Base-Controlled Three Component Reactions of Amines, Elemental Sulfur, and Styrenes: Synthesis of Thioamides under Metal-Free Conditions

Article abstract of DOI:10.1021/acs.joc.8b01721

Three component reactions of olefins, amines, and sulfur were studied. Thioamidation of styrenes is base-controlled, and 2-phenylethanethioamides and benzothioamides were obtained selectively in the presence of two different bases. This protocol offers a simple and efficient procedure for the synthesis of thioamides.

Full text of DOI:10.1021/acs.joc.8b01721

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Article
Base-Controlled Three Component Reactions of Amines, Elemental Sulfur,
and Styrenes: Synthesis of Thioamides under Metal-Free Conditions.
Pingshun Zhang, Wanzhi Chen, Miaochang Liu, and Huayue Wu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01721 • Publication Date (Web): 05 Nov 2018
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Base-Controlled Three Component Reactions of
Amines, Elemental Sulfur, and Styrenes: Synthesis
of Thioamides under Metal-Free Conditions
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Pingshun Zhang,† Wanzhi Chen,*† Miaochang Liu, ‡ and Huayue Wu‡*
† Department of Chemistry, Zhejiang University, Yuquan Campus, Hangzhou 310007, China
‡ College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou, 325027,
China.
Received 00th June 20xx,
Accepted 00th June 20xx
DOI: 10.1039/x0xx00000x
KEYWORDS: Base-Controlled, Metal-Free Conditions, Thioamides, Styrenes, Sulfur
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R2
R2
NH2
6
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8
9
KF, DMSO
N2, 100 oC
K3PO4, DMSO
N2, 100 oC
S
S
S
HN
HN
R1
R1
R2
R1
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R1 = CH3, C2H5, iPr, tBu, CF3,
OH, OCH3, OPh, NO2, halides;
R2 = Cl, F, CH3, tBu, OCH3.
ABSTRACT: Three component reactions of olefins, amines, and sulfur were studied.
Thioamidation of styrenes is base-controlled, and 2-phenylethanethioamides and
benzothioamides were obtained selectively in the presence of two different bases. This
protocol offers a simple and efficient procedure for the synthesis of thioamides.
Introduction
Thioamides constitute an important class of biologically active and pharmaceutical
compounds.1 Thioamides also serve as valuable synthons2 for the synthesis of various sulfur-
and nitrogen-containing heterocyclic compounds such as thioazoles,3 thioazoline,4 and
thiophens.5 Thioamides are small and can conceivably be scanned through a protein backbone
with minimal perturbation to native structure, and thus was used to design “turn-on”
fluorescent protease substrates.6 Fluorenscence sensors based on thioamides have also been
reported for the detection of inorganic ions.7 Thioamides are typically prepared via three
routes (1) reaction of amides with P2S5 or related Lawesson’s reagent;8 (2) Friedel−Crafts
thioacylation of arenes with isothiocyanates;9 (3) Willgerodt-Kindler reaction of aryl alkyl
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ketones, elemental sulfur, and secondary amines.10 Other methods to prepare thioamides were
also developed in recent years. Examples include three-component reactions of alkyl and aryl
aldehydes, sodium sulfide, and N-substituted formamides,11 and aerobic oxidative coupling of
thiols and amines.12 Taking account of environment benign, stable and nontoxic elemental
sulfur is the best choice of sulfurating reagent. It has been reported that three-component
reaction involving elemental sulfur and two different aliphatic amines has been successfully
used for the synthesis of thioamides at 130 oC.13 Three-component reaction between alkynes,
elemental sulfur, and alkylamines could also gave thioamides, which is the atom-, step-, and
redox-economical reaction.14 It has been briefly reported that Willgerodt-Kindler reaction of
styrene with morpholine afforded 2-phenylethanethioamide in moderate yields at 160- 175
oC15a,b or under microwave condition.15c,d In addition, thioamides could be easily transformed
into benzothiazoles using stoichiometric amount of oxidants or under catalytic conditions.16
We found that bases could significantly improve the efficiency and selectivity. In this paper
we report the three component reactions of anilines, olefins, and sulfur, which were controlled
by the bases. Two kinds of thioamides were selectively obtained in high yields through the
choice of bases.
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Results and discussion
Initially we investigated the reaction of 4-methoxyaniline 1a, 4-methylstyrene 2a, and
elemental sulfur 3a in the presence of a base to optimize the reaction conditions, and the results
were listed in Table 1. Compound 1a reacted readily and cleanly with 2a and 6 equiv. of sulfur
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to afford the unexpected product N-(4-methoxyphenyl)-4-methylbenzothioamide 4aa in an
almost quantitative yield at 100 oC in the presence of 3 equiv. of KF (Table 1, entry 1). When
the amount of KF was decreased to 2 equiv., the yield of 4aa was not affected (Table 1, entry
2). When the 1a:2a:3a ratio was lowered to 1: 1.5: 3 from 1:2:6, the yield of 4aa was reduced to
75% (Table 1, entry 3). Thus we decided to perform further studies at the 1a:2a:3a ratio of
1:2:4, and in such case 4aa was obtained in 95% yield (Table 1, entry 4). When KF was replaced
by KOAc, the three-component reaction gave a low conversion, and 4aa was obtained in only
45% yield. The use of K2CO3 as the base resulted in a mixture of 4aa and 5a (Table 1, entries 5
and 6). In the case of the strong base t-BuOK, only trace amount of 5a was obtained (Table 1,
entries 7). Organic bases such as Et3N and pyridine did not improve the reaction efficiency
(Table 1, entries 8 and 9). Without a base, we obtained a mixture of 4aa and 5a in 10% and
48% yields, respectively (Table 1, entry 10). Surprisingly, N-(4-methoxyphenyl)-2-(p-
tolyl)ethanethioamide 5a was the only product in the presence of 2 equiv. of K3PO4. In ethanol
and acetone, compound 5a was obtained in low yields. probably the cleavage of double bond
was inhibited by ethanol and acetone (Table 1, entries 12-15). Further screening of solvents
showed that DMSO was the optimal solvent. Finally, under an atmosphere of air or O2 the
reactions gave complex mixtues, and both the yields of 4aa and 5a were significantly lowered
(Table 1, entries 20 and 22). Probably the oxidation of styrene, aniline and sulfur would be
harmful to the reaction at 100oC under an atmosphere of O2.
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Table 1. Optimization of thioamidation of olefinsa
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H
N
NH2
6
7
8
9
S
4aa
O
H
base
S
N
N2, 100 oC
S
O
O
1a
3a
2a
5a
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Entry
1a: 2a:
3a
1: 2: 6
base ( equiv.) solvent
yields of
4aa/5a (%)
96/-
1
2
KF (3)
KF (2)
DMSO
DMSO
1: 2: 6
96/-
3
4
1: 1.5: 3
1: 2: 4
KF (2)
KF (2)
DMSO
DMSO
75/-
95/-
5
1: 2: 4
KOAc (2)
DMSO
45/-
6
1: 2: 4
1: 2: 4
1: 2: 4
1: 2: 4
1: 2: 4
1: 2: 4
1: 2: 4
1: 2: 4
K2CO3 (2)
t-BuOK (2)
Et3N (2)
Pyridine (2)
-
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
acetone
H2O
<5/16
-/<5
52/-
7
8
9
-/39
10
11
12
13
10/48
-/79
K3PO4 (2)
KF (2)
<5/21
-/-
KF (2)
14
1: 2: 4
K3PO4 (2)
ethanol
-/56
15
16b
17c
1: 2: 4
KF (2)
ethanol
-/45
1: 2: 4
1: 2: 4
KF (2)
KF (2)
DMSO
DMSO
85/-
10/16
18b
19d
20e
21d
22e
a
1: 2: 4
1: 2: 4
1: 2: 4
1: 2: 4
1: 2: 4
K3PO4 (2)
KF (2)
DMSO
DMSO
DMSO
DMSO
DMSO
-/39
28/-
<5/-
-/31
-/<5
KF (2)
K3PO4 (2)
K3PO4 (2)
Reaction conditions: amine 1a , alkene 2a, S8, and
base in solvent (1.5 mL) at 100 °C under N2 for 24 h. b
80 oC. c 60 oC. d air. e O2.
To examine the scope of the three-component reaction for the preparation of
benzothioamides 4, different amines and olefins were subjected to the reaction under the
optimized conditions, and the results were summarized in Table 2. Both primary and
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secondary amines with styrenes were proven to be appropriate substrates, and afforded
corresponding thioamides in good to excellent yields. para-Substitutents of anilines such as
alkyl, methoxy, hydroxyl, trifluoromethyl, and halogens were shown to be highly compatible
with the reaction conditions, and the corresponding thioamides 4aa-4aj were isolated in more
than 90% yields. Anilines bearing alkyl, alkoxyl, and chloro groups at meta and ortho positions
also gave thioamides 4ak-4ao in excellent yields. The reaction was not much sterically sensitive
as indicated by the isolation of ortho chloro-, ethyl-, and phenoxy-substituted thioamides
4am-4ao in more than 90% yields. Even the sterically bulky 2,6-diisopropylaniline could be
transformed to 4ap in 85% yield. However, 4- and 3-nitroaniline gave quite low yields of
thioamides 4ah and 4al. It seems that the low yields are not resulted from electronic deficiency,
since anilines bearing one or two CF3 also gave high yields of 4aj and 4aq. The low yields is
probably due to the partial oxidation of olefin and aniline by the nitro group. Under the same
conditions, N-methylaniline did not afford the required product. Aliphatic amines showed
much lower reactivities than aromatic amines. Reaction of n-butylamine with 4-
methylstyrene did not afford the expected N-butyl-4- methylbenzothioamide 4as, instead, N-
butyl-2-(p-tolyl)ethanethioamide 5j was obtained in 64% yield. Secondary acyclic amine
Et2NH and 8-aminoquinoline were totally inactive, and the starting materials could be
recovered. Reaction of benzylamine and p-phenylenediamine gave complicated mixtures.
However, the reaction of morpholine and 4-methylstyrene could afford 4au in moderate yield,
whereas piperidine gave a mixture of 4av and 5m in 37 and 59% yields, respectively.
Substituted styrenes containing a chloro, fluoro, and tBu could also react smoothly with 4-
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methoxyaniline giving the corresponding products 4ba, 4bb, and 4bc in high yields.
Unfortunately, aliphatic olefins such as oct-1-ene, cyclohexene, allylbenzene, and norbornene
are not compatible under the optimized conditions. We also failed to observe the formation of
thioamides in the reactions of DMF and styrene in DMSO, although amides are known to be
an efficient partner for the synthesis of thioamides.14c,17 However, we obtained a mixture of
4ax and 5p in 22% and 50% yields, respectively, when the reaction was performed in DMF.
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Table 2. Synthesis of thioamides 4
NH2
R2
H
N
KF, DMSO
R1
N2, 100 oC, 24 h
S
S
R1
R2NH
R
N
R2
R2
R
S
2
3
4
1
R1
H
H
H
N
N
N
S
S
S
R1
R1
R
1 = Cl, 96%
1 = CH2CH3, 97%
1 = OPh, 92%
1
1
4am
4an
4ao
R
1 = CH3, 96%
1 = NO2, 46%
4aa
4ab
4ac
4ad
4ae
4af
4ag
4ah
R = OCH3, 95%
R = Cl, 92%
4ak
4al
1
1
R
R
R = CH3, 95%
R = Br, 95%
R
1
R = H, 95%
R
1 = NO2, 54%
1
4ai
4aj
R = tBu 94%
R
1 = OH, 93%
1 = CF3, 91%
1
R = F, 98%
R
H
N
iPr
F3C
H
N
N
S
S
S
iPr
4ar,
CF3
0%
4ap,
85%
4aq,
95%
S
S
S
n-C4H9
N
N
N
O
H
4au,
60%
4at,
0%
4as,
0%
NH
S
O
S
R2
N
S
N
4ba
4bb
4bc
R
2 = Cl, 78%
2 = F, 83%
2 = tBu, 98%
4ax,
4av,
37%
22%
R
R
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Reaction conditions: amine 1 (0.3 mmol), alkene 2 (0.6 mmol), S8 (1.2 mmol), and KF (0.6
mmol) in DMSO (1.5 mL) at 100 oC under N2 for 24 h.
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We also evaluated the substrate scope of the three component reaction for the synthesis of
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o
thioamides 5. As shown in Table 3, when K3PO4 was used as the base at 100 C, substituted
anilines bearing a methyl, methoxyl, chloro, and tBu could be transformed into their
corresponding thioamides 5a-5d in good yields. meta-Substituted anilines having a methyl and
chloro also reacted with 4-methylstyrene to give 5e and 5f in moderate yields. Unlike KF,
K3PO4-mediated thioamidation reaction is quite sterically sensitive, both 2-ethylaniline and
2-phenoxylaniline were not reactive, and the expected thioamides 5g and 5h were not
detected. More steric 2,6- diisopropylaniline was also inactive. Similar to KF-mediated
reaction, the reaction of n-butylamine with 4-methylstyrene and sulfur resulted in a low yield
of 5j, whereas the corresponding reaction of diethylamine did not occur. Interestingly, cyclic
secondary amines showed their activities. In the case of piperidine a mixture of 4av and 5m
were isolated in 14% and 52% yields, respectively. However, the reaction of morpholine, 4-
methylstyrene, and sulfur afforded 5n as the only product in 62% yield. Similar to KF-
mediated reaction, two N,N-dimethyl thioamides 4ax and 5p were obtained in 12% and 54%
yields, respectively, when DMF was used as the solvent. Styrene and substituted styrenes
having a methoxy and tertiary butyl also reacted with 4-methoxyaniline to give corresponding
thioamides in good yields. However, styrenes having a para fluoro and chloro substituents did
not afford corresponding thioamides. The reason is not clearly understood at present. In
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addition, 2-vinylpyridine also reacted with 4-methoxyaniline to afford 5v in poor yield. In
contrast, the same reaction of 2-vinylpyridine did not occur in the presence of KF. Again,
aliphatic olefins such as oct-1-ene, cyclohexene, allylbenzene, and norbornene showed no
activities under the present conditions. We were able to obtain unsubstituted thioamides 5w
and 5x in 30% and 32% yields, when NH4HCO3 was employed as the NH3 source for
convenience.
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Table 3. Synthesis of thioamides 5
H
NH2
N
R1
S
R2
K3PO4, DMSO
R
N
S
R1
N2, 100 oC, 24 h
R
R2
S
R2NH
R2
5
2
3
1
H
R4
H
N
N
H
N
S
S
R1
S
R1
R
1 = OCH3, 79%
1 = CH3, 77%
1 = Cl, 75%
1 = tBu, 73%
5a
5b
5c
5d
5g
R
R
1 = CH2CH3, 0%
1 = OPh, 0%
R
1 = CH3, 58%
1 = Cl, 40%
5e
R
5h
5f
R
R
R
iPr
H
N
S
N
S
N
H
5j,
iPr
5i,
S
40%
5k,
0%
0%
S
S
S
N
N
N
O
5p,
54%
5n,
62%
5m,
52%
H
N
N
H
N
S
O
S
R2
5v,
34%
O
R2
2 = tBu, 75%
2 = OCH3, 92%
5q
5r
R
S
R
2 = H, 70%
2 = F, 0%
H2N
5s
5t
R
R
5w
5x
R
2 = CH3, 30%
2 = tBu, 32%
2 = Cl, 0%
5u
R
R
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Reaction conditions: amine 1 (0.3 mmol), alkene 2 (0.6 mmol), S8 (1.2 mmol), and K3PO4 (0.6
mmol) in DMSO (1.5 mL) at 100 oC under N2 for 24 h.
7
8
9
NH2
KF
K3PO4
4aa
4aa
5a
5a
93% +
10% +
-%
DMSO
N2, 100 o
S
C
62%
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O
Scheme 1. Thioamidation of 4-tolylacetylene
Alkyne could also be transformed to the corresponding thioamides, examples are shown
in Scheme 1. Under the optimized conditions, 4aa and 5a were afforded in 93 % and 62%
yields, respectively.
O
NH2
KF, DMSO
N2, 100 o
(1)
(2)
4aa
, < 10%
S
S
S
C
OMe
NH2
O
K3PO4, DMSO
N2, 100 o
4aa
, < 10%
C
OMe
NH2
COOH
KF or K3PO4
N2, 100 oC, DMSO
no reaction,
(3)
(4)
OMe
KF or K3PO4
N2, 100 oC, DMSO
no reaction
Et3N
S
TEMPO
(5)
(6)
4aa
5a
5%
:
81% +
KF, DMSO
NH2
BHT
N2, 100 o
C
4aa
, 84%
S
TEMPO
BHT
4aa
5a
13%
(7)
(8)
:
59% +
K3PO4, DMSO
N2, 100 o
O
C
5a
, 70%
Scheme 2. Control experiments
To gain an insight on the possible mechanism of the thioamidation of olefins, a few control
experiments were performed. Reactions of 4-methoxyaniline, 4-methylbenzaldehyde, and
sulfur were performed using either KF or K3PO4 as the bases, and the results showed that 4aa
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was obtained in less than 10% yields (Scheme 2, Eqs. 1 and 2). When 4-methylbenzaldehyde
was replaced by 4-methylbenzoic acid, no thioamide was observed (Eq. 3). These experiments
illustrated that the thioamidation of olefins might not proceed via benzaldehyde18 or benzoic
acid from oxidation of styrene. In addition, in the reaction of 4-methylstyrene, Et3N, and sulfur
at 100 oC, 4-methylstyrene was not consumed (Eq. 4). In the presence of 2 equiv. of BHT, KF-
mediated reaction of 4-methoxyaniline, 4-methylstyrene, and sulfur afforded 4aa in 84 %
yield, whereas the same reaction gave 5a in 70% yields in the presence of K3PO4. For
comparison, addition of 2 equiv. of TEMPO to the three-component reactions afforded
mixtures 4aa and 5a in 81%/5% and 59%/13% yields, respectively, when KF and K3PO4 were
used as the bases (Eqs 5-8). Obviously, the thioamidation reaction was not inhibited by the
radical scavenger. ESI-MS analysis of the yellow reaction mixture resulted from 4-
methoxyaniline and sulfur showed that several polysulfides were formed (Figure S1). Heating
the mixture of 4-methoxyaniline, sulfur, KF or K3PO4 in DMSO at 100 oC for 5-20 minutes
gave a red solution. Direct ESI-MS analysis of the filtrate showed a peak at ca. 320 due to 4-
MeOPhNHS5K, which was not observed in the absence of bases (Figures S2 andS4). The results
illustrated that 4-MeOPhNHS5- was selectively formed. The red mixture was added an excess
of 4-methylstyrene, and heated at 100 °C for another 15 minutes. ESI-MS spectrua of the deep
red filtrates showed peaks at ca. 523, 581, and 615 assigned to the intermediates C+H+ B+Na+,
and E+H+, respectively (Figures S3, S5 and Scheme 3). Thus based on the literature reports14a,19
and the experimental results, a plausible reaction mechanism was proposed. As shown in
Scheme 3, the reaction is probably initiated by the formation of RNHS5K from amine and
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sulfur.20 Subsequent oxidative coupling with styrene affords A. Nucleophilic addition of sulfur
generates polysulfides B and D in the presence of K3PO4 and KF respectively. Nucleophilic
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-
attack of D by a molecule of aniline under assistance of RNHS4 form E. Oxidative C-S coupling
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and further decomposition of F results in ring-opening and subsequent C-C cleavage, and
finally give 4. Nucleophilic addition of aniline towards A generates C. Elimination of a
-
molecule of RNHS4 yields 5. Reaction of 4-methoxyaniline, sulfur, and KF in EtOH or acetone
at 100 oC for 20 minutes gave a light yellow solution and a light brown solution, respectively.
The mixture was added an excess of 4-methylstyrene, and heated at 100 °C for another 15
minutes. ESI-MS spectra of the filtrates showed that the intermediates were similar to when
K3PO4 was acted as base in DMSO (Figures S6 and S7 ). However, we have not been able to
understand the role of bases.
-
RNHSn
S
S
S
S
S
S
S
S8
S
S
RHN
S5NHR
Ar
RNH2
RHN
Ar
S5NHR
RNH2 + S8
base
Ar
S5NHR
D
E
F
S8
KF
S
Ar
-
RNHS5
NHR
Ar
S8
A
S5NHR
K3PO4
Ar
S8
4
RNH2
Ar
S
NHR
S
RNH2
S
S
NHR
S5NHR
Ar
S
5
S
+
S5NHR
-
PhNHS4
Ar
C
B
Scheme 3. Plausible mechanism
CONCLUSION
In conclusion, we have described the three component reactions of olefins, amines, and
sulfur, which selectively afforded two kinds of thioamides through the choice of bases. The
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starting materials are easily available and cheap, and the reactions were carried out under
catalyst-free conditions. It offers an efficient synthetic protocol for thioamides. At present, we
have not been able to understand how the bases control the chemoselectivity of thioamides.
Further work is required to clarify the detailed mechanism.
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EXPERIMENTAL SECTION
All chemicals were of reagent grade quality obtained from commercial sources and used as
received.
General Procedure for Synthesis of 4. A 25 mL of Schlenk tube was charged with 4-
methoxyaniline 1a (0.3 mmol), 4-methylstyrene 2a (0.6 mmol), S8 (1.2 mmol), KF (0.6 mmol)
and DMSO (1.5 mL). The mixture was allowed to stir at 100 °C under N2 for 24 h, then the
mixture was cooled to room temperature. Water (15 mL) was added, and the mixture was
extracted with ethyl acetate (15 mL x 3). The organic phase was collected, washed with brine,
and dried over Na2SO4, then filtered and concentrated. The crude residue was purified by flash
column chromatography on silica gel using petroleum ether/ethyl acetate (PE: EA = 50:1-3:1)
as eluent to afford the desired product 4.
General Procedure for Synthesis of 5. A 25 mL of Schlenk tube was charged with 4-
methoxyaniline 1a (0.3 mmol), 4-methylstyrene 2a (0.6 mmol), S8 (1.2 mmol), K3PO4 (0.6
mmol) and DMSO (1.5 mL). The resulting suspension was allowed to stir at 100 °C under N2
for 24 h. The mixture was then cooled to room temperature. Water (15 mL) was added, and it
was extracted with ethyl acetate (15 mL x 3). The organic phase was collected and washed
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with brine, dried over Na2SO4, then filtered and concentrated. The crude residue was purified
by flash column chromatography on silica gel using petroleum ether/ethyl acetate (PE: EA =
50:1-3:1) as eluent to afford the desired product 5.
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N-(4-methoxyphenyl)-4-methylbenzothioamide (4aa)
Light yellow solid. Mp: 144-145 oC. Yield: 73.3 mg, 95%. 1H NMR (400 MHz, CDCl3): δ 2.40
(s, 3H), 2.83 (s, 3H), 6.95 (d, J = 9.2 Hz, 2H), 7.22 (d, J = 8.0 Hz, 2H), 7.60 (d, J = 8.8 Hz, 2H),
7.77 (d, J = 8.0 Hz, 2H), 8.95 (br, 1H). 13C NMR (100 MHz, CDCl3): δ 198.23, 158.20, 141.90,
140.06, 132.12, 129.26, 126.75, 125.77, 114.18, 55.51, 21.42. HRMS (EI-TOF) m/z: [M]+ Calcd.
for C15H15NOS+ 257.0874; Found 257.0874.
4-methyl-N-(p-tolyl)benzothioamide (4ab)
Light yellow solid. Mp: 133-134 oC. Yield: 68.7 mg, 95%. 1H NMR (400 MHz, CDCl3): δ 2.36
(s, 3H), 2.39 (s, 3H), 7.20-7.23 (m, 4H), 7.58 (d, J = 8.0 Hz, 2H), 7.75 d, J = 7.6 Hz, 2H), 8.98 (br,
13
1H). C NMR (100 MHz, CDCl3): δ 198.19, 141.88, 140.22, 136.93, 136.61, 129.61, 129.24,
126.77, 124.00, 21.42, 21.21. HRMS (EI-TOF) m/z: [M]+ Calcd. for C15H15NS+ 241.0925; found
241.0928.
4-methyl-N-phenylbenzothioamide (4ac)
Light yellow solid. Mp: 128-130 oC. Yield: 64.7 mg, 95%. 1H NMR (400 MHz, CDCl3): δ 2.38
(s, 3H), 7.19 (d, J = 6.8 Hz, 2H), 7.26-7.28 (m, 1H), 7.38-7.45 (m, 2H), 7.62-7.81 (m, 4H), 9.05
(br, 1H). 13C NMR (100 MHz, CDCl3): δ 198.30, 141.95, 140.28, 139.13, 129.25, 129.03, 126.91,
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126.81, 123.89, 21.44. HRMS (EI-TOF) m/z: [M]+ Calcd. for C14H13NS+ 227.0769; found
227.0772.
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N-(4-(tert-butyl)phenyl)-4-methylbenzothioamide (4ad)
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Light yellow solid. Mp: 117-119 oC. Yield: 79.8 mg, 94%. 1H NMR (400 MHz, CDCl3): δ 1.26
(s, 9H), 2.32 (s, 3H), 7.15 (d, J = 7.6 Hz, 2H), 7.37 (d, J = 8.0 Hz, 2H), 7.61 (d, J = 8.0 Hz, 2H),
7.68 (d, J = 7.6 Hz, 2H), 8.90 (br, 1H). 13C NMR (100 MHz, CDCl3): δ 197.83, 149.98, 141.87,
140.44, 136.54, 129.27, 126.73, 125.93, 123.30, 34.71, 31.33, 21.42. HRMS (EI-TOF) m/z: [M]+
Calcd. for C18H21NS+ 283.1395; found 283.1393.
N-(4-fluorophenyl)-4-methylbenzothioamide (4ae)
Light yellow solid. Mp: 106-108 oC. Yield: 72.1 mg, 98%. 1H NMR (400 MHz, CDCl3): δ 2.39,
2.40 (both, s, 3H), 7.08-7.12 (m, 2H), 7.21 (d, J = 7.6 Hz, 1H), 7.29-7.31 (m, 1H), 7.58-7.67 (m,
13
3H), 7.73 (d, J = 8.0 Hz, 1H), 9.05 (br, 1H). C NMR (100 MHz, CDCl3): δ 199.18, 198.76,
160.84 (d, JC-F = 245.5 Hz, C), 142.69, 142.17, 139.78, 138.61, 135.01, 132.25, 129.28, 128.55,
127.69, 126.80, 126.26, 126.13 (d, JC-F = 7.5 Hz, C), 123.62, 115.87 (d, JC-F = 22.8 Hz, C), 21.44,
21.40. HRMS (EI-TOF) m/z: [M]+ Calcd. for C14H12FNS+ 245.0674; found 245.0676.
N-(4-chlorophenyl)-4-methylbenzothioamide (4af)
Light yellow solid. Mp: 155-156 oC. Yield: 72.1 mg, 92%. 1H NMR (400 MHz, DMSO-d6): δ
2.37 (s, 3H), 7.28 (d, J = 8.0 Hz, 2H), 7.50 (d, J = 8.8 Hz, 2H), 7.78 (d, J = 8.0 Hz, 2H), 7.87 (d, J
= 8.8 Hz, 2H), 11.72 (br, 1H). 13C NMR (100 MHz, DMSO-d6): δ 197.60, 141.05, 139.60, 138.95,
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129.89, 128.51, 128.38, 127.54, 125.92, 20.88. HRMS (EI-TOF) m/z: [M]+ Calcd. for
C14H12ClNS+ 261.0379; found 261.0376.
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N-(4-bromophenyl)-4-methylbenzothioamide (4ag)
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Light yellow solid. Mp: 191-193 oC. Yield: 86.9 mg, 95%. 1H NMR (400 MHz, DMSO-d6): δ
2.37 (s, 3H), 7.28 (d, J = 8.0 Hz, 2H), 7.63 (d, J = 8.8 Hz, 2H), 7.77 (d, J = 8.0 Hz, 2H), 7.81 (d, J
= 8.4 Hz, 2H), 11.71 (br, 1H). 13C NMR (100 MHz, DMSO-d6): δ 197.57, 141.07, 139.61, 139.36,
131.32, 128.52, 127.54, 126.22, 118.20, 20.88. HRMS (EI-TOF) m/z: [M]+ Calcd. for
C14H12BrNS+ 304.9874; found 304.9871.
4-methyl-N-(4-nitrophenyl)benzothioamide (4ah)
Light yellow solid. Mp: 210-211 oC. Yield: 44.1 mg, 54%. 1H NMR (400 MHz, DMSO-d6): δ
2.38 (s, 3H), 7.31 (d, J = 8.0 Hz, 2H), 7.77 (d, J = 8.0 Hz, 2H), 8.21 (d, J = 8.4 Hz, 2H), 8.31 (d, J
= 9.2 Hz, 2H), 12.06 (br, 1H). 13C NMR (100 MHz, DMSO-d6): δ 198.89, 145.87, 144.04, 141.53,
139.80, 128.61, 127.68, 124.22, 123.81, 20.92. HRMS (EI-TOF) m/z: [M]+ Calcd. for
C14H12N2O2S+ 272.0619; found 272.0620.
N-(4-hydroxyphenyl)-4-methylbenzothioamide (4ai)
Orange yellow solid. Mp: 138-139 oC. Yield: 67.8 mg, 93%. 1H NMR (400 MHz, DMSO-d6):
δ 2.36 (s, 3H), 6.80 (d, J = 8.8 Hz, 2H), 7.26 d, J = 8.0 Hz, 2H), 7.56 (d, J = 8.8 Hz, 2H), 7.75 (d,
J = 8.4 Hz, 2H), 9.58 (br, 1H), 11.46 (br, 1H). 13C NMR (100 MHz, DMSO-d6): δ 196.16, 155.51,
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140.56, 139.66, 131.64, 128.41, 127.44, 125.82, 114.78, 20.85. HRMS (EI-TOF) m/z: [M]+ Calcd.
for C14H13NOS+ 243.0718; found 243.0720.
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4-methyl-N-(4-(trifluoromethyl)phenyl)benzothioamide (4aj)
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Light yellow solid. Mp: 178-180 oC. Yield: 80.6 mg, 91%. 1H NMR (400 MHz, DMSO-d6): δ
2.38 (s, 3H), 7.30 (d, J = 8.0 Hz, 2H), 7.78-7.82 (m, 4H), 8.10 (d, J = 7.2 Hz, 2H), 11.91 (br, 1H).
13C NMR (100 MHz, DMSO-d6): δ 198.37, 143.55, 141.27, 139.66, 128.56, 127.62, 125.94 (q,
JC-F = 31.6 Hz, C), 125.63 (q, JC-F = 3.6 Hz, C), 124.11 (q, JC-F = 270.3 Hz, C), 124.34, 20.89.
HRMS (EI-TOF) m/z: [M]+ Calcd. for C15H12F3NS+ 295.0643; found 295.0645.
4-methyl-N-(m-tolyl)benzothioamide (4ak)
Light yellow solid. Mp: 100-101 oC. Yield: 69.4 mg, 96%. 1H NMR (400 MHz, CDCl3): δ 2.31
(s, 6H), 7.02 (d, J = 7.2 Hz, 1H), 7.13 (d, J = 6.8 Hz, 2H), 7.21-7.25 (m, 1H), 7.39-7.54 (m, 2H),
7.67 (d, J = 7.2 Hz, 2H), 8.91 (br, 1H). 13C NMR (100 MHz, CDCl3): δ 198.19, 141.90, 140.37,
139.06, 129.25, 128.85, 127.77, 126.76, 124.40, 121.01，21.46, 21.43. HRMS (EI-TOF) m/z:
[M]+ Calcd. for C15H15NS+ 241.0925; found 241.0927.
4-methyl-N-(3-nitrophenyl)benzothioamide (4al)
Light yellow solid. Mp: 86-88 oC. Yield: 37.5 mg, 46%. 1H NMR (400 MHz, CDCl3): δ 2.41
(s, 3H), 7.25 (d, J = 9.2 Hz, 2H), 7.60 (t, J = 8.4 Hz, 1H), 7.76 (d, J = 7.6 Hz, 2H), 8.12-8.17 (m,
2H), 8.65 (s, 1H), 9.15 (br, 1H). 13C NMR (100 MHz, CDCl3): δ 199.34, 148.44, 142.68, 140.06,
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129.76, 129.60, 129.45, 126.80, 121.31, 118.73, 21.47. HRMS (EI-TOF) m/z: [M]+ Calcd. for
C14H12N2O2S+ 272.0619; found 272.0622.
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Light yellow solid. Mp: 98-99 oC. Yield: 75.2 mg, 96%. 1H NMR (400 MHz, CDCl3): δ 2.41
(s, 3H), 7.21-7.25 (m, 3H), 7.35 (t, J = 7.6 Hz, 1H), 7.48 (dd, J = 1.2, 8.0 Hz, 1H), 7.81 (d, J = 7.6
13
Hz, 2H), 8.69 (br, 1H), 9.29 (s, 1H). C NMR (100 MHz, CDCl3): δ 198.04, 142.25, 135.86,
129.56, 129.40, 127.40, 127.20, 126.93, 126.90, 125.07, 21.45. HRMS (EI-TOF) m/z: [M]+ Calcd.
for C14H12ClNS+ 261.0379; found 261.0378.
N-(2-ethylphenyl)-4-methylbenzothioamide (4an)
Light yellow solid. Mp: 73-74 oC. Yield: 74.2 mg, 97%. 1H NMR (400 MHz, CDCl3): δ 1.25
(t, J = 7.6 Hz, 3H), 2.42 (s, 3H), 2.66 (q, J = 7.6 Hz, 2H), 7.24 (d, J = 7.6 Hz, 2H), 7.30-7.35 (m,
3H), 7.49 (d, J = 7.6 Hz, 1H), 7.81 (d, J = 7.6 Hz, 2H), 8.88 (br, 1H). 13C NMR (100 MHz, CDCl3):
δ 199.72, 142.09, 139.91, 139.28, 137.19, 129.30, 129.12, 128.37, 127.46, 126.87, 126.71, 24.52,
21.47, 14.38. HRMS (EI-TOF) m/z: [M]+ Calcd. for C16H17NS+ 255.1082; found 255.1084.
4-methyl-N-(2-phenoxyphenyl)benzothioamide (4ao)
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Orange yellow oil. Yield: 88.1 mg, 92%. H NMR (400 MHz, CDCl3): δ 2.38 (s, 3H), 6.94-
6.97 (m, 1H), 7.07 (d, J = 7.6 Hz, 2H), 7.16-7.21 (m, 5H), 7.36-7.40 (m, 2H), 7.67 (d, J = 7.6 Hz,
2H), 9.12 (br, 1H), 9.56 (s, 1H). 13C NMR (100 MHz, CDCl3): δ 196.88, 156.13, 148.13, 141.82,
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130.74, 130.13, 129.28, 126.77, 124.29, 123.35, 123.04, 118.86, 118.00, 21.41. HRMS (EI-TOF)
m/z: [M]+ Calcd. for C20H17NOS+ 319.1031; found 319.1035.
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Light yellow solid. Mp: 144-145 oC. Yield: 79.3 mg, 85%. 1H NMR (400 MHz, CDCl3): δ 1.21
(d, J = 6.8 Hz, 6H), 1.29 (d, J = 6.8 Hz, 6H), 2.44 (s, 3H), 3.05-3.12 (m, 2H), 7.27 (s, 2H), 7.29 (s,
2H), 7.42 (t, J = 7.6 Hz, 1H), 7.87 (d, J = 8.4 Hz, 2H), 8.62 (br, 1H). 13C NMR (100 MHz, CDCl3):
δ 200.60, 145.92, 142.12, 138.84, 134.03, 129.37, 129.30, 126.76, 123.98, 28.91, 24.57, 23.30,
21.46. HRMS (EI-TOF) m/z: [M]+ Calcd. for C20H25NS+ 311.1708; found 311.1704.
N-(3,5-bis(trifluoromethyl)phenyl)-4-methylbenzothioamide (4aq)
Light yellow solid. Mp: 92-93 oC. Yield: 103.5 mg, 95%. 1H NMR (400 MHz, CDCl3): δ 2.41
(s, 3H), 7.24 (d, J = 8.0 Hz, 2H), 7.73-7.76 (m, 3H), 8.30 (s, 2H), 9.16 (br, 1H),. 13C NMR (100
MHz, CDCl3): δ 199.52, 142.88, 140.29, 139.38, 132.22 (q, JC-F = 33.5 Hz, C), 129.40, 126.81,
123.75, 123.72, 122.94 (q, JC-F = 271.4 Hz, C), 119.85-119.99 (m, C), 118.88, 21.39. HRMS (EI-
TOF) m/z: [M]+ Calcd. for C16H11F6NS+ 363.0516; found 363.0513.
morpholino(p-tolyl)methanethione (4au)
Light yellow solid. Mp: 115-116 oC. Yield: 39.8 mg, 60%. 1H NMR (400 MHz, CDCl3): δ 2.34
(s, 3H), 3.62 (s, 4H), 3.87 (t, J = 4.8 Hz, 2H), 4.42 (t, J = 4.8 Hz, 2H), 7.14-7.19 (m, 4H). 13C NMR
(100 MHz, CDCl3): δ 201.39, 139.69, 139.11, 129.12, 126.06, 66.78, 66.55, 52.59, 49.70, 21.28.
HRMS (EI-TOF) m/z: [M]+ Calcd. for C12H15NOS+ 221.0874; found 221.0875.
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piperidin-1-yl(p-tolyl)methanethione (4av)
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Light yellow solid. Mp: 65-67 oC. Yield: 24.3 mg, 37%. 1H NMR (400 MHz, CDCl3): δ 1.54-
1.59 (m, 2H), 1.71-1.77 (m, 2H), 1.79-1.84 (m, 2H), 2.35 (s, 3H), 3.54 (t, J = 5.6 Hz, 2H), 4.35
(t, J = 5.2 Hz, 2H), 7.13-7.19 (m, 4H). 13C NMR (100 MHz, CDCl3): δ 199.98, 140.63, 138.47,
128.98, 125.58, 53.21, 50.76, 26.91, 25.52, 24.21, 21.25. HRMS (EI-TOF) m/z: [M]+ Calcd. for
C13H17NS+ 219.1082; found 219.1085.
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N,N,4-trimethylbenzothioamide (4ax)
Light yellow oil. Yield: 11.8 mg, 22%. 1H NMR (400 MHz, CDCl3): δ 2.35 (s, 3H), 3.17, 3.18
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(both, s, 3H), 3.60, 3.60 (both, s, 3H), 7.06-7.14 (m, 2H), 7.16-7.23 (m, 2H). C NMR (100
MHz, CDCl3): δ 201.60, 143.38, 140.59, 138.73, 138.20, 129.33, 128.90, 128.22, 126.39, 125.91,
122.62, 44.21, 44.15, 43.36, 43.19, 29.71, 21.40, 21.27. HRMS (EI-TOF) m/z: [M]+ Calcd. for
C10H13NS+ 179.0769; found 179.0770.
4-chloro-N-(4-methoxyphenyl)benzothioamide (4ba)
Light yellow solid. Mp: 160-162 oC. Yield: 64.8 mg, 78%. 1H NMR (400 MHz, DMSO-d6): δ
3.79 (s, 3H), 7.00 (d, J = 9.2 Hz, 2H), 7.54 (d, J = 8.8 Hz, 2H), 7.72 (d, J = 8.8 Hz, 2H), 7.86 (d, J
= 8.8 Hz, 2H), 11.72 (br, 1H). 13C NMR (100 MHz, DMSO-d6): δ 195.11, 157.32, 141.07, 135.36,
132.87, 129.23, 127.95, 125.60, 113.58, 55.27. HRMS (EI-TOF) m/z: [M]+ Calcd. for
C14H12ClNOS+ 277.0328; found 277.0327.
4-fluoro-N-(4-methoxyphenyl)benzothioamide (4bb)
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Light yellow solid. Mp: 140-141 oC. Yield: 65.0 mg, 83%. 1H NMR (400 MHz, CDCl3): δ 3.83
(s, 3H), 6.94 (d, J = 8.8 Hz, 2H), 7.09 (t, J = 8.4 Hz, 2H), 7.57 (d, J = 8.8 Hz, 2H), 7.83-7.87 (m,
2H), 8.94 (br, 1H). 13C NMR (100 MHz, CDCl3): δ 196.96, 164.60 (d, JC-F = 251.1 Hz, C), 158.34,
138.97, 131.93, 129.00 (d, JC-F = 8.8 Hz, C), 125.75, 115.56 (d, JC-F = 21.8 Hz, C), 114.23, 55.52.
HRMS (EI-TOF) m/z: [M]+ Calcd. for C14H12FNOS+ 261.0624; found 261.0624.
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4-(tert-butyl)-N-(4-methoxyphenyl)benzothioamide (4bc)
Light yellow solid. Mp: 147-149 oC. Yield: 87.9 mg, 98%. 1H NMR (400 MHz, CDCl3): δ 1.34
(s, 9H), 3.82 (s, 3H), 6.93 (d, J = 9.2 Hz, 2H), 7.43 (d, J = 8.4 Hz, 2H), 7.60 (d, J = 8.8 Hz, 2H),
7.78 (d, J = 8.4 Hz, 2H), 9.00 (br, 1H). 13C NMR (100 MHz, CDCl3): δ 198.13, 158.17, 154.91,
140.00, 132.15, 126.61, 125.71, 125.57, 114.16, 55.52, 34.94, 31.18. HRMS (EI-TOF) m/z: [M]+
Calcd. for C18H21NOS+ 299.1344; found 299.1346.
N-(4-methoxyphenyl)-2-(p-tolyl)ethanethioamide (5a)
Light yellow solid. Mp: 132-133 oC. Yield: 64.3 mg, 79%. 1H NMR (400 MHz, CDCl3): δ 2.37
(s, 3H), 3.78 (s, 3H), 4.22 (s, 2H), 6.86 (d, J = 9.2 Hz, 2H), 7.23 (s, 4H), 7.40 (d, J = 9.2 Hz, 2H),
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8.45 (br, 1H). C NMR (100 MHz, CDCl3): δ 201.59, 158.24, 137.91, 131.76, 131.49, 130.14,
129.62, 125.55, 114.01, 55.48, 54.07, 21.20. HRMS (EI-TOF) m/z: [M]+ Calcd. for C16H17NOS+
271.1031; found 271.1032.
N,2-di-p-tolylethanethioamide (5b)
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Light yellow solid. Mp: 73-74 oC. Yield: 58.9 mg, 77%. 1H NMR (400 MHz, CDCl3): δ 2.33
(s, 3H), 2.38 (s, 3H), 4.23 (s, 2H), 7.15 (d, J = 8.4 Hz, 2H), 7.23 (s, 4H), 7.40 (d, J = 8.4 Hz, 2H),
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8.46 (br, 1H). C NMR (100 MHz, CDCl3): δ 201.52, 137.92, 137.01, 135.99, 131.76, 130.15,
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129.62, 129.45, 123.78, 54.34, 21.19, 21.15. HRMS (EI-TOF) m/z: [M]+ Calcd. for C16H17NS+
255.1082; found 255.1084.
N-(4-chlorophenyl)-2-(p-tolyl)ethanethioamide (5c)
Light yellow solid. Mp: 84-86 oC. Yield: 61.9 mg, 75%. 1H NMR (400 MHz, CDCl3): δ 2.38
(s, 3H), 4.23 (s, 2H), 7.23 (s, 4H), 7.30 (d, J = 8.8 Hz, 2H), 7.51 (d, J = 8.8 Hz, 2H), 8.41 (br, 1H).
13C NMR (100 MHz, CDCl3): δ 201.89, 138.14, 136.95, 132.16, 131.43, 130.27, 129.61, 128.97,
124.92, 54.58, 21.20. HRMS (EI-TOF) m/z: [M]+ Calcd. for C15H14ClNS+ 275.0535; found
275.0537.
N-(4-(tert-butyl)phenyl)-2-(p-tolyl)ethanethioamide (5d)
Brown solid. Mp: 51-53 oC. Yield: 65.1 mg, 73%. 1H NMR (400 MHz, CDCl3): δ 1.28 (s, 9H),
2.36 (s, 3H), 4.23 (s, 2H), 7.22 (s, 4H), 7.35 (d, J = 8.8 Hz, 2H), 7.47 (d, J = 8.4 Hz, 2H), 8.46 (br,
13
1H). C NMR (100 MHz, CDCl3): δ 201.13, 150.08, 137.93, 135.90, 131.73, 130.15, 129.62,
125.76, 123.19, 54.47, 34.64, 31.28, 21.19. HRMS (EI-TOF) m/z: [M]+ Calcd. for C19H23NS+
297.1551; found 297.1552.
N-(m-tolyl)-2-(p-tolyl)ethanethioamide (5e)
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Brown oil. Yield: 44.4 mg, 58%. 1H NMR (400 MHz, CDCl3): δ 2.33 (s, 3H), 2.37 (s, 3H), 4.24
(s, 2H), 7.04 (d, J = 8.0 Hz, 1H), 7.21-7.23 (m, 5H), 7.32 (br, 1H), 7.36 (d, J = 8.0 Hz, 1H), 8.41
(s, 1H). 13C NMR (100 MHz, CDCl3): δ 200.98, 138.43, 137.90, 137.49, 131.15, 129.70, 129.14,
128.21, 127.36, 123.69, 120.35, 54.05, 20.87, 20.69. HRMS (EI-TOF) m/z: [M]+ Calcd. for
C16H17NS+ 255.1082; found 255.1082.
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N-(3-chlorophenyl)-2-(p-tolyl)ethanethioamide (5f)
Brown oil. Yield: 33.0 mg, 40%. 1H NMR (400 MHz, CDCl3): δ 2.38 (s, 3H), 4.23 (s, 2H), 7.13-
7.15 (m, 1H), 7.19-7.21 (m, 1H), 7.23 (s, 2H), 7.25-7.27 (m, 1H), 7.29-7.34 (m, 1H), 7.45 (d, J =
8.0 Hz, 1H), 7.64-7.66 (m, 1H), 8.42 (br, 1H). 13C NMR (100 MHz, CDCl3): δ 202.03, 201.84,
139.50, 138.17, 134.42, 131.39, 130.39, 130.29, 129.84, 129.59, 129.46, 129.09, 127.00, 126.61,
123.59, 123.55, 121.73, 55.08, 54.71, 21.45, 21.20. HRMS (EI-TOF) m/z: [M]+ Calcd. for
C15H14ClNS+ 275.0535; found 275.0537.
N-butyl-2-(p-tolyl)ethanethioamide (5j)
Brown oil. Yield: 42.5 mg, 64%. 1H NMR (400 MHz, CDCl3): δ 0.88 (t, J = 7.2 Hz, 2H), 1.22-
1.31 (m, 2H), 1.47-1.54 (m, 2H), 2.36 (s, 3H), 3.58-3.63 (m, 2H), 4.10 (s, 2H), 6.98 (br, 1H), 7.12
13
(d, J = 8.0 Hz, 2H), 7.19 (d, J = 7.6 Hz, 2H). C NMR (100 MHz, CDCl3): δ 201.98, 137.70,
131.54, 129.98, 129.56, 52.77, 45.91, 29.82, 21.15, 20.04, 13.69. HRMS (EI-TOF) m/z: [M]+
Calcd. for C13H19NS+ 221.1238; found 221.1236.
1-(piperidin-1-yl)-2-(p-tolyl)ethane-1-thione (5m)
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Brown yellow solid. Mp: 117-118 C. Yield: 41.3 mg, 59%. H NMR (400 MHz, CDCl3): δ
1.28-1.34 (m, 2H), 1.59-1.69 (m, 4H), 2.32 (s, 3H), 3.58 (t, J = 5.6 Hz, 2H), 4.27 (t, J = 4.8 Hz,
2H), 4.30 (s, 2H), 7.12 (d, J = 7.6 Hz, 2H), 7.22 (d, J = 8.0 Hz, 2H). 13C NMR (100 MHz, CDCl3):
δ 198.63, 136.43, 133.05, 129.45, 127.75, 51.64, 51.57, 50.61, 26.25, 25.27, 23.87, 21.08. HRMS
(EI-TOF) m/z: [M]+ Calcd. for C14H19NS+ 233.1238; found 233.1237.
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1-morpholino-2-(p-tolyl)ethane-1-thione (5n)
Light yellow solid. Mp: 90-91 oC. Yield 43.7 mg, 62%. 1H NMR (400 MHz, CDCl3): δ 2.32 (s,
3H), 3.38 (t, J = 4.8 Hz, 2H), 3.62 (t, J = 4.8 Hz, 2H), 3.73 (t, J = 5.2 Hz, 2H), 4.30 (s, 2H), 4.34
(t, J = 4.8 Hz, 2H), 7.12 (d, J = 8.0 Hz, 2H), 7.19 (d, J = 8.0 Hz, 2H). 13C NMR (100 MHz, CDCl3):
δ 200.32, 136.75, 132.66, 129.63, 127.64, 66.35, 66.15, 50.77, 50.27, 50.18, 21.08. HRMS (EI-
TOF) m/z: [M]+ Calcd. for C13H17NOS+ 235.1031; found 235.1031.
N,N-dimethyl-2-(p-tolyl)ethanethioamide (5p)
Light yellow oil. Yield: 29.0 mg, 50%. 1H NMR (400 MHz, CDCl3): δ 2.33, 2.33 (both, s, 3H),
3.20 (s, 3H), 3.49, 3.50 (both, s, 3H), 4.27, 4.28 (both, s, 2H), 7.05-7.14 (m, 2H), 7.16-7.23 (m,
13
2H). C NMR (100 MHz, CDCl3): δ 200.99, 200.76, 138.52, 136.58, 135.57, 132.59, 129.48,
128.72, 128.67, 128.01, 127.73, 125.15, 50.98, 50.58, 44.85, 42.32, 42.26, 21.45, 21.07. HRMS
(EI-TOF) m/z: [M]+ Calcd. for C11H15NS+ 193.0925; found 193.0925.
2-(4-(tert-butyl)phenyl)-N-(4-methoxyphenyl)ethanethioamide (5q)
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Brown oil. Yield: 70.5 mg, 75%. 1H NMR (400 MHz, CDCl3): δ 1.33 (s, 9H), 3.78 (s, 3H), 4.23
(s, 2H), 6.86 (d, J = 8.8 Hz, 2H), 7.28 (d, J = 8.4 Hz, 2H), 7.39-7.44 (m, 4H), 8.47 (br, 1H). 13C
NMR (100 MHz, CDCl3): δ 201.68, 158.28, 151.10, 131.76, 131.52, 129.41, 126.40, 125.69,
114.03, 55.49, 53.99, 34.64, 31.33. HRMS (EI-TOF) m/z: [M]+ Calcd. for C19H23NOS+ 313.1500;
found 313.1504.
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N,2-bis(4-methoxyphenyl)ethanethioamide (5r)
Light yellow solid. Mp: 122-124 oC. Yield: 79.2 mg, 92%. 1H NMR (400 MHz, CDCl3): δ 3.78
(s, 3H), 3.82 (s, 3H), 4.19 (s, 2H), 6.86 (d, J = 9.2 Hz, 2H), 6.94 (d, J = 8.8 Hz, 2H), 7.26 (d, J =
13
8.8 Hz, 2H), 7.41 (d, J = 8.8 Hz, 2H), 8.47 (br, 1H). C NMR (100 MHz, CDCl3): δ 201.75,
159.37, 158.23, 131.49, 130.90, 126.76, 125.49, 114.81, 114.01, 55.48, 55.36, 53.63. HRMS (EI-
TOF) m/z: [M]+ Calcd. for C16H17NO2S+ 287.0980; found 287.0979.
N-(4-methoxyphenyl)-2-phenylethanethioamide (5s)
Orange solid. Mp: 66-68 oC. Yield: 54.0 mg, 70%. 1H NMR (400 MHz, CDCl3): δ 3.78 (s, 3H),
4.26 (s, 2H), 6.86 (d, J = 9.2 Hz, 2H), 7.35-7.37 (m, 3H), 7.39-7.42 (m, 4H), 8.46 (br, 1H). 13C
NMR (100 MHz, CDCl3): δ 201.28, 158.27, 135.01, 131.47, 129.65, 129.44, 128.08, 125.57,
114.04, 55.49, 54.47. HRMS (EI-TOF) m/z: [M]+ Calcd. for C15H15NOS+ 257.0874; found
257.0872.
N-(4-methoxyphenyl)-2-(pyridin-2-yl)ethanethioamide (5v)
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Light yellow solid. Mp: 114-115 oC. Yield: 26.3 mg, 34%. 1H NMR (400 MHz, CDCl3): δ 3.80
(s, 3H), 4.36 (s, 2H), 6.90 (d, J = 9.2 Hz, 2H), 7.26-7.29 (m, 1H), 7.35 (d, J = 8.0 Hz, 1H), 7.64
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(d, J = 8.8 Hz, 2H), 7.72 (dt, J = 2.0, 8.0 Hz, 1H), 8.58 (d, J = 4.4 Hz, 1H), 11.85 (br, 1H). C
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NMR (100 MHz, CDCl3): δ 196.82, 157.83, 156.30, 148.66, 137.74, 132.25, 124.86, 124.17,
122.53, 113.91, 55.48, 54.12. HRMS (EI-TOF) m/z: [M]+ Calcd. for C14H14N2OS+ 258.0827;
found 258.0824.
2-(p-tolyl)ethanethioamide (5w)
Brown oil. Yield: 15.0 mg, 30%. 1H NMR (400 MHz, CDCl3): δ 2.35, 2.36 (both, s, 3H), 4.07,
4.07 (both, s, 2H), 6.73 (br, 1H), 7.05-7.08 (m, 1H), 7.14-7.20 (m, 2H), 7.25-7.29 (m, 1H), 7.80
(br, 1H). 13C NMR (100 MHz, CDCl3): δ 207.84, 207.61, 139.18, 137.82, 134.74, 131.76, 130.18,
130.01, 129.37, 129.23, 128.75, 126.45, 52.05, 51.69, 21.37, 21.13. HRMS (EI-TOF) m/z: [M]+
Calcd. for C9H11NS+ 165.0612; found 165.0614.
2-(4-(tert-butyl)phenyl)ethanethioamide (5x)
Light yellow solid. Mp: 74-75 oC. Yield: 20.0 mg, 32%. 1H NMR (400 MHz, CDCl3): δ 1.32
(s, 9H), 4.09 (s, 2H), 6.71 (br, 1H), 7.20 (d, J = 8.0 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H), 7.72 (br,
13
1H). C NMR (100 MHz, CDCl3): δ 207.80, 151.08, 131.72, 129.19, 126.82, 126.30, 125.48,
51.63, 31.30, 29.72. HRMS (EI-TOF) m/z: [M]+ Calcd. for C12H17NS+ 207.1082; found 207.1082.
Supporting Information
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The Supporting Information is available free of charge on the ACS Publications website at
DOI: 1H NMR and 13C NMR spectra for new products (PDF).
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AUTHOR INFORMATION
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Corresponding Author
*E-mail: chenwzz@zju.edu.cn.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
The National Natural Science Foundation of China (21572203 and 21472140) and Zhejiang
Provincial Natural Science Foundation (LZ16B020001) are acknowledged for the financial
support.
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Electrochemical C−H Thiolation: Synthesis of Benzothiazoles and Thiazolopyridines from
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Jiang, J. J.; Li, G. Z.; Zhang, F.; Xie, H.; Deng, G. Aniline ortho C-H Sulfuration/Cyclization
with Elemental Sulfur for Efficient Synthesis of 2-Substituted Benzothiazoles under Metal-
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