Cyclodextrin-based ionic liquids as enantioselective stationary phases in gas chromatography

Article abstract of DOI:10.1002/cplu.201300229

New permethylated mono-6-deoxy-6-pyridin-1-ium and mono-6-deoxy-6-(1-vinyl- 1H-imidazol-3-ium)-α- and -β-cyclodextrin trifluoromethanesulfonate ionic liquids were synthesized from the corresponding permethylated mono-6-hydroxycyclodextrins in a one-pot reaction and solvent-free procedure. Regioselective transformation of native α- and β-cyclodextrins with the use of a bulky tert-butyldiphenylsilyl protecting group afforded the desired 6-monosubstituted permethylated cyclodextrin derivatives in moderate yields. The new ionic liquids were tested as stationary phases in capillary GC columns towards chiral discrimination in enantio-GC analysis of racemic mixtures. The permethylated 6-deoxy-6-pyridin-1-ium-α-cyclodextrin trifluoromethanesulfonate displayed good enantiomeric separations for some racemic esters and lactones, as well as epoxides. In particular, for both the racemic whiskey lactone and the high boiling point menthyl laurate, not successfully separated in a commercial cyclodextrin phase, the enantiomeric separations were achieved isothermally at 140 °C. In phase: Permethylated mono-6-hydroxy-α- and -β-cyclodextrins react with pyridine or 1-vinylimidazole in the presence of triflic anhydride in a solvent-free procedure to yield new roomerature ionic liquids (ILs). These ILs have been used as stationary phases in gas chromatography; enantiomeric separations are achieved (see figure for whiskey lactone) with permethylated mono-6-deoxy-6-(pyridin-1-ium)-α-cyclodextrin trifluoromethanesulfonate. Copyright

Full text of DOI:10.1002/cplu.201300229

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DOI: 10.1002/cplu.201300229
Cyclodextrin-Based Ionic Liquids as Enantioselective
Stationary Phases in Gas Chromatography
Nuno Costa, Sara Matos, Marco D. R. Gomes da Silva, and M. Manuela A. Pereira*[a]
New permethylated mono-6-deoxy-6-pyridin-1-ium and mono-
6-deoxy-6-(1-vinyl-1H-imidazol-3-ium)-a- and -b-cyclodextrin
trifluoromethanesulfonate ionic liquids were synthesized from
the corresponding permethylated mono-6-hydroxycyclodex-
trins in a one-pot reaction and solvent-free procedure. Regio-
selective transformation of native a- and b-cyclodextrins with
the use of a bulky tert-butyldiphenylsilyl protecting group af-
forded the desired 6-monosubstituted permethylated cyclo-
dextrin derivatives in moderate yields. The new ionic liquids
were tested as stationary phases in capillary GC columns to-
wards chiral discrimination in enantio-GC analysis of racemic
mixtures. The permethylated 6-deoxy-6-pyridin-1-ium-a-cyclo-
dextrin trifluoromethanesulfonate displayed good enantiomer-
ic separations for some racemic esters and lactones, as well as
epoxides. In particular, for both the racemic whiskey lactone
and the high boiling point menthyl laurate, not successfully
separated in a commercial cyclodextrin phase, the enantiomer-
ic separations were achieved isothermally at 1408C.
Introduction
Cyclodextrins (CDs) are very popular cyclic oligosaccharides
that are used widely in organic syntheses. CDs can bind sub-
strates and catalyze chemical reactions with high selectivity[1]
as well as transfer hydrophobic molecules into environmentally
friendly medium by supramolecular interaction through rever-
sible formation of host–guest complexes,[2] and have been
used as nanoreactors in various organic reactions representing
a significant moiety of artificial enzymes.[3]
CDs are naturally occurring water-soluble concave molecules
possessing hydrophobic cavities. They are made up of six,
seven, or eight glucopyranosidic units linked in an a-1,4 fash-
ion to form a- (1a), b- (1b), or g-CDs (1c), respectively
(Scheme 1). All three common CDs have a similar truncated
cone shape,[4] and such a geometry arranges all primary hy-
droxyl groups (6-OH groups) of the glucopyranosyl units to
the narrower end (primary rim) of the cone;[5] consequently,
between 6-OH groups of the adjacent pyranose units, there is
only a limited amount of space available. Chemical modifica-
tion of CDs with various functional groups has been investigat-
ed extensively.[6] Selective modifications of the CDs are difficult
to control because of problems arising from steric and statisti-
cal factors imposed by the torus structure and the large
number of hydroxyl groups. Usually, if a monofunctionalized
Scheme 1. a-, b-, and g-cyclodextrins 1a, 1b, and 1c, respectively.
CD is synthesized, positional isomers and homologous deriva-
tives with a higher degree of substitution are formed.[7]
CDs have the ability to form inclusion complexes with a vari-
ety of chiral compounds and are heavily exploited in chiral rec-
ognition and/or resolution of racemic compounds in natural
products[8] and the pharmaceutical,[9] agrochemical, and food
industries, in which they are employed either as mobile phase
additives or chiral stationary phases in high-performance liquid
chromatography (HPLC)[10] and gas chromatography (GC).[11]
Also, ionic liquids (ILs) have found many applications in a va-
riety of research areas. Emerging as possible substitutes for
volatile organic solvents, ILs have become important as a new
reaction medium for chemical and biochemical transforma-
tions[12] and also in analytical[11g,13] and separation techniques
applications.[14] Their unique properties and chemical stabili-
ty[15] make ILs intrinsically excellent candidates for industrial
solvent applications in contrast to conventional ones and offer
great potential to develop clean catalytic technologies. Com-
pared with traditional production methods, the new technolo-
gies integrated with ILs ensure many advantages, including
short reaction times, mild reaction conditions, simplified opera-
[a] Dr. N. Costa, Dr. S. Matos, Prof. M. D. R. Gomes da Silva,
Prof. M. M. A. Pereira
REQUIMTE, Chemistry Department
Faculdade de CiÞncias e Tecnologia
Universidade Nova de Lisboa
2827-516 Caparica (Portugal)
Fax: (+351)212958300
E-mail: manuela.pereira@fct.unl.pt
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/cplu.201300229.
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tion procedures, high yields and selectivity, ease of product
separation, and recyclability of catalysts and ILs.[16]
cation or the anion or even both can be responsible for the
chiral characteristic of the molecule. Recently, Armstrong and
co-workers[29] used charged CDs as a GC chiral selector. Perme-
thylated mono-6-deoxy-6-(1-butyl-1H-imidazol-3-ium)-b-cyclo-
dextrin (2b) and permethylated mono-6-deoxy-6-(tripropyl-
phosphonium)-b-cyclodextrin (3) paired with iodide, NTf2, and
trifluoromethanesulfonate anions were synthesized and evalu-
ated for optimization of the chiral stationary phase composi-
tion. High melting points of the CD salt derivatives prevent the
use of these derivatives in the pure form as stationary phases.
Application of monosubstituted positively charged CDs as
chiral stationary phases in the separation of enantiopure
amino acids and anionic analytes demonstrated their potential
as chiral selectors in HPLC and SFC.[26b,27]
As a result of their dual behavior, ILs are receiving increased
interest from the chromatography community for multiple
tasks. They can separate nonpolar and polar compounds de-
pending on whether they are used to produce apolar or polar
phases, respectively.[14b,17] Their unique properties, such as high
thermal stability and efficiency on the column, are used to im-
prove gas and liquid chromatographic techniques.[18] The diver-
sity of potential candidates is very wide, because their compo-
sition, and consequently the properties displayed, depends ex-
clusively on the cation and anion combinations. These are vir-
tually unlimited. Recently, a comprehensive review was pub-
lished containing structures and physical properties of
a diversity of chiral ILs that have been synthesized during the
last six years.[19] Applications in the fields of asymmetric organ-
ic synthesis, spectroscopy, and chromatography are also re-
ported.
Results and Discussion
Herein, we are interested in preparing stable room-tempera-
ture ILs derived from CDs with different cavity sizes able to be
used as chiral selectors in GC. The a- (1a) and b-CDs (1b) are
known as good chiral selectors and the opportunity to intro-
duce an ionic moiety at one C-6 center affording new thermal-
ly stable ionic salts of CD derivatives was considered. CD salts
melting around 1008C or below, which behave like room-tem-
perature ILs, could be used as chiral stationary phases in GC.
Ammonium, pyridinium, and imidazolium ILs are the most
popular because of their low vapor pressures and low melting
points. Herein, new trifluoromethanesulfonic salts of permethy-
ILs with trifluoromethanesulfonate anions are of interest for
practical applications in various fields. In general, trifluorome-
thanesulfonate ILs are hydrolytically stable and have fairly low
viscosity, and are typically prepared by means of the metathe-
sis reaction of the corresponding chlorides, bromides, or
methyl sulfates with metal trifluoromethanesulfonates.[20]
In the last decade, chiral ILs synthesized from carbohydrates
have found synthetic and analytical applications.[21] ILs derived
from isomannide and isosorbide were used as chiral catalysts
in phase-transfer reactions,[22] and a 6-deoxy-6-imidazolium salt
derivative from b-CD was used in the asymmetric reduction of
acetophenones providing alcohols in high enantioselectivity.[23]
A broad range of fundamental free-radical reactions employing
the b-CD IL mono-6-deoxy-6-(1-methyl-1H-imidazol-3-ium)-b-
cyclodextrin tosylate (2a) was investigated (Scheme 2).[24] The
low solubility of carbohydrate ILs in organic solvents was ex-
plored in the IL-supported synthesis of oligosaccharides as an
alternative process to the classical solid-phase synthesis.[25]
Cationic CDs containing imidazolium-, pyridinium-, or am-
monium-substituted b-CD derivatives were used as chiral selec-
tors or chiral additives for capillary electrophoresis and have
demonstrated efficient enantioseparations for some aromatic
carboxylic acids.[26] Applications in chiral stationary phases for
HPLC and supercritical fluid chromatography (SFC) of different
derivatives of cationic CDs were reported.[27] There are not
many cases described so far in which chiral ILs are synthesized
and used for chromatographic purposes.[28] Here again, the
lated
mono-6-deoxy-6-(pyridin-1-ium)-a-cyclodextrin (4a),
mono-6-deoxy-6-(pyridin-1-ium)-b-cyclodextrin (4b), mono-6-
deoxy-6-(1-vinyl-1H-imidazol-3-ium)-a-cyclodextrin (5a), and
mono-6-deoxy-6-(1-vinyl-1H-imidazol-3-ium)-b-cyclodextrin
(5b; Scheme 3) were synthesized by a protection/deprotection
strategy.[7,11j,30] This strategy deals with the use of chemo- and/
or regioselective reactions from native CDs including four main
steps: selective protection of one C-6 hydroxyl group, transfor-
mation of the remaining ones, deprotection, and finally, suita-
ble functionalization afforded by nucleophilic displacement.
As concerns the permethylated mono-6-O-modified CDs, the
tosyl group is the most popular protecting group of 6-OH.[3a,31]
Scheme 2. ILs derived from b-CD. Ts=toluenesulfonyl, Tf=trifluoromethane-
sulfonyl.
Scheme 3. New a- (4a, 5a) and b-CD (4b, 5b) ILs.
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Tosylate groups located on the C-6 position in mono-6-O-tosyl
CD derivatives have been used repeatedly as leaving groups
for nucleophilic substitutions, but displacement of the tosylate
group requires good nucleophiles, high temperatures, and
long reaction times, which yield several byproducts and rela-
tively low yields of the desired monosubstituted com-
pounds.[31b,32] However, the trifluoromethanesulfonate group
has been demonstrated to be a better leaving group than to-
sylate, and nucleophilic substitutions are accomplished at
room temperature in shorter reaction times and with better
yields.
chloride in DMF and in the presence of imidazole for 1 hour at
608C. Although some unreacted a-CD (1a) was still present in
the reaction mixture, longer reaction times or higher tempera-
tures resulted in the formation of several permethylated polysi-
lylated CD derivatives in complex mixtures. Further, methyla-
tion in situ with methyl iodide, after treatment with sodium hy-
dride, yielded the corresponding permethylated mono-6-O-
tert-butyldiphenylsilyl-a-cyclodextrin (6a) in 34.4% overall
yield, from a-CD. The same procedure was used to obtain the
permethylated mono-6-O-tert-butyldiphenylsilyl-b-cyclodextrin
(6b). In both transformations some permethylated a- and b-
CDs, 7a and 7b, respectively, were isolated.
Treatment of 6 with N-tetrabutylammonium fluoride in THF
at reflux afforded the corresponding permethylated mono-6-
hydroxy-CDs 8 after chromatographic purification. To over-
come the difficulties of a purification step owing to the pres-
ence of tetrabutylammonium salt, the use of NH4F as fluoride
ion source[30] was tested. A longer reaction time and uncom-
pleted transformation were observed if a solution of permethy-
lated mono-6-O-tert-butyldiphenylsilyl-a-cyclodextrin 6a in dry
methanol was heated at reflux in the presence of an excess of
ammonium fluoride for 9 days to yield 67% of the correspond-
ing deprotected a-CD (8a).
Regioselective introduction of a trifluoromethanesulfonate
group in the primary C-6-OH exclusively in one CD glucopyra-
noside unit was accomplished by reaction of one primary OH
group of native CD with a bulky silyl chloride derivative in the
presence of a base, followed by permethylation of the remain-
ing free hydroxyl groups. Further, the permethylated mono-6-
O-modified CDs required the selective removal of the silyl sub-
stituent by reaction with fluoride ion and subsequent introduc-
tion of a new leaving group susceptible to displacement by
a nucleophile (Scheme 4). Permethylated mono-6-O-tert-butyl-
To accomplish nucleophilic substitution at the C-6 center,
the 6-OH group of 8 should be replaced by a good leaving
group. Our attention was focused on the trifluoromethanesul-
fonic ester 9 (Scheme 5) because of its behavior as a good
Scheme 5. Trifluoromethanesulfonic esters 9a and 9b.
leaving group in nucleophilic displacement at room tempera-
ture, and also the possibility of synthesizing it under moderate
conditions. The use of trifluoromethanesulfonic esters was sup-
ported by their success as an excellent leaving group in nucle-
ophilic substitutions at room temperature.[20] High tempera-
tures should be avoided owing to the thermal lability of CD
derivatives.
Scheme 4. Synthesis of new ILs 4a,b and 5a,b.
dimethylsilyl CDs (6c, 6d) are the most popular mono-6-O-
modified CD derivatives.[7,33] Even using this bulky tert-butyldi-
methylsilyl substituent, the reactivity of one 6-OH primary
group was not selective and the presence of polysubstituted
silylated compounds resulted in low yields and tedious purifi-
cation steps of the desired mono-6-O-tert-butyldimethylsilyl CD
derivatives. Best results were found with the synthesis of tert-
butyldiphenylsilyl ether, and tert-butyldiphenylsilyl chloride
was a superior silylating reagent yielding the mono-6-O-tert-
butyldiphenylsilyl derivative of b-CD with reasonable regiospe-
cificity in the one-pot synthesis of permethylated mono-6-hy-
droxy-b-cyclodextrin (8b) as described by Lupescu et al.[30]
Herein, a modified previous procedure was followed to yield
permethylated mono-6-O-tert-butyldiphenylsilyl-a-cyclodextrin
(6a). Regioselectivity of primary OH monosilylation is very sen-
sitive to the reaction conditions and the best yield of 6a was
obtained if the CD was reacted with tert-butyldiphenylsilyl
To obtain the corresponding mono-C-6 trifluoromethanesul-
fonate derivative 9a, compound 8a was reacted with trifluoro-
methanesulfonic anhydride in dry dichloromethane and in the
presence of pyridine at room temperature, as described by Lu-
pescu et al.[30] for the b-CD derivative 8b. Surprisingly, a very
polar compound was formed. After workup and chromato-
graphic purification, the product 4a (34%) was characterized
(Table 1).
1
One of the most characteristic features of the H NMR spec-
trum of 4a demonstrated the presence of the positive aromat-
ic pyridinium ring with the nitrogen atom bonded to the C-6
of one glucopyranose unit of the permethylated mono-6-
deoxy-substituted CD (4a), in which aromatic protons shifted
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fonic anhydride in the presence of pyridine and other nucleo-
philes, such as 1-vinylimidazole, in solvent-free procedures.
Typically, trifluoromethanesulfonic ILs are prepared by
means of the metathesis reaction of the corresponding chlor-
ides or bromides with metal trifluoromethanesulfonates. Direct
alkylation of substituted pyridines with methyl trifluorometha-
nesulfonate was recently used to prepare halogen-free trifluor-
omethanosulfonate ILs.[20]
Table 1. Physical data of CD ILs 4 and 5 and compound 8a.
21
Compound
Yield [%]
M.p. [8C]
½aꢁD in CHCl3
4a
4b
5a
5b
34[a], 71[b]
38[b]
41.5[b]
29.5[b]
84–85
110–115
90–95
95–99
+126.8 (c=3.0)[c]
+91.6 (c=1.4)[c]
+101.9 (c=3.0)[c]
+117.1 (c=0.9)[c]
[a] In dichloromethane. [b] Solvent-free procedure. [c] c is concentration
in grams per 100 mL.
Herein, synthesis of permethylated mono-6-deoxy-6-pyridin-
1-ium-a-cyclodextrin trifluoromethanesulfonate (4a) was ac-
complished by the solvent-free reaction of compound 8a with
trifluoromethanesulfonic anhydride in pyridine at room tem-
perature for 2 days to yield 71% of the desired CD IL obtained
after chromatographic purification. Following the same proce-
dure the permethylated mono-6-deoxy-6-(pyridin-1-ium)-b-cy-
clodextrin trifluoromethanesulfonate (4b) was obtained from
8b in 41.5% yield.
downfield and resonated at 9.05 (H-2’’), 8.05 (H-3’’ and H-5’’),
and 8.54 (H-4’’) (Table 2). The resonance signals of the corre-
sponding two H-6 atoms bonded to the prochiral C-6 atom,
5.30 and 5.19 ppm, of the same glucopyranose unit shifted
downfield compared with the precursor compound 8a, for
The formation of 4 and 5 from 8 can be explained by reac-
tion of 8 with trifluoromethanesulfonic anhydride in the pres-
ence of pyridine to form the trifluoromethanesulfonic ester 9,
followed by nucleophilic attack of the pyridine nitrogen at C-6
bonded to the trifluoromethanesulfonate group with conse-
quent displacement of the trifluoromethanesulfonate anion
and formation of the corresponding compounds, 4 or 5, in
a one-pot reaction. During the transformation, pyridine or 1-vi-
nylimidazole acted as solvent, base, and nucleophile. This pro-
posal is supported by the presence of trace amounts of the
less polar compound 9a, detected by thin-layer chromatogra-
phy during the formation of 4a from 8a and of compound 9b,
isolated in 38% yield, during the formation of 5b from 8b for
38 hours at room temperature. After 3 days at room tempera-
ture, and under the same conditions, the yield of 9b decreased
to 18%.
Table 2. Typical proton and carbon NMR chemical shifts of CD ILs (4a,b
and 5a,b) and 8a,b. All chemical shift values are given in ppm.
4a
5.30
4b
5.35
5a
4.87
4.67
9.27
–
7.57
7.74
7.34
5.77
5.46
50.51
5b
8a
8b
H-6a
H-6b
H-2’’
H-3’’
H-4’’
H-5’’
H-6’’
H-7’’(trans)
H-7’’(cis)
C-6
4.84 3.98–3.32 3.92–3.72
4.61 3.98–3.32 3.92–3.72
9.44
–
7.55
7.80
7.34
5.76
5.45
5.19
9.05
8.05
8.54
8.05
9.05
–
5.12
9.11
8.06
8.54
8.06
9.11
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
Generally, permethylated mono-6-deoxy-6-(alkyl-1H-imidazol-
3-ium) salts of CDs were prepared from mono-6-O-tosylate CD
displacement by the corresponding imidazole nucleophile. Fur-
ther metathesis of the anion generated the corresponding de-
sired salts. Exploring the basicity and nucleophilic features of
1-vinylimidazole, compounds 8a and 8b were treated with tri-
fluoromethanesulfonic anhydride in dry 1-vinylimidazole for
2 days at room temperature to yield the corresponding ILs, the
permethylated mono-6-deoxy-6-(1-vinyl-1H-imidazol-3-ium)-a-
cyclodextrin trifluoromethanesulfonate (5a; 41%) and the per-
methylated mono-6-deoxy-6-(1-vinyl-1H-imidazol-3-ium)-b-cy-
clodextrin trifluoromethanesulfonate (5b; 29.5%), respectively.
As anticipated the 6-deoxy-6-(1-vinyl-1H-imidazol-3-ium) CD
trifluoromethanesulfonate salts (5a and 5b) displayed the
–
–
61.09
61.19
50.35 62.51
61.82
C-2’’
C-3’’
C-4’’
C-5’’
C-6’’
C-7’’
146.72 146.84 137.19 137.53
8.05 8.06
145.77 145.75 118.18 118.18
127.95 127.71 124.76 124.86
146.72 146.84 128.82 128.86
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
110.36 110.13
which the corresponding protons resonated between 3.98 and
3.32 ppm. Owing to the inductive effect along the sigma bond,
the resonance of C-6 was also affected by the positively
charged pyridinium ring and its signal shifted upfield by
1.42 ppm. The 19F NMR spectrum confirmed the presence of
the trifluoromethanesulfonate anion exhibiting a singlet at
ꢀ78.3 ppm. To our knowledge, compound 4a is the first pyridi-
nium room-temperature IL derivative from a-CD, melting at
84–858C.
1
same H and 13C NMR features as the pyridinium derivatives,
4a and 4b, respectively. The protons of the positive imidazoli-
um ring shifted downfield. The more acidic H-2’’ resonated at
9.27 and 9.44 ppm. Moreover, vinylic protons resonated at 7.34
(H-6’’), 5.77 (H-7’’trans), and 5.46 ppm (H-7’’cis) with Jtrans =15.5
and Jcis =8.6 Hz and J=2.9 Hz for the geminal coupling con-
stant in compound 5a, which demonstrated the presence of
the vinyl carbon double bound. Moreover, the two protons
bonded to prochiral C-6 shifted downfield by 1 ppm, less than
in the pyridinium derivative, and the C-6 signal shifted from
These findings encouraged us to investigate the transforma-
tion of permethylated mono-6-hydroxy-a-cyclodextrin (8a) and
mono-6-hydroxy-b-cyclodextrin (8b) with trifluoromethanesul-
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62.51 and 61.82 ppm in permethylated 6-mono-hydroxyl a-
(8a) and b-CDs (8b) to 50.51 and 50.35 ppm in 6-deoxy-6-(1-
vinyl-1H-imidazol-3-ium) CD trifluoromethanesulfonate salts 5a
and 5b, respectively.
rimetry (DSC) analyses. Figure 1 depicts the TG curve (trace a)
and DSC profile (trace b) of permethylated mono-6-deoxy-6-
(pyridin-1-ium)-a-cyclodextrin trifluoromethanesulfonate (4a)
on heating to 4108C under nitrogen (78Cminꢀ1). The onset of
the endothermic event appearing at 274.98C (peaking at
278.28C) corresponds to the decomposition of the compound
and is accompanied by about 46.5% weight losses by the end
of transition. The residual mass at 4108C is around 50%. The
thermal behavior of CD ILs 4b and 5a were very similar, with
the corresponding endothermic events at 270.88C (onset
267.78C) and 289.08C (onset 277.68C), respectively, whereas
for 5b a significantly lower decomposition temperature was
registered (peak at 244.18C, onset at 2158C). These events
were accompanied by approximately 64.0, 61.9, and 34.0%
weight loss by the end of the transitions, respectively. In gen-
eral, CD ILs (4a, 4b, 5a) were found to be stable up to 2508C,
as indicated by the TG analysis measurements.
As we expected, all CD salt derivatives prepared melted
below 1008C except the b-CD pyridinium trifluoromethanesul-
fonate 4b (m.p. 110–1158C; Table 2). The optical activities of all
the new CD derivatives were measured in chloroform solution
(Table 1). The cation and the anion in all CD ILs were identified
by electrospray ionization (ESI) high-resolution mass spectrom-
etry (Table 3). The CD-pyridinium cation 4a and 4b, and the
CD-imidazolium cation 5a and 5b were recorded in the posi-
tive mode, and the negative ionization mode was used to
record the mass spectra of anionic moieties of CD ILs, the
singly charged anion [CF3SO3ꢀ].
Table 3. High-resolution mass spectrometry data of CD ILs 4a,b and
5a,b.
To explore the properties of chiral selectivity and thermal
stability of the new chiral ILs (4 and 5) derived from a- (4a
and 5a) and b-CDs (4b and 5b), mono-6-deoxy-6-pyridin-1-
ium-a-cyclodextrin trifluoromethanesulfonate (4a) was used as
stationary phase in enantio-GC. The salt of a-CD 4a is a viscous
room-temperature IL, so it could be used in its neat form as
stationary phase to coat directly the silica tubing. A solution of
4a in dichloromethane (0.18% w/v) was used to fill 13 meters
of fused-silica capillary tubing and to obtain a stationary phase
film thickness of 0.11 mm.[34]
Compound MS positive analysis found/ MS negative analysis found/
ꢀ
calcd for [cation]
calcd for [CF3SO3
]
4a
4b
5a
5b
1272.6186/1272.6219
1476.7219/1476.7217
1287.6322/1287.6328
1491.7256/1491.7326
148.9523/148.9526
148.9530/148.9526
148.9526/148.9526
148.9529/148.9526
The MALDI-TOF spectrum of 4a, acquired from m/z=500–
2000 Da, displays the cluster m/z=1272.5670–1276.5570 Da,
which corresponds to the molecular cation, in a purity of
92.6% (calculated from the areas of the mass peaks, see the
Supporting Information). Considering that the matrix effect,
cluster m/z=1424.5673–1426.5763 Da, resulting from the in-
clusion of 2,5-dihydroxybenzoic acid (DHB, molar mass=
154.0266 Da) in the CD-based IL 4a, is responsible for 3.1% of
the peak area, the overall purity of 4a used to coat the
column was 95.7%. This achieved purity was considered
enough to claim that the column was coated with a high-
purity compound.
Supercooling, or glass formation, is a common characteristic
associated with many ILs.[35] Usually, imidazolium ILs exhibit
glass transition temperatures below the melting point temper-
ature. As reported,[36] the glass transition temperatures of some
imidazolium ILs are between ꢀ104 and ꢀ758C, depending on
the alkyl substituents in the imidazolium ring and on the
nature of the anion, whereas the corresponding melting points
are from ꢀ81 to 608C. Herein, a volatile solvent, dichlorome-
thane, was used to dissolve the stationary phase 4a during the
column coating procedure and was evaporated at 408C and
reduced pressure. Although this temperature is below the
melting point of 4a, it will be probably above its glass transi-
tion temperature, thus favoring an almost homogeneous dep-
osition of the stationary phase during solvent evaporation.
However, a higher evaporation
The thermal properties of the CD ILs 4 and 5 were evaluated
through thermogravimetric (TG) and differential scanning calo-
temperature, superior to the 4a
melting point (>858C), should
favor the homogeneity of depo-
sition and thus provide better
column efficiencies and separa-
tions.
The calculated efficiency at
1208C for tetradecane was
330 theoretical plates per meter
(k=6.6, with k the retention
factor (trꢀt0)/t0). The column ef-
ficiency is low, but nevertheless
some interesting enantiosepara-
tions were achieved. Some
Figure 1. TG (a) and DSC (b) thermograms of CD-based IL 4a measured in N2 (heating rate 78Cminꢀ1).
compound chemical families
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were separated successfully if enantiomeric mixtures were ana-
lyzed (Scheme 6). This problem is not new and has already
been reported by Huang et al.[29] In fact, probably the smaller
anion occupies the CD cavity, thereby reducing the inclusion
Figure 2. Separation of the four enantiomers of whiskey lactone (16) in
a sample solution. The GC instrument was operated using a split/splitless in-
jector set at 100 mLminꢀ1. The injector and FID were set at 2508C. The carri-
er gas was hydrogen adjusted to give a solvent peak after around 0.50 min.
A 1 mL portion of 150 ppm sample solution in hexane was injected. The GC
oven was operated exothermically at 1208C.
Scheme 6. Chiral compounds 10–17.
complexation interaction between the chiral phase and the
target analyte. On the other hand, the chiral selector 4a dis-
plays good enantiomeric separation for some esters and lac-
tones, as well as epoxides (Table 4). In the particular case of
constant at 1208C after submitting the column to 1608C over-
night, 16 h (Figure 2).
The column phase showed selectivity for some organic com-
pound families, such as epoxides 10 (ethers) and hydroxy
esters 11 and 12, lactones 13–16, and in particular a heavy
ester 17. Other compound families, such as hydrocarbons, ke-
tones, carboxylic acids, amines, and amides, were also assayed,
but no enantioselectivity was observed. Menthyl laurate (17)
racemic mixture was separated successfully at 1408C in this
stationary phase, which was not achieved if a commercial CD
column (CyclodexB, J&W, 30 mꢁ0.25 mm, 0.25 mm) was used.
In this commercial phase, after an isothermic run of 4 hours at
2108C, no elution occurred. This is quite remarkable, since
menthyl laurate (17) is a heavy molecular mass compound,
with low volatility.
Table 4. Enantioseparation of eight compounds (10–17) in a GC column
of permethylated mono-6-deoxy-6-(pyridin-1-ium)-a-cyclodextrin trifluor-
omethanesulfonate (4a) stationary phase. Summary of the chromato-
graphic parameters.
Compound
T [8C]
k’1
5.14
3.75
8.63
10.79
21.44
54.94
21.04
210.13
k’2
5.43
3.86
9.04
10.92
22.08
55.49
23.45
216.23
a1
Rs1
Nmꢀ1
10
11
120
130
140
140
140
140
120
140
1.06
1.03
1.05
1.01
1.03
1.01
1.11
1.03
0.27
0.10
0.30
0.13
0.19
0.03
1.50
1.01
353
13
1342
25
52
13
12
13
14
15
16[a]
17
1227
2819
Conclusion
[a] k’3=29.02 and k’4=31.90, a2=1.10 and Rs2 =1.79.
In summary, we have synthesized the first room-temperature
ionic liquids (ILs) derived from a- and b-cyclodextrins (CDs),
the permethylated mono-6-deoxy-6-piridin-1-ium and mono-6-
deoxy-6-(1-vinyl-1H-imidazol-3-ium) a-CD and b-CD trifluoro-
methanesulfonates at room temperature in a solvent-free pro-
cedure. Mono-6-deoxy-6-pyridin-1-ium-a-cyclodextrin trifluoro-
methanesulfonate (4a) was used as stationary phase in enan-
tio-GC and epoxides 10 (ethers) and hydroxy esters 11 and 12,
and lactones 13–16 in racemic mixtures were separated suc-
cessfully. Both enantiomers of (ꢂ)-menthyl laurate (17) were
discriminated at 1408C in this stationary phase, which was not
achieved if a commercial CD column was used. Further, the
synthesis of CD room-temperature ILs to be used as stationary
phases in enantio-GC is now under investigation.
racemic menthyl laurate 17 (Scheme 6), the enantiomeric sepa-
ration was achieved isothermally at 1408C despite its high boil-
ing point. The same racemic mixture was not separated suc-
cessfully in a commercial CD phase at 2108C.
The thermal stability of the phase was tested up to 1608C,
at which no significant bleeding was observed. A temperature
program run from 40 to 1608C (held overnight, 16 h) did not
result in an enhanced flame ionization detector (FID) response.
The chromatographic parameters and the enantioseparation
for the whiskey lactone 16 (four diastereoisomers) were kept
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Data for permethylated mono-6-trifluoromethanesulfonate-
b-cyclodextrin (9b)
Experimental Section
General methods and instrumentation
1H NMR (CDCl3): d=5.30–5.07 (m, 7H; 6ꢁH-1’ and H-1), 4.66 (dd,
J=17.8, 8.0 Hz, 1H; H-6), 4.56 (m, 1H; H-6), 4.00 (m, 1H; H-5),
3.95–3.37 (m, 92H; 6ꢁH-3’, 6ꢁH-4’, 6ꢁH-5’, H-3, H-4, 12ꢁH-6’,
20ꢁOCH3), 3.19 (dd, J=9.6, 3.0 Hz, 6H; 6ꢁH-2’), 3.14 ppm (dd, J=
9.7, 3.4 Hz, 1H; H-2); 13C NMR (CDCl3): d=99.61 (C-1’ or C-1), 99.56
(C-1’ or C-1), 99.48 (C-1’ or C-1), 99.38 (C-1’ or C-1), 99.13 (C-1’ or C-
1), 99.09 (C-1’ or C-1), 99.02 (C-1’ or C-1), 82.16, 82.12, 82.01, 81.91,
81.87, 81.83, 81.56, 81.47, 80.85, 80.75, 80.53, 80.46, 80.44, 80.41,
80.31, 80.12, 71.61 (C-6’), 71.58 (C-6’), 71.50 (C-6’), 71.45 (C-6’),
71.43 (C-6’), 71.40, 71.36, 71.32 (C-6’), 71.16, 71.12, 71.02, 68.56 (C-
6), 61.70, 61.69, 61.66, 61.61, 61.54, 61.46, 61.42, 59.17, 59.10, 59.06,
58.95, 58.84, 58.77, 58.65, 58.59, 58.55 ppm; FTIR (film): v˜ =2929 (C-
H), 2834 (C-H), 1455 (S=O), 1195, 1039, 972 cmꢀ1; HRMS (ESI): m/z
calcd for C63H111F3O37S+: 1548.6472 [M+2H+]; found: 1548.6467.
Thin-layer chromatography (TLC) was performed on silica gel
plates (60 F254, Merck, ref. 1.05554) and visualized either by spray-
ing with sulfuric acid/methanol (1:1) followed by heating at 1208C
or with iodine vapor. Silica gel (230–400 mesh ASTM, Merck) was
used for flash chromatography. a- and b-cyclodextrins (CDs) were
dried overnight 20 h under vacuum over P2O5 at 1008C. Imidazole
was dried overnight, 20 h under vacuum over P2O5 at room tem-
perature. Methanol was dried with sodium and distilled. Dimethyl-
formamide, pyridine, dichloromethane, and 1-vinylimidazole were
dried over 4 ꢂ molecular sieves previously ignited 30 min at 3008C.
All remaining materials were used without additional purification.
The IR spectra were recorded in a PerkinElmer Spectrum 1000
spectrometer. 1H NMR (400.13 MHz), 13C NMR (100.61 MHz), 1H–1H
correlation spectroscopy (COSY), 13C–1H heteronuclear single quan-
tum correlation (HSQC), heteronuclear multiple bond correlation
(HMBC), and 19F NMR (376 MHz) spectra were recorded in a suitable
solvent by using a Bruker ARX 400 spectrometer. The splitting pa-
Synthesis of permethylated mono-6-deoxy-6-(pyridin-1-
ium)-a-cyclodextrin trifluoromethanesulfonate (4a)
1
rameters for H NMR spectroscopy are denoted as follows: s (sin-
In dichloromethane: Trifluoromethanesulfonic anhydride (0.018 mL,
30 mg, 0.107 mmol) was added dropwise to a cool solution of 8a
(75 mg, 0.062 mmol) in dry pyridine (0.15 mL, 147.3 mg,
1.86 mmol) in dry dichloromethane (1 mL). The reaction mixture
was stirred for 7 days at room temperature under argon. TLC
(chloroform/methanol 10:1) showed that all starting material was
consumed and a new lower spot (Rf 0.11) was formed. The solution
was cooled to 08C, diluted with dichloromethane (10 mL), washed
with aqueous HCl 5% (5 mL), aqueous NaHCO3 5% (5 mL), and
water (2 mL), dried over anhydrous Na2SO4, filtered, and concen-
trated to dryness to give 4a (57 mg). Chromatography on silica gel
with chloroform/methanol (10:1) as eluent afforded pure 4a as
a solid (29.6 mg, 0.021 mmol, 33.9%).
glet), d (doublet), t (triplet), and m (multiplet). Spectra were ob-
tained in CDCl3 containing a trace of TMS (d=0 ppm) as the inter-
nal standard, using a d (ppm) scale. High-resolution mass spectra
(ESI-TOF) were obtained at the RIAIDT of Universidad de Santiago
de Compostela and measured on a Bruker Amazon ETD (micrO-
TOF) instrument. MALDI-TOF measurements were performed at
Laboratꢃrio de Analises/Requimte of the Universidade Nova de
Lisboa and measured on a Voyager-DETM PRO workstation, in posi-
tive mode using a DHB matrix. Optical rotations were recorded in
a PerkinElmer 241 MC polarimeter.
Thermogravimetric (TG) and differential scanning calorimetry (DSC)
analyses were performed on a Netzsch Luxx STA 409 PC, at a heat-
ing rate of 78Cminꢀ1 under nitrogen from 60 to 4108C at the
Centro de Investigażo de Engenharia Quꢄmica e Biotecnologia, In-
stituto Superior de Engenharia, Portugal. The analytical tests were
performed in a GC Trace instrument (Thermo Finnigan, USA)
equipped with a split/splitless injector and a flame ionization de-
tector (FID), both set at 2508C. The carrier gas was hydrogen, at
45 kPa. A sample volume (1 mL) was injected at a split flow of
150 mLminꢀ1. The chromatograms were processed by using the
automated data processing software Xcalibur from Thermo Finni-
gan (ThermoFinnigan, Austin, TX, USA).
Without solvent: A solution of 8a (100.7 mg, 0.083 mmol) in dry
pyridine (2 mL) was cooled to 08C and trifluoromethanesulfonic
anhydride (0.07 mL, 117.4 mg, 0.416 mmol) was added dropwise.
The reaction was stirred for 2 days at room temperature under
argon. TLC (chloroform/methanol 10:1) showed that all starting
material was consumed and a new lower spot (Rf 0.11) was formed.
The solution was cooled to 08C, diluted with dichloromethane
(70 mL), washed with aqueous HCl 5% (2ꢁ10 mL), aqueous
NaHCO3 5% (2ꢁ10 mL), and water (2ꢁ10 mL), dried over anhy-
drous Na2SO4, filtered, and concentrated to dryness to give 4a.
Chromatography on silica gel with chloroform/methanol (9:1) as
eluent afforded pure 4a (75.1 mg, 0.059 mmol, 71.1%) as a solid.
Synthesis of permethylated mono-6-trifluoromethanesulfo-
nate-b-cyclodextrin (9b)
Data for permethylated mono-6-deoxy-6-(pyridin-1-ium)-a-
cyclodextrin trifluoromethanesulfonate (4a)
Trifluoromethanesulfonic anhydride (0.198 g, 0.70 mmol) was
added dropwise to
a cold stirred solution of 8b (72.4 mg,
M.p. 84–858C; [a]D21 = +126.8 (c=3.0 in CHCl3); 1H NMR (CDCl3):
d=9.05 (d, J=5.8 Hz, 2H; H-2’’, H-6’’), 8.54 (t, J=7.8 Hz, 1H; H-4’’),
8.05 (m, 2H; H-3’’, H-5’’), 5.30 (dd, J=14.3, 2.7 Hz, 1H; H-6), 5.19
(dd, J=14.6, 3.7 Hz, 1H; H-6), 5.13 (d, J=3.1 Hz, 1H; H-1), 5.07 (m,
3H; 3ꢁH-1’), 4.97 (d, J=3.3 Hz, 1H; H-1’), 4.92 (d, J=3.5 Hz, 1H;
H-1’), 4.39–2.82 ppm (m, 85H; H-2, H-3, H-4, H-5, 5ꢁH-2’, 5ꢁH-3’,
5ꢁH-4’, 5ꢁH-5’, 10ꢁH-6’, 17ꢁOCH3); 13C NMR (CDCl3): d=146.72
(C-2’’, C-6’’), 145.77 (C-4’’), 127.95 (C-3’’, C-5’’), 100.54 (C-1’), 100.44
(C-1’), 100.26 (C-1’), 100.20 (C-1’), 99.41 (C-1), 83.63, 82.52, 82.47,
82.43, 82.34, 82.26, 82.21, 82.14, 82.08, 81.95, 81.91, 81.56, 81.41,
81.36, 81.22, 81.12, 80.90, 72.34 (C-6’), 72.18, 71.60, 71.47 (C-6’),
71.28 (C-6’), 71.15, 69.41, 62.12, 62.00, 61.94, 61.86, 61.8, 61.78,
0.051 mmol) in dry 1-vinylimidazole (1 mL). The reaction mixture
was allowed to warm to room temperature and stirred for 2 days.
TLC (EtOAc/CH3OH 10:1) showed the formation of two new com-
pounds, one at Rf =0 and the other with higher Rf than 8b. The so-
lution was cooled to 08C, diluted with cold CH2Cl2 (10 mL), washed
with cold aqueous HCl 5% (2ꢁ5 mL), cold aqueous NaHCO3 5%
(5 mL), and cold water (2 mL), dried over Na2SO4, filtered, and con-
centrated to dryness. The crude product was purified by column
chromatography on silica gel (CHCl3/CH3OH 10:2) to give pure 9b
(29.8 mg, 37.6%) as an oil.
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61.09 (C-6), 59.74, 59.27, 59.21, 59.15, 59.07, 58.78, 58.26, 58.11,
58.10, 57.99, 57.90 ppm; 19F NMR (CDCl3): d=ꢀ78.34 ppm (s,
CF3SO3ꢀ); FTIR (KBr): v˜ =2926, 2858, 1458, 1261, 1162, 1110,
81.22, 81.01, 72.51 (C-6’), 72.06 (C-6’), 71.59, 71.47 (C-6’), 71.41,
71.37, 68.72, 62.14, 62.00, 61.96, 61.84, 59.86, 59.29, 59.23, 59.19,
59.13, 58.75, 58.21, 58.11, 58.04, 58.02, 57.94, 50.51 ppm (C-6);
19F NMR (CDCl3): d=78.47 (s, CF3); FTIR (film): v˜ =2930, 2834, 1667,
1454, 1262, 1162, 1037, 639 cmꢀ1; HRMS (ESI): m/z calcd for
C58H99N2O29+: 1287.6328 [cation]; found: 1287.6322; m/z calcd for
CF3SO3ꢀ: 148.9526 [anion]; found: 148.9526.
1041 cmꢀ1; HRMS (ESI): m/z calcd for C58H98NO29+: 1272.6219
ꢀ
[cation]; found: 1272.6186; m/z calcd for CF3SO3
[anion]; found: 148.9523.
: 148.9526
Data for permethylated mono-6-deoxy-6-(pyridin-1-ium)-b-
cyclodextrin trifluoromethanesulfonate (4b)
Data for permethylated mono-6-deoxy-6-(1-vinyl-1H-imida-
zol-3-ium)-b-cyclodextrin trifluoromethanesulfonate (5b)
h=38.2%; m.p. 110–1158C; [a]D21 = +91.6 (c=1.4 in CHCl3);
1H NMR (CDCl3): d=9.11 (d, J=4.4 Hz, 2H; H-2’’ and H-5’’), 8.54 (t,
J=7.0 Hz, 1H; H-4’’), 8.06 (m, 2H; H-2’’ and H-4’’), 5.35 (d, J=
12.8 Hz, 1H; H-6), 5.17 (d, J=3.32 Hz, 1H; H-1’), 5.12 (m, 3H; H-6,
2ꢁH-1’), 5.09 (d, J=3.11 Hz, 1H; H-1’), 5.06 (d, J=3.44, 1H; H-1’),
5.00 (d, J=3.42 Hz, 1H; H-1’), 4.29 (d, J=8.8 Hz, 1H; H-5), 4.07–
2.92 (m, 99H; H-3, H-4, H-5, 6ꢁH-2’, 6ꢁH-3’, 6ꢁH-4’, 6ꢁH-5’, 12ꢁ
H-6’, 20ꢁOCH3), 2.94 ppm (dd, J=2.27, 9.62 Hz, 1H; H-2); 13C NMR
(CDCl3): d=146.84 (C-2’’, C-6’’), 145.75 (C-4’’), 127.79 (C-3’’, C-5’’),
100.38 (C-1’), 100.07 (C-1’), 99.35 (C-1’), 99.27 (C-1’), 99.12 (C-1’),
98.04 (C-1), 82.27, 82.19, 82.22, 82.12, 82.07, 81.96, 81.86, 81.81,
81.77, 81.58, 81.47, 81.34, 81.00, 80.82, 80.75, 80.42, 80.11, 79.81,
72.76 (C-6’), 71.76, 71.71 (C-6’), 71.44 (C-6’), 71.39 (C-6’), 71.29,
71.13, 71.08, 70.98, 69.28, 61.77, 61.63, 61.58, 61.53, 61.46, 61.36,
61.27, 61.19 (C-6), 59.75, 59.40, 59.33, 59.17, 59.13, 59.08, 58.84,
58.72, 58.61, 58.46, 58.43 ppm; 19F NMR (CDCl3): d=ꢀ78.00 ppm (s,
h=29.5%; m.p. 95–998C; [a]D21 = +117.1 (c=0.92 in CHCl3);
1H NMR (CDCl3): d=9.44 (s, 1H; H-2’’), 7.80 (s, 1H; H-5’’), 7.55 (s,
1H; H-4’’), 7.34 (dd, J=15.5, 8.6 Hz, 1H; H-6’’), 5.76 (dd, J=15.6,
2.8 Hz 1H; H-7’’trans), 5.45 (dd, J=8.6, 2.7 Hz, 1H; H-7’’cis), 5.17 (d,
J=3.4 Hz, 2H; 2ꢁH-1’), 5.15–5.10 (m, 2H; 2ꢁH-1’), 5.08 (d, J=
3.3 Hz, 1H; H-1’), 4.98 (d, J=3.7 Hz, 2H; H-1, H-1’), 4.84 (dd, J=
14.6, 2.8 Hz, 1H; H-6), 4.61 (dd, J=2.3, 14.4 Hz, 1H; H-6), 4.20–
2.96 ppm (m, 100H; H-2, H-3, H-4, H-5, 6ꢁH-2’, 6ꢁH-3’, 6ꢁH-4’, 6ꢁ
H-5’, 12ꢁH-6’, 20ꢁOCH3); 13C NMR (CDCl3): d=137.53 (C-2’’),
128.86 (C-6’’), 124.86 (C-5’’), 118.18 (C-4’’), 110.13 (C-7’’), 100.41 (C-
1’), 100.32 (C-1’), 99.27 (C-1’), 99.18 (C-1’), 98.07 (C-1), 82.53, 82.34,
82.23, 82.13, 81.85, 81.79, 81.62, 81.43, 81.22, 80.99, 80.78, 80.59,
80.00, 72.81 (C-6’), 71.90 (C-6’), 71.61, 71.49 (C-6’), 71.42, 71.37,
71.31, 71.16 (C-6’), 71.04, 68.54, 61.79, 61.59, 61.52, 61.43, 61.23,
59.83, 59.34, 59.17, 59.15, 59.09, 59.08, 58.98, 58.71, 58.48, 58.45,
58.40, 50.35 ppm (C-6); 19F NMR (CDCl3): d=ꢀ78.42 ppm (s,
CF3SO3ꢀ); FTIR (film): v˜ =2930 (C-H), 2833 (C-H), 1458, 1262, 1162,
CF3); FTIR (KBr): v˜ =2930, 2834, 1461, 1455, 1262, 1162, 1108, 1033,
639 cmꢀ1
;
HRMS (ESI): m/z calcd for C67H114NO34
:
1476.7217
+
1032, 639 cmꢀ1; HRMS (ESI): m/z calcd for C67H115N2O34+: 1491.7326
[cation]: found: 1476.7219; m/z calcd for CF3SO3ꢀ:148.9526 [anion];
2+
[cation]; found: 1491.7256; m/z calcd for C67H115N2NaO34
757.3609 [cation+Na+]; found 757.3601; m/z calcd for CF3SO3
148.9526 [anion]; found: 148.9529.
:
:
found: 148.9530.
ꢀ
Synthesis of permethylated mono-6-deoxy-6-(1-vinyl-1H-imi-
dazol-3-ium)-a-cyclodextrin trifluoromethanesulfonate (5a)
GC column coating
A solution of 8a (108.2 mg, 0.089 mmol) in dry 1-vinylimidazole
(2 mL) was stirred and cooled to 08C under an argon atmosphere.
Then trifluoromethanesulfonic anhydride (1.03 mL, 1.727 g,
6.12 mmol) was added dropwise. The reaction mixture was allowed
to warm to room temperature and stirred for 19 h. TLC (EtOAc/
CH3OH 10:1) showed the formation of two new spots, one at the
baseline and the other with higher Rf. The solution was cooled
again (08C), diluted with cold CH2Cl2 (10 mL), washed with cold
HCl 5% (2ꢁ5 mL), cold aqueous NaHCO3 5% (5 mL), and cold
water (2 mL), dried over Na2SO4, filtered, and concentrated to dry-
ness. The product obtained was subjected to column chromatogra-
phy on a silica gel with CHCl3/CH3OH (10:2) as eluent to give pure
5a (73.5 mg, 67.2%).
Untreated fused-silica capillary tubing (250 mm i.d.) was purchased
from SGE Analytical Science, Ringwood, Victoria, Australia; 13 m of
capillary tubing were used to prepare the column. Before coating,
the untreated fused-silica capillary tubing was rinsed with acetone
P.A. (2.6 mL, corresponding to four times the volume of the 13 m
coil). To remove the washing solvent, the coil was purged with
a stream of nitrogen for 15 min. To prepare the coating solution,
permethylated mono-6-deoxy-6-(pyridin-1-ium)-a-cyclodextrin tri-
fluoromethanesulfonate (4a; 18 mg) was dissolved in dichlorome-
thane P.A. (10 mL) to obtain a solution concentration of 0.18% (w/
v). Considering the diameter of the capillary tubing (250 mm i.d.)
and the percentage by weight concentration of the stationary
phase dissolved in dichloromethane, the estimated film thickness
was 0.11 mm.[18b,34] One end was sealed with an epoxy glue (Ceys
Araldit) and maintained 2 days at controlled ambient temperature
and humidity to dry. The filled coil was then submitted to 5.5 bar
pressure (helium) during 4 days to remove any air bubbles, which
could cripple the subsequent solvent evaporation step. The evapo-
ration process took place in a water bath at 408C under a reduced
pressure of 7 mm Hg. After 2 days, the solvent was evaporated
and the filled column was submitted to a helium flow for 2 h
(under a pressure of 0.5 bar) and then conditioned from 50 to
1208C at 18Cminꢀ1. This temperature was held overnight 20 h. The
efficiency of the coated column was tested with a standard solu-
tion of tetradecane in dichloromethane at 1208C. The calculated
retention factor (k) was 6.6. The calculated number of plates per
meter of column was 330. All further analyses were performed
under the same instrument conditions (see above for details).
Data for permethylated mono-6-deoxy-6-(1-vinyl-1H-imida-
zol-3-ium)-a-cyclodextrin trifluoromethanesulfonate (5a)
h=41.5%; m.p. 95–1008C; [a]D21 = +119.0 (c=1.03 in CHCl3);
1H NMR (CDCl3): d=9.27 (s, 1H; H-2’’), 7.74 (s, 1H; H-5’’), 7.57 (s,
1H; H-4’’), 7.34 (dd, J=15.5, 8.6 Hz, 1H; H-6’’), 5.77 (dd, J=15.6,
2.9 Hz, 1H; H-7’’trans), 5.46 (dd, J=8.6, 2.9 Hz, 1H; H-7’’cis), 5.18 (d,
J=3.0 Hz, 1H; H-1), 5.12–5.02 (m, 3H; 3ꢁH-1’), 4.99–4.84 (m, 3H;
H-6, 2ꢁH-1’), 4.67 (d, J=12.6 Hz, 1H; H-6), 4.16–3.29 (m, 79H; H-3,
H-4, H-5, 5ꢁH-3’, 5ꢁH-4’, 5ꢁH-5’, 10ꢁH-6’, 17ꢁOCH3), 3.24–
3.11 ppm (m, 6H; H-2, 5ꢁH-2’); 13C NMR (CDCl3): d=131.05 (C-2’’),
128.82 (C-6’’), 124.76 (C-5’’), 118.18 (C-4’’), 110.41 (C-7’’), 100.66 (C-
1’), 100.48 (C-1’), 100.36 (C-1’), 100.30 (C-1’), 100.27 (C-1’), 99.40 (C-
1), 83.76, 82.58, 82.51, 82.39, 82.27, 82.16, 82.00, 81.55, 81.39, 81.36,
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ChemPlusChem 2013, 78, 1466 – 1474 1473

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enantioselectivity
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chromatography · ionic liquids · regioselectivity
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Published online on October 2, 2013
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ChemPlusChem 2013, 78, 1466 – 1474 1474