Thio-Michael addition of α,β-unsaturated amides catalyzed by Nmm-based ionic liquids

Article abstract of DOI:10.1039/c7ra08956b

A simple and practical thio-Michael addition of α,β-unsaturated amides catalyzed by Nmm-based ionic liquids with a 1,2-propanediol group has been developed. All the α,β-unsaturated amides without substituents at the carbon end could smoothly react with su

Full text of DOI:10.1039/c7ra08956b

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Thio-Michael addition of a,b-unsaturated amides
catalyzed by Nmm-based ionic liquids†
Cite this: RSC Adv., 2017, 7, 43104
a
Yawei Liu,‡a Zhenzhen Lai,‡a Pengkun Yang,‡a Yuanqing Xu,a Wenkai Zhang,
a
a
a
a
ab
*
*
Baoying Liu, Minghua Lu, Haibo Chang, Tao Ding and Hao Xu
A simple and practical thio-Michael addition of a,b-unsaturated amides catalyzed by Nmm-based ionic
liquids with a 1,2-propanediol group has been developed. All the a,b-unsaturated amides without
substituents at the carbon end could smoothly react with sulfur-nucleophiles in water. Meanwhile for
thio-Michael addition of a,b-unsaturated amides with substituents at the carbon end, the relevant
product could also be obtained successfully under solvent-free conditions at 55 ꢀC. Furthermore, the IL-
catalyst is recyclable and applicable for gram-scale synthesis.
Received 13th August 2017
Accepted 31st August 2017
DOI: 10.1039/c7ra08956b
rsc.li/rsc-advances
transformed into the corresponding thio-Michael adduct easily
because of less steric hindrance. Therefore, the systematical
Introduction
research on thio-Michael addition of a,b-unsaturated amides is
very necessary.
Ionic liquids (ILs) are acknowledged as eco-friendly alternatives
to volatile organic solvents, because of their unique properties
like negligible vapor pressure, high thermal stability, excellent
dissolving capacity and ease of recyclability. In the past few
years, many functional ILs have been also employed as catalysts
for various reactions such as Michael addition,1 Knoevenagel
condensation2 and Mannich reaction.3 Furthermore, well-
designed ILs could signicantly improve the reactivity and
selectivity of reactions by modifying distinct cations and
anions.4 Therefore, it is highly desirable to explore rationally-
designed and readily available IL catalysts for different
reactions.
Thio-Michael reaction is one of the most important carbon–
sulfur bond forming reactions, and plays a key role in the
synthesis of many bioactive molecules.5 Traditionally, the
reaction is performed in organic solvent under base-mediated
or Lewis acid-mediated conditions.6 In recent years, some
catalytic methods have been developed in the presence of
catalysts including organic bases,7 Lewis or Brønsted acids,8
ionic liquids,9 enzymes10 and N-heterocyclic carbine.11 Although
these methods above are efficient, the range of Michael accep-
tors was limited to relatively active substrates such as acrylo-
nitrile, nitroalkenes, a,b-unsaturated ketones and esters.
Several examples attempted to employ a,b-unsaturated amides
as Michael acceptors (Scheme 1A and B),1c,8c,11,12 but only the
acrylamide without substituents at carbon end could be
“The best solvent is no solvent and if a solvent is needed it
should preferably be water” stated by R. A. Sheldon.13 Thio-
Michael addition in water is environmentally benign because
water is cheap and safe. Recently, several examples conducted
in water have been reported by employing catalysts including
NiFeO4 nanoparticle,14 boric acid,15 borax16 and b-cyclodextrin
(Scheme 1C).17 However, the poor tolerance for different a,b-
unsaturated amides is still the main hurdle with thio-Michael
addition in water, and only unsubstituted acrylamide was
tolerated for its less steric hindrance. Furthermore, the reaction
catalyzed by ionic liquid in water has not been found in the
literature. In our previous work, a serial of novel ionic liquids
aCollege of Chemistry and Chemical Engineering, Henan University, Kaifeng 475004,
P. R. China. E-mail: xuhao@henu.edu.cn; dingtao@henu.edu.cn
bKey Laboratory of Natural Medicine and Immuno-Engineering, Henan University,
Kaifeng 475004, P. R. China
† Electronic supplementary information (ESI) available: 1H, 13C NMR spectra of
these synthesized compounds. See DOI: 10.1039/c7ra08956b
‡ These authors contributed equally to this work.
Scheme 1 Thio-Michael addition of a,b-unsaturated amides.
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Table 1 Thio-Michael addition of propanethiol (1a) with N-phenyl-
acrylamide (2c) catalyzed by Nmm-based ionic liquids: optimization of
conditionsa
based on N-methyl morpholine (Nmm) and 3-chloro-1,2-
propanediol were synthesized and applied successfully in
Knoevenagel condensation.2a In continuation of our endeavors
to develop simple and practical methodology for organic
synthesis,18 herein we report a thio-Michael addition of a,b-
unsaturated amides catalyzed by Nmm-based ionic liquids in
water (Scheme 1D), and most of the substrates could provide
good yields in water. In addition, the catalysts are recyclable and
applicable for the gram-scale synthesis.
Entry
Cat.
Solvent
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
[Nmm-PDO][OH]
[Nmm-PDO][OAc]
[Nmm-PDO][BF4]
[Nmm-PDO][Gly]
[Nbmm][Gly]
H2O
H2O
H2O
H2O
H2O
H2O
CH2Cl2
CH3CN
Neat
H2O
10
10
10
10
10
24
10
10
10
24
48
95
85
65
96
60
Trace
83
73
90
Results and discussion
Five Nmm-based ionic liquids were synthesized by our previous
methods (Scheme 2).2a
Catalyst free
Initially, the thio-Michael addition of propanethiol (1a) with
N-phenylacrylamide (2c) was chosen as the model reaction to
optimize conditions including catalysts, solvents and the
amount of catalyst. As shown in Table 1, four Nmm-based IL
catalysts were screened using water as the solvent at room
temperature for 10 hours (Table 1, entries 1–4), and [Nmm-PDO]
[Gly] afforded the highest yield (entry 4). The reaction did not
work in the absence of IL catalysts, even reaction time was
extended to 24 h (entry 6). [Nbmm][Gly] was also used as the
catalyst for comparison, but it was inferior to [Nmm-PDO][Gly]
although the same glycine (Gly) anion existed in the two IL
catalysts (compare entry 4 with entry 5); the results hinted the
hydrogen bonding interaction between carbonyl group of N-
phenylacrylamide (2c) and hydroxyl groups in the cation of
[Nmm-PDO][Gly], which could increase the electrophilicity of
the amide as Michael acceptor. The effect of solvents was also
investigated (entries 4, 7, 8), and H2O was more suitable,
perhaps because of its better dissolving ability for IL-catalysts.
When the reaction was performed under solvent-free condi-
tion, an excellent yield could also be obtained (entry 9).
Furthermore, the effect of catalyst loading was also investigated;
when the amount of catalyst was decreased, the product (3n)
could still be generated in moderate to good yield, but more
reaction time was needed (entries 10, 11).
[Nmm-PDO][Gly]
[Nmm-PDO][Gly]
[Nmm-PDO][Gly]
[Nmm-PDO][Gly]
[Nmm-PDO][Gly]
9
10c
11d
86
52
H2O
a
Reaction conditions: propanethiol (0.5 mmol, 45 mL), N-
phenylacrylamide (0.5 mmol, 74 mg), catalyst (10 mol%), H2O (1 mL),
room temperature. Isolated yield. Catalyst (5 mol%). Catalyst
(1 mol%).
b
c
d
Especially for the substituted acrylamides with substituents at
carbon end, only trace amount of products could be monitored
by TLC; fortunately, the corresponding products could be ob-
tained in good yields under solvent-free conditions at 55 ꢀC
(entries 26–30). Furthermore, substituted propynamide could
also be transformed into relevant thio-Michael adduct in 42%
yield under solvent-free conditions (entry 31), and the reaction
is highly stereoselective for the Z-geometry. For the sulfur-
nucleophile, the reactivity of thiols was also affected by the
steric hindrance. Meanwhile the aromatic sulfur-nucleophile
could react with a,b-unsaturated amides smoothly too (entry
6–9, 12–13, 19–21, 27), perhaps because the proton (H+) could
be removed more easily than thiols although the steric
hindrance of phenyl group was relatively larger. In addition,
thiols with hydroxyl group or carbon–carbon double bond could
be tolerated as well (entries 22, 23, 28).
The reaction of propanethiol (1a) with N,N-dimethylacryla-
mide (2b) was chosen to examine the recyclability of IL-catalysts
and applicability in the large-scale synthesis. The result showed
that the catalyst still kept a high catalytic activity even in the
third run (see Table S1 in the ESI†). Furthermore, the scaled-up
experiment was performed on a gram-scale, and 2.90 g of 3j
were prepared in 82% yield (2g of 2b was used); the result
demonstrated that [Nmm-PDO][Gly] was also efficient catalyst
for gram-scale synthesis.
With the optimized conditions in hand (10 mol% of [Nmm-
PDO][OAc] as the catalyst, water as solvent, room temperature),
the scope of thio-Michael addition of a,b-unsaturated amides
catalyzed by Nmm-based ionic liquids in water was investigated;
and most of the substrates provided good yields as shown in
Table 2. For a,b-unsaturated amides, the steric hindrance had
a great impact on their reactivity; the substrates with larger
substituents showed lower reactivity (entries 1–5, 14–18).
A possible mechanism is proposed in Scheme 3 for the
[Nmm-PDO][Gly] catalyzed thio-Michael addition (herein, reac-
tion of propanethiol 1a with N,N-dimethylacrylamide 2b is
chosen as the example). Firstly, the hydrogen-bonding interac-
tions between the hydroxyl groups of [Nmm-PDO][Gly] and the
carbonyl group of 2b can be formed, which making 2b more
vulnerable by 1a. Then nucleophilic attack of thiol 1a on the
Scheme 2 Synthesis of the [Nmm-PDO][X] and [Nbmm][Gly] ionic
liquids.
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Table 2 Thio-Michael addition of a,b-unsaturated amides catalyzed by [Nmm-PDO][Gly]a
Entry
1
1
2
3
t/h
Yieldb/%
98
6
2
3
2a
2a
6
92
25
50(91c)
4
2a
6
88
5
6
2a
2a
6
6
87
78
7
8
9
2a
2a
2a
6
6
6
82
88
72
10
1a
6
90
11
12
1e
1f
2b
2b
6
6
92
94
13
1g
2b
6
96
14
15
1a
1b
10
10
96
80
2c
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Table 2 (Contd.)
Entry
16
1
2
3
t/h
Yieldb/%
44(81c)
1c
2c
25
17
18
1d
1e
2c
2c
10
10
85
86
19
20
1f
2c
2c
10
10
91
88
1g
21
1h
2c
10
91
22
23
2c
2c
10
10
34(60c)
95
24
25
26
1a
1f
6
98
90
78c
2d
6
1a
10
27
1f
2e
20
60c
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Table 2 (Contd.)
Entry
28
1
2
3
t/h
Yieldb/%
42c
1j
2e
10
29
30
31
1a
1a
16
25
88c
75c
1a
1a
15
20
42
32
62d
a
Reaction conditions: sulfur-nucleophile 1 (0.5 mmol), a,b-unsaturated amides 2 (0.5 mmol), catalyst [Nmm-PDO][Gly] (10 mol%), water (1 mL),
room temperature. Isolated yield. c Solvent-free at 55 ꢀC. d Sulfur-nucleophile 1a (1 mmol).
b
Scheme 3 Possible mechanism for the thio-Michael addition catalyzed by [Nmm-PDO][Gly] between propanethiol (1a) and N,N-dimethyla-
crylamide (2b).
b-carbon of N,N-dimethylacrylamide 2b lead to the intermediate to 1568 cmꢁ1 in the mixture; meanwhile we also compared
A. Intermediate A take the proton from glycine (Gly), generating the 13C NMR spectrum of N,N-dimethylacrylamide with N,N-
the thio-Michael product 3j.
dimethylacrylamide-[Nmm-PDO][Gly] mixture (Fig. S1 and S2 in
Additionally, we compared the FTIR spectrum of the N,N- the ESI†); the chemical shi of carbonyl group in N-phenyl-
dimethylacrylamide with N,N-dimethylacrylamide-[Nmm-PDO] acrylamide was 165.23, while it was 165.47 in the mixture. All
[Gly] mixture, and the results were shown in Fig. 1. It was the results hinted the existence of the hydrogen bonding
found that the absorption peak of carbonyl group in N,N- interactions between the carbonyl group of the N,N-dimethyla-
dimethylacrylamide was at 1648 cmꢁ1, while it was red-shied crylamide and the hydroxyl groups in [Nmm-PDO][Gly].
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[Nmm-PDO][OH]
1
ꢀ
Colourless liquid; H NMR (D2O, 400 MHz, 25 C): d 4.43–4.23
(m, 1H), 4.04 (s, 4H), 3.73–3.46 (m, 8H), 3.30 (s, 3H). 13C NMR
ꢀ
(D2O, 100 MHz, 25 C) d 66.5, 65.7, 63.7, 61.1, 60.7, 60.5, 48.4.
ESI-MS [Nmm-PDO]+ 176.12.
[Nmm-PDO][OAc]
1
ꢀ
Colourless liquid; H NMR (D2O, 400 MHz, 25 C): d 4.22–4.11
(m, 1H), 3.89 (s, 4H), 3.61–3.32 (m, 8H), 3.16 (s, 3H), 1.77 (s, 3H).
13C NMR (D2O, 100 MHz, 25 ꢀC): d 180.0, 66.4, 65.6, 63.6, 60.9,
60.6, 60.3, 48.3, 23.1. ESI-MS [Nmm-PDO]+ 176.12; ESI-MS
[CH3COO]ꢁ m/z 59.06.
Fig. 1 FTIR comparison of N,N-dimethylacrylamide with N,N-dime-
thylacryl-amide + [Nmm-PDO][Gly] mixture.
[Nmm-PDO][BF4]
1
ꢀ
Colourless liquid; H NMR (D2O, 400 MHz, 25 C): d 4.47–4.32
(m, 1H), 4.12 (s, 4Hꢀ), 3.81–3.51 (m, 8H), 3.37 (s, 3H). 13C NMR
(D2O, 100 MHz, 25 C) d 66.6, 65.8, 63.8, 61.2, 60.7, 60.5, 48.3.
ESI-MS [Nmm-PDO]+ 176.12; ESI-MS [BF4]ꢁ 87.03.
Conclusion
Readily available and eco-friendly Nmm-based ILs are devel-
oped as the practical and recyclable catalysts for the thio-
Michael addition of a,b-unsaturated amides. All the a,b-unsat-
urated amides without substituents at carbon end could
smoothly react with sulfur-nucleophile in water, and only
unsubstituted acrylamide was tolerated in water by the previous
methods. Meanwhile for thio-Michael addition of a,b-unsatu-
rated amides with substituents at carbon end, the relevant
product could be obtained successfully under solvent-free
condition at 55 ꢀC, which was hard to be prepared via thio-
Michael addition in the previous methods. Furthermore, the
IL-catalyst is recyclable and applicable for the gram-scale
synthesis. All the results above represent an efficient and eco-
friendly IL-catalyst for the thio-Michael addition of a,b-unsat-
urated amides.
[Nmm-PDO][Gly]
1
ꢀ
Colourless liquid; H NMR (D2O, 400 MHz, 25 C): d 4.30–4.20
(m, 1H), 3.97 (s, 4H), 3.66–3.39 (m, 8H), 3.23 (s, 3H), 1.81 (s, 2H).
13
ꢀ
C NMR (D2O, 100 MHz, 25 C) d 181.1, 66.4, 65.6, 63.6, 61.0,
60.6, 60.4, 48.3, 23.4. ESI-HRMS [Nmm-PDO]+ m/z calcd for
C8H18NO3 176.1281, found 176.1284; ESI-MS [Nmm-PDO]+
176.12; ESI-MS [NH2CH2COO]ꢁ m/z 74.01.
[Nbmm][Gly]
Colourless liquid; 1H NMR (D2O, 300 MHz, 25 ꢀC): d 3.95 (s, 4H),
3.50–3.31 (m, 6H), 3.10 (s, 3H), 1.82 (s, 2H), 1.76–1.61 (m, 2H),
1.41–1.24 (m, 2H), 0.88 (t, 3H). 13C NMR (D2O, 100 MHz, 25 ꢀC)
d 180.5, 65.1, 60.4, 59.5, 46.7, 44.6, 23.6, 22.9, 19.1, 12.9. ESI-MS
[Nbmm]+ m/z 158.25; ESI-MS [NH2CH2COO]ꢁ m/z 74.01.
General experimental procedures
General procedure for synthesis of compounds 3a–w
The reaction is carried out at room temperature in water or
solvent-free. NMR spectra were recorded on Bruker AVANCE III
HD 400 MHz; proton and carbon magnetic resonance spectra
(1H NMR and 13C NMR) were recorded using tetramethylsilane
(TMS) in the solvent of CDCl3 as the internal standard (1H NMR:
TMS at 0.00 ppm, CHCl3 at 7.26 ppm; 13C NMR: CDCl3 at 77.16
ppm) or were recorded using tetramethylsilane (TMS) in the
solvent of DMSO-d6 as the internal standard (1H NMR: TMS at
0.00 ppm, DMSO at 2.50 ppm; 13C NMR: DMSO at 39.51 ppm).
Sulfur-nucleophile (0.5 mmol), a,b-unsaturated amides (0.5
mmol), IL catalyst (10 mol%) and water (1 mL) was added into
25 mL Schlenk tube and stirred at room temperature. Upon
completion of the reaction (monitored by TLC), the reaction
mixture was extracted with ethyl acetate (3 ꢂ 5 mL), the organic
and aqueous layers were separated, and the aqueous layer was
extracted with EtOAc (2 ꢂ 5 mL). The combined organic layers
were dried over anhydrous Na2SO4, concentrated and puried
by column chromatography on silica gel employing petroleum
ether/ethyl acetate as eluent to afford target product 3 [the
products of 3z–3d0, 3f0 were prepared at 55 ꢀC under solvent-free
condition; upon completion of the reaction, the reaction
mixture was extracted with ethyl acetate (3 ꢂ 5 mL). The
combined organic layers were dried over anhydrous Na2SO4,
they were puried by column chromatography on silica gel
[Nmm-PDO][X] and [Nbmm][Gly]
Ionic liquids was synthesized by our previous method.2a
[Nmm-PDO][Cl]
1
White solid; H NMR (D2O, 400 MHz, 25 ꢀC): d 4.44–4.22 (m, using petroleum ether/ethyl acetate as the eluent].
1H), 4.03 (s, 4H), 3.72–3.46 (m, 8H), 3.30 (s, 3H). 13C NMR (D2O,
3-(Propylthio)propanamide (3a).19 Eluent: petroleum ether/
100 MHz, 25 ꢀC): d 66.4, 65.7, 63.7, 61.1, 60.9, 60.5, 48.4. ESI-MS ethyl acetate (4 : 1). Yield 72 mg (98%). White solid, mp 62–
[Nmm-PDO]+ 176.12.
63 ꢀC (lit.19 mp 59–61 ꢀC). 1H NMR (d6-DMSO, 400 MHz, 25 ꢀC)
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d 7.33 (s, 1H), 6.83 (s, 1H), 2.64 (t, J ¼ 7.4 Hz, 2H), 2.47 (t, J ¼
7.2 Hz, 2H), 2.31 (t, J ¼ 7.4 Hz, 2H), 1.59–1.47 (m, 2H), 0.93 (t, J ¼
7.3 Hz, 3H). 13C NMR (d6-DMSO, 100 MHz, 25 ꢀC) d 173.0, 36.1,
33.5, 27.3, 22.9, 13.7. ESI-MS [M + H]+ m/z 148.25; [M + Na]+
170.19.
3-(Thiophen-2-ylthio)propanamide (3i). Eluent: petroleum
ether/ethyl acetate (4 : 1). Yield 67 mg (72%). Yellow solid, mp
1
ꢀ
ꢀ
88–90 C. H NMR (CDCl3, 400 MHz, 25 C) d 7.30 (d, J ¼ 5.4,
1.3 Hz, 1H), 7.08 (d, J ¼ 3.5, 1.3 Hz, 1H), 6.92 (t, J ¼ 5.4, 3.5 Hz,
1H), 5.75 (d, J ¼ 120.5 Hz, 2H), 2.98 (t, J ¼ 7.2 Hz, 2H), 2.44 (t, J ¼
13
3-(Octylthio)propanamide (3b).19 Eluent: petroleum ether/
ethyl acetate (4 : 1). Yield 100 mg (92%). White solid, mp 90–
91 ꢀC (lit.19 mp 92–93 ꢀC). 1H NMR (CDCl3, 400 MHz, 25 ꢀC)
d 5.79 (s, 2H), 2.81 (t, J ¼ 7.2 Hz, 2H), 2.60–2.45 (m, 4H), 1.64–
1.53 (m, 2H), 1.42–1.23 (m, 10H), 0.88 (t, 3H). 13C NMR (CDCl3,
ꢀ
7.2 Hz, 2H). C NMR (CDCl3, 100 MHz, 25 C) d 173.3, 134.4,
133.6, 129.8, 127.7, 35.49, 33.98. ESI-HRMS [M + H]+ m/z calcd
for C7H10NOS2 188.0198, found 188.0210.
N,N-Dimethyl-3-(propylthio)propanamide
(3j).
Eluent:
petroleum ether/ethyl acetate (4 : 1). Yield 79 mg (90%). Yellow
liquid. 1H NMR (CDCl3, 400 MHz, 25 ꢀC) d 2.79 (s, 3H), 2.70 (s,
3H), 2.55 (t, 2H), 2.36 (t, J ¼ 7.6 Hz, 2H), 2.27 (t, J ¼ 7.3, 1.5 Hz,
2H), 1.43–1.30 (m, 2H), 0.73 (t, J ¼ 7.4, 1.4 Hz, 3H). 13C NMR
(CDCl3, 100 MHz, 25 ꢀC) d 171.0, 36.9, 35.1, 34.2, 33.6, 27.1, 22.7,
13.2. ESI-HRMS [M + H]+ m/z calcd for C8H18NOS 176.1104,
found 176.1115.
ꢀ
100 MHz, 25 C) d 173.8, 36.0, 32.4, 31.8, 29.6, 29.2, 28.9, 27.5,
22.7, 14.1. ESI-MS [M + H]+ m/z 218.28; [M + Na]+ 240.29.
3-(Dodecylthio)propanamide (3c). Eluent: petroleum ether/
ethyl acetate (4 : 1). Yield 68 mg (50%), solvent-free condition
yield 124 mg (91%). White solid, mp 84–86 ꢀC. 1H NMR (CDCl3,
ꢀ
400 MHz, 25 C) d 5.60 (d, J ¼ 94.4 Hz, 2H), 2.81 (t, J ¼ 7.2 Hz,
3-(Benzylthio)-N,N-dimethylpropanamide (3k).20 Eluent:
petroleum ether/ethyl acetate (4 : 1). Yield 103 mg (92%). Yellow
2H), 2.53 (m, J ¼ 14.2, 7.3 Hz, 4H), 1.67–1.53 (m, 5H), 1.41–1.19
(m, 19H), 0.88 (t, J ¼ 6.7 Hz, 3H). 13C NMR (d6-DMSO, 100 MHz,
25 ꢀC) d 173.1, 36.0, 31.8, 31.5, 29.6, 29.5, 29.2, 29.1, 28.7, 27.4,
22.6. ESI-HRMS [M + H]+ m/z calcd for C15H32NOS 274.2199,
found 274.2210.
1
ꢀ
liquid. H NMR (CDCl3, 400 MHz, 25 C) d 7.34–7.26 (m, 4H),
7.24–7.19 (m, 1H), 3.73 (s, 2H), 2.89 (d, J ¼ 8.4 Hz, 6H), 2.74 (t, J
¼ 8.2, 6.9 Hz, 2H), 2.48 (t, J ¼ 7.5 Hz, 2H). 13C NMR (CDCl3, 100
MHz, 25 ꢀC) d 171.1, 138.6, 128.8, 128.5, 127.0, 36.9, 35.4, 33.5,
27.0. ESI-HRMS [M + H]+ m/z calcd for C12H18NOS 224.1104,
found 224.1109.
3-(Cyclohexylthio)propanamide (3d).17 Eluent: petroleum
ether/ethyl acetate (4 : 1). Yield 82 mg (88%). White solid, mp
1
ꢀ
ꢀ
74–75 C. H NMR (d6-DMSO, 400 MHz, 25 C) d 7.35 (s, 1H),
6.85 (s, 1H), 2.66 (t, J ¼ 7.4 Hz, 3H), 2.30 (t, J ¼ 7.4 Hz, 2H), 1.89
(t, J ¼ 10.2, 4.9 Hz, 2H), 1.76–1.62 (m, 2H), 1.62–1.50 (m, 1H),
1.24 (m, J ¼ 14.3, 13.3, 7.1 Hz, 5H). 13C NMR (d6-DMSO, 100
MHz, 25 ꢀC) d 173.1, 43.0, 36.4, 33.7, 25.9, 25.7. ESI-MS [M + H]+
m/z 188.12; [M + Na]+ 210.11.
N,N-Dimethyl-3-(phenylthio)propanamide
(3l).
Eluent:
petroleum ether/ethyl acetate (4 : 1). Yield 98 mg (94%). Yellow
1
ꢀ
liquid. H NMR (CDCl3, 400 MHz, 25 C) d 7.26 (d, J ¼ 7.4 Hz,
2H), 7.19 (t, J ¼ 7.7 Hz, 2H), 7.08 (t, J ¼ 7.3 Hz, 1H), 3.15 (t, J ¼
7.5 Hz, 2H), 2.83 (d, J ¼ 6.8 Hz, 6H), 2.54 (t, J ¼ 7.5 Hz, 2H). 13
C
3-(Benzylthio)propanamide (3e).19 Eluent: petroleum ether/
ethyl acetate (4 : 1). Yield 85 mg (87%). White solid, mp 110–
111 ꢀC(lit.19 mp 104–105 ꢀC). 1H NMR (CDCl3, 400 MHz, 25 ꢀC)
d 7.35–7.22 (m, 5H), 5.73 (d, J ¼ 69.6 Hz, 2H), 3.74 (s, 2H), 2.72 (t,
J ¼ 7.2 Hz, 2H), 2.41 (t, J ¼ 7.2 Hz, 2H). 13C NMR (CDCl3, 100
MHz, 25 ꢀC) d 173.5, 138.2, 128.9, 128.6, 127.2, 36.7, 35.7, 27.0.
ESI-MS [M + H]+ m/z 196.14; [M + Na]+ 218.12.
NMR (CDCl3, 100 MHz, 25 ꢀC) d 170.9, 136.0, 129.1, 129.0, 126.0,
37.0, 35.4, 33.1, 28.9. ESI-HRMS [M + H]+ m/z calcd for
C
11H16NOS 210.0947, found 210.0947.
N,N-Dimethyl-3-(p-tolylthio)propanamide (3m). Eluent:
petroleum ether/ethyl acetate (4 : 1). Yield 107 mg (96%). Yellow
1
ꢀ
liquid. H NMR (CDCl3, 400 MHz, 25 C) d 7.18 (d, J ¼ 8.0 Hz,
2H), 7.01 (d, J ¼ 7.9 Hz, 2H), 3.14–3.05 (t, 2H), 2.83 (d, J ¼ 5.2 Hz,
6H), 2.51 (t, J ¼ 7.5 Hz, 2H), 2.22 (s, 3H). 13C NMR (CDCl3, 100
MHz, 25 ꢀC) d 171.0, 136.2, 132.1, 130.0, 129.7, 37.0, 35.4, 33.3,
29.6, 21.0. ESI-HRMS [M + H]+ m/z calcd for C12H18NOS
224.1104, found 224.1109.
3-(Phenylthio)propanamide (3f).14 Eluent: petroleum ether/
ethyl acetate (4 : 1). Yield 71 mg (78%). White solid, mp 116–
1
ꢀ
ꢀ
118 C. H NMR (CDCl3, 400 MHz, 25 C) d 7.40–7.34 (m, 2H),
7.33–7.27 (m, 2H), 7.24–7.18 (m, 1H), 5.71 (d, J ¼ 68.2 Hz, 2H),
3.20 (t, J ¼ 7.3 Hz, 2H), 2.52 (t, J ¼ 7.3 Hz, 2H). 13C NMR (CDCl3,
N-Phenyl-3-(propylthio)propanamide (3n). Eluent: petro-
leum ether/ethyl acetate (10 : 1). Yield 107 mg (96%). White
solid, mp 42–44 ꢀC. 1H NMR (CDCl3, 400 MHz, 25 ꢀC) d 8.53 (s,
1H), 7.43 (d, J ¼ 7.5 Hz, 2H), 7.17 (t, J ¼ 7.9 Hz, 2H), 6.98 (t, J ¼
7.4 Hz, 1H), 2.74 (t, J ¼ 7.2 Hz, 2H), 2.53 (t, J ¼ 7.3 Hz, 2H), 2.38
ꢀ
100 MHz, 25 C) d 173.3, 135.2, 129.8, 129.1, 126.5, 35.3, 29.1.
ESI-MS [M + H]+ m/z 182.18; [M + Na]+ 204.15.
3-(p-Tolylthio)propanamide (3g).17 Eluent: petroleum ether/
ethyl acetate (4 : 1). Yield 80 mg (82%). White solid, mp 111–
113 ꢀC. 1H NMR (CDCl3, 400 MHz, 25 ꢀC) d 7.28 (d, 2H), 7.12 (d, J
¼ 7.9 Hz, 2H), 5.69 (d, J ¼ 53.8 Hz, 2H), 3.15 (t, J ¼ 7.3 Hz, 2H),
2.49 (t, J ¼ 7.3 Hz, 2H), 2.33 (s, 3H). 13C NMR (CDCl3, 100 MHz,
25 ꢀC) d 173.38, 136.84, 131.30, 130.68, 129.87, 35.39, 29.89,
21.05. ESI-MS [M + H]+ m/z 196.14; [M + Na]+ 218.12.
(t, J ¼ 7.3 Hz, 2H), 1.55–1.40 (m, 2H), 0.85 (t, J ¼ 7.4 Hz, 3H). 13
C
NMR (CDCl3, 100 MHz, 25 ꢀC) d 170.4, 138.0, 128.9, 124.4, 120.4,
37.6, 34.4, 27.7, 22.9, 13.5. ESI-HRMS [M + H]+ m/z calcd for
C
12H18NOS 224.1104, found 224.1088.
3-(Octylthio)-N-phenylpropanamide (3o). Eluent: petroleum
3-[(4-Chlorophenyl)thio]propanamide (3h).17 Eluent: petro-
leum ether/ethyl acetate (4 : 1). Yield 95 mg (88%). White solid,
ether/ethyl acetate (10 : 1). Yield 117 mg (80%). White solid, mp
57–58 ꢀC. 1H NMR (CDCl3, 400 MHz, 25 ꢀC) d 7.76 (s, 1H), 7.52
(d, 2H), 7.31 (t, J ¼ 7.9 Hz, 2H), 7.10 (t, J ¼ 7.4 Hz, 1H), 2.89 (t, J ¼
7.0 Hz, 2H), 2.63 (t, J ¼ 7.0 Hz, 2H), 2.56 (t, J ¼ 7.4 Hz, 2H), 1.64–
1.54 (m, 2H), 1.41–1.20 (m, 10H), 0.88 (t, J ¼ 6.7 Hz, 3H). 13C
NMR (CDCl3, 100 MHz, 25 ꢀC) d 169.7, 137.8, 129.0, 124.4, 119.9,
1
ꢀ
ꢀ
mp 116–117 C. H NMR (CDCl3, 400 MHz, 25 C) d 7.34–7.23
(m, 4H), 5.63 (d, J ¼ 60.2 Hz, 2H), 3.19 (t, J ¼ 7.3 Hz, 2H), 2.51 (t,
J ¼ 7.3 Hz, 2H). 13C NMR (CDCl3, 100 MHz, 25 ꢀC) d 172.9, 133.9,
132.5, 131.1, 129.2, 35.2, 29.3. ESI-MS [M + H]+ m/z 216.11; [M +
Na]+ 238.09.
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37.8, 32.5, 31.8, 29.6, 29.2, 28.9, 27.7, 22.7, 14.1. ESI-HRMS [M + condition yield 66 mg (60%). White solid, mp 38–40 ꢀC. 1H
H]+ m/z calcd for C17H28NOS 294.1886, found 294.1890.
NMR (CDCl3, 400 MHz, 25 ꢀC) d 7.91 (s, 1H), 7.44 (d, J ¼ 7.9 Hz,
3-(Dodecylthio)-N-phenylpropanamide (3p). Eluent: petro- 2H), 7.22 (t, J ¼ 7.8 Hz, 2H), 7.02 (t, J ¼ 7.4 Hz, 1H), 5.79–5.61 (m,
leum ether/ethyl acetate (10 : 1). Yield 77 mg (44%), solvent-free 1H), 5.14–4.91 (m, 2H), 3.08 (d, J ¼ 7.2 Hz, 2H), 2.74 (t, J ¼
condition yield 142 mg (81%). White solid, mp 75–77 ꢀC. 1H 7.1 Hz, 2H), 2.53 (t, J ¼ 7.1 Hz, 2H). 13C NMR (CDCl3, 100 MHz,
ꢀ
NMR (CDCl3, 400 MHz, 25 C) d 7.66–7.42 (m, 3H), 7.33 (t, J ¼ 25 ꢀC) d 169.9, 137.8, 134.0, 129.0, 124.4, 120.1, 117.5, 37.4, 35.1,
7.9 Hz, 2H), 7.11 (t, J ¼ 7.4 Hz, 1H), 2.90 (t, J ¼ 7.0 Hz, 2H), 2.64 26.4. ESI-HRMS [M + H]+ m/z calcd for C12H16NOS 222.0947,
(t, J ¼ 7.0 Hz, 2H), 2.57 (t, J ¼ 7.4 Hz, 2H), 1.65–1.56 (m, 2H), found 222.0952.
1.46–1.16 (m, 18H), 0.88 (t, J ¼ 6.7 Hz, 3H). 13C NMR (CDCl3, 100
3-[(2-Hydroxyethyl)thio]-N-phenylpropanamide (3w). Eluent:
MHz, 25 ꢀC) d 169.8, 169.6, 137.8, 129.0, 124.4, 120.0, 119.9, petroleum ether/ethyl acetate (10 : 1). Yield 107 mg (95%).
1
50.9, 37.8, 37.7, 32.5, 31.9, 29.7, 29.6, 29.5, 29.4, 29.3, 28.9, 27.7, White solid, mp 74–76 ꢀC. H NMR (CDCl3, 300 MHz, 25 ꢀC)
22.7, 14.2. ESI-HRMS [M + H]+ m/z calcd for C21H36NOS d 7.92 (s, 1H), 7.54 (d, J ¼ 7.9 Hz, 2H), 7.33 (t, J ¼ 7.6 Hz, 2H),
350.2512, found 350.2517.
7.13 (t, J ¼ 7.4 Hz, 1H), 3.80 (t, J ¼ 5.4 Hz, 2H), 2.94 (t, J ¼ 6.9 Hz,
3-(Cyclohexylthio)-N-phenylpropanamide
(3q).
Eluent: 2H), 2.85 (s, 1H), 2.77 (t, J ¼ 5.8 Hz, 2H), 2.67 (t, J ¼ 6.9 Hz, 2H).
13
ꢀ
petroleum ether/ethyl acetate (10 : 1). Yield 112 mg (85%).
C NMR (CDCl3, 100 MHz, 25 C) d 169.7, 137.7, 129.0, 124.5,
1
White solid, mp 85–86 ꢀC. H NMR (CDCl3, 400 MHz, 25 ꢀC) 120.0, 61.0, 37.8, 35.6, 27.5. ESI-HRMS [M + H]+ m/z calcd for
d 7.78 (s, 1H), 7.52 (d, 2H), 7.31 (t, J ¼ 7.9 Hz, 2H), 7.11 (t, 1H),
C
11H16NO2S 226.0896, found 226.0897.
2-Methyl-3-(propylthio)propanamide (3x). Eluent: petroleum
2.91 (t, J ¼ 7.1 Hz, 2H), 2.75–2.66 (m, 1H), 2.62 (t, J ¼ 7.1 Hz, 2H),
2.03–1.94 (m, 2H), 1.80–1.73 (m, 2H), 1.65–1.57 (m, 1H), 1.38– ether/ethyl acetate (6 : 1). Yield 79 mg (98%). Yellow solid, mp
13
1
ꢀ
1.22 (m, 5H). C NMR (CDCl3, 100 MHz, 25 C) d 169.7, 137.8, 46–47 ꢀC. H NMR (CDCl3, 400 MHz, 25 ꢀC) d 6.46–5.84 (d, 2H),
129.0, 124.4, 119.9, 44.0, 38.0, 33.6, 26.1, 25.8, 25.7. ESI-HRMS 2.87–2.77 (m, 1H), 2.62–2.43 (m, 4H), 1.67–1.53 (m, 2H), 1.29–
[M + H]+ m/z calcd for C15H22NOS 264.1417, found 264.1416.
1.21 (d, 3H), 1.04–0.91 (t, 3H). 13C NMR (CDCl3, 100 MHz, 25 ꢀC)
3-(Benzylthio)-N-phenylpropanamide (3r). Eluent: petroleum d 177.7, 41.3, 35.9, 35.0, 23.0, 17.6, 13.5. ESI-HRMS [M + H]+ m/z
ether/ethyl acetate (10 : 1). Yield 117 mg (86%). White solid, mp calcd for C7H16NOS 162.0947, found 162.0947.
1
2-Methyl-3-(phenylthio)propanamide (3y).6d Eluent: petro-
ꢀ
ꢀ
80–82 C. H NMR (d6-DMSO, 400 MHz, 25 C) d 9.98 (s, 1H),
7.59 (d, J ¼ 8.0 Hz, 2H), 7.35–7.22 (m, 7H), 7.03 (t, J ¼ 7.4 Hz, leum ether/ethyl acetate (6 : 1). Yield 88 mg (90%). Yellow solid,
1H), 3.78 (s, 2H), 2.66 (t, J ¼ 6.3 Hz, 2H), 2.61 (t, J ¼ 6.2 Hz, 2H). mp 55–56 ꢀC. 1H NMR (CDCl3, 400 MHz, 25 ꢀC) d 7.32–7.26 (m,
13C NMR (d6-DMSO, 100 MHz, 25 ꢀC) d 167.0, 139.6, 139.0, 2H), 7.26–7.18 (m, 2H), 7.17–7.09 (m, 1H), 5.62 (d, J ¼ 76.1 Hz,
129.3, 129.2, 128.9, 127.3, 123.6, 119.5, 36.8, 35.4, 26.9. ESI- 2H), 3.25–3.10 (m, 1H), 2.94–2.84 (m, 1H), 2.47–2.36 (m, 1H),
HRMS [M + H]+ m/z calcd for C16H18NOS 272.1104, found 1.20 (d, J ¼ 6.9 Hz, 3H). 13C NMR (CDCl3, 100 MHz, 25 ꢀC)
272.1100.
d 177.0, 135.8, 129.6, 129.1, 126.4, 40.4, 37.3, 17.6. ESI-MS [M +
N-Phenyl-3-(phenylthio)propanamide (3s).21 Eluent: petro- H]+ m/z 196.16; [M + Na]+ 218.14.
leum ether/ethyl acetate (10 : 1). Yield 117 mg (91%). White
N-Phenyl-3-(propylthio)butanamide (3z). Eluent: petroleum
solid, mp 84–85 ꢀC. 1H NMR (CDCl3, 400 MHz, 25 ꢀC) d 7.48 (d, ether/ethyl acetate (10 : 1). Yield 93 mg (78%). Yellow liquid. 1H
2H), 7.42 (s, 1H), 7.38 (d, J ¼ 7.4 Hz, 2H), 7.34–7.27 (m, 4H), 7.22 NMR (CDCl3, 400 MHz, 25 ꢀC) d 8.26 (s, 1H), 7.45 (d, J ¼ 8.0 Hz,
(t, 1H), 7.10 (t, J ¼ 7.4 Hz, 1H), 3.28 (t, J ¼ 7.1 Hz, 2H), 2.64 (t, J ¼ 2H), 7.21 (t, J ¼ 7.8 Hz, 2H), 7.01 (t, J ¼ 7.4 Hz, 1H), 3.28–3.11 (m,
13
ꢀ
7.2 Hz, 2H). C NMR (CDCl3, 100 MHz, 25 C) d 169.4, 137.7, 1H), 2.57–2.39 (m, 4H), 1.59–1.46 (m, 2H), 1.27 (d, J ¼ 6.8 Hz,
135.2, 129.7, 129.2, 129.0, 126.6, 124.5, 120.1, 37.1, 29.3. ESI-MS 3H), 0.89 (t, J ¼ 7.4 Hz, 3H). 13C NMR (CDCl3, 100 MHz, 25 ꢀC)
[M + H]+ m/z 258.23; [M + Na]+ 280.21.
d 169.6, 137.9, 129.0, 124.4, 120.2, 45.2, 36.9, 33.1, 23.1, 21.8,
N-Phenyl-3-(p-tolylthio)propanamide (3t). Eluent: petroleum 13.6. ESI-HRMS [M + H]+ m/z calcd for C13H20NOS 238.1260,
ether/ethyl acetate (10 : 1). Yield 119 mg (88%). White solid, mp found 238.1268.
94–96 ꢀC. 1H NMR (CDCl3, 400 MHz, 25 ꢀC) d 7.64–7.41 (m, 3H),
N-Phenyl-3-(phenylthio)butanamide (3a0). Eluent: petroleum
7.34–7.25 (m, 4H), 7.10 (t, J ¼ 7.9 Hz, 3H), 3.22 (t, J ¼ 7.2 Hz, 2H), ether/ethyl acetate (10 : 1). Yield 81 mg (60%). White solid, mp
2.59 (t, J ¼ 7.1 Hz, 2H), 2.31 (s, 3H). 13C NMR (CDCl3, 100 MHz, 60–61 ꢀC. 1H NMR (CDCl3, 400 MHz, 25 ꢀC) d 7.80 (d, J ¼
25 ꢀC) d 169.5, 137.7, 136.9, 131.3, 130.7, 129.9, 129.0, 124.4, 25.2 Hz, 1H), 7.41 (d, J ¼ 8.0 Hz, 2H), 7.34 (d, J ¼ 7.1 Hz, 2H),
120.1, 37.2, 30.1, 21.1. ESI-HRMS [M + H]+ m/z calcd for 7.26–7.10 (m, 6H), 7.01 (t, J ¼ 7.4 Hz, 1H), 3.76–3.59 (m, 1H),
C
16H18NOS 272.1104, found 272.1100.
3-[(4-Chlorophenyl)thio]-N-phenylpropanamide (3u). Eluent:
2.67–2.50 (m, 1H), 2.49–2.27 (m, 1H), 1.29 (d, J ¼ 6.8 Hz, 3H).
13
ꢀ
C NMR (CDCl3, 100 MHz, 25 C) d 169.1, 137.7, 133.9, 132.4,
petroleum ether/ethyl acetate (10 : 1). Yield 133 mg (91%). 129.1, 129.0, 127.5, 124.5, 120.1, 44.5, 40.0, 21.0. ESI-HRMS [M +
1
White solid, mp 91–93 ꢀC. H NMR (CDCl3, 400 MHz, 25 ꢀC) H]+ m/z calcd for C16H18NOS 272.1104, found 272.1110.
d 7.53–7.42 (m, 2H), 7.38–7.20 (m, 8H), 7.12 (t, J ¼ 7.4 Hz, 1H),
3-(Allylthio)-N-phenylbutanamide (3b0). Eluent: petroleum
3.28 (t, J ¼ 7.1 Hz, 2H), 2.64 (t, J ¼ 7.1 Hz, 2H). 13C NMR (CDCl3, ether/ethyl acetate (10 : 1). Yield 49 mg (42%). Yellow solid, mp
100 MHz, 25 ꢀC) d 168.8, 137.5, 133.7, 132.6, 131.1, 129.3, 129.1, 55–56 ꢀC. 1H NMR (CDCl3, 400 MHz, 25 ꢀC) d 7.81 (s, 1H), 7.52
124.6, 119.9, 37.1, 29.6. ESI-HRMS [M + H]+ m/z calcd for C15
-
(d, J ¼ 7.2 Hz, 1H), 7.32 (t, J ¼ 7.9 Hz, 2H), 7.11 (t, J ¼ 7.4 Hz,
1H), 5.94–5.72 (m, 1H), 5.16 (d, J ¼ 16.9, 1.6 Hz, 1H), 5.11 (d, J ¼
H15ClNOS 292.0557, found 292.0554.
3-(Allylthio)-N-phenylpropanamide (3v). Eluent: petroleum 10.0 Hz, 1H), 3.33–3.17 (m, 3H), 2.67–2.57 (m, 1H), 2.57–2.46
ether/ethyl acetate (10 : 1). Yield 38 mg (34%), solvent-free (m, 1H), 1.37 (d, J ¼ 6.8 Hz, 3H). 13C NMR (CDCl3, 100 MHz,
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25 ꢀC) d 169.0, 137.8, 134.3, 129.0, 124.4, 120.0, 117.4, 45.1, 36.0,
34.3, 21.6. ESI-HRMS [M + H]+ m/z calcd for C16H18NOS
236.1104, found 236.1110.
Notes and references
1 (a) R. S. Tukhvatshin, A. S. Kucherenko, Y. V. Nelyubina and
S. G. Zlotin, ACS Catal., 2017, 7, 2981; (b) C. Yang, W.-Q. Su
and D.-Z. Xu, RSC Adv., 2016, 6, 99656; (c) Y.-Y. Song,
H.-W. Jing, B. Li and D.-S. Bai, Chem.–Eur. J., 2011, 17, 8731.
2 (a) H. Xu, L.-Y. Pan, X.-M. Fang, B.-Y. Liu, W.-K. Zhang,
M.-H. Lu, Y.-Q. Xu, T. Ding and H.-B. Chang, Tetrahedron
Lett., 2017, 58, 2360; (b) A.-G. Ying, Y.-X. Ni, S.-L. Xu,
S. Liu, J.-G. Yang and R.-R. Li, Ind. Eng. Chem. Res., 2014,
53, 5678; (c) D.-Z. Xu, Y.-J. Liu, S. Shi and Y.-M. Wang,
Green Chem., 2010, 12, 514.
N-Phenyl-3-(propylthio)hexanamide (3c0). Eluent: petroleum
ether/ethyl acetate (10 : 1). Yield 117 mg (88%). White solid, mp
55–57 ꢀC. 1H NMR (CDCl3, 400 MHz, 25 ꢀC) d 8.33 (s, 1H), 7.46
(d, 2H), 7.21 (t, J ¼ 7.7 Hz, 2H), 7.00 (t, J ¼ 7.4 Hz, 1H), 3.11–2.96
(m, 1H), 2.58–2.37 (m, 4H), 1.60–1.28 (m, 6H), 0.88 (t, J ¼ 7.3 Hz,
3H), 0.82 (t, J ¼ 7.1 Hz, 3H). 13C NMR (CDCl3, 100 MHz, 25 ꢀC)
d 169.9, 138.0, 128.9, 124.3, 120.1, 44.0, 42.5, 37.7, 33.3, 23.2,
20.1, 13.9, 13.6. ESI-HRMS [M + H]+ m/z calcd for C16H18NOS
266.1573, found 266.1574.
N-3-Diphenyl-3-(propylthio)propanamide
(3d0).
Eluent:
3 (a) W. Senapak, R. Saeeng and U. Sirion, RSC Adv., 2017, 7,
30380; (b) L.-C. Feng, Y.-W. Sun, W.-J. Tang, L.-J. Xu,
K.-L. Lam, Z.-Y. Zhou and A. S. C. Chan, Green Chem.,
2010, 12, 949.
petroleum ether/ethyl acetate (10 : 1). Yield 112 mg (75%).
1
White solid, mp 55–56 ꢀC. H NMR (CDCl3, 400 MHz, 25 ꢀC)
d 7.36–7.09 (m, 9H), 7.02–6.93 (m, 1H), 4.27 (t, J ¼ 7.5 Hz, 1H),
2.89–2.67 (m, 2H), 2.32–2.13 (m, 2H), 1.53–1.30 (m, 2H), 0.79 (t,
J ¼ 7.3 Hz, 3H). 13C NMR (CDCl3, 100 MHz, 25 ꢀC) d 167.6, 140.8,
136.6, 127.8, 127.6, 126.6, 126.4, 123.4, 119.2, 44.9, 44.0, 32.5,
21.5, 12.4. ESI-HRMS [M + H]+ m/z calcd for C18H22NOS
300.1417, found 300.1425.
N-Phenyl-3-(propylthio)acrylamide (3e0). Eluent: petroleum
ether/ethyl acetate (10 : 1). Yield 46 mg (42%). Yellow solid, mp
55–56 ꢀC. 1H NMR (CDCl3, 400 MHz, 25 ꢀC) d 7.51 (d, J ¼ 8.0 Hz,
2H), 7.29 (s, 1H), 7.21 (t, 2H), 7.00 (t, J ¼ 7.4 Hz, 1H), 6.91 (d, J ¼
9.9 Hz, 1H), 5.86 (d, J ¼ 10.0 Hz, 1H), 2.65 (t, J ¼ 7.3 Hz, 2H),
1.67–1.58 (m, 2H), 0.95 (t, J ¼ 7.3 Hz, 3H). 13C NMR (CDCl3, 100
MHz, 25 ꢀC) d 163.5, 146.8, 137.1, 127.9, 122.9, 118.5, 114.3,
37.5, 22.6, 12.1. ESI-HRMS [M + H]+ m/z calcd for C12H16NOS
222.0947, found 222.0952.
N-Phenyl-3,5-bis(propylthio)hexanamide (3f0). Eluent: petro-
leum ether/ethyl acetate (10 : 1). Yield 105 mg (62%). Yellow
liquid. 1H NMR (400 MHz, CDCl3) d 8.07 (d, J ¼ 6.4 Hz, 1H), 7.46
(t, J ¼ 8.0, 4.9 Hz, 2H), 7.24 (t, J ¼ 7.7 Hz, 2H), 7.03 (t, J ¼ 7.4 Hz,
1H), 3.42–3.15 (m, 1H), 3.07–2.86 (m, 1H), 2.62–2.39 (m, 6H),
1.81–1.44 (m, 6H), 1.23 (t, J ¼ 6.7, 5.4 Hz, 3H), 0.96–0.85 (m, 6H).
13C NMR (100 MHz, CDCl3) d 169.1, 137.9, 137.8, 129.0, 128.9,
124.3, 124.2, 120.0, 119.9, 99.9, 44.4, 43.8, 42.6, 42.5, 40.8, 40.3,
37.8, 37.1, 33.5, 33.1, 32.3, 31.9, 23.3, 23.2, 23.1, 22.6, 21.4, 13.7,
13.6. ESI-HRMS [M + H]+ m/z calcd for C18H30NOS2 340.1763,
found 340.1773.
4 R. L. J. Vekariya, J. Mol. Liq., 2017, 227, 44.
5 (a) Z.-C. Geng, N. Li, J. Chen, X.-F. Huang, B. Wu, G.-G. Liu
and X.-W. Wang, Chem. Commun., 2012, 48, 4713; (b)
A. Kumar, V. D. Tripathi, P. Kumar, L. P. Gupta, R. Trivedi,
H. Bid, V. L. Nayak, J. A. Siddiqui, B. Chakravarti,
R. Saxena, A. Dwivedi, M. I. Siddiquee, U. Siddiqui,
R. Konwar and N. Chattopadhyay, Bioorg. Med. Chem.,
2011, 19, 5409; (c) J. P. Cherkauskas and T. Cohen, J. Org.
Chem., 1992, 57, 6.
6 (a) G.-L. Huang and X. Li, Curr. Org. Chem., 2017, 14, 568; (b)
C. F. H. Allen, W. J. Humphlett and J. O. Fournier, Can. J.
Chem., 1964, 42, 2616; (c) L. A. Gorthey, M. Vairamani and
C. J. Djerassi, J. Org. Chem., 1985, 50, 4173; (d)
F. M. Moghaddam, G. R. Bardajee and R. O. C. Veranlou,
Synth. Commun., 2005, 35, 2427.
7 (a) A. C. Breman, S. E. M. Telderman, R. P. M. van Santen,
J. I. Scott, J. H. van Maarseveen, S. Ingemann and
H. Hiemstra, J. Org. Chem., 2015, 80, 10561; (b)
A. Mohammad, Tetrahedron Lett., 2012, 53, 3683; (c)
P. McDaid, Y. Chen and L. Deng, Angew. Chem., Int. Ed.,
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Conflicts of interest
There are no conicts to declare.
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Acknowledgements
This work was supported by National Natural Science Founda-
tion of China (Grant No. 21502042, 51403051, 21477033,
21204018), Scientic Research Key Project Fund of Henan
Provincial Education Department (Grant No. 15A150041,
16A150003), Scientic Research Fund of Henan University (No.
2013YBZR008).
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