The Sonogashira Reaction in Ionic Liquids

Article abstract of DOI:10.1007/s00706-002-0558-8

The Sonogashira reaction of iodobenzene with phenylacetylene in several room temperature ionic liquids was studied. A regeneration of the catalytical system immobilized in 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim]PF₆) has been als

Full text of DOI:10.1007/s00706-002-0558-8

Monatshefte f€ur Chemie 134, 545–549 (2003)
DOI 10.1007/s00706-002-0558-8
The Sonogashira Reaction in Ionic Liquids
´
´
Iveta Kmentova, Battsengel Gotov, Vladimır Gajda,
˘
Ã
ˇ
and Stefan Toma
Department of Organic Chemistry, Faculty of Natural Sciences, Comenius University,
SK-842 15 Bratislava, Slovakia
Received September 2, 2002; accepted September 9, 2002
Published online February 20, 2003 # Springer-Verlag 2003
Summary. The Sonogashira reaction of iodobenzene with phenylacetylene in several room temper-
ature ionic liquids was studied. A regeneration of the catalytical system immobilized in 1-butyl-3-
methylimidazolium hexafluorophosphate ([bmim]PF6) has been also investigated. The reactivity of
different iodoarenes with terminal alkynes in [bmim]PF6 was studied as well.
Keywords. Sonogashira reaction; Ionic liquids.
Introduction
Room temperature ionic liquids have been used frequently in the last years as an
alternative reaction medium for a broad range of different chemical transforma-
tions [1–6]. Ionic liquids have been utilized as solvents in many transition-metal
catalysed C–C bond formation reactions: Heck reactions [7–14], Stille-coupling
[15], Negishi-coupling [16], Suzuki-coupling [17], Kumada-coupling [18], Ullmann
reaction [19] and Tsuji-Trost allylation [20, 21]. Another important reaction for
C–C coupling is the Sonogashira reaction [22–29], which has been not yet studied
for its performance in ionic liquids [30].
Therefore, we decided to study the performance of the Sonogashira reaction in
several room temperature ionic liquids (Scheme 1).
Scheme 1
Ã
Corresponding author. E-mail: toma@fns.uniba.sk

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I. Kmentova et al.
546
Results and Discussion
At first, the reaction of iodobenzene (1a) with phenylacetylene (2a) catalyzed by
4 mol% Pd(OAc)2, 8 mol% PPh3, and 4 mol% CuI in the presence of NEt3 as base
in five different ionic liquids, namely, 1-butyl-3-methylimidazolium hexafluorophos-
phate ([bmim]PF6), 1-hexyl-3-methylimidazolium hexafluorophosphate ([hmim]
PF6), 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim]BF4), 1-hexyl-3-
methylimidazolium tetrafluoroborate ([hmim]BF4), and 1,3-dibutylimidazolium tet-
rafluoroborate ([dbim]BF4) was investigated. The expected product 3a was formed in
all cases in virtually quantitative yields after 2 hours at 80ꢀC (Table 1).
To examine the possibility for a catalyst=ionic liquid recovery system, we
tested the same reaction in [bmim]PF6 in several subsequent reactions. And indeed,
3a was obtained in high yield (93%) after the second run. However, during the next
three runs a more significant drop of activity was observed (67%, 58%, and 52%).
Nevertheless, when a small amount of catalyst (1 mol% Pd(OAc)2, 2 mol% PPh3,
and 1 mol% CuI) was added, 3a was again obtained in 94% yield. From the out-
come of the last experiment one can conclude that the decrease of reaction yields
probably is caused by catalyst leaching during the extractive work-up.
It was also found that the high yields of product were preserved in the first and
second runs (97% and 82%) when addition of CuI as a co-catalyst was omitted
(entries 11 and 12). However, in the third run a significant drop of the reaction yield
was observed (48%, entry 13).
Taking the developed reaction conditions as a standard, we next examined the
reactivity of several iodoarenes (1b–1g) with 2a in [bmim]PF6. The results (Table 2)
demonstrate that the reaction proceeds well for the various substrates under stand-
ard conditions, the yields (65–87%) should even be further increasable by individ-
ual optimization. In several cases the recovered ionic solvent, still containing the
Table 1. Yields of Sonogashira reaction of iodobenzene (1a) with phenylacetylene (2a) in different
ionic liquids
Entry
Ionic liquid
Comment
Yield=%a
1
2
[bmim]PF6
97
2. run
3. run
4. run
5. run
6. run
93
3
67
4
58
5
52
94b
6
7
[hmim]PF6
[bmim]BF4
[hmim]BF4
[dbim]BF4
[bmim]PF6
95
8
99
9
96
10
11
12
13
97
97c
82c
48c
2. run
3. run
a
b
c
isolated yields after column chromatography; after addition of catalyst, see text; reaction
performed without CuI

The Sonogashira Reaction in Ionic Liquids
547
Table 2. Yields of Sonogashira reaction of 2a with different iodoarenes in [bmim]PF6
Entry
Substrate
Ar
Comment
Yield=%a
1
2
1b
4-Cl–C6H4
87
65
57
65
38
71
84
71
69
87
79
80
2. run
3. run
3
4
1c
4-CH3O–C6H4
5
2. run
6
1d
1e
4-CH3–C6H4
7
4-CH3CO–C6H4
8
2. run
3. run
9
10
11
12
1f
1-Napthyl
2. run
1g
4-O2N–C6H4
a
isolated yields after column chromatography
Table 3. Yields of Sonogashira reaction of 1a with different 1-alkynes in [bmim]PF6
Entry
Alkyne
R
Comment
Yield=%a
1
2
3
4
5
6
2b
TMS
97
2. run
2. run
68
2b
TMS
31b
23b
46
2c
2c
Bu
Bu
41c
isolated yields after column chromatography; b isolated yield after distillation; c ZnBr2 was used as
a co-catalyst
a
catalytic system, was reused in a subsequent reaction. Furtheron an attempt
was made to employ the cheaper bromobenzene instead of iodobenzene, but the
product was obtained in 20% yield only after the first run and the reused catalyst
gave an 11% yield only. The formation of palladium black was also observed in
this case.
The reactivity of 1a with trimethylsilylacetylene (2b) and hex-1-yne (2c) was
studied as well (Table 3). Trimethylsilylacetylene gave good yields after extractive
isolation (97% after the first run and 68% after the second run, entries 1 and 2).
However, polymerisation was observed during the isolation of the product by vac-
uum distillation and it was obtained only in 31% and 23% yields in the two sub-
sequent experiments (entries 3 and 4). A reaction with 2c led to the product in 46%
yield and 42% yield when CuI was replaced by ZnBr2 [31] (entries 5 and 6).
In conclusion, we have demonstrated that the Sonogashira reaction pro-
ceeds with high yield in several different ionic liquids. In addition, the possibil-
ity of catalyst recovery in [bmim]PF6 was examined and found to be working
properly.

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I. Kmentova et al.
548
Experimental
Typical procedure: Pd(OAc)2 (4mol%) and PPh3 (8mol%) were added to 5 cm3 of pre-dried ionic
liquid and the mixture was stirred at 80ꢀC under Ar for 1 h. The resulting ionic liquid=catalyst system
was cooled to ambient temperature. CuI (4mol%), 2 mmol aryl halide, 1.2 eq. terminal alkyne, and
0.4 cm3 of NEt3 were added and the reaction mixture was stirred at 80ꢀC in a flask equipped with a
reflux condenser for 2 h under Ar. n-Hexane (10 cm3) was added to the cooled mixture, after vigorous
stirring for 5 min the hexane layer was collected and the procedure was repeated until no product was
detected in the hexane layer (about 10 times). The solvent was evaporated and the residue was purified
by chromatography on a SiO2-column with n-hexane as eluent. All reaction products had physical
constants and NMR spectra in accordance with published data. The ionic liquid=catalyst system was
dried in vacuo at 40ꢀC for 4 h and stored under Ar in the freezer before reuse in next reaction.
Acknowledgement
This work was supported by Comenius University Grant 98=2002=UK and VEGA Grant 1=0072=03.
´
We also thank VUOS a.s. Pardubice-Rybitvı, Czech Republic, for a generous gift of some of the ionic
liquids.
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