Synthesis of diselenides and selenides from elemental selenium

Article abstract of DOI:10.1016/S0040-4039(02)00277-0

Sodium hydride is able to reduce elemental selenium to sodium diselenide (Na₂Se₂), but not to sodium selenide (Na₂Se). Dialkyl diselenides and even dialkyl selenides, including unsymmetrical dialkyl selenides, can be nevertheless synthesized using the proper Se/NaH ratio (1/1 or 1/2).

Full text of DOI:10.1016/S0040-4039(02)00277-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 3083–3086
Synthesis of diselenides and selenides from elemental selenium
Alain Kriefa,* and Michel Derocka,b
aLaboratoire de Chimie Organique de Synthe`se, De´partement de Chimie, Faculte´s Universitaires Notre-Dame de la Paix,
61 rue de Bruxelles, Namur B-5000, Belgium
bFonds pour la Formation a` la Recherche dans l’Industrie et dans l’Agriculture, 5 Rue d’Egmont, Bruxelles B-1050, Belgium
Received 31 January 2001; revised 7 February 2002; accepted 8 February 2002
Abstract—Sodium hydride is able to reduce elemental selenium to sodium diselenide (Na2Se2), but not to sodium selenide (Na2Se).
Dialkyl diselenides and even dialkyl selenides, including unsymmetrical dialkyl selenides, can be nevertheless synthesized using the
proper Se/NaH ratio (1/1 or 1/2). © 2002 Elsevier Science Ltd. All rights reserved.
Over the last 25 years, organoselenium chemistry has
been the subject of constant scientific interest and has
been used intensively.1 Organoselenium compounds are
no longer systematically classified as toxic and some of
them can be bought not only from the chemical compa-
nies, but also in several supermarkets as a food
supplement.
The reaction is best achieved at 70°C for 2 h, using 1.1
mol equiv. of sodium hydride per mole of gray sele-
nium. Alkylation has been carried out at room temper-
ature using 1 mol equiv. of alkylating agent. Under
these conditions dialkyl diselenides 4 are produced
besides only a trace amount of dialkyl selenides 3 and
dialkyl triselenides 5 from which they can be easily
freed by distillation or by chromatography on silica gel
(Table 1).
The synthesis of organoselenium compounds always
implies at some stage the reaction with elemental sele-
nium 1. For example elemental selenium reacts: (i)
directly with organometallics (1 equiv.) to produce
organic selenolates and (ii) with several reducing agents
to produce selenides (Se−−) or diselenides (−SeSe−).
These, after reaction with electrophilic organic species
such as akylhalides or -pseudohalides, lead to diorganyl
selenides 3 or diorganyl diselenides 4, respectively.1
Although the reduction of elemental selenium can be
carried out at lower temperature, it is less selective and
produces higher amounts of 3 and 5 at the expense of 4.
The synthesis of diorganic diselenides has been also
performed in other solvents such as dimethyl sulfoxide
(DMSO), N-methylpyrrolidinone (NMP), dimethoxy-
Alkaline metals in liquid ammonia2 or in the presence
of an electron carrier in THF,3 zinc in the presence of
sodium hydroxide,4 samarium diiodide,5 metal
borohydrides6 and hydrazine7 in basic media are among
the reagents to allow, when used in stoichiometric
amounts, the efficient synthesis of metal diselenides.
The same reagents, with the exclusion of hydrazine, are
also able to generate dimetal selenides if used in at least
twice the amount.
Table 1. Synthesis of dialkyl diselenides according to
Scheme 1
Entry
RX
3/4/5 ratioa
4 (Yield%)
1
2
3
4
5
6
7
MeI
–/97/3b
–/92/8
3/89/8c
0/91/9
0/100/0
0/88/12
6/90/4
4a (60)
4a (72)
4b (70)
4c (80)
4d (88)
4e (70)
4f (75)
Me2SO4
n-BuBr
n-DecBr
i-PrBr
s-BuBr
PhCH2Br
We have now found that sodium hydride 2 is an
efficient reagent for the synthesis of sodium diselenide
in dimethylformamide (DMF), which is also one of the
most appropriate solvents for alkylation reactions.
a Most of the products have been already described.2–7
b Dimethyl selenide is too volatile to be detected by GC under the
conditions used.
* Corresponding author. Tel.: +32 8172 4539; fax: +32 8172 4536;
e-mail: alain.krief@fundp.ac.be
c 1NMR (CHCl3, l ppm): 3/4/5 M/D/D.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00277-0

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A. Krief, M. Derock / Tetrahedron Letters 43 (2002) 3083–3086
(ii) significant amounts of the unexpected dibenzyl
(i) DMF, 70°C, 2h
(ii) RX, 20°C, 1h
RSeR + RSeSeR + RSeSeSeR
Se + 1.1 NaH
selenoacetal of benzaldehyde 7f besides dibenzyl sele-
nide 3f on reaction with benzyl bromide (14/86 ratio;
43% isolated yield of dibenzyl selenide) (Scheme 3)8
(iii) substantial amounts of the dissymmetric n-butyl
i-propyl selenide 8a with very high selectivity on
sequential addition, on the reduced selenium species,
of mol equiv. of two different alkyl halides [(i) n-
butyl bromide (0°C, 0.2 h; 20°C, 2 h) then (ii) i-pro-
pyl bromide (20°C, 4 h) (Scheme 4, entry 1)].
1
2
3
4
5
Scheme 1.
ethane (DME) or tetrahydrofurane (THF), but none of
them proved as effective as DMF. For example, excel-
lent selectivity has been observed in DMSO at 70°C,
but the overall yields were modest, whereas poor selec-
tivities and yields have been found in NMP.
Such selectivity is unusual since it has been mentioned
in the literature on several occasions that the one-pot
sequential reaction of metal selenides with two different
alkyl halides or -pseudo halides leads to an intractable
mixture of all the possible selenides.6 This suggests that
(i) metal selenides and the related metal alkylselenolates
possess a very close nucleophilicity and (ii) sodium
selenide is not produced on reaction of gray selenium
with 2 mol equiv. of NaH in DMF (Scheme 5).
We have also carried out the reduction of elemental
selenium reaction with a different Se/NaH ratio (1/2
instead of 1/1.1) expecting the synthesis of sodium
selenide at first and dialkyl selenides 3 after alkylation.
When the reaction is performed with 2 mol equiv. of
NaH (DMF, 70°C, 2 h) and butyl bromide (2 mol
equiv., 20°C, 4 h, conditions A) dibutyl selenide 3b is
produced but mixed with substantial amounts of
dibutyl diselenide 4b (Scheme 2, entry 1).
We therefore proposed an alternative pathway (Scheme
6 instead of Scheme 5), to explain the formation of
dialkyl selenides 3 on sequential addition on elemental
selenium of sodium hydride (2 equiv.) and alkyl bro-
mide (2 equiv.). It involves:
(i) the formation of sodium diselenide, leaving unre-
acted half of the amount of the sodium hydride
introduced (Scheme 6, step a)
This could suggest that sodium selenide is the effective
intermediate. We were nevertheless surprised to get:
(i) a much poorer 3/4 ratio when longer straight
chain or branched chain alkyl bromides are used
instead (Table 2, entries 2–4)
(ii) dialkylation of sodium diselenide to produce
dialkyl diselenide, leaving an unreacted amount (half)
of the introduced alkyl halide (Scheme 6, step b)
(iii) cleavage of the dialkyl diselenide by the unre-
acted sodium hydride to generate sodium alkylseleno-
late (Scheme 6, step c)8
(i) DMF, 70°C, 4 h
(ii) Conditions A or B
Se + 2.1 NaH
RSeR + RSeSeR
1
2
4
3
Scheme 2.
Table 2. Synthesis of dialkyl selenides according to Scheme 2
Entry
RX
Conditions A
Conditions B
3/4 ratio
3 (%)a
3/4 ratio
3 (%)a
1
2
3
4
n-BuBr
n-HexBr
n-DecBr
i-PrBr
87/13
62/38
67/33
50/50
3b (64)
3g (38)
3c (33)
3d (–)
89/11
89/11
94/6
3b (67)
3g (67)
3c (59)
3d (50)
93/7
a Yields in analytically pure compounds.
(i) DMF, 70°C, 1 h
(ii) 2 mol equiv PhCH2Br,
20°C, 1h
PhCH2SeCH2Ph
PhCH(SeCH2Ph)2
+
Se + 2.1 NaH
1
2
3f
86 %
7f
14 %
Scheme 3.
Se
Se
+
+
R1
R2
8
3d
(i) DMF, 70°C, 2 h
(ii) 1 mol equiv R1Br, 0°C, 0.2 h
then 20°C, 2 h
Se + 2.1 NaH
1
2
Se
3b, 3g
R2
Diselenides
(iii) 1 mol equiv R2Br, 20°C, 4 h
R2
4
Scheme 4.

A. Krief, M. Derock / Tetrahedron Letters 43 (2002) 3083–3086
3085
(a)
(b)
[2 NaSeNa] + 2 H2
2 RSeR + 4 NaBr
2 Se + 4 NaH
[2 NaSeNa]
4 RBr
(e)
2 Se + 4 NaH + 4 RBr
2 Se + 4 NaH
2 RSeR + 4 NaBr + 2 H2
Scheme 5.
(a)
(b)
[NaSeSeNa + 2 NaH] + H2
4 RBr
[RSeSeR + 2 NaBr + 2 NaH + 2 RBr]
[NaSeSeNa + 2 NaH]
[RSeSeR + 2 NaH + 2 RBr]
[2 RSeNa + 2 RBr]
(c)
(d)
[2 RSeNa + 2 RBr] + H2
2 RSeR + 2 NaBr
(e)
2 Se + 4 NaH + 4 RBr
2 RSeR + 4 NaBr + 2 H2
Scheme 6.
(iv) alkylation of sodium alkylselenolates by the
unreacted alkyl halide (Scheme 6, step d).
sodium diselenide (61 ml [2.5 mmol] of dihydrogen
expected, Scheme 6, step a) and rules out the formation
of sodium selenide which would have instead produced
122 ml of dihydrogen (5 mmol, Scheme 5, step a).
In order to determine the real pathways (Scheme 5 or
Scheme 6 for example), we decided to monitor, by
volumetric titration, the amount of dihydrogen released
after addition of each reagent involved in the synthesis
of dialkyl selenides. For example, the amount of dihy-
drogen expelled prior to addition of any alkyl bromide
should be twice the amount, if Scheme 5 is operative, of
that expected if the reaction instead follows the path-
way disclosed in Scheme 6.
Addition, at that stage, of 2 mol equiv. (10 mmol) of
n-butyl bromide leads to the production of (i) 50 ml of
dihydrogen, (61 ml [2.5 mmol] expected, Scheme 6, step
c) and (ii) dibutyl selenide. These results unambiguously
support the sequence of reactions disclosed in Scheme
6.
Another support for this hypothesis arises from the
formation of dibutyl diselenide (94% yield) instead of
dibutyl selenide, when water is added prior to the
addition of n-butyl bromide (2 mol equiv.). This is due
to the destruction of the unreacted sodium hydride
which produces dihydrogen concomitantly (77 ml,
expected 61 ml, Scheme 8). Related results have been
obtained when propionic acid or aqueous hydrochloric
acid replaced water (dibutyldiselenide formed: 92%
yield, dihydrogen produced: 62 ml, expected 61 ml, in
each case).
Since some of the steps of this synthesis could be
identical to those implied in the related synthesis of
dialkyl diselenides (which only differs in that the Se/Na
ratio is 1/1 instead of 1/2, Scheme 7), we have, for
comparison purposes, monitored the amount of dihy-
drogen produced during the synthesis of dialkyl
diselenides.
We observed that the reaction between equivalent
amounts of selenium and sodium hydride (5 mmol
each) produces 58 ml of dihydrogen (61 ml [2.5 mmol]
of dihydrogen expected, Scheme 7, step a). This fully
agrees with the formation of sodium diselenide. Addi-
tion of 2 equiv. of n-butyl bromide provides dibutyl
diselenide (80% yield, Scheme 7, R=Bu) and as
expected no more dihydrogen is formed (Scheme 7, step
b).
We have used this information to propose a modified
and more appropriate experimental procedure to gener-
ate dialkyl selenides, which involves sequential addition
of each of the 2 equiv. of the alkyl halide [(i) elemental
selenium, 2 mol equiv. of NaH, DMF, 70°C, 2 h, (ii) 1
mol equiv. R1Br, 0°C, 0.2 h, (iii) 20°C, 2 h, (iv) 1 mol
equiv. R2Br 20°C, 6 h, conditions B, Scheme 2, Table
2]. These conditions significantly improve the yields in
symmetrical selenides (Table 2, compare conditions B
to conditions A).
“ It takes into account the observation that the two
alkyl groups present on the dialkyl selenide are not
delivered just one after the other as would have been
the case if sodium selenide was involved (compare
Scheme 6, steps b, d and Scheme 5).
Performing the reaction with twice the amount of
sodium hydride (10 mmol, Se/NaH ratio: 1/2), produces
69 ml of dihydrogen. This supports the formation of
(a)
[NaSeSeNa] + H2
RSeSeR + 2 NaBr
2 Se + 2 NaH
(b) [NaSeSeNa + 2 RBr]
“ It avoids the reaction between sodium hydride and
the second mol equiv. of the alkylating agent which
Scheme 7.

3086
A. Krief, M. Derock / Tetrahedron Letters 43 (2002) 3083–3086
DMF, 70°C
(a)
(b)
(c)
[NaSeSeNa + 2 NaH] + H2
2 Se + 4 NaH
4 h
excess H2O
20°C, 1h
[NaSeSeNa + 2 NaH]
[NaSeSeNa + 2 NaOH] + 2 H2
4 BuBr
[NaSeSeNa + 2 NaOH]
BuSeSeBu + 2 NaBr + 2 NaOH + 2 BuBr
94 %
Scheme 8.
Table 3. Synthesis of dissymmetric dialkyl selenides
ogy; Klayman, D. L.; Gu¨nther, W. H. H., Eds.; John
Wiley and Sons: Chichester, 1973; (c) Paulmier, C. In
Selenium Reagents and Intermediates in Organic Synthesis;
Baldwin, J. E., Ed.; Pergamon: Oxford, 1986; Vol. 5; (d)
The Chemistry of Organic Selenium and Tellurium Com-
pounds; Patai, S.; Rappoport, Z., Eds.; John Wiley and
Sons: Chichester, 1987; Vol. 2; (e) Krief, A. In Comprehen-
sive Organometallic Chemistry II; Abel, E. W.; Stone, F.
G. A.; Wilkinson, G.; McKillop, A., Eds.; Pergamon:
Oxford, 1995; Vol. 11, p. 516.
according to Scheme 4
Entry
R1Br
R2Br
8/3d/3b,g/4
8 (Yield%)
ratio
1
1
2
n-BuBr
n-HexBr
i-PrBr
i-PrBr
i-PrBr
n-HexBr
90/10
90/7/3
16/31/39/13
68
61
–
2. Brandsma, L.; Wijers, H. E. Rec. Trav. Chim. 1963, 82,
68–74.
could compete with the cleavage of the intermediate
dialkyl diselenide.
“ It allows the quite selective synthesis of dialkyl
selenides bearing two different alkyl groups, but only
when the first alkylating agent is primary (Table 3,
compare entry 2 to entry 3).
3. (a) Thompson, P. Boujouk 1988, 53, 2109–2112; (b) Syper,
L.; Mlochowski, J. Tetrahedron 1988, 44, 6119–6130.
4. Ping, L.; Xunjun, Z. Synth. Commun. 1993, 23, 1721–1725.
5. (a) Klayman, D. L.; Griffin, T. S. J. Am. Chem. Soc. 1973,
95, 197–199; (b) Gladysz, J. A.; Hornby, J. L.; Garbe, J. E.
J. Org. Chem. 1978, 1204–1208; (c) Bergman, J.; Engman,
L. Synthesis 1980, 569–570; (d) Yarada, K.; Fujita, T.;
Yanada, R. Synlett 1998, 971–972.
We are trying to improve the conditions for the one-pot
synthesis of unsymmetrical dialkylselenides and we will
apply the results described in this letter to the synthesis
of functionalized diselenides and selenides.
6. (a) Zang, Y.; Jia, X.; Zouh, X. Synth. Commun. 1994, 24,
1247–1252; (b) Jia, X.; Zang, Y.; Zouh, X. Synth. Com-
mun. 1993, 23, 1403–1408.
7. (a) Syper, L.; Mlochowski, J. Synthesis 1984, 439–442; (b)
Eggert, H.; Nielsen, O.; Henriksen, L. J. Am. Chem. Soc.
1986, 108, 1725–1730; (c) Li, J. Q.; Bao, W. L.; Lue, P.;
Zhou, X.-J. Synth. Commun. 1991, 21, 799–806.
8. (a) Krief, A.; Trabelsi, M.; Dumont, W. Synthesis 1992,
933–935; (b) Krief, A.; Trabelsi, M.; Dumont, W. Synlett
1992, 8, 638–640.
References
1. (a) Rheinboldt, H. In Schwefel-, Selen-, Tellur-Verbindun-
gen Methoden der Organische Chemie (Houben Weyl);
Mu¨ller, E., Ed.; Georg Thieme: Stuttgart, 1967; Vol. 9; (b)
Organic Selenium Compounds: Their Chemistry and Biol-