Ionic liquid-regulated sulfamic acid: Chemoselective catalyst for the transesterification of β-ketoesters

Article abstract of DOI:10.1016/S0040-4039(03)01187-0

1-Propyl-3-methylimidazolium chloride ([C₃MIm]Cl) ionic liquid and sulfamic acid (NH₂SO₃H), as a synergetic catalytic medium, were used for the transesterification of acetoacetate with alcohols of different structures. It shows the good ability for the chemoselective transesterificatin of β-ketoesters and maintains its catalytic activity in the reuse.

Full text of DOI:10.1016/S0040-4039(03)01187-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 5037–5039
Ionic liquid-regulated sulfamic acid: chemoselective catalyst for
the transesterification of b-ketoesters
Wang Bo, Yang Li Ming* and Suo Ji Shuan
State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics,
Chinese Academy of Sciences, Lanzhou 730000, China
Received 10 April 2003; revised 30 April 2003; accepted 7 May 2003
Abstract—1-Propyl-3-methylimidazolium chloride ([C3MIm]Cl) ionic liquid and sulfamic acid (NH2SO3H), as a synergetic
catalytic medium, were used for the transesterification of acetoacetate with alcohols of different structures. It shows the good
ability for the chemoselective transesterificatin of b-ketoesters and maintains its catalytic activity in the reuse. © 2003 Elsevier
Science Ltd. All rights reserved.
1. Introduction
b-ketoesters. A type of distannoxanes could catalyze
this process even in neutral conditions.12 Although
these methods are suitable for certain synthetic condi-
tions, sometimes, there exist some drawbacks such as
expensive reagents, long reaction time, tedious workup,
low selectivity, and large amounts of solid supports
which would eventually result in the generation of a
large amount of toxic waste.13 Biocatalytic transesterifi-
cation of b-ketoesters in ILs had been reported, but the
sensitivity and unstability of the catalysts were still
serious problems.14
Ionic liquids (ILs) consisting of 1,3-dialkylimidazolium
cations and their counter ions have attracted growing
interest in the last few years,1 and particularly in the
last two years, much efforts have paved the way for
alternative and new synthetic strategies in the realm of
synthetic organic chemistry, due to their advantages of
negligible vapor pressure and wide liquid range, etc.2 In
general, the thermodynamics and kinetics of the reac-
tions in ILs are very different from those in conven-
tional molecular solvents. Furthermore, ILs could even
control some reaction processes to selectively obtain
specific products, which was usually impossible in con-
ventional molecular solvents. ILs could provide some
reactions with particular controllability. In this paper,
we report an ionic liquid regulated catalyst, sulfamic
acid, which displays the ability to selectively catalyze
transesterification of b-ketoesters in an ionic liquid
medium, instead of ketalization.
The development of the mild, low-cost and high perfor-
mance acid catalysts for green chemistry have attracted
much interest.15 Sulfamic acid (NH2SO3H), with mild
acidity, involatility and incorrosivity, is insoluble in
Table 1. Comparison of transesterification in the
NH2SO3H/[C3MIm]Cl system within different mediuma
Entry
Solvent
Homo/
Conversion
(%)c
Selectivity
(%)c
heterob
b-Ketoesters are employed widely as chemical interme-
diates in the pharmaceutical, agrichemical, chemical
and polymer industries.3 A lot of useful catalysts,
including homogeneous ones of sulfated tin oxide,4
yttria-zirconia based strong Lewis acid,5 p-TSA,6 zinc,7
basic 4-DMAP8 and heterogeneous ones of zeolites,9
kaolinitic clay,10 montmorillomite K-1011 and so on,
have been efficiently employed in transesterification of
1
2
3
4
5
–
Hetero
Hetero
Hetero
Homo
Homo
95
93
92
96
94
79
80
75
98
99
Hexane
CH2Cl2
[C3MIm]Cl
[C5MIm]Cld
a Reaction conditions: 10 g [C3MIm]Cl or 10 ml organic solvents, 1.0
g sulfamic acid, 0.10 mol methyl acetoacetate, 0.12 mol butanol, 3.0
h, 80°C.
b Homo is the homogenous system, and hetero is the heterogenous
system.
Keywords: ionic liquid; sulfamic acid; chemoselective; transesterifica-
tion; b-ketoesters.
* Corresponding author.
c Detected by GC.
d 1-Pentyl-3-methylimidazolium chloride.
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01187-0

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W. Bo et al. / Tetrahedron Letters 44 (2003) 5037–5039
+
−
common organic solvents. It is very stable16 and has
been used as an efficient heterogeneous acid catalyst for
ketalization.17 The intrinsic ability of ILs to dissolve
substrates of wide diversity, from organics to
organometallics to inorganics, and its facility of recy-
cling add itself to the chemists’ arsenal for the execu-
tion of diverse processes. During the course of our
studies on ILs, we found 1-propyl-3-methylimidazole
chloride ([C3MIm]Cl) has the excellent solubility for
sulfamic acid, and its solubility in [C3MIm]Cl even
exceeded 80 g/100 ml at 80°C. This prompted us to
systematacially investigate the transesterification of b-
ketoesters using this homogeneous NH2SO3H/
[C3MIm]Cl system.
between ionic liquid and HN3SO3 when sulfamic acid
dissolved in [C3MIm]Cl, which would account for sul-
famic acid catalyzing ketalization in common organic
solvents and chemoselectively catalyzing the transester-
ification of b-ketoesters in [C3MIm]Cl ionic liquid.
However, the detailed mechanism was not explicit.
The transesterification between some alcohols and
methyl acetoacetate was conducted in the NH2SO3H/
[C3MIm]Cl system, and the results are listed in Table 2.
This method is quite efficient for a wide range of
structurally varied alcohols such as open chain, cyclic
and unsaturated ones. As for tert-butyl alcohol (entry
3), which is often problematic in acid-catalyzed reac-
tions, a moderate yield of product was achieved by this
method. With the unsaturated alcohols of low electron-
donating characteristics, the transesterification was suc-
cessfully performed with satisfactory yields in this
catalytic system (entries 6 and 7), which are rather
difficult by common methods because of Carroll
rearrangement.8
2. Results and discussion
The transesterification of methyl acetoacetate with
butanol catalyzed by sulfamic acid was investigated in
different medium (Table 1). Owing to the immiscibility
of sulfamic acid with common organic solvents, this
reaction was carried out in a heterogeneous system
(entries 1–3). Lots of ketals and hemiketals derived
from the ketalization of b-carbonyl of the acetoacetate
with alcohols were detected, so that the selectivity to
the desired product was poor. Similar results were
obtained in hexane and CH2Cl2. In contrast, NH2SO3H
can be dissolved in chloride-based ILs to form a homo-
geneous NH2SO3H/[C3MIm]Cl system, and the transes-
terification was successfully performed in it (entries 4
and 5). It is worthy to note that the selectivity to the
desired ester was significant higher in the ionic liquids
than in common organic solvents and the solvent-free
system, despite of the NH2SO3H catalyzing ketalization
reported by some other researchers.17 Therefore, it may
be supposed that the [C3MIm]Cl ionic liquid could not
only act as a solvent to dissolve NH2SO3H, but also
make it a chemoselective catalyst, and the attack of
alcohols to b-site of acetoacetate would be effectively
inhibited in this reaction environment (Scheme 1).
The reuse ability of this H2NSO3H/[C3MIm]Cl system
was studied in the transesterification between methyl
acetoacetate and butanol. The product could be simply
separated from [C3MIm]Cl by toluene extraction and
H2NSO3H was still left in [C3MIm]Cl, so that the
recover and reuse of the H2NSO3H/[C3MIm]Cl were
very convenient. As shown in entry 1, the yield of butyl
acetoacetate has only a little decrease after the reuse of
H2NSO3H/[C3MIm]Cl system for five times.
3. Conclusions
The [C3MIm]Cl ionic liquid could not only act as a
solvent to dissolve NH2SO3H, but also regulate it to
become a chemoselective catalyst for the transesterifica-
tion of b-ketoesters. Compared with common organic
solvents, the undesired reactions could be effectively
inhibited, and the selectivity to the desired ester was
markedly improved in the H2NSO3H/[C3MIm]Cl sys-
tem. The separation of the product and the reuse of the
catalytic system were very convenient.
It has already been manifested that sulfamic acid was
comprised not of the aminosulfonic acid form, but
rather of +H3NSO3 zwitterionic units by both X-ray
−
and neutron diffraction techniques18 (Scheme 2). There-
fore, it would be supposed that both sulfamic acid and
IL were in the form of inner salts to some extent. In
this way, there may be a synergetic effect constituted
4. Experimental
In a typical experiment, sulfamic acid (1.0 g) was
dissolved into [C3MIm]Cl ionic liquid (10 g) in a 100
mL round bottom flask equipped with a distillation
condenser at 80°C. Then methyl acetoacetate (0.10 mol)
and alcohol (0.12 mol) were introduced. The content
was stirred vigorously at 80°C. After the desired reac-
tion time, the reaction mixture was cooled to room
temperature, and then was extracted with toluene (10
mL×3). The combined organic extract was analyzed by
GC/MS. The pure transesterified products could be
obtained by concentrating the extract and then separat-
ing it on silica gel column using light petroleum and
diethyl ether as eluent.
Scheme 1.
Scheme 2.

W. Bo et al. / Tetrahedron Letters 44 (2003) 5037–5039
5039
Table 2. Transesterification of methyl acetoacetate with various alcohols in the NH2SO3H/[C3MIm]Cl systema
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