Synthesis, characterization and physicochemical properties of new chiral quinuclidinol quaternary ammonium salts

Article abstract of DOI:10.1016/j.molstruc.2020.127918

A new series of chiral quaternary ammonium salts (QASs) were successfully synthesized and characterized by FT-IR, NMR and MS. The thermal stability and melting point (mp) of the chiral QASs were measured. Moreover, basic physicochemical properties of the

Full text of DOI:10.1016/j.molstruc.2020.127918

Journal Pre-proof
Synthesis, characterization and physicochemical properties of new chiral quinuclidinol
quaternary ammonium salts
Ruoheng Li, Zhixia Wang, Qiwei Xu, Shun Yao, Zicheng Li, Hang Song
PII:
S0022-2860(20)30242-8
DOI:
https://doi.org/10.1016/j.molstruc.2020.127918
MOLSTR 127918
Reference:
To appear in: Journal of Molecular Structure
Received Date: 31 October 2019
Revised Date: 14 February 2020
Accepted Date: 15 February 2020
Please cite this article as: R. Li, Z. Wang, Q. Xu, S. Yao, Z. Li, H. Song, Synthesis, characterization and
physicochemical properties of new chiral quinuclidinol quaternary ammonium salts, Journal of Molecular
Structure (2020), doi: https://doi.org/10.1016/j.molstruc.2020.127918.
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CRediT author statement
Hang Song: Conceptualization, Methodology. Ruoheng Li: Experimental work, data
processing, Writing- Original draft preparation. Zhixia Wang: Supervision, Software
assistance. Qiwei Xu: Experiment assistance. Zicheng Li: The instruction of
synthesis route. Shun Yao: The instruction of spectral analysis.

OH
OH
O
O
O
N
Fe(ClO4)3
CH Cl2
·
6H20
Cl
RO
N
Cl-
RO
Cl
OH
+
OH
（
30
℃
）
EA（ 60℃）
2
1
OH
X-= BF -
2
3
4
O
4
R=
PF -
6
RO
N
Cl-
SO -
H O
CF
3
3
2
OH
O
NaBF
KPF6
4
white precipitate
H O
2
RO
N
KCF SO3
3
x-

Synthesis, Characterization and Physicochemical Properties of New
Chiral Quinuclidinol Quaternary Ammonium Salts
Ruoheng Li, Zhixia Wang, Qiwei Xu, Shun Yao, Zicheng Li, Hang Song*
School of Chemical Engineering, Sichuan University, Chengdu 610065, China
Abstract
A new series of chiral quaternary ammonium salts (QASs) were successfully
synthesized and characterized by FT-IR, NMR and MS. The thermal stability and
melting point (mp) of the chiral QASs were measured. Moreover, basic
physicochemical properties of the QAS solutions including density, viscosity,
conductivity and specific optical rotation were investigated. The solution properties
such as dissociation equilibrium constant (k) and critical micelle concentration (CMC)
were deduced with theoretical methods. All QASs exhibited good thermal stability
(decomposition temperature > 470 K) and large specific optical rotations (–228.12 to
–
156.83)
Keywords: Chiral quaternary ammonium salts; quinuclidinol; Synthesis;
Physicochemical properties
.
1
. Introduction
Quaternary ammonium salt ꢀQASꢁ was first reported in 1910s, and its main
function was to be used as bactericide [1]. The traditional quaternary ammonium salt
is generally composed of a positive nitrogen atom center of alkane substitution and an
inorganic anion [2]. With the lucubrating of research, more and more QASs have been
developed. The types of cation have gradually evolved from the simplest alkane
substituted to various organic skeleton substituted. The anions have also gradually
changed from halogen ions to other inorganic anions: tetrafluoroborate,
hexafluorophosphate, hydrogen sulfate, p-toluenesulfonate etc [3-5]. Nowadays, the
application fields of quaternary ammonium salt have become very extensive:
chemical field (phase transfer catalyst, seperation agent, extractant, fluorescent probe
etc.), material field (surfactant, bactericide, corrosion inhibitor etc), industrial field
(clay stabilizer, asphalt emulsifier etc), medicine field (insect repellent, disinfectant,
antifungal agent etc) [6-11]. Researchers can use different anions and cations to build
a quaternary ammonium salt that meets their needs. Many of QASs are composed of
imidazole, pyridine, quinoline and pyrrole etc [12,13]. Recently, many tropine-typed
hexafluorophosphate salts have also been synthesized in our group [14].
On account of designability of quaternary ammonium salts, many research groups
*
Corresponding author, Tel: +86-28-8540-5221; Fax: +86-28-8540-5221; E-mail address:
hangsong@vip.sina.com
1

have introduced chiral pool into the structure. Some researchers used the natural
chiral center of amino acids as an anion, and others transferred specific chiral
structure to nitrogen atom. Therefore, many chiral quaternary ammonium salts have
been developed, and most of them have been applied to asymmetric synthesis, chiral
resolution or NMR shift reagents etc [15-17]. Quinuclidinol is an important
intermediate for medicine, and it is widely used in the synthesis of solifenacin,
revatropate and talsaclidine etc [18-20]. However, to the best of our known, no group
has studied the quaternary ammonium salt with quinuclidinol as the nucleus. Because
of its good biocompatibility, low toxicity and acceptable economy, herein, we choose
quinuclidinol as nucleus. Based on its similar nucleus structure to quinine, through the
structural modification, the chiral pool can be introduced. And it is expected to play
an important role in asymmetric synthesis, chiral separation and natural product
extraction.
The dissociation equilibrium constant, limited molar conductivity and critical
micelle concentration of quaternary ammonium salt solution can be calculated by
theoretical method from measured conductivity [21-23]. The ion dissociation constant
∞
(
k) together with the limiting molar conductivity (Λ ) were established to obtain better
understanding of ion-ion, QAS-solvent interactions. Quaternary ammonium salt will
form micelles in solution, affecting their application, which make the measurement of
CMC an important procedure.
Viscosity and density of quaternary ammonium salt solution have a vital impact on
their use. Similar to the ionic liquid solution, the viscosity of quaternary ammonium
salt solution also increases compared with that of pure solvent, which could lead to
slow mass transfer process and low speed of reaction [24, 25]. Generally, with the
decrease of viscosity, the resistance of mass transfer between solutions increases and
the effective interaction between solution and solute decreases. As a result, the time
and yield of reaction also will be influenced. Density is also an important physical
property of salt solution
. At different temperatures, liquids have different densities
[
26]. The inaccurately density data are easy to cause serious experiment errors.
Therefore, it is essential to understand the viscosity and density parameters of the new
chiral QAS solutions.
Some quaternary ammonium salts will participate in the high temperature reaction
[
27]. In order to ensure the success of the reaction, researchers have to figure out the
2

temperature range at which quaternary ammonium salts can be used to keep the
structure unbreakable. Moreover, through the thermal degradation experiment, we can
also know whether they have the risk of combustion or explosion [28]. Hence,
researcher could make use of them safely in the future.
Different compounds have distinct specific optical rotations. The most efficient and
effortless way to confirm the success of the synthesis is to compare the literature
values with experimental results. Many chiral quaternary ammonium salts have been
reported their specific optical rotation, as the same time, many research groups have
developed quaternary ammonium salts with very large specific optical rotation, which
probably be used in drug determination in the future [29].
In this work, a series of new chiral QASs based on quinuclidinol-cation and
inorganic anion were synthesized with quaternarization and metathesis reactions and
1
13
were fully verified by FT-IR, H and C NMR. Our group wants to explain and
predict the micro behavior of QAS in the solution through the dissociation constant,
conductivity and CMC of the salt solution obtained by experiment and theoretical
calculation, so as to provide theoretical guidance for subsequent possible application.
At the same time, the fundamental solution properties (the viscosity and density) were
also measured for reducing the experiment errors. Through the thermal test, we can
find out the degradation temperature, flammability and explosiveness of QAS for use
them safely and effectively. Finally, the specific rotation of the chiral QAS solution
has also been determined, which not only makes us to have a deeper understanding of
the synthesized products, but also provides data support for the future development of
chiral medicines.
2
.Materials and methods
2
.1.Reagents and materials
R-3-Quinuclidinol was purchased from Sino-Strong Pharmaceutical Co. Ltd.
(Chengdu, China). Iron (III) perchlorate hydrate was purchased from Energy
Chemical (Shanghai, China). Potassium hexafluorophosphate and potassium
trifluoromethanesulfonate were purchased from Aladdin Industrial Co. Ltd. (Shanghai,
China). Sodium tetrafluoroborate and other solvents were purchased from Kelong
Chemical Co. Ltd. (Chengdu, China). Chloroacetic acid and L-menthol were
purchased from Macklin Biochemical Co. Ltd. (Shanghai, China). Thin layer
chromatography was carried out using Qingdao Ocean Chemical 60 F254 silica gel
plates. All reagents and solvents were of pure analytical grade and were used without
3

further purification.
Scheme.1 Synthesis of new chiral quaternary ammonium salt L-menthyl
chloroacetate.
Scheme.2 Anion exchange of chloride salt.
2
2
.2.Synthesis and characterization
.2.1.Synthesis of L-menthyl chloroacetate
The synthesis of this optically active ester was carried out according to the
literature [30].
1
H NMR (400 MHz, CDCl ) δ 4.77 (td, J = 4.4,10.9 Hz, 1H), 4.04 (m, 2H), 2.01 (d,
3
J = 5.3 Hz, 1H), 1.93-1.78 (m, 1H), 1.76 – 1.64 (m,2H), 1.60 – 1.34 (m, 3H), 1.13 –
13
0
.96 (m, 2H), 0.90 (dd, J = 8.4, 15.0 Hz, 6H), 0.77 (d, J = 7.0 Hz, 3H). C NMR (101
MHz, CDCl ) δ 166.91, 76.54, 46.94, 41.20, 40.62, 34.11, 31.40, 26.23, 23.38, 21.97,
3
2
2
0.72, 16.29.
.2.2.Synthesis of L-menthoxyacetyl quinuclidinol chloride [MenQu]Cl (1)
R-Quinuclidinol (0.636 g, 5 mmol) was dissolved in 30mL ethyl acetate, and then
L-menthyl chloroacetate (1.164 g, 5 mmol) was added into the solution. The reaction
solution was refluxed at 333 K for 5 h. After completion of the reaction, the solvent
and the residual menthyl chloride were removed under reduced pressure. The white
solids were then dried under vacuum at 323 K after being washed with ethyl acetate
for several times to give corresponding chloride salt.
4

1
H NMR (400 MHz, CDCl ) δ 4.78 (td, J = 10.8, 4.2 Hz, 1H), 4.62 (s, 1H), 4.55
3
–
1
=
4.28 (m, 3H), 4.02 – 3.72 (m, 7H), 2.35 – 2.58 (m, 2H), 2.12 – 1.76 (m, 5H), 1.74 –
.64 (m, 2H), 1.53 – 1.36 (m, 2H), 1.12–0.96 (m, 2H), 0.96 – 0.85 (m, 6H), 0.75 (d, J
1
3
6.8 Hz, 3H). C NMR (101 MHz, CDCl ) δ 164.18, 77.25, 65.60, 63.95, 61.76,
3
5
1
1
2
5.39, 53.83, 46.67, 40.64, 33.90, 31.48, 26.25, 26.15, 23.13, 21.93, 21.83, 20.85,
−
1
8.22, 16.29. IR (KBr, cm ):3357,3309,2947,2870,1745,1493,1465,1429,1413,1384,
+
327,1224,1128,1039,1016,985. ESI-MS: m/z = 324 [Mcation-H] .
.2.3.Synthesis of 1-menthoxyacetyl quinuclidinol tetrafluoroborate [MenQu]BF (2)
4
In a round bottom flask, 0.6 mmol of NaBF (65.9 mg) dissolved in distilled water.
4
Then, aqueous solutions with 0.5 mmol chloride salt (180.0 mg) was dropped in
slowly. The reaction mixture was stirred at room temperature for 5 h. Next, the
solvent was removed under reduced pressure. The white solids were dried under
vacuum at 323 K after being washed with distilled water for several times to give
target product.
1
H NMR (400 MHz, CDCl ) δ 4.80 (td, J = 10.5, 7.2 Hz, 1H), 4.37 (s, 1H),
3
4
1
3
4
.28-3.88 (m, 3H), 3.86 – 3.33 (m, 7H), 2.53 – 2.26 (m, 2H), 2.07 – 1.62 (m, 7H),
.53 –1.35 (m, 2H),1.13 – 0.97 (m, 2H), 0.95 – 0.81 (m, 6H), 0.75 (d, J = 6.4 Hz,
1
3
H). C NMR (101 MHz, CDCl ) δ 163.76, 77.73, 64.99, 64.35, 61.49, 55.41, 54.16,
3
6.65, 40.42, 33.89, 31.49, 26.17, 25.92, 23.17, 21.91, 21.47, 20.74, 17.87, 16.07. IR
−
1
(
KBr, cm ): 3467,3380,2955,2869,1742,1463,1415,1384,1227,1124,1084,1037,981,
+
9
2
55,522. ESI-MS: m/z = 324 [Mcation-H] .
.2.4.Synthesis of 1-menthoxyacetyl quinuclidinol hexafluorophosphate [MenQu]PF6
(3)
Similar procedure as earlier was carried out between quinuclidinol-based chloride
and potassium hexafluorophosphate, and the chloride salts were changed to the
product of [MenQu]PF through metathesis reaction with the yield of 78%, as shown
6
in Scheme. 2.
1
H NMR (400 MHz, CDCl ) δ 4.80 (td, J = 10.8, 4.1 Hz, 1H), 4.35 (s, 1H), 4.15 –
3
3
1
3
4
.82 (m, 3H), 3.80 – 3.40 (m, 5H), 2.52 – 2.30 (m, 2H), 2.16 – 1.61 (m, 7), 1.56 –
.34 (m, 2H), 1.15 – 0.97 (m, 2H), 0.90, 0.96 – 0.83 (m, 6H), 0.75 (d, J = 6.8 Hz,
1
3
H). C NMR (101 MHz, CDCl ) δ 163.53, 77.81, 64.35, 64.31, 61.36, 55.61, 54.45,
3
6.65, 40.28, 33.88, 31.46, 26.09, 25.81, 23.14, 21.87, 21.21, 20.66, 17.66, 15.96. IR
−
1
(
KBr, cm ): 3570,3430,2950,2870,1765,1464,1223,1129,843,559. ESI-MS: m/z =
+
3
24 [Mcation-H]
5

2
.2.5.Synthesis of 1-menthoxyacetyl quinuclidinol trifluoromethanesulfonate
[
MenQu]CF SO (4)
3
3
Similar procedure as earlier was carried out between quinuclidinol-based chloride
and potassium trifluoromethanesulfonate, and the chloride salts were changed to the
product of [MenQu]CF SO through metathesis reaction with the yield of 75%, as
3
3
shown in Scheme. 2
1
H NMR (400 MHz, CDCl3) δ 4.79 (td, J = 10.7, 3.7 Hz, 1H), 4.35 (s, 1H), 4.18 –
3
1
.95(m, 3H), 3.88 – 3.49 (m, 7H), 2.52 – 2.35 (m, 2H), 2.12 – 1.68 (m, 7H), 1.55 –
1
3
.35 (m, 2H), 1.12 – 0.98 (m, 2H), 0.95 – 0.85 (m, 6H), 0.74 (d, J = 6.6 Hz, 3H). C
NMR (101 MHz, CDCl3) δ 163.81, 77.67, 65.11, 64.20, 61.42, 55.48, 53.88, 46.67,
0.42, 33.88, 31.47, 26.12, 25.96, 23.12, 21.88, 21.51, 20.68, 17.91, 15.98. IR (KBr,
4
−
1
cm ): 3460,2960,2871,1757,1489,1462,1384,1285,1257,1227,1029,636,575,518.
+
ESI-MS: m/z = 324 [Mcation-H] .
2
.2.6.Spectroscopy measurement
All spectral measurements were made at ambient temperature. Infrared spectra
1
13
detection was performed using potassium bromide discs. When H and C NMR
spectra were measured, the sample was dissolved in CDCl , and TMS was used as an
3
internal standard. The melting points of four chiral QASs were determined by micro
melting point instrument. The mass spectrometric (EI-MS) analysis was carried out by
using a Finnigan TSQ quantum ultra mass spectrometer (Massachusetts, USA).
Table 1 Physical properties of synthesized chiral quaternary ammonium salts
Chiral QAS
Physical state
White solid
White solid
White solid
yield
93%
77%
78%
75%
Mp [K]
[
[
[
[
MeQu]Cl
456.2-457.7
416.2-417.5
411.9-412.3
415.8-416.3
MenQu]BF4
MenQu]PF6
MenQu]CF SO White solid
3
3
2
.3.Thermal analysis
[
MenQu]Cl was taken as an instance, the decomposition behavior of the chiral
−
1
QAS was determined on a Netzsch TG 209 at a heating rate of 10 K·min under
nitrogen atmosphere over a temperature range of 303 K to 873 K. The melting point
was measured by an X-48 micro melting point apparatus.
2
.4.Measurement of specific rotation
6
0 mg [MenQu]Cl were dissolved in 15 mL methanol, the determination of specific
6

rotation of [MenQu]Cl was carried on an Rudolph Autopol Ⅳ automatic polarimeter at
three kinds of temperature (288K/298K/308K) under different wavelengths.
2
.5.Measurement of density
First, measure the density of pure water at different temperatures with a pycnometer.
After filling the pycnometer with water, put it into the ultrasonic bath to degassing for
minutes, then refill the water and degas until the pycnometer has no bubble. Then
2
put the pycnometer in a temperature-controlled water bath, keep it at a constant
temperature for 20 minutes, promptly take out the pycnometer, wipe the water and
record the data. The measurement of the density of the quaternary ammonium salt
solution was also carried out in the same manner, and the data at each temperature
was measured three times to obtain an average value.
2
.6.Measurement of viscosity
The viscosity was measured using an Ostwald viscometer with temperatures
ranging from 278.15 to 313.15 K. After adding the solution to the viscometer, it was
putted in a temperature-controlled water bath for 30 minutes, and then the time for the
solution to flow through the mark line was recorded. The data at each temperature
was measured three times.
2
.7.Measurement of conductivity
The conductivity was measured using a Leici DDS-307A digital conductivity meter
−
1
(
Shanghai, China) with an electrode (parameter: 0.997 cm ). The solution was added
to the tube and putted it in a temperature-controlled water bath for 20 minutes,
recording the data after number be stabilized. Each temperature was measured three
times to get average value. Measure the temperature from 278.15 to 313.15 K. The
conductivity of different concentrations of quaternary ammonium salt solution at eight
temperatures was determined. The molar conductivity can be calculated according to
the following formula:
Λ = σ/ c
(1)
where c are the molarity of quaternary ammonium salt at certain temperature.
3
3
3
.Result and Discussion
.1. Chiral QASs characterization
.1.1 Infrared spectroscopy
The Fig. 1 shows the infrared spectroscopy of R-quinuclidinol and [MenQu]Cl.
−
1
They both have the similar absorbance ranges from 3600 to 3200 cm , which can be
assigned to O–H vibrational of the quinuclidinol, and their characteristic peaks 2950
7

−
1
and 2870 cm are attributed to the symmetric stretching and asymmetric stretching of
−
1
−1
C–H. The absorptions at 1128 cm and 1039 cm are ascribed to C–O and C–N
stretching vibrations on the quinuclidinol ring, respectively. Compared to
−1
R-quinuclidinol, [MenQu]Cl have new absorptions at 1745 and 1224 cm which can
be assigned to C=O and C−O stretching vibrations of ester. Thus, the ester group was
transferred to the nitrogen successfully.
Fig. 1 FT-IR spectrums of quinuclidinol, [MenQu]Cl
−
1
The IR spectrum of [MenQu]BF appears broad peak from 1100 to 950 cm and
4
−
1
weak absorptions at 522 cm , which can be assigned to stretching vibrations and
−
1
bending vibration of B−F. For the chiral QAS 3, the characteristic peaks at 840 cm
−
1
and 558 cm corresponded to the stretching and bending vibrations of P−F. The
−
1
−1
characteristic peaks in the range of 1300 – 1200 cm and 650 – 500 cm are related
to the stretching and bending vibrations of CF SO . The evidences above indicate that
3
3
anion exchange has been successfully achieved at the end of synthesis process.
8

Fig. 2 Structures of synthesized chiral quaternary ammonium salt
.1.2 Assignment of signals for 1H and 13C NMR spectroscopy
3
Since all quaternary ammonium salts have the same cation, [MenQu]Cl is used as
1
an example to analyze its signal peak. In the H spectrum, compared the nuclear
magnetic data of the L-menthyl chloroacetate and [MenQu]Cl, it can be found that
they both have td peaks at 4.77 ppm. The triplet double peaks of 4.77 ppm belong to
the H10, which firstly split into a double peak by coupling with the H11, and then
split into a triple-double peak by the influence of H15. The signal of 4.60 ppm is
assigned to the hydroxyl group. The protons H1 and H2 belong to the multiple peaks
of 4.55ꢂ4.28 ppm, and chemical shifts of H1 are increased because of the strong
electron-withdrawing effect of the nitrogen positive ion. Similarly, chemical shifts of
H2 are increased because of the strong deshielding effect of hydroxyl groups. The
multiple peaks around 0.9 ppm are assigned to the two methyl groups of C18, C19
and the double peaks at 0.75 ppm are attributed to the methyl proton signal of C16,
which can be correspond to menthol group.
1
3
In the C spectrum, the chemical shift at 164 ppm is ascribed to carbon of carbonyl,
and the signal at 77 ppm is assigned to carbon C10, because it was directly attached to
oxygen atom causing chemical shift transferred to downfield region. Moreover, there
are 7 more signals after menthyl chloroacetate attached to nitrogen atom. The signals
of 65.6 ppm, 63.95 ppm, and 61.76 ppm are related to C8, C2, and C1, respectively.
The signals at 55.39 ppm and 53.80 ppm are attributed to the C5 and C6 due to the
strong electron withdrawing of quaternary nitrogen.
3
3
.2.Thermal property and melting point of chiral QASs compounds
.2.1 Thermal property
The Fig. 3 is the mass-rate curves of [MenQu]Cl. In the thermogravimetric curve,
three different area of mass losing can be observed. The first segment from 303–473
K shows no obvious mass loss, which indicates [MenQu]Cl has a good
thermostability under 473 K. The second segment is from 473K to 553 K, possibly
[
MenQu]Cl decomposed to carbonyl, menthol and quinuclidinol under the heat. It is
likely that the quality loss caused by the gasified of menthol and quinuclidinol. As
shown in the picture, the maximum mass loss rate at about 493 K and 543 K, it could
be assigned to the break of ring skeleton of menthol and quinuclidinol. The last
9

segment is from 554–573 K, which could be extrapolated for the decomposition of
anion.
Fig. 3 TG-DTG curve of [MenQu]Cl.
3
.2.2 Melting point
Melting point data for quaternary ammonium salts have been shown in the Table
. Compared to chloride salts, the melting point of other chiral quaternary ammonium
1
salts were changed significantly after anion exchanged.
3
3
.3. Basic physicochemical properties of chiral QASs solutions
.3.1 Density
As shown in the Fig. 4, the density varies linearly with temperature. Concentration
of chiral QAS solution is 10 mg/ml, which is the most used concentration in our trial.
The density of the quaternary ammonium salt methanol solution decreases with
increasing temperature, and the change of the anion has little effect on their density.
Tables S2 shows the fitting results.
1
0

Fig. 4 Temperature dependence of density of chiral QASs.
Table 2 Density of chiral QAS-solutions at different temperatures.
-
3
ρ/g·cm
QASs\T (K)
278.15
283.15
288.15
293.15
298.15
303.15
0.79023
0.7895
0.78861
0.7884
308.15
313.15
[
[
[
[
MenQu]Cl
0.81298
0.81105
0.81078
0.81142
0.80953
0.80732
0.80708
0.80734
0.80445
0.80322
0.80297
0.80281
0.79986
0.79833
0.79936
0.7983
0.79485
0.79379
0.79461
0.79351
0.78537
0.78445
0.78491
0.7847
0.78119
0.78027
0.77976
0.77965
MenQu]BF
4
MenQu]PF
6
MenQu]CF
3
SO
3
3
.3.2 Viscosity
A polynomial fit was performed on the viscosity results of the quaternary
ammonium salt solution (C = 10 mg/ml ). It can be seen from the results that as the
temperature increases, the viscosity gradually decreases. Similarly, the effect of
anions on viscosity is not significant, and the four QASs solutions have similar
viscosities at the same temperature. Tables S3 and Fig. 5 shows the fitting results.
1
1

Fig. 5 Temperature dependence of viscosity of chiral QASs
Table 3 Viscosity of chiral QAS-solutions at different temperatures.
3
1
0 η/Pa·s
QASs\T(K)
278.15
1.060
1.110
1.070
1.080
283.15
1.020
1.010
0.999
1.030
288.15
0.945
0.948
0.936
0.967
293.15
0.901
0.908
0.880
0.902
298.15
0.840
0.836
0.821
0.847
303.15
0.797
0.792
0.774
0.784
308.15
0.726
0.749
0.731
0.744
313.15
0.682
0.692
0.691
0.695
[
[
[
[
MenQu]Cl
MenQu]BF4
MenQu]PF6
MenQu]CF SO3
3
The uncertainty of the viscosity is ±1%
3
.3.3 Conductivity
Table 4 displayed the details of measured conductivity and molar conductivity of
QASs methanol solution. The fitting results of conductivity could be described by
Arrhenius equation:
(2)
where
is the activation energy,
represents Boltzmann's constant,
is
specific constant. The fitting results are shown in Tables S4.
Fig. 8 and Fig. 9 exhibit the results of fitting the conductivity and molar
conductivity to temperature. The result shows at the same temperature, the
conductivity of QAS varies with different anions, which could be illuminated by the
different anions and cations have different binding energies. The tighter binding
between ions lowered their transfer speed which resulted in lower conductivity.
Furthermore, high temperature may cause the acceleration of ion motion, which leads
1
2

to the increase of conductivity.
A binary mixture system with different concentrations composed of [MenQu]Cl
and methanol was prepared. Table S5 shows the measured conductivity at different
temperatures and the calculated molar conductivity. Figure. 10 contains the fitting of
the conductivity (σ) to concentration. The fitting results show that the conductivity is
not linear with the concentration.
−
1
2
−1
Table 4 Conductivity (σ/mS·cm ) and molar conductivity (Λ/S·cm ·mol ) of chiral
QAS at different temperatures
[
MenQu]Cl
[MenQu]BF4
[MenQu]PF6
[MenQu]CF SO
3 3
T/K
σ
Λ
σ
Λ
σ
Λ
σ
Λ
2
2
2
2
2
3
3
3
78.15 0.1452 52.23 0.1496 53.813 0.1375 49.46 0.1214
43.67
83.15 0.1553 55.863 0.1597 57.446 0.1470 52.878 0.1301 46.799
88.15 0.1669 60.036 0.1705 61.331 0.1571 56.512 0.1395 50.179
93.15 0.1774 63.813 0.1825 65.647 0.1688 60.719 0.1488 53.525
98.15 0.1895 68.165 0.1946 70.000 0.1816 65.324 0.1584 56.978
03.15 0.2008 73.230 0.2070 74.460 0.1916 68.921 0.1678 60.359
08.15 0.2160 77.698 0.2240 80.576 0.2040 73.381 0.1801 64.784
13.15 0.2310 83.094 0.2380 85.612 0.2230 80.216 0.1915 68.885
The uncertainty of the electrical conductivity is ±1%
.3.4 Specific optical rotation
3
At different temperatures, data from different wavelengths has been shown in the
Table S1. As can be seen from Figure 2, as the temperature raises, the specific optical
rotation decreases slightly. All the synthesized salts showed negative specific rotations.
As evident from the literature [31], the specific rotation values of BF based chiral
4
QASs were found to be higher than that of PF based salts. It is possible that the
6
ultraviolet absorption wavelength of the ester group is relatively short, so the shorter
the wavelength, the larger the specific optical rotation.
3
3
.4. Solution properties
.4.1 Dissociation equilibrium constant
−
1
The dissociation equilibrium constant, k/L·mol , was calculated by the following
equation of Ostwald dilution law:
∞
∞
2
1
/
Λ
=1/
Λ
+ σ
/
(k (Λ
) )
(3)
∞
2
−1
Where Λ denotes the limiting molar conductivity (S·cm ·mol ) at infinite dilution, σ
1
3

is conductivity of IL solution. The calculated data presented in Table S6 indicates the
dissociation equilibrium constant of chiral QAS solution which decreased first and
then increased, finally decreased. This may because at low temperatures, the hydrogen
bonding was relatively strong, and as the temperature increased, the hydrogen bonds
between the molecules were diminished.
3
.4.2 Critical micelle concentration
Fig. 11 exhibits the results of a linear segmentation fit of [MenQu]Cl conductivity
versus concentration. The critical micelle concentration (CMC) data were obtained
from Fig. 11 and are listed in Table 5. The result shows that CMC of [MenQu]Cl
fluctuates as temperature rises, the reason could be the same with dissociation
equilibrium constant. The CMC value of 4.6 is much larger than 0.8 for [C mim]Br
4
[
32]. These results indicate the new chiral QASs is more difficult to form micelles
than imidazolium-based quaternary ammonium salts.
Table 5 CMC of [MenQu]Cl at different temperatures
T/K
278
283
288
293
298
303
308
313
-
2
-1
CMC × 10 mol·L
4.6165
4.6261
4.4204
4.6729
4.645
4.6663
4.6722
4.209
Fig. 6 specific rotation of four chiral QASs at different wavelengthes
1
4

Fig. 7 specific rotation of four chiral QASs at different temperatures.
Fig. 8. Temperature dependence of conductivity for chiral QASs.
1
5

Fig. 9. Temperature dependence of molar conductivity for chiral QASs.
Fig. 10. Plot of σ against C[MenQu]Cl
.
1
6

Fig. 11. Piecewise linear fitting of σ against C[MenQu]Cl
.
4
.Conclusion
A series of new chiral QASs were successfully synthesized and characterized by IR,
NMR and MS. It has been found that the QASs have good thermal stability
degradation temperature > 470 K). The chiral QASs have a short melting range (1.5
to 0.4 K) and melting point of chiral QASs was changed with different anion (456.2 to
11.9 K). The results show that the different anions have a great influence on the
(
4
optical rotation (–228.12 to –156.83), and the specific optical rotation decreases
slightly as temperature rises (–72.538 to –65.031). Moreover, dissociation equilibrium
∞
constant (k), limited molar conductivity (Λ ) and the CMC were calculated.
Dissociation equilibrium constant (k) and the CMC show the same variation trend
because of the combined effects of solvent and temperature possibly. The CMC 4.6
indicates these new chiral QASs are much difficult to form micelles than
imidazolium-based salt. More fundamental physical chemical properties (density,
viscosity) were also measured for future applications.
Acknowledgment
The authors thank the standard IR spectrum provided by SDBS (SDBSWeb :
https://sdbs.db.aist.go.jp (National Institute of Advanced Industrial Science and
Technology, date of access).
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2
0

Highlights
ꢀ
ꢀ
It is the first time that a serious of chiral quaternary ammonium salts
(QASs) with quinuclidinol core were synthesized.
The synthesized chiral quaternary ammonium salts have a large
specific optical rotation(–228.12 to –156.83 ) and good thermal
stability(decomposition temperature > 470 K ).
ꢀ
The basic physicochemical properties of chiral quaternary ammonium
salt solutions including density, viscosity and conductivity were
investigated and deduced with theoretical methods.

Declaration of interests
☒
The authors declare that they have no known competing financial interests or personal relationships
that could have appeared to influence the work reported in this paper.
☐
The authors declare the following financial interests/personal relationships which may be considered
as potential competing interests:
The authors declare that they have no known competing financial interests or personal relationships that
could have appeared to influence the work reported in this paper.