A facile and efficient nucleophilic displacement reaction at room temperature in ionic liquids

Article abstract of DOI:10.1016/S0040-4039(02)02327-4

We have investigated the use of room temperature ionic liquids as catalytic and environmentally benign solvents for the facile homogenous synthesis of benzyl salicylate by the nucleophilic displacement reaction between sodium salicylate and benzyl chloride. The reaction was found to proceed under relatively mild conditions with excellent conversion (up to 96%) without the use of PTCs. The ionic liquids were recycled and reused. The effect of temperature was also investigated. No by-products were observed after ¹H NMR and GC analysis.

Full text of DOI:10.1016/S0040-4039(02)02327-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 9381–9384
A facile and efficient nucleophilic displacement reaction at room
temperature in ionic liquids
Zaher M. A. Judeh,* Hao-Yu Shen, Bun Ching Chi, Li-Chun Feng and Selvaratnam Selvasothi
Chemical and Process Engineering Centre, National University of Singapore, 10 Kent Ridge Crescent, Singapore 117576
Received 17 September 2002; accepted 11 October 2002
Abstract—We have investigated the use of room temperature ionic liquids as catalytic and environmentally benign solvents for the
facile homogenous synthesis of benzyl salicylate by the nucleophilic displacement reaction between sodium salicylate and benzyl
chloride. The reaction was found to proceed under relatively mild conditions with excellent conversion (up to 96%) without the
use of PTCs. The ionic liquids were recycled and reused. The effect of temperature was also investigated. No by–products were
1
observed after H NMR and GC analysis. © 2002 Elsevier Science Ltd. All rights reserved.
7
1
. Introduction
Room-temperature ionic liquids are finding growing
8
applications in separations and organic transforma-
Recent examples of such transformations
include hydrogenations, Friedel–Crafts reactions,
Diels–Alder reactions, Heck reactions, Bischler–
Napieralski reactions, olefin hydrodimerizations and
olefin dimerizations. Ionic liquids are emerging as
novel replacements for volatile organic compounds
9–15
Benzyl salicylate, like other esters of aromatic acids, is
used in the perfumery and flavor industries. Its main
synthetic routes involve the use of phase transfer cata-
lysts (PTCs) in the heterogeneous reaction between
benzyl chloride and either sodium salicylate or salicylic
acid. Other methods involve the reaction of benzyl
tions.
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10
11
12
13
14
1
15
2
alcohol with salicylic acid in the presence of a catalyst
(
VOCs). The desirable advantages of ionic liquids such
3
4
(
e.g. organotin, nonquaternizable tertiary amines ) or
5
as lack of vapor pressure and thermal stability have
made them excellent reaction media and environmen-
tally benign solvents.
by transesterification of benzyl alcohol with methyl
salicylate using sodium methyl salicylate as catalyst.
The reaction between salicylic acid and benzyl bromide
proceeded slowly in 24 hours with 80% yield in the
6
We report here an efficient, homogenous and environ-
mentally friendly nucleophilic displacement reaction
using ionic liquids as a substitute for heterogeneous and
phase transfer catalysis methods. The reaction is inves-
tigated through the preparation of benzyl salicylate
presence of tetraalkylammonium fluoride catalyst. The
main drawbacks of these methods are the generation of
a number of undesired by-products (for example, benz-
yl alcohol, benzyl benzoate, salicylic acid, dibenzyl
ether) as a result of hydrolysis and side reactions and a
longer reaction time (8–24 hours) coupled with low
(
Scheme 1).
6
yields. The conventional PTC reactions involve the use
of environmentally unfavourable halogenated solvents
and catalyst separation is another major problem. We
envisaged that the use of ionic liquids as catalyst and
solvent will be advantageous in such a reaction where a
homogenous mixture is formed and thus omitting the
use of PTC. Moreover, the ionic liquids thus employed
can be recycled and reused.
2. Results and discussion
Nucleophilic displacement reactions using ionic liquids
as solvents are rare in the literature. We are not aware
of such reactions involving salts of organic compounds
16
Keywords: nucleophilic displacement; ionic liquids; sodium salicylate;
benzyl salicylate.
*
Corresponding author. Tel.: +65-8744216; fax: +65-68734805;
Scheme 1. Esterification of sodium salicylate with benzyl
e-mail: cpezj@nus.edu.sg
chloride.
0
040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)02327-4

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Z. M. A. Judeh et al. / Tetrahedron Letters 43 (2002) 9381–9384
sodium salicylate was 1.5 times the stoichiometric
amount of benzyl chloride. Initially, a clear homoge-
nous reaction mixture was observed which then turned
cloudy after 20 minutes due to sodium chloride forma-
tion indicating the onset of the reaction. As time passed
more sodium chloride was formed and the reaction
mixture turned cloudy due to poor solubility of sodium
chloride in the ionic liquid. The reaction was found to
proceed smoothly with high conversion (GC analysis,
Fig. 2) and the identity of the product was confirmed
by H NMR spectroscopic analysis where no decom-
position or by-products were observed. The effect of
temperature change on the conversion was also investi-
gated using the [hmim]BF4 ionic liquid. The above
reaction was repeated essentially under the same condi-
tions except that the reaction was done at 120°C
instead of 100°C. It can be seen clearly from Fig. 3 that
appreciable change is observed when the reaction tem-
perature is increased from 100 to 120°C especially at
the beginning of the reaction. The most dramatic
change was observed in the first half hour where the
Figure 1. Structures of the ionic liquids.
e.g. sodium salicylates). These reactions are normally
carried out in a heterogeneous medium using a PTC to
facilitate the reaction between the organic reactants and
the salts. The use of a PTC is important to activate the
anions and also to provide the contact between the
reactants in order for the reaction to proceed. The
effectiveness of the four ionic liquids, [omim]Cl,
1
18
(
[
hmim]BF , [omim]BF and [bmim]PF (Fig. 1), as cat-
4 4 6
alysts and solvents in the nucleophilic displacement
reactions was examined in the preparation of benzyl
salicylate. Since the ionic liquids used for this study
contain bulky, nitrogen-based, organic cations, it is
thought that they may act like nitrogen-based PTCs.
These ionic liquids could also activate the anions for
the reaction and thus result in an enhanced reaction
1
6
rate. The solubility of sodium salicylate in these ionic
liquids was investigated at 100°C since the solubility at
room temperature was low. Therefore, sodium salicyl-
ate was added portionwise under vigorous stirring to
four test tubes containing 2 mL each of the four ionic
liquids preheated to 100°C. Addition was stopped when
a slight cloudiness was observed. The solubility test
results in the four ionic liquids are shown in Table 1. It
is clear that sodium salicylate showed a more enhanced
solubility in [hmim]BF compared to its solubility in the
other ionic liquids. A comparable solubility was
4
Figure 2. Conversion of benzyl chloride at 100°C.
observed in [omim]Cl and [omim]BF while minimum
4
solubility was obtained in [bmim]PF . It is interesting
6
to note that further addition of sodium salicylate to
[
omim]Cl, [hmim]BF4 and [omim]BF4 ionic liquids
resulted in a more cloudy and viscous but still homoge-
nous solution while sodium salicylate precipitated out
when more was added to [bmim]PF . The influence of
6
the different cations and anions as well as the effect of
polarity on the solvating ability of ionic liquids is still
7
being investigated.
17
Initial reaction investigations
were done using
[
hmim]BF as a model ionic liquid reaction medium in
4
view of its high solvating ability for sodium salicylate.
The reaction procedure involved the addition of benzyl
chloride to a preheated (100°C) and well-stirred solu-
tion of sodium salicylate in [hmim]BF . The amount of
Figure 3. Conversion of benzyl chloride at 120°C.
4
Table 1. Solubility results of sodium salicylate at 100°C
Solvent
[
bmim]PF6
[omim]Cl
0.2170
[hmim]BF4
0.6937
[omim]BF4
0.2798
Solubility (g/2 mL)
0.1015

Z. M. A. Judeh et al. / Tetrahedron Letters 43 (2002) 9381–9384
9383
In conclusion, we have demonstrated that ionic liquids
can be successfully used for nucleophilic displacement
reactions involving organic substrates where one of the
reactants is in the form of a salt. The reaction was
found to proceed with high conversion (up to 96%)
under relatively shorter reaction times and lower tem-
peratures to give the desired benzyl salicylate as the sole
product. The process is also significant from the view-
point of pollution control where VOCs and PTC can be
avoided while the ionic liquids can be recycled.
conditions used for the [hmim]BF ionic liquid at 100°C
4
(
Fig. 2) and also at 120°C (Fig. 3). It was found that
Acknowledgements
[bmim]PF ionic liquid behaved in a similar fashion to
6
that of [hmim]BF at both reaction temperatures (100
4
and 120°C). The rate of formation of benzyl salicylate
We would like to thank the National University of
Singapore (NUS) and the Agency for Science, Technol-
ogy and Research (A*STAR) for financial support. We
also thank Roger Read for helpful discussions.
in [hmim]BF at 120°C seemed to be slightly higher
4
than that observed with [bmim]PF . It is important to
6
note that benzyl salicylate was the sole product
obtained in these reactions after analysis of the prod-
1
ucts by H NMR and GC. Sampling of the product
from the reaction using [omim]BF ionic liquid was
4
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half an hour.
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2
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