Chiral pool based synthesis of pyrrolidinium ionic liquids

Article abstract of DOI:10.1016/j.tetlet.2017.01.102

Chiral ionic liquids show promising applications in various different fields. A series of pyrrolidinium-based chiral ionic liquids bearing a chiral cation, a chiral anion or both was prepared in good yields using an efficient, economic and simple pathway.

Full text of DOI:10.1016/j.tetlet.2017.01.102

Accepted Manuscript
Chiral pool based synthesis of pyrrolidinium ionic liquids
Alexandra Brown, Victoria Hogan, Jacob Perry, Renuka Manchanayakage
PII:
S0040-4039(17)30147-8
DOI:
http://dx.doi.org/10.1016/j.tetlet.2017.01.102
TETL 48605
Reference:
Tetrahedron Letters
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Revised Date:
Accepted Date:
10 January 2017
24 January 2017
30 January 2017
Please cite this article as: Brown, A., Hogan, V., Perry, J., Manchanayakage, R., Chiral pool based synthesis of
pyrrolidinium ionic liquids, Tetrahedron Letters (2017), doi: http://dx.doi.org/10.1016/j.tetlet.2017.01.102
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Chiral pool based synthesis of pyrrolidinium
ionic liquids
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Alexandra Brown, Victoria Hogan, Jacob Perry, and Renuka Manchanayakage

1
Tetrahedron Letters
Chiral pool based synthesis of pyrrolidinium ionic liquids
Alexandra Browna, Victoria Hoganb, Jacob Perrya, and Renuka Manchanayakagea*
aDepartment of Chemistry, St. John Fisher College, 3690 East Avenue, Rochester, NY 14618
bDepartment of Chemistry, Susquehanna University, 514 University Avenue, Selinsgrove, PA 17870
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Chiral ionic liquids show promising applications in various different fields. A series of
pyrrolidinium-based chiral ionic liquids bearing a chiral cation, a chiral anion or both was
prepared in good yields using an efficient, economic and simple pathway. The chirality
was introduced using (L)-lactate and (L)-menthol derivatives. The resultant chiral
compounds were characterized by both spectroscopy and polarimetry. We envision that
these new chiral compounds can serve as effective reaction media and chiral catalysts for
asymmetric reactions, which are presently being investigated in our lab.
Available online
Keywords:
Ionic liquids
Chirality
2009 Elsevier Ltd. All rights reserved.
Pyrrolidine
Chiral solvents
Enantiomerically pure synthesis
*Corresponding author. Tel.: +1-585-385-8102; fax: +1-585-385-7311; e-mail: rmanchanayakage@sjfc.edu

2
In the recent years, there has been a growing demand in the
use of the room-temperature ionic liquids (RTIL) as new
reaction media.1 One of the main expected applications of
ionic liquids is to replace the volatile organic solvents
traditionally used in large scale in industry.2 Ionic liquids
possess a number of interesting properties over commonly
used organic solvents, such as lack of significant vapor
pressure, absence of flammability, tolerance for large
temperature variations and ease of reuse.3 They have been
extensively used in chemical syntheses and electrosyntheses.4
Armed with this information, we discuss the synthesis and
characterization of a series of pyrrolidinium-based chiral ionic
liquids. Chirality is introduced to the cation by using a
menthol derivative and to the anion by sing a lactate salt. The
presence of functional groups makes them potential task-
specific chiral ionic liquids.13 The concept of tailor-made
task-specific chiral ionic liquids is rather new, and the
synthesis of a series of new chiral ionic liquids with unique
properties will benefit the collection of compounds that is
currently limited in scope.
This project focused on the synthesis and characterization of
pyrrolidinium-based chiral ionic liquids bearing a chiral
cation, chiral anion or both using an economic, simple and
efficient pathway. The enantiomerically pure ionic liquids can
be prepared using chiral precursors such as aminoacids,
aminoalcohols, hydroxyacids, amines, alkaloids or
halogenoalkanes derived from a chiral pool for the generation
of the chiral ionic liquid’s anion, cation, or both.5 In our
project, the chirality for the ionic liquids was introduced using
inexpensive and readily available (L)-lactate and (L)-menthol
derivatives. 1-methylpyrrolidine or 1-butylpyrrolidine was
heated to reflux in acetonitrile for 48h with (-)-chloromethyl
menthyl ether (Scheme 1).14 The intermediate chiral ionic
salts, 1-butyl-1-menthoxymethylpyrrolidinium chloride and 1-
Chiral ionic liquids (CILs) are one of the latest branches of
ionic liquid research and are promising chiral solvents for
many applications.5 Chiral ionic liquids are particularly
attractive due to their potential for chiral discrimination, as in
asymmetric synthesis and optical resolution of racemates.6
Because of their highly-organized nature and ionic properties,
an obvious potential exists for solvent-solute interaction that
may provide a mechanism for substantial improvement over
conventional chiral solvents.7 So far, chiral ionic liquids have
been successfully applied in asymmetric synthesis,
stereoselective polymerization, chiral stationary phases in
chromatographic techniques, and chiral shift reagents in NMR
spectroscopy.8 Other advantages of using chiral ionic liquids
include the following: (1) the chiral ionic liquids are easily
and inexpensively prepared and can be recycled; (2) the
opposite enantiomers of the chiral ionic liquids can be
produced in order to enantioselectively create the desired
enantiomer in excess; (3) it is possible and easy to remove the
chiral ionic liquids from the final reaction mixture so that no
interference is occurred. Therefore, it is important to have a
range of chiral ionic liquids with different properties that can
be used in various applications.
The more efficient, economic and simple way to prepare
enantiomerically pure ionic liquids with central chirality is the
use of precursors derived from the chiral pool either for the
generation of the CIL’s anion or cation or for both.9 Chirality
has been introduced to the cation using various methods and
the imidazolium cation has been widely used in these
preparations.10 Under most circumstances, the imidazole-
derived ionic liquids are considered to be stable and “inert”
solvents, but the 2-position can be deprotonated to form a
stabilized carbene which could be problematic for some
applications.11 This situation can be avoided by the use of
pyrrolidinium and benzimidazolium cations. However, less
attention has been given to the cations such as pyrrolidinium
and benzimidazolium in the preparation of chiral ionic liquids.
Additionally, recent research shows that some pyrrolidinium-
based ionic liquids have excellent electrochemical and
mechanical performances and are promising electrolytes for
lithium batteries.12
methyl-1-menthoxymethylpyrrolidinium
chloride
were
formed in good yields; 90% and 92% respectively. The
spectroscopic analysis of intermediate ionic salts confirmed
the purity of the products. The specific rotation was
determined by polarimetry. The intermediate salts were then
subjected to anion exchange without further purification.
Ionic
chloride
salts, 1-butyl-1-menthoxymethylpyrrolidinium
and 1-methyl-1-menthoxymethylpyrrolidinium
chloride were separately reacted with tetrafluoroboric acid,
potassium hexafluorophosphate and lithium
bis(trifluoromethane)sulfonimide by replacing the chloride
anion with tetraflouroborate, hexafluorophosphate and
bis(trifluoromethane)sulfonimide respectively (Scheme 1).14
These anion exchange reactions resulted six new ionic liquids
bearing a chiral cation in good yields (Table 1; 1a-1c and 1e-
1g). Additionally, the intermediate ionic salts were further
reacted with sodium L-lactate by exchanging the chloride
anion with L-lactate anion providing two chiral ionic liquids
bearing both a chiral anion and a cation (Table 1; 1d and 1h).
Both 1-butyl-1-menthoxymethylpyrrolidinium L-lactate and
1-methyl-1-menthoxymethylpyrrolidinium L-lactate were
semi-solids at room temperature and obtained in good yields.
The structure and the purity of final chiral ionic liquids were
confirmed by 1H NMR, 13C NMR and IR spectroscopy.15 The
polarimetry was performed in methanol at 583 nm to
determine the specific rotation for the final chiral ionic liquids
(Table 1).15
Scheme 1: Synthesis of chiral ionic liquids from the reactions of 1-alkylpyrrolidine and (-)-chloromethyl menthyl ether.

3
Table 1: 1-alkyl-1-menthoxymethylpyrralodinium chiral ionic liquids synthesized in the lab
Next we focused on the synthesis of functionalized chiral
ionic liquids that have the potential of using as task specific
chiral ionic liquids. The synthesis was started by preparing
(-)-menthyl chloroacetate by the reaction of (-)-menthol,
chloroacetyl chloride and triethyl amine in THF (Scheme 2).16
The resultant (-)-menthyl chloroacetate was purified by
column chromatography and analyzed by spectroscopy. It was
then used to introduce the chirality for the cation. The ionic
salts; 1-butyl-1-menthoxyacetylpyrrolidinium chloride and 1-
menthoxyacetylpyrrolidinium chloride and 1-methyl-1-
menthoxyacetylpyrrolidinium chloride with sodium L-lactate
resulted two chiral ionic liquids bearing both a chiral cation
and a chiral anion, by exchanging the chloride anion with L-
lactate
anion
(Scheme
3).17
Both
1-butyl-1-
menthoxyacetylpyrrolidinium L-lactate and 1-methyl-1-
menthoxyacetylpyrrolidinium L-lactate were low melting
solids at room temperature and obtained in excellent yields
(Table 2; 2d and 2h). The structure and the purity of final
chiral ionic liquids were confirmed by NMR and IR
spectroscopic methods and the polarimetry was used in
methanol at 583 nm to determine the specific rotation.18
methyl-1-menthoxyacetylpyrrolidinium
chloride
were
prepared in good yields (87% and 91% respectively) by
reacting (-)-menthyl chloroacetate with 1-butylpyrrolidine or
1-methylpyrrolidine respectively (Scheme 3).17 After
confirming the structure and the purity using spectroscopic
methods, these intermediate ionic salts were then used in
anion exchange reactions with tetrafluoroboric acid,
potassium
hexafluorophosphate
and
lithium
bis(trifluoromethane)sulfonimide without further purification
(Scheme 3). The new ionic liquids bearing a chiral cation
were obtained in good yields and their physical properties
varied from liquids to semisolids to low melting solids (Table
2; 2a-2c and 2e-2g). The reaction of ionic salts, 1-butyl-1-
Scheme 2: Synthesis of (-)-menthyl chloroacetate.

4
Scheme 3: Synthesis of chiral ionic liquids from the reactions of 1-alkylpyrrolidine and (-)-menthyl chloroacetate.
Table 2: 1-alkyl-1-menthoxyacetylpyrrolodinium chiral ionic liquids synthesized in the lab
In conclusion, we have synthesized sixteen pyrrolidinium-
based chiral ionic liquids of which twelve ionic liquids are
bearing a chiral cation and four of them are bearing both a
chiral cation and a chiral anion. These chiral ionic liquids
have been prepared in good yields and characterized using
spectroscopy and polarimetry. Efforts are currently underway
in our lab to use these chiral compounds as effective reaction
media as well as chiral catalysts in asymmetric ring opening
of epoxides and the results will be reported in due course.
References and notes
1. Wasserscheid, P.; Welton, T. Eds. Ionic Liquids in
Synthesis; Wiley-VCH: Weinheim, 2002.
2. (a) Marrucho, I. M.; Branco, L. C.; Rebelo, L. P. N. Annu.
Rev. Chem. Biomol. Eng. 2014, 5, 527–46. (b) Hallett, J. P.;
Welton, T. Chem. Rev. 2011, 111(5), 3508-3576.
3. (a) Prechtl, M. H. G.; Scholten, J. D.; Dupont, J.
Molecules 2010, 15, 3441-3461. (b) Lin, Y.; Tsai, S-C.; Yu,
S. J. J. Org. Chem. 2008, 73, 4920-4928. (c) Slaton, R.;
Petrone, A.; Manchanayakage, R. Tetrahedron Lett. 2011, 52,
5073-5076.
Acknowledgement
The authors thank Summer Science Fellows program and the
chemistry department at St. John Fisher College for the
financial support of this research.
4. (a) Plechkova, N. V.; Seddon, K. R. Chem. Soc. Rev. 2008,
37, 123-150. (b) Kronenwetter, H.; Husek, J.; Jones, A.; Etz,

5
B.; Manchanayakage, R. Green Chem. 2014, 16, 1489-1495.
(c) Jones, A.; Kronenwetter, H.; Manchanayakage, R.
Electrochem. Comm. 2012, 25, 8-10.
5. Baudequin, C.; Bregeon, D.; Levillain, J.; Guillen, F.;
Plaqueventb, J.; Gaumont, A. Tetrahedron: Asymmetry, 2005,
16, 3921–3945.
(d, J = 7.9 Hz, 6H), 0.76 (d, J = 7.5 Hz, 3H); 13C NMR (100
MHz, CDCl3, δ): 83.1, 80.9, 60.0, 59.8, 59.7, 48.1, 40.2, 34.1,
31.2, 25.9, 25.3, 22.8, 22.3, 22.1 (2C), 21.1, 19.7, 15.9, 13.6;
IR (/cm-1): 2930, 2910, 1215, 1062.
Table
1,
1b:
Butyl
[(1R,2S,5R)-(-)-
menthoxymethyl]pyrrolidinium
hexafluorophosphate
(semisolid; yield = 81.8%), []20 -47.0; 1H NMR (400 MHz,
6. Wang, Z.; Wang, Q.; Zhang, Y.; Bao, W. Tetrahedron Lett.
2005, 46, 4657-4660.
D
CDCl3, ): 4.50, 4.40 (d, J = 8.1 Hz, 2H), 3.58 (t, J = 5.9 Hz,
2H), 3.40 (t, J = 5.7 Hz, 2H), 3.25 (t, J = 5.7 Hz, 2H), 3.15
(dt, J = 4.0, 8.0 Hz, 1H), 2.13 (t, J = 5.7 Hz, 4H), 1.64-1.62
(m, 2H), 1.39-1.37 (m, 2H), 2.09-0.88 (m, 9H), 0.94 (t, J = 8.7
Hz, 3H), 0.89 (d, J = 7.8 Hz, 6H), 0.77 (d, J = 6.6 Hz, 3H);
13C NMR (100 MHz, CDCl3, δ): 83.2, 81.0, 60.1, 59.9, 59.8,
48.0, 40.1, 34.1, 31.2, 25.9, 25.2, 22.9, 22.4, 22.3 (2C), 21.0,
19.7, 15.8, 13.5; IR (/cm-1): 2930, 2910, 1220, 1062, 840.
7. Ding, J.; Vasumathi, D.; Han, X.; Xiao, T. L.; Ding, R.;
Jenks, W.; Armstrong, D. W. Org. Lett. 2005, 7, 335-337.
8. (a) Pegot, B.; Vo-Thanh, G.; Loupy, A. Tetrahedron Lett.
2004, 45, 6425–6428. (b) Biedron, T.; Kubisa, P. Polym. Int.
2003, 52, 1584–1588. (c) Biedron, T.; Kubisa, P. J. Polym.
Sci. Part A: Polym. Chem. 2005, 43, 3454–3459. (d) Ding, J.;
Welton, T.; Armstrong, D. W. Anal. Chem. 2004, 76, 6819–
6822.
9. Fukumoto, K.; Yoshizawa, M.; Ohno, H. J. Am. Chem. Soc.
2005, 127, 2398–2399.
10. Headley, A. D.; Ni, B. AldrichimicaACTA, 2007, 40, 107-
117.
11. Handy, S. T. J. Org. Chem. 2006, 71, 4659-4662.
12. Samori, C.; Campisi, T.; Fagnoni, M.; Galletti, P.;
Pasteris, A.; Pezzolesi, L.; Protti, S.; Ravelli, D.; Tagliavini,
E. ACS Sustain Chem Eng. 2015, 3, 1860-1865.
13. Ranu, B. C.; Banerjee, S. Org. Lett. 2005, 7, 3049-3052.
Table
1,
1c:
Butyl
[(1R,2S,5R)-(-)-
menthoxymethyl]pyrrolidinium
bis(trifluoromethane)sulfonimide (semisolid; yield = 89.4%),
[]20 -32.9; 1H NMR (400 MHz, CDCl3, ): 4.51, 4.41 (d, J
D
= 8.0 Hz, 2H), 3.59 (t, J = 6.0 Hz, 2H), 3.40 (t, J = 5.7 Hz,
2H), 3.27 (t, J = 5.7 Hz, 2H), 3.17 (dt, J = 4.1, 7.9 Hz, 1H),
2.18 (t, J = 5.7 Hz, 4H), 1.67-1.63 (m, 2H), 1.36-1.34 (m,
2H), 2.09-0.92 (m, 9H), 0.91 (t, J = 8.7 Hz, 3H), 0.90 (d, J =
8.4 Hz, 6H), 0.77 (d, J = 6.9 Hz, 3H); 13C NMR (100 MHz,
CDCl3, δ): 121.8, 118.6, 83.0, 81.0, 60.0, 59.9 (2C), 48.0,
40.1, 34.0, 31.2, 25.9, 25.3, 22.8, 22.4, 22.3 (2C), 21.9, 19.6,
15.7, 13.4; IR (/cm-1): 2930, 2910, 1220, 1062, 840.
14. Representative Procedure for the Synthesis of alkyl
[(1R,2S,5R)-(-)-menthoxymethyl]pyrrolidinium ionic liquids
(1a – 1h): In a round-bottomed flask, 1-alkylpyrrolidine (0.01
mol) was mixed with (1R,2S,5R)-(-)-chloromethyl menthyl
ether (0.01 mol) in acetonitrile under nitrogen atmosphere.
The reaction mixture was heated to reflux for 48 h. After the
reaction time, the solvent was evaporated using a rotary
evaporator and the resultant, alkyl [(1R,2S,5R (-)-1-
menthoxymethyl]pyrrolidinium chloride, was dried in a
vacuum line overnight. In the second step, chloride of the
ionic liquid was replaced with tetrafluoroborate,
hexafluorophosphate, bistrifluoromethane sulfonimide, or L-
lactate by reacting with HBF4, KPF6, or bis(trifluoromethane)
sulfonimide lithium salt in water or sodium L-lactate in
acetone, respectively. The product was extracted into
methylene chloride (2 x 10 mL) and the combined organic
layers were dried with anhydrous Na2SO4. The solvent was
evaporated using a rotary evaporator and the final ionic
liquids were dried in a vacuum line prior to characterization.
Table
1,
1d:
Butyl
[(1R,2S,5R)-(-)-
menthoxymethyl]pyrrolidinium L-lactate (semisolid; yield =
89.5%), []20 -44.2; H NMR (400 MHz, CDCl3, ): 4.68,
1
D
4.59 (d, J = 7.2 Hz, 2H), 4.12 (q, J = 8.0 Hz, 1H), 3.58 (t, J =
5.8 Hz, 2H), 3.56 (t, J = 5.7 Hz, 2H), 3.35 (t, J = 5.7 Hz, 2H),
3.18 (dt, J = 4.0, 7.0 Hz, 1H), 3.04 (bs, 1H, OH), 2.23 (t, J =
5.8 Hz, 4H), 1.71- 1.70 (m, 2H), 1.38-1.36 (m, 2H), 1.33 (d, J
= 4.0 Hz, 3H), 2.16-0.97 (m, 9H), 0.95 (t, J = 7.6 Hz, 3H),
0.94 (d, J = 7.7 Hz, 6H), 0.84 (d, J = 8.6 Hz, 3H); 13C NMR
(100 MHz, CDCl3, δ): 182.2, 83.5, 80.6, 68.6, 60.6, 60.3,
59.6, 48.5, 40.1, 34.5, 31.1, 25.8, 25.0, 22.3, 22.1, 22.0 (2C),
21.1, 20.3, 19.6, 15.8, 13.3; IR (/cm-1): 3600-2500 (br),
2990, 1730, 1225, 1066.
Methyl
[(1R,2S,5R)-(-)-menthoxymethyl]pyrrolidinium
chloride (92.0%), []20 -59.8; H NMR (400 MHz, CDCl3,
1
D
): 4.90, 4.89 (d, J = 7.9 Hz, 2H), 3.79 (t, J = 5.9 Hz, 2H),
3.65 (t, J = 5.9 Hz, 2H), 3.46 (dt, J = 3.9, 7.8 Hz, 1H), 3.28 (s,
3H), 2.29 (t, J = 5.8 Hz, 4H), 2.29-0.84 (m, 9H), 0.83 (d, J =
7.9 Hz, 6H), 0.81 (d, J = 7.9 Hz, 3H); 13C NMR (100 MHz,
CDCl3, δ): 87.1, 81.5, 61.0(2C), 48.2, 47.8, 40.6, 34.0, 31.2,
25.8, 22.8, 22.2, 22.1, 21.1(2C), 16.0; IR (/cm-1): 2980,
2920, 1050, 920.
15. All products exhibited spectral properties consistent
with the assigned structures. Butyl [(1R,2S,5R)-(-)-
menthoxymethyl]pyrrolidinium chloride (90.0%), []20
D
Table
1,
1e:
Methyl
[(1R,2S,5R)-(-)-
-59.6; 1H NMR (400 MHz, CDCl3, ): 4.65, 4.61 (d, J = 8.0
Hz, 2H), 3.72 (t, J = 5.9 Hz, 2H), 3.50 (t, J = 5.9 Hz, 2H),
3.33 (t, J = 6.9 Hz, 2H), 2.93 (dt, J = 4.0, 8.0 Hz, 1H), 2.10 (t,
J = 6.2 Hz, 4H), 1.49–1.46 (m, 2H), 1.24-1.22 (m, 2H), 2.09-
0.77 (m, 9H), 0.96 (t, J = 9.0 Hz, 3H), 0.89 (d, J = 8.0 Hz,
6H), 0.74 (d, J = 8.0 Hz, 3H); 13C NMR (100 MHz, CDCl3,
δ): 83.4, 80.7, 59.9, 59.7, 59.2, 47.9, 40.3, 33.9, 31.1, 25.8,
25.3, 22.6, 22.3, 21.9 (2C), 20.9, 19.7, 15.7, 13.6; IR (/cm-1):
2940, 2920, 1110, 1050.
menthoxymethyl]pyrrolidinium tetrafluoroborate (solid; m.p.
= 134-136 C; yield = 82.3%), []20 -61.3; H NMR (400
o
1
D
MHz, CDCl3, ): 4.62, 4.59 (d, J = 8.1 Hz, 2H), 3.63 (t, J =
5.8 Hz, 2H), 3.45 (t, J = 5.8 Hz, 2H), 3.44 (dt, J = 3.8, 7.9 Hz,
1H), 3.10 (s, 3H), 2.22 (t, J = 5.9 Hz, 4H), 2.06-0.90 (m, 9H),
0.89 (d, J = 7.8 Hz, 6H), 0.78 (d, J = 7.9 Hz, 3H); 13C NMR
(100 MHz, CDCl3, δ): 87.3, 81.6, 61.2(2C), 48.2, 48.0, 40.3,
34.1, 31.2, 25.9, 22.8, 22.3, 22.1, 21.1(2C), 15.9; IR (/cm-1):
2990, 2915, 1110, 940.
Table
1,
1a:
Butyl
[(1R,2S,5R)-(-)-
Table
1,
1f:
Methyl
[(1R,2S,5R)-(-)-
menthoxymethyl]pyrrolidinium tetrafluoroborate (semisolid;
menthoxymethyl]pyrrolidinium hexafluorophosphate (solid;
yield = 84.5%), []20 -52.4; 1H NMR (400 MHz, CDCl3, ):
D
m.p. = 178-181 C; yield = 81.0%), []20 -53.3; H NMR
o
1
D
4.55, 4.47 (d, J = 8.1 Hz, 2H), 3.61 (t, J = 5.8 Hz, 2H), 3.45 (t,
J = 5.8 Hz, 2H), 3.30 (t, J = 5.9 Hz, 2H), 3.12 (dt, J = 4.0, 8.1
Hz, 1H), 2.14 (t, J = 6.1 Hz, 4H), 1.63-1.61 (m, 2H), 1.38-
1.36 (m, 2H), 2.08-0.76 (m, 9H), 0.95 (t, J = 8.8 Hz, 3H), 0.88
(400 MHz, CDCl3, ): 4.56, 4.52 (d, J = 8.0 Hz, 2H), 3.63 (t,
J = 5.8 Hz, 2H), 3.46 (dt, J = 4.4, 8.0 Hz, 1H), 3.40 (t, J = 5.8
Hz, 2H), 3.11 (s, 3H), 2.23 (t, J = 5.9 Hz, 4H), 2.04-0.91 (m,
9H), 0.89 (d, J = 7.9 Hz, 6H), 0.78 (d, J = 7.8 Hz, 3H); 13C

6
NMR (100 MHz, CDCl3, δ): 87.4, 81.7, 61.3(2C), 48.2, 48.1,
40.2, 34.1, 31.3, 25.9, 22.7, 22.4, 22.1, 21.1(2C), 15.8; IR
(/cm-1): 2995, 2920, 1200, 1050.
5.8 Hz, 4H), 1.50-1.47 (m, 2H), 1.20-1.18 (m, 2H), 2.05–
0.90 (m, 9H), 0.91 (t, J = 7.2 Hz, 3H), 0.88 (d, J = 7.0 Hz,
3H), 0.76 (d, J = 6.7 Hz, 3H), 0.68 (d, J = 6.5 Hz, 3H); 13C
NMR (100 MHz, CDCl3, δ): 164.5, 77.4, 71.0, 64.3, 64.2,
60.9, 46.5, 40.4, 33.7, 31.3, 26.2, 25.6, 22.9, 21.8, 21.6, 21.0,
20.6, 19.6, 16.1, 13.6; IR (/cm-1): 2983, 1742, 1188, 1091.
Table
1,
1g:
Methyl
[(1R,2S,5R)-(-)-
menthoxymethyl]pyrrolidinium
bis(trifluoromethane)sulfonamide (semisolid; yield = 84.4%),
[]20 -36.3; 1H NMR (400 MHz, CDCl3, ): 4.55, 4.50 (d, J
Table
2,
2a:
Butyl
[(1R,2S,5R)-(-)-
D
menthoxyacetyl]pyrrolidinium tetrafluoroborate (solid; m.p. =
= 8.0 Hz, 2H), 3.56 (t, J = 5.9 Hz, 2H), 3.42 (dt, J = 4.4, 8.0
Hz, 1H), 3.38 (t, J = 5.9 Hz, 2H), 3.03 (s, 3H), 2.20 (t, J = 5.8
Hz, 4H), 2.02-0.90 (m, 9H), 0.87 (d, J = 7.8 Hz, 6H), 0.75 (d,
J = 7.9 Hz, 3H); 13C NMR (100 MHz, CDCl3, δ): 121.8,
118.9, 87.7, 81.7, 61.4(2C), 48.1, 48.0, 40.2, 34.0, 31.2, 25.9,
22.8, 22.2, 22.1, 21.9(2C), 15.7; IR (/cm-1): 2996, 2912,
1290, 1030.
52-54 oC; yield = 81.7%), []20 - 42.1; 1H NMR (400 MHz,
D
CDCl3, ): 4.77 (dt, J = 4.0, 10.7 Hz, 1H), 4.13, 4.11 (d, J =
7.6 Hz, 2H), 3.79 (t, J = 5.8 Hz, 4H), 3.37 (t, J = 5.9 Hz, 2H),
2.23 (t, J = 5.7 Hz, 4H), 1.67-1.65 (m, 2H), 1.36-1.34 (m,
2H), 2.12–0.98 (m, 9H), 0.92 (t, J = 7.1 Hz, 3H), 0.87 (d, J =
7.0 Hz, 3H), 0.76 (d, J = 6.6 Hz, 3H), 0.69 (d, J = 6.6 Hz,
3H); 13C NMR (100 MHz, CDCl3, δ): 164.4, 77.6, 71.5, 64.7,
64.5, 61.1, 46.7, 40.4, 34.6, 31.5, 25.9, 25.7, 23.2, 22.2, 21.9,
21.0, 20.7, 19.6, 16.0, 13.5; IR (/cm-1): 2973, 1748, 1211,
1033.
Table
1,
1h:
Methyl
[(1R,2S,5R)-(-)-
menthoxymethyl]pyrrolidinium L-lactate (semisolid; yield =
1
86.4%), []20 -67.8; H NMR (400 MHz, CDCl3, ): 4.89,
D
4.73 (d, J = 7.0 Hz, 2H), 3.94 (q, J = 5.4 Hz, 1H), 3.80 (t, J =
5.8 Hz, 2H), 3.64 (t, J = 5.8 Hz, 2H), 3.48 (dt, J = 4.4, 8.0 Hz,
1H), 3.28 (s, 3H), 2.76 (bs, 1H, OH), 2.25 (t, J = 5.9 Hz, 4H),
1.55 (d, J = 5.9 Hz, 3H), 2.14-0.92 (m, 9H), 0.87 (d, J = 7.8
Hz, 6H), 0.82 (d, J = 7.9 Hz, 3H); 13C NMR (100 MHz,
CDCl3, δ): 180.1, 87.3, 81.5, 71.4, 61.0(2C), 48.6, 48.2, 40.2,
34.0, 31.6, 25.9, 22.3, 22.2, 22.1, 21.1(2C), 21.0, 16.1; IR
(/cm-1): 3580-2525 (br), 2970, 1730, 1200, 1025.
Table
2,
2b:
Butyl
[(1R,2S,5R)-(-)-
menthoxyacetyl]pyrrolidinium hexafluorophosphate (solid;
m.p. = 38-39 oC; yield = 87.7%), []20 -40.2; 1H NMR (400
D
MHz, CDCl3, ): 4.76 (dt, J = 4.2, 11.0 Hz, 1H), 4.07, 4.02
(d, J = 7.6 Hz, 2H), 3.67 (t, J = 5.9 Hz, 4H), 3.37 (t, J = 5.4
Hz, 2H), 2.21 (t, J = 5.7 Hz, 4H), 1.60-1.58 (m, 2H), 1.39-
1.36 (m, 2H), 2.09–0.92 (m, 9H), 0.93 (t, J = 7.0 Hz, 3H),
0.88 (d, J = 7.0 Hz, 3H), 0.76 (d, J = 6.7 Hz, 3H), 0.71 (d, J =
6.7 Hz, 3H); 13C NMR (100 MHz, CDCl3, δ): 164.1, 77.4,
71.6, 64.8, 64.6, 61.4, 46.7, 40.3, 33.9, 31.7, 25.3, 25.0, 23.4,
21.9, 21.8, 21.6, 20.7, 19.5, 16.0, 13.4; IR (/cm-1): 2979,
1750, 1207, 1056.
16. Procedure for the synthesis of (1R,2S,5R)-(-)-menthyl
chloroacetate: (1R,2S,5R)-(-)-menthol (0.10 mol) was reacted
with chloroacetyl chloride (0.11 mol) and trimethylamine
(0.11 mol) in THF, stirring overnight at room temperature.
After the reaction time, the solvent was evaporated and the
product was purified by silica gel flash column
chromatography using a gradient mixture of hexanes/ethyl
Table
2,
2c:
Butyl
[(1R,2S,5R)-(-)-
menthoxyacetyl]pyrrolidinium
bis(trifluoromethane)sulfonimide (liquid; yield = 92.8%)
1
[]20 -32.1; H NMR (400 MHz, CDCl3, ): 4.80 (dt, J =
1
acetate as the mobile phase. (85.6%); H NMR (400 MHz,
D
CDCl3, ): 4.70 (dt, J = 6.0, 11.0 Hz, 1H), 3.97 (s, 2H), 2.14-
0.91 (m, 9H), 0.86 (d, J = 7.9 Hz, 6H), 0.73 (d, J = 7.8 Hz,
3H); 13C NMR (100 MHz, CDCl3, δ): 166.9, 87.4, 81.7,
61.3(2C), 48.2, 48.1, 40.2, 34.1, 31.3, 25.9, 22.7, 22.4, 22.1,
21.1(2C), 15.8; IR (/cm-1): 2995, 2920, 1200, 1050.
4.0, 10.6 Hz, 1H), 4.10, 4.09 (d, J = 7.5 Hz, 2H), 3.70 (t, J =
5.8 Hz, 4H), 3.38 (t, J = 5.4 Hz, 2H), 2.24 (t, J = 5.7 Hz, 4H),
1.67-1.66 (m, 2H), 1.41-1.37 (m, 2H), 2.13–0.98 (m, 9H),
0.95 (t, J = 6.8 Hz, 3H), 0.88 (d, J = 7.0 Hz, 3H), 0.77 (d, J =
6.7 Hz, 3H), 0.72 (d, J = 6.7 Hz, 3H); 13C NMR (100 MHz,
CDCl3, δ): 164.1, 120.9, 118.0, 77.2, 71.5, 64.7, 64.6, 61.4,
46.7, 40.3, 33.9, 31.7, 25.6, 25.2, 23.6, 21.8, 21.7, 21.0, 20.6,
19.5, 16.0, 13.3; IR (/cm-1): 2991, 1744, 1284, 1006.
17. Representative Procedure for the Synthesis of alkyl
[(1R,2S,5R)-(-)-menthoxyacetyl]pyrrolidinium ionic liquids
(2a – 2h): In a round-bottomed flask, 1-alkylpyrrolidine (0.01
mol) was mixed with (1R,2S,5R)-(-)-menthyl chloroacetate
(0.01 mol) in acetonitrile under nitrogen atmosphere. The
reaction mixture was heated to reflux for 48 h. After the
reaction time, the solvent was evaporated using a rotary
evaporator and the resultant, alkyl [(1R,2S,5R (-)-1-
menthoxyacetyl]pyrrolidinium chloride, was dried in a
vacuum line overnight. In the second step, chloride of the
ionic liquid was replaced with tetrafluoroborate,
hexafluorophosphate, bistrifluoromethane sulfonimide, or L-
lactate by reacting with HBF4, KPF6, or bis(trifluoromethane)
sulfonimide lithium salt in water or sodium L-lactate in
acetone, respectively. The product was extracted into
methylene chloride (2 x 10 mL) and the combined organic
layers were dried with anhydrous Na2SO4. The solvent was
evaporated using a rotary evaporator and the final ionic
liquids were dried in a vacuum line prior to characterization.
Table
2,
2d:
Butyl
[(1R,2S,5R)-(-)-
menthoxyacetyl]pyrrolidinium L-lactate (semisolid; yield =
1
84.4%), []20 -39.8; H NMR (400 MHz, CDCl3, ): 4.65
D
(dt, J = 4.0, 10.4 Hz, 1H), 4.62, 4.36 (d, J = 7.6 Hz, 2H), 4.05
(q, J = 5.5 Hz, 1H), 3.75 (t, J = 5.7 Hz, 4H), 3.42 (t, J = 5.9
Hz, 2H), 2.93 (bs, 1H, OH), 2.20 (t, J = 5.6 Hz, 4H), 1.55-
1.52 (m, 2H), 1.29-1.26 (m, 2H), 1.19 (d, J = 6.0 Hz, 3H),
2.07–0.98 (m, 9H), 0.88 (t, J = 6.7 Hz, 3H), 0.76 (d, J = 7.0
Hz, 3H), 0.74 (d, J = 6.8 Hz, 3H), 0.73 (d, J = 6.8 Hz, 3H);
13C NMR (100 MHz, CDCl3, δ): 182.4, 164.7, 77.6, 71.1,
67.9, 64.4, 64.0, 60.2, 46.6, 40.5, 34.5, 31.6, 25.6, 25.3, 23.6,
21.8, 21.6, 21.2, 20.7, 20.3, 19.7, 16.0, 13.5; IR (/cm-1):
2996, 1758, 1749, 1233, 1016.
Methyl
[(1R,2S,5R)-(-)-menthoxyacetyl]pyrrolidinium
chloride (91%), []20 -54.0; 1H NMR (400 MHz, CDCl3, ):
D
4.91, 4.75 (d, J = 11.1 Hz, 2H), 4.71 (dt, J = 4.5, 11.1 Hz,
1H), 3.98 (t, J = 5.8 Hz, 4H), 3.37 (s, 3H), 2.20 (t, J = 5.8 Hz,
4H), 2.05–0.95 (m, 9H), 0.90 (d, J = 7.5 Hz, 3H), 0.80 (d, J =
6.7 Hz, 3H), 0.76 (d, J = 6.9 Hz, 3H); 13C NMR (100 MHz,
CDCl3, δ): 165.0, 77.6, 71.1, 65.2, 65.1, 50.1, 46.4, 40.6, 33.7,
31.5, 26.1, 23.1, 21.8, 21.4, 21.0, 20.8, 16.1; IR (/cm-1):
2980, 1740, 1180, 1090.
18. All products exhibited spectral properties consistent
with the assigned structures. Butyl [(1R,2S,5R)-(-)-
menthoxyacetyl]pyrrolidinium chloride (87%), []20 - 35.2;
D
1H NMR (400 MHz, CDCl3, ): 4.60 (dt, J = 4.2, 10.1 Hz,
1H), 4.54, 4.27 (d, J = 10.6 Hz, 2H), 3.98 (t, J = 5.8 Hz, 2H),
3.70 (t, J = 5.8 Hz, 2H), 3.39 (t, J = 5.8 Hz, 2H), 2.13 (t, J =
Table
2,
2e:
Methyl
[(1R,2S,5R)-(-)-
menthoxyacetyl]pyrrolidinium tetrafluoroborate (solid; m.p. =

7
o
63-64 C; yield = 85.1%), []20 -49.7; 1H NMR (400 MHz,
4.9, 11.0 Hz, 1H), 4.21, 4.18 (d, J = 5.4 Hz, 2H), 3.78 (t, J =
D
5.9 Hz, 2H), 3.66 (t, J = 5.9 Hz, 2H), 3.24 (s, 3H), 2.26 (t, J =
5.8 Hz, 4H), 2.15-0.96 (m, 9H), 0.90 (d, J = 7.2 Hz, 3H), 0.79
(d, J = 7.0 Hz, 3H), 0.77 (d, J = 7.1 Hz, 3H); 13C NMR (100
MHz, CDCl3, δ): 164.2, 121.9, 119.0, 78.0, 71.6, 65.8, 65.7,
50.1, 46.7, 40.4, 34.6, 31.7, 26.2, 23.2, 21.8, 21.5, 21.0, 20.6,
16.2; IR (/cm-1): 2986, 1744, 1222, 1025.
CDCl3, ): 4.76 (dt, J = 4.7, 11.2 Hz, 1H), 4.26, 4.25 (d, J =
7.0 Hz, 2H), 3.78 (t, J = 5.8 Hz, 2H), 3.68 (t, J = 5.8 Hz, 2H),
3.25 (s, 3H), 2.24 (t, J = 5.8 Hz, 4H), 2.12–0.90 (m, 9H), 0.90
(d, J = 6.8 Hz, 3H), 0.84 (d, J = 7.6 Hz, 3H), 0.77 (d, J = 6.8
Hz, 3H); 13C NMR (100 MHz, CDCl3, δ): 164.5, 77.4, 71.6,
65.5 (2C), 50.1, 46.7, 40.2, 34.6, 31.5, 25.9, 23.3, 21.9, 21.6,
21.1, 20.7, 16.1; IR (/cm-1): 2994, 1742, 1220, 1060.
Table
2,
2h:
Methyl
[(1R,2S,5R)-(-)-
menthoxyacetyl]pyrrolidinium L-lactate (semisolid; yield =
Table
2,
2f:
Methyl
[(1R,2S,5R)-(-)-
1
84.1%), []20 -48.0; H NMR (400 MHz, CDCl3, ): 4.89
menthoxyacetyl]pyrrolidinium hexafluorophosphate (solid;
D
m.p. = 64-66 oC; yield = 90.3%), []20 -48.6; 1H NMR (400
(dt, J = 4.9, 11.0 Hz, 1H), 4.41, 4.37 (d, J = 5.4 Hz, 2H), 4.10
(q, J = 4.5 Hz, 1H), 3.78 (t, J = 5.4 Hz, 2H), 3.66 (t, J = 5.4
Hz, 2H), 3.26 (s, 3H), 2.25 (t, J = 5.8 Hz, 4H), 1.32 (d, J = 5.8
Hz, 3H), 2.03-0.90 (m, 9H), 0.91 (d, J = 7.2 Hz, 3H), 0.88 (d,
J = 6.8 Hz, 3H), 0.78 (d, J = 7.1 Hz, 3H); 13C NMR (100
MHz, CDCl3, δ): 182.4, 164.2, 77.8, 68.6 (2C), 66.2, 62.7,
49.9, 46.6, 40.1, 34.1, 31.5, 26.2, 23.4, 23.3, 23.4, 21.8, 20.5,
20.4, 16.0; ; IR (/cm-1): 3555-2480 (br), 1744, 1734, 1218,
1009.
D
MHz, CDCl3, ): 4.78 (dt, J = 4.8, 11.1 Hz, 1H), 4.17, 4.12
(d, J = 5.9 Hz, 2H), 3.78 (t, J = 5.7 Hz, 2H), 3.64 (t, J = 5.7
Hz, 2H), 3.23 (s, 3H), 2.25 (t, J = 5.8 Hz, 4H), 2.14-0.91 (m,
1H), 0.90 (d, J = 6.9 Hz, 3H), 0.85 (d, J = 6.0 Hz, 3H), 0.79
(d, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3, δ): 164.3,
77.9, 71.6, 65.7 (2C), 50.1, 46.7, 40.4, 34.6, 31.5, 26.1, 23.2,
21.9, 21.6, 21.1, 20.7, 16.2; IR (/cm-1): 2990, 1745, 1217,
1053.
Table
2,
2g:
Methyl
[(1R,2S,5R)-(-)-
menthoxyacetyl]pyrrolidinium
bis(trifluoromethane)sulfonamide (liquid; yield = 82.6%),
1
[]20 -35.8; H NMR (400 MHz, CDCl3, ): 4.79 (dt, J =
D

8
Highlights

A series of pyrrolidinium-based chiral ionic liquids bearing
a chiral cation, a chiral anion or both was prepared in
good yields.



The synthesis used an efficient, economic and simple
pathway.
The chirality was introduced using inexpensive and readily
available compounds from a chiral pool.
The new chiral ionic liquids were characterized by both
spectroscopy and polarimetry.