Straightforward and highly efficient synthesis of diselenocarbamates

Article abstract of DOI:10.1021/ol3028626

A highly efficient and simple synthesis of diselenocarbamates, based on a one-pot reaction of amines, CSe₂, and alkyl halides in the absence of a catalyst under solvent-free conditions, is reported. The first efficient synthesis of diselenocarbamates via Michael addition of electron-deficient alkenes with aliphatic amines and CSe₂ in solid media silica gel is also presented.

Full text of DOI:10.1021/ol3028626

ORGANIC
LETTERS
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Vol. XX, No. XX
000–000
Straightforward and Highly Efficient
Synthesis of Diselenocarbamates
Xiangqiang Pan, Jian Zhu, Jianping Zou, Zhengbiao Zhang, Zhenping Cheng,
Nianchen Zhou, Wei Zhang, and Xiulin Zhu*
Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application,
Department of Polymer Science and Engineering, College of Chemistry, Chemical
Engineering and Materials Science, Soochow University, Suzhou, 215123, P. R. China
xlzhu@suda.edu.cn
Received October 17, 2012
ABSTRACT
A highly efficient and simple synthesis of diselenocarbamates, based on a one-pot reaction of amines, CSe2, and alkyl halides in the absence of a
catalyst under solvent-free conditions, is reported. The first efficient synthesis of diselenocarbamates via Michael addition of electron-deficient
alkenes with aliphatic amines and CSe2 in solid media silica gel is also presented.
During the last few decades, many syntheses of com-
pounds containing selenium have been reported because
of their interesting reactivity and potential biological
activity.1 The biological and pharmacological activity of
selenium and organoselenium compounds are of increas-
ing interest because of their antioxidant, antitumor, and
antiviral properties.2 The selenium compounds have also
showntheabilitytocontrol thefree-radicalpolymerization
of vinyl monomers.3 A number of methods for the synthesis
of organoselenium compounds have been published in the
literature.4 Among the organoselenium compounds, diseleno-
carbamates have received less attention,5 and the synthesis of
diselenocarbamates has rarely been reported. General meth-
ods for their synthesis involve the reaction of an amine with
isoselenocyanate6 or the reaction of N,N-dimethylselenocar-
bamoyl chloride with lithium alkylselenolate.7
Scheme 1. Reaction of Amines and CSe2
(1) (a) Jensen, K. A.; Kjaer, A. In The Chemistry of Organic Selenium
and Tellurium Compounds; Patai, S., Rappoport, Z., Eds.; Wiley-Interscience:
New York, 1987; Vol. 1, pp 13. (b) Klayman, D. L.; Shine, R. J. J. Org. Chem.
1969, 34, 3549. (c) Comasseto, J. V.; Ling, L. W.; Petragnani, N.; Stefani,
H. A. Synthesis 1997, 373. (d) Li, G. M.; Zingaro, R. A. J. Chem. Soc.,
Perkin Trans. 1 1998, 647. (e) Koketsu, M.; Suzuki, N.; Ishihara, H. J. Org.
Chem. 1999, 64, 6473.
(2) (a) Mugesh, G.; Mont, W. W.; Sies, H. Chem. Rev. 2001, 101,
2125. (b) Nogueira, C. W.; Zeni, G.; Rocha, J. B. T. Chem. Rev. 2004,
104, 6255. (c) Mukherjee, A. J.; Zade, S. S.; Singh, H. B.; Sunoj, R. B.
Chem. Rev. 2010, 110, 4357.
(3) Zeng, J.; Zhu, J.; Zhang, Z.; Pan, X.; Zhang, W.; Cheng, Z.; Zhu,
X. J. Polym. Sci., Polym. Chem. 2012, 50, 2211–2218.
~
(4) (a) Perin, G.; Lenardao, E. J.; Jacob, R. G.; Panatieri, R. B. Chem.
Rev. 2009, 109, 1277. (b) Murai, T.; Kato, S. In Organoselenium
Chemistry. Modern Developments in Organic Synthesis; Springer-Verlag:
New York, 2000; p 177.
Scheme 2. One-Pot Synthesis of Se-Alkyl Diselenocarbamates
(5) (a) Barnard, D.; Woodbridge, D. T. J. Chem. Soc. 1961, 2922.
(b) Monteiro, O. C.; Trindade, T.; Paz, F. A. A.; Klinowski, J.; Waters,
J.; O’Brien, P. J. Mater. Chem. 2003, 13, 3006. (c) Christensen, J. B.;
Bechgaard, K.; Paquignon, G. J. Labelled Compd. Radiopharm. 2001,
44, 1035. (d) Jensen, K. A.; Krishnan, V. Acta Chem. Scand. 1967, 21,
2904.
r
10.1021/ol3028626
XXXX American Chemical Society

Carbon diselenide can be used as the key reagent for the
synthesis of diselenocarbamates5 but is rarely mentioned in
the literature. Carbon diselenide can polymerize in the
presence of amines,5a and some transition-metal diseleno-
carbamate complex can be prepared by the reaction of
carbon diselenide (CSe2) with secondary amines and metal
salts (Scheme 1).5b However, the efficient synthesis of
diselenocarbamates from CSe2 has rarely been described.5c
During the course of a study aimed at improving the
ecocompatibility of certain organic processes, some organic
transformations under solvent-free conditions were per-
formed to develop environmentally benign reactions.8
Herein, an efficient, novel, and highly simple procedure
for the direct synthesis of diselenocarbamates from a one-
pot reaction of simple compounds (e.g., amines, CSe2, and
alkyl halides) without the use of a catalyst and under
solvent-free conditions at low temperature is described
(Scheme 2).
Scheme 3. Screening of Solvents
In our approach, CSe2 was prepared by reaction of
Se with an excess of CH2Cl2 according to a previously
published protocol.9 First, the treatment of CSe2 (1 mmol)
and benzyl chloride (1 mmol) with diethylamine (2 mmol)
Table 1. One-Pot Synthesis of Se-Alkyl Diselenocarbamates without a Catalyst under Solvent-Free Conditionsa
a Reaction conditions: amine (2 mmol), CSe2 (1 mmol), alkyl halide (1 mmol), À10 °C. Isolated yields are based on the alkyl halide. For a detailed
experimental procedure, see the Supporting Information.
B
Org. Lett., Vol. XX, No. XX, XXXX

was examined (Table 1, entry 1). Surprisingly, the reaction
occurredreadily atÀ10°C, and product 1cwas obtained in
92% yield after workup of the reaction mixture (Table 1,
entry 1). The reaction was also performed in organic
solvents, such as CH2Cl2, THF, diethyl ether, CH3CN,
and ethanol, for comparison. Moderate yields of the
product were obtainedin organic solvents, such as CH3CN
and CH2Cl2, after 30 min (Scheme 3). However, the best
result was obtained from a one-pot reaction under solvent-
free conditions at À10 °C affording the Se-alkyl diseleno-
carbamate in excellent yield without the use of a catalyst.
The structure of 1c was elucidated by 1H NMR, 13C NMR,
and LCMS studies.
Scheme 4. Mechanism of the One-Pot Reaction
Next, the scope and limitations of this simple process
were explored using a wide range of alkyl halides and
secondary amines. A variety of structurally diverse amines
and alkyl halides, including chloride, bromide, and iodide,
were employed in the one-pot reaction in the absence of a
catalyst or solvent to afford the corresponding Se-alkyl
diselenocarbamate derivatives in moderate to high yields
(higher than 72%). The results are summarized in Table 1.
The generality of the present method was also extended to
primary amines. However, unidentified side products were
obtained in the reaction of aniline (Table 1, entry 26).
Monosubstituted diselenocarbamate has been reported to
be unstable and could decompose or undergo nucleophilic
addition with another primary amine to afford selenourea
or other byproducts.10
Scheme 5. Nucleophilic Addition of Aminium
Diselenocarbamate to Michael Acceptors
Table 2. One-Pot Synthesis of Se-Alkyl Diselenocarbamates
under Solvent-Free Conditionsa
The reactions reached completion after 10À30 min with
72À95% yields. Commercially available alkyl halides and
secondary amines were employed under the same condi-
tions for both reactive and unreactive alkyl halides and
amines. Therefore, a diverse set of synthetically useful
diselencarbamate products can potentially be prepared in
one step by this method. In this reaction, CSe2 was first
attacked by the secondary amine to yield the aminium
diselenocarbamate, which converted directly to the disele-
nocarbamate derivatives with the alkyl halide (Scheme 4).
The yield of this reaction was controlled by the steric
hindrance in the alkyl halides, which decreased in the
following order: primary alkyl halides > secondary alkyl
halides, with tertiary alkyl halides yielding trace amounts
of diselenocarbamate (Table 1, entry 25). Many of the
synthesized diselenocarbamates are yellow solids and dis-
play good stability in the refrigerator but slowly decom-
pose at room temperature.
To exploit the in situ generated aminium diselenocarba-
mate for other useful reactions, we explored a Michael-
type addition to conjugated alkenes (Scheme 4).11 First,
(6) (a) Garud, D. R.; Tanahashi, N.; Ninomiya, M.; Koketsu, M.
Tetrahedron 2009, 65, 4775. (b) Koketsu, M.; Yamamura, Y.; Ishihara,
H. Synthesis 2006, 2738.
(7) (a) Koketsu, M.; Fukuta, Y.; Ishihara, H. J. Org. Chem. 2002, 67,
1008. (b) Ishihara, H.; Koketsu, M.; Fukuta, Y.; Nada, F. J. Am. Chem.
Soc. 2001, 123, 8408.
(8) Azizi, N.; Aryanasab, F.; Saidi, M. R. Org. Lett. 2006, 8, 5275.
(9) Pan, W. H.; Fackler, J. P., Jr. Inorg. Synth. 1982, 21, 6.
(10) Warxer, J. S. J. Org. Chem. 1962, 28, 1462.
(11) In ref 6, the Michael addition of diselenocarbamate intermedi-
ates was studied, and moderate yields were obtained in that reaction.
a Reaction conditions: amine (2 mmol), CSe2 (1 mmol), Michael
acceptors (1.5 mmol), rt. For a detailed experimental procedure, see the
Supporting Information.
Org. Lett., Vol. XX, No. XX, XXXX
C

piperidine was reacted with CSe2 and methyl acrylate
to screen various media. After optimizing the condi-
tions, silica gel exhibited the best result among the
screened media, (i.e., silica gel, alkaline Al2O3, solvent-free
and diverse solvents (CH2Cl2, CH3CN, n-hexane, and
water)).
In summary, we have developed a highly practical and
reliable procedure for the synthesis of a wide range of
diselenocarbamates using CSe2 and readily available start-
ing materials in one pot. In addition, the Michael-type
addition of the aminium diselenocarbamate was reported.
In general, the solvent-free reaction is experimentally simple
and generates virtually no byproducts. Equally important is
the wide scope, high selectivity, and nearly quantitative
yields of this transformation, which collectively allow sig-
nificant structural diversity to be incorporated into the
products; that was not possible via the previously published
procedures. Our procedure provides a new route for the
assembly of diselenocarbamates from simple starting mate-
rials. Further exploitation of this methodology is currently
underway in our laboratories. The exploration of these
compounds as mediators in the free-radical polymerization
of vinyl monomers is also underway in our laboratories.
With optimal conditions in hand, we examined the
generality of these conditions to other substrates by using
different amines and R,β-unsaturated compounds. The
results are summarized in Table 2. All of the reactions
proceeded smoothly under the optimized conditions by
stirring all of the reagents together in the presence of silica
gel. Using methyl acrylate and acrylonitrile as a Michael
receptor, all of the tested aliphatic amines afforded the
expected products with good to excellent yields (Table 2,
entries 1À9). However, the reactions of primary amines
cannot give good results due to the instability of the
intermediates. When using substituted R,β-unsaturated
compounds, such as cyclohexenone and chalcone, as Mi-
chael receptors, the addition reaction does not proceed
effectively. The nucleophilicity of the diselenocarbamic
anion and the steric hindrance of R,β-unsaturated com-
pounds most likely played a role under these conditions.
In this reaction, the aminium diselenocarbamate is
also the key intermediate which was first obtained in the
reaction of CSe2 with the amine and then underwent
Michael-type addition to conjugated alkenes to afford
the substituted diselenocarbamate. The amine might be
absorbed on the surface of the silica gel, and the Lewis acid
catalytic activity of silica gel could promote the nucleo-
philic addition of the intermediate to conjugated alkenes
(Scheme 5).
Acknowledgment. This work was supported by the
National Natural Science Foundation of China (No.
21074082), China Postdoctoral Science Foundation (No.
2012M511315), the Priority Academic Program Develop-
ment of Jiangsu Higher Education Institutions, and the
Natural Science Foundation of the Jiangsu Higher Educa-
tion Institutions of China (No. 12KJB150021).
Supporting Information Available. General experimen-
1
tal details and spectral data (IR, H NMR, 13C NMR,
LCMS) of compounds. This material is available free of
charge via the Internet at http://pubs.acs.org.
The authors declare no competing financial interest.
D
Org. Lett., Vol. XX, No. XX, XXXX