K2S2O8-promoted aryl thioamides synthesis from aryl aldehydes using thiourea as the sulfur source

Article abstract of DOI:10.3390/molecules23092225

Thiourea as a sulfur atom transfer reagent was applied for the synthesis of aryl thioamides through a three-component coupling reaction with aryl aldehydes and N,N-dimethylformamide (DMF) or N,N-dimethylacetamide (DMAC). The reaction could tolerate various functional groups and gave moderate to good yields of desired products under the transition-metal-free condition.

Full text of DOI:10.3390/molecules23092225

molecules
Article
K2S2O8-Promoted Aryl Thioamides Synthesis from
Aryl Aldehydes Using Thiourea as the Sulfur Source
Yongjun Bian *,†, Xingyu Qu †, Yongqiang Chen, Jun Li and Leng Liu
College of Chemistry and Chemical Engineering, Jinzhong University, Yuci 030619, China;
quxy@jzxy.edu.cn (X.Q.); chenyongqiang@jzxy.edu.cn (Y.C.); hxx406@126.com (J.L.); liuleng@jzxy.edu.cn (L.L.)
* Correspondence: yjbian2013@jzxy.edu.cn; Tel.: +86-0351-398-5774
† These authors contributed equally to this work
ꢀꢁꢂꢀꢃꢄꢅꢆꢇ
ꢀꢁꢂꢃꢄꢅꢆ
Received: 30 July 2018; Accepted: 29 August 2018; Published: 1 September 2018
Abstract: Thiourea as a sulfur atom transfer reagent was applied for the synthesis of aryl thioamides
through a three-component coupling reaction with aryl aldehydes and N,N-dimethylformamide
(DMF) or N,N-dimethylacetamide (DMAC). The reaction could tolerate various functional groups
and gave moderate to good yields of desired products under the transition-metal-free condition.
Keywords: aryl thioamides; thiourea; C-H/C-N activation; C-S formation; transition-metal-free
1. Introduction
The synthesis of sulfur-containing organic compounds has received much attention in recent
years, due to their wide applications in biology, chemistry, and materials science [
many sulfur reagents for their synthesis, such as P2S5 [11], Lawesson’s reagent [12], disulfides [13
thiols [16 19], sulfonyl hydrazides [20 23], sodium sulfonate [24 28], and elemental sulfur [29–
1
–
10]. There are
15],
32].
–
–
–
–
Among them, both P2S5 and Lawesson’s reagent are the most widely used reagents, and yet they
have an obvious drawback of being sensitive to moisture. Therefore, much better sulfur reagents have
been pursued by the organic chemists for the past decades [33]. Thioamides, as an important class of
sulfur-containing organic compounds, have been synthesized by applying different sulfur reagents as
the sulfur source [1,34–39]. For example, Jiang et al. [35] reported that sodium sulfide as a sulfur source
was applied for the synthesis of thioamides using aldehydes and N-substituted formamides. More
recently, a coupling reaction between quaternary ammoniums, N-substituted formamides, and sodium
disulfide was accomplished for rapid access to aryl thioamides [36]. Thiourea as an inexpensive and
easy-to-handle sulfur atom transfer reagent, was used extensively as well, mainly for the synthesis of
inorganic metal sulfides [40–42], organic thioethers [43–47], and thioesters [48,49]. As far as we known,
a similar reaction using thiourea and aldehydes to prepare thioamides has not yet been introduced.
Hence, we want to report a new three-component coupling reaction between aryl aldehydes, thiourea
as an effective sulfur source, and DMF or DMAC, for the synthesis of various aryl thioamides.
2. Results and Discussion
Initially, we treated the reaction of 4-chlorobenzaldehyde 1a in DMF and H2O at 125 ◦C in the
presence of thiourea using the benzoyl peroxide (BPO) as an oxidant. After 24 h, the desired thioamide
product 3a was isolated in 58% yield (Table 1, Entry 1). Subsequently, various oxidants, which are
commonly used in C-H activation, such as p-benzoquinone (BQ), di-t-butyl peroxide (DTBP), tert-butyl
hydroperoxide (TBHP), K2S2O8, or (NH4)2S2O8, were attempted, to optimize the reaction condition
(Table 1, Entries 2–6). Among them, K2S2O8 proved to be best to give the desired thioamide product
3a in 69% yield (Table 1, Entry 5). For this transformation, H2O played an extremely important role.
No desired product 3a was observed when increasing the concentration of H2O to 42 M or without
Molecules 2018, 23, 2225; doi:10.3390/molecules23092225
www.mdpi.com/journal/molecules

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addition of H2O (Table 1, Entries 7 and 9). Slightly enhancing or reducing the loading amount of
K2S2O8, the yield of 3a was not obviously changeable (Table 1, Entries 10–11). When the 20% of
Cu(OAc)2 were used as a catalyst, only 54% yield of 3a was afforded (Table 1, Entry 12) [36]. To our
delight, the yield of 3a was further promoted to 80% when 5 equiv. of pyridine (Py) as an additive
were added (Table 1, Entry 13) [35].
Table 1. Optimization of reaction conditions a.
O
S
CS(NH2)2
Oxidant
O
+
H
N
H
N
H2O, 125℃
Cl
Cl
1a
2
3a
Yield (%) b
Entry
Oxidant (Equiv)
Concentration of H2O (M)
1
2
3
4
5
6
7
8
9
10
11
12
13
BPO (2)
BQ (2)
DTBP (2)
14
14
14
14
14
14
42
8
58
0
<5
20
69
55
TBHP (2)
K2S2O8 (2)
(NH4)2S2O8 (2)
K2S2O8 (2)
K2S2O8 (2)
K2S2O8 (2)
K2S2O8 (3)
K2S2O8 (1.8)
K2S2O8 (2)
K2S2O8 (2)
0 c
65 d
0 e
68
0
14
14
14
14
61
54 f
80 g
a
b
c
Condition: 1a (0.25 mmol),
2
(9.6 M), thiourea (0.5 mmol), oxidant, H2O, 125 ◦C, 24 h. Isolated yield. 3.4 M
d
e
f
of DMF were used. 11 M of DMF were used. 13 M of DMF were used. 20 mol% of Cu(OAc)2 were added.
g
5 equiv. of pyridine (Py) were added.
After establishing the optimized conditions, this procedure was applied to access a variety of aryl
thioamide derivatives. Several different aryl aldehydes could undergo this transformation smoothly in
a mild condition to give the desired products 3a–r (Scheme 1). The results indicated that many popular
functional groups were well tolerated, such as methyl, methoxyl, chloro, bromo, fluoro, trifluoromethyl,
and tert-butyl. Furthermore, the substrate bearing a sensitive hydroxy group, which was generally
protected in the presence of an oxidant could be also tolerated in this transformation, and afforded
the desired product 3o in 83% yield. A substituted amino was suitable as well, and gave 88% yield of
3p. The substituents on aromatic aldehydes had a certain influence on this transformation. When the
substituents were strong electron-withdrawing groups, either lower yield of desired products, or no
desired products were obtained (3j and 3r). The desired product 3m was not afforded possibly due to
the steric hindrance. Moreover, our experiments demonstrated that 2-naphthaldehyde was a suitable
substrate for this transformation, and gave the desired product 3q a good yield.
To further expand the substrate scope, some selected heterocyclic aldehydes and an aliphatic
aldehyde were examined under the optimal condition (Scheme 2). Generally, five or six members
heterocyclic derivatives were suitable for this transformation, such as furan-2-carbaldehyde,
thiophene-2-carbaldehyde, and nicotinaldehyde, giving the corresponding thioamide products 3s, 3t,
and 3u 54%, 74%, and 37% yields, respectively. In addition, aliphatic aldehyde did not accomplish this
transformation (3w).
We attempted to explore the different N-substituted formamides for this transformation
in additional solvent. No good results were provided when the normal solvents such as
N-methyl-2-pyrrolidone (NMP), 1,4-dioxane, 1,2-dichloroethane (DCE), toluene, chlorobenzene (PhCl),
dimethyl sulfoxide (DMSO), ethylene glycol, were used (see Supporting Information). Unexpectedly,

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N,N-dimethylacetamide (DMAC), which was seldom used as an amine source by the acyl C-N bond
activation [37], could replace DMF to give the same desired product in good yield. Subsequently,
the reactions of aryl aldehydes with thiourea in DMAC were examined under the similar reaction
condition (Table 2). The results demonstrated that various groups were tolerated well, such as methyl,
chloro, and bromo, and the good yields of the desired products were isolated.
S
O
R
O
K2S2O8 (2 equiv)
R
CS(NH2)2 (2 equiv)
N
+
H
H
N
H2O, Py, 125 ℃
1
2
3
S
S
N
S
N
N
Cl
3a 80%
3b 72%
3c 70%
S
S
S
N
N
N
Br
F
O
3d 68%
3f 80%
3e 75%
S
S
S
Cl
Br
N
N
N
N
3g 73%
3h 74%
3i 71%
S
S
S
t-Bu
N
N
F3C
t-Bu
t-Bu
3l 59%
3j 46%
3k 75%
S
S
S
N
N
N
HO
Ph
3m 0%
3n 78%
3o 83%
S
S
S
N
N
N
O2N
N
3p 88%
3q 81%
3r 0%
Scheme 1. The substrate scope of substituted benzaldehydes. Reaction condition: aryl aldehyde
1
(0.25 mmol), thiourea (0.5 mmol), H2O (14 M), K2S2O8 (0.5 mmol) and Py (5 equiv.) in DMF (1.5 mL) at
◦
125 C for 24 h in sealed tube. Isolated yields were given.

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O
S
K2S2O8(2 equiv)
CS(NH2)2 (2 equiv)
O
+
H
N
R
N
R
H
H2O, Py, 120 ℃
1
2
3
S
S
N
S
N
N
S
O
N
(3s 54%)
(3t 74%)
(3u 37%)
S
N
S
S
N
N
(3v 66%)
(3w 0%)
Scheme 2. The substrate scope of other aldehydes. Reaction condition: aldehyde
thiourea (0.5 mmol), H2O (14 M), K2S2O8 (0.5 mmol), and Py (5 equiv.) in DMF (1.5 mL) at 125 C for
24 h in sealed tube. Isolated yields were given.
1 (0.25 mmol),
◦
Table 2. The synthesis of aryl thioamides by DMAC a.
O
S
O
K2S2O8 (2 equiv)
CS(NH2)2 (2 equiv)
+
H
N
N
R
R
H2O, Py, 125 ℃
1
4
3
Yield (%) of 3 b
Entry
R
1
2
3
4
5
6
4-Cl
H
4-CH3
3-Br
3-CH3
4-Ph
63 (3a)
52 (3b)
55 (3c)
48 (3h)
51 (3i)
60 (3n)
a
Condition: 1 (0.25 mmol), 4 (1.5 mL), thiourea (0.5 mmol), K2S2O8 (0.5 mmol), H2O (0.5 mL), Py (1.25 mmol),
125 ◦C, 36 h. Isolated yield.
b
In addition, extremely small amounts of amide products were observed, along with the generation
of thioamide products under the optimal condition. So, two control experiments were conducted to
explain the tentative reaction mechanism (see Supporting Information). First, no thioamide product
was formed in the absence of thiourea, and only trace amounts of amide product were observed.
Second, when the N,N-dimethylbenzamide replacing the benzaldehyde was manipulated under the
standard condition, no desired thioamide was observed.
Based on our experimental results and previous reports [35], a proposed reaction mechanism
for this transformation is described in Scheme 3. First, an aryl aldehyde undergoes a nucleophilic
attack by a dimethylamine, which is from the hydrolysis of DMF, to generate iminium intermediate
A
. The iminium
A
then is directly attacked by thiourea to form the intermediate
B, together with
the release of urea [43,47,49]. Finally, intermediate B is oxidized by K2S2O8 to afford the desired
thioamide product.

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O
O
H2O
Ar
H
H
N
N
H
N
Ar
H
A
H2N
H2N
S
+
H2O
H2N
H2N
O
S
N
K2S2O8
Ar
N
Ar
S
B
2-
2SO4
Scheme 3. Plausible reaction pathway.
3. Materials and Methods
Unless otherwise stated, all reagents and solvents were purchased from commercial suppliers,
and were used without further purification. Reactions were monitored by thin layer chromatography
(TLC) analysis on silica gel 60 F254, and visualization was accomplished by irradiation with short
1
wave UV light at 254 nm. H-NMR and 13C-NMR spectra were recorded on a Bruker Avance 400 or a
500 MHz spectrometer (Bruker, Karlsruhe, Germany), with tetramethylsilane (TMS) as the internal
standard. The coupling constants J are given in Hz. Mass spectra were measured with the Thermo
Scientific LTQ Orbitrap XL MS spectrometer (Thermo Fisher Scientific, Waltham, MA, USA) or GC-MS
QP2010 (Comfort Technology Limited, Kowloon, Hong Kong).
A mixture of aldehyde
1
(0.25 mmol), thiourea (0.5 mmol), K2S2O8 (0.5 mmol), and Py (1.25 mmol)
◦
in 2.0 mL DMF/H2O (v/v = 3:1) was stirred in a sealed tube under air at 125 C for 24 h. After
the reaction was achieved, the crude mixture was purified by column chromatography (silica gel,
EtOAc/petroleum ether) to afford the desired product 3.
4-Chloro-N,N-dimethylbenzothioamide (3a) [35]. 1H-NMR (CDCl3, 400 MHz):
δ
δ
(ppm): 7.36–7.33 (m,
(ppm): 199.91, 141.66,
2H), 7.29–7.26 (m, 2H), 3.61 (s, 3H), 3.19 (s, 3H); 13C-NMR (CDCl3, 100 MHz):
134.60, 128.58, 127.29, 44.18, 43.32; HRMS (ESI) m/z calculated (calcd.) for C9H11ClNS+ (M + H)+
200.02952, found 200.02971.
1
N,N-Dimethylbenzothioamide (3b) [35]. H-NMR (CDCl3, 400 MHz):
δ (ppm): 7.37–7.30 (m, 5H), 3.62 (s,
3H), 3.19 (s, 3H); 13C-NMR (CDCl3, 100 MHz):
43.53; GC-MS (EI) m/z (%) 165.10 (70, M+), 164.05 (98), 121.05 (100), 77.00 (46).
δ (ppm): 201.65, 143.69, 128.89, 128.64, 126.04, 44.44,
1
4-Methyl-N,N-dimethylbenzothioamide 3c
[
35]. H-NMR (CDCl3, 400 MHz):
δ
(ppm): 7.23 (d, J = 8 Hz,
(ppm):
2H), 7.16 (d, J = 8 Hz, 2H), 3.61 (s, 3H), 3.20 (s, 3H), 2.36 (s, 3H); 13C-NMR (CDCl3, 100 MHz):
δ
201.55, 140.59, 138.68, 128.89, 125.89, 44.22, 43.35, 21.27; GC-MS (EI) m/z (%) 179.05 (80, M+). 178.05
(100), 145.10 (50), 135.05 (98), 91.05 (45).
4-Methoxy-N,N-dimethylbenzothioamide (3d) [35]. 1H-NMR (CDCl3, 400 MHz):
J = 12 Hz, 2H), 6.87 (d, J = 12 Hz, 2H), 3.82 (s, 3H), 3.59 (s, 3H), 3.22 (s, 3H); 13C-NMR (CDCl3,
δ (ppm): 7.31 (d,
100 MHz):
δ (ppm): 201.31, 160.02, 135.82, 127.90, 113.51, 55.40, 44.37, 43.59; GC-MS (EI) m/z (%) 195.05
(M+, 84), 194.05 (93), 151.05 (100).
4-Bromo-N,N-dimethylbenzothioamide (3e) [35]. 1H-NMR (CDCl3, 400 MHz):
δ
δ
(ppm): 7.53–7.50 (m,
(ppm): 199.79, 142.12,
2H), 7.23–7.19 (m, 2H), 3.60 (s, 3H), 3.19 (s, 3H); 13C-NMR (CDCl3, 100 MHz):

Molecules 2018, 23, 2225
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131.53, 127.52, 122.73, 44.20, 44.30; GC-MS (EI) m/z (%) 242.95 (63, M+), 243.90 (100), 242.95 (63), 241.90
(92), 200.85 (47), 198.90 (48), 120.00 (54).
1
4-Fluoro-N,N-dimethylbenzothioamide (3f) [35]. H-NMR (CDCl3, 400 MHz):
δ
(ppm): 7.32–7.28 (m, 2 H),
7.05–6.99 (m, 2H), 3.58 (s, 3H), 3.16 (s, 3H); 13C-NMR (CDCl3, 100 MHz):
δ (ppm): 200.19, 162.66 (d,
J = 248 Hz), 139.44 (d, J = 4 Hz), 128.00 (d, J = 9 Hz), 115.33 (d, J = 22 Hz), 44.24, 43.45.
1
3-Chloro-N,N-dimethylbenzothioamide (3g) [35]. H-NMR (CDCl3, 400 MHz):
δ
δ
(ppm): 7.33–7.25 (m,
(ppm): 199.11, 144.78,
3H), 7.20–7.18 (m, 1H), 3.60 (s, 3H), 3.19 (s, 3H); 13C-NMR (CDCl3, 100 MHz):
134.29, 129.76, 128.63, 125.89, 123.83, 44.18, 43.18; GC-MS (EI) m/z (%) 200.00 (43), 199.0 (69, M+). 198.00
(100), 165.00 (32), 157.00 (26), 155.00 (74), 111.00 (24).
1
3-Bromo-N,N-dimethylbenzothioamide (3h) [35]. H-NMR (CDCl3, 400 MHz):
δ
δ
(ppm): 7.50–7.46 (m,
(ppm): 199.01, 144.98,
2H), 7.27–7.22 (m, 2H), 3.60 (s, 3H), 3.19 (s, 3H); 13C-NMR (CDCl3, 100 MHz):
131.56, 129.99, 128.68, 124.30, 122.38, 44.19, 43.19; GC-MS (EI) m/z (%) 244.95 (64), 243.95 (100), 242.95
(65, M+), 241.95 (95), 200.90 (43), 198.90 (43), 120.00 (51).
1
3-Methyl-N,N-dimethylbenzothioamide (3i) [35]. H-NMR (CDCl3, 400 MHz):
δ (ppm): 7.34–7.24 (m, 1H),
7.17 (d, J = 6.0 Hz, 2H), 7.11 (d, J = 7.5 Hz, 1H), 3.64 (s, 3H), 3.21 (s, 3H), 2.40 (s, 3H); 13C-NMR (CDCl3,
100 MHz): δ (ppm): 201.2, 143.2, 138.0, 129.1, 128.0, 126.1, 122.4, 44.0, 43.0, 21.2.
1
4-(Trifluoromethyl)-N,N-dimethylbenzothioamide (3j) [35]. H-NMR (CDCl3, 400 MHz):
δ
(ppm): 7.64 (d,
(ppm):
J = 8 Hz, 2H), 7.43 (d, J = 12 Hz, 2H), 3.63 (s, 3H), 3.18 (s, 3H); 13C-NMR (CDCl3, 100 MHz):
δ
199.30, 146.56,130.46 (q, J = 32.6 Hz),126.02, 125.56 (q, J = 3.8 Hz), 123.73 (q, J = 270.5 Hz), 44.07, 43.09;
GC-MS (EI) m/z (%) 233.00 (M+, 71), 232.00 (100), 199.05 (37), 189.00 (64).
1
4-tert-Butyl-N,N-dimethylbenzothioamide (3k) [37]. H-NMR (CDCl3, 400 MHz):
δ
(ppm): 7.38–7.35 (m,
(ppm):
2H), 7.28–7.24 (m, 2H), 3.61 (s, 3H), 3.21 (s, 3H), 1.32 (s, 9H); 13C-NMR (CDCl3, 100 MHz):
201.64, 151.78, 140.49, 125.67, 125.22, 44.27, 43.34, 34.70, 31.23. GC-MS (EI) m/z (%) 221.10 (70, M+),
δ
220.05 (70), 147.05 (24).
1
3,5-di-tert-Butyl-N,N-dimethylbenzothioamide (3l). H-NMR (CDCl3, 400 MHz):
δ
(ppm): 7.39 (t, J = 4 Hz,
(ppm):
1H), 7.15 (d, J = 4 Hz, 2H), 3.63 (s, 3H), 3.16 (s, 3H), 1.33 (s, 18H); 13C-NMR (CDCl3, 100 MHz):
δ
202.78, 150.70, 142.63, 122.75, 120.13, 44.21, 43.32, 34.92, 31.40. GC-MS (EI) m/z (%) 277.15 (86, M+),
276.15 (100), 220.05 (80). HRMS (ESI) m/z calcd. for C17H28NS+ (M + H)+ 278.19370, found 278.19366.
1
4-Benzyl-N,N-dimethylbenzothioamide (3n) [38]. H-NMR (CDCl3, 400 MHz):
δ
(ppm): 7.59–7.56 (m, 4H),
(ppm):
7.47–7.43 (m, 2H), 7.41–7.34 (m, 3H),3.62 (s, 3H), 3.23 (s, 3H); 13C-NMR (CDCl3, 100 MHz):
δ
201.04, 142.17, 141.56, 140.33, 128.89, 127.69, 127.10, 127.09, 126.39, 44.28, 43.32. GC-MS (EI) m/z (%)
241.05 (78, M+), 240.05 (100), 197.00 (58), 181.05 (66), 152.05 (74).
1
4-Hydroxy-N,N-dimethylbenzothioamide (3o) [35]. H-NMR (CDCl3, 400 MHz):
δ
(ppm): 7.21–7.15 (m,
(ppm):
2H), 6.75–6.70 (m, 2H), 5.89 (br s, 1H), 3.59 (s, 3H), 3.21 (s, 3H); 13C-NMR (CDCl3, 100 MHz):
200.97, 156. 03, 136. 00, 127.45, 114.85, 43.97, 43.20; GC-MS (EI) m/z (%) 181.05 (M+, 74), 180.05 (79),
δ
147.10 (31), 137.05 (100).
1
4-(Dimethylamino)-N,N-dimethylbenzothioamide (3p) [50]. H-NMR (CDCl3, 400 MHz):
δ (ppm): 7.32 (d,
J = 8 Hz, 2H), 7.63 (d, J = 8 Hz, 2H), 3.59 (s, 3H), 3.28 (s, 3H), 2.99 (s, 6H); 13C-NMR (CDCl3, 100 MHz):
(ppm): 201.64, 150.54, 130.30, 127.98, 110.56, 44.19, 43.40, 39.86; GC-MS (EI) m/z (%) 208.05 (M+, 74),
207.05 (46), 164.05 (100), 148.10 (57).
δ
1
N,N-Dimethylnaphthalene-2-carbothioamide (3q) [35]. H-NMR (CDCl3, 400 MHz):
δ (ppm): 7.82–7.81
(m, 3H), 7.77 (s, 1H), 7.53–7.46 (m, 2H), 7.44–7.41(m, 1H), 3.64 (s, 3H), 3.19 (s, 3H); 13C-NMR (CDCl3,
100 MHz): δ (ppm): 201.21, 140.60, 128.38, 128.20, 127.75, 126.78, 126.74, 124.73, 123.94, 44.27, 43.31.
1
N,N-Dimethylfuran-2-carbothioamide (3s) [51]. H-NMR (CDCl3, 400 MHz):
δ (ppm): 7.47 (d, J = 4 Hz,
1H), 7.09 (d, J = 4 Hz, 1H), 6.46 (d, J = 4 Hz, 1H),3.56 (s, 3H), 3.45 (s, 3H); 13C-NMR (CDCl3, 100 MHz):

Molecules 2018, 23, 2225
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δ
(ppm): 158.31, 151.98, 142.80, 117.27, 111.49, 44.01, 43.80. GC-MS (EI) m/z (%) 155.05 (100, M+), 111.00
(70), 73.95 (27).
1
N,N-Dimethylthiophene-2-carbothioamide (3t) [35]. H-NMR (CDCl3, 400 MHz):
δ
(ppm): 7.41 (dd, J = 4.8,
0.8 Hz, 1H), 7.12 (dd, J = 4.0, 1.2 Hz, 1H), 6.99–6.97 (m, 1H), 3.58 (s, 3H), 3.45 (s, 3H); 13C-NMR (CDCl3,
100 MHz):
127.00 (100).
δ
(ppm):191.63, 145.23, 129.30, 126.50, 126.45, 44.65. GC-MS (EI) m/z (%) 171.00 (77, M+),
N,N-Dimethylpyridine-3-carbothioamide (3u) [52]. 1H-NMR (CDCl3, 400 MHz):
(m, 2H),7.69 (dt, J = 8.0, 2.0 Hz, 1H), 7.33–7.30 (m, 1H), 3.63 (s, 3H), 3.23 (s, 3H); 13C-NMR (CDCl3,
δ (ppm): 8.59–8.57
100 MHz):
δ (ppm):197.59, 149.63, 146.19, 133.70, 123.18, 44.25, 43.37. GC-MS (EI) m/z (%) 166.05 (85,
M+), 165.05 (88), 149.10 (35), 122.00 (100), 106.05 (38), 78.00 (62).
1
N,N-Dimethyl-5-(quinolin-2-yl) thiophene-2-carbothioamide (3v). H-NMR (CDCl3, 400 MHz):
δ (ppm):
8.15 (d, J = 8 Hz, 1H), 8.08 (d, J = 8 Hz, 1H), 7.78 (t, J = 8 Hz, 2H), 7.74–7.69 (m, 1H), 7.59 (d, J = 4 Hz,
1H), 7.54–7.49 (m, 1H), 7.19 (d, J = 4 Hz, 1H), 3.56 (d, J = 40 Hz, 6H); 13C-NMR (CDCl3, 100 MHz):
δ
(ppm): 191.56, 151.54, 148.18, 148.08, 146.86, 136.77, 130.01, 129.37, 127.82, 127.53, 127.40, 126.49,
124.94, 117.42, 44.54. HRMS (ESI) m/z calculated (calcd.) for C16H15N2S2 (M + H)+ 299.06712, found
+
299.06706.
4. Conclusions
In conclusion, we have demonstrated an efficient and transitional-metal-free method for the
synthesis of aryl thioamides derived from aryl aldehydes using thiourea as a sulfur source in the
presence of potassium persulfate, in DMF or DMAC. This strategy has the advantages of good
functional-group tolerance and gives moderate to good yields of desired products. Further studies on
synthetic applications are currently under way.
Supplementary Materials: The following are available online at http://www.mdpi.com/1420-3049/23/9/2225/
s1, Table S1: Screening of various solvents, Figure S1: Three control experiments for mechanism study, 1H-NMR,
13C-NMR, and MS spectrum of 3a–w.
Author Contributions: X.Q. conceived and designed the experiments; Y.B. performed the experiments; Y.C.
contributed reagents/materials; J.L. and L.L. wrote the paper.
Funding: This work was supported by Scientific and Technological Innovation Programs of Higher Education
Institutions in Shanxi (NO. 2015176), the Doctoral Scientific Research Foundation of Jinzhong University (NO.
bsjj2015213 and NO. bsjj2015214) and the Construction plan of the ‘1331 engineering’ photoelectric material
innovation team of Jinzhong University.
Conflicts of Interest: The authors declare no conflict of interest.
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Sample Availability: Sample Availability: Not available.
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