New facile one-pot synthesis of S-alkyl thiolcarbamates from xanthogenate in water

Article abstract of DOI:10.1007/s00706-013-1083-7

A simple and efficient one-pot synthesis was developed for the preparation of S-alkyl thiolcarbamates from xanthogenate without catalyst using water as a solvent. The water can be recycled after removal of the product. The significant features of this protocol are: operational simplicity, mild reaction conditions, recycling of solvent and high product yields. Starting basic alkyl xanthogenate reacts with alkyl ammonium sulfate (aryl ammonium sulfate) and hydrogen peroxide (molar ratio 1:0.55:1) in water at 40 C for 1 h, followed by additional heating at 70-110 C for 1-2.3 h. Good to excellent yields were achieved using ammonium sulfate in 10 % molar excess. Graphical abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s00706-013-1083-7

Monatsh Chem (2013) 144:1833–1837
DOI 10.1007/s00706-013-1083-7
ORIGINAL PAPER
New facile one-pot synthesis of S-alkyl thiolcarbamates
from xanthogenate in water
ˇ
Milutin M. Milosavljevic Dusan Z. Mijin
•
•
´
ˇ
•
Smiljka S. Milisavljevic Natasa M. Elezovic
•
´
ˇ
´
´
Jelena K. Milanovic
Received: 9 January 2013 / Accepted: 4 September 2013 / Published online: 1 October 2013
Ó Springer-Verlag Wien 2013
Abstract A simple and efficient one-pot synthesis was
developed for the preparation of S-alkyl thiolcarbamates
from xanthogenate without catalyst using water as a sol-
vent. The water can be recycled after removal of the
product. The significant features of this protocol are:
operational simplicity, mild reaction conditions, recycling
of solvent and high product yields. Starting basic alkyl
xanthogenate reacts with alkyl ammonium sulfate (aryl
ammonium sulfate) and hydrogen peroxide (molar ratio
1:0.55:1) in water at 40 °C for 1 h, followed by additional
heating at 70–110 °C for 1–2.3 h. Good to excellent yields
were achieved using ammonium sulfate in 10 % molar
excess.
other commercial applications and in household products.
Some of them are used for vector control in public health
[1–5]. In addition, they also have bactericidal, anesthetic
and antiviral properties [6–9].
Due to their importance and wide application, synthesis
of S-alkyl thiocarbamates has been widely investigated (for
reviews, see [10–13]). Rearrangement of O-alkyl thiocar-
bamates to S-alkyl thiocarbamates was also studied. This
rearrangement proceeds in the presence [14–16] or in the
absence of catalyst [16]. Thermal rearrangement of O-allyl
thiocarbamates to S-allyl thiocarbamates was performed at
120–150 °C [16]. Intramolecular thermal rearrangement
was also investigated in the synthesis of thiolcarbamates
from 2-oxo-2H-chromen-7-yl dimethylcarbamates using
microwave irradiation in DMF. Only one product was
obtained in a yield of 89 %. Starting 2-oxo-2H-chromen-7-
yl dimethylcarbamate was obtained from 7-hydroxycoum-
arin, which was treated with NaH and subsequently reacted
with the relevant carbamoyl chloride. The rearrangement
occurs through a four-membered cyclic transition state in a
concerted fashion [17]. Another intramolecular thermal
rearrangement through a four-membered cyclic transition
state is described. Various aryl thionobenzoates were pre-
pared and rearranged to aryl thiolbenzoates. A four-
membered cyclic transition state is formed by a nucleo-
philic attack of thiocarbonyl sulfur on the migrating ring
[18]. It was previously shown that there is no intramole-
cular thermal rearrangement of O-alkyl thioncarbamate to
S-alkyl thiolcarbamate without catalyst even if a reactant is
heated to a boiling point for a long period of time [19].
During our previous studies of carbamate synthesis, we
noticed that when the reaction mixture, which contains
alkyl ammonium salt of xanthic acid, hydrogen peroxide
and ammonium sulfate in excess, is heated after the dis-
appearance of ammonium salt particles (end of oxidation
Keywords Amines ꢀ Catalyst-free reaction ꢀ Fungicides ꢀ
Alkyl ammonium sulfate ꢀ Aryl ammonium sulfate
Introduction
Thiocarbamates, especially S-alkyl thiocarbamates, are
mainly used in agriculture as insecticides, herbicides and
fungicides. They are also used as biocides for industrial or
´
´
´
M. M. Milosavljevic ꢀ S. S. Milisavljevic ꢀ N. M. Elezovic
Technological Faculty of Kosovska Mitrovica of University of
Kosovska Mitrovica, Kosovska Mitrovica, Serbia
ˇ
D. Z. Mijin (&)
Faculty of Technology and Metallurgy, University of Belgrade,
Belgrade, Serbia
e-mail: kavur@tmf.bg.ac.rs
´
J. K. Milanovic
College for Business and Industrial Management,
ˇ
Krusevac, Serbia
123

´
M. M. Milosavljevic et al.
1834
Scheme 1
Scheme 2
O
S
1 R2R3NH . H2SO4
excess
S
S
,
)
R3
R3
NH2
R2R3NH . H
2SO4
R1
N
S
2 H O
R1
)
2
2
O
S
3 45 80 oC
a
N
R1
R1
O
O
S
S
R2
-
=
H
p
min
7 21
0
,
,
)
a
N
R2
1
2
3
1
H
2O2
S
S
and complete conversion of xanthogenate to O-alkyl thi-
oncarbamate), the formation of a new compound (GC
analysis). This new compound indicated the formation of
S-alkyl thiolcarbamate. This led to the conclusion that an
excess of ammonium sulfate influences the intramolecular
rearrangement of thioncarbamate to thiolcarbamate.
In this article we describe one-pot synthesis of various
S-alkyl(aryl) thiolcarbamates. Reactions take place by
successive addition of reactants in aqueous media without
the presence of any organic solvent. From an ecological
point of view, water is the most acceptable solvent.
H
2O2
R1
O
S
R1
O
S
4
R2R3NH
S
R3
N
R3
NH2
S
+
R1
O
S
R1
R2
O
S
-
R2
3
5
[ ]
S
O
S
R2R3NH . H
R3
Results and discussion
excess
R3
2SO4
,
R1
N
S
R1
N
O
R2
6
R2
A new synthetic procedure for the preparation of N-alkyl-
(N-aryl-) and N,N-dialkyl-substituted S-alkyl thiolcarba-
mates 2, starting from basic xanthogenate 1, alkyl (aryl)
ammonium sulfate (in excess) and hydrogen peroxide, is
described (Scheme 1). The one-pot three-step procedure
takes place without catalyst and organic solvent. This article
is the continuation of our previous ones regarding the syn-
thesis of S-alkyl thiolcarbamates without previous isolation
of thioncarbamate from the reaction mixture [20, 21].
In the first step, when a solution of alkyl ammonium
sulfate (aryl ammonium sulfate) is introduced into an
aqueous solution of sodium alkyl xanthogenate 1 (equi-
2
R1 Et i P i B
=
=
=
- r - u
,
,
,
,
R2 Et
R3 Et
P
i P Ph 4
l
H4
4
H
H4
3OC6
n- r - r
-
-
-
H4 4 H
C
,
C C6
C
3C6
,
,
,
,
,
n- r - r
i P
P
H
,
be reused in another makes this procedure ecologically
acceptable. In such a manner, waste water can be recycled,
and after several syntheses water can be removed by
evaporation to obtain sodium sulfate. This can be important
for the industrial application of the procedure.
molar amounts),
a
suspension of
a
corresponding
The reaction presented in Scheme 1 proceeds in three
steps (Scheme 2). In the first step, alkyl ammonium salt of
xanthic acid 3 is formed instantly. In the second step,
oxidation by hydrogen peroxide yields dixanthogenate 4,
which is then subjected to nucleophilic attack of the amine
on the S–S bond to give the corresponding sulfenamide 5.
Sulfenamide is transformed to thioncarbamate 6 by sulfur
elimination. In the third step, thioncarbamate isomerizes to
the corresponding thiolcarbamate 7 in the presence of
excess of ammonium sulfate (Scheme 2).
ammonium xanthogenate 3 is formed (Scheme 2). In the
second step, an oxidation using hydrogen peroxide takes
place. After oxidation, the reaction mixture pH is adjusted
to 7 using a 10 % solution of sulfuric acid. Disappearance of
particles of ammonium xanthogenate indicates the forma-
tion of corresponding thioncarbamate 6. By using a solution
of alkyl ammonium sulfate in excess of 10 % and prolonged
heating, the formation of thiolcarbamate 2 is observed (GC
analysis). This clearly implies the transformation of alkyl
xanthogenate to the corresponding thiolcarbamate.
The use of p-substituted arylamines gives solid thiolc-
arbamates, which can be easily separated from the reaction
mixture by simple filtration. The crude products can be
purified by washing with an inert solvent or recrystallizing
from a non-polar solvent such as benzene, or a mixture of
such solvents. N-alkyl-(N-aryl-) and N,N-dialkyl-substi-
tuted S-alkyl thiolcarbamates obtained in this work are
summarized in Table 1.
Synthesized S-alkyl thiolcarbamate is isolated from the
previously neutralized reaction mixture by simple filtration
and separation of the organic phase from the aqueous. Pure
product is then obtained by fractional vacuum distillation
of the organic phase. The filtration cake contains sulfur,
while the aqueous phase can be used again in the next
synthesis. The fact that waste water from one synthesis can
123

New facile one-pot synthesis
1835
Table 1 Synthesis of S-alky lthiolcarbamates
Entry
R1
R2
R3
Conditions
Time/ha
Yield/%c
B.p. or m.p./°C
Found (reported)
t/°Cb
1
2
3
4
Et
Et
Et
Et
Et
H
1.0/2.3
1.2/2.2
1.2/2.3
1.0/1.0
40/80
71
81
73
94
146.0–148.1/13.3d
(116–118/32) [22]
151.0–153.0/13.3d
Et
Et
45/80
40/80
40/70
(141.5–142.0/87) [11]
157.0–159.0/13.3d
(120.5–120.7/20) [11]
117.0–118.0/22.5d
(137.0–138.0/40) [11]
59.5–60.0 (60) [10]
113.0–114.0/16.0d
(113.0–114.0/28.6) [11]
142.0–148.0/13.1d, e [19]
120.0–120.2/10.5d, e [19]
124.0–126.0/10.5d
(97/0.66) [23, 24]
131.0–134.0/10.5d, e [19]
125.0–128.0/10.5d, e [19]
132.0–133.0/10.5d, e [19]
112.1–113.0
n-Pr
n-Pr
H
n-Pr
5
6
Et
Et
i-Pr
i-Pr
H
1.2/2.3
1.5/2.2
40/75
45/75
76
92
i-Pr
7
8
9
i-Pr
i-Pr
i-Pr
Et
H
Et
H
1.0/2.1
1.2/2.2
1.2/2.3
40/80
45/80
40/80
75
83
85
Et
n-Pr
10
11
12
13
i-Pr
i-Pr
i-Pr
i-Pr
n-Pr
i-Pr
i-Pr
Ph
n-Pr
H
1.0/2.0
1.3/2.2
1.4/2.3
1.0/2.0
40/70
45/80
45/80
40/100
95
94
96
96
i-Pr
H
(112–113) [12]
14
15
16
i-Pr
i-Pr
i-Bu
4-ClC6H4
H
H
H
1.1/2.2
1.1/2.2
1.0/2.0
40/90
40/80
40/105
94
97
96
102.5–103.2
(102.7–103.3) [25, 26]
60.1–60.8
4-MeOC6H4
4-MeC6H4
(60.0–60.5) [27]
69.5–70.0
(70) [28, 29]
Reaction conditions: xanthogenate (1.0 mol), alkyl (aryl) ammonium sulfate (0.55 mol), hydrogen peroxide (1.0 mol), pH = 7
a
First and second step reaction time/third step reaction time
b
First and second step reaction temperature/third step reaction temperature
c
Isolated yield
d
Boiling point in vacuum in mbar
1
IR and H NMR spectra were found to be identical to the ones described in the reference
e
Good to excellent yields of the synthesized thiolcarba-
substituents were attached to nitrogen and oxygen atoms,
mate were achieved (Table 1). It should be pointed out that
higher yields were achieved when secondary amines were
used instead of primary ones. When arylamines were
concerned, the highest yields were obtained from aryl-
amines with electron donor groups as substituent.
Therefore, the highest yields achieved were 96 and 97 %
when alkylamines (diisopropylamine) and arylamines were
used (4-methoxyaniline), respectively.
whether S-ethyl- or S-isopropyl thiolcarbamates were
concerned.
It is well known that transformation of O-aryl thiocar-
bamates to S-aryl thiocarbamates is an intramolecular
thermal rearrangement that occurs through a four-member
cyclic transition state in a concerted fashion [19, 30, 31].
This type of rearrangement is known as the Newman-
Kwart rearrangement type [32]. It has been established that
in order for this concerted process of C–O bond breaking
and C–S bond formation in the transition state to occur, a
p-system connected via oxygen to the thiocarbonyl moiety
is essential. It was also established that an electron-
accepting group in para position in the phenyl ring and an
electron-donating group on nitrogen facilitate the reaction
It was previously shown [19] that aryl thiolcarbamate
synthesis can be achieved by heating of the starting aryl
thioncarbamate without catalyst. On the other hand, heat-
ing of certain alkyl thioncarbamates without diethyl sulfate
gives no product [19, 30, 31]. It can be seen from Table 1
that good yields were obtained when a variety of
123

´
M. M. Milosavljevic et al.
1836
spectrometer at 250 MHz for 1H NMR and 62.89 MHz for
13C NMR spectra. The spectra were recorded at room
temperature in deuterated solvent (CDCl3) in 5-mm tubes.
FT-IR spectra were recorded in transmission mode using a
BOMEM 100 (Hartmann and Braun) spectrometer. GC
analysis was performed with a Perkin-Elmer 8700 equip-
ped with an FID detector and a column packed with 5 %
OV-210 on Gas-Chrom Q [length 2 m, diameter 0.3175 cm
(1/800)]; conditions were injector temperature 250 °C,
detector temperature 270 °C, column program mode:
50 °C (5 min) ? 10 °C/min ? 130 °C (15 min), carrier
gas nitrogen (purity 99.99 %, flow 1 cm3/min), air flow
250 cm3/min (purity 99.99 %) and hydrogen flow 25 cm3/
min (purity 99.99 %).
Scheme 3
C
δ -
C
O
S
+
δ
R2R3N
O
S
-
δ
X
+
δ
N
[19] (Scheme 3, left). A corresponding four-membered
cyclic transition state for intramolecular rearrangement of
O-alkyl thioncarbamates has the structure shown in
Scheme 3 on the right [19]. S-Thiolcarbamate is then
formed by the migration of the alkyl group from oxygen to
sulfur.
The transition state formed during rearrangement of aryl
thioncarbamates is more stable in comparison to the tran-
sition state of alkyl thioncarbamates because of the
resonance stabilization of partial negative charges. If
present, the electron-accepting group will additionally
stabilize the transition state. Since there is no resonance
stabilization in a transition state formed during alkyl thi-
Typical procedure exemplified by the preparation
of S-isopropyl ethyl carbamothioate (iPrSCONHEt)
using excess ammonium sulfate
In a 2,000-cm3 three-neck round flask equipped with a
condenser, dropping funnel and thermometer, 192.0 g
(1.0 mol) of 82.4 % sodium isopropyl xanthogenate and
400 cm3 of water were added with stirring. After the
xanthogenate was completely dissolved, 210 cm3 ethyl
ammonium sulfate solution (0.55 mol) was added.
Hydrogen peroxide (26.98 cm3, 1.0 mol) was then added
gradually for 1.2 h while the reaction temperature was
maintained at 40 °C. The pH of the reaction mixture at the
end of this step was 12. Then, 10 % solution of sulfuric
acid was added in order to adjust the pH of the reaction
mixture to 7. The reaction temperature was then increased
to 75 °C and heated for an additional 2.3 h.
The reaction mixture was filtered through a Bu¨chner
funnel, separating sulfur (25.6 g, 80 % compared to the
used xantogenate) from an aqueous phase that contained S-
isopropyl ethyl carbamothioate. The filtrate was then
transferred to a separation funnel, and the organic phase
was separated as the upper layer. The product was obtained
by vacuum distillation at 104–108 °C (660 Pa) yielding
143 g of colorless S-isopropyl ethyl carbamothioate
(75 %). The purity of the product was determined by GC
analysis (99.0 %). The water phase, which contained
0.05 mol of ethyl ammonium sulfate, could then be used
for a new synthesis.
oncarbamate rearrangement,
a
certain degree of
stabilization is achieved by the positive inductive effect of
alkyl groups on nitrogen. The presence of voluminous alkyl
groups such as propyl and isopropyl influence the stability
of the transition state by increasing the entropy factor of
free energy, thus favoring the reaction (Table 1).
Usually, the Newman-Kwart rearrangement type pro-
ceeds at high temperatures (180–300 °C) or in the presence
of catalyst [19, 32]. It was also reported that the O-alkyl
thiocarbamate to S-alkyl thiocarbamate rearrangement
proceeds in the presence of dimethyl sulfate at 130–180 °C
[30, 31] or 120–150 °C without catalyst (O-allyl thiocar-
bamate) [16]. Our procedure requires no catalyst, low
reaction temperatures of 40–80 °C and a 10 % excess of
ammonium sulfate.
In conclusion, this work provides a new powerful and
versatile procedure for the preparation of S-alkyl thiolcar-
bamates from xanthogenate without catalyst using water as
a solvent. This method is characterized by simplicity of
operation, mild reaction conditions and high product
yields, avoiding hazardous organic solvents, and toxic and
expensive reagents. This environmentally friendly process
is a suitable alternative to existing methods.
Preparation of ethyl ammonium sulfate: In a 250-cm3
three-neck round flask equipped with a condenser, drop-
ping funnel and thermometer, 35.4 g 70 % ethylamine
(0.55 mol) and 75 cm3 of water were added with stirring.
After that, diluted sulfuric acid [28.1 g (0.275 mol) of
96 % sulfuric acid diluted with 75 cm3 of water] was
added, while keeping the reaction temperature at 30 °C, to
obtain a pH of 6–7 in the reaction mixture.
Experimental
All products were characterized by comparison of their
spectral and physical data with those of known samples. 1H
NMR spectra were recorded on a Bruker AC 250
123

New facile one-pot synthesis
1837
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Typical procedure exemplified by the preparation
of S-isopropyl 4-chlorophenycarbamothioate
(iPrSCONH(4-ClC6H4)) using excess ammonium
sulfate
In a 2,000-cm3 three-neck round flask equipped with con-
denser, dropping funnel and thermometer, 192.0 g of
82.4 % sodium isopropyl xanthogenate (1.0 mol) and
400 cm3 of water were added, with stirring. After the
xanthogenate had been completely dissolved, 230 cm3
4-ClC6H4NH2ꢀH2SO4 solution (0.55 mol) was added. The
ammonium solution was prepared as described before.
Hydrogen peroxide (26.98 cm3, 1.0 mol) was then added
gradually for 1.1 h while the reaction temperature was
maintained at 40 °C. The pH of the reaction mixture at the
end of this step was 12. Then, 10 % sulfuric acid solution
was added in order to adjust the pH of the reaction mixture
to 7. After that, the reaction temperature was increased to
90 °C and heated for an additional 2.2 h.
The reaction mixture was cooled to room temperature
and filtered through a Bu¨chner funnel, thus separating
sulfur and S-isopropyl 4-chlorophenycarbamothioate as a
cake from an aqueous phase. The cake was washed with
water, and the product was purified by crystallization from
benzene. N-(4-chlorophenyl)-S-isopropyl thiolcarbamate
was obtained in 94 % (215.95 g). GC purity of the product
was 99.4 %, melting point 102.5–103.0 °C ([25, 26],
102.7–103.3 °C). The amount of isolated sulfur was 25.8 g
(80.1 % compared to the used xanthogenate). The water
phase, which contained 0.05 mol of 4-ClC6H4NH2ꢀH2SO4,
can be used for a new synthesis.
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Acknowledgments This work was supported by the Ministry of
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