Liquid-liquid biphasic synthesis of long chain wax esters using the Lewis acidic ionic liquid choline chloride·2ZnCl2

Article abstract of DOI:10.1016/j.tetlet.2007.07.159

The first liquid-liquid biphasic synthesis of wax esters in a Lewis acidic ionic liquid, choline chloride·2ZnCl₂ by the esterification of long chain carboxylic acids with long chain alcohols is described. The reported reaction system has the advantages of both homogeneous and heterogeneous catalysis with high product yield and the ease of product as well as catalyst separation without the use of an organic solvent. The ionic liquid studied plays the dual role of solvent as well as catalyst and is recycled up to six times without any significant loss of activity.

Full text of DOI:10.1016/j.tetlet.2007.07.159

Tetrahedron Letters 48 (2007) 6962–6965
Liquid–liquid biphasic synthesis of long chain wax esters using
I
the Lewis acidic ionic liquid choline chlorideÆ2ZnCl2
Sadula Sunitha, Sanjit Kanjilal, P. Srinivasa Reddy and Rachapudi B. N. Prasad*
Lipid Science and Technology Division, Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500 007, India
Received 23 May 2007; revised 14 July 2007; accepted 25 July 2007
Available online 28 July 2007
Abstract—The first liquid–liquid biphasic synthesis of wax esters in a Lewis acidic ionic liquid, choline chlorideÆ2ZnCl2 by the ester-
ification of long chain carboxylic acids with long chain alcohols is described. The reported reaction system has the advantages of
both homogeneous and heterogeneous catalysis with high product yield and the ease of product as well as catalyst separation with-
out the use of an organic solvent. The ionic liquid studied plays the dual role of solvent as well as catalyst and is recycled up to six
times without any significant loss of activity.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
Ionic liquids (IL) are an extensively used eco-friendly,
non-conventional reaction medium for many chemical
and biochemical transformations.13 Fraga-Dubreuil
et al.14 reported the first esterification of acetic acid
and methyl malonic acid with alcohols of chain lengths
C5–C10 in imidazolium-based IL with acidic counteri-
Esters of long chain carboxylic acids and long chain
alcohols, typically referred to as ‘wax esters’ are an
important class of fine organics that are widely used as
base materials in cosmetics, pharmaceuticals, lubricants,
paints, wood coatings and perfumery products.1–4 Many
attractive features such as biodegradability, non-toxicity
and preparation from vegetable oils make wax esters
industrially important chemicals. Speciality liquid wax
esters such as jojoba and sperm whale oil have wide
industrial applications as premium lubricants, parting
agents, anti foaming agents and in cosmetics.
À
ons, HSO4 and H2PO4À. However, no attempt was
made at the esterification of long chain carboxylic acids
with long chain alcohols. A new approach using a Bron-
sted acidic IL in the dual role of solvent/catalyst for
esterification has also been reported in the litera-
ture.15–18 However, the success of this chemistry was
limited to esters less than C10 in either carboxylic acid
or alcohol chain length.
Esterification of carboxylic acids with alcohols using
homogeneous and heterogeneous catalysts is well known
in the literature.4–12 However, several limitations such as
an excess of the catalysts or amounts of reactants to
achieve efficient conversion, removal of water during
the reaction, long reaction times and large amounts of
effluent generation during work-up are associated with
these processes. A recent report4 on the synthesis of
wax esters using ZrOCl2Æ8H2O has an additional limita-
tion of lower yields in the case of acids and alcohols with
greater than C14 chain length.
Thus there is a need to develop an environmentally be-
nign synthetic method for the synthesis of long-chain
wax esters. ‘Liquid–liquid biphasic catalysis’ can address
effectively the advantages of both homogeneous and
heterogeneous catalysis and an IL would be a potent
‘biphasic catalyst’ due to well-known physical proper-
ties.19–24 Abott et al. reported25 a new class of moisture
insensitive IL composed of choline chloride and ZnCl2
which has been utilized extensively as a Lewis acid cat-
alyst as well as a reaction medium in carrying out
Diels–Alder reactions,26 Fischer indole annulation,27
O-acetylation of cellulose and monosaccharides28 and
protection of carbonyls.29 The Lewis acidic activity is
primarily due to the presence of complex zinc chloride
ions, [ZnCl3]À, [Zn2Cl5]À and [Zn3Cl7]À along with some
higher clusters of low intensity as confirmed by FAB
mass study.26,30 In the present work, we report the first
Keywords: Wax esters; Lewis acidic ionic liquid; Long chain carboxylic
acid; Long chain alcohol.
q IICT Communication No. 070304.
*
Corresponding author. Tel.: +91 40 27193179; fax: +91 40
27193370; e-mail: rbnprasad@iict.res.in
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.07.159

S. Sunitha et al. / Tetrahedron Letters 48 (2007) 6962–6965
6963
example of choline chlorideÆ2ZnCl2 as a recyclable green
catalyst and reaction media for the practical and highly
efficient liquid–liquid biphasic esterification of long
chain aliphatic carboxylic acids with long chain alco-
hols. The IL remains in one phase and the reactants in
the liquid or molten state remain in the other phase
and the esterification reaction occurs at the interface.
The synthesis of esters mimicking the natural liquid
wax esters was also carried out in choline
chlorideÆ2ZnCl2.
The condensation of carboxylic acids and alcohols of
different chain lengths (C8–C22) were conducted and
the results are outlined in Table 2. All the substrates re-
acted smoothly to give the corresponding esters in excel-
lent yields. High conversions to liquid wax esters, such
as erucyl erucate and oleyl oleate were also achieved (en-
tries 18 and 19). The methodology was extended to the
synthesis of long chain esters of dicarboxylic acids,
namely behenyl sebacate, behenyl adipate and 2-ethyl-
hexyl sebacate by esterification of 1:2 molar equivalents
of dicarboxylic acid and long chain alcohol (Table 3).
The esterification of palmitic acid with cetyl alcohol was
chosen as a model reaction (Scheme 1) to standardize
the reaction parameters such as the amount of choline
chlorideÆ2ZnCl2, reaction temperature and time (Table
1). A good yield of cetyl palmitate was observed in the
presence of 0.1 mol equiv of IL (Table 1, entry 1), dem-
onstrating the efficacy of the IL as an esterification cat-
alyst. However, most of these long chain wax esters are
of high melting point and are poorly soluble in many
commonly used organic solvents. To overcome the
extraction related problems and also to fulfill the advan-
tages of liquid–liquid biphasic catalysis, the synthesis of
other wax esters was conducted by reacting equimolar
amounts of acid, alcohol and IL at 110 °C.
The feasibility of any catalytic process depends on the
reusability of the catalyst. In the present work, the IL
plays the dual role of solvent and catalyst. In order to
investigate the reusability of the IL, the esterification
of octanoic acid and cetyl alcohol was conducted in cho-
line chlorideÆ2ZnCl2 over six successive cycles without
any pre-treatment of the IL. The results shown in Table
4, indicate no significant loss of the Lewis acidic nature
of the IL.
In conclusion, a novel, efficient and environmentally be-
nign method for the synthesis of long chain wax esters
Table 2. Esterification of carboxylic acids with alcohols of different
chain lengthsa
O
Entry Acid
Alcohol
Time Isolated
(h)
yield (%)
OH
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
Palmitic acid
1-Octanol
4b
6
6
8
10
10
12
12
6
6
6
8
10
12
12
12
12
12
12
99
99
99
99
97
96
94
95
99
99
99
99
99
96
97
95
95
93
98
+
Palmitic acid
Palmitic acid
Palmitic acid
Palmitic acid
Palmitic acid
Palmitic acid
Palmitic acid
Octanoic acid
Capric acid
Capryl alcohol
Lauryl alcohol
Myristyl alcohol
Cetyl alcohol
Stearyl alcohol
Erucyl alcohol
Behenyl alcohol
Cetyl alcohol
Cetyl alcohol
OH
110 oC HO-(CH2)2N +(CH3)3Cl -. 2 ZnCl2
Undecenoic acid Cetyl alcohol
O
O
Lauric acid
Myristic acid
Stearic acid
Oleic acid
Behenic acid
Erucic acidb
Erucic acidb
Oleic acid
Cetyl alcohol
Cetyl alcohol
Cetyl alcohol
Cetyl alcohol
Cetyl alcohol
Cetyl alcohol
Erucyl alcohol
Oleyl alcohol
Scheme 1.
a Reaction conditions: acid (2.4 mmol), alcohol (2.4 mmol); choline
chlorideÆ2ZnCl2 (2.4 mmol); reaction temperature: 110 °C.
b GC composition of technical grade erucic acid (in wt %): erucic acid,
94.6%; other fatty acids, 5.4%.
Table 1. Optimization of the reaction conditions for the preparation of
cetyl palmitatea
Entry
Acid:ILb
Temperature
Time
(h)
Isolated
(mol/mol)
(°C)
yield (%)
1
2
3
4
5
6
7
1.0:0.1
1.0:0.25
1.0:0.5
1.0:0.5
1.0:1.0
1.0:1.0
1.0:1.5
110
110
80
110
80
12
12
24
12
24
12
12
90
92
53
95
76
97
98.5
a
Table 3. Preparation of diesters using choline chlorideÆ2ZnCl2
Entry Acid
Alcohol
Time (h) Isolated
yield (%)
1
2
3
Sebacic acid 2-Ethylhexanol
Sebacic acid Behenyl alcohol 24
Adipic acid Behenyl alcohol 24
16
99
88
92
110
110
a Reaction conditions: palmitic acid (2.4 mmol), cetyl alcohol
(2.4 mmol).
b Choline chlorideÆ2ZnCl2.
a Reaction conditions: acid (2.4 mmol), alcohol (4.8 mmol), choline
chlorideÆ2ZnCl2 (2.4 mmol), reaction temperature 110 °C.

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S. Sunitha et al. / Tetrahedron Letters 48 (2007) 6962–6965
Table 4. Recycling of choline chlorideÆ2ZnCl2 in the synthesis of cetyl
29.16, 29.19, 29.27, 29.44, 29.48, 29.55, 29.58, 31.82,
33.68, 34.31, 64.31, 76.59, 76.90, 77.22, 114.03; IR
(Film): m 1739, 1642, 1172, 1029 cmÀ1. Anal. Calcd for
C27H52O2: C, 79.35; H, 12.82. Found: C, 78.89; H,
12.73. EI-MS: m/z 408 [M]+, 269 [MÀ139]+, 166
[MÀ241]+.
octanoatea
Cycle
Conversionb (%)
Time (h)
1
2
3
4
5
6
99
99
98
98
96
95
5
5
5
5
5
5
2.4. Erucyl erucate (Table 2, entry 18)
a Reaction conditions: octanoic acid (2.4 mmol), cetyl alcohol
(2.4 mmol), choline chlorideÆ2ZnCl2 (1.2 mmol), reaction tempera-
1H NMR (200 MHz, CDCl3): d 0.88–0.90 (6H, br t),
1.22–1.39 (56H, br s), 1.55–1.68 (4H, br m), 1.92–2.08
(10H, br m), 2.26 (2H, t, J = 7.8 Hz), 4.03 (2H, t,
J = 6.1 Hz), 5.28–5.35 (4H, br m); 13C NMR
(75 MHz, CDCl3): d 14.33, 22.91, 25.26, 26.17, 27.44,
28.89, 29.40, 29.50, 29.55, 29.71, 29.75, 29.79, 29.87,
30.00, 32.13, 34.65, 64.63, 130.11, 130.13, 174.25; IR
(KBr): m 1739, 1654, 1240, 1173 cmÀ1. Anal. Calcd for
C44H84O2: C, 81.92; H, 13.12. Found: C, 79.33; H,
11.99. EI-MS: m/z 645 [M+1]+, 321 [MÀ324]+, 306
[MÀ338]+.
ture 110 °C.
b Based on GC.
and diesters using the Lewis acidic IL, choline chlo-
rideÆ2ZnCl2 as solvent/catalyst is reported. The present
‘liquid–liquid biphasic’ method has the following advan-
tages over existing methods for wax ester synthesis: (a)
choline chlorideÆ2ZnCl2 shows superior catalytic activity
than reported systems; (b) this IL is cheap and easy to
prepare compared to imidazolium based ILs; (c) as the
IL is moisture insensitive, there is no need to remove
water produced during the reactions and the IL can be
reused for at least six cycles without any pre-treatment
or significant loss of activity, and (d) liquid esters (as a
separate phase) can be conveniently decanted above
their melting point avoiding the use of volatile organic
solvents.
2.5. Di-2-ethylhexyl sebacate (Table 3, entry 1)
1H NMR (200 MHz, CDCl3): d 0.88–0.90 (12H, br t),
1.21–1.39 (24H, br s), 1.51–1.67 (6H, br m), 2.27 (4H,
t, J = 7.5 Hz), 3.95 (4H, d, J = 7.5 Hz); 13C NMR
(75 MHz, CDCl3): d 10.89, 13.94, 22.87, 23.69, 24.9,
28.82, 29.0, 30.32, 34.31, 38.63, 66.53, 76.61, 76.93,
77.24, 173.86; IR (Film): m 1738, 1172, 1039 cmÀ1. Anal.
Calcd for C26H50O4: C, 73.19; H, 11.81. Found: C,
73.05; H, 11.38. EI-MS: m/z 427 [M+1]+, 315
[MÀ111]+, 297 [MÀ129]+, 185 [MÀ241]+.
2. Experimental
2.1. Preparation of choline chlorideÆ2ZnCl2
Choline chloride (20 mmol) was mixed with zinc chlo-
ride (40 mmol) and heated to 150 °C with stirring until
a clear colourless liquid was obtained.25
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