Copper-Catalyzed Synthesis of Aryl Thioamides from Aryl Aldehydes and Tetramethylthiuram Disulfide

Article abstract of DOI:10.1055/s-0036-1590936

A novel and convenient method for the synthesis of aryl thioamides from aryl aldehydes and tetramethylthiuram disulfide (TMTD) without the use of sulfurating reagent was explored. In the presence of CuI and di- tert -butyl peroxide (DTBP), various aryl thioamides were prepared with good to excellent yields, tetramethylthiuram disulfide as thioamide source is essential for this transformation. The protocol features broad substrate scope, nice yields, operability and commercially available and inexpensive raw materials, showing its practical synthetic value in organic synthesis.

Full text of DOI:10.1055/s-0036-1590936

SYNTHESIS
0
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1
1
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-
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1
0
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© Georg Thieme Verlag Stuttgart · New York
2017, 49, A–G
paper
A
en
M.-T. Zeng et al.
Paper
Synthesis
Copper-Catalyzed Synthesis of Aryl Thioamides from Aryl Aldehydes
and Tetramethylthiuram Disulfide
Meng-Tian Zeng§
Min Wang§
S
S
CHO
S
N
N
Han-Ying Peng
Yu Cheng
CuI (10 mol%), DTBP (4.0 equiv)
EtOAc, 120 °C, 7–8 h
N
S
+
S
FG
FG
Zhi-Bing Dong*
FG: H, Me, MeO, tBu,
F, Cl, Br, I, CF3
16 examples
yield: 77–85%
School of Chemistry and Environmental Engineering, Wuhan
Institute of Technology, Wuhan 430205, P. R. of China
dzb04982@wit.edu.cn
§ These authors contributed equally to this work
Dedicated to Professor Herbert Mayr at Ludwig-Maximilians
Universität on the occasion of his 70th birthday.
Received: 03.09.2017
Accepted after revision: 25.09.2017
Published online: 12.10.2017
N-substituted formamides16 or ketones with O,O-diethyl
dithiophosphoric acid.17 However, the use of some sulfurat-
ing reagents suffer from environmental and operational is-
sues due to their fuming, corrosive and pungent smelling
nature. To our knowledge, the reaction of aryl aldehydes
and tetramethylthiuram disulfide (TMTD) to generate aryl
thioamide has not been explored. As part of our longstand-
ing interest in developing TMTD and the relevant applica-
tions in our laboratory (Scheme 2, a and b),18 we hereby re-
port a new method for the synthesis of aryl thioamides us-
ing aryl aldehydes and TMTD in the presence of CuI/DTBP
without any sulfurating reagent (Scheme 2, c).
DOI: 10.1055/s-0036-1590936; Art ID: ss-2017-z0520-op
Abstract A novel and convenient method for the synthesis of aryl thio-
amides from aryl aldehydes and tetramethylthiuram disulfide (TMTD)
without the use of sulfurating reagent was explored. In the presence of
CuI and di-tert-butyl peroxide (DTBP), various aryl thioamides were pre-
pared with good to excellent yields, tetramethylthiuram disulfide as
thioamide source is essential for this transformation. The protocol fea-
tures broad substrate scope, nice yields, operability and commercially
available and inexpensive raw materials, showing its practical synthetic
value in organic synthesis.
Key words aryl thioamide, benzaldehyde, tetramethylthiuram disul-
fide, copper, di-tert-butyl peroxide
S
S
MeO
P
O
S
S
P
S
OMe
R1
S
R1
Thioamides are popular structural units that are found
widely in biological and pharmaceutically active molecules,
such as plasma-stable and cell-permeable inhibitors,1 DNA
gyrase inhibitors,2 antibiotics,3 and potent HIV-1 reverse
transcriptase inhibitors.4 At the same time, compounds
with the thioamide moiety are useful synthons for prepar-
ing sulfur-containing heterocycles,5 such as thiazoles,6 thi-
azolines, and aminothiazoles.7 Moreover, several thioam-
ides were found as the core substrate of the catalytic enan-
tioselective total synthesis of caprazamycin B,8 and has
been used in catalytic asymmetric Mannich type reactions.9
Different routes for the preparation of thioamides have
been described, with the most conventional methods being
cross-coupling reaction of Grignard reagents with thionyl
chloride,10 thionation reaction by using Lawesson’s reagent
(Scheme 1, a),11 and the Willgerodt–Kindler reaction
(Scheme 1, b).12 Similarly, amide compounds could be con-
verted into thioamides by Lawesson’s reagent analogues of
P4S10,13 H2NS2P(OEt)2,14 and (NH4)2S15 (Scheme 1, c). Recent-
ly, alternative means to prepare thioamides were reported
by the reaction of alkyl/aryl aldehydes, sodium sulfide and
R
N
R
R
N
R2
(a)
(b)
R2
Lawesson's reagent
H
N
R1
S8
N
R2
+
ArX
R1
Willgerodt–Kindler reaction
R2
CH
Ac, CH2CO2H, HC CHCO2H
X = CH2CN, CHO, CH2NH2, C
R = Ar, CH2Ar
O
S
P4S10, H2NS2P(OEt)2, (NH4)2S
R1
R1
(c)
R
N
R2
R
N
R2
Scheme 1 Conventional methods for the synthesis of thioamide
For initial studies, benzaldehyde (1a) and TMTD (2a)
were selected as substrates for the model reaction under
various conditions (Table 1). To begin with, the reaction of
1a and 2a was carried out in the presence of H2O2/EtOAc at
70 °C. To our delight, the desired product 3a was obtained
in 30% yield (entry 1). Various other oxidants, for example,
KMnO4, FeCl3, O2, PhI(OAc)2, Na2S2O8, and DTBP, which
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–G

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M.-T. Zeng et al.
Paper
Synthesis
Our previous work:
O
R
N
(a)
(b)
S
R
OH
or
S
R = aryl, alkyl
S
N
+
N
S
O
S
COOH
N
R1
R1
R1 = F, Br, Cl, NO2, MeO, Ph, etc.
This work:
CHO
S
S
S
N
N
CuI (10 mol%), DTBP (4.0 equiv)
EtOAc, 120 °C, 7–8 h
(c)
N
S
+
S
FG
FG
Scheme 2 Our studies on TMTD and relevant applications
might promote the model reaction, were surveyed (entries
2–7); the results showed that DTBP was more reactive than
others (entry 7). Solvent screening (entries 7–12) showed
that ethyl acetate (EtOAc) was more suitable, furnishing the
product in 39% yield. The yields increased when the tem-
perature was raised (entries 13–16), and it was found that
120 °C was the most suitable temperature (entry 15). Stud-
ies on DTBP loading (entries 17–19) revealed that 4.0 equiv-
alents of DTBP was reasonable, and the molar ratio survey
for substrates (entries 20 and 21) showed that a ratio of
1a/2a of 1.0:1.1 was optimal (entry 21). Screening for a va-
riety of catalysts, such as copper, iron, palladium and nickel
(entries 22–33) revealed that these catalysts were not (or
less) effective with respect to yield, although the use of CuI
could shorten the reaction time from 12 to 7 hours (entry
30). The yield was not further promoted by increasing the
loading of CuI to 20 mol% (entry 34), and the reaction time
required was extended to 10 hours by reducing the loading
of CuI to 5 mol% (entry 35). The optimized reaction condi-
tions are summarized in Table 1, entry 30.
Under the optimized reaction conditions, various func-
tionalized benzaldehydes (1a–p) and TMTD (2a) reacted
smoothly, providing the corresponding N,N-dimethylben-
zothioamide in good yields (Table 2). Substrate scope ex-
periments revealed that benzaldehydes with electron-do-
nating (1b–e) or electron-withdrawing groups (1f–n) react-
ed well with TMTD (2a), giving the target product in 77–
85% yield (entries 2–14). ortho-Substituted substrates gave
lower yields compared with para- or meta-substituted sub-
strates, because of the possible steric hindrance (entries 3,
6, 9, and 13). For example, 4-chloro-benzaldehyde or 3-
chlorobenzaldehyde gave the corresponding products in 85
and 84% yield, respectively, whereas 2-chlorobenzaldehyde
resulted in 78% yield (entries 6–8). Similar results were ob-
tained in the reaction starting from p-bromobenzaldehyde,
m-bromobenzaldehyde and o-bromobenzaldehyde, which
afforded the corresponding products in 82, 80, and 77%
yield, respectively (entries 9–11). Benzaldehydes bearing
multiply substituted electron-withdrawing or electron-
donating groups could furnish the corresponding aryl thio-
amides 3o and 3p successfully (entries 15 and 16). In gener-
al, this reaction was not affected by the electronic proper-
ties, and only slightly influenced by steric hindrance, show-
ing its good substrate suitability.
Table 1 Optimization of the Reaction Conditionsa
S
S
CHO
+
S
N
conditions
N
N
S
S
1a
2a
3a
Entry Catalyst (mol%) Oxidant
Solvent
Temp (°C) Yield (%)b
1
2
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
H2O2
KMnO4
FeCl3
O2
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
DMSO
DMAC
DMF
70
70
30
N.R
N.R
N.R
28
N.R
39
25
30
31
28
25
45
55
58
58
71
79
79
3
70
4
70
5
PhI(OAc)2
Na2S2O8
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
70
6
70
7
70
8
70
9
70
10
11
12
13
14
15
16
17c
18d
19e
70
PhCH3
PhNO2
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
70
70
90
110
120
130
120
120
120
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–G

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M.-T. Zeng et al.
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Synthesis
Although the reaction mechanism is not clear at this
stage, we speculate that the reaction might proceed
through copper-catalyzed oxidative decarboxylation (de-
carbonylsulfide, -COS).19 Further details of the mechanism
and the development of related applications for this proto-
col are under study in our laboratory.
In summary, we have presented a novel and practical
method for the synthesis of aryl thioamides from aryl alde-
hydes and TMTD without sulfurating reagent. In the pres-
ence of CuI and DTBP, various aryl thioamides could be ob-
tained in good yields. Aryl aldehydes are amenable to this
protocol with good functional group tolerance, and readily
available, inexpensive TMTD serves as thioamide source in
this reaction, which makes the method more convenient
and efficient, and might afford an alternative way for the
preparation of biologically or pharmaceutically active com-
pounds.
Entry Catalyst (mol%) Oxidant
Solvent
Temp (°C) Yield (%)b
20f
21g
22
23
24
25
26
27
28
29
30
31
32
33
34h
35i
–
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
40
81
80
79
81
80
79
81
76
78
82
74
67
69
82
81
–
CuO
Cu2O
CuBr
CuBr2
CuCl
Cu(OAc)2
CuSO4
Cu(OTf)2
CuI
FeCl2
Pd(OAc)2
NiBr2
CuI
All starting materials were purchased from commercial suppliers and
used without further purification unless otherwise stated. Yields re-
fer to isolated compounds estimated to be >95% pure as determined
by 1H NMR and capillary GC analysis. NMR spectra were recorded
with a Bruker AM400 NMR (1H NMR at 400 Hz, 13C NMR at 100 Hz)
instrument in CDCl3 using tetramethylsilane as an internal standard.
Chemical shifts are given in ppm and coupling constants (J) are given
in Hz. Melting points were determined with a Kofler micro melting
point apparatus without correction. High-resolution mass spectra
(HRMS) were recorded with a Finnigan MAT 95Q or Finnigan 90 mass
instrument (ESI). TLC was performed using aluminum plates coated
with SiO2 (Merck 60, F-254) and visualized with UV light at 254 nm.
Column chromatography was performed on silica gel (200–300
mesh) with PE–EtOAc as eluent.
CuI
a Reaction conditions: 1a (1.0 mmol), 2a (1.0 mmol), oxidant (2.0 equiv),
catalyst (10 mol%), solvent (2 mL), 7–12 h.
b Isolated yield.
c With DTBP (3.0 equiv).
d With DTBP (4.0 equiv).
e With DTBP (5.0 equiv).
f With 1a (2.0 mmol) and 2a (1.0 mmol).
g With 1a (1.0 mmol) and 2a (1.1 mmol).
h With CuI (20 mol%).
i With CuI (5 mol%).
Table 2 Synthesis of Aryl Thioamides from Benzaldehydes and Tetramethylthiuram Disulfidea
S
S
CHO
CuI (10 mol%), DTBP (4.0 equiv)
S
N
N
+
N
S
EtOAc, 120 °C, 7–8 h
S
1
2
3
Entry
1
Benzaldehyde
Product
Yield (%)b
82
S
CHO
N
S
1a
3a
3b
3c
CHO
N
2
3
83
79
1b
1c
S
CHO
N
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–G

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M.-T. Zeng et al.
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Synthesis
Table 2 (continued)
Entry
Benzaldehyde
Product
Yield (%)b
82
S
S
CHO
CHO
N
N
4
5
6
O
1d
O
3d
83
78
1e
1f
3e
3f
S
CHO
Cl
N
N
Cl
S
CHO
7
84
Cl
Cl
1g
3g
S
CHO
N
8
9
85
77
Cl
1h
Cl
3h
S
CHO
Br
N
N
Br
S
1i
1j
3i
CHO
10
11
12
13
80
82
83
79
Br
Br
3j
S
CHO
N
Br
1k
Br
3k
S
CHO
N
I
I
1l
3l
S
F
CHO
F
N
1m
3m
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Synthesis
Table 2 (continued)
Entry
Benzaldehyde
Product
Yield (%)b
S
CHO
N
14
15
16
78
CF3
CF3
1n
3n
S
CHO
Cl
N
80
79
Cl
1o
Cl
Cl
3o
S
O
O
CHO
O
O
N
O
O
1p
3p
a Reaction conditions: 1 (1.0 mmol), 2 (1.1 mmol), CuI (10 mol%), DTBP (4.0 equiv), EtOAc (2 mL), 110 °C, 7–8 h.
b Isolated yield.
Preparation of Aryl Thioamides in the Presence of CuI and DTBP;
Typical Procedure (TP)
HRMS (ESI): m/z calcd for C10H13NS: 179.0769; found: 179.0765.
N,N-2-Trimethylbenzothioamide (3c)
Benzaldehyde (1.0 mmol), TMTD (1.1 mmol), CuI (10 mol%), and
DTBP (4.0 equiv) were added to a dried sealed tube equipped with a
septum and magnetic stirrer bar, EtOAc (2 mL) was then added. (Cau-
tion! The sealed tube is a pressure-proof tube with a septum.) The
mixture was stirred at 120 °C and checked by thin-layer chromatogra-
phy (TLC) until the starting material was consumed (ca. 7–8 h). The
reaction was cooled to r.t., quenched with sat. NH4Cl solution (5 mL),
and then extracted with EtOAc (3 × 10 mL). The crude solution was
dried over anhydrous Na2SO4 and evaporated under vacuum. The res-
idue was purified by flash column chromatography to afford the de-
sired product.
According to the TP, the residue was purified by flash chromatogra-
phy on silica gel (EtOAc/PE, 1:8) to give the target compound 3c.
Yield: 141.4 mg (79%); yellow oil.
1H NMR (CDCl3, 400 MHz): δ = 7.33–7.27 (m, 1 H), 7.18 (d, J = 6.0 Hz,
2 H), 7.12 (d, J = 7.6 Hz, 1 H), 3.64 (s, 3 H), 3.21 (s, 3 H), 2.40 (s, 3 H).
13C NMR (CDCl3, 100 MHz): δ = 201.4, 143.3, 138.0, 129.2, 128.1,
126.2, 122.5, 44.0, 43.0, 21.2.
HRMS (ESI): m/z calcd for C10H13NS: 179.0769; found: 179.0768.
4-Methoxy-N,N-dimethylbenzothioamide (3d)
N,N-Dimethylbenzothioamide (3a)
According to the TP, the residue was purified by flash chromatogra-
phy on silica gel (EtOAc/PE, 1:8) to give the target compound 3d.
According to the TP, the residue was purified by flash chromatogra-
phy on silica gel (EtOAc/PE, 1:8) to give the target compound 3a.
Yield: 159.9 mg (82%); yellow oil.
1H NMR (CDCl3, 400 MHz): δ = 7.30 (d, J = 8.6 Hz, 2 H), 6.86 (d, J =
8.8 Hz, 2 H), 3.81 (s, 3 H), 3.58 (s, 3 H), 3.21 (s, 3 H).
13C NMR (CDCl3, 100 MHz): δ = 201.1, 159.9, 135.7, 127.92, 113.4,
Yield: 135.3 mg (82%); yellow solid; mp 69–71 °C.
1H NMR (CDCl3, 400 MHz): δ = 7.34–7.27 (m, 5 H), 3.57 (s, 3 H), 3.13
(s, 3 H).
13C NMR (CDCl3, 100 MHz): δ = 201.03, 143.3, 128.5, 128.3, 125.7,
44.2, 43.2.
55.4, 44.5, 43.6.
HRMS (ESI): m/z calcd for C10H13NOS: 195.0718; found: 195.0715.
HRMS (ESI): m/z calcd for C9H11NS: 165.0612; found: 165.0614.
4-tert-Butyl-N,N-dimethylbenzothioamide (3e)
N,N-4-Trimethylbenzothioamide (3b)
According to the TP, the residue was purified by flash chromatogra-
phy on silica gel (EtOAc/PE, 1:8) to give the target compound 3d.
According to the TP, the residue was purified by flash chromatogra-
phy on silica gel (EtOAc/PE, 1:8) to give the target compound 3b.
Yield: 183.4 mg (83%); yellow oil.
1H NMR (CDCl3, 400 MHz): δ = 7.35 (d, J = 8.0 Hz, 2 H), 7.24 (d, J =
8.0 Hz, 2 H), 3.59 (s, 3 H), 3.19 (s, 3 H), 1.31 (s, 9 H).
13C NMR (CDCl3, 100 MHz): δ = 201.5, 151.7, 140.5, 125.6, 125.2, 44.3,
Yield: 148.6 mg (83%); yellow oil.
1H NMR (CDCl3, 400 MHz): δ = 7.21 (d, J = 8.0 Hz, 2 H), 7.14 (d, J =
7.8 Hz, 2 H), 3.59 (s, 3 H), 3.18 (s, 3 H), 2.35 (s, 3 H).
13C NMR (CDCl3, 100 MHz): δ = 201.5, 140.5, 138.7, 128.9, 125.9, 44.3,
43.4, 34.7, 31.3.
43.4, 21.3.
HRMS (ESI): m/z calcd for C13H19NS: 221.1238; found: 221.1236.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–G

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M.-T. Zeng et al.
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Synthesis
2-Chloro-N,N-dimethylbenzothioamide (3f)
1H NMR (CDCl3, 400 MHz): δ = 7.48 (d, J = 8.4 Hz, 2 H), 7.19 (d, J =
8.2 Hz, 2 H), 3.58 (s, 3 H), 3.17 (s, 3 H).
According to the TP, the residue was purified by flash chromatogra-
13C NMR (CDCl3, 100 MHz): δ = 199.7, 142.1, 131.5, 127.5, 122.7, 44.2,
phy on silica gel (EtOAc/PE, 1:8) to give the target compound 3f.
43.3.
Yield: 155.2 mg (78%); yellow oil.
1H NMR (CDCl3, 400 MHz): δ = 7.26–7.35 (m, 4 H), 3.61 (s, 3 H), 3.11
HRMS (ESI): m/z calcd for C9H10BrNS: 242.9717; found: 242.9723.
(s, 3 H).
3-Iodo-N,N-dimethylbenzothioamide (3l)
13C NMR (CDCl3, 100 MHz): δ = 196.8, 142.0, 129.6, 129.2, 128.1,
According to the TP, the residue was purified by flash chromatogra-
127.7, 127.3, 42.8, 42.3.
phy on silica gel (EtOAc/PE, 1:8) to give the target compound 3l.
HRMS (ESI): m/z calcd for C9H10ClNS: 199.0222; found: 199.0224.
Yield: 241.5 mg (83%); yellow oil.
3-Chloro-N,N-dimethylbenzothioamide (3g)
1H NMR (CDCl3, 400 MHz): δ = 7.64–7.66 (m, 1 H), 7.23–7.27 (m, 2 H),
7.06–7.11 (m, 1 H), 3.56 (s, 3 H), 3.15 (s, 3 H).
According to the TP, the residue was purified by flash chromatogra-
13C NMR (CDCl3, 100 MHz): δ = 198.8, 145.0, 137.5, 134.2, 130.0,
phy on silica gel (EtOAc/PE, 1:8) to give the target compound 3g.
124.8, 94.0, 43.1, 44.1.
Yield: 167.2 mg (84%); yellow oil.
1H NMR (CDCl3, 400 MHz): δ = 7.33–7.25 (m, 3 H), 7.21–7.13 (m, 1 H),
HRMS (ESI): m/z calcd for C9H10INS: 290.9597; found: 290.9591.
3.58 (s, 3 H), 3.16 (s, 3 H).
2-Fluoro-N,N-dimethylbenzothioamide (3m)
13C NMR (CDCl3, 100 MHz): δ = 198.9, 144.7, 134.2, 129.8, 128.6,
According to the TP, the residue was purified by flash chromatogra-
125.9, 123.8, 44.2, 43.2.
phy on silica gel (EtOAc/PE, 1:8) to give the target compound 3m.
HRMS (ESI): m/z calcd for C9H10ClNS: 199.0222; found: 199.0226.
Yield: 144.6 mg (79%); colorless oil.
4-Chloro-N,N-dimethylbenzothioamide (3h)
1H NMR (CDCl3, 400 MHz): δ = 7.44–7.37 (m, 1 H), 7.35–7.28 (m, 1 H),
7.16 (t, J = 7.2 Hz, 1 H), 7.04 (t, J = 9.0 Hz, 1 H), 3.61 (s, 3 H), 3.17 (s,
3 H).
According to the TP, the residue was purified by flash chromatogra-
phy on silica gel (EtOAc/PE, 1:8) to give the target compound 3h.
13C NMR (CDCl3, 100 MHz): δ = 194.2, 155.6 (d, 1JC–F = 245.0 Hz), 131.0
Yield: 169.2 mg (85%); yellow solid; mp 80–82 °C.
1H NMR (CDCl3, 400 MHz): δ = 7.33 (d, J = 8.2 Hz, 2 H), 7.25 (d, J =
8.6 Hz, 2 H), 3.59 (s, 3 H), 3.17 (s, 3 H).
2
3
4
(d, JC–F = 16.5 Hz), 130.5 (d, JC–F = 7.0 Hz), 129.2 (d, JC–F = 2.7 Hz),
124.6 (d, 3JC–F = 4.0 Hz), 115.6 (d, 2JC–F = 21.0 Hz), 43.22, 42.86.
HRMS (ESI): m/z calcd for C9H10FNS: 183.0518; found: 183.0512.
3-Trifluoromethyl-N,N-dimethylbenzothioamide (3n)
13C NMR (CDCl3, 100 MHz): δ = 199.8, 141.6, 134.5, 128.6, 127.3, 44.2,
43.4.
HRMS (ESI): m/z calcd for C9H10ClNS: 199.0222; found: 199.0229.
According to the TP, the residue was purified by flash chromatogra-
phy on silica gel (EtOAc/PE, 1:8) to give the target compound 3n.
2-Bromo-N,N-dimethylbenzothioamide (3i)
Yield: 181.7 mg (78%); yellow oil.
1H NMR (CDCl3, 400 MHz): δ = 7.56–7.47 (m, 4 H), 3.59 (s, 3 H), 3.15
(s, 3 H).
13C NMR (CDCl3, 100 MHz): δ = 199.0, 143.8, 130.7 (q, 2JC–F = 32.6 Hz),
129.0, 128.8, 125.1 (q, 3JC–F = 3.7 Hz), 123.5 (q, 1JC–F = 271 Hz), 122.5 (q,
3JC–F = 3.9 Hz), 44.1, 43.1.
According to the TP, the residue was purified by flash chromatogra-
phy on silica gel (EtOAc/PE, 1:8) to give the target compound 3i.
Yield: 187.03 mg (77%); yellow oil.
1H NMR (CDCl3, 400 MHz): δ = 7.53 (d, J = 8.0 Hz, 1 H), 7.35–7.27 (m,
2 H), 7.19–7.17 (m, 1 H), 3.60 (s, 3 H), 3.10 (s, 3 H).
13C NMR (CDCl3, 100 MHz): δ = 197.8, 143.9, 132.7, 129.4, 127.9,
HRMS (ESI): m/z calcd for C9H10FNS: 233.0486; found: 233.0489.
127.5, 117.5, 43.0, 42.3.
HRMS (ESI): m/z calcd for C9H10BrNS: 242.9717; found: 242.9710.
2,4-Dichloro-N,N-dimethylbenzothioamide (3o)
According to the TP, the residue was purified by flash chromatogra-
phy on silica gel (EtOAc/PE, 1:8) to give the target compound 3o.
3-Bromo-N,N-dimethylbenzothioamide (3j)
According to the TP, the residue was purified by flash chromatogra-
phy on silica gel (EtOAc/PE, 1:8) to give the target compound 3j.
Yield: 186.4 mg (80%); yellow oil.
1H NMR (CDCl3, 400 MHz): δ = 7.38 (s, 1 H), 7.28 (t, J = 5.2 Hz, 2 H),
3.59 (s, 3 H), 3.12 (s, 3 H).
13C NMR (CDCl3, 100 MHz): δ = 195.4, 140.4, 134.5, 129.4, 129.0,
Yield: 194.3 mg (80%); yellow oil.
1H NMR (CDCl3, 400 MHz): δ = 7.47–7.45 (m, 2 H), 7.23–7.22 (m, 2 H),
3.58 (s, 3 H), 3.17 (s, 3 H).
13C NMR (CDCl3, 100 MHz): δ = 198.9, 144.9, 131.5, 130.0, 128.6,
128.6, 127.7, 42.9, 42.4.
HRMS (ESI): m/z calcd for C9H9Cl2NS: 232.9833; found: 232.9837.
124.3, 122.3, 44.2, 43.2.
HRMS (ESI): m/z calcd for C9H10BrNS: 242.9717; found: 242.9721.
3,4,5-Trimethoxy-N,N-dimethylbenzothioamide (3p)
According to the TP, the residue was purified by flash chromatogra-
phy on silica gel (EtOAc/PE, 1:8) to give the target compound 3p.
4-Bromo-N,N-dimethylbenzothioamide (3k)
According to the TP, the residue was purified by flash chromatogra-
phy on silica gel (EtOAc/PE, 1:8) to give the target compound 3k.
Yield: 201.5 mg (79%); yellow solid; mp 100–102 °C.
1H NMR (CDCl3, 400 MHz): δ = 6.51 (s, 2 H), 3.84 (s, 6 H), 3.83 (s, 3 H),
3.58 (s, 3 H), 3.19 (s, 3 H).
Yield: 199.2 mg (82%); yellow solid; mp 120–122 °C.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–G

G
M.-T. Zeng et al.
Paper
Synthesis
13C NMR (CDCl3, 100 MHz): δ = 201.0, 153.1, 138.8, 138.1, 103.1, 60.8,
56.2, 44.2, 43.1.
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HRMS (ESI): m/z calcd for C12H17NO3S: 255.0929; found: 255.0934.
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Funding Information
We thank the financial support from National Natural Science Foun-
dation of China (21302150), Hubei Provincial Department of Educa-
tion (D20131501), Scientific Research Foundation for the Returned
Overseas Chinese Scholars, State Education Ministry [2012]1707,
foundation of Chutian distinguished fellow from Hubei Provincial De-
partment of Education, and the foundation of High-end Talent Culti-
vation Program from Wuhan Institute of Technology.
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(10) Babudri, F.; Fiandanese, V.; Marchese, G. Synlett 1994, 719.
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Acknowledgment
We thank Professor Aiwen Lei at Wuhan University (China) for his
kind NMR analysis support, we also thank Dr. Yi-Hung Chen at
Ludwig-Maximilians Universität (Germany) for helpful discussions.
(12) (a) Priebbenow, L. D.; Bolm, C. Chem. Soc. Rev. 2013, 42, 7870.
(b) Qu, Y. Y.; Li, Z. K.; Xiang, H. F.; Zhou, X. G. Adv. Synth. Catal.
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Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1590936.
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–G