Carbocation-forming reactions in ionic liquids

Article abstract of DOI:10.1021/ja0536623

A number of trifluoroacetates, mesylates, and triflates have been studied in ionic liquids. Several lines of evidence indicate that all of these substrates react via ionization to give carbocationic intermediates. For example, cumyl trifluoroacetates give mainly the elimination products, but the Hammett ρ⁺ value of -3.74 is consistent with a carbocationic process. The analogous exo-2-phenyl-endo-3-deutero-endo-bicyclo-[2.2.1]hept-2-yl trifluoroacetate gives an elimination where loss of the exo-hydrogen occurs from a cationic intermediate. 1-Adamantyl mesylate and 2-adamantyl triflate react to give simple substitution products derived from capture of 1- and 2-adamantyl carbocations by the residual water in the ionic liquid. The triflate derivative of pivaloin, trans-2-phenylcyclopropylcarbinyl mesylate, 2,2-dimethoxycyclobutyl triflate, the mesylate derivative of diethyl (phenylhydroxymethyl)-thiophosphonate, and Z-1-phenyl-5-trimethylsilyl-3-penten- 1-yl trifluoroacetate all give products derived carbocation rearrangements (k_Δ processes), anti-7-Norbornenyl mesylate gives products with complete retention of configuration, indicative of involvement of the delocalized 7-norbornenyl cation. 1,6-Methano[10]annulen-11-yl triflate reacts in [BMIM][NTf₂] to give 1,6-methano[10]annulen-11-ol, along with naphthalene, an oxidized product derived from loss of trifluoromethanesulfinate ion. Analogous loss of CF₃SO₂^- can be seen in reaction of PhCH(CF₃)OTf. Ionic liquids are therefore viable solvents for formation of carbocationic intermediates via k_c and k _Δ processes.

Full text of DOI:10.1021/ja0536623

Published on Web 12/06/2005
Carbocation-Forming Reactions in Ionic Liquids
Xavier Creary,* Elizabeth D. Willis, and Madeleine Gagnon
Contribution from the Department of Chemistry and Biochemistry, UniVersity of Notre Dame,
Notre Dame, Indiana 46556
Received June 3, 2005; E-mail: creary.1@nd.edu
Abstract: A number of trifluoroacetates, mesylates, and triflates have been studied in ionic liquids. Several
lines of evidence indicate that all of these substrates react via ionization to give carbocationic intermediates.
For example, cumyl trifluoroacetates give mainly the elimination products, but the Hammett F+ value of
-3.74 is consistent with a carbocationic process. The analogous exo-2-phenyl-endo-3-deutero-endo-bicyclo-
[2.2.1]hept-2-yl trifluoroacetate gives an elimination where loss of the exo-hydrogen occurs from a cationic
intermediate. 1-Adamantyl mesylate and 2-adamantyl triflate react to give simple substitution products
derived from capture of 1- and 2-adamantyl carbocations by the residual water in the ionic liquid. The
triflate derivative of pivaloin, trans-2-phenylcyclopropylcarbinyl mesylate, 2,2-dimethoxycyclobutyl triflate,
the mesylate derivative of diethyl (phenylhydroxymethyl)-thiophosphonate, and Z-1-phenyl-5-trimethylsilyl-
3-penten-1-yl trifluoroacetate all give products derived carbocation rearrangements (k∆ processes). anti-
7-Norbornenyl mesylate gives products with complete retention of configuration, indicative of involvement
of the delocalized 7-norbornenyl cation. 1,6-Methano[10]annulen-11-yl triflate reacts in [BMIM][NTf2] to give
1,6-methano[10]annulen-11-ol, along with naphthalene, an oxidized product derived from loss of trifluo-
romethanesulfinate ion. Analogous loss of CF3SO2- can be seen in reaction of PhCH(CF3)OTf. Ionic liquids
are therefore viable solvents for formation of carbocationic intermediates via kC and k∆ processes.
Introduction
out in ionic liquids, a number of classic reactions have been
reported. These include Grignard,5 Reformatsky,6 Friedel-
The effect of solvent on rates of reactions where carbocations
are involved is profound. Thus model substrates such as tert-
butyl chloride and 2-adamantyl tosylate show solvolysis rate
differences of 104.5 and 105.4 respectively as solvent is varied
from ethanol to the more “highly ionizing” hexafluoroisopropyl
alcohol.1 The increased ability of polar protic solvents to solvate
(and stabilize) developing cations and anions accounts for these
large rate effects. While dimethyl sulfoxide (DMSO) has long
been recognized as an outstanding solvent for SN2 reactions,
we have recently found that this polar aprotic substance is also
a reasonable solvent for SN1-type reactions.2 Thus a variety of
carbocationic intermediates could be generated in DMSO despite
the inability to solvate the developing anion via hydrogen
bonding. Certain triflates were especially prone to give car-
bocation chemistry in DMSO.3 We are therefore interested in
the ability of novel or unusual solvents to support carbocationic
intermediates.
Crafts,7 Beckmann,8 aromatic nitration,9 and SN2 reactions.10-12
In a study of nucleophilic reactions of azide ion with various
substrates in ionic liquids, 1-iodoadamantane was reported to
react to form 1-azidoadamantane, presumably via the 1-ada-
mantyl cation.12 We have now carried out a number of studies
designed to evaluate whether carbocations can be generated via
SN1 reactions in ionic liquids. Reported here are the results of
these studies.
Results and Discussion
kC Substrates. In evaluating the viability of forming car-
bocations in ionic liquids, kinetic studies would be of great
value. The first decisions involved choices of solvent and
substrates. We initially chose the ionic liquid 1-butyl-3-
methylimidazolium triflamide, [BMIM][NTf2], 1.13 It is rela-
tively easy to prepare, recover, and recycle. Additionally, this
Ionic liquids are an emerging class of solvents that are of
much recent interest for organic reactions.4 As nonvolatile,
nonflammable, nontoxic, and potentially recyclable liquids, these
substances have potential as environmentally benign “green”
solvents. Among the many reactions that have now been carried
(5) Ramnial, T.; Ino, D. D.; Clyburne, J. A. C. Chem. Commun. 2005, 325.
(6) Reformatsky reaction in organic liquids. Tomoya Kitazume, T.; Kasai, K.
Green Chem. 2001, 3, 30.
(7) Earle, M. J.; Hakala, U.; Hardacre, C.; Karkkainen, J.; McAuley, B. J.;
Rooney, D. W.; Seddon, K. R.; Thompson, J. M.; Wa¨ha¨la¨, K. Chem.
Commun. 2005, 903.
(8) Peng, J.; Deng, Y. Tetrahedron Lett. 2001, 42, 403.
(9) Lancaster, N. L.; Llopis-Mestre, V. Chem. Commun. 2003, 2812.
(10) (a) Crowhurst, L.; Lancaster, N. L.; Arlandis, J. M. P.; Welton, T. J. Am.
Chem. Soc. 2004, 126, 11549. (b) Lancaster, N. L.; Welton, T. J. Org.
Chem. 2004, 69, 5986.
(11) (a) Kim, D. W.; Song, C. E.; Chi, D. Y. J. Org. Chem. 2003, 68, 4281. (b)
Kim, D. W.; Song, C. E.; Chi, D. Y. J. Am. Chem. Soc. 2002, 124, 10278.
(12) Chiappe, C.; Pieraccini, D.; Saullo, P. J. Org. Chem. 2003, 68, 6710.
(13) Bonhoˆte, P.; Dias, A.-P.; Papageorgiou, N.; Kalyanasundaram, K.; Gra¨tzel,
M. Inorg. Chem. 1996, 35, 1168.
(1) (a) Schadt, F. L.; Bentley, T. W.; Schleyer, P. v. R. J. Am. Chem. Soc.
1976, 98, 7667. (b) Bentley, T. W.; Bowen, C. T.; Morten, D. H.; Schleyer,
P. v. R. J. Am. Chem. Soc. 1981, 103, 5466.
(2) Creary, X.; Burtch, E.; Jiang, Z. J. Org. Chem. 2003, 68, 1117.
(3) Creary, X.; Burtch, E. J. Org. Chem. 2004, 69, 1227.
(4) (a) Welton, T. Chem. ReV. 1999, 99, 2071. (b) Ionic Liquids in Synthesis;
Welton, T., Wasserscheid, P.; Eds.; Wiley-VCH: Weinheim, Germany,
2002.
9
18114
J. AM. CHEM. SOC. 2005, 127, 18114-18120
10.1021/ja0536623 CCC: $30.25 © 2005 American Chemical Society

Carbocation-Forming Reactions in Ionic Liquids
A R T I C L E S
Scheme 1. Reaction of Cumyl Trifluoroacetates in [BMIM][NTf2]
1
ionic liquid is also one of the least viscous, and recording H
and 19F NMR spectra in this solvent are therefore quite easy.
Although somewhat hygroscopic, the amount of water present
can be easily determined by NMR. Hence kinetic studies can
be conveniently carried out in essentially neat [BMIM][NTf2]
by 1H or 19F NMR in the unlocked mode (recently termed No-D
NMR).14
1
Figure 1. First-order plot for the reaction of 2c in [BMIM][NTf2] by H
NMR at 25.0 °C.
Table 1. Solvolysis Rate Constants for Cumyl Trifluoroacetates 2
in [BMIM][NTf2] at 25.0 °C
1
a
substrate
k (s-
)
2a Ar ) p-CH3C6H4
2b Ar ) p-F-C6H4
2c Ar ) C6H5
3.67 × 10-4
4.04 × 10-5
2.74 × 10-5
1.13 × 10-3b
3.71 × 10-4c
8.41 × 10-6
1.17 × 10-6
2.93 × 10-7
The cumyl system is classic in the history of carbocation
chemistry15 and for this reason, the cumyl trifluoroacetates 2
were chosen for study. We wanted to compare the behavior of
2 in ionic liquids to that of classic cumyl systems in more
traditional polar protic solvents. When the trifluoroacetates 2a-
2f were dissolved in [BMIM][NTf2] containing buffering 2,6-
lutidine, reaction occurred smoothly to give the alkenes 3 as
the major product. Also formed were varying amounts of the
alcohols 4, which arise from traces of water (0.2-0.5%) in the
solvent. For example, in “dry”[BMIM] [NTf2], R-methylstyrene,
3c, is the sole product from 2c, while 24% of cumyl alcohol,
4c, is formed when the ionic liquid contains 0.5% water. The
methyl signal of the 2,6-lutidine, which becomes increasingly
protonated by the developing trifluoroacetic acid, shifts down-
field as the reaction proceeds. This allows the first-order rate
constant for the reaction to be determined (Figure 1).16
Alternatively, first order rate constants could be readily ob-
tained from 19F NMR data. Although the solvent [BMIM][NTf2]
is fluorinated, solvent suppression routines allow accurate
determination by 19F NMR of the amount of substrates 2
remaining relative to trifluoroacetate ion formed as the reaction
proceeds.17
2c Ar ) C6H5
2c Ar ) C6H5
2d Ar ) p-Cl-C6H4
2e Ar ) m-F-C6H4
2f Ar ) m-CF3-C6H4
a See Experimental section for kinetic method. b CH3OH solvent; ref 17.
c HOAc solvent; ref 17.
Scheme 2. Mechanism for Elimination Reaction of
Trifluoroacetate 5 in [BMIM][NTf2]
Rate data for the substrates 2 are summarized in Table 1.
There is a large change in rate constant as the electronic
character of the substituents is varied. The corresponding
Hammett F value is -3.74 and is indicative of a large amount
of cationic character in the transition state. For comparison
purposes, the F values for substituted cumyl chlorides in
methanol, ethanol, 2-propanol, and 90% aqueous acetone are
-4.82, -4.67, -4.43, and -4.54, respectively.15e These data
implicate carbocation intermediates when substrates 2 react in
[BMIM][NTf2].
Since the F value in solvolyses of 2 in [BMIM][NTf2] was
less than that of cumyl chlorides in protic solvents, the
possibility of a concerted elimination process was considered.
The bicyclic trifluoroacetate 5, which we have previously used
as a probe for concerted elimination,2,18 was therefore solvolyzed
in [BMIM][NTf2], where it undergoes facile elimination to give
the deuterated alkene 6 exclusively. This stereochemical result
is consistent with involvement of cation 7, which preferentially
loses the exo-H. A concerted ester type pyrolytic elimination
of trifluoroacetic acid is ruled out since this would be a syn
process involving loss of the endo-D.19 A bimolecular E2 type
of elimination would also involve loss of endo-D since a 0°
dihedral angle is preferred in bimolecular eliminations in
norbornyl systems.20Attention was next turned to the adamantyl
systems 8 and 11 which have been used as models for substrates
(14) (a) Hoye, T. R.; Eklov, B. M.; Ryba, T. D.; Voloshin, M.; Yao, L. J. Org.
Lett. 2004, 6, 953. (b) Hoye, T. R.; Eklov, B. M.; Voloshin, M. Org. Lett.
2004, 6, 2567.
(15) (a) Brown, H. C.; Brady, J. D.; Grayson, M.; Bonner, W. H. J. Am. Chem.
Soc. 1957, 79, 1897. (b) Brown, H. C.; Okamoto, Y.; Ham, G. J. Am. Chem.
Soc. 1957, 79, 1906. (c) Okamoto, Y.; Brown, H. C. J. Am. Chem. Soc.
1957, 79, 1909. (d) Okamoto, Y.; Inukai, T.; Brown, H. C. J. Am. Chem.
Soc. 1958, 80, 4969. (e) Okamoto, Y.; Inukai, T.; Brown, H. C. J. Am.
Chem. Soc. 1958, 80, 4972. (f) Brown, H. C.; Okamoto, Y. J. Am. Chem.
Soc. 1958, 80, 4979.
(18) Creary, X.; Casingal, V. P.; Leahy, C. J. Am. Chem. Soc. 1993, 115, 1734.
(19) For leading references see (a) Smith, G. G.; Kelly, F. W. Prog. Phys. Org.
Chem. 1971, 8, 75. (b) Maccoll, A. AdV. Phys. Org. Chem. 1965, 3, 91.
(20) Coke, J. L.; Cooke, M. P., Jr. J. Am. Chem. Soc. 1967, 89, 6701.
(16) Creary, X.; Jiang, Z. J. Org. Chem. 1994, 59, 5106.
(17) Creary, X.; Wang, Y.-X. J. Org. Chem. 1992, 57, 4761.
9
J. AM. CHEM. SOC. VOL. 127, NO. 51, 2005 18115

A R T I C L E S
Creary et al.
Scheme 4. Reaction of 1-Adamantyl Mesylate in [BMIM][NTf2]
Scheme 3. Reaction of 2-Adamantyl Triflate in [BMIM][NTf2]
Table 2. Solvolysis Rate Constants for 1-Adamantyl Mesylate, 11,
in Various Solvents at 25.0 °C
1
solvent
k (s-
)
YOMs
[BMIM][NTf2] (0.11% H2O)
[BMIM][NTf2] (0.34% H2O)
[BMIM][NTf2] (0.52% H2O)
[BMIM][NTf2] (0.69% H2O)
[BMIM][NTf2] (0.99% H2O)
97% CF3CH2OHa
1.52 × 10-6
3.38 × 10-6
6.10 × 10-6
8.63 × 10-6
1.64 × 10-5
3.5 × 10-1
-3.44
-3.09
-2.83
-2.68
-2.41
1.92
80% EtOH/20% H2Oa
4.17 × 10-3
2.81 × 10-4
6.58 × 10-4
4.21 × 10-7
0.00
Scheme 5. Rearrangement Reaction of Triflate 15 in [BMIM][NTf2]
CH3OHa
-1.17
-0.80
-4.00
CD3CO2D
b
DMSO-d6
a Reference 21. b Reference 2.
resulted in a rate increase of more than a factor of 10. A reviewer
has suggested that it may be due to rate determining trapping
of a reversibly formed ion pair by water, i.e., formation of ion
pair 14 may be reversible. This is the process originally
suggested by Sneen25 in his controversial unified mechanism
scheme, and we cannot rule out this possibility. Another
possibility involves hydrogen bonding of water to the developing
mesylate anion as the ionization proceeds. Since the ionic liquid
is presumably less capable of hydrogen bonding to the develop-
ing mesylate ion, small amounts of water may exert an
unexpectedly large effect on the developing mesylate anion,
which demands solvation and hence dramatically increases
solvolysis rates.
Of interest is the reactivity of mesylate 11 in [BMIM][NTf2]
relative to protic solvents. Data in Table 2 allows this
comparison. The reactivity of 11 is less than in typical polar
protic solvents, but greater than in DMSO-d6, a polar aprotic
solvent recently found to support carbocation forming reactions.2
Carbocation Rearrangements and k∆ Processes. One of
the fundamental processes that carbocations can undergo is
rearrangement. To obtain further evidence for the involvement
of carbocationic intermediates in ionic liquids, as opposed to
SN2 reactions with cationic character in the transition state,
substrates capable of rearrangement were therefore investigated.
The substrates examined include those with a range of leaving
groups. They also reflect the historic nature of carbocation
chemistry, ranging from carbocations of very recent interest to
some of the old classic rearrangements. Substrates have also
been chosen that reflect the interests of our laboratory.The
R-keto triflate 1526 was dissolved in [BMIM][NTf2] where it
undergoes first-order reaction at convenient rates at room
temperature to give mixtures of the rearranged alkene 16 and
Figure 2. A plot of rate of reaction of 11 in [BMIM][NTf2] at 25.0 °C vs
% water in the solvent.
that react via kC routes.1,21 2-Adamantyl triflate, 8, is a highly
reactive substrate in protic solvents.22,23 We have now found
that 8 is also quite reactive in [BMIM][NTf2]. At 25 °C it readily
converts in a first-order fashion to the alcohol substitution
product 10 with a half-life of 5.4 min. This high reactivity
contrasts with that of 2-bromoadamantane, which is reported
to be unreactive in ionic liquids at 80 °C.12 This is undoubtedly
due to the much greater leaving group ability of the triflate
nucleofuge, which has been estimated to react 107 times faster
than bromides.24 The 2-adamantyl cation, 9, is presumably the
intermediate in this transformation.1-Adamantyl mesylate, 11,
reacted in [BMIM][NTf2] (containing 0.34% H2O) to give a
mixture of the alcohol 12 along with the ether 13. First-order
rate constants (Table 2), as well as product ratios, are quite
dependent on the amount of water present in the solvent as
illustrated in Figure 2. Activation parameters (0.11% H2O in
[BMIM][NTf2]: ∆H ) 22.7 kcal/mol; ∆S ) -9 eu) are in line
with a carbocation mechanism. Of interest is the unusually large
rate effect induced by only small amounts of water in the ionic
liquid. An increase in water concentration of less than 1%
(21) Bentley, T. W.; Carter, G. E. J. Org. Chem. 1983, 48, 579.
(22) Creary, X, J. Am. Chem. Soc. 1976, 98, 6608.
(23) Kevill, D. N.; Anderson, S. W. J. Org. Chem. 1985, 50, 3330.
(24) See Noyce, D. S.; Virgilio, J. A. J. Org. Chem. 1972, 37, 2643.
(25) (a) Sneen, R. A.; Robbins, H. M. J. Am. Chem. Soc. 1972, 94, 7868. (b)
Sneen, R. A. Acc. Chem. Res. 1973, 6, 46.
(26) Creary, X. J. Org. Chem. 1979, 44, 3938.
9
18116 J. AM. CHEM. SOC. VOL. 127, NO. 51, 2005

Carbocation-Forming Reactions in Ionic Liquids
A R T I C L E S
Table 3. Solvolysis Rate Constants for Triflate 15 in Various
Solvents at 25.0 °C
Scheme 7. Reaction of Triflate 27 in [BMIM][NTf2]
1
solvent
k (s-
)
krelative
[BMIM][NTf2] (0.17% H2O)
[BMIM][NTf2] (0.30% H2O)
[BMIM][NTf2] (0.78% H2O)
[BMIM][NTf2] (1.40% H2O)
[BMIM][BF4] (0.2% H2O)
[BMIM][PF6]
4.08 × 10-5
4.36 × 10-5
4.83 × 10-5
5.49 × 10-5
3.93 × 10-4
1.54 × 10-4
5.20 × 10-4
2.00 × 10-5
4.95 × 10-5
4.36 × 10-5
5.98 × 10-6
1.82 × 10-4
4.15 × 10-6
1.05 × 10-3
1.00
1.07
1.18
1.35
9.63
3.77
12.7
0.49
1.21
1.07
0.15
4.46
0.10
25.7
[BMIM][N(CN)2]
[MeN(n-Bu)3][NTf2]
[n-Bu-Pyridinium][NTf2]
CF3CH2OH
CH3CH2OH
97% (CF3)2CHOH
CH3CO2H
Scheme 8. Reaction of Mesylate 33 in [BMIM][NTf2]
DMSO-d6
Scheme 6. Competing Reactions of Triflate 19 in [BMIM][NTf2]
alcohol 29 is derived from carbocation 28, while the ketone 32
is proposed to arise via S-O bond cleavage of 27 along with
hydride migration. As before, the trifluoromethanesulfinate ion
25 can be observed by 19F NMR spectroscopy.
Other rearrangement processes attest to the involvement of
carbocations when certain substrates are dissolved in ionic
liquids. The rearrangement propensity of the 2-phenylcyclo-
propylcarbinyl cation29,30 has made this system of interest with
respect to the mechanism of enzyme catalyzed hydroxylation
of methylcyclopropanes.31,32 We have now examined mesylate
33 in [BMIM][NTf2] where it readily reacts at room temperature
to give a rearranged set of products, 34 and 35, derived from
the homoallylic cation 36. This classic rearrangement of 33 in
the ionic liquid is consistent with relatively facile carbocation
formation.The triflate 3733 and the mesylate 4034 represent
additional k∆ substrates that have been studied in our laboratory.
These substrates react in [BMIM][NTf2] by first-order processes
to give rearranged products 38 and 41. Additionally the Taylor
laboratory has recently studied the rearrangement of silyl
activated homoallylic alcohols to cyclopropanes via carbocation
intermediates.35 In situ conversion of 45 (a mixture of E and Z
isomers) to the mesylate led to the vinylcyclopropanes 44,
presumably via a k∆ process.36 We have now studied the
Z-trifluoroacetate 43 in [BMIM][BF4] since a side reaction
alcohol 17. Rate data are given in Table 3. Unlike the solvolysis
of mesylate 11, addition of small amounts of water have only
minimal effects on reaction rate of triflate 15. The rearranged
products are consistent with involvement of the rearranged
carbocation 18. Table 3 also gives solvolysis rates of triflate
15 in five other ionic liquids as well as in other protic solvents.
The rate of ionization of triflate 15 in all of the ionic liquids
studied is quite facile and exceeds that in many common protic
solvents used in solvolysis studies.
The triflate 1927 shows unusual behavior in [BMIM][NTf2].
Reaction at 70 °C leads to the alcohol 20 in addition to the
fragmentation products naphthalene, 21, and 1-naphthaldehyde,
22. These products are all consistent with cationic processes,
with the alcohol 20 being derived from reaction of the
carbocation 23 with water in the solvent. Competing with this
kC process is a process where the S-O bond of the triflate
fragments via transition state 24 to give the trifluoromethane-
sulfinate anion 25, which can be identified by 19F NMR. Further
fragmentation leads to the product naphthalene, 21, along with
the formyl cation 26, which is the source of the 1-naphthalde-
hyde, 22, via formylation of 21.
(29) Sneen, R. A.; Lewandowski, K. M.; Taha, I. A. I.; Smith, B. R. J. Am.
Chem. Soc. 1961, 83, 4843.
(30) Shono, T.; Nishiguchi, I.; Oda, R. J. Org. Chem. 1970, 35, 42.
(31) (a) Newcomb, M.; Aebisher, D.; Shen, R.; Chandrasena, R. E. P.;
Hollenberg, P. F.; Coon, M. J. J. Am. Chem. Soc. 2003, 125, 6064. (b)
Chandrasena, R. E. P.; Vatsis, K. P.; Coon, M. J.; Newcomb, M. J. Am.
Chem. Soc. 2004, 126, 115.
(32) Kumar, D. K.; de Visser, S. P.; Sharma, P. K.; Cohen, S.; Shaik, S. J. Am.
Chem. Soc. 2004, 126, 1907.
(33) The analogous tosylate has previously been studied. See: Creary, X.; Rollin,
A. J. J. Org. Chem. 1977, 42, 4231.
This unusual S-O cleavage process in solvolysis of 19 can
also be seen when triflate 2728 reacts in [BMIM] [NTf2]. Major
products are alcohol 29 and trifluoroacetophenone 32. The
(34) Creary, X.; Mehrsheikh-Mohammadi, M. E. J. Org. Chem. 1986, 51, 1, 7.
(35) (a) Taylor, R.; Engelhardt, F. C.; Schmitt, M. J.; Yuan, H. J. Am. Chem.
Soc. 2001, 123, 2964. (b) Taylor, R.; Schmitt, M. J.; Yuan, H. Org. Lett.
2000, 2, 601. (c) Taylor, R.; Engelhardt, F. C.; Yuan, H. Org. Lett. 1999,
1, 1257. (d) Taylor, R. E.; Ameriks, M. K.; LaMarche, M. J. Tetrahedron
Lett. 1997, 38, 2057.
(27) Creary, X.; Miller, K. J. Org. Chem. 2003, 68, 8683.
(28) Allen, A. D.; Ambridge, I. C.; Che, C.; Micheal, H.; Muir, R. J.; Tidwell.
T. T. J. Am. Chem. Soc. 1983, 105, 2343.
(36) Unpublished work of R. Taylor and B. Melancon.
9
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A R T I C L E S
Creary et al.
Scheme 10. Reaction of anti-7-Norbornenyl Mesylate 47 in
Scheme 9. Rearrangement Reactions of k∆ Substrates in Ionic
Liquids
[BMIM][NTf2]
Table 4. Solvolysis Rate Constants in [BMIM] [NTf2] at 25.0 °C
1
substrate
k (s-
)
8
2.13 × 10-3 (0.57% H2O)
3.00 × 10-7 (0.50% H2O)
9.54 × 10-6 (0.33% H2O)
3.32 × 10-5 (0.42% H2O)
6.02 × 10-3 (0.75% H2O)
1.87 × 10-7 (0.33% H2O)
3.48 × 10-5 (0.40% H2O)
19
27
33
37
40
47
involving hydrolysis of the trifluoroacetate group of 43 by acyl-
oxygen cleavage to give the alcohol 45 occurs more readily in
[BMIM][NTf2]. At 70 °C trifluoroacetate 43 reacts in [BMIM]-
[BF4] to give the rearranged cyclopropanes 44 (trans:cis ratio
) 95:5) along with a smaller amount of the ester hydrolysis
product, the unrearranged alcohol 45.
Chart 1. Solvolysis Rates in [BMIM][NTf2] Relative to Rates in
Acetic Acid
These structurally rearranged products attest to the formation
of cationic intermediates 39, 42, and 46 in ionic liquids.
Neighboring cyclobutane σ-bond participation in 37 leads to
methoxy stabilized cation 39, while neighboring sulfur partici-
pation gives the cyclized intermediate 42, the precursor to the
sulfur migration product 41. Homoallylic π-participation by the
silyl activated double bond of 43 leads to silyl stabilized cation
46, the precursor of the cyclopropanes 44.
Attention was finally turned to the anti-7-norbornenyl system,
a classic k∆ system of perhaps the most renown. anti-7-
Norbornenyl tosylate exhibits an extraordinary large acetolysis
rate relative to the saturated analogue and products form with
complete retention.37 Reaction of 7-norbornenyl mesylate, 47,
in [BMIM][NTf2] at room temperature gives the alcohol 48
(complete retention) along with smaller amounts of the ether
49. As in protic solvents, the delocalized bishomoaromatic
7-norbornenyl cation 50 accounts for these products and
provides additional evidence for the involvement of carboca-
tionic intermediates in [BMIM][NTf2].
“Solvent Ionizing Power” of Ionic Liquids. While our
studies show that carbocations form in ionic liquids, rates of
ionization of typical substrates are, in general, not extraordinarily
rapid. Thus triflates 8, 15, 27, and 37 are slightly more reactive
in [BMIM][NTf2] than in acetic acid, a commonly used solvent
for SN1 reactions. Trifluoroacetates 2c and 5 are about an order
of magnitude less reactive in BMIM NTf2 than in acetic acid,
while mesylates 11 and 40 are roughly 100 times less reactive.
These studies suggest that Y values for ionic liquids are quite
dependent on leaving group. The ionizing power of [BMIM]-
[NTf2] can be classified as “low” for mesylates, where reactivity
is comparable to that in ethanol. However, for triflates, the
ionizing power of [BMIM][NTf2] is “moderate” and can exceed
that of common polar protic solvents such as acetic acid, ethanol,
and methanol.
Given the nature of ionic liquids (cations and anions), why
are Y values for solvolysis reactions, where carbocations and
anions are formed, not incredibly large? It is suggested that ionic
liquids have a decreased ability to hydrogen bond to the
developing anion in the transition state (relative to polar protic
solvents) and this is, in part, responsible for the generally low
Y values for ionic liquids. In the case of the triflate leaving
group, where the demand for stabilization of the developing
triflate anion is much less, and there is decreased demand for
hydrogen bonding, then the ionizing power of ionic liquids is
higher.
Welton has carried out kinetic studies on SN2 reactions in
ionic liquids.10 He has concluded that nucleophiles such as halide
are fully coordinated in ionic liquids and that one face of the
halide must become uncoordinated before SN2 reaction can
occur. In the case of neutral amine nucleophiles, hydrogen
bonding of the ionic liquid with the emerging ammonium ion
leads to increased reactivity of amines in ionic liquids. With
these findings in mind, some further speculation concerning the
nature of the involvement of ionic liquids in cationic solvolyses
is therefore in order. We envisage a developing transition state
(leading to an ion-pair) where the loosely organized ionic liquid
becomes much more ordered as charge develops (Chart 2). The
importance of trace amounts of water in determining rates of
1-adamantyl mesylate, 11, as well as the significant amount of
ether product, suggests a role of water (or alcohol) in the
(37) Winstein, S.; Shatavsky, M.; Norton, C.; Woodward, R. B. J. Am. Chem.
Soc. 1955, 77, 4183. (b) Winstein, S.; Shatavsky, M. J. Am. Chem. Soc.
1956, 78, 592.
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Carbocation-Forming Reactions in Ionic Liquids
A R T I C L E S
Chart 2. Schematic Representation of Reorganization of an Ionic Liquid in the Transition State during an SN1 Process
Preparation of Substrates. The preparations of 2,41 5,18 8,23 11,22,42
15,26 19,27 27,28 and 4034 have previously been described. Mesylates
33 and 47 were prepared by reaction of CH3SO2Cl and Et3N with the
appropriate alcohols, trans-2-phenylcyclopropylcarbinol29 and anti-7-
norbornenol.43 Triflate 37 was prepared by reaction of 1-hydroxy-2,2-
dimethoxycyclobutanol33 with triflic anhydride and 2,6-lutidine in
CH2Cl2. Trifluoroacetate 43 was prepared by reaction of alcohol 4536a
with trifluoroacetic anhydride and 2,6-lutidine in ether.
transition state. It is suggested that the function of trace amounts
of water (or alcohol) is to more effectively hydrogen bond to
the developing anion. As the reaction proceeds and alcohol
product builds up, the hydrogen bonding of alcohol to the
developing mesylate anion results in alcohol being present in
the vicinity of the initially formed ion pair. This leads to facile
ether formation. In the case of triflates such as 15, the decreased
need for hydrogen bonding for anion stabilization results in a
much smaller rate effect of added water.
Conclusions. A wide variety of substrates undergo clean first-
order solvolysis reactions in ionic liquids. Cationic intermediates
are involved as evidenced by a Hammett F+ value of -3.74 for
reaction of cumyl trifluoroacetates. 1-Adamantyl mesylate and
2-adamantyl triflate also react readily by cationic mechanisms.
Further evidence for cationic intermediates comes from the
observation of cationic rearrangement processes in a number
of triflates, mesylates, and trifluoroacetates. Rates of reaction
of substrates in ionic liquids are not extraordinarily high relative
to rates in polar protic solvents. Certain triflates react in [BMIM]-
[NTf2] to give products derived from competing loss of
CF3SO2-. This unusual S-O fragmentation, as well as facile
ether formation, suggests that carbocation chemistry in ionic
liquids is not only viable but also somewhat different from the
chemistry observed in protic solvents.
Reaction of 106 mg of trans-2-phenylcyclopropylcarbinol29 with 100
mg of CH3SO2Cl and 105 mg of Et3N gave mesylate 33 as an unstable
1
oil. H NMR of 33 (CDCl3) δ 7.27 (t, J ) 8 Hz, 2 H), 7.19 (t, J ) 8
Hz, 1 H), 7.09 (d, J ) 8 Hz, 2 H), 4.24 (m, 2 H), 3.021 (s, 3 H), 2.00
(m, 1 H), 1.57 (m, 1 H), 1.13 (m, 1 H), 1.07 (m, 1 H). 13C NMR of 33
(CDCl3) δ 140.9, 128.5, 126.2, 126.0, 73.8, 38.1, 22.3, 21.4, 14.1.
Reaction of 201 mg of 1-hydroxy-2,2-dimethoxycyclobutanol33 with
490 mg of (CF3SO2)2O and 225 mg of 2,6-lutidine gave triflate 37 as
1
an unstable oil. H NMR of 37 (CDCl3) δ 5.09 (t, J ) 7.6 Hz, 1 H),
3.323 (s, 3 H), 3.262 (s, 3 H), 2.8 (m, 2 H), 2.10 (m, 1 H), 1.78 (m, 1
H). 13C NMR of 37 (CDCl3) δ 118.4 (q, J ) 319 Hz), 103.2, 83.0,
49.7, 49.5, 25.7, 22.2.
Reaction of 77 mg of alcohol 4535a with 90 mg of (CF3CO)2O and
53 mg of 2,6-lutidine gave trifluoroacetate 43 as an oil. 1H NMR of 43
(CDCl3) δ 7.42-7.34 (m, 5 H), 5.88 (d of d, J ) 8, 6 Hz, 1 H), 5.58
(m, 1 H), 5.17 (m, 1 H), 2.78 (m, 1 H), 2.60 (m, 1 H), 1.48 (m, 2 H),
0.015 (s, 9 H). 13C NMR of 43 (CDCl3) δ 156.8 (q, J ) 42 Hz), 114.6
(q, J ) 286 Hz), 138.0, 130.1, 128.9, 128.8, 126.6, 119.9, 80.4, 33.7,
18.8, -1.8.
Reaction of 114 mg of anti-7-norbornenol43 with 165 mg of CH3-
SO2Cl and 183 mg of Et3N gave anti-7-norbornenyl mesylate 47 as an
unstable oil. 1H NMR of 47 (CDCl3) δ 6.02 (t, J ) 2.3 Hz, 2 H), 4.27
(br s, 1 H), 3.00 (s, 3 H), 2.88 (m, 2 H), 1.88 (m, 2 H), 1.13 (m, 2 H).
13C NMR of 47 (CDCl3) δ 133.5, 86.7, 44.2, 38.4, 21.4.
Solvolyses in Ionic Liquids. Kinetics Procedures. Rates of reaction
of triflates, mesylates, and trifluoroacetates were determined by 1H and
19F NMR methods. Spectra were recorded in the unlocked mode using
recently described methods.14
Experimental Section
Preparation of Ionic Liquids. The ionic liquids used in these studies
were prepared by the general procedures previously described.38-40
Thus, in a typical procedure for the preparation of [BMIM][NTf2], 11.3
g of 1-butyl-3-methylimidazolium chloride was dissolved in 35 mL of
distilled water and 20.2 g of lithium triflamide was added with vigorous
stirring. After 30 min, the phases were allowed to separate and the
upper aqueous phase was decanted. Distilled water (20 mL) was added
to the ionic liquid phase and the mixture was stirred for 15 min. The
upper aqueous phase was removed, and 40 mL of CH2Cl2 was added
to the remaining ionic liquid. A small amount of Na2SO4 was added to
the solution followed by MgSO4. After filtration, the solvent was
removed using a rotary evaporator. The last traces of CH2Cl2 were
removed by heating the residue at 50 °C at 15 mm pressure until the
weight of the residue remained constant. The yield of [BMIM][NTf2]
Method 1:16 Approximately 5 mg of substrate was dissolved in 0.7
mL of the appropriate ionic liquid with stirring and approximately 5
mg of 2,6-lutidine was added. The sample was placed in an NMR tube,
and the tube was placed in a constant-temperature bath at the appropriate
temperature or in the probe of the NMR at 25.0 °C. At appropriate
time intervals, the tube was withdrawn from the bath and analyzed by
1H NMR and the shift of the singlet due to the 2,6-lutidine was
determined. The shift of the 2,6-lutidine, which moves downfield as a
function of time, was monitored. After 10 half lives, a final reading
was taken. First-order rate constants were calculated by standard least
squares procedures. Rates of 2c, 2f, 8, 11, 15, 19, 27, 37, and 47 were
measured by this method.
1
was 26.8 g (99% yield), and the H NMR spectrum showed no trace
of CH2Cl2. The water content was <0.03% (as can be determined by
integration of the water signal which appears between δ 2.6 and 2.8).
Ionic liquids are hygroscopic, and the amount of water present was
determined by NMR. In certain studies, trace amounts of water were
added to the ionic liquid.
Method 2:44 Approximately 5 mg of substrate was dissolved in 0.7
of the appropriate ionic liquid with stirring and approximately 5 mg of
(38) Seddon, K. R.; Stark, A.; Torres, M.-J. Pure Appl. Chem. 2000, 72,
2275.
(39) Dupont, J.; Consorti, C. S.; Suarez, P. A. Z.; de Sousa, R. F. Org. Synth.
2002 79, 236.
(41) Creary, X.; Hatoum, H.; Barton, A.; Aldridge, T. E. J. Org. Chem. 1992,
56, 1887.
(42) Crossland, R. K.; Servis, K. L. J. Org. Chem. 1970, 35, 3195.
(43) Story, P. R. J. Org. Chem. 1961, 26, 287.
(40) Fredlake, C. P.; Crosthwaite, J. M.; Hert, D. G.; Aki, S. N. V. K.; Brennecke,
J. F. J. Chem. Eng. Data 2004, 49, 954.
9
J. AM. CHEM. SOC. VOL. 127, NO. 51, 2005 18119

A R T I C L E S
Creary et al.
2,6-lutidine was added. The sample was placed in an NMR tube, and
the tube was placed in a constant-temperature bath at the appropriate
temperature or in the probe of the NMR spectrometer at 25.0 °C. At
appropriate time intervals, the NMR tube was analyzed by 19F NMR
and the relative areas of unreacted trifluoroacetate and trifluoroacetate
anion were determined. A solvent suppression routine was used to
eliminate most of the signal due to the triflamide anion of the ionic
liquid. Rates of 2a, 2b, 2d, and 2e were measured by this method.
Method 3: A sample of substrate in the appropriate ionic liquid
prepared as described above was placed in an NMR tube, and the tube
was placed in a constant-temperature bath at the appropriate temper-
ature. At appropriate time intervals, the tube was analyzed by 600 MHz
1H NMR and areas due to unreacted mesylate and mesylate anion were
measured. Rates of 33 and 40 were measured by this method.
Solvolyses in Ionic Liquids. Product Studies. Approximately 5-10
mg of the appropriate substrate was dissolved in 1 mL of the ionic
liquid and 2,6-lutidine was added. The mixture was kept at the
appropriate temperature for 8 half lives and then analyzed by 1H NMR
spectroscopy. All products (except ether 49) were identified by spectral
comparisons with authentic samples. In certain cases, the reaction
mixture was extracted into hexane or C6D6 before recording NMR
spectra. Product ratios were determined by integration of the appropriate
signals in the 1H NMR spectra. The following procedures for solvolyses
of trifluoroacetate 5, mesylate 11, triflate 19, and mesylate 33, are
representative.
A solution of 10 mg of trifluoroacetate 518 (99% D incorporation)
and 8 mg of 2,6-lutidine in 1.0 mL of [BMIM][NTf2] containing 0.3%
H2O was kept at room temperature for 8 h. The mixture was then
extracted with 3 mL of hexane, and the hexane was filtered through a
small amount of silica gel in a pipet. The solvent was removed using
a rotary evaporator and the residue was dissolved in CDCl3 and analyzed
by 1H and 13C NMR. The 1H NMR showed only alkene 6, which
contained 99% deuterium as determined from the residual undeuterated
alkene signal at δ 6.59.
A solution of 11.3 mg of 1-adamantyl mesylate, 11, and 9 mg of
2,6-lutidine in 1.1 mL of [BMIM][NTf2] containing 0.1% H2O was
heated at 70 °C for 6.5 h. 1H NMR analysis showed a mixture of
1-adamantanol, 12, and di-1-adamantyl ether, 13,45 in a 4:1 ratio. The
mixture was then extracted with 3 mL of hexane, and the hexane was
filtered through a small amount of silica gel in a pipet. The solvent
was removed using a rotary evaporator. The residue was identified as
di-1-adamantyl ether, 13,45 by 1H NMR and mass spectrometry which
showed m/e ) 286. The 1-adamantanol did not extract into the hexane.
In a separate run containing 0.35% H2O, extraction of the solvolysis
1
mixture with two 3 mL portions of ether and analysis by H NMR
showed 12 and 13 in a 90:10 ratio.
A solution of 4.6 mg of triflate 19 and 4.5 mg of 2,6-lutidine in 1.1
mL of [BMIM][NTf2] containing 0.5% H2O was heated at 70 °C for 3
h and then heated at 80 °C for 3 h. At the completion of the reaction,
the mixture was analyzed by 19F NMR which showed CF3SO3- located
0.47 ppm downfield from the solvent NTf2- signal and CF3SO2- located
1
8.31 ppm upfield from the solvent signal. H NMR analysis showed
alcohol 20, naphthalene, 21, and 1-naphthaldehyde, 22, in a 61:29:10
ratio. These products were identified by spectral comparisons with
authentic samples run in [BMIM][NTf2].
A solution of 8.4 mg of mesylate 33 and 8.2 mg of 2,6-lutidine in
1.5 g of [BMIM][NTf2] containing 0.4% H2O was kept at 25 °C for 24
h and then heated at 45 °C for 5 h. During the course of the reaction,
the solution was analyzed by 1H NMR which showed the starting
-
mesylate at δ 3.04 as well as a signal due to mesylate ion (CH3SO3
)
which grows in at δ 2.7. Also appearing is a transient signal which
grows in at δ 2.87 which is due to a rearranged and reactive mesylate
tentatively identified as 1-phenyl-3-buten-1-yl mesylate. At the comple-
tion of the reaction 1H NMR analysis showed only 1-phenyl-1,3-
butadiene, 34,46 and 1-phenyl-3-buten-1-ol, 35,47 in a 59:41 ratio. These
products were identified by spectral comparisons with authentic
samples.
Supporting Information Available: 1NMR spectra illustrating
the determination of water content in ionic liquids, 1NMR and
19F NMR spectra showing the kinetic methods, the Hammett
1
plot for the data in Table 1, and H and 13C NMR spectra of
compounds 33, 37, 43, and 47. This material is available free
of charge via the Internet at http://pubs.acs.org.
JA0536623
(45) Kraatz, U. Chem. Ber. 1973, 106, 3095.
(46) Coyner, E. C.; Ropp, G. A. J. Am. Chem. Soc. 1947, 69, 2231.
(47) Smith, G. G.; Voorhees, K. J. J. Org. Chem. 1970, 35, 2182.
(44) Creary, X.; Wang, Y.-X. J. Org. Chem. 1992, 57, 4761.
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18120 J. AM. CHEM. SOC. VOL. 127, NO. 51, 2005