Synthesis, Characterisation, and Determination of Physical Properties of New Two-Protonic Acid Ionic Liquid and its Catalytic Application in the Esterification

Article abstract of DOI:10.1071/CH20153

A new ionic liquid was synthesised, and its chemical structure was elucidated by FT-IR, 1D NMR, 2D NMR, and mass analyses. Some physical properties, thermal behaviour, and thermal stability of this ionic liquid were investigated. The formation of a two-protonic acid salt namely 4,4′-trimethylene-N,N′-dipiperidinium sulfate instead of 4,4′-trimethylene-N,N′-dipiperidinium hydrogensulfate was evidenced by NMR analyses. The catalytic activity of this ionic liquid was demonstrated in the esterification reaction of n-butanol and glacial acetic acid under different conditions. The desired acetate was obtained in 62-88 % yield without using a Dean-Stark apparatus under optimal conditions of 10 mol-% of the ionic liquid, an alcohol to glacial acetic acid mole ratio of 1.3: 1.0, a temperature of 75-100°C, and a reaction time of 4 h. α-Tocopherol (α-TCP), a highly efficient form of vitamin E, was also treated with glacial acetic acid in the presence of the ionic liquid, and O-acetyl-α-tocopherol (Ac-TCP) was obtained in 88.4 % yield. The separation of esters was conducted during workup without the utilisation of high-cost column chromatography. The residue and ionic liquid were used in subsequent runs after the extraction of desired products. The ionic liquid exhibited high catalytic activity even after five runs with no significant change in its chemical structure and catalytic efficiency.

Full text of DOI:10.1071/CH20153

CSIRO PUBLISHING
Aust. J. Chem.
Full Paper
https://doi.org/10.1071/CH20153
Synthesis, Characterisation, and Determination of Physical
Properties of New Two-Protonic Acid Ionic Liquid and
its Catalytic Application in the Esterification
A
A
,
A C
Zohreh Shahnavaz, Lia Zaharani, Nader Ghaffari Khaligh,
B
A
Taraneh Mihankhah, and Mohd Rafie Johan
A
Nanotechnology and Catalysis Research Center, 3rd Floor, Block A, Institute of
Postgraduate Studies, University of Malaya, 50603, Kuala Lumpur, Malaysia.
Environmental Research Laboratory, Department of Water and Environmental
B
Engineering, School of Civil Engineering, Iran University of Science and Technology,
16765-163, Tehran, Iran.
C
Corresponding author. Email: ngkhaligh@um.edu.my
A new ionic liquid was synthesised, and its chemical structure was elucidated by FT-IR, 1D NMR, 2D NMR, and mass
analyses. Some physical properties, thermal behaviour, and thermal stability of this ionic liquid were investigated. The
0
0
0
formation of a two-protonic acid salt namely 4,4 -trimethylene-N,N -dipiperidinium sulfate instead of 4,4 -trimethylene-
0
N,N -dipiperidinium hydrogensulfate was evidenced by NMR analyses. The catalytic activity of this ionic liquid was
demonstrated in the esterification reaction of n-butanol and glacial acetic acid under different conditions. The desired
acetate was obtained in 62–88 % yield without using a Dean–Stark apparatus under optimal conditions of 10 mol-% of the
ionic liquid, an alcohol to glacial acetic acid mole ratio of 1.3 : 1.0, a temperature of 75–1008C, and a reaction time of 4 h.
a-Tocopherol (a-TCP), a highly efficient form of vitamin E, was also treated with glacial acetic acid in the presence of the
ionic liquid, and O-acetyl-a-tocopherol (Ac-TCP) was obtained in 88.4 % yield. The separation of esters was conducted
during workup without the utilisation of high-cost column chromatography. The residue and ionic liquid were used in
subsequent runs after the extraction of desired products. The ionic liquid exhibited high catalytic activity even after five
runs with no significant change in its chemical structure and catalytic efficiency.
Manuscript received: 9 May 2020.
Manuscript accepted: 15 July 2020.
Published online: 28 August 2020.
Introduction
[7–16]
esterification has been reported using various catalysts;
nonetheless, there are some drawbacks, for example
Catalysis is a vital topic in organic chemistry, and has been
employed in a broad range of sectors, products, and processes.
The current trend in catalysis research is to design greener cat-
alysts and eco-friendly technologies, as well as directing the
activities towards sustainability and investigating the catalytic
activity under realistic conditions regarding temperature and
pressure.
Natural and synthetic esters have been utilised in different
fields, including pharmaceuticals, perfumes, flavours, cos-
metics, adhesives, detergents, solvents, plasticisers, lubricants,
a) use of excessive reagents and dehydration agents or Dean–
Stark apparatus,
b) use of expensive, toxic, or corrosive reagents and catalysts,
c) limited substrate-scope, especially substrates bearing acid or
base sensitive groups,
d) use of an activated carboxylic acids together with a stoichio-
metric base,
e) the generation of a large amount of waste during the process,
f) use of non-recyclable catalysts and inactivation of catalytic
sites, and
[1,2]
electronic materials, and daily and fine chemicals, etc.
molecular mass esters have been widely found in fragrances and
Low
[
3]
[4]
g) a tedious process for the preparation of catalysts, and the
[
separation and purification of products.
essential oils and pheromones.
The carboxylic acid esters can be synthesised using various
5]
[5]
chemical reactants, catalysts, and reaction media. Although
numerous papers have appeared for the esterification reaction,
the development of an efficient synthesis of carboxylic acid
esters using carboxylic acids instead of acid anhydride is still an
exciting research topic.
Therefore, it is required to develop an efficient and greener
methodology to overcome some drawbacks and achieve a
suitable balance between the economic and ecological aspects
of production.
Due to the outstanding properties of ionic liquids (ILs), such
as thermal and chemical stability, low vapour pressure, and
recoverability, they have been extensively employed as an
The Fischer esterification is the conventional and most
[
6]
common process for the esterification reaction. The catalytic
Journal compilation � CSIRO 2020
www.publish.csiro.au/journals/ajc

B
Z. Shahnavaz et al.
O
S
O
H
S
H
O
O
O
O
H
O
O
H
N
N
H
H
[
TMDP(SO H) ][HSO ] (I)
3 2 4 2
H SO (98 %,1.0 or 2.0 equiv.)
2
4
HN
NH
CH Cl , ice-bath to r.t., overnight
O
S
2
2
O
O
TMDP
O
H
H
N
H
N
H
[
TMDPH ][SO ] (II)
2 4
Scheme 1. The proposed chemical structures for the new ionic liquid.
Table 1. The 1D NMR data of [TMDPH
2
][SO
4
] in DMSO-d
6
and D
2
O
β
'
'
2
4
4
' 2
6
3
3
H
6
H
N
H
5
α
5
'
'
N
H
α
[
TMDPH2]2+
Atom
DMSO-d
6
2
D O
d
H
[ppm]
J [Hz]
d
C
[ppm]
d
H
[ppm]
J [Hz]
d
C
[ppm]
þ
NH (eq)
8.46
8.17
3.23
2.82
1.77
br s
—
—
—
br s
—
—
þ
NH (ax)
br s
—
br s
0
0
0
0
0
0
0
0
CH-2, CH-2 , CH-6, and CH-6 (eq)
d, 12.1
43.57
43.57
28.57
28.57
35.64
32.95
22.76
3.29
2.85
1.83
d, 12.8
44.15
44.15
28.37
28.37
34.97
32.76
22.29
CH-2, CH-2 , CH-6, and CH-6 (ax)
dd, 11.5 and 22.6
td, 2.5 and 12.9
CH-3, CH-3 , CH-5, and CH-5 (eq)
d, 13.2
M
d, 14.0
CH-3, CH-3 , CH-5, and CH-5 (ax)
0
1.26–1.18
1.53–1.43
1.26–1.18
1.26–1.18
1.27–1.17
1.53–1.46
1.27–1.17
1.27–1.17
m
m
m
m
CH-4 and CH-4
M
CH
CH
2
-a
-b
M
2
M
eco-friendly solvent and/or catalyst in a variety of reactions,
[
ice-bath and then stirring the mixture at room temperature
overnight afforded a pale yellow sticky solid. The pale yellow
crystals were obtained from methanol through crystallisation
(mp 74–758C) (see Supplementary Material, Fig. S1). Further
studies, including FT-IR, 1D and 2D NMR, and mass spec-
trometry, were conducted to find the chemical structure of the
new IL.
17–23]
such as esterification.
0
In continuing our previous works on
[24–26]
4
,4 -trimethylenedipiperidine (TMDP),
the synthesis of a
new IL was designed and carried out through stirring TMDP and
sulfuric acid (98 %) in CH Cl . The chemical structure of the
new ionic liquid ([TMDPH ][SO ]) was characterised by FT-IR,
2
2
2
4
1
sulfate anion, instead of hydrogen sulfate, was evidenced by
D NMR, 2D NMR, and mass analysis. The existence of a
1
The H NMR spectrum of new IL showed two pseudo-singlet
1
detailed H NMR analyses. The physical properties of the new
peaks at 8.46 and 8.17 ppm. Regarding the magnetic anisotropy
of the chair conformation of two piperidinium rings, these
protons were attributed to the protons at the equatorial and axial
IL have been determined and are reported herein. The catalytic
activity of the new IL was studied for the direct esterification of
various carboxylic acids and alcohols under obtained optimal
reaction conditions.
þ
positions of .NH , respectively (see Supplementary Material,
2
[
27]
Fig. S2). The presence of acidic protons on nitrogen atoms at
a downfield position showed that intramolecular hydrogen
bonding in the new IL was weakened.
Results and Discussion
Synthesis and the Structure Elucidation of New Ionic Liquid
The chemical shift and coupling constant of the equatorial
and axial hydrogens (Heq and H ) of the two piperidinium rings
TMDP was treated with one and two equivalent(s) of sulfuric
acid to investigate the two possible chemical structures of the
new IL that could be formed by an acid–base reaction of TMDP
bearing two piperidine rings and sulfuric acid as a two-protonic
acid (Scheme 1).
ax
as well as protons of the three-carbon spacer are given for the
new IL in DMSO-d and D O in Table 1. The observation of a
6
2
singlet and a triplet signal at 3.63 and 7.15 ppm corresponding to
H O and HDO, respectively, demonstrated a slow rate of
2
Dropwise addition of two equivalents of sulfuric acid
98 %) into a solution of TMDP in dichloromethane in an
exchange between H O and HDO (see Supplementary Material,
2
Fig. S2).
(

Two-Protonic Acid Ionic Liquid and Esterification
C
As one can see in Fig. S3 (see Supplementary Material), the
þ
complete deprotonation of the sulfuric acid likely occurs by
TMDP under our reaction conditions.
protons of .NH2 disappeared in D O due to fast hydrogen
2
exchange with the deuterium of D O.
2
The carbons of new IL are detected at 43.57, 35.64, 32.95,
8.57, and 22.76 ppm and 44.15, 34.97, 32.76, 28.37, 22.29 ppm
Physical Properties of [TMDPH ][SO ]
2
4
2
in DMSO-d and D O, respectively (see Supplementary Mate-
The bulk amount of [TMDPH ][SO ] could be liquefied at
2
4
6
2
,
1108C in an oil bath (mp 74–758C). The ionic conduction
rial, Figs S4 and S5).
The 2D COSY spectra of new IL displayed correlations
ꢀ1
value (s) of new IL was 1.82 ꢁ 0.04 mS cm at 858C. The total
water content of [TMDPH ][SO ] was determined 0.18 ꢁ 0.02
þ
2
4
between the acidic protons of .NH at 8.46 and 8.17 ppm with
2
wt-% under ambient humidity and temperature. Although
[TMDPH ][SO ] was soluble in water, dimethyl sulfoxide,
0
0
the equatorial and axial protons of C2, C2 , C6, C6 at 3.23 and
2
2 4
.82 ppm, respectively (see Supplementary Material, Fig. S6).
The reaction of TMDP and sulfuric acid was also carried out
in CH Cl at a ratio of 1 : 1 at room temperature overnight, which
gave a white solid. The H and C NMR spectra of the TMDP
and sulfuric acid at a ratio of 1 : 1 were recorded in DMSO-d6
methanol, and acetic acid, it was immiscible with ethanol,
acetonitrile, ethyl acetate, acetone, chloroform, dichlor-
omethane, and n-hexane at room temperature.
2
2
1
13
Thermal Behaviour of [TMDPH ][SO ]
2
4
(see Supplementary Material, Fig. S7). One and two equi-
valent(s) of sulfuric acid (98 %) was then directly added to the
NMR tube containing TMDP and sulphuric acid at a ratio of 1 : 1
The thermal behaviour of [TMDPH
][SO ] was investigated by
4
2
a differential scanning calorimetry (DSC) plot in two cycles
over temperature ranges of 30–300 and 30–5008C (see Sup-
plementary Material, Fig. S12). DSC of pure TMDP has been
1
in DMSO-d , and the H NMR spectra were recorded (see
Supplementary Material, Fig. S8).
6
[
26]
The single peak of water at 3.92 ppm moved to the downfield
region, and a broadened multiplet and singlet signal were
observed at 4.45–4.43 and 6.96 ppm, respectively (see Figs
S7a, S8a, and S8b, Supplementary Material). The C NMR
spectra showed negligible shifts before and after adding sulfuric
1
acid. The H NMR spectrum of sulfuric acid was also investi-
previously reported in the literature, and it displays two sharp
and one broad endothermic peak centred at 58, 110, and 3328C.
The peaks at 52.3 and 332.58C were attributed to the melting and
boiling points of TMDP, respectively. The second endothermic
broad peak at a range of 76–1578C was attributed to the
desorption of trapped moisture in TMDP.
1
3
gated, which showed a relatively sharp singlet at 7.13 ppm in
DMSO-d (see Supplementary Material, Fig. S9).
Under a nitrogen atmosphere and at a range of 30–3008C,
three sharp and one weak endothermic peak(s) were displayed
on the DSC curve of [TMDPH ][SO ], and no exothermic peak
2 4
6
1
The H NMR spectrum of new IL did not show any peaks at a
region of 4.38–5.25. Moreover, no sharp or broadened peak was
detected at a range of 4.0 to 8.5 ppm and above 9.5 ppm.
Therefore, the existence of excess sulfuric acid or formation
of an acidic anion, namely hydrogen sulfate, could be excluded.
The infrared spectrum of new IL is shown in Figure S10 (see
was observed. The first sharp peak was assigned to the melting
of the IL which began at 85.28C and ended at 111.78C with a
ꢀ1
latent heat of fusion of 140.8 J g , which was in good agree-
ment with the obtained melting point achieved using an open
capillary tube in a B u¨ chi B-545 apparatus (mp 74–758C). The
second endothermic sharp peak was observed in the range
131.3–175.58C centred at 160.28C, which was assigned to the
dehydration and degassing of the IL with a latent heat of
ꢀ1
Supplementary Material). The broadened peak at 3407 cm
can be attributed to the N–H vibration mode at the .NH
þ
2
ꢀ1
groups. Two bands at 3034, 2923, and 1321 cm were assigned
to the symmetric, antisymmetric stretching vibrational, and
wagging mode of methylene groups in the piperidinium rings,
respectively. All absorption peaks at a range of 2848 to
ꢀ1
evaporation of 38.0 J g . Two sharp peaks were observed at a
range of 248.2 to 294.78C, which were assigned as the boiling
point decomposition of [TMDPH ][SO ] due to an appreciable
2 4
ꢀ1
2
shift towards this region are probably due to the strong interac-
524 cm were assigned to the N–H stretching band and their
loss of weight, a remarkable change in heat capacity of the
sample, and an exothermic baseline shift. The latent heat of
evaporation and decomposition of the [TMDPH ][SO ] were
þ
tions between .NH and the sulfate anion through hydrogen
2
2
4
[
bonding. The deformation vibration modes of .NH at 1616
28]
þ
ꢀ1
276.3 and 187.0 J g , respectively. There was no exothermic
and endothermic peak in the second cycle at a range of 30–
5008C, which supports the evaporation/decomposition of the
2
ꢀ
1
[28]
and 1462 cm are characteristic of secondary amine salts.
The asymmetric and symmetric SO2 stretching vibrations
ꢀ1
appeared at 1215, 1151, and 1029 cm , respectively. The
[TMDPH
Moreover, the thermal stability of [TMDPH ][SO ] was
2 4
2 4
][SO ] below 3008C in the first cycle.
ꢀ
1
sharp bands at 877 and 577 cm , as well as a medium band at
ꢀ
1
87 cm , were assigned to the S–O stretching modes and SO
4
bending, respectively.
studied in a temperature range from 30 to 8008C under a nitrogen
atmosphere through thermogravimetric analysis/differential
thermal analysis (TGA/DTA) (see Supplementary Material,
Fig. S13). Three peaks were observed on the DTA curve, and
2
[
29]
Electrospray ionisation–mass spectrometry (ESI-MS) analy-
ses in the negative and positive ionisation modes were conducted
on the sample. Both negative and positive ion modes of analysis
[TMDPH ][SO ] started to decompose at 2708C, which was in
2 4
gave sensitive and good spectra data. The positive ionisation
þ
good agreement with the result of DSC. The thermal decompo-
sition was mainly completed at 4508C. The first peak was
observed below 2008C with a maximum mass loss of 6.1 %;
this loss was related to the removal and evaporation of the
trapped and adsorbed moisture in [TMDPH ][SO ]. The second
2 4
and third peaks showed a maximum mass loss of 31.5 and
34.4 % at 250–290 and 290–3308C, respectively, which were
spectrum of the new ILrecordedprominent [Mþ EtOH þ NH ]
4
þ
and [M þ EtOH þ CO þ NH ] peaks (where M corresponds to
2
4
TMDP) at m/z 274.2753 and 318.3014, respectively (see Supple-
mentary Material, Fig. S11-A). Moreover, the negative ionisation
spectrum of the new IL displayed a weak ion at m/z 339.2005
ꢀ
assigned to [M þ H þ SO þ CH OH] (see Supplementary
4
3
Material, Fig. S11-B).
Based on our results, structure II was demonstrated for the
related to the total decomposition of [TMDPH
and TGA/DTA results showed that [TMDPH
mally stable up to 2708C, probably owing to the strong
2
][SO
4
]. The DSC
][SO
] is ther-
2
4
new IL evidencing it to be [TMDPH ][SO ], and indicate that
2
4

D
Z. Shahnavaz et al.
Table 2. Optimisation of the esterification of n-butanol and glacial acetic acid
A
Yield [%]
Entry
2 4
[TMDPH ][SO ] [mol-%]
Molar ratio of n-butanol to acetic acid
Temp. [8C]
Reaction time [h]
1
2
3
4
5
6
7
8
9
—
5
1.0 : 1.0
1.0 : 1.0
1.0 : 1.0
1.0 : 1.0
1.1 : 1.0
1.2 : 1.0
1.3 : 1.0
1.4 : 1.0
1.3 : 1.0
1.3 : 1.0
1.3 : 1.0
1.3 : 1.0
1.3 : 1.0
1.3 : 1.0
1.3 : 1.0
60
60
60
60
60
60
60
60
65
75
85
100
85
85
85
4.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
2.0
6.0
8.0
12
34
42
42
52
58
68
68
72
78
88
88
54
81
75
10
15
10
10
10
10
10
10
10
10
1.0
1.0
1.0
1
1
1
1
1
1
0
1
2
3
4
5
B
A
B
GC yield.
The chosen optimal conditions.
O
O
[
TMDPH ][SO ] (10 mol-%)
2 4
R
OH
+
R
H C
OH
H C
O
3
3
cyclohexane, 75–85°C, 4 h
1a–v
2a–h
GC-MS yield 62–88 %
2 4
Scheme 2. Esterification of various alcohols and glacial acetic acid in the presence of [TMDPH ][SO ].
electrostatic attractions between the piperidinium cations and
the sulfate anion in the structure of the [TMDPH ][SO ].
(Table 3, entries 1–14). Moreover, competitive dehydration
was observed for the secondary and tertiary alcohols under
optimised reaction conditions (Table 3, entries 10–14). The
substituents at the ortho-position of the benzyl alcohols gave
lower yields of acetate esters than the same substituents at the
para-position, which is probably due to the steric effect of the
substituents (Table 3, entries 15–22), as well as the hydrogen
2
4
Esterification of Alcohols and Glacial Acetic Acid Using
TMDPH ][SO ] as a Catalyst
[
2
4
Initially, the esterification of n-butanol (1e) and acetic acid was
chosen as a model reaction. The influence of four parameters,
including the amount of [TMDPH ][SO ], the ratio of n-butanol
bond formation between –NO and –Cl and the hydroxy group
2
2
4
to acetic acid, temperature, and reaction time were studied to
find the optimised reaction conditions. As the results show in
Table 2, the yield of esterification increased with an increase in
the catalyst loading, and the highest yield was observed with 10
mol-% of the catalyst (Table 2, entries 1–4). The most effective
molar ratio of n-butanol to glacial acetic acid was 1.3 at 608C
within 4 h (Table 2, entries 5–8).
of the benzyl alcohols (Table 3, entries 21 and 22).
The enantioselectivity of the current protocol was investi-
gated throughthe reaction ofglacialaceticacid with (ꢀ)-menthol
([a] ꢀ50 ꢁ 18, c 10% ethanol, $ 99 % e.e.) and (þ)-borneol
D
([a] þ37 ꢁ 28, c 5 % in ethanol, 99% e.e.) under optimal
D
conditions, which gave (ꢀ)-menthyl acetate ([a] ¼ ꢀ808, in
D
benzene, 97% e.e.) and (þ)-bornyl acetate ([a] ¼ þ418, neat,
D
A significant improvement in the yield was observed when
the model reaction was carried out at higher temperatures up to
96 % e.e.) with retention of the configuration at the chiral centre
in 72 and 70 % yield, respectively (Table 3, entries 11 and 12).
The optical rotation of the desired acetates was recorded and
reported based on samples from Sigma–Aldrich.
9
08C; however, no change occurred in yield at a higher temper-
ature (1008C) (Table 2, entries 9–12). A shorter or longer
reaction time of about 4 h resulted in lower yields of the desired
product (Table 2, entries 13–15), which can probably be due to
the reversibility of the esterification process. Based on our
results, entry 11 in Table 2 was selected as the best experimental
conditions, i.e., 10 mol-% catalyst, 1.3 : 1.0 molar ratio of
n-butanol to acetic acid, 858C, and 4 h reaction time.
According to a proposed mechanism, the glacial acetic acid is
initially activated by [TMDPH ][SO ] through hydrogen bond
2
4
formation (Scheme 3). A nucleophilic attack of the alcohol to
the activated acetic acid leads to the formation of intermediate
III. Hydrogen rearrangement and dehydration of intermediate
III gives the alkyl acetate. The dehydration step can be pro-
moted by the hygroscopic property of [TMDPH ][SO ]. More-
The catalytic activity of [TMDPH ][SO ] was demonstrated
2
4
2
4
for the esterification of other alcohols and glacial acetic acid
under optimised reaction conditions (Scheme 2).
over, the cyclohexane can favour the forward reaction through
extraction and separation of the produced alkyl acetate.
The reusability of [TMDPH ][SO ] was also studied using
the model reaction at optimal conditions, which afforded 2e in
88–82 % yield over five catalytic cycles.
A variety of alcohols were treated with acetic acid under
optimised reaction conditions (Table 3). The results showed
that the primary alcohols gave higher yields than secondary
alcohols, which afforded a slightly higher yield than tertiary
alcohols, which can be attributed to the acidity of alcohol
2
4
In another experiment, the model reaction was monitored
for a longer reaction time. Aliquots were analysed by gas

Two-Protonic Acid Ionic Liquid and Esterification
E
Table 3. Esterification of various alcohols and glacial acetic acid in the presence of [TMDPH
][SO ] under optimised reaction conditions
2 4
A
B
Yield [%]
Entry
Alcohol 1a–v
Ester 2a–h
Temp. [8C]
1
2
3
4
5
6
7
8
CH
CH
CH
3
3
3
OH
2a
2b
2c
2d
2e
2f
75
85
85
85
85
85
85
85
85
82 ꢁ 2
85 ꢁ 2
88 ꢁ 3
85 ꢁ 2
88 ꢁ 3
80 ꢁ 1
85 ꢁ 2
82 ꢁ 2
75 ꢁ 3
CH
CH
2
OH
CH
2
2
OH
(CH
CH
(CH
CH
(CH
3
)
2
CHOH
CH CH CH
CHCH OH
CH CH CH CH
CH OH
3
2
2
2
OH
3
)
2
2
3
2
2
2
2
OH
2g
2h
2i
3
)
2
CHCH
2
2
10
OH
1
1
2j
85
85
72 ꢁ 1
OH
12
2k
70 ꢁ 1
H
OH
1
3
4
O
H
2l
85
85
76 ꢁ 2
62 ꢁ 3
1
2m
OH
15
16
17
18
19
20
21
22
4-MeO-C
4-Me-C
4-NO -C
4-Cl-C
2-MeO-C
2-Me-C
2-NO -C
2-Cl-C
6
H
4
-CH
2
OH
OH
OH
OH
-CH OH
-CH OH
-CH OH
-CH OH
2n
2o
2p
2q
2r
2s
75
75
75
75
75
75
75
75
82 ꢁ 2
83 ꢁ 1
85 ꢁ 3
83 ꢁ 2
78 ꢁ 2
76 ꢁ 1
74 ꢁ 1
75 ꢁ 1
6
H
4
-CH
2
2
6
H
4
-CH
2
6
H
4
-CH
2
6
H
4
2
6
H
4
2
2
6
H
4
2
2t
6
H
4
2
2v
A
B
2 4
Reaction conditions: alcohol 1a–v (0.13 mol), glacial acetic acid (0.1 mol), cyclohexane (1.5 mL), [TMDPH ][SO ] (0.01 mmol), reaction time (4 h).
GC-MS yield. The esterification reactions were carried out in triplicate and conducted at least twice on separate days.
[
TMDPH ][SO ]
2 4
H
H
H
H
H
H
O
H
O
O
O
O
H
H C
O
H
H
R
H
O
3
H C
O
H
3
H C
O
H C
O
3
3
O
R
R
H O
2
H
III
Transfer to cyclohexane phase
R
2 4
Scheme 3. A schematic reaction mechanism of the esterification in the presence of [TMDPH ][SO ].

F
Z. Shahnavaz et al.
OH
O
CH3
O
[TMDPH ][SO ](10 mol-%)
2 4
+
O
O
HO
30 mmol
Scheme 4. Esterification of a-tocopherol (a-TCP) with glacial acetic acid using [TMDPH
CH3
Cyclohexane, 60°C, 4 h
O
20 mmol
HPLC yield 88.4 %
4
][SO ].
2
Table 4. Catalytic efficiency of five ionic liquid catalysts for the esterification of n-butanol and glacial acetic acid
A
B
Yield [%]
Entry
Ionic liquid
Reaction time [min]
1
2
3
4
5
TMDPS
230
240
180
200
240
85 ꢁ 2
80 ꢁ 2
88 ꢁ 2
85 ꢁ 2
85 ꢁ 2
4
[TEA][HSO ]
[MIm-C4-MIm][HSO
[Im-C4-Im(SO H) Cl
[TMDPH ][SO
4 2
]
3
2 2
]
2
4
]
A
Reaction conditions: n-butanol (0.13 mol), glacial acetic acid (0.1 mol), cyclohexane (1.5 mL), ionic liquid (0.01 mmol).
B
GC-MS yield.
ꢀ
1
chromatography–mass spectrometry (GC-MS) at intervals of
1
range of 4000–400cm . The amount of water in the liquid salt
was determined by Karl Fisher (KF) titration, using a Metrohm
831 kF coulometer in conditions of ambient humidity and room
temperature. The ionic conductivity (s) was measured using a
h, while the stirring of the reaction mixture continued under
optimised reaction conditions. Complete (100 %) conversion of
glacial acetic acid was observed after 430 ꢁ 10 min.
1
Finally, the esterification of a-tocopherol (a-TCP) was
conducted to show the potential of the current method for a
scale-up application. It is well known that tocopherols, an
isoform of vitamin E, are sensitive to light and air. Their
Mettler Toledo Seven Easy conductivity meter at 258C. The H
1
3
and C NMR spectra were recordedwithBruker Avance600 and
400MHz instruments. All chemical shifts are quoted in parts per
million (ppm) relative to TMS using a deuterated solvent. DSC
curves were obtained with the use of a DSC-Mettler Toledo DSC
822e calorimeter. The measurements were performed in alu-
minium pans with a pierced lidwith a sample mass 9.24mg under
[
30]
antioxidant efficiency is rapidly reduced,
isoforms exhibited moderate to good stability to light and air.
while their ester
[
31]
Large scale acetylation of a-tocopherol (a-TCP) (20 mmol) with
glacial acetic acid (30 mmol) was carried out using [TMDPH2]
ꢀ
1
a dry nitrogen gas atmosphere (10 mL min ). Dynamic scans
ꢀ
1
[SO ] (10 mol-%) at 608C, which gave 8.11 g (88.4 % yield)
after 4 h incubation in the absence of light under N atmosphere
were performed at a heating rate of 108C min in two temper-
ature cycles at a range of 30–300 and 30–5008C. TGA/DTA
curves were obtained with the use of a Mettler Toledo TGA/
4
2
(
Scheme 4).
Very recently, our group reported the synthesis, characteri-
SDTA 851e. All measurements were performed in an Al O3
2
sation, and catalytic application of a low viscous ionic liquid,
0
32]
crucible with a sample mass of 10.65 mg under a nitrogen
ꢀ1
0
namely 4,4 -trimethylene-N,N -sulfonic acid-dipiperidinium
[
atmosphere (10 mL min ). Dynamic scans were performed at a
ꢀ1
chloride (TMDPS).
We investigated the structure–activity
relationship of the two ionic liquids [TMDPH ][SO ] and
heating rate of 108C min in the temperature range of 30–8008C.
The purity and yield of the products were determined using GC-
MS on an Agilent 6890GC/5973MSD analysis instrument under
70 eVconditions. Melting pointswererecordedona B u¨ chi B-545
apparatus in open capillary tubes. Positive and negative ion ESI-
MS analyses were performed using an Agilent 6560 iFunnel
Q-TOF LC-MS instrument.
2
4
TMDPS on the model esterification. The model reaction was
0
also carried out using 10 mol-% of TMDPS, 1,1 -butylenebis-
(3-sulfo-3H-imidazol-1-ium) chloride ([Im-C4-Im(SO H) ]
Cl), 1,1 -butylenebis(3-methyl-3H-imidazol-1-ium) dihydro-
3 2 2-
0
gensulfate ([MIm-C4-MIm][HSO ] ), and triethylammonium
4
2
hydrogen sulfate ([TEA][HSO ]). The ILs were fabricated
4
[
7,25,32–33]
according to the literature methods.
Although the five
Synthesis using TMDP and Sufuric Acid at a Ratio of 1 : 1
ILs can be interchanged under appropriate conditions, the ILs
that contained two sulfonic acid moieties or two acidic anions,
namely hydrogen sulfate, showed higher yields within shorter
reaction times (Table 4, entries 1, 3, and 4). The anion and cation
effect for [TMDPH ][SO ] and [TEA][HSO ] on the yield and
0
A flask containing a solution of 4,4 -trimethylene-dipiperidine
(4.21 g, 20 mmol) in dry CH Cl (20 mL) was cooled to a low
temperature by an ice bath. Sulfuric acid (98 %, 1.840 g mL
2 2
ꢀ1
)
(
1.1 mL, ,20 mmol) was added dropwise to the solution at low
2
4
4
temperature (ice bath). Two phases were formed after stirring
at room temperature overnight. After the decantation of the
upper phase, the white waxy residue was washed with CH Cl2
rate are negligible within experimental error in the measure-
ments (Table 4, entries 2 and 5).
2
(
3 ꢂ 10 mL), and excess solvent was removed by a rotary
Experimental
evaporator under vacuum. The obtained white solid was crys-
tallised from methanol.
General
Unless specified, all chemicals were of analytical grade and
purchased from Merck, Aldrich, and Fluka Chemical Companies
and used without further purification. The FT-IR spectra were
recorded on a Perkin Elmer RX1 FT-IR spectrophotometer in the
Synthesis of [TMDPH ][SO ]
2
4
0
A flask containing a solution of 4,4 -trimethylene-dipiperidine
(4.21 g, 20 mmol) in dry CH Cl (20 mL) was cooled to a low
2
2

Two-Protonic Acid Ionic Liquid and Esterification
G
ꢀ
1
temperature by an ice bath. Sulfuric acid (98 %, 1.840 g mL
(
)
thankful to staff members in the Analytical and Testing Center of Nano-
technology and Catalysis Research Center, the University of Malaya, which
partially supported this work.
2.18 mL, ,40 mmol) was added dropwise to the solution at low
temperature (ice bath). Two phases were formed after stirring at
room temperature overnight. The upper phase was removed by
decantation, and the pale yellow sticky residue was washed with
CH Cl (3 ꢂ 10 mL). After evaporation of excess solvent under
References
2
2
[
1] J. Otera, J. Nishikido, Esterification: Methods, Reactions, and Appli-
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[
2] P. Siengalewicz, J. Mulzer, U. Rinner, in Comprehensive Organic
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[
[
[
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Glacial acetic acid (0.600 g, 0.572 mL, 10 mmol), n-butanol
(9.694 g, 11.968 mL, 13 mmol), [TMDPH ][SO ] (0.308 g,
2 4
1
2
.0 mmol), and cyclohexane (1.157 g, 15 mL) were taken into a
5 mL three necked flask. The flask was equipped with a man-
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ifold and a condenser. After an appropriate reaction time (4 h), a
liquid bi-phase formed in the flask. The liquid phase containing
the ester was isolated by separating funnel and was analysed by
GC-MS. [TMDPH ][SO ] was isolated after removing the
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2
4
product and water by separating funnel and drying in a vacuum
oven at 508C overnight before being tested for reusability.
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[
Esterification of a-TCP with Glacial Acetic Acid
1
a-TCP (20 mmol), glacial acetic acid (30 mmol), and [TMDPH2]
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[SO ] (0.616 g) were mixed and stirred at 608C under N atmo-
4 2
sphere for 2 h in a 100 mL round bottom flask covered with tin
foil. Liquid chromatography–mass spectrometry was utilised to
determine the purity and yield of O-acetyl-a-tocopherol (Ac-
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external standard. The identification of Ac-TCP was performed
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[
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[
35]
equation in the literature.
2
Conclusion
In conclusion, a novel bis-core dicationic TMDP salt containing a
sulfate counterionwas synthesised, and its chemicalstructure was
elucidated by FT-IR, 1D and 2D NMR, and mass analyses. Some
physicalproperties and thermal behaviour and thermal stability of
the new IL were recorded and investigated. The structure eluci-
dation showed that the new IL is a diprotic acid like sulfuric acid,
which can be used as a safe alternative of sulfuric acid. The
catalytic activity of [TMDPH ][SO ] was employed to promote
[
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4
the esterification process under mild conditions. A simple
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method isavoiding and reducing heavy metal and corrosive waste
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ratio of 1 : 1 and 1 : 2 with promising results.
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