Chiral ionic liquids: Synthesis, properties, and enantiomeric recognition

Article abstract of DOI:10.1021/jo702368t

(Chemical Equation Presented) We have synthesized a series of structurally novel chiral ionic liquids which have a either chiral cation, chiral anion, or both. Cations are an imidazolium group, while anions are based on a borate ion with spiral structure and chiral substituents. Both (or all) stereoisomeric forms of each compound in the series can be readily synthesized in optically pure form by a simple one-step process from commercially available reagents. In addition to the ease of preparation, most of the chiral ILs in this series are liquid at room temperature with a solid to liquid transformation temperature as low as -70°C and have relatively high thermal stability (up to at least 300°C). Circular dichroism and X-ray crystallographic results confirm that the reaction to form the chiral spiral borate anion is stereospecific, namely, only one of two possible spiral stereoisomers was formed. Results of NMR studies including ¹H{¹⁵N} heteronuclear single quantum coherence (HSQC) show that these chiral ILs exhibit intramolecular as well as intermolecular enantiomeric recognition. Intramolecularly, the chiral anion of an IL was found to exhibit chiral recognition toward the cation. Specifically, for a chiral IL composing with a chiral anion and a racemic cation, enantiomeric recognition of the chiral anion toward both enantiomers of the cation lead to pronounced differences in the NMR bands of the cation enantiomers. The chiral recognition was found to be dependent on solvent dielectric constant, concentration, and structure of the ILs. Stronger enantiomeric recognition was found in solvent with relatively lower dielectric constants (CDCl₃ compared to CD₃CN) and at higher concentration of ILs. Also, stronger chiral recognition was found for anions with a relatively larger substituent group (e.g., chiral anion with a phenylmethyl group exhibits stronger chiral recognition compared to that with a phenyl group, and an anion with an isobutyl group has the weakest chiral recognition). Chiral anions were also found to exhibit intermolecular chiral recognition. Enantiomeric discrimination was found for a chiral IL composed of a chiral anion and achiral cation toward another chiral molecule such as a quinine derivative.

Full text of DOI:10.1021/jo702368t

Chiral Ionic Liquids: Synthesis, Properties, and Enantiomeric
Recognition†
Shaofang Yu, Sergey Lindeman, and Chieu D. Tran*
Department of Chemistry, Marquette UniVersity, P. O. Box 1881, Milwaukee, Wisconsin 53201-1881
chieu.tran@marquette.edu
ReceiVed NoVember 14, 2007
We have synthesized a series of structurally novel chiral ionic liquids which have a either chiral cation,
chiral anion, or both. Cations are an imidazolium group, while anions are based on a borate ion with
spiral structure and chiral substituents. Both (or all) stereoisomeric forms of each compound in the series
can be readily synthesized in optically pure form by a simple one-step process from commercially available
reagents. In addition to the ease of preparation, most of the chiral ILs in this series are liquid at room
temperature with a solid to liquid transformation temperature as low as -70 °C and have relatively high
thermal stability (up to at least 300 °C). Circular dichroism and X-ray crystallographic results confirm
that the reaction to form the chiral spiral borate anion is stereospecific, namely, only one of two possible
spiral stereoisomers was formed. Results of NMR studies including 1H{15N} heteronuclear single quantum
coherence (HSQC) show that these chiral ILs exhibit intramolecular as well as intermolecular enantiomeric
recognition. Intramolecularly, the chiral anion of an IL was found to exhibit chiral recognition toward
the cation. Specifically, for a chiral IL composing with a chiral anion and a racemic cation, enantiomeric
recognition of the chiral anion toward both enantiomers of the cation lead to pronounced differences in
the NMR bands of the cation enantiomers. The chiral recognition was found to be dependent on solvent
dielectric constant, concentration, and structure of the ILs. Stronger enantiomeric recognition was found
in solvent with relatively lower dielectric constants (CDCl3 compared to CD3CN) and at higher
concentration of ILs. Also, stronger chiral recognition was found for anions with a relatively larger
substituent group (e.g., chiral anion with a phenylmethyl group exhibits stronger chiral recognition
compared to that with a phenyl group, and an anion with an isobutyl group has the weakest chiral
recognition). Chiral anions were also found to exhibit intermolecular chiral recognition. Enantiomeric
discrimination was found for a chiral IL composed of a chiral anion and achiral cation toward another
chiral molecule such as a quinine derivative.
Introduction
high solubility power, and virtually no vapor pressure.1-13
Because of these properties, they can serve as a “green”
recyclable alternative to the volatile organic compounds that
are traditionally used as industrial solvents.1-13 The ILs have,
in fact, been successfully used in many applications, including
Ionic liquids (ILs) are a group of organic salts that are liquid
at room temperature.1-13 They have unique chemical and
physical properties, including being air and moisture stable, a
† Taken, in part, from the dissertation of Shaofang Yu of the Dept. of
Chemistry, Marquette University, December 2006..
(1) Welton, T. Chem. ReV. 1999, 99, 2071-2083.
(2) Wasserscheid, P., Welton, T., Eds. Ionic Liquids in Synthesis; Wiley-
VCH: Weinheim, Germany, 2003.
(3) Ohno, H., Eds. Electrochemical Aspects of Ionic Liquids; Wiley: New
York, 2005.
(4) Tundo, P.; Perosa, A. Chem. Soc. ReV. 2007, 36, 532-550.
(5) Tran, C. D.; Lacerda, S. H. P. Anal. Chem. 2002, 74, 5337-5341.
(6) Tran, C. D.; Lacerda; S. H. P.; Oliveira, D. Appl. Spectrosc. 2003,
57, 152-157.
(7) Mele, A.; Tran, C. D.; Lacerda, S. H. P. Angew. Chem., Int. Ed.
2003, 42, 4364-4366.
(8) Blanchard, L. A.; Hancu, D.; Beckman, E. J.; Brennecke, J. F. Nature
1999, 399, 28-29.
(9) Huddleston, J. G.; Willauer, R. P.; Swatloski, A. E.; Visser, A. E.;
Rogers, R. D. Chem. Commun. 1998, 1765-1766.
10.1021/jo702368t CCC: $40.75 © 2008 American Chemical Society
Published on Web 03/01/2008
2576
J. Org. Chem. 2008, 73, 2576-2591

Chiral Ionic Liquids
SCHEME 1. Shows the General Synthetic Method Used to Synthesize the Chiral ILs
replacing traditional organic solvents in organic and inorganic
syntheses, solvent extractions, liquid-liquid extractions, and
electrochemical reactions as well as medium to enhance the
sensitivity of thermal lens measurements.1-13 Advances in ILs
have made synthesis of chiral ILs a subject of intense study in
recent years.14-26 The popularity stems from the fact that it is
possible to use chiral ILs as chiral solvents for optical resolution,
for asymmetric induction in synthesis, as a chiral stationary
phase in chromatography, and as both a solvent and chiral
selector for the determination of pharmaceutical compounds.14-26
However, in spite of their potentials, to date, only a few chiral
ILs with limited structure and stereochemistry are reported.
Furthermore, their syntheses required rather expensive reagents
and elaborate synthesis schemes.
To date, most of the reported ILs are those based on chiral
cations. Only a very limited number of chiral ILs contain chiral
anions.14-26 A chiral IL having both a chiral cation and a chiral
anion has not been reported.14-26 Such a chiral IL is of extreme
importance since it will have at least four different optical
isomers. Detailed and systematic investigations of chemical and
physical properties of these chiral ILs and their isomers will
provide insight into effects of chemical structures and stereo-
chemistry of the cation and the anion on properties of ILs; e.g.,
mp’s, solubility, polarity, viscosity, and other physical and
chemical properties. Such data will also provide an invaluable
tool for the development of molecular models and calculations
to predict properties of unknown ILs and to guide the synthesis
of novel ILs. Of equal importance is the knowledge gained when
this type of chiral IL is used as solvent in asymmetric synthesis
and the chiral stationary phase in chromatographic separation.
They will provide valuable information on mechanisms of
reactions and separationssinformation which, to date, is not
possible since such a chiral solvent is not known.
Such considerations prompted us to initiate this study, which
aims (1) to develop novel and facile synthetic methods for a
series of novel and fundamentally important class of chiral
compounds, in general, and chiral ILs, in particular. These
compounds will have chiral centers not only on the cation but
also on the anion as well, (2) to use various spectroscopic
methods (NMR, CD, DSC, TGA, MS) to characterize them as
well as (3) to determine their enantiomeric recognition.
Results and Discussion
(10) Blanchard, L. A.; Brennecke, J. F. Ind. Eng. Chem. Res. 2001, 40,
287-292.
1. Synthesis, Properties, and Structure. 1.1. Synthesis.
Complete synthesis procedures for each IL are described, in
detail, in the Supporting Information. In general, as illustrated
in Scheme 1, the reaction started with 2-hydroxy-2-R1-acetic
acid (where R1 is methyl, isopropyl, isobutyl, phenyl, phenyl-
methyl, or cyclohexanyl), boric acid, and lithium carbonate in
2:1:1 molar ratio. After reacting for 1 h at about 55 °C, the
reaction mixture was cooled to room temperature. The product
of the first step reaction, lithium borate salt, was not isolated
but rather allowed to proceed to the next reaction. For example,
either BMIm+Cl- or EMIm+Br- or S-2-Me-BMIm+Br- was
added to the reaction mixture to induce metathesis reaction
between imidazolium salt and lithium borate salt. Depending
on the R1 group, the product can be either a solid which
precipitated out (when R1 is either phenyl or cyclohexanyl or
phenylmethyl group) or a liquid which is miscible with water.
Dichloromethane was used to extract the product in both cases.
(11) Quinn, B. M.; Ding, Z.; Moulton, R.; Bard, A. J. Langmuir 2002,
18, 1734-1742.
(12) Mwongela, S. M.; Numan, A.; Gill, N. L.; Agbaria, R. A.; Warner,
I. M. Anal. Chem. 2003, 75, 6089-6096.
(13) Tran, C. D.; Challa, S.; Franko, M. Anal. Chem. 2005, 77, 7442-
2447.
(14) Earle, M. J.; McCormac, P. B.; Seddon, K. R. Green Chem. 1999,
1, 23-28.
(15) Wasserscheid, P.; Bosmann, A.; Bolm, C. Chem. Commun. 2002,
200-201.
(16) Levillain, J.; Dubant, G.; Abrunhosa, I.; Gulea, M.; Gaumont, A.
C. Chem. Commun. 2003, 2914-2915.
(17) Fukumoto, K.; Yoshizawa, M.; Ohno, H. J. J. Am. Chem. Soc. 2005,
127, 2398-2399.
(18) Ding, J.; Desikan, V.; Han, X.; Xiao, T. L.; Ding, R.; Jenks, W. S.;
Armstrong, D. W. Org. Lett. 2005, 7, 335-337.
(19) Baudequin, C.; Baudoux, J.; Levillain, J.; Cahard, D.; Gaumont,
A.; Plaquevent, J. Tetrahedron: Asymmetry 2003, 14, 3081.
(20) Bao, W.; Wang, Z.; Li, Y. J. Org. Chem. 2003, 68, 591.
(21) Ishida, Y.; Miyauchi, H.; Saigo, K. Chem. Commun. 2002, 2240.
(22) Vo-Thanh, G.; Pegot, B.; Loupy, A. Eur. J. Org. Chem. 2004, 5,
1112.
(23) Pegot, B.; Vo-Thanh, G.; Gori, D.; Loupy, A. Tetrahedron Lett.
2004, 45, 6425.
(24) Howarth, J.; Hanlon, K.; Fayne, D.; McCormac, P. Tetrahedron
Lett. 1997, 38, 3097.
(25) Tran, C. D.; Oliveira, D.; Yu, S. Anal. Chem. 2006, 78, 1349-
1356.
(26) Tran, C. D.; Oliveira, D. Anal. Biochem. 2006, 356, 51-58.
(27) Tran, C. D., Yu, S. J. Phys. Chem. B 2005, 109 (25), 12627-12635.
(28) Linder, W.; Lammerhofer, M.; Maier, N. M., PCT/EP97/02888,
1997.
(29) Ngo, H. L.; LeCompte, K.; Hargens, L.; McEwen, A. B. Thermo-
chim. Acta 2000, 357-358, 97-105.
(30) Kosmulski, M.; Gustafsson, J.; Rosenholm, J. B. Thermochim. Acta
2004, 412, 47-55.
In general, chiral ionic liquids synthesized in this work can
be categorically divided into two different classes: (1) those
with an achiral cation and chiral anion and (2) those with both
a chiral cation and chiral anion. Table 1 lists three cations (or
four if both enantiomers of the chiral cation are counted) and
six anions (or twelve anions if both enantiomers for each
compound are counted) used in this work. There are a total of
48 possible chiral ILs which can be synthesized by appropriately
combining these cations and anions. However, instead of
synthesizing all possible 48 compounds, our initial synthesis
was performed for only one enantiomer for each compound.
Determination of physical properties, namely, the solid/liquid
transition temperature, of the ILs obtained enabled us to focus
our subsequent efforts only on ILs which are liquid at room
(31) Sheldrick, G. M. SHELXS-97, Program for Crystal Structure
Solution; University of Go¨ttingen: Germany, 1997.
(32) Sheldrick, G. M. SHELXS-97, Program for Crystal Structure
Refinement; University of Go¨ttingen: Germany, 1997.
J. Org. Chem, Vol. 73, No. 7, 2008 2577

Yu et al.
TABLE 1. Structure and Properties of Chiral Ionic Liquids
2578 J. Org. Chem., Vol. 73, No. 7, 2008

Chiral Ionic Liquids
FIGURE 1. Thermal gravimetric analysis scans of (L)-1 (black 9),
(R)-2 (red B), (S)-(R)-8 (green 2), (S)-(S)-8 (blue 1) (S)-(L)-9 (green
(), and (S)-(L)-10 (pink triangle pointing left).
temperature. Table 1 lists 16 ILs which are either liquid at room
temperature (first 12 ILs) or of fundamental importance.
1.2. Properties. All of the 16 ionic liquids synthesized are
soluble in polar medium as well as polar solvents including
dichloromethane, chloroform, acetone, acetonitrile, and metha-
nol. They are not soluble in nonpolar organic solvents, e.g.,
hexane and heptane. The solubility of these ionic liquids in water
decreases as the R1 group becomes more hydrophobic. When
R1 is the methyl, isopropyl, or isobutyl group, the ILs are easily
miscible with water but become barely soluble when it is the
phenyl, cyclohexanyl, or phenylmethyl group. Attempts have
been made, without much success, to prepare EMIm+BLLB-
and EMIm+BLHvB-. We found that not only the yield of the
reactions is low but also products were contaminated with the
starting material EMIm+Br-. These may be due to the fact that
solubility of these two ionic liquids in water is relatively higher
than in dichloromethane which was used as the extraction
solvent in the purification process.
Solid to liquid transformation temperatures (Tsl) of the ILs
were determined using the differential scanning calorimetry
(DSC). Results obtained are listed in Table 1. As stated in a
previous section, we concentrated our synthetic efforts on ILs
which are liquid at room temperature; only a few ILs which
are solid were listed for comparison. At least 14 ILs were found
to be liquid at room temperature with a solid/liquid transforma-
tion temperature as low as -70.4 °C (see, for example (L)-1
and (D)-1). None of the ILs with BRHMB- as the anion are
liquid at room temperature. Regarding cations, all ILs with the
chiral S-2-Me-BMIm+ as the cation are solid at room temper-
ature, except S-2-Me-BMIm+BRMB- and S-2-Me-BMIm+-
BSMB-. However, there does not seem to be a clear correlation
between the molecular structure and Tsl. For example, Tsl for
BMIm+BRMB- is -12.7 °C. Replacing the BMIm+ with
EMIm+ led to the increase in the Tsl value to -0.53 °C.
However, the reverse is true when the anion is BLBPB-;
namely, the Tsl of EMIm+BLBPB- is -7.64 °C, but the BMIm+
BLBPB- is a solid at room temperature with Tsl ) 112 °C.
Thermal stability of the ILs was investigated using thermal
gravimetric analysis (TGA). It was found that all of these ILs
are highly thermally stable. Shown in Figure 1 are TGA scans
of (L)-1, (R)-2, (S)-(R)-8, (S)-(S)-8, (S)-(L)-9, and (S)-(L)-10.
As illustrated, these chiral ionic liquids are thermally stable up
to 250 °C. Even at temperatures as high as 280 °C, they lose
only about 1% of their weights. They retain at least 90% of
their weight at an elevated temperature of 375 °C.
FIGURE 2. Structure of (L)-5 as drawn by the ORTEP program.
Mass spectra of the ILs were also taken using electrospray
ionization with the detector set for detection of either positive
or negative ions. Mass spectra obtained together with detailed
information can be found in the Supporting Information. As
described in the Supporting Information, the ILs synthesized
here exhibit similar behavior as those reported previously.33
Specifically, the MS spectra are dominated by aggregations of
the ILs. Not only do the ILs undergo extensive aggregations,
but also the aggregations were observed for cations as well as
for anions. However, in spite of extensive aggregation, each IL
can still be detected at m/z with either positive or negative ion
detection.
1.3. X-Ray Structure. (L)-5 was crystallized from its aqueous
solution by slowly evaporating water. Its crystal structure is
shown in Figure 2, and its crystallographic parameters and
selected bond lengths and angels are listed in Tables 2 and 3.
As listed in Table 2, the crystal was solved in monoclinic space
group P2(1) with Z ) 2. The central boron atom is bonded to
four oxygen atoms from two molecules of L-â-phenyllactic acid
with two kinds of average B-O distances of 1.5054 (15) Å
and 1.4394 (15) Å. These four oxygen atoms adopt a slightly
distorted tetrahedral arrangement about the boron with the angels
ranging from 105.15(9)° to 113.21(9)°. Two distinctly different
C-O bond lengths with average distances of 1.3174 (15) Å
and 1.4104 (13) Å are also shown in the anion.
Hydrogen bonding in ionic liquids, which contain an imida-
zolium ring, have been studied both theoretically and experi-
mentally.7,34-37 It has been proposed that the positive charge
on the imidazolium ring acidifies or activates the three C-H
bonds on it (C19-H19a, C20-H20a, C21-H21a) and two
C-H bonds which are connected to it (C22-H22a, C22-H22b,
C26-H26a, C26-H26b, C26-H26c). As a consequence, it is
(33) Zhao, D. Aust. J. Chem 2004, 57, 509-510.
(34) Del Popolo, M. G.; Lynden-Bell, R. M.; Kohanoff, J. J. Phys. Chem.
B 2005, 109 (12), 5895-5902.
(35) Talaty, E. R.; Raja, S.; Storhaug, V. J.; Dolle, A.; Carper, W. R. J.
Phys. Chem. B 2004, 108 (35), 13177-13184.
(36) Choudhury, A. R.; Winterton, N.; Steiner, A.; Cooper, A. I.; Johnson,
K. A. J. Am. Chem. Soc. 2005, 127 (48), 16792-16793.
(37) Chang, H.; Jiang, J.; Tsai, W.; Chen, G.; Lin, S. J. Phys. Chem. B
2006, 110 (7), 3302-3307.
J. Org. Chem, Vol. 73, No. 7, 2008 2579

Yu et al.
TABLE 2. Crystal Data and Structure Refinement for (L)-5, (S)-(L)-10, and (D)-5
(L)-5
(S)-(L)-10
(D)-5
Empirical formula
Formula weight
Temperature
C26 H31 B N2 O6
478.34
C19 H33 B N2 O6
396.28
C26 H31 B N2 O6
478.34
100(2) K
100(2) K
100(2) K
Wavelength
0.71073 Å
0.71073 Å
Orthorhombic
P 21 21 21
a ) 8.6900(10) Å
b ) 15.1044(17) Å
c ) 17.1893(19) Å
1.54178 Å
Crystal system
Space group
Unit cell dimensions
Monoclinic
Monoclinic
P 21
P 21
a ) 9.3437(8) Å
b ) 10.8094(9) Å
c ) 13.0215(11) Å
â ) 104.5640(10)°
1272.91(19) Å3
2
a ) 9.3360(7) Å
b ) 10.8109(8) Å
c ) 13.0020(9) Å
â) 104.314(3)°
1271.56(16) Å3
2
Volume
Z
2256.2(4) Å3
4
Density (calculated)
Absorption coefficient
F(000)
1.248 Mg/m3
1.167 Mg/m3
1.249 Mg/m3
0.719 mm-1
508
0.088 mm-1
0.085 mm-1
508
856
Crystal size
0.65 × 0.2 × 0.15 mm3
1.62 to 31.91°
20587
0.32 × 0.28 × 0.16 mm3
0.70 × 0.45 × 0.08 mm3
4.89 to 66.72°.
10018
θ range for data collection
Reflections collected
Independent reflections
Absorption correction
Refinement method
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I > 2σ(I)]
R indices (all data)
Absolute structure parameter
Largest diff. peak and hole
1.79 to 31.90°.
36999
8096 [R(int) ) 0.0230]
Semiempirical from equivalents
Full-matrix least-squares on F2
8096/1/316
7400 [R(int) ) 0.0324]
Semiempirical from equivalents
Full-matrix least-squares on F2
7400/5/347
3470 [R(int) ) 0.0208]
Semiempirical from equivalents
Full-matrix least-squares on F2
3470/1/440
1.067
1.027
0.973
R1 ) 0.0384, wR2 ) 0.1012
R1 ) 0.0425, wR2 ) 0.1041
-0.2(5)
R1 ) 0.0438, wR2 ) 0.1071
R1 ) 0.0559, wR2 ) 0.1138
0.5(6)
R1 ) 0.0215, wR2 ) 0.0561
R1 ) 0.0220, wR2 ) 0.0564
0.15(10)
0.457 and -0.176 e.Å-3
0.270 and -0.285 e.Å-3
0.114 and -0.134 e.Å-3
TABLE 3. Selected Bond Lengths [Å] and Angles [°] for (L)-5 and (D)-5
(L)-5
(D)-5
O(1)-C(1)
1.3204(15)
1.5049(15)
1.2087(15)
1.4147(13)
1.4368(14)
1.3143(15)
1.5058(15)
1.2117(15)
1.4060(13)
1.4420(15)
1.5252(16)
1.5270(16)
1.5226(16)
1.5419(16)
1.3298(16)
1.3784(15)
1.4758(16)
1.3283(16)
1.3778(15)
1.4647(17)
1.3548(18)
C(10)-O(4)-B(1)
C(11)-O(6)-B(1)
O(3)-B(1)-O(6)
109.78(9)
1.3229(18)
1.5082(18)
1.2148(17)
1.4179(17)
1.4328(19)
1.3166(17)
1.5118(19)
1.2137(18)
1.4089(17)
1.4423(18)
1.521(2)
1.530(2)
1.519(2)
1.542(2)
1.3317(19)
1.377(2)
C(10)-O(4)-B(1)
109.69(10)
109.63(11)
112.99(12)
105.01(11)
113.16(11)
113.23(11)
104.52(11)
108.02(12)
124.41(14)
126.14(14)
109.46(11)
104.85(11)
111.65(11)
111.66(12)
111.04(12)
124.96(13)
125.74(13)
109.28(12)
105.03(11)
111.74(11)
111.26(12)
110.66(12)
O(1)-B(1)
109.50(9)
112.59(9)
105.15(9)
113.21(9)
113.08(9)
104.68(9)
108.25(9)
124.59(11)
126.16(12)
109.25(9)
105.05(9)
111.94(9)
111.40(9)
111.03(9)
125.29(12)
125.53(12)
109.16(10)
104.95(9)
111.81(9)
110.94(9)
110.37(9)
C(11)-O(6)-B(1)
O(3)-B(1)-O(6)
O(3)-B(1)-O(1)
O(6)-B(1)-O(1)
O(3)-B(1)-O(4)
O(6)-B(1)-O(4)
O(1)-B(1)-O(4)
O(2)-C(1)-O(1)
O(2)-C(1)-C(2)
O(1)-C(1)-C(2)
O(3)-C(2)-C(1)
O(3)-C(2)-C(3)
C(1)-C(2)-C(3)
C(4)-C(3)-C(2)
O(5)-C(10)-O(4)
O(5)-C(10)-C(11)
O(4)-C(10)-C(11)
O(6)-C(11)-C(10)
O(6)-C(11)-C(12)
C(10)-C(11)-C(12)
C(13)-C(12)-C(11)
O(2)-C(1)
O(3)-C(2)
O(3)-B(1)-O(1)
O(3)-B(1)
O(6)-B(1)-O(1)
O(3)-B(1)-O(4)
O(6)-B(1)-O(4)
O(1)-B(1)-O(4)
O(2)-C(1)-O(1)
O(2)-C(1)-C(2)
O(1)-C(1)-C(2)
O(3)-C(2)-C(1)
O(3)-C(2)-C(3)
C(1)-C(2)-C(3)
C(4)-C(3)-C(2)
O(5)-C(10)-O(4)
O(5)-C(10)-C(11)
O(4)-C(10)-C(11)
O(6)-C(11)-C(10)
O(6)-C(11)-C(12)
C(10)-C(11)-C(12)
C(13)-C(12)-C(11)
O(4)-C(10)
O(4)-B(1)
O(5)-C(10)
O(6)-C(11)
O(6)-B(1)
C(1)-C(2)
C(2)-C(3)
C(10)-C(11)
C(11)-C(12)
N(1)-C(19)
N(1)-C(21)
N(1)-C(22)
N(2)-C(19)
N(2)-C(20)
N(2)-C(26)
C(20)-C(21)
C(1)-O(1)-B(1)
C(2)-O(3)-B(1)
1.4769(18)
1.333(2)
1.3769(19)
1.4659(19)
1.349(2)
109.75(9)
109.72(8)
109.60(11)
110.02(10)
TABLE 4. Bond Lengths, Angels, and C-O Distances of C-H‚‚‚O
relatively easier for this type of IL to form hydrogen bonds
with other electron donor atoms,7,34-37 e.g., oxygen atoms. To
determine C-H‚‚‚O hydrogen bonds, 2.7 Å was set up as the
cutoff limit for the distance of H‚‚‚O (dH‚‚‚O), and the angle of
C-H‚‚‚O must be bigger than 90°.38-40 Based on this assump-
tion, there are seven kinds of C-H‚‚‚O hydrogen bonds in the
crystal structure of BMIm+BLPLB- (Table 4). Six of them (No.
1-No. 6 in Table 3) exist between the aforementioned activated
C-H bonds on the BMIm+ and oxygen atoms on the anion
BLPLB-. The seventh (No. 7 in Table 3) is between aromatic
Hydrogen Bonds in the Crystal of (L)-5 and (D)-5
(L)-5
dC-O dH‚‚‚O
(Å) (Å)
(D)-5
dC-O dH‚‚‚O
(Å) (Å)
C-H‚‚‚O
(°)
C-H‚‚‚O
(°)
C-H‚‚‚O
C19-H19a‚‚‚O6 3.098 2.197 158.00 3.105 2.217 162.92
C19-H19a‚‚‚O3 3.296 2.586 131.83 3.312 2.621 132.69
C26-H26a‚‚‚O3 3.240 2.373 147.10 3.249 2.409 151.62
C20-H20a‚‚‚O5 3.065 2.208 149.39 3.082 2.255 151.59
C21-H21a‚‚‚O2 3.378 2.615 137.50 3.373 2.592 144.49
C22-H22a‚‚‚O1 3.387 2.666 129.82 3.399 2.640 132.73
C8-H8a‚‚‚O2
3.421 2.487 167.90 3.419 2.459 166.88
(38) Wang, X.; Woo, H.; Kiran, B.; Wang, L. Angew. Chem., Int. Ed.
2005, 44 (31), 4968-4972.
(39) Steiner, T.; Saenger, W. J. Am. Chem. Soc. 1992, 114 (26), 10146-
10154.
C8-H8a and O2. Even though the distance of O4-H24b is
2.682 Å, it was not considered as a hydrogen bond since C24-
H24b is not activated. They were probably brought together by
2580 J. Org. Chem., Vol. 73, No. 7, 2008

Chiral Ionic Liquids
FIGURE 4. Structure of (S)-(L)-10 drawn by the ORTEP program.
TABLE 6. Bond Lengths, Angels, and C-O Distances of C-H‚‚‚O
Hydrogen Bonds in the Crystal Structure of (S)-(L)-10
FIGURE 3. Molecular packing of (L)-5 along a and b axes.
C-H‚‚‚O
dC-O (Å)
dH‚‚‚O (Å)
C-H‚‚‚O (°)
TABLE 5. Selected Bond Lengths [Å] and Angles [°] for (S)-(L)-10
C12-H12‚‚‚O1
C14-H14b‚‚‚O1
C13-H13‚‚‚O5
C13-H13‚‚‚O4
C11-H11‚‚‚O6
C11-H11‚‚‚O3
C15-H15b‚‚‚O6
3.136
3.274
3.208
3.467
3.117
3.221
3.393
2.454
2.662
2.321
2.681
2.345
2.437
2.563
129.98
124.42
157.57
141.93
147.48
149.53
149.52
O(1)-C(1)
O(1)-B(1)
O(2)-C(1)
O(3)-C(2)
O(3)-B(1)
O(4)-C(6)
O(4)-B(1)
O(5)-C(6)
O(6)-C(7)
O(6)-B(1)
C(1)-C(2)
C(6)-C(7)
N(1)-C(11)
N(1)-C(12)
N(2)-C(11)
N(2)-C(13)
C(11)-H(11)
C(12)-C(13)
C(12)-H(12)
C(13)-H(13)
1.3204(16)
1.4963(17)
1.2119(17)
1.4186(15)
1.4436(16)
1.3237(16)
1.4953(16)
1.2038(16)
1.4087(16)
1.4425(16)
1.5167(18)
1.520(2)
1.3233(17)
1.3743(17)
1.3245(18)
1.3775(17)
0.872(18)
1.346(2)
O(3)-B(1)-O(1)
O(4)-B(1)-O(1)
C(1)-O(1)-B(1)
C(2)-O(3)-B(1)
C(6)-O(4)-B(1)
C(7)-O(6)-B(1)
O(2)-C(1)-O(1)
O(2)-C(1)-C(2)
O(1)-C(1)-C(2)
O(3)-C(2)-C(1)
O(3)-C(2)-C(3)
C(1)-C(2)-C(3)
O(5)-C(6)-C(7)
O(4)-C(6)-C(7)
O(6)-C(7)-C(6)
O(6)-C(7)-C(8)
C(6)-C(7)-C(8)
O(6)-B(1)-O(3)
O(6)-B(1)-O(4)
O(3)-B(1)-O(4)
O(6)-B(1)-O(1)
104.41(10)
108.84(10)
110.48(10)
110.71(10)
110.29(10)
111.11(10)
123.75(12)
126.58(12)
109.67(11)
104.61(10)
113.07(10)
112.65(11)
126.55(13)
109.56(11)
104.56(10)
111.63(11)
113.30(12)
113.74(11)
104.37(10)
113.16(11)
112.44(11)
0.935(18)
0.937(15)
packing of the anions. Both the cation BMIm+ and anion
BLPLB- adopt two different conformations in the crystal. One
imidazolium cation interacts with the first borate anion through
three hygrogen bonds (No. 1-No. 3) and with the second one
through one hydrogen bond which is No. 4 and with the third
one through two weak hydrogen bonds (No. 5 and No. 6) whose
H‚‚‚O distances are 2.615 and 2.666 Å. Similarly, one anion
interacts with three cations. O2 forms a weak hydrogen bond
(No.7) with H8a which is on an aromatic ring of another anion,
and the hydrogen bond results in packing of the aromatic ring
in the crystal. Packings of the molecules are shown in Figure
3.
Crystals of (S)-(L)-10 were obtained after slow evaporation
of acetronitrile. Its structure was solved in orthorhombic space
group P212121 with Z ) 4 (Table 5). Unlike (L)-5, the
2-methyl-butyl chain on the imidazolium ring is in a disorder
state. Its crystal structure unit is shown in Figure 4, and its
crystallographic parameters and selected bond lengths and angles
are listed in Tables 5 and 6. The bond lengths and angles around
FIGURE 5. Molecular packing of (L)-5 along a and b axes.
the boron atom are similar to those in (L)-5. Using the same
assumptions as those used for (L)-5, there seems to be seven
types of C-H‚‚‚O hydrogen bonds between cations and anions
in (S)-(L)-10 (Table 6). No interanionic hydrogen bond was
found. Similar to (L)-5, one cation of (S)-(L)-10 in the crystal
structure interacts with three anions around it through No. 1
and No. 2 hydrogen bonds, No. 3 and No. 4 hydrogen bonds,
and No. 5, No. 6, and No. 7 hydrogen bonds. Both the cation
-2-Me-BMIm+ and anion BLHvB- adopt four different
conformations in the crystal. Its structure and packings of the
molecules are shown in Figures 4 and 5.
Since the center atom boron of all the anions of these chiral
ionic liquids is coordinated with two identical unsymmetrical
(40) Jeffery, G. A. An Introduction to Hydrogen Bonding; New York:
Oxford University Press, 1997.
J. Org. Chem, Vol. 73, No. 7, 2008 2581

Yu et al.
2582 J. Org. Chem., Vol. 73, No. 7, 2008

Chiral Ionic Liquids
1
FIGURE 6. Expanded H NMR spectra of H6 and H6′ with splitting values labeled.
SCHEME 2. Structure of a Chiral Ionic Liquid Having a
Chiral Anion and a Racemic Cation
TABLE 7. Band Splitting Values of H6 and H6′ for Ionic Liquids
with Different Anions
in CDCl3
(50 mM)
in CDCl3
(100 mM)
in CD3CN
(50 mM)
∆δH6 ∆δH6′ ∆δH6 ∆δH6′ ∆δH6 ∆δH6′
(Hz) (Hz) (Hz) (Hz) (Hz) (Hz)
FIGURE 7. NMR spectra of (A) (S)-(S)-8 (71.44 mM) and (B) a
mixture of 35.72 mM (S)-(R)-8 and 35.72 mM (S)-(S)-8.
ionic liquid
R1 group
(R,S)-(L)-10 Isopropyl
(R,S)-(L)-9 Isobutyl
(R,S)-(S)-8 Phenyl
0
1.5
2.7
0
0
0
--
0
0
--
0
0
structure have exactly the same cell dimensions as those of (L)-5
but also the crystals are entirely in the r configuration regarding
the Spirane chirality. Additionally, its crystal structure shows
that (L)-5 and (D)-5 are enantiomers, not diastereomers. If (S-
s-S), where s represents the Spirane-like chiral entity for the
anion and S represents the chiral centers of the two ligands, is
used to characterize the chiralily of (L)-5, (D)-5 will be (R-r-
R). It is pleasing to observe that the Spirane-like chiral entity
for the anion of (S)-(L)-10 whose crystals were obtained after
slow and complete evaporation of acetonitrile is also s, which
means that it has the same descriptor (S-s-S) as that of (L)-5. It
is, therefore, evident from the results presented that each of the
ILs synthesized in this work has only one stereoisomer on the
spirane boron. Efforts have been made to try to obtain crystals
of other ILs in a capillary at low temperature,36 but with no
success.
2. Stability of ILs. It was reported that some borate-
containing compounds may undergo dissociation reaction. To
address this possibility, we have performed additional studies
which aim to investigate the stability of the chiral ILs under
different conditions. The first set of experiments was designed
to investigate the stability of the ILs, particularly (S)-2, under
different storage conditions; namely, a freshly prepared sample
of (S)-2 was divided into several baths, and each of them was
kept under different conditions: exposed to laboratory environ-
ment (35% humidity at 25 °C) for 19 days and (sample 2) for
45 days, (sample 3) stored in a glovebox for 20 days (sample
4), stored under dried air in a desicator for 20 days (sample 5),
under argon atmosphere for 20 days (sample 6), and stored under
1.5
1.2
7.8
2.1
3.6
10.5
2.1
2.4
9.6
(R,S)-(L)-11 Phenylmethyl 9.5
1.65 1.65
bidentate ligands, a new “Spirane”-like chiral entity is formed
of which the configuration can be assigned “s” and “r”
descriptors (s and r were used here to differentiate them from
those used to assign the chirality of the cation and anion of the
ILs).41,42 We have, therefore, performed systematic investiga-
tions which aim to determine enantiomers that stem from this
chirality.43 For (L)-5, it is anticipated that the Spirane-like chiral
entity for the anion is a mixture of s and r in a ratio of 1:1
since during reaction the mandelic acid would randomly
coordinate with boron. Surprisingly and interestingly, results
from X-ray diffraction studies show that this is not the case.
The crystals formed after complete evaporation of water are
uniform, and its crystal structure shows that this chiral entity is
entirely in the s configuration. No r configuration was obserVed.
It is important to add that the experiments were repeated several
times, and the same results were observed. To further verify
this observation, similar experiments were performed on the
enantiomer of (L)-5, i.e., (D)-5. As expected, the crystals of
(D)-5 are uniform. Furthermore, not only does the crystal
(41) Cahn, R. S.; Ingold, C.; Prelog, V. Angew. Chem., Int. Ed. Engl.
1966, 5 (4), 385-415.
(42) Lacour, J.; Hebbe-Viton, V. Chem. Soc. ReV. 2003, 32 (6), 373-
382.
(43) Green, S.; Nelson, A.; Warriner, S.; Whittaker, B. J. Chem. Soc.,
Perkin Trans. 1 2000, 24, 4403-4408.
J. Org. Chem, Vol. 73, No. 7, 2008 2583

Yu et al.
FIGURE 8. NMR spectra of (A) a mixture of 100 mM (R)-6 and 30 mM tBuCQN; and (B) a mixture of 100 mM (S)-6 and 30 mM of tBuCQN.
TABLE 8. 1H NMR Chemical Shifts of tBuCQN‚HCl, (R)-2/tBuCQN‚HCl, and (S)-2/tBuCQN‚HCl and Chemical Shift Changes upon Forming
Complexes with tBuCQN‚HCl
δ(tBuCQN‚HCl)
δ(R)-2/(tBuCQN‚HCl)
δ(S)-2/(tBuCQN‚HCl)
∆δ(R)-2/(tBuCQN‚HCl)
∆δ(S)-2/tBuCQN‚HCl
H2
H3
H5
H7
H12
H14
8.834
8.386
8.028
5.825
5.636
4.238
8.639
8.202
7.892
6.395
5.524
4.128
8.390
8.176
7.866
6.860
5.500
4.093
0.195
0.184
0.136
-0.570
0.112
0.444
0.210
0.162
-1.035
0.136
0.110
0.145
a flowing stream of dried O2 for 27 days (sample 7). As evident
from the 1H NMR spectra shown in the Supporting Information,
the spectrum of a freshly prepared (S)-2 sample (sample 1)
seems to be the same as those of (S)-2 samples stored under a
flow of dried air, in a glovebox, under flowing dried O2, and
under an argon atmosphere even when these samples were kept
under these conditions for many days (e.g., 20 days). Con-
versely, the spectrum of the sample stored under moist air for
an extended period of time (19 days or more) is different from
the spectrum of the freshly prepared sample (see Supporting
Information for spectra); namely, the spectrum of the former
has not only new peaks but also chemical shifts that change
with time (i.e., chemical shifts are different among three samples
(samples 1, 2, and 3). These results seem to suggest that
compound (S)-2 is stable in dried air, dried O2, and argon but
is not stable under air with high moisture. To address the
whether they can be effectively used as chiral solvents,18,23 chiral
catalysts, a chiral selector for CE, and/or chiral stationary phase
in GC.18 Experiments were designed to determine if chiral
anions of the chiral ionic liquids have any chiral recognition
ability. They were accomplished by analyzing NMR spectra of
ionic liquids composed of chiral anions and a racemic 1-methyl-
3-(2-methyl-butyl) imidazolium cation (i.e., (R,S)-2-Me-BMIm+).
These ionic liquids were prepared using a procedure similar to
those used to synthesize corresponding chiral ILs containing
both a chiral anion and a chiral cation, but in this case, the
racemic (R,S)-2-Me-BMIm+Cl- was used in the metathesis
reaction instead of the optically active S-2-Me-BMIm+Br-.
Scheme 2 shows a general structure of a chiral IL having a
chiral anion and a racemic cation whose hydrogen atoms are
labeled. Figure 6A shows three NMR spectra of (R,S)-(L)-11
in two different solvents (CD3CN and CDCl3) and three different
concentrations (50 mM in CD3CN (top), 50 mM in CDCl3
(middle), and 100 mM in CDCl3 (bottom)). As shown in the
spectra, interactions between the anion and the cation lead to
the splitting of the peaks of H6 and H6′. For clarity, splitting
values for these two protons are labeled in the figure. Interest-
ingly, it seems that the splittings are dependent not only on the
type of solvent but also on the concentration of the IL. A larger
splitting value was found in CDCl3 (9.5 and 7.8 Hz) compared
to that in CD3CN (1.65 and 1.65 Hz). Increasing the IL
concentration from 50 (in CDCl3) to 100 mM also leads to an
increase in the splitting (from 9.5 and 7.8 Hz to 10.5 and 9.6
Hz, respectively). It is important to add that these observations
are not specific to (R,S)-(L)-11 but are general for other ILs as
well. Figure 6B-D shows NMR spectra of the other three ILs,
(R,S)-(L)-9 (Figure 6B), (R,S)-(S)-8 (Figure 6C), and (R,S)-
1
stability of the chiral ILs in water, we compared H NMR
spectra of (S)-2 freshly dissolved in a mixture of 60:40 CD3-
CN:D2O solvent (sample 1) to that of the same sample but under
argon for 1 day (sample 2) and for 3 days (sample 3). Because
there is no difference among spectra of these samples (spectra
are listed in the Supporting Information), the chiral IL (S)-2
seem sto be stable in water. Taken together, the results presented
seem to indicate that the chiral ILs, particularly (S)-2, are stable
under dried air, dried O2, or argon as well as in water. They
may not be stable when stored for an extended period (many
days) under conditions where both water and air are present
(i.e., air with high humidity).
3. Intramolecular Chiral Recognition: Enantiomeric
Recognition of Chiral Anions. The enantiomeric recognition
ability of ionic liquids is an important factor to determine
2584 J. Org. Chem., Vol. 73, No. 7, 2008

Chiral Ionic Liquids
1
FIGURE 10. 1D H{15N} HSQC NMR spectra of (bottom) 40 mM
tBuCQN‚HCl (40 mM); (middle) a mixture of 40 mM (R)-6 and 40
mM tBuCQN‚HCl; and (top) a mixture of 40 mM (S)-6 and 40 mM
tBuCQN‚HCl.
(S)-12 (Figure 6D), in two different solvents (CD3CN and
CDCl3) and at two different concentrations (50 and 100 mM).
For clarity, the splitting values for all ILs are listed in Table 7.
As listed in the table, in all cases, higher splitting values were
found in solvent with relatively lower dielectric constant
(CDCl3) and at higher IL concentration. Furthermore, the same
solvent at the same concentration IL whose R1 group is more
bulkly produces larger splitting. For example, at 50 mM in
CDCl3, the splitting values in (R,S)-(L)-11 which has the
relatively largest R1 group (phenylmethyl) are 9.5 and 7.8 Hz
which are much larger than the values of 2.7 and 1.2 Hz found
for (R,S)-(S)-8 (R1 ) phenyl) and 1.5 and 1.5 Hz found
for (R,S)-(L)-9 (R1 ) isobutyl). Since CDCl3 has a relatively
lower dielectric constant (4.81) than CD3CN (37.5), the results
seem to indicate that an ion pair is formed between the anion
and the cation of the IL and that the ion pair formation is
stronger in a solvent with lower dielectric constant (CDCl3).
This, in turn, will bring the anion closer to the cation and make
their interaction stronger and, hence, produce larger splitting
values.
Interestingly, while chiral anions exhibit relatively strong
enantiomeric recognition toward the racemic cation ((R,S)-2-
Me-BMIm+), the reverse is not true; namely, the chiral cation
S-2-Me-BMIm+ does not shown any observable chiral recogni-
tion toward racemic anions. Figure 7 shows NMR spectra of
two samples: sample 1 is (S)-(S)-8 (71.44 mM) which is an
ionic liquid composed of a chiral anion and a chiral cation, and
sample 2 which is a mixture of (S)-(R)-8 (35.72 mM) and (S)-
(S)-8 (35.72 mM). This mixture sample corresponds to an ionic
liquid with a racemic anion and chiral cation at the same
concentration (71.44 mM). As shown in the spectra, they have
the same chemical shifts, and there is no splitting for any peaks
of the racemic anion.
Intermolecular Chiral Recognition: Chiral Recognition
of tBUCQN‚HCl toward (S)-6 and (R)-6. Results presented
in the previous section clearly show that the chiral anion of the
ILs can exert strong enantiomeric recognition toward the chiral
cation. Experiments were then designed to investigate if the
chiral recognition is only intramolecularly between the chiral
anion and chiral cation (of the IL) or if it can be extended
intermolecularly to other chiral molecules. O-(tert-Butylcar-
bamoyl)quinine or tBuCQN (structure below) was selected for
this study as it was demonstrated that tBuCQN exhibits relatively
strong enantiomeric recognition toward many compounds. In
fact, tBuCQN has been successfully used as a chiral selector in
FIGURE 9. NMR spectra of (top) 30 mM tBuCQN‚HCl; (middle) a
mixture of 30 mM tBuCQN‚HCl and 100 mM (R)-6, and (bottom) a
mixture of 30 mM tBuCQN‚HCl and 100 mM (S)-6 with arrows
showing shifts of chemical shifts.
J. Org. Chem, Vol. 73, No. 7, 2008 2585

Yu et al.
1
FIGURE 11. 2D H{15N} HSQC NMR spectra of (A) a mixture of 40 mM (R)-6 and 40 mM tBuCQN‚HCl; and (B) a mixture of 40 mM (S)-6
and 40 mM tBuCQN‚HCl.
various enantiomeric separation techniques, including HPLC,
CE, and capillary electrochromatography (CEC).44-49 Further-
more, its chiral recognition mechanism has been theoretically
investigated and verified experimentally.27,44-49
The initial study was aimed to determine if tBuCQN would
(44) Piette, V.; Lindner, W.; Crommen, J. J. Chromatogr. A 2000, 894,
63-71.
(45) Piette, V.; Lindner, W.; Crommen, J. J. Chromatogr. A 2002, 948,
295-302.
(46) Oberleitner, W. R.; Maier, N. M.; Lindner, J. Chromatogr. A 2002,
960, 97-108.
(47) Piette, V.; La¨mmerhofer, M.; Lindner, W.; Crommen, J. J. Chro-
matogr. A 2003, 987, 421-427.
(48) La¨mmerhofer, M.; Peters, E. C.; Yu, C.; Svec, F.; Frechet, J. M. J.;
Lindner, W. Anal. Chem. 2000, 72 (19), 4614-4622.
(49) La¨mmerhofer, M.; Svec, F.; Frechet, J. M. J.; Lindner, W. Anal.
Chem. 2000, 72 (19), 4623-4628.
2586 J. Org. Chem., Vol. 73, No. 7, 2008

Chiral Ionic Liquids
1
FIGURE 14. Expanded H NMR spectra of (S)-(R)-8 in solvents of
various dielectric constants.
FIGURE 12. Hydrogen and carbon peak splitting for (S)-2 (50 mM)
in chloroform with integration ratio labeled.
FIGURE 15. (A) 1H NMR and (B) expanded 1H NMR of (S)-2
solutions of different concentrations.
tBuCQN) and (100 mM of (S)-6 + 30 mM of tBuCQN). As
illustrated, the two spectra are identical which suggests that
under this condition tBuCQN does not exhibit any observable
chiral recognition toward the enantiomeric pair of this IL.
Subsequently, tBuCQN in the free-base form was replaced
by its protonated form, tBuCQN‚HCl, and similar experiments
were performed. Figure 9 shows NMR spectra of two mix-
tures: (100 mM of (R)-6 + 30 mM of tBuCQN‚HCl) and (100
mM of (S)-6 + 30 mM of tBuCQN‚HCl). (Bands due to
hydrogens of tBuCQN‚HCl were partially labeled.) Pronounced
FIGURE 13. Hydrogen and carbon peak splitting for (S)-(S)-8 (50
mM) in chloroform with integration ratio labeled.
have any chiral recogition toward the enantiomeric pair of
EMIm+BMB-, i.e., (S)-6 and (R)-6. Figure 8 shows NMR
spectra of two mixtures: (100 mM of (R)-6 + 30 mM of
J. Org. Chem, Vol. 73, No. 7, 2008 2587

Yu et al.
FIGURE 16. Plots of integration ratio of two peaks of H2′ versus concentration and chemical shift of hydrogens of anion vs concentration in
chloroform for (S)-2.
differences were observed between these two mixtures. For
clarity, chemical shifts and chemical shift differences between
these two mixtures are partially listed in Table 8. As illustrated,
tBuCQN‚HCl undergoes significant chemical shift changes
when mixing with (R)-6 and (S)-6. As shown in Figure 9, the
positive charge of the protonated quinuclidine moiety (of
tBuCQN‚HCl) seems to exert strong electrostatic interaction
with the anion part of the ionic liquids. This, in turn, brought
two molecules closer to produce additional interactions. This
deduction stems from careful inspection of chemical shifts and
differences. For example, upfield shifts of the aromatic protons
of tBuCQN‚HCl (H2, H3, H5, H1, and H4) after interacting with
(R)-6 and (S)-6 seem to indicate that there exists a π-π
interaction between electron-rich quinoline and the electron-
deficient imidazolium.50 Additionally, there might be hydrogen-
bond forming between the hydrogen (H7) attached to the amide
and the carbonyl groups of the anion because this hydrogen
experiences a large downfield shift. And also, there is a steric
effect between them as reflected by the fact that the chemical
(50) Jung, D.; De Ropp, J. S.; Ebeler, S. E. J. Agric. Food Chem. 2000,
48 (2), 407-412.
2588 J. Org. Chem., Vol. 73, No. 7, 2008

Chiral Ionic Liquids
shifts for hydrogens on quinuclidine and on its branch (H10,
H11, and H12) also changed.
Figure 9 shows that (R)-6/tBuCQN‚HCl and (S)-6/tBuCQN‚
HCl have different chemical shift changes based on chemical
shifts of tBuCQN‚HCl. For example, H2 shifts from 8.834 to
8.734 ppm for (R)-6/tBuCQN‚HCl and to 8.595 ppm for (S)-
6/tBuCQN‚HCl. H3 shifts from 8.386 to 8.103 ppm for (R)-6/
tBuCQN‚HCl and to 8.110 ppm for (S)-6/tBuCQN‚HCl. H5
shifts from 8.028 to 7.734 ppm for (R)-6/tBuCQN‚HCl and to
7.75 ppm for (S)-6/tBuCQN‚HCl. H7 shifts from 5.825 to 6.346
ppm for (R)-6/tBuCQN‚HCl and to 6.553 ppm for (S)-6/
tBuCQN‚HCl. These differences indicate that (R)-6/tBuCQN‚
HCl has different intermolecular interactions from (S)-6/
tBuCQN‚HCl.
Since the natural abundance of 15N is only 0.37%, the
sensitivity of 15N NMR is relatively low. However, the presence
of an amide bond in tBuCQN‚HCl makes it possible to perform
1H{15N} heteronuclear single quantum coherence (HSQC) NMR
experiments.51,52 This type of experiment makes it possible to
observe nitrogen NMR signals with a sensitivity approaching
1
that of protons.51,52 The H{15N} HSQC NMR spectra were
taken at room temperature on Varian 800 MHz using states-
TPPI quatrature detection, and the operating 1H frequency is
799.809 MHz and 15N frequency is 81.05 MHz. These
experiments were performed using the following parameters for
the 1H and 15N dimensions, respectively: sweep widths 16 000
Hz (1H) and 3000.1 Hz (15N); 4000 data points (1H) and 32
data points (15N). Because there is only one nitrogen atom
1
attached to hydrogen, it is expected that only one spot in H-
15N 2D spectra will be seen. The 1D spectra (Figure 10) show
the chemical shift of the hydrogen which is attached to the
nitrogen on the amide group. The chemical shift for this
hydrogen is 5.911 ppm for solution containng only 40 mM
tBuCQN‚HCl (bottom spectrum). It is shifted to 6.452 ppm
when (R)-6 is added to the solution, i.e., for solutions containing
40 mM (R)-6 and 40 mM tBuCQN‚HCl (middle spectrum).
Replacing (R)-6 with (S)-6 (solution containing 40 mM (S)-6
and 40 mM tBuCQN‚HCl) shifted the band to 6.700 ppm (top
spectrum). The 2D 1H{15N} HSQC spectra were shown in
Figure 11. The result clearly confirms that tBuCQN‚HCl exhibits
different interactions with (S)-6 and (R)-6; i.e., tBuCQN‚HCl
exhibits strong enantiomeric recognition toward (S)-6 and
(R)-6.
1
1
FIGURE 17. (A) H NMR and (B) expanded H NMR of (S)-(S)-8
solutions of different concentrations.
the ratio of these two sets of resonances depends not only on
the properties of the solvent but also on the concentration of
the ionic liquid. Specifically, in a solvent with low dielectric
constant, a higher splitting ratio was observed. Take (S)-(R)-8
1
for an example. Its expanded H NMR spectra in solvents of
varying dielectric constants were shown in Figure 14. Mixtues
of dichloromethane and chloroform with different volume ratios
were used to produce solvents with different dielectric constants.
As illustrated, the splitting ratio for H2′ decreases from 2.67:1
to 1.29:1 when the dielectric constant increases from 4.8 to 5.66.
The splitting ratio becomes larger when the concentration of
the ionic liquid was decreased (from 452.40 to 0.98 mM) (see,
for example, Figures 15A, 16A, 17B, and 18A). For (S)-2, the
splitting ratio of H2′ changed from a value of 5 for the 0.98
mM solution to 2.23 for the 50.00 mM solution to 1.745 for a
solution of 452.40 mM. Similarly, for (S)-(S)-8, the splitting
ratio of H2′ decreased from 5.81 (3.06 mM solution) to 2.40
(69.56 mM) to 1.70 (450.00 mM). Taken together, the results
seem to suggest that the anions may not exist entirely in
monomeric form in solution. Chemical shift versus ionic liquid
concentration and splitting ratio of H2′ versus concentration of
ionic liquid in chloroform were then plotted to gain more insight
into the nature of these forms. As illustrated in Figures 16A-F
and 18A-F, all of the plots exhibit abrupt changes at a certain
concentration range. These abrupt changes are more pronounced
in some plots such as Figures 16A, 16C, 16D, 18A, 18C, and
18D. These abrupt changes are similar to those observed for
surfactants in solutions and seem to suggest that the ionic liquids
5. Chemical States of Ionic Liquids in Solution. 1H NMR
and 13C NMR spectra of synthesized chiral ionic liquids seem
to be more complicated compared to those expected from their
1
structures. Carefully inspecting both H and 13C NMR spectra
reveals that there are, in fact, two sets of resonances for
hydrogens and carbons of the anions. The splitting ratio of
hydrogen is the same as that of carbon within experimental error
(Figures 12 and 13). For a solution of 50.0 mM (S)-2 in
chloroform, the splitting ratio for H2′ is 2.29:1, and those for
carbons are 2.25:1, 2.23:1, 2.11:1, 2.15:1, 2.34:1, and 2.35:1.
Similarly, for (S)-(S)-8 (50 mM in chloroform), the splitting
ratio for H2′ is 2.17:1, and those for carbons are 2.11:1, 2.04:1,
2.06:1, 2.16:1, 2.11:1, and 2.19:1. (It it relatively difficult to
evaluate other hydrogens because their bands are severely
overlapped among one another.) Furthermore, it was found that
(51) Pintacuda, G.; Huber, T.; Keniry, M. A.; Park, A. Y.; Dixon, N.
E.; Otting, G. Mod. Magnon. Res. 2006, 2, 1245-1251.
(52) Xia, C.; Forsterling, F. H.; Petering D. H. Biochemistry, 2003, 42,
6559-6564.
J. Org. Chem, Vol. 73, No. 7, 2008 2589

Yu et al.
FIGURE 18. Plots of integration ratio of two peaks of H2′ versus concentration and chemical shift of hydrogens of anion versus concentration in
chloroform for (S)-(S)-8.
may undergo aggregation in solution when their concentrations
reach a certain range. The concentration range was found to be
from 50 to 100 mM in chloroform for (S)-2 and from 70 to
120 mM in chloroform for (S)-(S)-8. The observation of two
different dominating species present in the solution at different
concentration ranges is, in fact, agreement with the monomeric
and aggregated forms. It is pleasing to see that splitting ratio
of H2′ versus concentration also shows the same trend as
chemical shift versus concentration (Figures 16A and 18A). And
the abrupt changes that appear at the same concentration range
solutions is not specific to only the ionic liquids synthesized in
this work. It has, in fact, been previously found that other ionic
liquids including those based on alkylmethylimidazolium and
N-alkyl-N-methylpyrrolidinium behave like surfactants in solu-
tions; namely, they undergo aggregation in solutions.7,53-55
Conclusions
In summary, a series of structurally novel chiral ionic liquids
which have either chiral cation, chiral anion, or both have been
1
(53) Tran, C. D.; Yu, S. J. Colloid Interface Sci. 2005, 283, 613-618.
(54) Dong, B.; Li, N.; Wheng, L.; Yu, L.; Inoue, T. Langmuir 2007, 23,
4178-4182.
(55) Vanyur, R.; Biczok, L.; Miskolczy, Z. Colliods Surf., A 2007, 299,
256-261.
for different plots of two sets of resonances in H NMR and
13C NMR spectra again confirm the conclusion that they are
from the monomeric and aggregated form of the ionic liquids.
It is noteworthy to add that aggregation of ionic liquids in
2590 J. Org. Chem., Vol. 73, No. 7, 2008

Chiral Ionic Liquids
Methods. O-(tert-Butylcarbamoyl) quinine (tBuCQN) was syn-
thesized using a previously reported procedure.27,28 O-(tert-
Butylcarbamoyl)quinine‚HCl or tBuCQN‚HCl was prepared from
successfully synthesized. Cations are an imidazolium group,
while anions are based on the borate ion with spiral structure
and chiral substituents. Both (or all) stereoisomeric forms of
each compound in the series can be readily synthesized in
optically pure form by a simple one-step process from com-
mercially available reagents. In addition to the ease of prepara-
tion, most of the chiral ILs in this series are liquid at room
temperature, with a solid to liquid transformation temperature
as low as -70 °C, and have relatively high thermal stability
(up to at least 300 °C). Circular dichroism and X-ray crystal-
lographic results confirm that the reaction to form the chiral
spiral borate anion is stereospecific; namely, only one of two
possible spiral stereoisomers was formed. Results of NMR
studies including 1H{15N} heteronuclear single quantum coher-
ence (HSQC) show that these chiral ILs exhibit intramolecular
as well as intermolecular enantiomeric recognition. Intramo-
lecularly, the chiral anion of an IL was found to exhibit chiral
recognition toward the cation. Specifically, for a chiral IL
composing with a chiral anion and a racemic cation, enantio-
meric recognition of the chiral anion toward both enantiomers
of the cation lead to pronounced differences in the NMR bands
of the cation enantiomers. The chiral recognition was found to
be dependent on solvent dielectric constant, concentration, and
structure of the ILs. Stronger enantiomeric recognition was
found in solvent with relatively lower dielectric constants
(CDCl3 compared to CD3CN) and at a higher concentration of
ILs. Also stronger chiral recognition was found for an anion
with a relatively larger substituent group (e.g., a chiral anion
with a phenylmethyl group exhibits stronger chiral recognition
compared to that with a phenyl group, and an anion with an
isobutyl group has the weakest chiral recognition). Chiral anions
were also found to exhibit intermolecular chiral recognition.
Enantiomeric discrimination was found for a chiral IL composed
of a chiral anion and achiral cation toward another chiral
molecule such as a quinine derivative. Structurally novel and
strong intra- and intermolecular chiral recognition ability of these
chiral ILs indicate that they can be used in a variety of
applications including as chiral solvent for asymmetric synthesis
and as chiral stationary phase for chromatographic separations.
These possibilities are the subject of our current intense
investigation.
1
tBuCQN. They were characterized using H and 13C NMR. The
complete synthesis procedure and NMR spectra of these compounds
are included in the Supporting Information.
All of the ILs synthesized were characterized using 1H, 13C, and
11B NMR (taken at room temperature on a 300 MHz spectrometer
at 300, 75, and 96 MHz (with BF3‚Et2O in CDCl3 as external
reference), respectively), thermal gravimetric analysis (TGA), and
electrospray ionization (ESI) mass spectrometry, differential scan-
ning calorimetry (DSC), and circular dichroism spectropolarimeter.
The spectra are included in the Supporting Information.
In the thermal gravimetric analysis (TGA), to avoid any possible
reaction between ionic liquids and the sample crucible made from
quartz or aluminum at elevated temperature,29,30 we lined the quartz
crucibles with silver foil before placing the sample into it. The
sample size was in the (∼40 to 60) mg range. Measurements were
performed under a flowing nitrogen atmosphere (at a flow rate of
80 mL/min) at a scan rate of 20 °C/min from 20 to 700 °C. All
TGA results are the average of at least three measurements. The
temperature reproducibility of the TGA is ( 3 °C, and the error
range of the nonvolatile fraction at 700 °C is ( 3 °C.
Differential scanning calorimetric (DSC) measurements were
performed using a differential scanning calorimeter. Optical rotation
was determined on a polarimeter at 589 nm at room temperature.
A spectropolarimeter was used to record CD spectra. Electrospray
mass spectra were taken on an ESI-MS instrument.
Crystal structures were determined by single-crystal X-ray
diffraction using a diffractometer equipped with an APEX CCD
detector with graphite-monochromated Mo-KR radiation (λ )
0.71073 Å) at a temperature of 100 ( 2 °K (except in the case of
D-5 where Cu-KR radiation (λ ) 1.54178 Å) was used to
determine its absolute configuration). The structures were solved
by direct methods using the available program31 and were refined
with full-matrix least-squares on F2 techniques.32 Non-hydrogen
atoms were refined freely with anisotropic displacement parameters,
and hydrogen atoms were refined as rigid groups. For S-2-Me-
BMIm+BLHvB-, the (S)-2-methylbutyl group was refined with a
disorder model. Detailed information on the crystal structure
determinations is provided in the Supporting Information.
Acknowledgment. The authors would like to acknowledge
Dr. Patrick Ting of the Miller Brewing Company for his help
and for the use of circular dichroism and the mass spectrometer
and Prof. Daniel Sem for his competent assistance with NMR
measurements. Acknowledgment is also made to Prof. Andrea
Mele of Politecnico di Milano, Italy for his help and stimulated
discussion.
Experimental Section
Chemicals. Methylimidazole, 1-chlorobutane, bromoethane, (S)-
(+)-1-bromo-2-methylbutane, 1-chloro-2-methylbutane, lithium
carbonate, boric acid, L-(+)-lactic acid solution (85%+), R-
mandelic acid, S-mandelic acid, (R)-(-)-hexahydromandelic acid,
(S)-(+)-hexahydromandelic acid, and quinine were used as obtained
from the manufacturer. D-(-)-Lactic acid, L-R-hydroxyisocaproic
acid, D-R-hydroxyisocaproic acid, L-R-hydroxyisovaleric acid, D-R-
hydroxyisovaleric acid, L-â-phenyllactic acid, and D-â-phenyllactic
acid were purchased from various manufacturers.
Supporting Information Available: Experimental procedures,
properties, spectroscopic data, and X-ray structure of compounds
reported in this work. This material is available free of charge via
the Internet at http://pubs.acs.org.
JO702368T
J. Org. Chem, Vol. 73, No. 7, 2008 2591