Synthesis, characterization and applications of some novel DMAP-based chiral ionic liquids

Article abstract of DOI:10.1016/j.molliq.2018.06.058

A convenient and efficient procedure for the synthesis of some novel chiral ionic liquids (CILs) from 4-dimethylaminopyridinium cation has been reported. The synthesis of the CILs includes the treatment of optically active (?)-menthyl ester with 4-dimethy

Full text of DOI:10.1016/j.molliq.2018.06.058

Accepted Manuscript
Synthesis, characterization and applications of some novel
DMAP-based chiral ionic liquids
Avtar Singh, Harish Kumar Chopra
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DOI:
Reference:
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doi:10.1016/j.molliq.2018.06.058
MOLLIQ 9256
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14 June 2018
Please cite this article as: Avtar Singh, Harish Kumar Chopra , Synthesis, characterization
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doi:10.1016/j.molliq.2018.06.058
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ACCEPTED MANUSCRIPT
Synthesis, Characterization and Applications of Some Novel DMAP-based
Chiral Ionic Liquids
Avtar Singh and Harish Kumar Chopra*
*Department of Chemistry, Sant Longowal Institute of Engineering and Technology, Longowal -
148106,
Distt. Sangrur (Pb.), India, Email: hk67@rediffmail.com,
Tel: +91-1672-253204, Fax: +91-1672-280072.
______________________________________________________________________________
Abstract
A convenient and efficient procedure for the synthesis of some novel chiral ionic liquids (CILs)
from 4-dimethylaminopyridinium cation has been reported. The synthesis of the CILs includes
the treatment of optically active (-)-menthyl ester with 4-dimethylaminopyridine and after that
the anion exchange reactions in water. The synthesized ionic salts have been characterized using
polarimetry, NMR spectroscopy and EI-MS techniques. The synthesized CIL was used in chiral
recognition of Mosher’s acid by 1H NMR and also to induce the enantioselectivity in the sodium
borohydride reduction of some prochiral ketones.
Keywords: Chiral Ionic Liquids; Asymmetric reduction; Enantiomeric excess; Chirality; Chiral
recognition.
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1. Introduction
Ionic liquids (ILs), due to their non-volatility, have appeared as the lucrative alternative to the
volatile organic compounds [1-3]. These compounds exhibit several peculiar properties such as
low vapour pressure, wide electrochemical potential window, solvent and catalytic potential,
reusability etc [4-5]. The most commonly synthesized ILs are N,N-dialkyl imidazolium, N-alkyl
pyridinium, tetra-alkyl phosphonium and tetra-alkyl ammonium salts. ILs are composed of ions
only and are very important in the field of organic synthesis and catalysis [6-7], analytical
techniques [8-10], energy storage [11-12] and biotechnology [13] etc.
CILs are the compounds which consist of any sort of chirality in the cation or anion or in both
cation and anion. They possess all the above-quoted properties of the ionic liquids and are further
important due to their chiral discrimination properties. They exhibit prominent applications in
asymmetric synthesis and organocatalysis [14-17], polymerization [18-19], resolution of
racemates [20-21] etc. In some cases, CILs provide better results in catalysis than enzyme and
transition-metal based catalysts. Their most advantageous property is that they can be recovered
and reused in the reaction procedures [22-23]. These can be used as chiral additives and/or chiral
stationary phase in advanced analytical methods such as liquid/gas chromatography [24-25] and
capillary electrophoresis [26-27]. One can aim at the synthesis of CILs either from the chiral
pool or by asymmetric synthetic methods. The chiral pool based synthesis is preferable because
of the availability of the inexpensive chiral building blocks.
Chiral recognition is a diastereomeric interaction between a chiral selector and the two
enantiomers of the racemate which leads to their enantiodifferentiation. Chiral recognition plays
an important role in the determination of absolute configuration and chirality transfer
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mechanisms. CILs are also important in chiral recognition of numerous compounds using
spectroscopic methods [28-31].
The synthesis and separation of the chiral molecules is an important aspect of chemistry and
biology. The chiral secondary alcohols are valuable compounds in pharmaceutics and
agrochemicals. Many reports about the synthesis of these scaffolds using metal and biocatalysts
can be found in the recent literature [32-34]. CILs are also important in context to the synthesis
of these compounds [35-37]. We have already reported the synthesis of some CILs from the
natural chiral materials for their application in asymmetric sodium borohydride reduction [38-
40].
In this report, we have provided a straightforward method for the synthesis of DMAP-based
CILs and also studied their application in chiral molecular recognition and enantioselective
sodium borohydride reduction reactions. Although there are some examples about the synthesis
of simple ionic liquids from DMAP moiety [41-42], to the best of our knowledge, it is the first
report about the synthesis of CILs from DMAP. The easily available and cheap starting
materials; very moderate reaction conditions and excellent yields are the advantageous points of
these CILs. Moreover, these CILs are also valuable due to their multifaceted applications in
chiral recognition and organocatalysis.
2. Experimental
2.1 Materials and methods
All the chemicals were purchased from Sigma-Aldrich, Acros Organics, Alfa Aesar and LOBA
Chemie and were used as such unless stated otherwise. The solvents were dried using
appropriate drying techniques. The pre-coated Merck TLC silica gel 60 sheets were used to
monitor the progress of all the reactions. Optical rotation values were measured on Anton Paar
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polarimeter MCP 500 at 589 nm using a cell of length 1 dm at room temperature. Melting points
of all the synthesized compounds were determined by using a digital melting point apparatus and
are reported as such. The mass spectra were taken on a Shimadzu GCMS-QP 2010 Ultra in
1
31
electron ionization (EI) mode. H, 13C, 11B and P NMR spectra of all the salts were taken on a
1
Bruker Advance II, 400 MHz NMR spectrometer. In chiral recognition experiments, H NMR
spectra were recorded on a 400 MHz JEOL ECS instrument. The enantiomeric excess of the
synthesized secondary alcohols has been determined by using GC-FID analysis using a
Shimadzu GCMS-QP 2010 Ultra in split mode. Before injection, samples were dissolved in
HPLC grade methanol and passed through a 0.22 μm syringe filters.
2.2 Procedure for the quaternization reaction (Synthesis of CIL 2)
The synthesis of (-)-menthyl chloroacetate has been carried out according to our previously
reported procedure [38]. Next, to a solution of 4-dimethylaminopyridine (4 mmol, 489 mg), an
equimolar quantity of (-)-menthyl chloroacetate was added. The reaction mixture was then
o
refluxed at 70 C. The progress of the reaction was checked by TLC (chloroform:methanol).
After completion of the reaction, 15 ml of 1 N sulphuric acid was added and the product
extraction was carried out using dichloromethane (3×10). The combined dichloromethane layers
were then dried over anhydrous Na2SO4. Finally, the solvent was removed in vaccuo and the CIL
2 was obtained in good yield (78%).
2.2.1 4-(dimethylamino)-1-(2-((1R,2S,5R)-2-isopropyl-5-methylcyclohexyloxy)-2-oxoethyl)-
pyridinium chloride (2)
Produced as white solid in 78% yield, mp: 242-244 oC, [α]D25= -45.9o (c 0.25, MeOH), 1H NMR
(CDCl3, 400MHz): δ 8.47-8.45 (d, 2H, J=7.52, Ar), 6.96-6.94 (d, 2H, J=7.52, Ar), 5.57-5.52 (d,
1H, J=17.52, -NCH2), 5.41-5.36 (d, 1H, J=17.52, -NCH2), 4.79-4.72 (td, 1H, J=4.44 and J=6.48,
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-OCH), 3.28 (s, 6H, -N(CH3)2), 2.03-2.0 (m, 1H), 1.86-1.82 (m, 1H), 1.70-1.66 (m, 2H), 1.46-
1.39 (m, 2H), 1.10-1.01 (m, 2H), 0.91-0.85 (m, 7H, isopropyl group of menthol), 0.75-0.73 (d,
3H, J=6.92 methyl group of the menthol). 13C NMR (CDCl3, 100MHz): δ 166.84, 156.54, 143.86
107.68, 57.56, 46.77, 40.63, 40.52, 33.95, 31.45, 26.07, 23.15, 21.93, 20.85, 16.17. EI-MS: m/z
= 319(M+cation), m/z = 289(M+cation-2CH3).
2.3 General procedure for the synthesis of CILs (3-7)
The synthesized chloride salt (2 mmol) was dissolved in 15-20 ml of distilled water and small
excess of the various sodium or potassium salts has been added. The reaction mixture was then
stirred overnight at room temperature. The products were extracted with dichloromethane and
dried over anhydrous Na2SO4. The solvent was evaporated using a rotary evaporater to afford
excellent yields of the CILs (3-7).
2.3.1 4-(dimethylamino)-1-(2-((1R,2S,5R)-2-isopropyl-5-methylcyclohexyloxy)-2-oxoethyl)-
pyridinium tetrafluoroborate (3)
o
1
Produced as off-white solid in 92% yield. mp: 134-138 C, [α]D25= -41.6o (c 0.25, MeOH), H
NMR (CDCl3, 400MHz): δ 7.96-7.94 (d, 2H, J=7.52, Ar), 6.88-6.86 (d, 2H, J=7.56, Ar), 4.95 (s,
2H, -NCH2), 4.79-4.73 (td, 1H, J=4.44 and J=6.52, -OCH), 3.24 (s, 6H, -N(CH3)2), 2.03-2.0 (m,
1H), 1.90-1.81 (m, 1H), 1.70-1.66 (m, 2H), 1.47-1.36 (m, 2H), 1.09-0.98 (m, 2H), 0.91-0.85 (m,
13
7H, isopropyl group of menthol), 0.75-0.73 (d, 3H, J=6.92, methyl group of the menthol). C
NMR (CDCl3, 100MHz): δ 166.91, 156.53, 143.07, 107.67, 57.50, 46.80, 40.47, 40.28, 33.95,
31.44, 26.06, 23.18, 21.93, 20.78, 16.12. 11B NMR (CDCl3, 400MHz): δ -1.00 (s). EI-MS: m/z =
319(M+cation), m/z = 289(M+cation-2CH3).
2.3.2 4-(dimethylamino)-1-(2-((1R,2S,5R)-2-isopropyl-5-methylcyclohexyloxy)-2-oxoethyl)-
pyridinium hexafluorophosphate (4)
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o
1
Produced as off-white solid in 89% yield. mp: 126-130 C, [α]D25= -39.1o (c 0.25, MeOH), H
NMR (CDCl3, 400MHz): δ 7.86-7.84 (d, 2H, J=7.68, Ar), 6.84-6.82 (d, 2H, J=7.72, Ar), 4.86 (s,
2H, -NCH2), 4.79-4.73 (td, 1H, J=4.44, and J=6.48, -OCH), 3.23 (s, 6H, -N(CH3)2), 2.00-1.99
(m, 1H), 1.84-1.80 (m, 1H), 1.71-1.66 (m, 2H), 1.47-1.37 (m, 2H), 1.10-1.01 (m, 2H), 0.91-0.85
(m, 7H, isopropyl group of menthol), 0.75-0.73 (d, 3H, J=6.92, methyl group of the menthol).
13C NMR (CDCl3, 100MHz): δ 166.22, 156.52, 142.76, 107.67, 57.48, 46.78, 40.40, 40.29,
31
33.93, 31.44, 26.06, 23.17, 21.90, 20.75, 16.07. P NMR (CDCl3, 400MHz): δ -131.16-157.56
(hept). EI-MS: m/z = 319(M+cation), m/z = 289(M+cation-2CH3).
2.3.3 4-(dimethylamino)-1-(2-((1R,2S,5R)-2-isopropyl-5-methylcyclohexyloxy)-2-oxoethyl)-
pyridinium hexafluoroantimonate (5)
o
1
Produced as off-white solid in 86% yield. mp: 104-106 C, [α]D25= -30.6o (c 0.25, MeOH), H
NMR (CDCl3, 400MHz): δ 7.88-7.86 (d, 2H, J=7.68, Ar), 6.85-6.83 (d, 2H, J=7.68, Ar), 4.89 (s,
2H, -NCH2), 4.79-4.73 (td, 1H, J=4.44, and J=6.48, -OCH), 3.22 (s, 6H, -N(CH3)2), 2.03-2.00
(m, 1H), 1.84-1.80 (m, 1H), 1.70-1.66 (m, 2H), 1.47-1.38 (m, 2H), 1.10-0.98 (m, 2H), 0.93-0.82
(m, 7H, isopropyl group of menthol), 0.75-0.73 (d, 3H, J=6.92, methyl group of the menthol).
13CNMR (CDCl3, 100MHz): δ 166.43, 156.56, 142.84, 107.76, 57.64, 46.78, 40.46, 40.30, 33.93,
31.44, 26.13, 23.18, 21.96, 20.76, 16.10. EI-MS: m/z = 319(M+cation), m/z = 289(M+cation-2CH3).
2.3.4 4-(dimethylamino)-1-(2-((1R,2S,5R)-2-isopropyl-5-methylcyclohexyloxy)-2-oxoethyl)-
pyridinium bromoethanesulfonate (6)
o
1
Produced as off-white solid in 87% yield. mp: 138-142 C, [α]D25= -37.1o (c 0.25, Acetone), H
NMR (CDCl3, 400MHz): δ 8.23-8.21 (d, 2H, J=7.68, Ar), 6.93-6.91 (d, 2H, J=7.68, Ar), 5.24-
5.11 (q, 2H, J=17.76 and J=16.56, -NCH2), 4.80-4.74 (td, 1H, J=4.44 and J=6.48, -OCH), 3.74-
3.70 (m, 2H), 3.32-3.28 (m, 2H), 3.27 (s, 6H, -N(CH3)2), 2.03-2.00 (m, 1H), 1.85-1.81 (m, 1H),
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1.71-1.67 (m, 2H), 1.48-1.38 (m, 2H), 1.11-0.99 (m, 2H), 0.93-0.84 (m, 7H, isopropyl group of
menthol), 0.76-0.74 (d, 3H, J=6.96, methyl group of the menthol). 13C NMR (CDCl3, 100MHz):
δ 166.70, 156.54, 143.70, 107.71, 57.66, 54.58, 46.74, 40.60, 40.43, 33.91, 31.44, 29.69, 26.67,
26.13, 23.17, 21.94, 20.81, 16.18. EI-MS: m/z = 319(M+cation), m/z = 289(M+cation-2CH3).
2.3.5 4-(dimethylamino)-1-(2-((1R,2S,5R)-2-isopropyl-5-methylcyclohexyloxy)-2-oxoethyl)-
pyridinium trifluoromethanesulfonate (7)
1
Produced as semi-solid in 87% yield, [α]D25= -28.6o (c 0.25, MeOH), H NMR (CDCl3,
400MHz): δ 7.86-7.84 (d, 2H, J=7.76, Ar), 6.84-6.82 (d, 2H, J=7.40, Ar), 5.04 (s, 2H, -NCH2),
4.80-4.73 (td, 1H, J=4.44, and J=6.48, -OCH), 3.24 (s, 6H, -N(CH3)2), 2.02-1.99 (m, 2H), 1.84-
1.80 (m, 1H), 1.71-1.67 (m, 2H), 1.45-1.37 (m, 2H), 1.09-1.01 (m, 2H), 0.92-0.85 (m, 7H,
13
isopropyl group of menthol), 0.75-0.73 (d, 3H, J=6.92, methyl group of the menthol). C NMR
(CDCl3, 100MHz): δ 166.43, 156.57, 143.33, 107.74, 57.66, 46.78, 40.50, 40.44, 33.93, 31.44,
29.71, 26.10, 23.16, 21.91, 20.76, 16.10. EI-MS: m/z = 319(M+cation), m/z = 289(M+cation-2CH3).
2.4 Procedure for the reduction of ketones in the presence of CILs:
The asymmetric sodium borohydride reduction has been carried out according to our previously
reported procedure [39]. The GC chromatograms of synthesized secondary alcohols are given in
the supplementary information file.
(-)-1-Phenylethanol: GC analysis-Rt-βDEXsm column, split mode, carrier gas helium, makeup
gas helium, column oven temperature= 120 oC, injection temperature 230 oC, flow rate 0.80 mL/
min, tR1 = 11.93 min; tR2= 12.10 min.
(-)-1-(4-Bromophenyl)-ethanol: GC analysis-Rt-βDEXsm column, split mode, carrier gas
o
o
helium, makeup gas helium, column oven temperature= 120 C, injection temperature 230 C,
flow rate 0.80 mL/min, tR1 = 19.60 min; tR2= 19.71 min.
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(-)-1-(4-Hydroxyphenyl)-ethanol: GC analysis-Rt-βDEXsm column, split mode, carrier gas
o
o
helium, makeup gas helium, column oven temperature= 120 C, injection temperature 230 C,
flow rate 0.80 mL/min, tR1 = 15.80 min; tR2= 15.89 min.
(-)-1-(4-Methoxyphenyl)-ethanol: GC analysis-Rt-βDEXsm column, split mode, carrier gas
o
o
helium, makeup gas helium, column oven temperature= 120 C, injection temperature 230 C,
flow rate 1.30 mL/min, tR1 = 16.00 min; tR2= 16.07 min.
(-)-1-(4-Chlorophenyl)-ethanol: GC analysis-Rt-βDEXsm column, carrier gas helium, column
oven temperature= 120 oC, injection temperature 230 oC, flow rate 0.80 mL/min, tR1 = 16.64 min;
tR2= 16.73 min.
(-)-1-(4-Methylphenyl)-ethanol: GC analysis-Rt-βDEXsm column, split mode, carrier gas
o
o
helium, makeup gas helium, column oven temperature= 120 C, injection temperature 230 C,
flow rate 0.80 mL/min, tR1 = 15.05 min; tR2= 15.21 min.
(-)-1-(2-Hydroxyphenyl)-ethanol: GC analysis-Rt-βDEXsm column, split mode, carrier gas
helium, makeup gas helium, column oven temperature= 120 oC, injection temperature 230 oC
flow rate 1.30 mL/min, tR1 = 16.02 min; tR2= 16.09 min.
(-)-2,3-Dihydro-1H-inden-1-ol: GC analysis-Rt-βDEXsm column, split mode, carrier gas
o
o
helium, makeup gas helium, column oven temperature= 120 C, injection temperature 230 C,
flow rate 0.80 mL/min, tR1 = 14.46 min (100% ee).
2.5 Procedure for the enantiomeric recognition using Mosher’s acid salt
For recognition experiment, 10.2 mg ( 0.04 equivalent) of racemic Mosher’s acid sodium salt
was added to 42.6 mg ( 0.12 equivalent) of CIL 2, taken in a RBF. Then water was added and the
mixture was stirred overnight for anion exchange. After that, water was removed in vacuo and
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the resultant solid was dissolved in a mixture of CDCl3 and DMSO-d6 then filtered to take the
NMR spectrum.
3. Results and discussion
3.1 Synthesis and characterization of the CILs
In continuation to our efforts towards the synthesis and applications of new CILs from the
natural available chiral precursors [14, 38-40, 43]; herein, we have reported the synthesis and
applications of (-)-menthyl ester based CILs. These CILs can be synthesized under very mild
conditions, as depicted in the Scheme 1, from commercially available (-)-menthol. The synthesis
of (-)-menthyl ester was carried out under ultrasonication in the presence of Iron(III)perchlorate
hexahydrate [38]. After that, quaternization of DMAP was achieved in acetonitrile. The
1
quaternization reaction of DMAP with (-)-menthyl ester occurs by an SN mechanism. In the last
step, anion exchange reactions have been performed at room temperature to produce the CIL (3-
7) containing different anions. All the CILs were obtained in excellent yields and the physical
properties of the CILs are enlisted in Table 1.
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Scheme 1: Synthesis of DMAP-based CIL
Table 1: Physical properties of the DMAP-based CILs
Entry
CIL
Anion
Cl
BF4
PF6
SbF6
Physical State
White solid
Yield
78%
92%
89%
86%
87%
87%
Mp [oC]
242-244
134-138
126-130
104-106
138-142
Semi solid
[α]D25(c 0.25)*
-45.9
1
2
3
4
5
6
2
3
4
5
6
7
Off-white solid
Off-white solid
Off-white solid
Off-white solid
Semi-solid
-41.6
-39.1
-30.6
-37.1
BrCH2CH2SO3
CF3SO3
-28.6
*For CIL 6 (entry 5) acetone was used for dilution, for all the other enteries methanol was used
From the above table, it is evident that melting points of these CILs are dependent on the anion
size; the salts with larger anions exhibit lower melting points. This can be explained by the fact
that with the increase in size, the ions are not closely packed in the lattice thus resulting in the
decrease in melting point. The specific rotation values of all the CILs are found to be negative. In
the 1H NMR spectra, the downfield signals in case of CIL 2 and 6 reveal the strong coordination
of the chloride and bromoethanesulfonate ions with the cationic moieties. An upfield shift of
-
0.71 and 0.62 ppm has been observed for -NCH2 protons when Cl- ion was replaced with PF6
-
and BF4 ions respectively. The almost similar trend was seen in the case of CF3SO3 and SbF6
ions. This upfield effect has also been observed in case of the aromatic protons of the DMAP
ring and the change in chemical shift is more marked in the case of the protons which are close
to the positively charged nitrogen atom of the ring. The effect of various anions on chemical shift
values is given in Table 2. The similar anion effects have also been reported in the literature
[44].
Table 2: Effect of various anions on chemical shift values*
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Entry
CIL
Anion
NCH2 (C12)
5.57 (two d)
4.95 (s)
Ar-CH (C13, C14)
8.47 (d)
Ar-CH (C15, C16)
6.96 (d)
1
2
3
4
5
6
2
3
4
5
6
7
Cl-
-
BF4-
7.96 (d)
7.86 (d)
8.06 (d)
8.23 (d)
6.87 (d)
6.84 (d)
6.90 (d)
6.93 (d)
PF6
4.86 (s)
5.02 (s)
5.84 (q)
4.89 (s)
-
CF3SO3
-
BrCH2CH2SO3
-
SbF6
7.88 (d)
6.85 (d)
*chemical shift values in ppm
3.2 Application of the CILs in asymmetric reduction of prochiral ketones
Our previous reports consist of the use of the CILs in asymmetric sodium borohydride reduction
of some prochiral substrates to the corresponding enantiopure alcohols [38-40]. Here, we have
also employed CIL 2 in the reduction of some acetophenone derivatives (Scheme 2).
Scheme 2: Synthesis of optically active alcohols from prochiral ketones using CIL 2
For the reduction reaction, 1 equivalent of each substrate, 0.1 equivalent of CIL 2 and 1.5
o
equivalent of sodium borohydride was added and the mixture was stirred at 35 C. The optical
purity and percentage yields of the alcohols are mentioned in Table 3.
Table 3: Various parameters for the reduction of ketones
Entry
Substrate
Yield (%)
Enantiomeric excess (%)*
1
2
3
4
5
6
7
8
Acetophenone
76
78
78
75
72
69
72
74
Rac
5
10
13
17
4
p-Cl Acetophenone
p-Br Acetophenone
p-OMe Acetophenone
p-OH Acetophenone
p-Me Acetophenone
o-OH Acetophenone
1-Indanone
8
100
*ee values have been determined by GC analysis on a Rt-βDEXsm capillary column
From the Table 3, one can find that all the substrates can be converted to the corresponding
products in substantial yields. The enantiomeric excess in case of acetophenone, p-methyl
acetophenone is very low. For 1-indanone, the enantiomeric excess is very high (100%). The
11

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excellent enantiomeric excess in case of 1-indanone is probably due to the fact that; the carbonyl
group in 1-indanone is presnt as a part of the ring system so the hydride attack is favourable from
one side only. This favoured attack leads to higher enantiopurity of the corresponding secondary
alcohol. The higher enantiomeric excess in case of 1-indanone can also be found in literature
reports [36]. In all the other cases moderate enantiomeric excess has been achieved. As shown in
Scheme 3, we have also proposed a mechanism for the formation of the optically active
secondary alcohols. In the proposed transition state (TS), there is an interaction between
borohydride anion and the quaternary nitrogen atom of the CIL. The hydride transfer from
borohydride to the ketonic substrate and subsequent proton abstraction from the solvent yields
secondary alcohols.
Scheme 3: Plausible mechanism for the asymmetric reduction
3.3 Application of the CIL 2 in Chiral Recognition by Mosher’s acid
Inspired from the induction of chirality in sodium borohydride reduction; we have also employed
the CIL 2 in the chiral molecular recognition of Mosher’s acid salt. To evaluate the chiral
recognition properties of the synthesized CILs sodium salt of Mosher’s acid was used. The CILs
were treated with Mosher’s acid salt to produce diastereomeric complexes. The chiral
12

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recognition mechanism can be explained on the basis of three-point interaction model [45]. As
depicted in the Fig. 1 the CILs show different interactions with the enantiomers of Mosher’s
acid. There is greater possibility of the H-bonding with –CF3 group, in case of R enantiomer of
the acid than the S enantiomer. The selective interactions of the two enantiomers with CILs leads
to the recognition of the enantiomers. The splitting of the –OCH3 signal was found to be 12 Hz
in case of CIL 2. The similar results for the splitting of the signal of the –OCH3 group of
Mosher’s acid have also been reported by Heckel et al using nicotine based CILs [46].
Fig. 1: Diastereomeric interactions between the two enatiomers of Mosher’s acid salt and CILs
4. Conclusions
To summarize, a number of DMAP based CILs have been synthesized in excellent yields under
1
13
11
very mild conditions. These CILs have been fully characterized using polarimetry, H, C, B,
31P NMR and EI-MS techniques. The synthesized CIL was successfully employed for the chiral
recognition of racemic Mosher’s acid salt through NMR spectroscopy. The CIL has also been
utilised in the asymmetric reduction of some prochiral ketones using sodium borohydride as a
hydrogen source. High yields and low to excellent enantiomeric excess has been obtained in the
reduction of the prochiral ketones.
Acknowledgements
The author (Avtar Singh) gratefully acknowledge the financial assistance from DST (Department
of Science and Technology, MHRD, Govt. of India) under INSPIRE Fellowship scheme
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(INSPIRE Fellow No. IF140327). Authors are thankful to the SAIF/CIL, Panjab University,
Chandigarh for NMR analysis. Authors are also thankful to the Director, Sant Longowal
Institute of Engineering and Technology, Longowal (India) for providing various lab facilities to
carry out this research work. Authors also acknowledge Dr Payal Malik for valuable suggestions.
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Graphical abstract
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Highlights
 Report about the first synthesis of DMAP-based CILs
 A very efficient and simple method for the synthesis of CILs in high yields
 Synthesized CILs were used in enantioselective reductions
 The CILs were also effective in chiral recognition of Mosher’s acid salt
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