Glaser oxidative coupling in ionic liquids: An improved synthesis of conjugated 1,3-diynes

Article abstract of DOI:10.1016/S0040-4039(03)01565-X

Terminal alkynes undergo oxidative-coupling smoothly in the presence of the CuCl-TMEDA catalytic system in hydrophobic [bmim]PF₆ ionic liquid under aerobic conditions to produce 1,3-diynes in excellent yields under mild conditions. The substrates, alkynes, show enhanced reactivity and selectivity in ionic liquids (ILs). The recovery of the catalyst is facilitated by the hydrophobic nature of the [bmim]PF₆ ionic liquid.

Full text of DOI:10.1016/S0040-4039(03)01565-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 6493–6496
Glaser oxidative coupling in ionic liquids: an improved synthesis
of conjugated 1,3-diynes
J. S. Yadav,* B. V. S. Reddy, K. Bhaskar Reddy, K. Uma Gayathri and A. R. Prasad
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 24 March 2003; revised 10 June 2003; accepted 20 June 2003
Abstract—Terminal alkynes undergo oxidative-coupling smoothly in the presence of the CuCl-TMEDA catalytic system in
hydrophobic [bmim]PF6 ionic liquid under aerobic conditions to produce 1,3-diynes in excellent yields under mild conditions. The
substrates, alkynes, show enhanced reactivity and selectivity in ionic liquids (ILs). The recovery of the catalyst is facilitated by the
hydrophobic nature of the [bmim]PF6 ionic liquid.
© 2003 Elsevier Ltd. All rights reserved.
Conjugated polyyne structures have attracted much
attention,1 since they are found in many natural prod-
ucts,2 particularly anti-fungal agents.3 They are useful
precursors for the synthesis of monomers, polymers and
functional host molecules.4 The preparation of 1,3-diy-
nes via coupling between sp-hybridized atoms repre-
sents one of the most important carbonꢀcarbon bond
formations in organic synthesis.5 The Glaser coupling6
and Eglinton procedures7 for direct coupling of termi-
nal alkynes and modifications thereof represent the
most widely used alkyne coupling reactions for the
synthesis of 1,3-diynes.8,9 The classical oxidative
alkyne-dimerization reactions are generally carried out
in organic solvents such as methanol, acetone, pyridine,
methyl cellosolve and toluene. However, many of these
methods often require large volumes of organic solvents
which always demand an aqueous work-up for their
separation or recycling or disposal. Consequently,
methods that successfully minimize their use are the
focus of much attention. Thus, the use of solvents like
water, supercritical fluids and ionic liquids has received
a great deal of attention in recent times in the area of
green synthesis.
Ionic liquids have recently gained recognition as possi-
ble environmentally benign alternative solvents in vari-
ous chemical processes. Accordingly, they are emerging
as a set of green solvents with unique properties such as
good solvating ability, wide liquid range, tunable polar-
ity, negligible vapor pressure, high thermal stability and
ease of recyclability. Ionic liquids are attractive espe-
cially for the immobilization of transition metal based
catalysts, Lewis acids and enzymes.10 Their unprece-
dented ability to solvate a broad spectrum of substrates
has widened the horizon of their applicability. The
properties of ionic liquids can be tailored by the fine-
Scheme 1.
Keywords: ionic liquids (ILs); alkynes; oxidative-coupling; 1,3-diynes.
* Corresponding author. Fax: 91-40-27160512; e-mail: yadav@iict.ap.nic.in
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01565-X

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tuning of parameters such as the choice of organic
cation, inorganic anion and the length of alkyl chain
attached to an organic cation. These structural varia-
tions offer flexibility to the chemist to devise the most
idealized solvent, catering for the needs of any particu-
lar process.
Table 1. Oxidative coupling of acetylenes in ionic liquids at room temperature

J. S. Yada6 et al. / Tetrahedron Letters 44 (2003) 6493–6496
6495
Table 2. Recyclability of 2 mL of [bmim]PF6 ionic liquid
another advantage of the use of ionic liquids for hydro-
genation or aerobic oxidation reactions. In particular,
the recovery of the catalyst is extremely simple in ionic
liquids (ILs) when compared to organic solvents. As is
evident from Table 1, acid sensitive protecting groups
such as THP, TBDMS and allyl ethers are compatible
with these reaction conditions.12 Thus, the present
method is mild enough to tolerate a wide range of
functional groups present in the substrate. Finally, the
reactivity of various alkynes was tested in the
for oxidative dimerizaton of 2-propyn-1-ol
Runs
2-Propyn-1-ol % CuCl/
Time (h)
Yield (%)
(mmol)
TMEDA
1
2
3
4
5
6
1
1
1
1
1
1
0.2/0.2 mmol
0.2/0.2 mmol
0.2/0.2 mmol
7.5
8.5
6.0
7.5
5.5
6.5
89
87
92
90
95
92
hydrophilic
[bmim]BF4
and
the
hydrophobic
[bmim]PF6 ionic liquids. The [bmim]BF4 ionic liquid
was found to be equally good for this conversion. Both
−
−
the PF6 and BF4 ionic liquids were obtained from
Fluka and used without any further purification. Ionic
liquids have also been prepared in our laboratory from
the readily available and inexpensive N-methyl imida-
zole, 1-chlorobutane and hexafluorophosphoric acid or
sodium tetrafluroborate. The purity of the ionic liquids
prepared in the lab was determined by comparison of
Hence, there is significant interest in using them as
replacements for conventional organic solvents. How-
ever, there are no examples of the use of ionic liquids as
solvents for the oxidative coupling of alkynes.
In this paper, we wish to report the use of ionic liquids
as solvents for the oxidative-dimerization of alkynes to
produce 1,3-diynes under mild conditions. Ionic liquids
allow the recycling and reuse of this catalytic system.
Thus, the treatment of phenylacetylene with 0.2 mol%
CuCl and TMEDA (0.2 mol%) in [bmim]PF6 ionic
liquid under an oxygen atmosphere afforded the corre-
sponding 1,4-diphenyl-1,3-butadiyne in 95% yield
(Scheme 1).
1
their H NMR spectra with commercial samples. The
purity of [bmim]PF6 ionic liquid was ]97.0% (NMR).
In summary, this paper describes a novel and efficient
protocol for the synthesis of conjugated diynes through
oxidative dimerization of terminal alkynes in ionic liq-
uids. The alkynes show a significant increase in reactiv-
ity in ionic liquids thereby reducing the reaction times
and improving the yields. The simple experimental and
product isolation procedures combined with ease of
recovery and reuse of this novel reaction media is
expected to contribute to the development of this green
strategy for the synthesis of 1,3-conjugated diynes.
These results prompted us to investigate the scope of
this process for various alkynes. Interestingly, a wide
range of alkynes underwent oxidative-dimerization
under these reaction conditions to produce the corre-
sponding 1,3-diynes in excellent yields (see Table 1).
The reactions proceed smoothly at room temperature
with high functional group selectivity. The products
were obtained in high to quantitative yields after simple
extraction with toluene. In contrast to organic solvents,
enhanced reaction rates, improved yields and high func-
tional group compatibility are features obtained in ionic
liquids. For example, the treatment of phenylacetylene
with 0.2 mol% CuCl and TMEDA (0.2 mol%) in
[bmim]PF6 for 4.5 h afforded the corresponding 1,4-
diphenyl-1,3-butadiyne 2a in 95% yield whereas the
same reaction in methanol after 12 h gave the product
in 75% yield. The major advantage of the use of ionic
liquids as reaction media is that these ionic liquids can
be easily recovered and recycled in subsequent runs.
Since the products were moderately soluble in the ionic
phase, they can be easily separated by simple extraction
either with toluene or with ether. The remaining ionic
liquid was further washed with toluene and reused in
four to six successive runs. The yields gradually
decreased in runs carried out using recovered ionic
liquid. However, on the addition of more catalyst to
each alternate run, the yields and reaction rates were
enhanced significantly as shown in Table 2.
Acknowledgements
B.V.S., K.B.R. thank CSIR, New Delhi, for the award
of fellowships.
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1
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