Deep eutectic solvent promoted hydrothiocyanation of alkynoates leading to Z-3-thiocyanatoacrylates

Article abstract of DOI:10.1016/j.tet.2019.07.014

A mild and efficient protocol for the selective construction of Z-3-thiocyanatoacrylates is described. Various alkynoates reacted with KSCN and H₂O by using cheap and recyclable deep eutectic solvent as the catalyst and reaction media to produce the corresponding products in excellent yields with mild reaction conditions and wide substrate scope.

Full text of DOI:10.1016/j.tet.2019.07.014

Accepted Manuscript
Deep eutectic solvent promoted hydrothiocyanation of alkynoates leading to Z-3-
thiocyanatoacrylates
Meng Sun, Jun Jiang, Jialiang Chen, Qiao Yang, Xianyong Yu
PII:
S0040-4020(19)30756-2
https://doi.org/10.1016/j.tet.2019.07.014
TET 30456
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 28 June 2019
Accepted Date: 8 July 2019
Please cite this article as: Sun M, Jiang J, Chen J, Yang Q, Yu X, Deep eutectic solvent promoted
hydrothiocyanation of alkynoates leading to Z-3-thiocyanatoacrylates, Tetrahedron (2019), doi: https://
doi.org/10.1016/j.tet.2019.07.014.
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Deep eutectic solvent catalyzed hydrothiocyanation
of alkynoates leading to Z-3-thiocyanatoacrylates
Meng Sun, Jun Jiang,* Jialiang Chen, Qiao Yang, Xianyong Yu*
School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Taoyuan Road
No. 9, Xiangtan 411201, China
A mild and efficient method for the selective construction of Z-3-thiocyanatoacrylates by using cheap and
recyclable deep eutectic solvent as the catalyst and reaction media is described.
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Graphical Abstract
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Deep eutectic solvent promoted hydrothiocyanation
of alkynoates leading to Z-3-thiocyanatoacrylates
Meng Sun, Jun Jiang,* Jialiang Chen, Qiao Yang, Xianyong Yu*
School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Taoyuan Road
No. 9, Xiangtan 411201, China
A mild and efficient method for the selective construction of Z-3-thiocyanatoacrylates by using cheap and
recyclable deep eutectic solvent as the catalyst and reaction media is described.
O
H2O (1 equv.)
O
NCS
R1
OR2
KSCN (1.3 equiv.)
OR2
ChCl/glycolic acid (1:2) (3 equiv.)
H
R1
24 examples, up to 95% Yield
Fonts or abstract dimensions should not be changed or altered.

1
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Tetrahedron
journal homepage: www.elsevier.com
Deep eutectic solvent promoted hydrothiocyanation of alkynoates leading to Z-3-
thiocyanatoacrylates
Meng Sun, Jun Jiang,* Jialiang Chen, Qiao Yang, Xianyong Yu*
School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Taoyuan Road No. 9, Xiangtan 411201, China
ARTICLE INFO
ABSTRACT
A mild and efficient protocol for the selective construction of Z-3-thiocyanatoacrylates is
described. Various alkynoates reacted with KSCN and H2O by using cheap and recyclable
deep eutectic solvent as the catalyst and reaction media to produce the corresponding products
in excellent yields with mild reaction conditions and wide substrate scope.
Article history:
Received
Received in revised form
Accepted
Available online
Keywords:
deep eutectic solvent
KSCN
2019 Elsevier Ltd. All rights reserved
.
alkynoate
green chemistry
Z-3-thiocyanatoacrylates
1. Introduction
inexpensive and readily accessibility. A number of organic
transformation with DES as catalyst or reaction media have been
developed during the past few years.12 However, a novel method
for the regio- and stereoselective hydrothiocyanation of various
alkynoates to access Z-3-thiocyanatoacrylates has never been
reported. Herein, we report an environment-friendly method for
the selective synthesis of Z-3-thiocyanatoacrylates through DES-
catalyzed hydrothiocyanation of alkynoates (Scheme 1b). In this
process, both the high efficiency and excellent selectivities were
achieved with the help of hydrogen bond.
The organosulfur compounds are fundamental motifs in
organic chemistry because they ubiquitously appear in natural
products, pharmaceuticals and fine chemicals.1,2 Among
numerous sulfur-containing compounds, organic thiocyanates are
a useful structural motif found in various biologically active
natural products, unnatural drugs, and functional materials.3 They
also serve as versatile building blocks toward a broad range of
organosulfur compounds.4 Over the past years, a number of
methods have been well-established for the synthesis of alkyl5,
alkenyl,6 and aromatic thiocyanates7. However, the novel and
practical
protocol
for
the
direct
construction
of
thiocyanatoacrylate, particularly regio- and stereoselective
synthesis of Z-3-thiocyanatoacrylates from simple and safe raw
materials under environmentally friendly conditions is still
remains rarely. For example, He and co-workers has pioneered a
direct construction of Z-3-thiocyanatoacrylates through room-
temperature ionic liquid-catalyzed catalyzed reaction of
alkynoates8, KSCN and water9. Although this methodology
represents a remarkable advance, it still needs to use toxic and
expensive ionic liquids and proceeds with moderate
stereoselectivities (Scheme 1a). Improved protocols for the
preparation selective regio- and stereoselective synthesis of Z-3-
thiocyanatoacrylates are therefore highly desirable.
Green Chemistry emphasizes the establishment of
environmentally friendly chemical reaction that avoids the usage
of toxic reagents and the utilization of eco-friendly substances
and nontoxic solvents.10 Recently, deep eutectic solvents (DES)
have attracted much attention from synthetic and pharmaceutical
chemists.11 DES not only has the close physico-chemical
properties with ionic liquid, but also has a lot of advantages than
ionic liquid, including nontoxicity, simple and green preparation,
Scheme 1. Synthetic route of Z-3-thiocyanatoacrylates
2. Results and discussion
To find the optimized conditions for the construction of Z-3-
thiocyanatoacrylates, the reaction of benzyl propiolate (1a),
KSCN and water was selected as the model reaction. We first
performed the hydrothiocyanation reaction using hydrochloric
acid (1M) as the solvent at ambient temperature for 10 h, and a
20% yield of (Z)-benzyl 3-thiocyanatoacrylate (2a) was obtained
with complex mixtures that included un-reacted substrate 1a.
Next, the effect of solvent on the hydrothiocyanation reaction
efficiency was investigated (entires 2-10). These results revealed
that deep eutectic ChCl/glycolic acid (1:2, 1 mL) was a superior

2
Tetrahedron
ACCEPTED MANUSCRIPT
reaction medium with a 52% NMR yield (entry 5). Glycolic acid
aqueous solution or ChCl aqueous aqueous solution alone gave
low or no conversions of 1a (entries 3 and 10). These obvious
differences suggested that the synergetic function of glycolic acid
and ChCl resulted in such an efficient conversion. Decreasing the
loading of ChCl/glycolic acid to 3 equivalents had virtually no
effect on the yield. Attempted to lower the reaction medium
loading to 2 equivalents was unsuccessful and yield dropped to
45% (entry 13). Switching the thiocyanate salt from KSCN to
NaSCN or NH4SCN led to a lower yield of 2a by prolong the
reaction time to 16 hour. Further optimization of the optimal
amount of KSCN (entries 12 and 16-18) showed that 1.3
equivalents of KSCN (entry 16) was the suitable loading.
Elevating the reaction temperature from room temperature to
50ꢀ not only resulted in an excellent yield of 2a but also
accelerated the reaction rate. Further increasing the reaction
temperature to 60ꢀ did not improve the reaction efficiency
(entry 20). No conversation of 1a was detected in the absence of
deep eutectic ChCl/glycolic acid (entry 21).
2k). All primary, secondary and tertiary alkyl alcohol esters were
compatible under the standard reaction conditions. The present
method also works well with aromatic, polycyclic aromatic and
heteroaromatic alcohol esters, delivering the corresponding
products in good to excellent yields (2l - 2p). Propargylic
carboxylates containing natural alcohol, such as furfuryl alcohol,
cinnamyl alcohol and piperonyl alcohol, were also well-tolerated
under optimal conditions, leading to the corresponding products
in good yields (2q - 2s). The (2Z,2'Z)-ethane-1,2-diyl bis(3-
thiocyanatoacrylate) 2t was obtained in 93% yield by direct
double thiocyanation under the optimal conditions. Furthermore,
the relatively low activity of internal alkynoates, such as but-3-
yn-2-one and diethyl acetylenedicarboxylate can also be used as
the substrates, furnishing the desired thiocyanation products (2u -
2w) in good yields and excellent stereoselectivities. However,
when 4,4,4-trifluorobut-2-ynoate or 3-phenylpropiolate were
used as reaction substrates, only a trace amount of the desired
product could be observed.
Table 2. Substrate scopea, b
Table 1. Optimization of reaction conditionsa
H2O (1 equiv.)
KSCN (1.3 equiv.)
NCS
CO2R2
H
CO2R2
ChCl/glycolic acid (1:2) (3 equiv.)
50 oC, 10 h
R2
R1
CO2Bn NCS
NCS
H
CO2Me NCS
CO2Et
SCN O
Me
5
H
O
H
H
H
H
H
H
2a
2b
2c
, 92%, 26/1
, 83%, 28/1
SCN O
, 93%, 25/1
2d
, 76%, 29/1
Entry
Solvent
[SCN]
Yieldb
Z/Eb
SCN O
SCN O
(X equiv)
KSCN (1.5)
OH
OMe
1
2
HCl (1M, 1mL)
20
15
10:1
10:1
11:1
23:1
25:1
22:1
20:1
24:1
--
H
O
H
O
H
O
H
2f
HOAc (1M, 1mL)
KSCN (1.5)
KSCN (1.5)
KSCN (1.5)
KSCN (1.5)
KSCN (1.5)
KSCN (1.5)
KSCN (1.5)
KSCN (1.5)
KSCN (1.5)
KSCN (1.5)
KSCN (1.5)
KSCN (1.5)
H
2e
H
2g
, 91%, 32/1
, 88%, 30/1
,82%, 30/1
3
glycolic acid (1M, 1mL)
28
nPr
nPr
SCN O
4
ChCl/glycolicacid(1:2)(1M, 1mL)
ChCl/glycolic acid(1:2)(1 mL)
ChCl/oxalic acid(1:1)(1 mL)
ChCl/citric acid(1:1)(1 mL)
ChCl/glycolic acid(1:1)(1mL)
ChCl/urea (1:1)(1mL)
40
SCN O
SCN O
Br
OTs
5
52
H
O
H
O
H
H
O
6
20
H
H
H
2h
7
25
2i
2j
, 79%, 24/1
, 82%, 21/1
, 84%, 30/1
8
40
SCN O
Me
Me
SCN O
SCN O
9
trace
N.D.
52
H
O
Me
O
H
O
10
11c
12
13
14
15
16
17
18
19d
20e
21d
ChCl (1 M, 1mL)
--
H
H
H
ChCl/glycolic acid(1:2) (5 equiv.)
ChCl/glycolic acid(1:2) (3 equiv.)
ChCl/glycolic acid(1:2) (2 equiv.)
>25:1
>25:1
>25:1
>25:1
>25:1
>25:1
>25:1
>25:1
>25:1
>25:1
--
2k
, 78%, 36/1
2l
2m
, 75%, 14/1
, 78%, 30/1
52
O
SCN
H
Me
SCN O
45
SCN O
O
ChCl/glycolic acid(1:2) (3 equiv.) NaSCN (1.5)
48
H
O
H
H
O
H
S
H
NH4SCN (1.5)
KSCN (1.3)
KSCN (1.2)
KSCN (1.1)
KSCN (1.3)
KSCN (1.3)
KSCN (1.3)
ChCl/glycolic acid(1:2) (3 equiv.)
ChCl/glycolic acid(1:2) (3 equiv.)
ChCl/glycolic acid(1:2) (3 equiv.)
ChCl/glycolic acid(1:2) (3 equiv.)
ChCl/glycolic acid(1:2) (3 equiv.)
ChCl/glycolic acid(1:2) (3 equiv.)
--
43
H
52
2o
2p
, 95%, 38/1
, 83%, 28/1
O
2n
, 74%, 14/1
48
SCN O
H
SCN O
SCN O
43
O
O
H
O
H
H
O
92
H
H
O
89
2q
, 87%, 29/1
2r
, 78%, 19/1
2s
, 88%, 36/1
N.D.
a Reaction conditions: 1a (0.3 mmol), “SCN”source, water (0.3mmol),
NCS
CO2Et
H
H
O
SCN
O
NCS
Me
H
O
rt.
O
H
b NMR yields based on 1a. The Z/E ratios was estimated by 1H NMR.
of glycolic acid.
EtO2C
SCN O
2tc
H
2u
H
2v
, 81%, 18/1
, 87%, 28/1
, 93%
c5 equiv. of deep eutectic ChCl/glycolic acid(1:2) composes of 5 equiv. of ChCl
and 10 equiv. of glycolic acid.
NCS
CO2Et
CO2Et
NCS
dAt 50ꢀ
eAt 60ꢀ
Me
H
Br
2x
H
2w
, 87%, 35/1
, 79%, 15/1
a Reaction conditions: 1 (0.3 mmol), KSCN (0.39 mmol), ChCl/glycolic
acidꢁ0.27 gꢂ, water (6 mg), 50oC, 10 h.
b Isolated yields based on 1.
With the optimal reaction conditions in hand (Table 1, entry19),
we proceeded to evaluate the substrate scope of the three-
component reaction and these results are shown in Table 2. To
our delight, a series of alkynoates bearing varied carbon chain
lengths and diverse isomeric structures employed for
hydrothiocyanation to provide the desired Z-β-thiocyanate
acrylates in 74–95% yields with excellent stereoselectivities (2a-
c 0.78 mmol of KSCN was used.
It is well known that the scalability and reusability of a
catalytic reaction system are of significant importance from the
views of green chemistry and industrial manufacturing. In order

3
Ethyl acetate (ACS grade), hexanes (ACS grade) were
to demonstrate the scalability of the hydrothiocyanation reaction,
a large-scale reaction (10 mmol) was conducted under the
optimal reaction conditions (Scheme 2). The experimental result
showed that a 90% yield of 2a was obtained, suggesting that the
present reaction system is easy to scale up. The reusability of
deep eutectic ChCl/glycolic acid (1:2) was then investigated.
Generally, after completion of the reaction, the product was
extracted for the determination of yield by 1H NMR and the deep
eutectic ChCl/glycolic acid (1:2) was reused directly. Empolying
substrate 1a as example, the experimental results revealed that
the deep eutectic solvent could be reused without significant
reduction in catalytic activity in five consecutive runs.
ACCEPTED MANUSCRIPT
purchased from J&K Scientific Ltd. and used without further
purification. Commercially available reagents were used without
further purification. Reactions were monitored by TLC. Flash
column chromatography was performed over silica gel (200-300
mesh). 1H NMR and 13C NMR spectra were recorded on a Bruker
AV-II 500 MHz NMR spectrometer. High-resolution mass
spectra were performed on a Q-TOF microspectrometer.
4.2. General Procedure for the Synthesis of 2.
In a vial was placed alkyne (0.3 mmol), ChCl/glycolic acid
(1:2) (270 mg, 0.9 mmol), KSCN (38 mg, 0.39 mmol), water (0.3
mmol), and then the contents were reacted at 50 ꢀ. Upon
completion, the reaction mixture was purified by column
chromatography on silicagel (eluent: hexanes/ethyl acetate) to
afford 2.
H2O (1 equiv.)
KSCN (1.3 equiv.)
NCS
CO2Et
CO2Bn
ChCl/glycolic acid (3 equiv), 50 oC
H
H
4.3. Larger-scale Synthesis of 2a
2a, 90%, 1.97g
1a, 10 mmol, 1.6g
In a vial was placed benzyl propiolate (1.6 g, 10 mmol),
ChCl/glycolic acid (1:2) (9 g, 30 mmol), KSCN (1.26 g, 13
mmol), water (10 mmol), and then the contents were reacted at
50ꢀ. Upon completion, the reaction mixture was purified by
column chromatography on silica gel (eluent: hexanes/ethyl
acetate) to afford 2a.
1st run 90%; 2nd run 88%; 3rd run 85%; 4th run 83%; 5th run 80%
Scheme 2. Large-scale synthesis and reusable experiment.
Based on these results obtained in Table 1 and previous reports,
a reasonable mechanism for the regio- and stereoselective
13
hydrothiocyanation reaction is depicted in Scheme 3. Stronger
hydrogen bond capabilities of deep eutectic ChCl/glycolic acid
activated alkynoates to in situ generate an allenolate intermediate
A through the formation of an intermolecular hydrogen bond
between glycolic acid and substrate 1a. Then, the thiocyanate
anion nucleophilic attacked the β-carbon atom of intermediate B
to deliver the intermediate C. Meanwhile, an intramolecular
hydrogen bond between the hydroxyl group of ChCl and the
nitrogen atom of “SCN” motif was formed in this intermediate.
Finally, the trapping of a proton (in situ generated from
ionization of water) occurs from the less hindered face, trans to
“SCN”, thus resulted in the production of (Z)-benzyl 3-
thiocyanatoacrylate 2a.
4.4. Recycling research of ChCl/glycolic acid (1:2)
In a vial was consecutively placed benzyl propiolate (1.6 g,
10 mmol), ChCl/glycolic acid (1:2) (9 g, 30 mmol), KSCN (1.26
g, 13 mmol) and H2O (0.18 g, 10 mmol), then the mixtures were
stired at 50ꢀ for 10 h. Upon completion, the reaction mixture
was extracted with cyclpentyl methyl ether (10 mL × 3). The
extraction was product with high purity. The yield was estimated
by gas chromatography. To the recycled ChCl/glycolic acid (1:2),
only 10 mmol of 1a, 13 mmol of KSCN, 10 mmol of H2O were
added to the filter residue, and the next cycle was carried out
under the same reaction conditions.
4.5. Characterization of the compounds
4.5.1. (Z)-benzyl 3-thiocyanatoacrylate (2a).9
Colorless oil (60.4 mg, 92%); 1H NMR (500 MHz, CDCl3) δ =
7.42 – 7.33 (m, 5H), 7.17 (d, J = 9.3, 1H), 6.30 (d, J = 9.3, 1H),
5.22 (s, 2H); 13C NMR (125 MHz, CDCl3) δ 166.17, 138.92,
134.87, 128.89, 128.87, 128.71, 119.75, 112.36, 67.53.
4.5.2. (Z)-methyl 3-thiocyanatoacrylate (2b).9
Colorless oil (35.6 mg, 83%); 1H NMR (500 MHz, CDCl3) δ =
7.15 (d, J = 9.3, 1H), 6.26 (d, J = 9.3, 1H), 3.79 (s, 3H).13C
NMR (125 MHz, CDCl3) δ 166.74, 138.61, 119.54, 112.24, 52.46.
Scheme 3. Possible reaction mechanism.
3. Conclusion
4.5.3. (Z)-ethyl 3-thiocyanatoacrylate (2c).9
Colorless oil (40.5 mg, 86%);1H NMR (500 MHz, CDCl3) δ
7.14 (d, J = 9.2 Hz, 1H), 6.26 (d, J = 9.2 Hz, 1H), 4.25 (q, J = 7.2
Hz, 2H), 1.31 (t, J = 7.2 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ
166.42, 138.25, 120.01, 112.55, 61.81, 14.25.
In summary, we have developed a practical and environment-
friendly protocol for the selective synthesis of Z-3-
thiocyanatoacrylates through deep eutectic solvent-catalyzed
hydrothiocyanation reaction. Both the high efficiency (74-95%
yield) and excellent stereoselectivities (Z:E > 12:1) were
achieved through intramolecular and intermolecular hydrogen
bond. In this process, the inexpensive and green deep eutectic
ChCl/glycolic acid not only acts as recycled reaction media, but
also serves as catalyst. The present reaction could be readily
scaled up to a large scale, providing a good opportunity for
applications in synthetic chemistry and industry production.
4.5.4. (Z)-propyl 3-thiocyanatoacrylate (2d).
1
White solid (39.0 mg, 76%); H NMR (500 MHz, CDCl3) δ =
7.13 (d, J = 9.2, 1H), 6.25 (d, J = 9.2, 1H), 4.17 (t, J = 6.8, 2H),
1.67 – 1.63 (m, 2H), 1.38 – 1.21 (m, 10H), 0.87 (t, J = 7.0, 3H);
13C NMR (125 MHz, CDCl3) δ 166.48, 138.18, 120.01, 112.50,
65.93, 31.76, 28.94, 28.55, 25.85, 22.66, 14.16. HRMS Calcd
(EI) m/z for C7H9NO2S: [M]+ 171.0354, found: 171.0356.
4.5.5.(Z)-cyclopropylmethyl 3-thiocyanatoacrylate (2e).9
4. Experimental Section
4.1. General methods and materials

4
Tetrahedron
1
ACCEPTED MANUSCRIPTCalcd
Colorless oil (48.3 mg, 88%); H NMR (500 MHz, CDCl3) δ =
21.02. HRMS
(EI) m/z for C11H9NO2S: [M]+
7.15 (d, J = 9.3, 1H), 6.29 (d, J = 9.3, 1H), 4.02 (d, J = 7.4, 2H),
0.87-0.81 (m, 1H), 0.64 – 0.57 (m, 2H), 0.34-0.29 (m, 2H); 13C
NMR (125 MHz, CDCl3) δ 166.49, 138.27, 120.10, 112.56,
70.70, 29.85, 9.78.
219.0354,found: 219.0352.
4.5.15. (Z)-naphthalen-2-yl 3-thiocyanatoacrylate (2o).9
1
White solid (72.7 mg, 95%); H NMR (400 MHz, CDCl3) δ =
7.92 – 7.80 (m, 3H), 7.65 – 7.61 (m, 1H), 7.55 – 7.47 (m, 2H),
7.37 (d, J = 9.3, 1H), 7.28 – 7.25 (m, 1H), 6.56 (d, J = 9.3, 1H);
13C NMR (101 MHz, CDCl3) δ 165.01, 147.62, 141.01, 133.73,
131.82, 129.85, 127.96, 127.88, 127.00, 126.27, 120.46, 119.30,
118.47, 111.95.
4.5.6. (Z)-2-hydroxyethyl 3-thiocyanatoacrylate(2f).9
Colorless oil (42.3 mg, 82%); 1H NMR (500 MHz, CDCl3) δ
= 7.23 (d, J = 9.3, 1H), 6.35 (d, J = 9.3, 1H), 4.37 – 4.30 (m, 2H),
3.91 – 3.86 (m, 2H), 2.67 (s, 1H); 13C NMR (125 MHz, CDCl3) δ
166.43, 138.96, 119.56, 112.26, 66.94, 60.63.
4.5.16. (Z)-thiophen-3-ylmethyl 3-thiocyanatoacrylate(2p).
4.5.7. (Z)-2-methoxyethyl 3-thiocyanatoacrylate (2g).9
White solid (56.0 mg, 83%); 1H NMR (500 MHz, CDCl3) δ =
7.36 – 7.31 (m, 2H), 7.16 (d, J=9.3, 1H), 7.13-7.08 (m, 1H),
6.28 (d, J=9.3, 1H), 5.22 (s, 2H); 13C NMR (125 MHz, CDCl3)
δ 166.04, 138.83, 135.66, 127.72, 126.68, 125.37, 119.69,
112.24, 62.24. HRMS Calcd (EI) m/z for C9H7NO2S2: [M]+
224.9918, found: 224.9915.
Colorless oil (51.1 mg, 91%); 1H NMR (500 MHz, CDCl3) δ =
7.16 (d, J = 9.4, 1H), 6.30 (d, J = 9.4, 1H), 4.33 – 4.31 (m, 2H),
3.62 – 3.59 (m, 2H), 3.37 (s, 3H); 13C NMR (125 MHz, CDCl3) δ
166.23, 138.76, 119.66, 112.25, 70.10, 64.55, 59.07.
4.5.8. (Z)-2-(tosyloxy)ethyl 3-thiocyanatoacrylate (2h).9
4.5.17. (Z)-furan-2-ylmethyl 3-thiocyanatoacrylate (2q).9
White solid (80.4 mg, 82%); 1H NMR (500 MHz,
Chloroform-d) δ = 7.79 (d, J=8.4, 2H), 7.36 (d, J=7.9, 2H),
7.18 (d, J=9.4, 1H), 6.20 (d, J=9.3, 1H), 4.37 – 4.35 (m, 2H),
4.27 – 4.25 (m, 2H), 2.46 (s, 3H); 13C NMR (125 MHz,
CDCl3) δ 165.69, 145.40, 139.56, 132.75, 130.12, 128.10,
119.20, 111.95, 67.10, 62.78, 21.83.
1
White solid (54.5 mg, 87%); H NMR (500 MHz, CDCl3) δ =
7.44 (dd, J = 1.8, 0.9, 1H), 7.17 (d, J = 9.3, 1H), 6.48 – 6.44 (m,
1H), 6.38 (dd, J = 3.3, 1.8, 1H), 6.27 (d, J = 9.3, 1H), 5.17 (s,
2H); 13C NMR (125 MHz, CDCl3) δ 165.89, 148.45, 143.84,
139.14, 119.56, 112.23, 111.68, 110.86, 59.02.
4.5.9. (Z)-2-bromoethyl 3-thiocyanatoacrylate (2i) 9
4.5.18. (Z)-cinnamyl 3-thiocyanatoacrylate (2r).9
Light yellow solid (60.0 mg, 85%); 1H NMR (500 MHz,
CDCl3) δ = 7.22 (d, J = 9.2, 1H), 6.31 (d, J = 9.2, 1H), 4.50 (t, J
= 6.0, 2H), 3.54 (t, J = 6.0, 2H); 13C NMR (125 MHz, CDCl3) δ
165.73, 139.58, 119.25, 112.04, 64.84, 28.10.
Colorless oil (57.3 mg, 78%); 1H NMR (400 MHz, CDCl3) δ =
7.47 – 7.29 (m, 5H), 7.19 (d, J = 9.3, 1H), 6.72 (dd, J = 15.9, 1.5,
1H), 6.37 – 6.24 (m, 2H), 4.87 (dd, J = 6.7, 1.3, 2H); 13C NMR
(101 MHz, CDCl3) δ 166.14, 138.77, 135.87, 135.52, 128.78,
128.50, 126.79, 121.97, 119.72, 112.39, 66.29.
4.5.10. (Z)-heptan-4-yl 3-thiocyanatoacrylate(2j).
4.5.19. (Z)-benzo[d][1,3]dioxol-5-ylmethyl 3-thiocyanatoacrylate
1
White solid (40.5 mg, 79%); H NMR (500 MHz, CDCl3) δ =
(2s).9
7.12 (d, J = 9.2, 1H), 6.24 (d, J = 9.2, 1H), 4.97 (tt, J = 7.3, 5.2,
1H), 1.58 – 1.51 (m, 4H), 1.35 – 1.28 (m, 4H), 0.90 (t, J = 7.3,
6H); 13C NMR (125 MHz, CDCl3) δ 166.29, 137.97, 120.40,
112.68, 76.17, 36.27, 18.65, 14.05. HRMS Calcd (EI) m/z for
C7H9NO2S: [M]+ 171.0354, found: 171.0352.
1
White solid (69.4 mg, 88%); H NMR (500 MHz, CDCl3) δ =
7.16 (d, J = 9.4, 1H), 6.88 – 6.82 (m, 2H), 6.79 (d, J = 8.4, 1H),
6.27 (d, J = 9.4, 1H), 5.97 (s, 2H), 5.11 (s, 2H); 13C NMR (125
MHz, CDCl3) δ 166.10, 148.17, 148.05, 138.82, 128.60, 122.89,
119.79, 112.28, 109.37, 108.48, 101.42, 67.50, 29.82.
4.5.11. (Z)-cyclohexyl 3-thiocyanatoacrylate (2k).9
4.5.20. (2Z,2’Z)-ethane-1,2-diyl bis(3-thiocyanatoacrylate) (2t).
Colorless oil (49.4 mg, 78%); 1H NMR (500 MHz, CDCl3) δ =
7.11 (dd, J = 9.3, 4.3, 1H), 6.23 (dd, J = 9.3, 4.3, 1H), 4.89 –
4.76 (m, 1H), 1.92 – 1.84 (m, 2H), 1.77 – 1.71 (m, 2H), 1.51 –
1.30 (m, 6H); 13C NMR (125 MHz, CDCl3) δ 165.92, 137.84,
120.56, 112.66, 74.67, 31.64, 25.32, 23.77.
1
White solid (79.2 mg, 93%); H NMR (500 MHz, CDCl3) δ =
7.22 (d, J = 9.3, 2H), 6.29 (d, J = 9.3, 2H), 4.44 (s, 4H); 13C
NMR (125 MHz, CDCl3) δ 165.91, 139.69, 119.24, 111.95,
62.90. HRMS Calcd (EI) m/z for C10H8N2O4S2: [M]+ 283.9925,
found: 283.9924.
4.5.12. (Z)-tert-butyl 3-thiocyanatoacrylate (2l).
4.5.21. (Z)-4-thiocyanatobut-3-en-2-one (2u).9
Colorless oil (43.3 mg, 78%); 1H NMR (500 MHz, CDCl3) δ =
7.04 (d, J = 9.3, 1H), 6.16 (d, J = 9.3, 1H), 1.49 (s, 9H); 13C
NMR (125 MHz, CDCl3) δ 165.78, 136.71, 121.76, 112.93,
83.12, 28.18.
4.5.13. (Z)-phenyl 3-thiocyanatoacrylate (2m).9
Colorless oil (46.1 mg, 75%); 1H NMR (500 MHz,
Colorless oil (33.1 mg, 87%); 1H NMR (500 MHz, CDCl3) δ =
7.16 (d, J = 8.8, 1H), 6.67 (d, J = 8.8, 1H), 2.33 (s, 3H); 13C
NMR (125 MHz, CDCl3) δ 198.28, 138.34, 124.88, 113.58,
30.03.
4.5.22. diethyl 2-thiocyanatofumarate (2v).9
Chloroform-d) δ = 7.46 – 7.39 (m, 2H), 7.35 (d, J=9.3, 1H),
White solid (55.6 mg, 81%); 1H NMR (500 MHz, Chloroform-
d) δ = 6.84 (s, 1H), 4.42 (q, J=7.1, 2H), 4.29 (q, J=7.2, 2H), 1.41
(t, J=7.2, 3H), 1.33 (t, J=7.2, 3H); 13C NMR (125 MHz, CDCl3) δ
164.64, 161.56, 138.28, 126.50, 108.91, 64.17, 62.43, 14.20,
14.04.
4.5.23. (Z)-ethyl 3-thiocyanatobut-2-enoate (2w).9
Colorless oil (44.6 mg, 87%); 1H NMR (500 MHz,
7.29 (t, J=7.5, 1H), 7.17 – 7.12 (m, 2H), 6.51 (d, J=9.3, 1H)
13C NMR (125 MHz, CDCl3) δ 164.74, 149.88, 140.73,
129.64, 126.54, 121.15, 119.15, 111.84
;
.
4.5.14. (Z)-p-tolyl 3-thiocyanatoacrylate(2n).
Colorless oil (48.6 mg, 74%); 1H NMR (400 MHz, CDCl3) δ =
7.32 (d, J = 9.3, 1H), 7.20 (d, J = 9.0, 2H), 7.01 (d, J = 8.6, 2H),
6.49 (d, J = 9.0, 1H), 2.36 (s, 3H); 13C NMR (101 MHz, CDCl3)
δ 165.07, 147.78, 140.66, 136.41, 130.23, 120.91, 119.33, 112.04,
Chloroform-d) δ = 6.13 (d, J=1.4, 1H), 4.21 (q, J=7.1, 2H), 2.47

5
(d, J=1.4, 3H), 1.29 (t, J=7.1, 3H); 13C NMR (125 MHz, CDCl3)
δ 166.13, 146.78, 117.48, 110.45, 61.33, 25.96, 14.29.
(8) Wu, C.; Lu, L.-H.; Peng, A.-Z.; Jia, G.-K.; Peng, C.; Cao, Z.; Tang, Z.;
He, W.-M.; Xu, X. Green Chem. 2018, 20, 3683.
ACCEPTED MANUSCRIPT
(9) (a) Liu, K.-J.; Jiang, S.; Lu, L.-H.; Tang, L.-L.; Tang, S.-S.; Tang, H.-S.;
Tang, Z.; He, W.-M.; Xu, X. Green Chem. 2018, 20, 3038; (b) Yang, J.; Mei,
F.; Fu, S.; Gu, Y. Green Chem. 2018, 20, 1367; (c) Li, J.; Tang, W.; Ren, D.;
Xu, J.; Yang, Z. Green Chem. 2019; (d) Liu, Q.; Wang, L.; Yue, H.; Li, J.-S.;
Luo, Z.; Wei, W. Green Chem. 2019; (e) Bao, P.; Wang, L.; Liu, Q.; Yang,
D.; Wang, H.; Zhao, X.; Yue, H.; Wei, W. Tetrahedron Lett. 2019, 60, 214; (f)
Lu, L.-H.; Wang, Z.; Xia, W.; Cheng, P.; Zhang, B.; Cao, Z.; He, W.-M.
Chin. Chem. Lett. 2019, 30, 1237; (g) Xie, L.-Y.; Peng, S.; Liu, F.; Liu, Y.-F.;
Sun, M.; Tang, Z.-L.; Jiang, S.; Cao, Z.; He, W.-M. ACS Sustainable Chem.
Eng. 2019, 7, 7193; (h) Dong, D.-Q.; Chen, W.-J.; Yang, Y.; Gao, X.; Wang,
Z.-L. ChemistrySelect 2019, 4, 2480.
4.5.24. (E)-ethyl 3-bromo-3-thiocyanatoacrylate (2x).8
White solid (55.7 mg, 79%); 1H NMR (500 MHz, Chloroform-
d) δ = 6.73 (s, 1H), 4.24 (q, J=7.2, 2H), 1.31 (t, J=7.1, 3H); 13C
NMR (125 MHz, CDCl3) δ 165.17, 126.31, 125.02, 109.60,
62.09, 14.21.
Corresponding authors.
Jun Jiang: 1060151@hnust.edu.cn
Xianyong Yu: yu_xianyong@163.com
Acknowledgements
(10) (a) Clarke, C. J.; Tu, W.-C.; Levers, O.; Bröhl, A.; Hallett, J. P. Chem.
Rev. 2018, 118, 747; (b) Liu, P.; Hao, J.-W.; Mo, L.-P.; Zhang, Z.-H. RSC
Adv. 2015, 5, 48675; (c) Alonso, D. A.; Baeza, A.; Chinchilla, R.; Guillena,
G.; Pastor, I. M.; Ramón, D. J. Eur. J. Org. Chem. 2016, 612.
(11) (a) Xu, J.; Huang, W.; Bai, R.; Queneau, Y.; Jérôme, F.; Gu, Y. Green
Chem. 2019; (b) Yang, J.; De Oliveira Vigier, K.; Gu, Y.; Jérôme, F.
ChemSusChem 2014, 8, 269; (c) Ma, C.-T.; Liu, P.; Wu, W.; Zhang, Z.-H. J.
Mol. Liq. 2017, 242, 606; (d) Liu, P.; Hao, J.-W.; Liang, S.-J.; Liang, G.-L.;
Wang, J.-Y.; Zhang, Z.-H. Monatsh. Chem. 2016, 147, 801.
This work was supported by Scientific Research Fund of
Hunan Provincial Education Department (18A192).
(12) Xie, P.; Wang, J.; Liu, Y.; Fan, J.; Wo, X.; Fu, W.; Sun, Z.; Loh, T.-P.
Nat. Commun. 2018, 9, 1321.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.****
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