Synthesis Of di- and tri-substituted thiourea derivatives in water using choline chloride–urea catalyst

Article abstract of DOI:10.1080/17415993.2018.1533014

In this work, di- and tri-substituted thiourea derivatives have been synthesized via a one-pot, three-component reaction from carbon disulfide and aliphatic or aromatic amines using choline chloride-urea deep eutectic solvent as a catalyst in water. Both cyclic and acyclic thiourea derivatives with two or three substituents were synthesized successfully. The reactions were done at 25–100°C, using 5–20 mol% catalyst, in 3–5 h and the GC-Mass yields were between 60% and 95%. All products were characterized using FT-IR, ¹H-NMR, ¹³C-NMR, GC-MS and melting point analyses. The results showed that both water and the DES have important effects on the yield and the rate of this reaction and both of them are necessary to obtain higher yields in less time. The extra experiment, which was designed to study the mechanism of the reaction, showed that an isothiocyanate intermediate was formed in the reaction. Finally, the results showed that by the increase of the amine's nucleophilicity, the reaction occurs faster and gives higher yield.

Full text of DOI:10.1080/17415993.2018.1533014

Journal of Sulfur Chemistry
ISSN: 1741-5993 (Print) 1741-6000 (Online) Journal homepage: http://www.tandfonline.com/loi/gsrp20
Synthesis Of di- and tri-substituted thiourea
derivatives in water using choline chloride–urea
catalyst
Hossein Tavakol, Amir Mahmoudi & Mohammad-Amin Ranjbari
To cite this article: Hossein Tavakol, Amir Mahmoudi & Mohammad-Amin Ranjbari (2018):
Synthesis Of di- and tri-substituted thiourea derivatives in water using choline chloride–urea
catalyst, Journal of Sulfur Chemistry, DOI: 10.1080/17415993.2018.1533014
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JOURNAL OF SULFUR CHEMISTRY
https://doi.org/10.1080/17415993.2018.1533014
Synthesis Of di- and tri-substituted thiourea derivatives in
water using choline chloride–urea catalyst
Hossein Tavakol , Amir Mahmoudi and Mohammad-Amin Ranjbari
Department of Chemistry, Isfahan University of Technology, Isfahan, Iran
ABSTRACT
ARTICLE HISTORY
Received 2 March 2018
Accepted 3 October 2018
In this work, di- and tri-substituted thiourea derivatives have been
synthesized via a one-pot, three-component reaction from carbon
disulfide and aliphatic or aromatic amines using choline chloride-
urea deep eutectic solvent as a catalyst in water. Both cyclic and
acyclic thiourea derivatives with two or three substituents were syn-
thesized successfully. The reactions were done at 25–100°C, using
5–20 mol% catalyst, in 3–5 h and the GC-Mass yields were between
60% and 95%. All products were characterized using FT-IR, 1H-NMR,
13C-NMR, GC-MS and melting point analyses. The results showed
that both water and the DES have important effects on the yield
and the rate of this reaction and both of them are necessary to
obtain higher yields in less time. The extra experiment, which was
designed to study the mechanism of the reaction, showed that an
isothiocyanate intermediate was formed in the reaction. Finally, the
resultsshowedthatbytheincreaseoftheamine’snucleophilicity, the
reaction occurs faster and gives higher yield.
KEYWORDS
Green; thiourea; DES; water;
carbon disulfide
1. Introduction
Thiourea is a valuable functional group in organic chemistry. Therefore, the syntheses of
its derivatives have been the subject of significant interest for many years. These com-
pounds have various applications in medicinal chemistry and biological purposes such
CONTACT Hossein Tavakol
h_tavakol@cc.iut.ac.ir
Supplemental data for this article can be accessed here. https://doi.org/10.1080/17415993.2018.1533014
© 2018 Informa UK Limited, trading as Taylor & Francis Group

2
H. TAVAKOL ET AL.
as in fungicides, herbicides [1], phenoloxidase [2] and enzymatic inhibitors [3]. More-
over, thiourea and its derivatives are important building blocks in the synthesis of various
heterocycles [4–6] and they have been used as organocatalysts in several synthetic method-
ologies. The importance of chiral derivatives of thiourea is especially evident from their
potencies as enantioselective or stereoselective catalysts [7–9]. However, despite several
reported studies of the synthesis and applications of thiourea derivatives [10,11], the exist-
ing methodologies for the synthesis of these materials are not sufficient and some of the
developed methods suffer synthetic or environmental limitations. Therefore, research in
this area is important for synthetic chemists in order to develop new methodologies, espe-
cially with less environmental and synthetic problems. During previous decades, many
attempts have been made to perform organic reactions in water, [12,13] and this approach
has been taken here for the synthesis of these thiourea derivatives. However, finding appro-
priate catalysts to perform chemical reactions in water is very difficult. However, ionic
liquids and their new generation, deep eutectic solvents (DESs) showed promising catalytic
abilities in water, as well as potencies in other reaction media.
DESs were introduced in 2003 by Abbott and co-workers [14]. Since then, they have
been used extensively in organic synthesis and other applications [15]. These solvents (or
mixtures) do not suffer some of the disadvantages of ILs, while they benefit from all the
advantages of ILs. Therefore, the use of these solvents has increased in recent years [16], in
different scientific and industrial applications such as in the synthesis of organic and inor-
ganic compounds [17,18], extraction of heavy metals [19] and in the construction of solar
cells [20]. These solvents are typically made up of a quaternary ammonium or phospho-
nium salt and a hydrogen bond donor agent such as alcohols or inorganic salts [21]. A lot of
DESs have been introduced in recent years and among them, the mixture of choline chlo-
ride (ChCl)–urea (mostly in 1:2 ratio) has been considered as an appropriate candidate for
synthetic purposes. It can be employed as a catalyst, solvent or both, because of its unique
properties such as strong catalytic potency, good solubility and fluidity at room tempera-
ture [21]. Therefore, in the continuation of our studies on organic synthesis development,
especially using DESs [22–24], and due to the valuable properties of thiourea derivatives,
we have focused on their preparation using ChCl–urea DES.
Various methods have been reported in the literature for the synthesis of these com-
pounds, including reactions starting from isothiocyanates, carbon disulfide, thiophosgene
or urea [25]. In this work, the reaction between amine and carbon disulfide has chosen for
the synthesis of thiourea derivatives, because of the high atom economy and the high over-
all yield of this method. The green reaction media (water) and the green and inexpensive
catalyst (choline chloride–urea DES) were selected to perform this transformation. Vari-
ous thiourea derivatives with 2 and 3 substitutions have been synthesized successfully via
this method. The results of this study and the details of the employed methodologies are
mentioned in the next sections.
2. Materials and methods
Chemical compounds were purchased from Merck (Germany) and Dae-Jung (South
Korea) companies. The employed amines were purified before the first use and the other
starting materials were used without further purifications. Melting points were deter-
mined using Gallen Kamp apparatus. Thin-layer chromatography (TLC) was employed

JOURNAL OF SULFUR CHEMISTRY
3
to monitor the reaction and check the purities. FT-IR spectra were recorded using KBr
pellets by JASCO FT-IR instrument. 1H-NMR and 13C-NMR spectra were recorded using
Brucker Ultrashield 400 MHz NMR instrument and CDCl3 or DMSO were used as sol-
vents. Chemical shifts were expressed in ppm versus the chemical shift of tetramethylsilane
(TMS) as a reference. Mass spectra and GC-Mass analyses were recorded on Agilent
GC-MS-5975C with Triple-Axis Detector.
2.1. Preparation of ChCl–urea DES
ChCl–urea chloride eutectic solvent was prepared according to the reported procedure in
the literature. For this preparation, ChCl was dried under vacuum at 120°C for three hours.
Then, ChCl (10 mmol) was mixed with urea (20 mmol) and heated to 100°C in air with
stirring until a clear liquid was obtained. This mixture was used in the next experiment
without needing further purification.
2.2. General procedure for the synthesis of thiourea derivatives from one amine
In a 10 mL round-bottom flask (equipped with a basic gas trap to neutralize exhausted
hydrogen sulfide), 2 mmol amine was added to 3 mL distilled water and 0.1 mmol of DES
(ChCl–urea). The flask was placed in an ice bath over the magnetic heater-stirrer and the
mixture was stirred vigorously. Then, 1 mmol carbon disulfide was added to the mixture
during the stirring. The reaction was monitored by TLC, with ethyl acetate-hexane (3:7)
mixture as eluent, up to the completion of the reactant. The ice bath was then removed
and replaced with an oil bath, the flask was equipped with a condenser and the reaction
was heated to 100°C and stirred for 3 h with refluxing. Then, the heating was stopped and
the reaction was allowed to reach to room temperature. The precipitated product (during
the cooling), was purified by recrystallization in ethanol and used for the next analyses.
All products are known compounds and their structures were confirmed by comparison
1
of their mass specta, IR, H-NMR and 13C-NMR spectra, and melting points with the
reported values in the literature [26–30]. The selected physical properties, GC-Mass results
and spectroscopic data for all products are listed in section 2.4 and all original spectral data
(IR, NMR and mass spectrometry) are shown in the supplementary information.
2.3. General procedure for the synthesis of thiourea derivatives from two different
amines
In a 10 mL round-bottom flask (equipped with a basic gas trap to neutralize exhausted
hydrogen sulfide), 1 mmol amine (first amine) was added to 3 mL distilled water and
0.1 mmol of DES (ChCl–urea). The flask was placed on an ice bath over a magnetic heater-
stirrer and the mixture was stirred vigorously. Then, 1 mmol carbon disulfide was added
to the mixture at low temperature during stirring. The reaction was monitored by TLC
with ethyl acetate-hexane (3:7) mixture as eluent up to the completion of the reaction.
After this, 1 mmol of the second amine was added to the reaction mixture, the ice bath was
removed and replaced with an oil bath, the flask was equipped with a condenser and the
reaction was heated to 100°C and stirred for 3 h (or more, in some derivatives) with reflux-
ing. The heating was stopped and the reaction was allowed to reach room temperature.

4
H. TAVAKOL ET AL.
The precipitated product (during the cooling), was purified by recrystallization in ethanol
and used for the next analyses. All products are known compounds and their structures
were confirmed by comparison of their mass spectrometry, IR, 1H-NMR and 13C-NMR
spectroscopy, and melting points with the reported values in the literature [26–30]. The
physical properties, GC-Mass results and spectroscopic data for all products are listed in
section 2.4 and the original spectra (IR, NMR and mass spectrometry) are shown in the
supplementary information.
2.4. Physical and spectroscopic data for products
2.4.1. 1,3-dibenzylthiourea (3a)
White crystal (Yield: 90%); m.p. 145°C. FT-IR (KBr): 3289, 3080, 2983, 1553, 1500, 1452,
1393, 1280, 740 cm−1. 1H-NMR (400 MHz, DMSO-d6): δ 4.73 (s, 4H), 7.34 (m, 10H), 7.97
(s, 2H) ppm; 13C-NMR (100 MHz, CDCl3): δ 48.5, 127.6, 128.0, 129.0, 136.7, 182.2 ppm;
GC-MS: m/z (%):65 (18.0), 79 (20.1), 91 (83.2), 106 (100), 256 50.9) [M + ].
2.4.2. 1,3-diphenylthiourea (3b)
White crystal (Yield: 80%); m.p. 150–153°C. FT-IR (KBr): 3200, 3035, 1660, 1450, 1380,
930, 750, 630 cm−1. 1H-NMR (400 MHz, CDCl3) 7.1–7.5 (m, 10H), 9.79 (s, 2H) ppm. 13C-
NMR (101 MHz, CDCl3) δ 124.11, 124.89, 128.91, 139.94, 180.10 ppm. GC-MS: m/z (%):
65, 91, 134, 169, 226 [M+].
2.4.3. 1,3-bis(3-hydroxyphenyl)thiourea (3c)
Yellow oil (Yield: 60%). FT-IR (KBr): 3350, 3000, 1600, 1550, 1200 cm−1 13C NMR
.
(101 MHz, DMSO-d6) δ 178.90, 157.34, 140.43, 129.10, 113.89, 111.42, 110.25. 1H NMR
(400 MHz, DMSO-d6) δ 9.65 (s, 2H), 9.46 (s, 2H), 7.10 (t, J = 8.0 Hz, 2H), 7.01 (t,
J = 2.2 Hz, 2H), 6.86 (d, J = 8.0 Hz, 2H), 6.52 (dd, J = 7.7, 1.9 Hz, 2H). 13C-NMR
(101 MHz, DMSO-d6) 110.25, 111.42, 113.89, 129.10, 149.43, 157.34, 178.90 ppm. The
signals of ethyl acetate (purification solvent) were remained in both NMR spectra.
2.5. 1,3-bis(3,4-dimethoxyphenethyl)thiourea (3d)
White crystal (yield: 90%); m.p. 145–146°C. FT-IR (KBr): 3350, 3250, 2990, 1630, 1550,
1280 cm−1. 1H NMR (400 MHz, DMSO-d6) δ 7.40 (s, 2H), 6.86 (d, J = 8.1 Hz, 2H), 6.81
(d, J = 2.0 Hz, 2H), 6.72 (dd, J = 8.2, 2.0 Hz, 2H), 3.74 (s, 6H), 3.72 (s, 6H), 3.67–3.50 (m,
4H), 2.72 (t, J = 7.3 Hz, 4H). 13C-NMR (101 MHz, DMSO-d6) 34.31, 44.98, 55.32, 55.46,
111.80, 112.44, 120.42, 131.74, 141.17, 148.55, 180.10 ppm.
2.5.1. Tetrahydropyrimidine-2(1H)-thione (5a)
White crystal (Yield: 90%); m.p. 183°C. FT-IR (KBr): 3250, 3160, 3090, 2950, 1550, 1425,
1310, 1190 cm−1. 1H NMR (400 MHz, DMSO-d6) δ 1.72 (m, 2H), 3.1 (m, 4H), 7.8 (s, 2H);
13C-NMR (101 MHz, DMSO-d6) δ 19.69, 40.25, 176.10 ppm. GC-MS: m/z (%): 60 (12.6),
74 (9.9), 116 (100) [M + ] [28].

JOURNAL OF SULFUR CHEMISTRY
5
2.5.2. 1,3-dihydro-2H-benzo[d]imidazole-2-thione (5b)
White crystal (Yield: 75%); m.p. 145°C. FT-IR (KBr):1200, 1315, 1550, 3150, 3235 cm−1
.
1H-NMR (400 MHz, DMSO-d6) 7.2 (m, 4H), 12.32 (s, 2H). 13C-NMR (101 MHz, DMSO-
d6) δ 109.93, 122.76, 132.71, 168.59 ppm. GC-MS: m/z (%): 45, 78, 105, 150.0 (99.74) [M+].
2.5.3. 1-benzyl-3-phenylthiourea (7a)
White crystal (Yield: 60%); m.p. 159–163°C. FT-IR (KBr): 3450, 3300, 3230, 3190, 1650,
1610, 1490, 960, 790 cm−1; GC-MS: m/z (%): 28 (18.0), 51(7.1), 79 (19.9), 106 (100), 149
(22.3), 207 (6.8), 240 (44.1), 242 (7.30) [M + ] [29].
2.5.4. N-benzylmorpholine-4-carbothioamide (7b)
White crystal (Yield: 65%)„ m.p. 85°C. FT-IR (KBr): 3200, 3025, 1460, 1540, 1100, 940,
730, 690 cm−1. 1H-NMR (400 MHz, CDCl3): 3.77 (t, 4H), 3.88 (t, 4H), 4.9 (d, 2H), 5.63
(s, 1H), 7.34 (m, 5H). 13C NMR (101 MHz, CDCl3) δ 47.54, 50.48, 66.15, 127.93, 128.22,
128.90, 137.66, 182.76 ppm. GC-MS: m/z (%): 57, 65, 87, 91, 149 (87 + 149 = 236) [M+].
2.5.5. N-phenylmorpholine-4-carbothioamide (7c)
White crystal (Yield: 65%), m.p. 115°C. FT-IR (KBr): 3390, 3035, 3950, 1550, 1500, 1213,
950, 740, 690 cm−1. 1H-NMR (400 MHz): 3.65 (t, 4H), 3.76 (t, 4H), 7.06–7.29 (m, 5H), 7.2
(s, 1H) ppm. 13C-NMR (101 MHz, CDCl3) δ 49.72, 66.12, 123.02, 125.40, 129.26, 139.84,
183.75 ppm. GC-MS: m/z (%): 42, 51, 57, 71, 87, 108, 135 (135 + 87 = 222) [M+].
2.5.6. N-benzylhydrazinecarbothioamide (7d)
White crystal (Yield: 75%); m.p. 133°C. FT-IR (KBr): 3450, 3300, 3230, 3190, 1650, 1610,
1490, 960, 790 cm−1; 1H-NMR (400 MHz, CDCl3): 3.78 (2H, bs), 4.87 (2H, d), 7.2–7.45
(overlapping with solvent signal, 5H, m), 7.75 (2H, s) [30].
3. Results and discussion
After the synthesis of the catalyst (ChCl–urea DES), it was characterized using melting
point and FT-IR spectroscopy (the results are shown in Fig. S1 in supporting information)
and compared to the results from previous reports. Then, the DES was used to prepare
various thiourea derivatives in water solution. The general reactions for these syntheses
are shown in Scheme 1. As shown in the above scheme and in the experimental section,
products from one amine or from two different amines were prepared using different pro-
cedures. In addition, the reactivity’s of aliphatic and aromatic amines were not the same.
Therefore, we had to separately obtain the optimized parameters for each category of reac-
tion. To obtain these optimized parameters, a model reaction was employed, consisting
of the reaction between benzyl amine as the aliphatic amine and aniline as the aromatic
amine and carbon disulfide in water at different reaction temperatures, times and catalyst
amounts.
First, we examined this reaction without catalyst, using only ChCl (20 mol%) and using
only urea (20 mol%). Under these conditions, the reaction did not go to completion. There-
fore, the use of DES is necessary for completion of this reaction. In addition, using urea as
catalyst gave better results than ChCl, showing higher, but not sufficient, catalytic ability.

6
H. TAVAKOL ET AL.
Scheme 1. The general reactions for the synthesis of various thiourea derivatives.
After this step, the other reaction parameters were changed to obtain the optimized condi-
tions for both steps of the model reaction using both aliphatic and aromatic amines. Brief
results of these optimizations are listed in Table 1 (many extra experiments were done that
were not mentioned here to save space). For each part, the bolded row shows the opti-
mized condition. It should be noticed that for all optimizations, temperatures less than
room temperature and times less than 5 min have not been examined.
Optimizations (Table 1) of the reactions using a single amine to give products 3a,b and
5a,b demonstrated that the aliphatic or aromatic amines showed different results. The reac-
tions of the aliphatic amines, which reacted faster, were optimized using 5 mol% catalyst
at 25°C and were complete in 5 min, while the reactions of the aromatic amines, which
are less reactive, were optimized using 10 mol% catalyst at 25°C and were complete in
45 min. The reactions using two different amines (products 7a-d) precede much slower and
required harsher conditions. Optimization with two aliphatic amines, required 10 mol%
catalyst, 100°C temperature and 3 h. Optimization with two aromatic amines required
twice the catalyst (20 mol% catalyst) but the same temperature (100°C) and time (3 h) as
the aliphatic amines. In addition, it was demonstrated that exclusion of water decreased
both the reaction rate and yield.
Various derivatives of thiourea were synthesized using these optimized conditions but
with variable reactions times to maximize the yields, and the results are reported in Table 2.
The primary amines were more nucleophilic, reacting more rapidly than the secondary
amines probably due to their less hindered structures. In addition, they produced fewer
byproducts and their yields are higher than those of secondary amines. The highest yield
(90%) were observed during preparation of thiourea derivatives from benzyl amine or
1,3-propane diamine (3a and 5a) while the lowest yields were observed in producing the
derivatives obtained from two different amines (7a-7d). There is a guess that this decrease

JOURNAL OF SULFUR CHEMISTRY
7
Table 1. The brief results of optimization processes for the reaction according to the model reactiona.
For 3a, 5a (products obtained from one
aliphatic amine)
For 3b, 5b (products obtained from
one aromatic amine)
% Catalystb
Temp. (°C)
Time (min)
Yield (%)
% Catalystb
Temp. (°C)
Time (min)
Yield (%)
20
20
10
10
5
5
5
25
25
25
25
25
25
25
25
25
25
30
10
30
10
30
10
5
5
5
5
> 95
> 95
> 95
> 95
> 95
> 95
> 95
> 95
> 95
> 95
5
5
10
10
10
25
25
25
25
25
25
25
25
25
25
15
30
15
30
45
15
45
60
60
30
30
50
80
90
> 90
80
> 90
Trace
Trace
Trace
20
20
Urea (20%)
ChCl (20%)
Free catalyst
Urea(20%)
ChCl(20%)
Freecatalyst
For 7b (product obtained from two
aliphatic amines)c
For 7a, 7c, 7d (products obtained from one aliphatic and
one aromatic amines)c
5
10
25
25
60
60
10
20
5
10
25
25
60
60
< 10
20
20
25
60
25
20
25
60
25
10
60
60
40
20
60
60
40
10
80
60
55
20
80
60
50
10
10
10
10
90
60
60
120
180
240
60
60
70
80
> 90
> 90
Trace
-
20
20
20
20
30
100
100
100
100
100
60
60
60
75
> 80
> 80
> 80
Trace
-
-
100
100
100
100
60
120
180
240
180
60
10
Urea (20%)
ChCl (20%)
Free catalyst
Urea(20%)
ChCl(20%)
Freecatalyst
60
60
60
60
60
60
60
60
-
aThe model reaction involved 2 mmol (1 mmol for each step) of aliphatic (benzyl) amine or aromatic amine (aniline), 1 mmol
CS2 in 3 mL distilled water.
bin mol%, for ChCl–urea DES or as defined.
cfor derivatives with two different amines. Symmetric derivatives are consisted of only 1 step.
in the yield is maybe because of the formation of symmetrical thiourea derivatives (as
byproduct) from the reaction of each of two existed amines with carbon disulfide. This
guess was confirmed by the comparison of the TLC of the mixture of product with the
possible symmetric amines.
In order to determine the effect of the strength of the amine’s nucleophilicity on the
efficiency of this reaction, several nitrogen-containing compounds such as amino acids,
amides, aromatic amines and the presence of electron withdrawing groups have been
used. In accordance with our prediction, no products have been observed in any of these
reactions due to the very low nucleophilicity of these compounds, even in the presence
of higher concentration of catalyst and higher temperatures during a reaction time of
24 h.
Finally, we have conducted some studies to examine the mechanism for the formation of
thiourea under our reported reaction conditions. According to published studies, several
mechanisms have been proposed for this reaction as shown in Scheme 2. In the first sug-
gested mechanism, the amine and carbon disulfide in the presence of the catalyst initially
form dithiocarbamic acid which decomposed to form isothiocyanate as the main reac-
tion intermediate [24] (Scheme 2(a)). In another proposed mechanism (Scheme 2(b)), the
isothiocyanate was not produced as an intermediate in the reaction process [25]. Instead,

Table 2. The list of prepared thiourea derivatives with the yield of each product.
Entry
Time (h)
Product
Yield (%)a
Ref
Entry
Time (h)
4
Product
Yield (%)a
75
Ref
3a
3
90
[26]
5b
[28]
3b
3c
5
5
80
60
[27]
-
7a
7b
4.5
4
60
65
[29]
[28]
3d
5a
3
3
90
90
-
7c
5
3
65
75
[29]
[30]
[28]
7d
aGC-Mass yields.

JOURNAL OF SULFUR CHEMISTRY
9
Scheme 2. Suggested mechanism for preparation of thiourea derivatives from carbon disulfide.
the second equivalent of amine directly attacks the dithiocarbamic acid intermediate and
produces the corresponding thiourea derivative after the removal of H2S.
To provide evidence for the confirmation or rejection of the reported mechanisms in
Scheme 2, we have analyzed the intermediates of the reaction before the addition of the
second equivalent of amine with FTIR spectroscopy. Indeed as reported [31], the isothio-
cyanate signals were observed consistent with mechanism a. This conclusion is consistent
with the previously reported evidence [32,33]. Nevertheless, we decided to do an additional
study to confirm the operation of mechanism a. We decided to switch the order of addition
of the amines by adding the secondary amine in the first step followed by the addition of
the primary amine in the second step. Our hypothesis was that, since the secondary amine
could not produce the isothiocyanate intermediate, if the thiourea product was formed the
isothiocyanate is not a necessary intermediate in this reaction. However, we observed that
the reaction did not produce any product using these conditions. Therefore, we concluded
that the isothiocyanate is a necessary intermediate in this reaction providing confirmation
for mechanism a.
4. Conclusion
In this work, di- and tri-substituted thiourea derivatives from carbon disulfide and amines
were successfully synthesized using ChCl–urea DES as a catalyst in the green media water.
Both cyclic and acyclic products with two or three substituents were synthesized using
aliphatic and aromatic amines. The reactions were done at 25–100C, using 5–20 mol% cat-
alyst, in 3–5 h and yields between 60% and 95% (obtained by GC-Mass) were obtained.
The results showed that both water and the DES have important effects on the yield and
rate of the reaction and are both required for the reactions to go to completion. The study
we designed to examine the order of addition of secondary and primary amines pro-
vided compelling evidence that an isothiocyanate is a required intermediate. Finally, the

10
H. TAVAKOL ET AL.
results show that the reaction rate increases and higher yields are obtained with increasing
nucleophilicity of the amine.
Acknowledgements
We acknowledge the Institute of organic chemistry, University of Innsbruck (UIBK) for providing
NMR facility. We have special thanks to Professor Ronald Micura (the head of the institute) and
Professor Christoph Kreutz for their valuable assistances.
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
This work was supported by the research affairs of Isfahan University of technology.
ORCID
Hossein Tavakol http://orcid.org/0000-0002-3296-9575
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