°C for 2 days with only a 15% conversion of 2,2′-bipyridine.
However, when the neat mixture of 2,2′-bipyridine with 1.5
equiv of butyl iodide was heated at 100∼110 °C for 24 h,
only the monoquaternary product was formed. No diquater-
nary salt was formed even upon the addition of more
iodobutane with concomitant heating at higher temperature
Scheme 1. Synthesis of IL 1
(140 °C). This is not surprising since the monoquaternary
salt is insoluble in butyl iodide and thus is unavailable to be
butylated further. Subsequent metathetical reaction with
lithium bis(trifluoromethanesulfonyl)amide resulted in the
formation of ionic liquid 1. Excess butyl iodide was
recovered by trapping at -195 °C in vacuo. Under these
reaction conditions, a small trace of 2,2′-bipyridine remains,
but 1 can be purified by removing the latter by sublimation.
This method is particularly effective when the reaction scale
is above 1 g of 2,2′-bipyridine. To our delight, the product
can be classified as a room-temperature ionic liquid with a
glass transition temperature of -58.79 °C and with high
stability toward water and air. This ionic liquid containing
the bis(trifluoromethanesulfonyl)amide as an anion was
completely soluble in acetone, methylene chloride, and
acetonitrile but insoluble in water and ether. In addition, it
is thermally stable up to 308 °C (DSC).
can be used as both a recyclable solvent and an efficient
ligand for Heck and Suzuki reactions. In our efforts to
4
synthesize this kind of ionic liquid with multiple centers
available for quaternization, we now have extended our
research to 2,2′-bipyridine, which is commercially available,
and have investigated its application in copper-catalyzed
cross-coupling reactions between perfluoroalkyl or penta-
fluorophenyl halides and aryl iodides.
The replacement of a hydrogen atom in aromatic com-
pounds by a perfluoroalkyl group can bring about some
remarkable changes in the physical properties, chemical
reactivity, and biological activity of the derived fluorinated
compounds. As a result, considerable effort has been devoted
to the development of useful methods for efficient and
selective introduction of a perfluoroalkyl group into organic
Given the straightforward synthesis of the monoquaternary
ionic liquid 1, we began to investigate its efficacy as a solvent
for copper-catalyzed cross-coupling perfluoroalkylation reac-
tions. Activated copper (1 equiv), iodobenzene (1 equiv),
and perfluorobutyl iodide (1 equiv) were added directly into
5
compounds. Among them, copper-catalyzed cross-coupling
3
g of 1 under a dinitrogen atomosphere (Table 1). Initially,
reactions between perfluoroalkyl halides and iodoaromatics
6
are a direct and convenient method. The main disadvantage
of this process lies in the use of vigorous conditions, e.g.,
polar aprotic solvents such as DMSO, 110∼130 °C or even
higher reaction temperature, and usually a large stoichio-
metric excess of copper employed to drive the reaction.
However, the reaction proceeded at 70 °C with 2,2′-
bipyridine as an additive, but a longer reaction time (>72
Table 1. Copper-Catalyzed Perfluorobutylation in 1 and the
Recycling of 1a
7
h) was still required. Here, 2,2′-bipyridine assisted the
reaction by acting as a ligand for the fluoroalkylcopper
intermediate. Hence, polar aprotic solvents may be required
to adequately immobilize this intermediate. Considering the
high polarity of ionic liquids and the coordination ability of
monoquaternary ionic liquids, it was of interest to synthesize
a monoquaternary 2,2′-bipyridinium-based ionic liquid to use
it as both the solvent and the ligand to promote such copper-
catalyzed cross-coupling reactions.
cycle
yield (%)
1
88
2
85
3
90
4
87
5
89
b
a
All reactions were performed using a 1:1:1 mixture of iodobenzene,
perfluorobutyl iodide, and copper. b Isolated yields after silica chromatog-
raphy.
the reaction was carried out at room temperature. However,
no reaction occurred after 24 h. Screening of various reaction
conditions revealed that perfluorobutyl iodide was completely
converted after heating at 75 °C for 20 h (checked by GC-
MS). The reaction is remarkably clean, and no biphenyl, from
Ullmann coupling, was observed. These are mild reaction
The route to 1-butyl-2,2′-bipyridinium bis(trifluoromethane-
sulfonyl)amide (1) is depicted in Scheme 1. Initially, 2,2′-
bipyridine was mixed with an excess of butyl iodide at 80
(
4) (a) Xiao, J.-C.; Twamley, B.; Shreeve, J. M. Org. Lett. 2004, 6, 3845-
847. (b) Xiao, J.-C.; Shreeve, J. M. J. Org. Chem. 2005, 70, 3072-3078.
5) (a) Welch, J. T. Tetrahedron 1987, 43, 3123-3197. (b) Organof-
3
6
(
conditions compared with those used previously. Although
luorine Chemistry: Principles and Commercial Applications; Banks, R.
E., Smart, B. E., Tatlow, J. C., Eds.; Plenum Press: New York, 1994. (c)
Chambers, R. D. Fluorine in Organic Chemistry; CRC Press: Boca Raton,
FL, 2004. (d) Kirsch, P. Modern Fluoroorganic Chemistry; Wiley-VCH:
Weinheim, Germany, 2004.
it was not possible to isolate the pure complex, one
explanation for these observations is that the highly polar
ionic liquid 1 acts as both the solvent and the ligand for
perfluorobutylcopper. It is likely that the ionic liquid-
coordinated copper complex facilitated the cross-coupling
reaction with iodobenzene. Importantly, the product, per-
fluorobutyl benzene, was easily separated by simple extrac-
(
6) Mcloughlin, V. C. R.; Thrower, J. Tetrahedron 1969, 25, 5921-
940.
7) (a) Croxtall, B.; Fawcett, J.; Hope, E. G.; Stuart, A. M. J. Chem.
5
(
Soc., Dalton Trans. 2002, 491-499. (b) Wiedenfeld, D.; Niyogi, S.;
Chakrabarti, D. J. Fluorine Chem. 2000, 104, 303-306.
1964
Org. Lett., Vol. 7, No. 10, 2005
Xiao, Ji-Chang
