A new and facile route for the synthesis of thiocarbamates from aniline, carbon monoxide, and thiols mediated by selenium

Article abstract of DOI:10.1246/cl.2005.606

A new and facile route for the synthesis of thiocarbamates was reported. Mediated by selenium, aniline reacts very readily with carbon monoxide and thiols in the presence of triethylamine, to afford the corresponding thiocarbamates mostly in moderate to excellent yields under mild reaction conditions. Selenium can be easily recovered and recycled. Copyright

Full text of DOI:10.1246/cl.2005.606

606
Chemistry Letters Vol.34, No.4 (2005)
A New and Facile Route for the Synthesis of Thiocarbamates from Aniline,
Carbon Monoxide, and Thiols Mediated by Selenium
Xiaopeng Zhangy;yy and Shiwei Luꢀy;yy
yNational Engineering Research Center for Catalysis, Dalian Institute of Chemical Physics, Chinese Academy of Sciences,
161 Zhongshan Road, Dalian 116011, Liaoning, P. R. China
yyGraduate School of Chinese Academy of Sciences, Beijing, P. R. China
(Received January 21, 2005; CL-050096)
A new and facile route for the synthesis of thiocarbamates
monoxide, to afford the corresponding thiocarbamates and
hydrogen selenide (Eq 1). Selenium can be easily recovered by
oxidizing hydrogen selenide in the open air (Eq 2) and can be
recycled.
was reported. Mediated by selenium, aniline reacts very readily
with carbon monoxide and thiols in the presence of triethyl-
amine, to afford the corresponding thiocarbamates mostly in
moderate to excellent yields under mild reaction conditions.
Selenium can be easily recovered and recycled.
In order to find the optimal experimental conditions, the re-
action of aniline with propanethiol was examined. All reagents
were used directly without further purification. In the absence
of selenium or triethylamine, the reaction couldn’t proceed at
all. Other bases commonly used such as organic bases pyridine
and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and inorganic
bases sodium acetate, sodium hydroxide and potassium hydrox-
ide did not work (Table 1, Entries 2–6). The reaction was con-
ducted at ambient temperature, for the higher the temperature,
the more the side-product diphenylurea (Table 1, Entries 7–9).
The reaction proceeded well without solvent, reaching comple-
tion within 10 h. The desired product phenylthiocarbamic acid
S-propyl ester was obtained in high yield in addition to a little
side-product diphenylurea. Selenium can be easily recovered
from the reaction mixture by simple filtration after its precipita-
tion. The product was purified either by column chromatography
or by recrystallization from light petroleum ether.14
To demonstrate the scope and efficiency of the present meth-
od, a variety of thiols were tested under the optimal conditions
and the results were summarized in Table 2. As shown in
Table 2, the reaction is amenable to a range of thiols. For straight
chain thiols, the reaction proceeded well to give the correspond-
ing thiocarbamates in high yields (Entries 1, 2, 4, 6, 7). Phenyl-
thiocarbamic acid S-benzyl ester (2i) was obtained in excellent
yields (Entry 9). Steric factors seemed to explain the lower
yields of thiocarbamates with branch components (Entries 3,
Thiocarbamates have received considerable attention owing
to their importance in medicine as bactericides1 and antivirus;2
in biology as bioregulators3 and enzyme inhibitors;4 and in agri-
culture as pesticides5 and herbicides.6 Various methods are
known in the literature for the synthesis of thiocarbamates. Most
frequently used approaches include; (1) the reaction of amine
with carbon monoxide and element sulfur, followed by alkyla-
tion with alkyl halides;6c,6e,7 however, this method suffers from
drawbacks such as multistep approaches, voluminous solvent re-
quired; (2) Intramolecular rearrangements of various deriva-
tives; however, these methods are extremely limited in starting
materials;8 (3) Addition of thiols to isocyanates; deleterious, ex-
pensive and less readily available isocyanates and catalysts are
limitations associated with these methods;6d,9 (4) Oxidative cou-
pling of aryl thiols with amines and carbon monoxide; but this
method usually requires complex and expensive catalysts.10 In
addition, thiocarbamates synthesis has also been accomplished
by selenium-catalyzed carbonylation of amine and disulfide.11
Cyclic thiocarbamates can be obtained from the reaction of ami-
no thiols with carbon monoxide in the presence of selenium.12
A recent report disclosed the synthesis of thiocarbamates by
a two-step approach making use of trichloroacetyl chloride,
thiols, and amines.13 Although this method proceeds in high
yields, it posed the following problem: incorporating moisture-
sensitive reaction which need cautious operations and applying
significant excess of trichloroacetyl chloride and amines.
Table 1. The influence of base and temperature on the carbon-
ylation of aniline to thiocarbamatesa
Entry
Base
Temp.
Yieldb/%
NH2
+
+
+
Se
CO
RSH
1
1
2
3
4
5
6
7
8
9
None
Pyridine
DBU
NaOAc
NaOH
KOH
Et3N
Et3N
Et3N
Ambient Temp.
Ambient Temp.
Ambient Temp.
Ambient Temp.
Ambient Temp.
Ambient Temp.
Ambient Temp.
30 ꢁC
0
0
0
0
0
0
(1)
(2)
Et3N
+
+
H2Se
NHCOSR
2
86(6)c
77(15)c
36(57)c
+ 1/2 O2
H2Se
Se
H2O
70 ꢁC
Herein, we describe a new and facile one-pot approach to
thiocarbamates. Mediated by stoichiometric selenium, aniline
reacts very readily with thiols in the presence of triethylamine
at ambient temperature under atmospheric pressure of carbon
aReaction conditions: aniline, 5 mmol; propanethiol, 5 mmol;
Se, 5 mmol; base, 10 mmol; 10 h; atmospheric pressure of
carbon monoxide. Isolated yield. cDiphenylurea.
b
Copyright Ó 2005 The Chemical Society of Japan

Chemistry Letters Vol.34, No.4 (2005)
607
Table 2. Isolated yields of thiocarbamate using aniline as one
of the reactantsa
J. Enzyme Inhib., 16, 95 (2001). c) R. M. Nathan and C. J.
Peter, J. Med. Chem., 46, 1066 (2003).
5
6
a) ‘‘The Pesticide Mannal,’’ 9th ed., ed. by C. R. Worthing,
British Crop Protection Council, London (1991). b) W. A.
Breiter, J. M. Baker, and W. C. Koskinen, J. Agric.
Food Chem., 46, 1624 (1998). c) S. J. Lee, P. Caboni, M.
Tomizawa, and J. E. Casida, J. Agric. Food Chem., 52, 95
(2004).
Entry
Thiol
R
Product
Yield/%
1
2
3
4
5
6
7
8
9b
10
11c
12
13
1a
1b
1c
1d
1e
1f
1g
1h
1i
Ethyl
Propyl
Isopropyl
Butyl
tert-Butyl
Pentyl
Hexyl
Cyclohexyl
Benzyl
Phenyl
2a
2b
2c
2d
2e
2f
2g
2h
2i
86
86
64
83
17
83
83
74
90
31
22
40
53
a) Y. S. Chen, I. Schuphan, and J. E. Casida, J. Agric. Food
Chem., 27, 709 (1979). b) H. J. Sanders, Chem. Eng. News,
59, 20 (1981). c) T. Mizuno, I. Nishiguchi, T. Okushi, and
T. Hirashima, Tetrahedron Lett., 32, 6867 (1991). d) Y.
Nagao, Y. Abe, T. Misono, N. Ichizen, Y. Shima, H. Iesaka,
and M. Furushima, Nippon Kagaku Kaishi, 1993, 719. e) N.
Sonoda, T. Mizuno, S. Murakami, K. Konda, A. Ogawa, and
I. Ryu, Angew. Chem., Int. Ed. Engl., 28, 452 (1989).
a) T. Mizuno, I. Nishiguchi, and N. Sonoda, Tetrahedron, 50,
5669 (1994). b) T. Mizuno, T. Daigaku, and I. Nishiguchi,
Tetrahedron Lett., 36, 1533 (1995). c) T. Mizuno, T. Junko,
and A. Ogawa, Tetrahedron, 59, 1327 (2003). d) T. Mizuno,
T. Iwai, A. Ogawa, and T. Ito, Tetrahedron, 60, 2869 (2004).
a) H. Kwart and E. R. Evans, J. Org. Chem., 31, 410 (1966).
b) R. E. Hackler and T. W. Balko, J. Org. Chem., 38, 2106
(1973). c) M. Sakamoto, M. Yoshiaki, M. Takahashi, T.
Fujita, and S. Watanabe, J. Chem. Soc., Perkin Trans. 1,
1995, 373. d) A. Bohme and H. J. Gais, Tetrahedron:
Asymmetry, 10, 2511 (1999).
1j
1k
1l
2
2k
2l
4-Chlorophenyl
4-Methylphenyl
4-Methoxyphenyl
1m
2m
7
8
aReaction conditions: aniline, 5 mmol; thiol, 5 mmol; Se,
5 mmol; Et3N, 10 mmol; 10 h; ambient temperature; atmo-
spheric pressure of carbon monoxide. 8 h. 2 mL acetone.
b
c
5, 8). When aryl thiols were used instead of alkyl thiols in the
reactions, poor yields were obtained (Entries 10–13). This is
mostly due to the weak nucleophilicity of aryl thiols. Electric ef-
fect of aryl thiols seemed to affect the reaction observably. The
aryl thiol bearing electron-donating group is more reactive than
that with electron-withdrawing group, resulting in the higher
product yield of the former (Entry 13, 1m) than the latter
(Entry 11, 1k).
9
A. Ricci, R. Danieli, and G. Pirazzini, J. Chem. Soc., Perkin
Trans. 1, 1977, 1069.
Recycling of selenium was carried out by filtration of cata-
lyst from the crude reaction mixture followed by drying it. Using
the reaction of aniline with propanethiol as an example, the re-
usability of the catalyst was tested and the product yield only
dropped from 86 to 78% after five recycles.
10 a) W. D. Jones, K. A. Reynolds, C. K. Sperry, R. J.
Lachicotte, S. A. Godleski, and R. R. Valente, Organometal-
lics, 19, 1661 (2000). b) J. Jacob, K. A. Reynolds, W. D.
Jones, S. A. Godleski, and R. R. Valente, Organometallics,
20, 1028 (2001).
In summary, we have developed a new and facile one-pot
approach to thiocarbamates. Using straight or less hindered alkyl
thiols as thiol reactant, this reaction can proceed well with ani-
line to thiocarbamates in high yields. Simple starting materials,
cheap and recyclable selenium, one-pot synthesis, mild reaction
conditions, simple operation of the reaction, and simple purifica-
tion of the products make the present method very significant
from the view point of application.
11 P. Koch, Tetrahedron Lett., 25, 2087 (1975).
12 N. Sonoda, G. Yamamoto, K. Natsukawa, K. Kondo, and S.
Murai, Tetrahedron Lett., 24, 1969 (1975).
13 J. H. Wynne, S. D. Jensen, and A. W. Snow, J. Org. Chem.,
68, 3733 (2003).
14 Typical experimental procedure is as follows (Table 2,
Entry 2): To a 500-mL three-neck round-bottom flask, sele-
nium (5 mmol), aniline (5 mmol), propanethiol (5 mmol),
and triethylamine (10 mmol) were added. The reactor was
sealed, and then vacuumized. Then carbon monoxide was in-
troduced to it. The reactor was then connectted with atmo-
spheric pressure of carbon monoxide. The reaction proceed-
ed at ambient temperature with stirring. After 10 h, the appa-
ratus was placed in the open air. The crude product was then
dissolved in THF and stirred for another 30 min to precipitate
selenium. Selenium was then recovered by filtration. The fil-
trate was concentrated. The pure phenylthiocarbamic acid S-
propyl ester (2b) was obtained either by column chromatog-
raphy (silica gel, chloroform/petroleum ether, 2/1) in 86%
yield or by recrystallization from light petroleum ether in
73% yield as colorless needles. mp: 83–84 ꢁC (lit.15 mp:
84 ꢁC); 1H NMR (400 MHz, CDCl3) ꢀ 7.42–7.07 (m,6H),
2.95 (t, J ¼ 8:0 Hz, 2H), 1.68 (sextet, J ¼ 8:0 Hz, 2H),
0.99 (t, J ¼ 8:0 Hz, 3H).
References and Notes
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3
4
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Published on the web (Advance View) March 19, 2005; DOI 10.1246/cl.2005.606