September 1998
SYNLETT
971
Reduction of Selenium with BER in Methanol. Application to Synthesis of Dialkyl Selenides
*a
a
b
Kazuo Yanada, Tetsuro Fujita, and Reiko Yanada
a
Faculty of Pharmaceutical Sciences, Setsunan University, Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan
b
Faculty of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan
FAX 0720-66-3146; E-mail: yanada@pharm.setsunan.ac.jp
Received 8 June 1998
Abstract: Selenium was reduced with borohydride exchange resin
(BER) in methanol at room temperature to give probably a selenide
exchange resin. It reacted with alkyl halide or tosylate to give dialkyl
selenides selectively in a quantitative or high yield without forming
toxic hydrogen selenide and/or foul-smelling selenol.
benzyl chloride, dibenzyl selenide was produced in 96% or 92% yield,
respectively, after 24 h.
Scheme 2 shows the plausible mechanism. In the first stage, gray
-
selenium is reduced with BER to the selenide anion (probably HSe ) and
it is quickly exchanged for the borohydride anion while the liberated
borane is eliminated with the solvent methanol. When the resin in this
stage was filtered off and exposed to air, a black coating of selenium was
Selenium, which is an essential trace element, has been recognized to
function as an active center of redox enzyme such as glutathione
-
observed. In the second stage, the SeH anion on the resin reacts with
-
8,9
1
RX to give an RSe anion on the resin. In the third stage, it reacts with
RX and the product RSeR is released from the resin.
peroxidase and as a modifying factor in the toxicities of heavy metals.
Previously, when we synthesized dialkyl selenide from selenium by
reducing with sodium borohydride and the following reaction with alkyl
2
bromide, we were troubled with the foul smell of the by-product
selenol and toxic hydrogen selenide. Borohydride exchange resin (BER)
is
a
quarternary ammonium borohydride and exhibits unique
3
selectivities which were not realized with sodium borohydride. It has
been shown that diphenyl diselenide was readily reduced with BER and
the following addition with alkyl halide gave alkyl phenyl selenides.
4
However, there is no example where selenium is reduced with BER. We
have been studying the selenium-catalyzed reduction with sodium
5
borohydride from the biomimetic standpoint. The mildness and
operational simplicity of this new protocol encouraged us to further
investigate its scope and utility with the reaction of a borohydride
derivative and selenium. We report here that powdered elemental gray
selenium was reduced readily with BER in methanol to give probably a
selenide exchange resin and it can be utilized directly in a typical
nucleophilic displacement reaction such as with alkyl halide or tosylate
to prepare dialkyl selenide selectively without emitting foul smell
(Scheme 1).
Scheme 1
Scheme 2
The typical experiment was performed as follows: Powdered gray
selenium (1 mmol) and BER (9 mmol) are stirred vigorously in
methanol (12 ml) under an argon atmosphere for 18 h. To the reaction
mixture was added a solution of alkyl halide (2.4 mmol) in methanol (3
ml) and then it was stirred for 2 h. After the resin was filtered off, the
filtrate was evaporated and purified by column chromatography.
In conclusion, BER is a more practical reagent for the preparation of
dialkyl selenide than sodium borohydride. There is no foul smell
because selenolate and hydrogen selenide are probably trapped on the
anion-exchange resin. And then the resin is removed easily by filtration.
Now we are investigating use of this method for the synthesis of
unsymmetrical selenides.
6
Table 1 summarizes the results. Primary benzyl halide such as benzyl
bromide or benzyl chloride gave dibenzyl selenide in 96% or 92%,
respectively (Runs 1 and 2). Secondary benzyl bromide such as 1-
References and Notes
7
(1) For reviews see: Tanaka, J. Kikan Kagaku Sosetsu 1995, 27, 120;
Chem. Abstr. 1995, 124, 338600. Masukawa, T. In The Chemistry
of Organic Selenium and Tellurium Compounds, Vol. 2; Patai, S.
Ed.; John Wiley & Sons Ltd.: Chichester, 1987; Chap. 9.
bromo-1-phenylethane gave bis(1-phenylethyl) selenide in 98% (Run
3). Primary alkyl halide such as 1-bromo-2-phenylethane gave bis(2-
phenylethyl) selenide in 97% (Run 4). Tosylate such as 2-phenylethyl
tosylate reacted similarly to 1-bromo-2-phenylethane (Run 5). Alkyl
iodide such as decyl iodide gave didecyl selenide (Run 6), but an
aromatic iodide such as iodobenzene was inert. Water could be used for
the solvent instead of methanol. When benzyl bromide was reacted in
water under similar conditions, dibenzyl selenide was obtained
quantitatively. The reaction proceeded also when all reagents were
stirred at the same time in methanol. In the case of benzyl bromide or
(2) (a) Klayman, D. L.; Griffin, T. S. J. Am. Chem. Soc. 1973, 95, 197.
(b) See review for the synthetic use of organoselenium
compounds: Swiss, K. A.; Liotta, D. C. In Comprehensive
Organic Synthesis, Vol. 7; Trost, B.M.; Fleming, I.; Ley, S.V., Eds;
Pergamon Press: Oxford, 1991, p 515. (c) See review for the
reduction of elemental selenium: Paulmier, C. Selenium Reagents
Yanada, Kazuo
