Using geminal dicationic ionic liquids as solvents for high-temperature organic reactions

Article abstract of DOI:10.1021/ol051637w

(Chemical Equation Presented) Several organic reactions conducted at high temperatures, including the isomerization reaction, the Claisen rearrangement, and the Diels-Alder reaction, were investigated in three geminal dicationic ionic liquids with high thermal stability. High to moderate yields of the products for most entries were obtained. Advantages of these approaches are discussed. These ionic liquids were shown to be recyclable. The utility of these ionic liquid solvents for high-temperature organic reactions was demonstrated.

Full text of DOI:10.1021/ol051637w

ORGANIC
LETTERS
2
005
Vol. 7, No. 19
205-4208
Using Geminal Dicationic Ionic Liquids
as Solvents for High-Temperature
Organic Reactions
4
Xinxin Han and Daniel W. Armstrong*
Department of Chemistry, Iowa State UniVersity, Ames, Iowa 50011
sec4dwa@iastate.edu
Received July 12, 2005
ABSTRACT
Several organic reactions conducted at high temperatures, including the isomerization reaction, the Claisen rearrangement, and the Diels
−
Alder reaction, were investigated in three geminal dicationic ionic liquids with high thermal stability. High to moderate yields of the products
for most entries were obtained. Advantages of these approaches are discussed. These ionic liquids were shown to be recyclable. The utility
of these ionic liquid solvents for high-temperature organic reactions was demonstrated.
Room-temperature ionic liquids (ILs) have been touted as
replacements for traditional molecular solvents in synthesis
because of their nonvolatility, nonflammability, stability, and
anhydrous scandium trifluoromethanesulfonate at 200 °C in
ionic liquids to obtain dihydrobenzo[b]furan derivatives.6a
With microwave heating, high-speed Heck reactions were
1
6b
ease of recyclability. In recent years, numerous applications
done in [bmim][PF
6
] at 180 or 220 °C. To our knowledge,
of room-temperature ionic liquids have been investigated in
no other synthetic organic reactions in ionic liquids at
temperature above 200 °C have been reported.
1a,d,2
1-3
1d,3b,4
organic,
organometallic, and enzymatic synthesis
5
as well as in chemical analysis. Presumably, due to their
high stability and low volatility, ionic liquids are promising
solvents for organic reactions carried out at high tempera-
tures. Surprisingly, there are few reports on high-temperature
organic reactions in these new solvents.6 Zulfiqar and
Kitazume reported a sequential reaction which involved a
Claisen rearrangement and cyclization reaction catalyzed by
It has been reported that the decomposition/volatilization
temperatures of monocationic ionic liquids is high in most
7
cases. Recent research indicated that the thermal stability
8,5e
of these ionic liquids has been overestimated. Inverse gas
chromatographic tests showed that thermal degradation of
imidazolium-based ionic liquids occur at temperatures below
(
5) (a) Huddleston, J. G.; Willauer, H. D.; Swatloski, R. P.; Visser, A.
(
1) (a) Welton, T. Chem. ReV. 1999, 99, 2071-2083. (b) Wasserscheid,
E.; Rogers, R. D. Chem. Commun. 1998, 1765-1766. (b) Branco, L. C.;
Crespo, J. G.; Afonso, C. A. M. Angew. Chem., Int. Ed. 2002, 41, 2771-
2773. (c) Armstrong, D. W.; He, L.; Liu, Y.-S. Anal. Chem. 1999, 71, 3873-
3876. (d)Armstrong, D. W.; Zhang, L.-K.; He, L.; Gross, M. L. Anal. Chem.
2001, 73, 3679-3686. (e) Anderson, J. L.; Armstrong, D. W. Anal. Chem.
2003, 75, 4851-4858. (f) Carda-Broth, S.; Berthod, A.; Armstrong, D. W.
Rapid Commun. Mass Spectrom. 2003, 17, 553-560. (g) Ding, J.; Welton,
T.; Armstrong, D. W. Anal. Chem. 2004, 76, 6819-6822. (h) Yu, L.; Garcia,
D.; Ren, R.; Zeng, X. Chem. Commun. 2005, 2277-2279. (i) Baker, G.
A.; Baker, S. N.; Pandey, S.; Bright, F. V. Analyst 2005, 130, 800-808.
(6) (a) Zulfiqar, F.; Kitazume, T. Green Chem. 2000, 2, 296-297. (b)
Vallin, K. S. A.; Emilsson, P.; Larhed, M.; Hallberg, A. J. Org. Chem.
2002, 67, 6243-6246.
P.; Keim, W. Angew. Chem., Int. Ed. 2000, 39, 3772-3789. (c) Dupont,
J.; de Souza, R. F.; Suarez, P. A. Z. Chem. ReV. 2002, 102, 3667-3692.
d) Jain, N.; Kumar, A.; Chauhan, S.; Chausan, S. M. S. Tetrahedron 2005,
(
6
1, 1015-1060.
2) (a) Olivier-Bourbigou, H.; Magna, L. J. Mol. Catal. A: Chem. 2002,
82-183, 419-437. (b) Baudequin, C.; Baudoux, J.; Levillain, J.; Cahard,
(
1
D.; Gaumont, A.-C.; Plaquevent, J.-C. Tetrahedron: Asymmetry 2003, 14,
081-3093.
3) (a) Sheldon, R. Chem. Commun. 2001, 2399-2407. (b) Gordon, C.
M. Appl. Catal. A: Gen. 2001, 222, 101-117.
4) Sheldon, R. A.; Lau, R. M.; Sorgedrager, M. J.; van Rantwijk, F.;
Seddon, K. R. Green Chem. 2002, 4, 147-151.
3
(
(
1
0.1021/ol051637w CCC: $30.25
© 2005 American Chemical Society
Published on Web 08/23/2005

5e
2
00 °C. Similar conclusions were reached by Scott and co-
workers using “precise thermogravimetric analysis (TGA)
Table 1. Isomerization of Carvone in Dicationic Ionic Liquids
8
a
measurements”. It was found that degradation of ionic
liquids occurred at temperatures much lower than the ones
reported previously. Organic reactions done at temperatures
above 200 °C require ionic liquid solvents with higher
thermal stability. Most recently, a series of geminal dicationic
ionic liquids with high thermal stabilities was prepared by
9
our group. The degradation/volatization onset temperatures
a
of these geminal dicationic ionic liquids ranged from 330 to
entry
ionic liquid
T (°C)
time (h)
yield (%)
>
400 °C. These high-stability ionic liquids are promising
1
2
3
4
5
6
C9(bim)2-NTf2
250
300
250
300
250
300
3
0.5
4
0.5
4
0.5
52
58
43
68
49
75
solvents for high-temperature organic reactions. In this
communication, the utility of three high-stability ionic liquid
solvents (Figure 1) for high-temperature organic reactions,
C (mim) -NTf
2
9
2
C9(mpy)2-NTf2
a
Isolated yield.
liquids. Compared to Strauss’s method,10 in which the
isomerization of carvone is done in water at 250 °C, the
optimum yield of this method is slightly lower. However,
this procedure has the advantage that the reaction in ionic
liquid can be done at atmospheric pressure, thus avoiding
the use of a more complex high-pressure reactor.
The second reaction investigated was the Claisen rear-
rangement of allyl phenyl ether (Table 2). The reaction was
Figure 1. Structure of the dicationic ionic liquid used in this paper.
Table 2. Claisen Rearrangement of Allyl Phenyl Ether in
Dicationic Ionic Liquids
including the isomerization reaction, the Claisen rearrange-
ment, and the thermo-induced Diels-Alder reaction, were
investigated. The effects of temperature and type of dicationic
ionic liquid on the reaction times and yields are discussed.
The first thermal reaction investigated was the isomeriza-
tion of carvone to carvacrol (Table 1). After carvone was
dissolved in the dicationic ionic liquids, the temperature was
kept at 250 °C and the reaction was finished in 3-4 h
a
entry
ionic liquid
T (°C)
yield (%)
7
8
9
0
1
C9(bim)2-NTf2
250
300
250
300
250
300
63
10
75
20
35
18
(monitored by TLC, see the Supporting Information), the
product was extracted with ethyl ether, and moderate yields
of carvacrol were obtained. When the reaction was done at
C9(mim)2-NTf2
C9(mpy)2-NTf2
1
1
300 °C, both the reaction rate and yield increased. The
increase in reaction rate was expected, while the enhanced
yield was an added benefit. The nature/type of ionic liquid
also affects this isomerization reaction. At 300 °C, the yield
12
a
Isolated yield.
of the carvone isomerization in C
9
(mpy)
2
-NTf
2
was higher
. In this
than those in C (bim) -NTf and C
9
2
2
9
(mim)
2
-NTf
2
complete in 10 min in these ionic liquids. In contrast to the
isomerization of carvone, the yield was much higher at 250
case, the aliphatic ionic liquid solvent produced higher yields
than did the aromatic-imidazolium-based dicationic ionic
°
C than at 300 °C. Further, increasing the reaction time
resulted in side reactions and decreasing yields of the
expected product. One of the side products was very difficult
to separate from the rearrangement product by flash chro-
matography, which made the isolation and purification
process difficult. In addition, low yields of 2-methyl-2,3-
dihydrobenzo[b]furan were obtained when the reaction time
(
7) (a) Bonh oˆ te, P.; Dias, A.-P.; Papageorgiou, N.; Kalyanasundaram,
K.; Gr a¨ tzel, M. Inorg. Chem. 1996, 35, 1168-1178. (b) Huddleston, J. G.;
Visser, A. E.; Reichert, W. M.; Willauer, H. D.; Broker, G. A.; Rogers, R.
D. Green Chem. 2001, 3, 156-164. (c) Wilkes, J. S. J. Mol. Catal. A:
Chem. 2004, 214, 11-17. (d) Zhang, Z.; Reddy, R. G. EPD Congress 2002;
Taylor, P. R., Ed.; TMS: Warrendale, PA, 2002; pp 33-39.
(8) (a) Baranyai, K. J.; Deacon, G. B.; MacFarlane, D. R.; Pringle, J.
M.; Scott, J. L. Aust. J. Chem. 2004, 57, 145-147. (b) Scammells, P. J.;
Scott, J. L.; Singer, R. D. Aust. J. Chem. 2005, 58, 155-169.
(9) Anderson, J. L.; Ding, R.; Ellern, A.; Armstrong, D. W. J. Am. Chem.
(10) An, J.; Bagnell, L.; Cablewski, T.; Strauss, C. R.; Trainor, R. W. J.
Org. Chem. 1997, 62, 2505-2511.
Soc. 2005, 127, 593-604.
4206
Org. Lett., Vol. 7, No. 19, 2005

was increased to 60 min at 250 °C in the C
ionic liquid. Different ionic liquids also affected the reaction.
In this case, much better yields were obtained in the
9
(mpy)
2
-NTf
2
No significant regioselectivity for these reactions was
observed when different dicationic ionic liquid were used.
Similar ratios of the two isomeric products were observed
imidazolium-based C
ionic liquids than in the C
9
(mim)
2
-NTf
2
and C
9
(bim)
2
-NTf
2
for all the rearrangements in C
NTf . The rearrangement of m-methoxy allyl phenyl ether
shows the highest regioselectivity in the C
ionic liquid. The ratio of the two isomers was 1:2.4.
The Claisen rearrangement in C (mim) -NTf
9
(mim)
2
-NTf
2 9 2
and C (mpy) -
9
(mpy)
2
-NTf
2
ionic liquid.
2
9
(mpy)
2
-NTf
2
The Claisen rearrangements of three meta-substituted allyl
phenyl ethers in the dicationic ionic liquids at 250 °C were
investigated. The results are shown in Table 3. The nature
9
2
2
has
significant advantages over the reaction in traditional mono-
6
cationic ionic liquids. First, there is no need for a Lewis
acid catalyst. Second, the reaction time decreases greatly
Table 3. Claisen Rearrangement of Meta-Substituted Allyl
Phenyl Ether in Dicationic Ionic Liquids
(10 min vs 10 h). Claisen rearrangement products are
obtained in the dicationic ionic liquid while the products
obtained in the monocationic ionic liquid under Lewis acid
catalysis are dihydrobenzo[b]furan derivatives.6 Com-
pared to the analogous Claisen rearrangement performed
1
0
in superheated water, the reaction for this IL method was
done at atmosphereic pressure (i.e., no autoclaves are
needed).
The last reaction investigated was a thermally induced
Diels-Alder reaction of anthracene with diethyl fumarate
(Table 4). In these three dicationic ionic liquids, the reaction
a
entry
R
ionic liquid
1/2
yield (%)
13
14
15
16
17
18
19
20
21
OMe
C9(bim)2-NTf2
C9(mim)2-NTf2
C9(mpy)2-NTf2
C9(bim)2-NTf2
C9(mim)2-NTf2
C9(mpy)2-NTf2
C9(bim)2-NTf2
C9(mim)2-NTf2
C9(mpy)2-NTf2
1:1.8
1:2.4
82
34
Table 4. Diels-Alder Reaction of Anthracene and Diethyl
Fumarate in Dicationic Ionic liquids
Me
4:5
1:1
87
44
CF3
1:1.2
1:1
77
74
a
Isolated yield.
entry
ionic liquid
conversiona,b (%)
22
23
24
C9(bim)2-NTf2
C9(mim)2-NTf2
C9(mpy)2-NTf2
45
71
66
of the ionic liquid had a substantial effect on both the yield
and the product ratio. The reactions were negligible in the
C
9
(bim)
2 2
-NTf IL (i.e., none of the products were the
a
Although a reasonable conversion of starting materials to products is
expected rearrangements products). Only cyclization dihy-
drobenzo[b]furan products and decomposition products,
m-trifluoromethylphenol, were obtained with low yields for
the rearrangement of m-trifluoromethyl allyl phenyl ether in
obtained in 10 min, the product is difficult to remove from the IL by simple
solvent extraction using ether; for example, five extractions of 23 removed
7
2% of the product. b Conversion was determined by HPLC (C18, ACN/
water ) 50:50, detection wavelength ) 254 nm, flow rate ) 1.0 mL/min)
analysis of the IL solution based on diethyl fumarate.
this ionic liquid. The pyrrolidinium-based C
9
(mpy)
2
-NTf
2
IL is only a moderately effective solvent for these Claisen
rearrangements. Modest yields for the reaction of m-methoxy
allyl phenyl ether and m-methyl allyl phenyl ether were
obtained. However, a good yield for the rearrangement of
m-trifluoromethyl allyl phenyl ether was observed. The best
was finished in 10 min at 220 °C. Reasonable yields were
9
obtained in the C (mim)
2
-NTf
2
(51%) and C
9
(mpy)
2
-NTf
2
(47%) ionic liquids. Increasing reaction time or temperature
resulted in the volatilization of the anthracene; therefore, the
equilibrium moved to the left and the conversion decreased.
The low isolated yield of this reaction is due to the high
solubility of the product in these ionic liquids. Even after
five equal-volume extractions by ethyl ether, a relatively large
amount of product still stayed in the ionic liquids (from
TLC).
IL solvent for these reactions was C
9
(mim)
2
2
-NTf . The
reaction was quite clean, and high yields of the expected
Claisen rearrangement products were attained for all of the
substituted allyl phenyl ethers. Also, no significant side
reaction products were found in this ionic liquid. In addition,
clean Claisen rearrangement products only were obtained in
the C
9
(mim)
2
-NTf
2
ionic liquid. Some unidentified side
Although the dicationic liquid used for the reaction
darkened somewhat after exposure to high temperatures, they
products, which are difficult to separate from the expected
product by flash chromatography, were observed for the
reactions in the other two dicationic ionic liquids. The
explanation for this phenomenon is not yet clear.
still can be recycled and used for additional runs. C
9 2
(mim) -
NTf and C (mpy) -NTf were chosen to investigated the
2
9
2
2
recyclability of these solvents for the Claisen rearrangement
Org. Lett., Vol. 7, No. 19, 2005
4207

of allyl phenyl ether and the isomerization of carvone,
respectively. Table 5 shows that these two ionic liquids can
liquids. The results showed that the application of these new
thermal stable IL solvents for high-temperature organic
synthesis is promising and that these dicationic ILs can be
reused/recycled. Differences in the structure of the cation
affects the reaction significantly. Generally, for the isomer-
Table 5. Reaction Conversions and Yields with Reused/
Recycled Dicationic IL Solvents
9 2 2
ization of carvone, C (mpy) -NTf was the optimum solvent,
a
a
while for the Claisen rearrangement and the Diels-Alder
reaction
1
ionic liquid
cycle conversion (%) yield (%)
reactions in this work, C
results.
9
(mim)
2
2
-NTf produced the best
C9(mpy)2-NTf2
1
2
3
1
2
3
99
99
98
93
87
88
74
81
79
80
77
75
2
C9(mim)2-NTf2
Acknowledgment. This work was supported by the
National Institues of Health (Grant No. NIH RO1 GM53825-
0
8).
a
Conversion and yield were determined by HPLC (C18, ACN/water )
0:50, detection wavelength ) 254 nm, flow rate ) 1.0 mL/min) analysis
5
of the mixtures extracted from IL solution by ether.
Supporting Information Available: Details of the ex-
periments, characterization of the products, and NMR spectra.
This material is available free of charge via the Internet at
http://pubs.acs.org.
be reused without significant decreases in the conversion or
yield.
In summary, three classes of high-temperature organic
reactions were investigated in three geminal dicationic ionic
OL051637W
4208
Org. Lett., Vol. 7, No. 19, 2005