Copper- and ligand-free Sonogashira reaction catalyzed by Pd(0) nanoparticles at ambient conditions under ultrasound irradiation

Article abstract of DOI:10.1021/jo0503815

The Sonogashira reaction proceeds at ambient temperature (30°C) in acetone or room-temperature ionic liquid, 1,3-di-n-butylimidazolium tetrafluoroborate ([bbim]BF₄), as solvent under ultrasound irradiation to give enhanced reaction rates, excellent chemoselectivity, and high yields in the absence of a copper cocatalyst and a phosphine ligand. TEM analysis showed the formation of stable, crystalline, and polydispersed Pd(0) nanoparticles as catalyst for the reaction.

Full text of DOI:10.1021/jo0503815

optoelectronic applications.3 Since its introduction in
1975, the reaction has been well studied, making use of
a variety of ligands and copper salts as cocatalysts.4
However, the copper salts used as cocatalysts can also
induce Glaser-type homocoupling5 of the alkynes to the
corresponding symmetrical diyne via., the copper acetyl-
ide formed. To avoid this, copper- and phosphine-free
Sonogashira reactions have been developed in recent
times resulting in excellent chemoselectivity.6,7 Extensive
research continues to push the limits of this methodology
to more and more facile procedures wherein attempts
may be made to practice this reaction at ambient tem-
perature without the use of a copper cocatalyst and a
ligand. Herein, we report for the first time a copper- and
ligand-free Sonogashira reaction at ambient temperature
under ultrasound irradiation in a molecular solvent such
as acetone as well as a room-temperature ionic liquid (IL),
1,3-di-n-butylimidazolium tetrafluoroborate ([bbim]BF4),
in excellent chemoselectivity with considerably enhanced
reaction rates through the formation of stable and
crystalline clusters of zerovalent Pd nanoparticles.
The sonochemical reactions were carried out in a
thermostated (30 ( 1 °C) ultrasonic cleaning bath of
frequency 50 kHz in an inert atmosphere of argon. A
variety of aryl halides consisting of substituted iodo- and
bromobenzenes were reacted with terminal acetylenic
compounds in the absence of any added copper cocatalyst
Copper- and Ligand-Free Sonogashira
Reaction Catalyzed by Pd(0) Nanoparticles
at Ambient Conditions under Ultrasound
Irradiation
Atul R. Gholap,† K. Venkatesan,† Renu Pasricha,‡
Thomas Daniel,† Rajgopal J. Lahoti,† and
Kumar V. Srinivasan*,†
Organic Chemistry; Technology Division, and Centre for
Material Characterization, National Chemical Laboratory,
Dr. Homi Bhabha Road, Pune - 411 008, India
kvsri@dalton.ncl.res.in
Received March 1, 2005
The Sonogashira reaction proceeds at ambient temperature
(30 °C) in acetone or room-temperature ionic liquid, 1,3-di-
n-butylimidazolium tetrafluoroborate ([bbim]BF4), as solvent
under ultrasound irradiation to give enhanced reaction rates,
excellent chemoselectivity, and high yields in the absence
of a copper cocatalyst and a phosphine ligand. TEM analysis
showed the formation of stable, crystalline, and polydis-
persed Pd(0) nanoparticles as catalyst for the reaction.
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is a powerful method for the formation of substituted
acetylenes.1 This reaction is frequently utilized as a key
step in natural product chemistry2 and for the synthesis
of acetylene compounds which are potentially useful in
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* Corresponding author. Tel: +91-20-25889089. Fax: +91-20-
25893614.
† Organic Chemistry; Technology Division.
‡ Centre for Material Characterization.
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10.1021/jo0503815 CCC: $30.25 © 2005 American Chemical Society
Published on Web 05/07/2005
J. Org. Chem. 2005, 70, 4869-4872
4869

TABLE 1. Synthesis of Diacetylene Derivatives 3
4870 J. Org. Chem., Vol. 70, No. 12, 2005

Table 1 (Continued)
*New compounds. a Isolated yields after column chromatography.
TABLE 2. Reuse of Catalyst System for Synthesis of
Diphenylacetylene (entry1)
SCHEME 1
entry
yield (%)
1
93
2
91
3
89
4
88
5
85
In all cases, pure products were isolated by subjecting
the organic layer to column chromatography and char-
acterized by mp, spectral, and elemental analyses. The
results are recorded in Table 1.
and phosphine ligands in acetone or the IL [bbim]BF4
as solvent using PdCl2 as catalyst and triethylamine as
base under ultrasonic irradiation (Scheme 1).
As is evident, the ultrasound-assisted Sonogashira
reaction proceeds smoothly at ambient temperature even
in the absence of copper cocatalyst and phosphine ligands
to afford the products in excellent isolated yields. The
reactions were significantly faster in acetone as the
reaction medium (15-90 min) as compared to those in
the IL (2-3 h). However, the reactions in the IL afforded
the products in relatively higher yields with the added
advantage of the recyclability of both catalyst and the
reaction medium. The IL consisting of the Pd catalyst
was recycled five times for the reaction of iodobenzene
with ethynylbenzene. The results are recorded in Table
2. It was observed that the catalyst exhibits only a
marginal loss in activity spread over five recycle batches.
It was important to note that no Glaser coupling
product even in traces could be observed for all the
reactions involving iodobenzenes. However, in the case
of less reactive bromobenzenes, the homocoupled product
arising out of the terminal acetylene was formed to an
extent of 6-7%. The extent of formation of Glaser
coupling product was determined by GC analysis. It can
be observed that the process tolerates both electron-
donating and electron-withdrawing substituents in the
aryl halides as well as terminal acetylenes.
In the case of acetone, the products were isolated by
evaporation of the solvent followed by extraction with
10% ethyl acetate in petroleum ether (bp 60-80 °C) and
filtration through a Celite bed to separate the Pd catalyst.
The Pd catalyst in the form of Pd(0) nanoparticles was
difficult to recover and recycle. However, from the point
of view of ease of recovery and recycle of the expensive
Pd catalyst, the reactions were performed in the IL [bbim]-
BF4. In this case, the products were selectively extracted
with 10% ethyl acetate in petroleum ether leaving behind
the Pd catalyst in the form of Pd(0) nanoparticles as a
solution in IL. As reported previously,8a,b the complete
formation of a Pd-biscarbene complex (A) takes place
during the reaction in [bbim]BF4 as solvent. This complex
(A) formed “in situ” was selectively extracted into chlo-
roform separating it from the ionic liquid medium,
purified by column chromatography, and completely
characterized. The complex (A) under the sonochemical
conditions gives rise to the stable, crystalline, and
polydispersed Pd(0) nanoparticles as the catalyst for the
reaction.
A Pd(0) species stabilized by ligands is proposed to be
involved in the catalytic cycle comprising of oxidative
insertion, trans-metalation, and reductive elimination of
the Sonogashira reaction. Consequently, the formation
of such Pd(0) nanoparticles was investigated in the
present work by subjecting the reaction mixture after a
successful Sonogashira reaction of iodobenzene with
1-ethynylbenzene in acetone and the IL respectively
under the sonochemical conditions for “in situ” TEM
analysis. TEM analysis was carried out in a Transmission
(8) (a) Deshmukh, R. R.; Rajagopal, R.; Srinivasan, K. V. Chem.
Commun. 2001, 1544. (b) Rajagopal, R.; Jarikote, D. V.; Srinivasan,
K. V. Chem. Commun. 2002, 616. (c) Palimkar, S. S.; Siddiqui, S. A.;
Daniel, T.; Lahoti, R. J.; Srinivasan, K. V. J. Org. Chem. 2003, 68,
9371.
J. Org. Chem, Vol. 70, No. 12, 2005 4871

TABLE 3. Synthesis of Diphenylacetylene in Various
ILs
entry
ionic liquid
reaction time (h)
yielda (%)
1
2
3
4
5
6
7
8
9
[bmim]Br
[beim]BF4
[bpim]Br
[emim]BF4
[bbim]Cl
2
2
2
2
2
2
2
2
2
89
90
92
89
88
92
93
90
85
[bbim]Br
[bbim]BF4
[bbim]PF6
[bbim]ClO4
a Isolated yields after column chromatography.
FIGURE 1. TEM measurements in acetone.
promotes the activity of the catalytic species in the
oxidative insertion, trans-metalation, and reductive elimi-
nation catalytic cycle of the Sonogashira reaction. This
is made possible by the phenomenon of acoustic cavita-
tion generating transient cavitation bubbles of very short
lifetimes (∼10-9 s), the implosive collapse of which under
adiabatic conditions gives rise to high temperatures and
pressures.9
It was interesting to ascertain whether this reaction
is effective with similar room-temperature ILs belonging
to the imidazolium class. Thus, a variety of ILs as shown
in Table 3 were screened as solvents for the synthesis of
diphenylacetylene under identical sonochemical reaction
conditions. It was also observed that all the ionic liquids
with varying cations and anions were found to give more
or less similar results as shown in Table 3.
FIGURE 2. TEM measurements in [bbim]BF4.
Electron Microscope operated at 100 kV with the mag-
nification varying from 100 to 300 k. The sample after
appropriate dilution with isopropyl alcohol was directly
deposited on carbon coated 400 mesh Cu TEM grids. The
TEM measurements for the acetone medium (Figure 1)
show the presence of polydispersed Pd(0) nanoparticles
of irregular morphology varying in diameter from 3 to 8
nm. For the reaction in the IL medium (Figure 2), TEM
measurements show that the particles are almost spheri-
cal in shape and the boundaries are clear. They are well
dispersed and show the size to be in the range of 10-20
nm. The crystallinity and crystallography of the nano-
particles obtained from both the medium are proved by
selected area electron diffraction (SAED) patterns which
indicate that the Pd(0) nanoparticles are polycrystalline
in nature and can be indexed as face-centered cubic (fcc)
crystals from the allowed reflections.
It is important to note that the reaction of 4-iodotolu-
ene with 1-ethynylbenzene in acetone or IL at room
temperature under similar conditions but in the absence
of ultrasound (silent condition) did not show the forma-
tion of any cross-coupled product even after several hours
(6 h) of stirring. Moreover, in a blank experiment, Pd(0)
nanoparticles were formed by sonicating a mixture of
PdCl2 and triethylamine in either acetone or IL, respec-
tively. To this were added the reactants, viz. 4-iodotolu-
ene and 1-ethynylbenzene, and the mixture was stirred
for 6 h at ambient temperature under silent conditions.
The cross-coupled product 4-(phenylethynyl)toluene was
obtained to an extent of 36% and 38% (isolated yields)
in acetone and the IL, respectively, as against the 75%
and 85% yields obtained in the total sonochemical reac-
tion. This implies that ultrasound not only brings about
the formation of highly crystalline, active Pd(0) nano-
particles required for the Sonogashira reaction but also
In conclusion, the Sonogashira reaction has been
achieved in short reaction times, excellent chemoselec-
tivity, and high isolated yields at ambient temperature
under ultrasonic irradiation in a molecular solvent as
well as a room-temperature ionic liquid even in the
absence of a phosphine ligand and copper cocatalysts. For
iodobenzenes, no traces of Glaser coupling product were
detected, whereas in the case of bromobenzenes the
homocoupled product was formed to the extent of 6-7%
only. The formation of stable and crystalline Pd(0)
nanoparticles under the sonochemical conditions has
been shown by TEM measurements. It was ascertained
that ultrasound not only generated the Pd(0) nano-
particles as the active catalyst for the reaction but also
promoted and enhanced the catalytic activity of this
species in the catalytic cycle of the Sonogashira cross-
coupling reaction. The short reaction times, excellent
chemoselectivity, high isolated yields, and easy workup
procedure make this sonochemical methodology an ef-
ficient protocol for the rapid synthesis of disubstituted
acetylene libraries.
Acknowledgment. A.R.G. and K.V. thank CSIR
and UGC for the award of research fellowships.
Supporting Information Available: Representative pro-
cedures, TEM measurements, characterization data and 1H
and 13C NMR spectra for all products listed in Table 1. This
material is available free of charge via the Internet at
http://pubs.acs.org.
JO0503815
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4872 J. Org. Chem., Vol. 70, No. 12, 2005