New benzimidazolium-based chiral ionic liquids: Synthesis and application in enantioselective sodium borohydride reductions in water

Article abstract of DOI:10.1016/j.tetasy.2016.04.004

New chiral ionic liquids based on benzimidazolium salts have been synthesized from the reaction of (-)-menthol or (-)-borneol, chloroacetic acid and 1-methylbenzimidazole. The structures of these chiral ionic liquids have been confirmed from ¹H

Full text of DOI:10.1016/j.tetasy.2016.04.004

Tetrahedron: Asymmetry xxx (2016) xxx–xxx
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
New benzimidazolium-based chiral ionic liquids: synthesis and
application in enantioselective sodium borohydride reductions in
water
⇑
Avtar Singh, Harish Kumar Chopra
Department of Chemistry, Sant Longowal Institute of Engineering and Technology, Distt. Sangrur (Pb.), Longowal 148106, India
a r t i c l e i n f o
a b s t r a c t
Article history:
New chiral ionic liquids based on benzimidazolium salts have been synthesized from the reaction of (À)-
menthol or (À)-borneol, chloroacetic acid and 1-methylbenzimidazole. The structures of these chiral
ionic liquids have been confirmed from 1H, 13C NMR and mass spectral studies. The application of these
chiral ionic liquids in enantioselective sodium borohydride reductions of prochiral ketones to produce
optically active alcohols has been studied. The effect of the solvent on the enantioselectivity and reusabil-
ity of the chiral catalyst has also been studied.
Received 19 March 2016
Accepted 13 April 2016
Available online xxxx
Ó 2016 Elsevier Ltd. All rights reserved.
1. Introduction
organocatalysts and/or solvents for asymmetric synthesis in
addition to their applications in ligand exchange chromatogra-
Ionic liquids are a class of organic salts, typically containing an
organic cation with a delocalized charge and an inorganic anion.
These have shown great potential due to their unique properties
such as lack of measurable vapor pressure, high thermal stability,
conductivity, reasonable viscosity and recyclability. Such proper-
ties make ionic liquids relatively benign solvents for cleaner pro-
cesses to minimize toxic chemical waste, which has become a
priority for chemical industries. Due to their non-volatile nature
and catalytic properties, the use of ionic liquids in the improve-
ment of organic synthesis is well known. In addition to their use
as solvents and catalysts in synthetic chemistry,1 ionic liquids have
found numerous industrial applications2–7 such as electrolytes in
batteries, fuel cells, liquid crystal displays, as lubricants and addi-
tives and also in liquid–liquid extractions. Based on the presence or
absence of a stereogenic unit, ionic liquids can be divided into two
categories; achiral ionic liquids and chiral ionic liquids. Chiral ionic
liquids can be synthesized by asymmetric synthesis or by using
pre-existing homochiral molecules. The readily availability of nat-
urally occurring homochiral compounds has been proven to be
very beneficial in the synthesis of chiral ionic liquids. Naturally
occurring amino acids,8 carbohydrates,9 terpenoids and alkaloids10
have been employed to synthesize chiral ionic liquids. Over the last
few years, chiral ionic liquids have been found as potential
phy,11 capillary electrophoresis,12 liquid and gas chromatogra-
phy,13 chiral recognition and chiral shift reagents in NMR
spectroscopy.14 In recent years, several reports in the literature
have shown that chiral ionic liquids are also effective organocata-
lysts and/or solvents in enantioselective synthesis.15
Chiral alcohols are important starting materials for the synthe-
sis of many important agrochemicals, food chemicals and pharma-
ceuticals.16 Numerous organocatalysts have been employed for the
synthesis of chiral alcohols.17 The increased interest in the utiliza-
tion of chiral ionic liquids as organocatalysts for asymmetric syn-
thesis has led us to explore the synthesis and applications of
chiral benzimidazolium-based salts, which have not been studied
as much as the main emphasis of the researchers have been on imi-
dazolium-based salts.
Herein we describe the synthesis of new benzimidazolium-
based chiral ionic liquids from commonly available natural chiral
building blocks such as (À)-menthol or (À)-borneol. The synthe-
sized chiral ionic liquids have been characterized by 1H NMR, 13C
NMR, 31P NMR, 11B NMR and EI-MS techniques. The synthesized
salts were found to have high thermal stability and exhibited
excellent fluorescence activity. Furthermore, the application of
these synthesized chiral ionic liquids in enantioselective NaBH4
reductions of prochiral ketones to produce chiral alcohols with
moderate to good enantiomeric excess (ee) have been studied
using acetophenone derivatives. The effect of the solvent on the
enantioselectivity and the reusability of these chiral salts have also
been studied.
⇑
Corresponding author. Tel.: +91 1672 253204; fax: +91 1672 280072.
E-mail address: hk67@rediffmail.com (H.K. Chopra).
http://dx.doi.org/10.1016/j.tetasy.2016.04.004
0957-4166/Ó 2016 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Singh, A.; Chopra, H. K. Tetrahedron: Asymmetry (2016), http://dx.doi.org/10.1016/j.tetasy.2016.04.004

2
A. Singh, H. K. Chopra / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
Various prochiral ketones were reduced to the corresponding
2. Results and discussion
chiral alcohols using NaBH4 in presence of chiral ionic liquid 1a.
Sodium borohydride (1.5 mol) was used for the reduction of ace-
tophenone derivatives (1 mol) and 10 mol % of the catalyst was
found to be sufficient to transfer the chirality. Initially, all of the
synthesized compounds were tested for their catalytic activity,
using o-hydroxyacetophenone as the substrate shown in Table 2;
the enantiomeric excess was highest when chiral ionic liquid 1a
was used as the catalyst.
In continuation of our research to develop new reagents in
organic synthesis,18 we herein describe the synthesis of benzimi-
dazolium-based chiral ionic liquids 1a–d and 2a–d and their appli-
cation in enantioselective NaBH4 reduction of prochiral ketones.
The chiral ionic liquids have been synthesized in a three step
synthetic strategy as described in Scheme 1. For the synthesis of
chiral ionic liquids 1a–d, (À)-menthol was treated with chloroace-
tic acid in the presence of iron(III) perchlorate hydrate as the
catalyst in an ultrasonic bath to produce optically active (À)-menthyl
chloroacetate, which was refluxed with 1-methylbenzimidazole in
MeCN to furnish 1-[(À)-menthoxycarbonylmethylene]-3-methyl
benzimidazolium chloride [AMeMBI]Cl 1a in good yield. In
the last step, anion exchange reactions were carried out with
sodium tetrafluoroborate, potassium hexafluorophosphate and
sodium b-bromoethylsulfonate to produce the chiral ionic liquids,
1-[(À)-menthoxycarbonylmethylene]-3-methyl benzimidazolium
tetrafluoroborate [AMeMBI]BF4 1b, 1-[(À)-menthoxycarbonyl-
methylene]-3-methyl benzimidazolium hexafluorophosphate
[AMeMBI]PF6 1c and 1-[(À)-Menthoxycarbonylmethylene]-3-
methyl benzimidazolium b-bromoethylsulfonate [AMeMBI]OSO2-
CH2CH2Br] 1d, respectively.
Table 2
Optimization of catalyst for asymmetric NaBH4 reduction of o-hydroxyacetophenone
OH
O
chiral ionic liquid (10mol%), NaBH4
H2O
R
CH3
R
CH3
Entry
Chiral ionic liquid
Time (h)
%Yield
%ee*
1
2
3
4
5
6
7
8
1a
1b
1c
1d
2a
2b
2c
2d
2
2
2
2
2
2
2
2
68
72
76
74
76
76
71
74
92
68
79
87
90
85
85
87
*
Determined by chiral HPLC using Chiralcel OD-H column.
O
O
Fe(ClO4)3.6H2O
Cl
N
Cl
Solvent screening was also carried out using 2-hydroxyace-
or
OH
+
HO
RO
CH2Cl2
ultrasonication
tophenone as model substrate. As can be seen from Table 3, the
best enantiomeric excess was obtained using water as the solvent.
The ionic liquid catalyst was obtained from the reaction mixture
and tested for its catalytic activity for the second time and it was
found to have proficient catalytic activity for a second cycle; there
was also significant reduction in catalytic activity for a third cycle.
After optimization of the reaction conditions, a number of ace-
tophenone derivatives were reduced to the corresponding alcohols
as illustrated in Scheme 2.
1 or 2
OH
O
MeCN
reflux
N
O
R
R
X
O
O
Cl
N
N
N
NaX or KX
H2O, RT, 12 h
N
1b-d
2b-d
Table 3
1a or 2a
Solvent optimization for enantioselective NaBH4 reduction
X= -Cl, -BF4, -PF6, -OSO2CH2CH2Br
OH
O
chiral ionic liquid 1a (10mol%), NaBH4
2a: R =
1a
: R =
R
CH3
R
CH3
solvent
Entry Acetophenone/ Chiral ionic Solvent Time (h) %Yield %ee
Scheme 1. Synthetic route for chiral ionic liquids.
NaBH4
liquid
1
2
3
1:1.5
1:1.5
1:1.5
1a
1a
1a
EtOH
MeOH
H2O
2
2
2
62
78
68
92
91
92
All of the synthesized salts exhibited negative specific rotations.
As evident from the literature,19 the specific rotation values of BF4À
based chiral ionic liquids were found to be higher than that of PF6À
based salts. Similarly, chiral ionic liquids 2a–d were synthesized by
replacing (À)-menthol with (À)-borneol. The structures of all of the
chiral ionic liquids synthesized were confirmed from 1H NMR, 13C
NMR and EI-MS technique. Table 1 summarizes the important
physical properties of the chiral ionic liquids.
The reaction times, yields and enantiomeric excesses for various
acetophenone derivatives are given in Table 4. The synthesized
secondary alcohols were characterized by 1H NMR spectroscopy.
The NMR spectra of alcohols were found to be in agreement with
literature reports.20 These chiral alcohols also exhibited negative
Table 1
Physical properties of synthesized chiral ionic liquids
25
a
Entry
Chiral ionic liquid
Name
Physical state
Yield%
[
a
]
Mp [°C]
Td [°C]
D
1
2
3
4
5
6
7
8
1a
1b
1c
1d
2a
2b
2c
2d
[AMeMBI]Cl
[AMeMBI]BF4
[AMeMBI]PF6
[AMeMBI]OSO2CH2CH2Br
[ABoMBI]Cl
[ABoMBI]BF4
[ABoMBI]PF6
[ABoMBI]OSO2CH2CH2Br
White solid
White solid
Off-white solid
White solid
White solid
Off-white solid
Off-white solid
Off-white solid
72
84
81
85
76
86
84
83
À35.7
À25.6
À19.8
À18.6
À22.5
À28.7
À16.2
À15.6
152–155
92–94
102–104
62–64
178–180
107–108
118–120
90–92
225
252
260
220
242
255
262
—
a
Determined by thermogravimetric analysis studies.
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A. Singh, H. K. Chopra / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
3
Thermogravimetric analysis revealed that all of the synthesized
compounds showed good thermal stability. The thermal decompo-
sition temperature of these salts lies in a range of 220–260 °C. The
UV–Vis spectra of these salts show that an absorption maximum
occurs in the wavelength range of 255–280 nm. The fluorescence
excitation and emission wavelength for various compounds are
shown in Table 6.
OH
O
chiral ionic liquid 1a (10mol%), NaBH4
R
CH3
R
CH3
H2O
Scheme 2. Enantioselective reduction of prochiral ketones with NaBH4 using chiral
ionic liquid 1a.
Table 4
Enantioselective reduction of prochiral ketones using NaBH4
Table 6
25
Entry
R
Time (h)
Yield
%ee*
[a]
D
Excitation and emission wavelength for chiral ionic liquids
1
2
3
4
5
6
Ph
2
2.5
2.5
2
2
2
75
72
68
69
76
68
8
72
32
72
8
À23.7
À2.6
Entry
Chiral ionic liquid
Excitation
wavelength (nm)
Emission
wavelength (nm)
4-NO2-Ph
4-Br-Ph
4-OH-Ph
4-OMe-Ph
2-OH-Ph
À27.4
À20.3
À3.4
1
2
3
4
5
6
7
8
1a
1b
1c
1d
2a
2b
2c
2d
271
257
256
271
271
270
270
271
357
385
383
376
354
370
368
373
92
À9.8
*
Determined by chiral HPLC using Chiralcel OD-H column using 2-propanol-
hexane as the mobile phase.
specific rotation values. The enantiomeric excess of these sec-
ondary alcohols were determined by using chiral HPLC.
A plausible mechanism for the asymmetric reduction is shown
in Scheme 3. In the first step of the mechanism, there is interaction
between the quaternary nitrogen atom of the chiral ionic liquid
and the boron atom of the borohydride moiety. Next, a hydride
transfer takes place from the less hindered side and the oxygen
atom abstracts a proton from water to give enantioriched alcohols.
The results obtained for the enantioselective reduction have
also been compared with the reported methods. A comparison of
the results of other asymmetric catalysts with our studies is given
in Table 5.
A graph between wavelength and peak intensity is shown in
Figure 1 and it can be seen that all of the compounds exhibited
good fluorescence activity. The fluorescence activities of 2b and
2c were much higher than the other salts.
1a
1b
1c
1d
2a
2b
2c
2d
400
300
200
100
0
H
OH
H
B
H
R'
N
O
R'
N
H
Cl-
H
H
O
- NaCl
N
NaBH4
+
N
O
HO
R' =
O
300
350
400
450
Wavelength
Figure 1. Fluorescence spectra of synthesized chiral ionic liquids.
Scheme 3. Proposed mechanism for the reduction reaction.
3. Conclusion
From Table 5, it can be seen that chiral ionic liquids are efficient
catalysts in asymmetric NaBH4 reduction reactions with moderate
to high enantiomeric excesses being obtained under mild condi-
tions and small reaction times.
In conclusion, eight new benzimidazolium-based chiral ionic liq-
uids have been synthesized by a three step methodology under mild
conditions. The application to the enantioselective reduction of
prochiral ketones has been studied using these chiral ionic liquids.
These chiral ionic liquids also proved to be very effective organocat-
alysts with high enantioselectivity being observed in NaBH4 reduc-
tions. Furthermore, the synthesized chiral ionic liquids exhibited
good thermal stability and fluorescence activity. The biological
activity and applications of these chiral ionic liquids in molecular
chiral recognition are currently being studied in our laboratory.
Table 5
Comparison of chiral ionic liquid 1a with other catalytic systems
Entry Catalytic system
%ee range Time
References
20a
1
2
Ru(p-cymene)Cl2 + chiral
ionic liquid
40–73
67–95
24 h
[Ru(p-cymene)
Cl2]2 + chiral amino
alcohol
Nicotinium based chiral
ionic liquid
[Ru(p-cymene)
Cl2]2 + chiral amino
alcohol
2–10 h
21
4. Experimental
4.1. General
3
4
27–61
12–71
5–50 min
24–72 h
20b
22
1-Methylbenzimidazole (Acros organics), (À)-menthol and (À)-
5
Chiral PNNP type ligand
84–99
24 h
23
borneol (Merck), iron(III) perchlorate hydrate (Sigma–Aldrich),
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A. Singh, H. K. Chopra / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
chloroacetic acid, sodium tetrafluoroborate, potassium hexafluo-
rophosphate and the sodium salt of 2-bromoethanesulphonic acid
(HIMEDIA) were used as received. The reaction progress was mon-
itored by pre coated Merck TLC silica gel 60 sheets. The melting
points of all the synthesized compounds were determined by melt-
ing point apparatus and are reported uncorrected. Optical rotations
were measured on an Anton Paar polarimeter MCP 500 at 589 nm.
1H, 31P, 11B and 13C NMR spectra were taken in CDCl3 on Bruker
Advance II, 400 MHz NMR spectrometer. 1H chemical shift values
are expressed in ppm relative to TMS. The mass spectra were taken
on Shimadzu GCMS-QP 2010 Ultra in EI mode. HPLC analysis was
carried out on Waters HPLC in normal phase mode using Chiralcel
OD-H column and photodiode array detector. The UV–Visible
absorption spectra were taken on Shimadzu UV-1800 spectropho-
tometer. The fluorescence spectra of 10À4 molar solutions of various
salts were recorded on Shimadzu RF-5301PC spectrofluoropho-
tometer. The thermogravimetric analysis was carried out by using
Hitachi TG/DTA 7200. For thermogravimetric analysis, sample was
heated from 50 °C to 600 °C at a rate of 10 °C/min using nitrogen
as a carrier gas.
4.3.1. 1-[(À)-Menthoxycarbonylmethylene]-3-methyl benzimida-
zolium chloride [AMeMBI]Cl 1a
Yield = 72%, mp = 150–152 °C, [
a
]
25 = À35.7 (c 0.25, EtOH). 1H
D
NMR (CDCl3, 100 MHz): d 11.5 (s, 1H NH), 7.75–7.64 (m, 3H, Ar),
7.5 (m, 1H, Ar), 5.65 (d, 2H, N-CH2), 4.85–4.76 (m, 1 H), 4.29 (s,
3H, NCH3), 2.19 (s, 2H), 2.06–1.98 (d, 1 H), 1.84–1.75 (m, 1H),
1.73–1.65 (m, 2H), 1.49–1.38 (m, 2H), 1.13–0.98 (m, 2H), 0.90–
0.87 (d, 3H, CH3 of isopropyl group), 0.93–0.90 (d, 3H, CH3 of iso-
propyl group), 0.79–0.72 (d, 3H, CH3 of menthol). 13C NMR (CDCl3,
400 MHz):
d 165.30, 144.86, 131.78, 127.48, 122.15, 120.19,
112.84, 109.37, 48.16, 46.92, 40.59, 33.91, 31.38, 26.24, 23.18,
21.95, 20.74, 16.13. EI-MS: 329 [M+cation], m/z = 314 [M+cationÀCH3].
4.3.2. 1-[(À)-Borneoxycarbonylmethylene]-3-methyl benzimida-
zolium chloride [ABoMBI]Cl 2a
Yield = 76%, mp = 178–180 °C [
a]
25 = À22.6 (c 0.25, EtOH). 1H
D
NMR (CDCl3, 400 MHz): d 11.53 (s, 1H), 7.81–7.75 (m, 1H, Ar),
7.71–7.65 (m, 2H, Ar), 7.63–7.59 (m, 1H, Ar), 5.80–5.62 (q, 2H,
NCH2), 5.02–4.72 (d, 1 H), 4.29 (s, 3H, NCH3), 2.41–2.30 (m, 1H),
1.81–1.77 (m, 3H), 1.36–1.20 (m, 2H), 1.12–1.08 (m, 1H),
0.89–0.85 (d, 6H) 0.82 (s, 3H). 13C NMR (CDCl3, 100 MHz): d
165.92, 144.76, 131.71, 131.51, 127.53, 127.38, 113.96, 112.92,
83.39, 48.97, 48.20, 47.97, 44.70, 36.45, 33.89, 27.83, 26.93,
19.61, 18.74, 13.55. EI-MS: m/z = 327 [M+cation], m/z = 312
[M+cationÀCH3].
4.2. Synthesis of (À)-menthyl chloroacetate 1 or (À)-bornyl
chloroacetate 2
To a cold solution 10 mmol of (À)-menthol (1.56 g) or (À)-bor-
neol (1.54 g) in dichloromethane in a round bottom flask was
added a pre-cold solution of chloroacetic acid (20 mmol, 1.89 g).
The mixture was kept in an ice bath for 10 min after which iron
(III) perchlorate hydrate (1 mmol, 354 mg) was added to the mix-
ture. Next, the reaction was carried out in ultra-sonicator bath at
30 °C and the reaction progress was checked by TLC (hexane: chlo-
roform). After completion of the reaction (6 h), the reaction mix-
ture was washed twice with a saturated solution of sodium
bicarbonate to remove the unreacted acid. The organic phase was
collected and dried over anhydrous sodium sulfate. The solvent
was evaporated on a rotary evaporator to afford the corresponding
esters.
4.4. General procedure for anion exchange (synthesis of 1b–d
and 2b–d)
A solution of 1 mmol of chloride salt 1a or 2a in distilled water
was treated with equimolar quantity of various salts (NaBF4, KPF6,
2-BrCH2CH2SO3Na). The reaction mixture was stirred at room tem-
perature for 12 h. Next, the reaction mixture was extracted twice
with CH2Cl2. The organic layer was dried over anhydrous Na2SO4
and then CH2Cl2 was evaporated on a rotary evaporator to give var-
ious chiral ionic liquids 1b–d and 2b–d.
4.4.1. 1-[(À)-Menthoxycarbonylmethylene]-3-methyl benzimida-
4.2.1. (À)-Menthyl chloroacetate 1
zolium tetrafluoroborate [AMeMBI]BF4 1b
Yield = 68%, mp = 35–36 °C, [
a
]
D
25 = À77.1 (c 1, EtOH). 1H NMR
White solid, Yield = 84%, mp = 92–94 °C, [
a]
25 = À25.6 (c 0.25,
D
(CDCl3, 400 MHz): d 4.81–4.73 (m, 1H), 4.3 (s, 2H, CH2), 2.05–
1.98 (d, 1H), 1.9–1.81 (m, 1H), 1.74–1.64 (m, 2H), 1.52–1.38 (m,
2H), 1.12–0.98 (m, 2H) 0.96–0.88 (two d, 6H), 0.79–0.75 (d, 3H).
13C NMR (CDCl3, 100 MHz): d 165.01, 74.63, 45.07, 39.30, 38.74,
32.24, 29.52, 24.36, 21.52, 20.09, 18.83, 14.41.
EtOH). 1H NMR (CDCl3, 400 MHz): d 9.80 (s, 1H, NH), 7.78–7.72
(m, 1H, Ar), 7.72–7.64 (m, 2H, Ar), 7.59–7.52 (m, 1H, Ar), 5.36 (s,
2H, NCH2), 4.85–4.76 (m, 1 H), 4.19 (s, 3H, NCH3), 2.08–1.99 (d,
1H), 1.85–1.75 (m, 1H), 1.69 (broad s, 4H), 1.52–1.47 (t, 2H),
1.15–0.98 (m, 2H), 0.96–0.82 (two d, 6H, two CH3 of isopropyl
group), 0.77–.71 (d, 3H, CH3 of menthol). 13C NMR (CDCl3,
4.2.2. (À)-Bornyl chloroacetate 2
100 MHz): d 165.25, 143.57, 131.80, 127.51, 122.93, 120.23,
Yield = 73%, [
a]
25 = À35 (c 1, EtOH). 1H NMR (CDCl3, 400 MHz):
112.84, 109.37, 47.83, 46.78, 40.44, 33.93, 31.43, 26.22, 23.21,
21.89, 20.70, 16.09. 11B NMR (CDCl3, 400 MHz): d À0.98 (s), EI-
MS: m/z = 328 [McationÀH]+, m/z = 314 [M+cationÀCH3].
D
d 4.71–4.63 (m, 1H), 3.82 (s, 2H), 2.12–2.08 (m, 1H), 1.68–1.61 (m,
1H), 1.51–1.42 (m, 1H), 1.49–1.42 (t, 1H), 1.02–0.94 (m, 2H), 0.75–
0.69 (dd, 1H), 0.66 (s, 3H), 0.63 (s, 3H), 0.59 (s, 3H). 13C NMR
(CDCl3, 100 MHz): d 167.55, 82.08, 48.95, 47.92, 44.81, 41.17,
36.52, 27.95, 26.95, 19.65, 18.80, 13.43.
4.4.2. 1-[(À)-Menthoxycarbonylmethylene]-3-methyl benzimida-
zolium hexafluorophosphate [AMeMBI]PF6 1c
Off-white solid, Yield = 81%, mp = 102–104 °C, [
a]
25 = À19.5 (c
D
4.3. Synthesis of chloride salts; chiral ionic liquid 1a and 2a
0.25, EtOH). 1H NMR (CDCl3, 400 MHz): d 9.15 (s, 1H, NH), 7.76–
7.7.71 (m, 1H, Ar), 7.71–7.63 (m, 2H, Ar), 7.59–7.53 (m, 1H, Ar),
5.23–5.18 (d, 2H), 4.83–4.75 (m, 1 H), 4.11 (t, 3H, NCH3), 2.06–
1.98 (d, 1H), 1.81–1.72 (m, 1H), 1.72–1.59 (m, 3H), 1.48–1.37 (t,
2H), 1.14–0.97 (m, 2H), 0.96–0.82 (two d, 6H, two methyl of iso-
propyl group), 0.77–.71 (d, 3H, CH3 of menthol). 13C NMR (CDCl3,
1-Methylbenzimidazole (5 mmol, 661 mg) was added to a solu-
tion of (À)-menthyl chloroacetate 1 (5 mmol, 1164 mg) or (À)-bor-
nyl chloroacetate
2 (5 mmol, 1151 mg) in acetonitrile. After
mixing, the contents were refluxed and reaction progress was
checked by TLC. After completion of the reaction (48–50 h), water
was added into the flask and the product was extracted twice with
dichloromethane and placed over anhydrous Na2SO4, after which
the solvent was evaporated under reduced pressure on rotary
evaporator to give the products.
400 MHz):
d 165.03, 142.96, 131.74, 127.65, 122.94, 120.25,
113.07, 109.46, 47.76, 46.77, 40.38, 33.92, 31.44, 26.21, 23.20,
21.87, 20.68, 16.04. 31P NMR (CDCl3, 400 MHz): d À131.13–
157.52 (hept), EI-MS: m/z = 328 [McationÀH]+, m/z = 314
[M+cationÀCH3].
Please cite this article in press as: Singh, A.; Chopra, H. K. Tetrahedron: Asymmetry (2016), http://dx.doi.org/10.1016/j.tetasy.2016.04.004

A. Singh, H. K. Chopra / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
5
4.4.3. 1-[(À)-Menthoxycarbonylmethylene]-3-methyl benzimida-
d 4.92–4.88 (q, 1H, CH), d 1.88 (broad s, 1H, OH), d 1.52–1.48
(d, 3H, CH3). HPLC (Chiralcel OD-H column, hexane/i-PrOH 95:5,
flow rate 1 mL/min, tR (minor) = 9.40 min; tR (major) = 11.28 min).
zolium 2-bromoethylsulfonate [AMeMBI]OSO2CH2CH2Br 1d
White solid, Yield = 85%, mp = 62–64 °C, [
a
]
25 = À18.6 (c 0.25,
D
EtOH). 1H NMR (CDCl3, 400 MHz): d 10.56 (s, 1H), 7.76–7.65 (m,
3H, Ar), 7.56–7.52 (m, 1H, Ar), 5.48 (s, 2H, NCH2), 4.85–4.76 (m,
1 H), 4.22 (s, 3H, NCH3), 3.74–3.68 (t, 2H), 3.37–3.31 (t, 2H),
2.20–1.99 (m, 3H), 1.86–1.78 (m, 1H), 1.74–1.66 (d, 2H), 1.52–
1.49 (m, 2H), 1.16–1.02 (m, 2H), 1.1 (m, 2H), 0.96–0.89 (two d,
6H, two methyl of isopropyl group), 0.78–0.72 (d, 3H, CH3 of men-
thol). 13C NMR (CDCl3, 100 MHz): d 165.43, 144.83, 131.78, 131.49,
127.54, 127.38, 112.87, 112.72, 54.45, 47.91, 46.77, 40.59, 33.90,
33.74, 31.44, 29.71, 26.28, 23.18, 21.94, 20.76, 16.16. EI-MS: 329
[M+cation], m/z = 314 [M+cationÀCH3].
4.5.2. (À)-1-(4-Methoxyphenyl)-ethanol
Yield = 76%,
[
a
]
25 = À3.4 (c 0.25, MeOH). 1H NMR (CDCl3,
D
400 MHz): d 7.32–7.28 (d, 2H, Ar), d 6.89–6.86 (d, 2H, Ar), d
4.88–4.22 (q, 1H, CH), d 3.80 (broad s, 3H, OH), d 1.82 (s, 1H), d
1.52–1.44 (d, 3H, CH3). HPLC (Chiralcel OD-H column, hexane/
i-PrOH 95:5, flow rate 0.8 mL/min, tR (minor) = 20.11 min; tR
(major) = 22.67 min).
4.5.3. (À)-1-(4-Nitrophenyl)-ethanol
Yield = 72%,
[
a
]
25 = À2.6 (c 0.25, MeOH). 1H NMR (CDCl3,
D
4.4.4. 1-[(À)-Borneoxycarbonylmethylene]-3-methyl benzimida-
400 MHz): d 8.21–8.16 (d, 2H, Ar), d 7.57–7.51 (d, 2H, Ar), d
5.15–4.98 (q, 1H, CH), d 2.28 (broad s, 1H, OH), d 1.516–1.49 (d,
3H, CH3). HPLC (Chiralcel OD-H column, hexane/i-PrOH 95:5, flow
rate 0.8 mL/min, tR (minor) = 22.23 min; tR (major) = 25.63 min).
zolium tetrafluoroborate [ABoMBI]BF4 2b
Off-white solid, Yield = 87%, mp = 108–110 °C, [
a
]
25 = À28.7 (c
D
0.25, EtOH). 1H NMR (CDCl3, 400 MHz): d 9.70 (s, 1H), 7.72–7.48
(m, 4H, Ar), 5.33 (s, 2H, NCH2), 4.98–4.72 (d, 1 H), 4.11 (s, 3H N-
CH3), 2.31–2.16 (m, 1H), 1.70–1.56 (m, 3H), 1.18 (s, 3H), 1.15–
0.98 (d, 1H), 0.81 (s, 6H) 0.75 (s, 3H). 13C NMR (CDCl3, 400 MHz):
d 165.93, 143.85, 131.77, 131.56, 127.54, 127.37, 112.97, 112.93,
83.49, 48.98, 47.98, 47.80, 44.74, 36.34, 33.65, 27.78, 26.91,
19.63, 18.77, 13.45. 11B NMR (CDCl3, 400 MHz): d À0.96 (s), EI-
MS: 326 [McationÀH]+, m/z = 312 [M+cationÀCH3].
4.5.4. (À)-1-(4-Bromophenyl)-ethanol
Yield = 68%, [
a
]
25 = À27.4 (c 0.25, MeOH). 1H NMR (CDCl3,
D
400 MHz): d 7.47–7.44 (d, 2H, Ar), d 7.26–7.22 (m, 2H, Ar), d
4.88–4.81 (q, 1H, CH), d 1.98 (broad s, 1H, OH), d 1.48–1.42 (d,
3H, CH3). HPLC (Chiralcel OD-H column, hexane/i-PrOH 95:5, flow
rate 1 mL/min, tR (minor) = 9.63 min; tR (major) = 13.28 min).
4.4.5. 1-[(À)-Borneoxycarbonylmethylene]-3-methyl benzimida-
zolium hexafluorophosphate [ABoMBI]PF6 2c
4.5.5. (À)-1-(4-Hydroxyphenyl)-ethanol
25 = À16.2 (c
Yield = 69%. [a]
25 = À20.3 (c 0.25, MeOH). HPLC (Chiralcel OD-H
Off-white solid, Yield = 84%, mp = 118–120 °C, [
a]
D
D
0.25, EtOH). 1H NMR (CDCl3, 400 MHz): d 9.16 (s, 1H), 7.75–7.60
(m, 4H, Ar), 5.26 (s, 2H, NCH2), 5.11–4.91 (d, 1 H), 4.11 (s, 3H,
NCH3), 2.48–2.22 (m, 1H), 1.73–1.63 (m, 4H), 1.26 (s, 3H), 1.12–
1.04 (d, 1H), 0.86 (s, 6H) 0.78 (s, 3H). 13C NMR (CDCl3, 400 MHz):
d 165.70, 143.00, 131.71, 131.52, 127.67, 127.50, 113.01, 112.95,
83.67, 48.97, 47.96, 47.80, 44.74, 36.25, 33.65, 27.71, 26.88,
19.63, 18.77, 13.37. 31P NMR (CDCl3, 400 MHz): d À131.10–
157.50 (hept), EI-MS: m/z = 327 [M+cation], m/z = 312 [M+cationÀCH3].
column, hexane/i-PrOH 95:5, flow rate 1 mL/min, tR (minor) =
9.74 min; tR (major) = 15.65 min).
4.5.6. (À)-1-(2-Hydroxyphenyl)-ethanol
Yield = 68%. [
a
]
25 = À9.8 (c 0.25, MeOH). HPLC (Chiralcel OD-H
D
column, hexane/i-PrOH 95:5, flow rate 0.8 mL/min, tR (minor) =
9.61 min; tR (major) = 15.50 min).
Acknowledgements
4.4.6. 1-[(À)-Borneoxycarbonylmethylene]-3-methyl benzimida-
zolium 2-bromoethylsulfonate [ABoMBI]OSO2CH2CH2Br 2d
The authors are highly thankful to the DST (Department of
Science and Technology, Govt. of India) for providing funds under
INSPIRE Fellowship (INSPIRE Fellow No. IF 140327). Authors are
also acknowledged to Sant Longowal Institute of Engineering and
Technology, Longowal (India) for providing various research
facilities.
Off-white solid Yield = 83%, mp = 96–98 °C, [
a
]
25 = À15.6 (c
D
0.25, EtOH). 1H NMR (CDCl3, 400 MHz): d 10. 35 (s, 1H), 7.78–
7.68 (d, 1H, Ar), 7.60 (s, 3H, Ar), 5.47 (s, 2H NCH2), 5.44–5.35 (d,
1 H), 4.13 (s, 3H N-CH3), 3.60–3.52 (t, 2H), 3.20–3.07 (t, 2H),
2.31–2.19 (m, 1H), 1.72–1.56 (m, 3H), 1.19 (s, 3H), 1.02–0.97 (d,
1H), 0.80 (s, 6H), 0.74 (s, 3H). 13C NMR (CDCl3, 400 MHz): d
166.09, 144.39, 131.67, 131.47, 127.46, 127.32, 113.07, 112.93,
83.16, 54.40, 48.93, 47.91, 44.64, 36.34, 33.76, 29.59, 27.79,
26.87, 26.29, 19.58, 18.72, 13.47. EI-MS: m/z = 327 [M+cation],
m/z = 312 [M+cationÀCH3].
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetasy.2016.04.
004.
4.5. General procedure for NaBH4 reduction in presence of
chiral ionic liquid 1a
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In a round bottom flask, 1.5 mmol of ketone and 0.15 mmol
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was dried over Na2SO4 and the solvent was evaporated to offer cor-
respond alcohols in substantial yield.
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