
GC-MS: m/z=203 (M ÀH), 134 (M ÀCF ); HR-MS (EI):
3
3
13
3
1
F): C NMR (101 MHz, CDCl ): d=158.3 (q, J=2.6 Hz),
m/z=203.9964, calcd. for C H N F S: 203.9969.
3
7
3
2
3
45.5 (s), 143.1 (s), 132.3 (s), 128.4 (q, J=309.3 Hz), 124.2
2-Methyl-3-nitro-5-[(trifluoromethyl)thio]pyridine
(3k):
(
1
q, J=2.6 Hz); IR (KBr): n=2923, 1731, 1592, 1521, 1347,
Obtained as a yellow liquid in 23% yield (16 mg). R (dieth-
f
À1
1
139, 1079, 1012, 854, 748 cm ; GC-MS: m/z=223
yl ether/n-pentane 1:10)=0.48. H NMR (400 MHz, CDCl ):
3
+
+
19
(
M ÀH), 154 (M ÀCF ); HR-MS (EI): m/z=223.9863,
d=8.95 (s, 1H), 8.58 (s, 1H), 2.94 (s, 3H); F NMR
3
1
3
calcd. for C H N O SF : 223.9867.
(376 MHz, CDCl ): d=À41.9 (s, 3F); C NMR (101 MHz,
6
3
2
2
3
3
2-Methyl-3-nitro-6-[(trifluoromethyl)thio]pyridine
(3f):
CDCl ): d=158.2 (q, J=0.7 Hz), 156.5 (s), 153.9 (s), 139.3
3
Obtained as an orange liquid in 85% yield (61 mg). R (di-
ethyl ether/n-pentane 1:10)=0.73. H NMR (400 MHz,
(s), 128.7 (q, J=309.5 Hz), 120.4 (q, J=2.1 Hz), 23.9 (s); IR
(KBr): n=2962, 1589, 1561, 1520, 1428, 1344, 1259, 1139,
f
1
À1
CDCl ): d=8.32 (d, J=8.6 Hz, 1H), 7.50 (d, J=8.6 Hz, 1H),
1093, 985, 901, 825, 753, 717, 501, 480 cm ; GC-MS: m/z=
3
19
+
+
2
.89 (s, 3H); F NMR (376 MHz, CDCl ): d=À39.8 (s, 3F);
237 (M ÀH), 168(M ÀCF ); HR-MS (EI): m/z=238.0022,
3
3
1
3
C NMR (101 MHz, CDCl ): d=155.4 (q, J=2.6 Hz), 155.1
calcd. for C H N O F S: 238.0024.
3
7
5
2
2 3
(s), 144.4 (s), 133.9 (s), 128.6 (q, J=309.0 Hz), 122.3 (q, J=
Methyl 5-[(trifluoromethyl)thio]nicotinate (3l): Obtained
2
1
2
.6 Hz), 23.9 (s); IR (KBr): n=2963, 1590, 1561, 1521, 1344,
as an orange liquid in 21% yield (15 mg). R (diethyl ether/
f
À1
1
139, 1093, 901, 825, 799, 753, 718, 501 cm ; GC-MS: m/z=
n-pentane 1:5)=0.42. H NMR (400 MHz, CDCl ): d=9.33
3
+
+
19
37 (M ÀH), 168 (M ÀCF ); HR-MS (EI): m/z=238.0022,
(s, 1H), 9.01 (s, 1H), 8.61 (s, 1H), 4.02 (s, 3H); F NMR
3
1
3
calcd. for C H N O F S: 238.0024.
(376 MHz, CDCl ): d=À42.0 (s, 3F); C NMR (101 MHz,
7
5
2
2
3
3
5-Methoxy-2-[(trifluoromethyl)thio]pyridine (3g): Ob-
CDCl ): d=164.4 (s), 159.0 (s), 152.6 (s), 144.3 (s), 128.9 (q,
3
tained as a yellow liquid in 72% yield (45 mg). R (diethyl
J=308.9 Hz), 126.9 (s), 122.3 (q, J=2.1 Hz), 52.8 (s); IR
(KBr): n=2957, 1731, 1582, 1277, 1167, 1108, 1099, 1025,
f
1
ether/n-pentane 1:10)=0.40. H NMR (400 MHz, CDCl ):
3
À1
d=8.37 (d, J=3.1 Hz, 1H), 7.63 (d, J=8.6 Hz, 1H), 7.24
905, 729, 697, 650, 509, 449 cm ; GC-MS: m/z=236
1
9
+
+
(
dd, J=8.6, 3.1 Hz, 1H), 3.91 (s, 3H); F NMR (376 MHz,
(M ÀH), 167 (M ÀCF ); HR-MS (EI): m/z=237.0075,
3
13
CDCl ): d=À41.4 (s, 3F); C NMR (101 MHz, CDCl ): d=
calcd. for C H NO F S: 237.0071.
3
3
8
6
2 3
1
1
56.7 (s), 139.1 (s), 138.2 (q, J=2.8 Hz), 131.6 (q, J=
.3 Hz), 129.7 (q, J=308.5 Hz), 121.7 (s), 55.8 (s); IR (KBr):
Methyl 5-[(trifluoromethyl)thio]picolinate (3m): Obtained
as a yellow liquid in 72% yield (51 mg). R (diethyl ether/n-
f
1
n=2941, 1567, 1462, 1295, 1273, 1116, 1083, 1023, 1010, 829,
pentane 1:10)=0.15. H NMR (400 MHz, CDCl ): d=8.96
3
À1
+
7
(
56, 649, 546, 473 cm ; GC-MS: m/z=208 (M ÀH), 139
(s, 1H), 8.22 (d, J=8.2 Hz, 1H), 8.17 (d, J=8.2 Hz, 1H),
+
19
M ÀCF ); HR-MS (EI): m/z=209.0124, calcd. for
4.06 (s, 3H); F NMR (376 MHz, CDCl ): d=À41.5 (s, 3F);
3
3
1
3
C H NOF S: 209.0122.
C NMR (101 MHz, CDCl ): d=164.8 (s), 155.0 (q, J=
3
7
6
3
(
4’-Methoxy-[1,1’-biphenyl]-3-yl)(trifluoromethyl)sulfane
1.0 Hz), 149.4 (s), 144.2 (s), 129.9 (q, J=309.1 Hz), 126.2 (q,
J=2.2 Hz), 125.5 (s), 53.3 (s); IR (KBr): n=2955, 1727,
1556, 1437, 1308, 1233, 1126, 1094, 1015, 903, 727, 700, 649,
(
3h): Obtained as a white solid in 84% yield (72 mg). R (di-
ethyl ether/n-pentane 1:10)=0.63. H NMR (400 MHz,
CDCl ): d=8.01 (d, J=8.8 Hz, 2H), 7.73 (t, J=7.8 Hz, 1H),
.67 (d, J=7.9 Hz, 1H), 7.40 (d, J=7.5 Hz, 1H), 7.02 (d, J=
f
1
À1
+
+
503 cm ; GC-MS: m/z=236 (M ÀH), 167 (M ÀCF ); HR-
3
3
7
8
MS (EI): m/z=237.0069, calcd. for C H NO F S: 237.0071.
8
6
2 3
19
.8 Hz, 2H), 3.89 (s, 3H); F NMR (376 MHz, CDCl ): d=
3-Methoxy-5-[(trifluoromethyl)thio]pyridine (3n): Ob-
3
13
À39.8 (s, 3F); C NMR (101 MHz, CDCl ): d=161.1(s),
tained as an orange liquid in 41% yield (26 mg). R (diethyl
3
f
1
1
58.0 (s), 149.5 (q, J=2.5 Hz), 138.1 (s), 130.4 (s), 129.5 (q,
ether/n-pentane 1:5)=0.26; H NMR (400 MHz, CDCl ):
3
1
9
J=308.2 Hz), 128.3 (s), 124.2 (q, J=2.1 Hz), 118.9 (s), 114.2
s), 55.4 (s); IR (KBr): n=2917, 2838, 1433, 1253, 1137,
d=8.45 (s, 2H), 7.49 (s, 1H), 3.93 (s, 3H); F NMR
1
3
(
1
(
(376 MHz, CDCl ): d=À42.2 (s, 3F); C NMR (101 MHz,
3
À1
+
093, 1055, 1029, 790 cm ; GC-MS: m/z=284 (M ÀH), 215
CDCl ): d=155.8 (s), 147.6 (q, J=1.0 Hz), 140.2 (s), 129.2
3
+
M ÀCF ); HR-MS (EI): m/z=285.0439, calcd. for
(q, J=308.6 Hz), 127.1 (s), 121.8 (q, J=2.3 Hz), 55.9 (s); IR
(KBr): n=2940, 1574, 1413, 1267, 1111, 1096, 1031, 1011,
3
C H F ONS: 285.0435.
1
3
10 3
À1
3
-Chloro-2-[(trifluoromethyl)thio]pyridine (3i): Obtained
873, 701, 675, 565, 454, 429 cm ; GC-MS: m/z=208
+
+
as an orange liquid in 92% yield (58 mg). R (diethyl ether/
n-pentane 1:10)=0.63. H NMR (400 MHz, CDCl ): d=8.52
(M ÀH), 139 (M ÀCF ); HR-MS (EI): m/z=209.0124,
f
3
1
calcd.forC H NOF S: 209.0122.
3
7
6
3
(
(
dd, J=4.7, 1.5 Hz, 1H), 7.73 (dd, J=8.0, 1.5 Hz, 1H), 7.23
2-(Thiophen-3-yl)-5-[(trifluoromethyl)thio]pyridine (3o):
19
dd, J=8.1, 4.7 Hz, 1H); F NMR (376 MHz, CDCl ): d=
Obtained as a yellow solid in 43% yield (34 mg). R (diethyl
3
f
13
1
À39.8 (s, 3F); C NMR (101 MHz, CDCl ): d=149.8 (q, J=
ether/n-pentane 1:10)=0.61. H NMR (400 MHz, CDCl ):
3
3
Adv. Synth. Catal. 2016, 358, 386 – 394
ꢁ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
391

Mengjia Zhang and Zhiqiang Weng
FULL PAPERS
1
d=8.84 (s, 1H), 8.06–8.02 (m, 1H), 8.00 (d, J=8.3 Hz, 1H),
pentane 1:10)=0.47. H NMR (400 MHz, CDCl ): d=9.05
3
19
7
.74–7.67 (m, 2H), 7.48–7.43 (m, 1H); F NMR (376 MHz,
(s, 1H), 8.53 (s, 1H), 8.18 (d, J=8.5 Hz, 1H), 7.91–7.80 (m,
2H), 7.65 (t, J=7.5 Hz, 1H); F NMR (376 MHz, CDCl ):
13
19
CDCl ): d=À42.7 (s, 3F); C NMR (101 MHz, CDCl ): d=
3
3
3
1
3
155.9 (q, J=0.9 Hz), 155.4 (s), 144.3 (q, J=0.6 Hz), 140.8
d=À42.3 (s, 3F); C NMR (101 MHz, CDCl ): d=154.6 (s),
3
(s), 129.1 (q, J=308.9 Hz), 126.8 (s), 126.2 (s), 125.5 (s),
151.4 (s), 148.4 (s), 144.7 (s), 131.7 (s), 129.6 (s), 129.2 (q,
1
1
20.6 (s), 119.2 (q, J=1.7 Hz); IR (KBr): n=2926, 1577,
J=308.9 Hz), 128.1 (s), 127.8 (s), 118.3 (q, J=1.9 Hz); GC-
À1
+
+
466, 1122, 1097, 1011, 904, 730, 648, 520, 492, 474 cm ;
MS: m/z=228 (M ÀH), 159 (M ÀCF ).
3
+
+
[13a]
GC-MS: m/z=260 (M ÀH), 191 (M ÀCF ); HR-MS (EI):
8-[(Trifluoromethyl)thio]quinoline
(5b): Obtained as
1
3
m/z=260.9888, calcd. for C H NF S :260.9894.
an orange liquid in 31% yield (21 mg). H NMR (400 MHz,
10
6
3 2
2-(p-Tolyl)-4-[(trifluoromethyl)thio]pyridine (3p): Ob-
CDCl ): d=9.05–8.99 (m, 1H), 8.19 (d, J=8.3 Hz, 1H), 8.07
3
tained as an orange liquid in 56% yield (45 mg). R (diethyl
(d, J=7.1 Hz, 1H), 7.87 (d, J=8.2 Hz, 1H), 7.56 (t, J=
f
1
19
ether/n-pentane 1:10)=0.50. H NMR (400 MHz, CDCl ):
8.3 Hz, 1H), 7.52–7.45 (m, 1H); F NMR (376 MHz,
3
1
3
d=8.73 (d, J=5.1 Hz, 1H), 7.96–7.90 (m, 3H), 7.43 (d, J=
CDCl ): d=À41.1 (s, 3F); C NMR (101 MHz, CDCl ): d=
3
3
1
9
5
(
.0 Hz, 1H), 7.33 (d, J=7.9 Hz, 2H), 2.45 (s, 3H); F NMR
150.7 (s), 146.7 (s), 136.5 (s), 133.9 (q, J=1.4 Hz), 130.0 (q,
J=308.6 Hz), 129.6 (s), 128.8 (s), 126.9 (q, J=1.6 Hz), 126.6
13
376 MHz, CDCl ): d=À40.4 (s, 3F); C NMR (101 MHz,
3
+
+
CDCl ): d=158.8 (s), 150.3 (s), 139.9 (s), 136.2 (q, J=
(s), 122.1 (s); GC-MS: m/z=228 (M ÀH), 159 (M ÀCF ).
3
3
[
11c]
2
1
.2 Hz), 135.3 (s), 129.7 (s), 129.1 (q, J=308.7 Hz), 126.9 (s),
25.7 (q, J=1.0 Hz), 124.6 (q, J=1.1 Hz), 21.3 (s); IR
2-[(Trifluoromethyl)thio]quinoxaline
(5c): Obtained as
an orange solid in 87% yield (60 mg). R (diethyl ether/n-
f
1
(
9
KBr): n=3033, 1570, 1542, 1426, 1376, 1161, 1121, 1104,
pentane 1:10)=0.50. H NMR (400 MHz, CDCl ): d=8.96
(s, 1H), 8.17–8.11 (m, 2H), 7.88–7.82 (m, 2H); F NMR
3
À1
+
19
05, 816, 731, 616 cm ; GC-MS: m/z=268 (M ÀH), 199
+
13
(
M ÀCF ); HR-MS (EI): m/z=269.0477, calcd. for
(376 MHz, CDCl ): d=À38.7 (s, 3F). C NMR (101 MHz,
3
3
C H NF S: 269.0486.
CDCl ): d=146.0 (q, J=2.2 Hz), 142.8 (s), 141.5 (s), 131.3
1
3
10
3
3
2
-(4-Chlorophenyl)-4-[(trifluoromethyl)thio]pyridine (3q):
(s), 131.2 (s), 130.9 (s), 129.5 (s), 129.4 (s), 128.9 (q, J=
+
+
Obtained as a white solid in 25% yield (22 mg). R (diethyl
ether/n-pentane 1:10)=0.75. H NMR (400 MHz, CDCl ):
309.5 Hz); GC-MS: m/z=230 (M ÀH), 160 (M -ÀCF ).
f
3
1
[24]
2-(Trifluoromethylthio)pyrimidine
(5d): Obtained as
3
d=8.90 (s, 1H), 8.11–7.94 (m, 3H), 7.56–7.41 (m, 3H);
a yellow liquid in 92% yield (49 mg). R (diethyl ether/n-
f
19
13
1
F NMR (376 MHz, CDCl ): d=À42.4 (s, 3F); C NMR
pentane 1:10)=0.56. H NMR (400 MHz, CDCl ): d=8.66
3
3
19
(
(
(
101 MHz, CDCl ): d=158.2 (s), 155.8 (q, J=0.9 Hz), 150.8
(s, 1H), 8.65 (s, 1H), 7.20 (t, J=4.9 Hz, 1H); F NMR
3
1
3
s), 144.4 (q, J=0.5 Hz), 139.4 (s), 136.3 (s), 136.2 (s), 129.2
s), 129.1 (q, J=308.8 Hz), 129.0 (s), 128.5 (s), 120.6 (s),
(376 MHz, CDCl ): d=À41.1 (s, 3F); C NMR (101 MHz,
3
CDCl ): d=165.94 (q, J=3.1 Hz), 158.0 (s), 128.3 (q, J=
307.8 Hz), 119.0 (s); GC-MS: m/z=180 (M ÀH), 110
3
+
1
1
20.2 (q, J=2.1 Hz); IR (KBr): n=1577, 1460, 1124, 1093,
À1
+
011, 903, 819, 726, 649, 539, 497 cm . GC-MS: m/z=288
(M ÀCF ).
3
+
+
(M ÀH), 219 (M ÀCF ); HR-MS (EI): m/z=288.9939,
5-[(Trifluoromethyl)thio]pyrimidine (5e): Quantitative
9
3
1
calcd. for C H NF SCl: 288.9940.
F NMR analysis of the reaction mixture indicated that 5e
12
7
3
2
-([1,1’-Biphenyl]-4-yl)-6-[(trifluoromethyl)thio]pyridine
was produced in 19% yield. Obtained as a yellow liquid. Rf
(diethyl ether/n-pentane 1:5)=0.45. H NMR (400 MHz,
1
(
3r): Obtained as a white solid in 26% yield (26 mg). R (di-
ethyl ether/n-pentane 1:10)=0.54. H NMR (400 MHz,
CDCl ): d=8.78 (d, J=5.1 Hz, 1H), 8.13 (d, J=8.2 Hz, 2H),
.99 (s, 1H), 7.77 (d, J=8.2 Hz, 2H), 7.70 (d, J=7.6 Hz,
f
1
19
CDCl ): d=9.34 (s, 1H), 9.00 (s, 2H); F NMR (376 MHz,
3
1
3
CDCl ): d=À41.9 (s, 3F); C NMR (101 MHz, CDCl ): d=
3
3
3
7
2
(
162.8 (q, J=0.6 Hz), 160.0 (s), 128.5 (q, J=309.3 Hz), 121.8
(q, J=2.1 Hz); IR (KBr): n=2919, 1544, 1399, 1104, 1025,
1
9
H), 7.55–7.47 (m, 3H), 7.45–7.39 (m, 1H); F NMR
13
À1
+
376 MHz, CDCl ): d=À40.3 (s, 3F); C NMR (101 MHz,
905, 757, 716, 649, 625 cm ; GC-MS: m/z=180 (M ), 111
(M ÀCF ); HR-MS (EI): m/z=179.9972, calcd. for
3
+
CDCl ): d=158.3 (s), 150.5 (s), 142.6 (s), 140.3 (s), 136.9 (s),
3
3
1
36.3 (q, J=2.1 Hz), 129.2 (q, J=310.1 Hz), 128.9 (s), 127.8
C H N F S: 179.9969.
5
3
2
3
(
(
9
s), 127.6 (s), 127.5 (s), 127.2 (s), 126.0 (s), 124.7 (s); IR
2-Methoxy-5-[(trifluoromethyl)thio]pyrimidine (5f): Ob-
KBr): n=3035, 1572, 1462, 1375, 1147, 1119, 1102, 1056,
tained as a yellow liquid in 38% yield (24 mg). R (diethyl
f
À1
1
06, 830, 769, 736, 692, 617 cm ; GC-MS: m/z=330
ether/n-pentane 1:5)=0.50. H NMR (400 MHz, CDCl ):
d=8.73 (s, 2H), 4.10 (s, 3H); F NMR (376 MHz, CDCl ):
3
+
+
19
(
M ÀH), 261 (M ÀCF ); HR-MS (EI): m/z=331.0635,
3
3
1
3
calcd. for C H NF S: 331.0643.
d=À43.5 (s, 3F); C NMR (101 MHz, CDCl ): d=166.6 (s),
18
12
3
3
2-(Thiophen-3-yl)-4-[(trifluoromethyl)thio]pyridine (3s):
165.8 (q, J=1.5 Hz), 128.6 (q, J=309.2 Hz), 113.1 (q, J=
2.2 Hz), 55.7 (s); IR (KBr): n=2957, 1731, 1582, 1277, 1167,
Obtained as a white solid in 39% yield (31 mg). R (diethyl
ether/n-pentane 1:10)=0.82. H NMR (400 MHz, CDCl ):
d=8.67 (d, J=4.5 Hz, 1H), 7.99 (s, 1H), 7.81 (s, 1H), 7.71–
7
f
1
À1
1109, 1099, 1025, 905, 729, 697, 650, 509, 449 cm ; GC-MS
m/z=210 (M ), 141 (M ÀCF ); HR-MS (EI): m/z=
3
+
+
3
19
.65 (m, 1H), 7.46–7.36 (m, 2H); F NMR (376 MHz,
210.0079, calcd. for C H N OF S: 210.0075.
6
5
2
3
13
CDCl ): d=À40.4 (s, 3F); C NMR (101 MHz, CDCl ): d=
6-[(Trifluoromethyl)thio]imidazo[1,2-a]pyrazine (5g): Ob-
3
3
1
54.7 (s), 150.4 (s), 140.9 (s), 136.2 (q, J=1.9 Hz), 129.1 (q,
tained as an orange solid in 54% yield (35 mg). R (diethyl
f
1
J=308.7 Hz), 126.8 (s), 126.1 (s), 125.7 (s), 124.8 (s), 124.5
ether)=0.50. H NMR (400 MHz, CDCl ): d=9.15 (dd, J=
3
(
7
s); IR (KBr): n=2927, 1574, 1181, 1095, 1055, 906, 788,
1.3, 0.7 Hz, 1H), 8.58 (d, J=1.4 Hz, 1H), 7.95 (d, J=1.1 Hz,
À1
+
19
35, 650, 477 cm ; GC-MS: m/z=260 (M ÀH), 191
1H), 7.83–7.80 (m, 1H); F NMR (376 MHz, CDCl ): d=
3
+
13
(
M ÀCF ); HR-MS (EI): m/z=260.9888, calcd. for
À41.7 (s, 3F); C NMR (101 MHz, CDCl ): d=144.1 (s),
3
3
C H NF S : 260.9894.
139.8 (s), 137.2 (s), 129.1 (q, J=308.8 Hz), 128.2 (q, J=
2.9 Hz), 126.2 (s), 114.4 (s); IR (KBr): n=1500, 1431, 1320,
1
0
6
3 2
[12b]
3
-[(Trifluoromethyl)thio]quinoline
(5a): Obtained as
f
À1
a yellow liquid in 45% yield (31 mg). R (diethyl ether/n-
1302, 1111, 1507, 904, 726, 648, 473 cm ; GC-MS: m/z=219
3
92
asc.wiley-vch.de
ꢁ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2016, 358, 386 – 394

FULL PAPERS
Copper-Mediated Trifluoromethylthiolation of Heteroaryl Bromides
+
+
+
+
(
M ), 150 (M ÀCF ); HR-MS (EI): m/z=219.0075, calcd.
244 (M ÀH), 143 (M ÀCF ); HR-MS (EI): m/z=245.0122,
3
3
for C H N F S: 219.0078.
calcd. for C10H NOSF : 245.0119.
6 3
7
4
3
3
6
-[(Trifluoromethyl)thio]imidazo[1,2-a]pyridine (5h): Ob-
3-(Trifluoromethylthio)benzo[b]furan (5n): Quantitative
1
9
tained as a red solid in 25% yield (16 mg). R (diethyl
ether)=0.50. H NMR (400 MHz, CDCl ): d=8.53 (s, 1H),
.77–7.66 (m, 3H), 7.37 (d, J=9.3 Hz, 1H); F NMR
F NMR analysis of the reaction mixture indicated that 5n
f
1
19
was produced in 4% yield. F NMR (376 MHz, CDCl
): d=
).
Methyl 3-[(Ttrifluoromethyl)thio]thiophene-2-carboxylate
3
3
1
9
+
+
7
(
À43.1 (s, 3F); GC-MS: m/z=216 (M ), 115 (M ÀCF
3
13
376 MHz, CDCl ): d=À43.4 (s, 3F); C NMR (101 MHz,
3
1
9
(
5o): Quantitative F NMR analysis of the reaction mixture
indicated that 5o was produced in 17% yield. F NMR
CDCl ): d=144.8 (s), 135.1 (s), 133.3 (s), 130.4 (s), 129.1 (q,
3
19
J=309.1 Hz), 118.3 (s), 113.1 (s), 109.7 (q, J=2.6 Hz); IR
KBr): n=3075, 1716, 1623, 1426, 1307, 1104, 1071, 904, 803,
(
376 MHz, CDCl ): d=À41.4 (s, 3F); GC-MS: m/z=242
(
7
(
3
+
+
À1
+
(M ), 141 (M ÀCF ).
11, 605, 541, 471 cm ; GC-MS: m/z=218 (M ), 149
3
+
3-[(Trifluoromethyl)thio]benzo[b]thiophene (5p): Quanti-
M ÀCF ); HR-MS (EI): m/z=218.0128, calcd. for
3
1
9
tative F NMR analysis of the reaction mixture indicated
that 5p was produced in 8% yield. F NMR (376 MHz,
CDCl ): d=À42.6 (s, 3F); GC-MS: m/z=234 (M ), 133
C H N F S: 218.0126.
8
5
2
3
1
9
1-Methyl-2-[(trifluoromethyl)thio]-1H-benzo[d]imidazole
+
3
(
5i): Obtained as a yellow solid in 75% yield (52 mg). R (di-
ethyl ether/n-pentane 1:3)=0.35. H NMR (400 MHz,
CDCl ): d=7.88 (d, J=8.1 Hz, 1H), 7.45–7.41 (m, 2H),
.40–7.34 (m, 1H), 3.97 (s, 3H); F NMR (376 MHz,
f
+
1
(M ÀCF
).
3
3
-Bromo-2-[(trifluoromethyl)thio]pyridine (7): Quantita-
tive F NMR analysis of the reaction mixture indicated that
was produced in 79% yield. F NMR (376 MHz, CDCl ):
3
+
d=À40.3 (s, 3F); GC-MS: m/z=259 (M +H), 158
3
19
19
7
19
7
13
CDCl ): d=À40.2 (s, 3F); C NMR (101 MHz, CDCl ): d=
3
3
1
(
43.3 (s), 137.6 (s), 136.7 (s), 128.2 (q, J=311.5 Hz), 125.0
+
(
M ÀCF ).
3
s), 123.4 (s), 121.0 (s), 110.3 (s), 31.3 (d, J=0.6 Hz); GC-
2
,3-Bis[(trifluoromethyl)thio]pyridine (8): Quantitative
+
+
MS: m/z=231 (M ÀH), 130 (M ÀCF ); HR-MS (EI):
19
3
F NMR analysis of the reaction mixture indicated that 8
m/z=232.0283, calcd. for C H N SF : 232.0282.
19
9
7
2
3
was produced in 21% yield. F NMR (376 MHz, CDCl ):
3
+
5-Methyl-2-[(trifluoromethyl)thio]thiazole (5j): Obtained
d=À40.4 (s, 3F), À41.7 (s, 3F); GC-MS: m/z=279 (M ),
as an orange liquid in 80% yield (48 mg). R (diethyl ether/
n-pentane 1:10)=0.63. H NMR (400 MHz, CDCl ): d=7.68
+
f
1
78 (M ÀCF ); HR-MS (EI): m/z=278.9606, calcd. for
3
1
3
C H NS F : 278.9611.
7 3 2 6
19
(
(
s, 1H), 2.56 (s, 3H); F NMR (376 MHz, CDCl ): d=À42.2
3
13
s, 3F); C NMR (101 MHz, CDCl ): d=146.3 (q, J=
3
3.2 Hz), 143.3 (s), 142.6 (s), 128.1 (q, J=310.9 Hz), 12.2 (s);
IR (KBr): n=2927, 1514, 1443, 1374, 1144, 1105, 1022, 905,
Acknowledgements
À1
+
8
1
50, 729, 648, 516, 462, 445 cm ; GC-MS: m/z=199 (M ),
+
30 (M ÀCF ); HR-MS (EI): m/z=198.9736, calcd. for
3
Financial support from National Natural Science Foundation
of China (21372044), Research Fund for the Doctoral Pro-
gram of Higher Education of China (No. 20123514110003),
the SRF for ROCS, SEM, China (2012-1707), the Science
Foundation of the Fujian Province, China (2013J01040), and
Fuzhou University (022494) is gratefully acknowledged.
C H NF S : 198.9737.
5
4
3 2
[13a]
2
-[(Trifluoromethyl)thio]benzothiazole
(5k): Obtained
as a yellow liquid in 92% yield (65 mg). R (diethyl ether/n-
f
1
pentane 1:30)=0.50. H NMR (400 MHz, CDCl ): d=8.16
3
(
7
d, J=8.3 Hz, 1H), 7.92 (d, J=7.9 Hz, 1H), 7.58 (t, J=
19
.6 Hz, 1H), 7.51 (t, J=7.6 Hz, 1H); F NMR (376 MHz,
13
CDCl ): d=À40.2 (s, 3F); C NMR (101 MHz, CDCl ): d=
3
3
1
3
53.1 (s), 151.7 (q, J=3.0 Hz), 137.9 (s), 128.2 (q, J=
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+
+
m/z=234 (M ), 165 (M ÀCF ).
3
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C H NOF S : 264.9843.
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