Conditions-driven selective synthesis of selenides and selenols from elemental selenium

Article abstract of DOI:10.1055/s-2004-829554

Sodium borohydride in DMF is able to reduce elemental selenium in the presence of ethanol. Alkylation of the species resulting from the reaction of 2:1 molar equivalents of NaBH₄/Se allows the selective synthesis, under very mild conditions, of symmetrical dialkyl selenides. Addition of formic acid, prior to that of the electrophile, permits the synthesis of the corresponding selenols.

Full text of DOI:10.1055/s-2004-829554

LETTER
1751
Conditions-Driven Selective Synthesis of Selenides and Selenols from
Elemental Selenium
a
a
a
a,b
S
A
elective Synthesi
l
s of Se
l
a
enide
s
and
i
S
eleno
n
ls Krief,* Mahmoud Trabelsi, Willy Dumont, Michel Derock
a
Laboratoire de Chimie Organique de Synthèse, Département de Chimie, Facultés Universitaires Notre-Dame de la Paix,
1 rue de Bruxelles, B-5000 Namur, Belgium
6
Fax +32(81)724536; E-mail: alain.krief@fundp.ac.be
b
Fonds pour la Formation à la Recherche dans l’Industrie et l’Agriculture, 5 rue d’Egmont, Bruxelles 1000, Belgium
Received 16 April 2004
In memoriam Dr Anne Giese, née Ghosez, for her contribution to the development of Organic Chemistry through Synlett.
This complex is prepared by adding ethanol to a seleni-
um–sodium borohydride solid mixture maintained at
Abstract: Sodium borohydride in DMF is able to reduce elemental
selenium in the presence of ethanol. Alkylation of the species result-
2
0 °C. The alkylation is then performed at room tempera-
ing from the reaction of 2:1 molar equivalents of NaBH /Se allows
4
ture on the colourless solution of that complex in DMF.
the selective synthesis, under very mild conditions, of symmetrical
dialkyl selenides. Addition of formic acid, prior to that of the elec- Performing the reaction in that order avoids the formation
trophile, permits the synthesis of the corresponding selenols.
of by products resulting from the decomposition of DMF.
Key words: elemental selenium, sodium borohydride, alkylation,
alkyl halides, benzyl halides
The reaction proceeds extremely well at room tempera-
ture providing primary and secondary dialkyl and diben-
zyl selenides in very high yield (Scheme 1, Table 1).
Interestingly, dialkyl diselenides 2, which are often con-
comitantly formed in the synthesis of dialkyl selenides 1¢,
have not been found using our procedure (Scheme 1).
1
Selenides 1 are valuable synthetic intermediates which
have been often prepared by alkylation of metal selenides
1
1
(
MSeM) or organic selenolates (RSeM).
1
Those, as well as metal hydroselenides (HSeM), are
available by reduction of elemental selenium either by
DMF
2 RX
-[H2]
2
NaBH4 + Se(0) + 6 EtOH
[Complex A]
RSeR + 7 H2
-[6 H2]
1'
2
3
metals, or by 4 metal hydrides, m5 etal hydroxy-
Scheme 1 Synthesis of symmetrical selenides 1¢
Table 1 Reaction Conditions of the Synthesis of Dialkyl Selenides 1¢
methanesulfinates and organometallics.
3
a
Sodium borohydride was the first hydride used for that
purpose. It possesses the advantage to be commercially
available and is easy to handle but the reaction is limited.
It has been carried out on benzyl chloride, one of the most
reactive electrophile, in water whose use is inadequate for
organic reactions.
Ammonium borohydride3c and borohydride3d exchange
resin have been proposed as alternative reagents. The later
avoids the inconveniencies reported above and allows the
synthesis of a few primary dialkyl selenides as well as a
primary and a secondary benzyl selenide, but the method
Entry
RX
1¢:2
Yield (%) of 1¢
a
b
c
d
e
f
n-Bu-Br
n-Dec-Br
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
93
100
97
PhCH -Br
2
PhCH -Cl
95
2
sec-Octyl-Br
sec-Bu-Br
92
3
d
carries its proper limitations.
92
g
h
iso-Pr-I
91
Synthesis of Symmetrical Dialkyl Selenides 1¢
PhCH(Me)-Br
98
We now report that symmetrical dialkyl selenides 1¢ can
be efficiently produced in DMF from elemental selenium,
two molar equivalents of sodium borohydride and two
equivalents of alkyl halides at the condition that 6 equiv-
alents of ethanol are present in the medium prior the
The amount of ethanol used is not crucial for the reaction
to proceed at the condition that it is higher than 6 equiva-
lents and not so high that it plays the role of the solvent.3f
Other alcohols such as i-propanol and t-butanol can be
used in place of ethanol. However, they do not offer spe-
cific advantages. Methanol should not be used since it re-
acts too rapidly with sodium borohydride.
3
f
alkylation step (Complex A).
We have carefully monitored the evolution of hydrogen
generated in this process and found that 6 molar equiva-
lents escape from the medium (experimentally 97% of this
amount) just before the alkyl halide is added and another
SYNLETT 2004, No. 10, pp 1751–1754
Advanced online publication: 15.07.2004
DOI: 10.1055/s-2004-829554; Art ID: G13004ST
0
9
.0
8
.2
0
0
4
©
Georg Thieme Verlag Stuttgart · New York

1
752
A. Krief et al.
LETTER
Dec-Se-CH2Ph
"a
DMF
(i) Dec-Br
1
2
NaBH4 + Se + 6 EtOH
Complex A
2
0 °C, 1 h
(ii) PhCH2Cl
(Dec)2Se + (PhCH2)2Se
1'a 1'b
Scheme 2
Decyl-Se-H
(i) Decyl-Br
DMF
0 °C, 1 h
3a
2
NaBH4 + Se + 6 EtOH
Complex A
2
(ii) HCO2H
(Decyl)2Se
1'a
Scheme 3
Table 2 Reaction Conditions of the Synthesis of Alkyl Selenols 3
one (experimentally 1.2 molar equivalents of this amount)
on addition of the alkyl halide.
Entry
n
RX
3:1:2
Yield (%) of 3
We also found that almost no hydrogen is evolved if
ethanol is missing in this mixture (experimentally 0.4
a
b
c
d
e
f
2.5
2.5
2.5
4
n-Dec-Br
n-Hex-Br
97:0/3
96:0:4
73:27:0
93:0.7:0
88:0:12
98:0:2
100:0:0
78:0:8
91
76
48
69
63
76
78
76
3
f
equiv H produced). This suggests that addition of sele-
2
nium to the mixture of sodium borohydride and ethanol
enhances the reactivity of these two species.
PhCH -Br
2
Sequential addition of two different alkyl halides (R X
PhCH -Br
2
1
and R X, 1 equiv each) to the Complex A, disclosed
2
2.5
4
PhCH -Cl
2
above, does not allow the selective synthesis of the mixed
3
b
selenide 1¢¢ but leads instead to one to one mixture of the
PhCH -Cl
2
two possible symmetrical selenides 1¢ (Scheme 2, 1¢a:
g
h
4
PhCH(Me)-Br
5
0% 1¢b: 50%).
2.5
sec-Octyl-Br
Furthermore, sequential addition of decyl bromide and
formic acid does not produce decylselenol 3a but leads
instead to didecyl selenide 1¢a (49% relative Se; 97%
relative to decyl bromide, Scheme 3).
Synthesis of Unsymmetrical Dialkyl Selenides 1¢¢
We have used this finding to develop a multistage proce-
dure to synthesise unsymmetrical dialkyl selenides 1¢¢ in a
single pot (Scheme 5, Table 3). This novel method takes
Synthesis of Selenols 3
We have been able to synthesise selectively decylselenol advantage of (i) the efficient synthesis of selenols 3 re-
a by simply interchanging the order of addition of decyl ported above and (ii) the fact that selenols 3 do not react
with alkyl halides in the absence of a base.6
bromide and formic acid (Scheme 4, Table 2, entry a).
3
The reaction proved to be general and allows quite selec- We have thus introduced in the reaction medium enough
tively the synthesis of a large array of primary and second- base to neutralise formic acid and to transform the alkyl
ary alkyl- and benzyl-selenols at the condition that 2.5 selenols 3 to alkyl selenolates prior the addition of the
equivalents of formic acid are used with alkyl halides and alkylating agent [(i) 2 equiv NaBH , DMF (ii) 1 equiv Se
4
4
equivalents with benzyl halides (Table 2, entries d, f, g; (iii) EtOH, 20 °C, 0.5 h (iv) 4 equiv HCO H (v) 1 equiv
2
1
1
compare entry d to c and f to e).
R X , 20 °C, 4 h (vi) 5 equiv NaOH or 4 equiv NaH
DMF
(i) n HCO2H
Complex A
RSeH + R2Se + R2Se2
1'
2.2 NaBH4 + 1.1 Se + 6.6 EtOH
2
0 °C, 1 h
(ii) RX
3
2
Scheme 4 Synthesis of alkyl selenols 3
DMF
(i) n HCO2H
1
2
1
1
Complex A
R -Se-R + R -Se-R
1"
1'
2
NaBH4 + Se + 6 EtOH
2
0 °C, 1 h
1 1
(
(
(
ii) R X
iii) Base
2
2
iv) R X
Scheme 5 Synthesis of unsymmetrical dialkyl selenides 1¢¢
Synlett 2004, No. 10, 1751–1754 © Thieme Stuttgart · New York

LETTER
Selective Synthesis of Selenides and Selenols
1753
Table 3 Reaction Conditions of the Synthesis of Unsymmetrical Dialkyl Selenides
1
1
2
2
Entry
R X
R X
Base
1¢¢:1¢
Yield (%) of 1¢¢
a
b
c
d
e
f
n-Bu-Br
sec-Octyl-Br
n-Bu-Br
n-Bu-Br
iso-Pr-I
5 equiv NaOH
5 equiv NaOH
4 equiv NaH
4 equiv NaH
4 equiv NaH
4 equiv NaH
100:0
80:20
90:10
84:12
95:05
85:15
69
60
78
67
66
60
sec-Octyl-Br
n-Dec-Br
n-Dec-Br
sec-Octyl-I
iso-Pr-I
PhCH -Cl
iso-Pr-I
2
2
2
Typical Procedures
(
vii) R X , 20 °C, 2–4 h]. Under these conditions unsym-
Synthesis of Complex A. A solid mixture of sodium borohydride
0.38 g, 10 mmol) and elemental selenium (0.40 g, 5 mmol) is
stirred in a two naked flask under argon and maintained at 20 °C
using a water bath. Dropwise addition of anhydrous EtOH (1.40 g,
metrical dialkyl selenides 1¢¢ bearing primary- or second-
ary alkyl or benzyl groups have been produced in fair
yield (60–78%). Small amount of the symmetrical dialkyl
selenides 1¢ has been separated after distillation.
(
3
0 mmol) to this mixture favours the rapid evolvement of hydrogen
and produces a white-grey solid. Addition of anhydrous DMF (10
mL) produces a red-brown solution, which slowly leads to a colour-
less one (Complex A).
Conclusion
Synthesis of Symmetrical Dialkyl- and Dibenzyl-selenides 1¢
from Complex A.
Alkyl- or benzyl halide (10 mmol) is added dropwise to the solution
of Complex A reported above. The resulting milky medium is
The real nature of the species involved in the formation of
symmetrical dialkyl selenides 1¢, selenols 3 and unsym-
metrical substituted dialkyl selenides 1¢¢ is not well de-
fined and this is attested by (i) the presence in the medium stirred before hydrolysis and extraction with Et O as reported in
2
of boron derivatives, probably complexed triethylborate Scheme 1.
(
ii) the gas volumetric measurement reported at the begin-
Synthesis of Alkyl and Benzyl Selenols 3 from Complex A.
Addition of formic acid (0.575 g, 12.5 mmol for alkyl halides or
ning of this work which parallels the synthesis of dialkyl
selenides and which does not correspond to a well define
stoichiometry.
0
.92 g, 20 mmol for benzyl halides) to the solution of Complex A,
reported above, initiates the formation of hydrogen and the produc-
tion of a white precipitate. The electrophile (5 mmol) is then added
and the resulting suspension is stirred for 2–5 h prior to hydrolysis
3
f
The presence of ethanol is essential and probably allows
the substitution of hydrides on boron by ethoxide groups.
Ethanol can also play the role of the solvent but the reac-
tions are slower and the yields of dialkyl selenides 1¢¢
poorer.
and extraction of the selenol with Et O (Scheme 4).
2
Synthesis of Unsymmetrical Dialkyl- and Dibenzyl-selenides 1¢¢
from Complex A.
Addition of formic acid (0.575 g, 12.5 mmol) to the stirred solution
of Complex A reported above, initiates the formation of hydrogen
and the production of a white precipitate. The first equivalent of
alkyl halide (5 mmol) is then added dropwise and the resulting
white mixture is stirred at r.t. for at least 4 h prior the addition of the
Anyhow, (i) the former reagent plays the role of a selenide
2
–
dianion (Se ), which is the precursor of symmetrical di-
alkyl selenides 1¢ on alkylation (ii) addition of formic acid
to the medium allows the formation of a reagent which
–
7
plays the role of hydroselenide anion (HSe ) the precur- base (20–25 mmol). This leads to the formation of large amounts of
sor of alkyl selenols 3 on alkylation (iii) treatment of the a precipitate. The second electrophile (5 mmol) is then subsequently
introduced and the mixture stirred for 2–4 h more prior to hydrolysis
later in situ with a base is expected to produce a reagent
which plays the role of alkyl selenolate anions (RSe ) the
–
and extraction with Et O (Scheme 5).
2
precursor of unsymmetrical selenides 1¢¢ on alkylation.
References
Depending on the conditions used symmetrical selenides
1
¢, unsymmetical selenides 1¢¢ and selenols 3 can be selec-
(
1) (a) Rheinboldt, H. Schwefel-, Selen-, Tellur-Verbindungen,
In Methoden der Organische Chemie (Houben Weyl), Vol.
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easily handled sodium borohydride, elemental selenium
and alkyl halides. Those reactions provide a large variety
of these organoselenium compounds at the exclusion of
those derived from tertiary alkyl- or tertiary benzyl
halides. We are currently working to apply our finding to
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(
b) Organic Selenium Compounds: Their Chemistry and
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Synlett 2004, No. 10, 1751–1754 © Thieme Stuttgart · New York

1
754
A. Krief et al.
LETTER
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to Scheme 4).
(4) Bird, M. L.; Challenger, F. J. Chem. Soc. 1942, 570.
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(
(
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1
A. A.
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selenol 3a does not react with decyl bromide or methyl
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out in the presence of sodium formate (1 equiv). The reaction
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diselenides 2 resulting from the oxidative coupling of the
selenolates.
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Synlett 2004, No. 10, 1751–1754 © Thieme Stuttgart · New York