Rational design of sugar-based-surfactant combined catalysts for promoting glycerol as a solvent

Article abstract of DOI:10.1002/chem.200801495

The use of glycerol as a solvent for environmentally friendly organic reactions has been demonstrated. It was observed that the surfactant combined catalysts (SCCs) with glycerol can enhance the diffusion of organic substrate in the glycerol. The study found that micellar catalysis in glycerol form a unstable emulsions. The study also investigated the reaction of 1,2-epoxydodecane with dodecanoic acid at at temperature of 110°C in glycerol. Diethoanolamine with dodecanoic acid can be used as a phase-transfer agent which can accelerate the diffusion of organic substrate in the glycerol. The study also concluded that the surfactant need to be use with a catalysis to use glycerol as solvent for the improved diffusion of organic compounds. The study used renewable resources to provide an eco-friendly environment during all reactions.

Full text of DOI:10.1002/chem.200801495

DOI: 10.1002/chem.200801495
Rational Design of Sugar-Based-Surfactant Combined Catalysts for
Promoting Glycerol as a Solvent
Ayman Karam,[a] Nicolas Villandier,[a] Mathieu Delample,[a, c] Carmen Klein Koerkamp,[b]
Jean-Paul Douliez,[c] Robert Granet,[b] Pierre Krausz,[b] Joꢀl Barrault,[a] and
FranÅois Jꢁrꢂme*[a]
Since the last decade, catalysis in water has attracted a lot
of attention.[1] Indeed, it has been well established that the
design of catalytic processes in water offers indisputably en-
vironmentally friendlier pathways. However, to get over the
reactivity of water and the low solubility of most of organic
substrates in water, researchers, especially Kobayashiꢀs
group, have developed a new concept based on the use of
surfactant combined catalysts (SCCs).[2] These SCCs are
able to form stable emulsions in water, which results in a
considerable increase in both the reaction selectivity and the
reaction rate. However, even if spectacular results were re-
ported under micellar catalysis, emulsification of the reac-
tion mixture unfortunately makes extraction of the reaction
products highly difficult. Indeed, in most cases assistance of
an organic solvent is required, which considerably decreases
the environmental benefit of using water as solvent.[2,3] It
has to be noted that cyclodextrins appear to be a good alter-
native to overcome this issue because these carbohydrates
avoid emulsification of the reaction media while maintaining
a good diffusion of the organic reactants in the aqueous
phase.[4] However, even if extraction of the reaction prod-
ucts was considerably facilitated, the use of highly hydro-
phobic substrates is still subject to strict limitations.
Seeking new improvements for catalysis in water, we
found that using glycerol as a solvent offers as many advan-
tages as water, and our aim herein is to convince the reader
that glycerol could be familiarly considered as “organic
water”. Indeed, like water, glycerol is natural, highly hydro-
philic, nontoxic (LD50 (oral rat)=12600 mgKgÀ1), abun-
dant (1.5MtyearÀ1 in 2008), biodegradable and very cheap
(ꢀ1E/kg).[5] Moreover, compared with water, glycerol has a
higher boiling point (2908C) and a lower vapour pressure
(<1 mmHg at 508C), which makes the development of cata-
lytic processes at temperatures around 1008C technically
easier. Surprisingly, despite having very similar solvent prop-
erties to those of water, only pioneer catalytic studies have
been investigated in glycerol.[6] This tendency might arise
from 1) the very low solubility of organic substrates in glyc-
erol and 2) the intrinsic reactivity of this natural polyol,
which leads to the formation of side products.
Herein, we wish to show that the use of SCCs allow all
drawbacks to the use of glycerol as a solvent to be overcome
by favouring a better diffusion of organic substrates in the
glycerol phase and creating some hydrophobic environments
inside which it is possible to inhibit the reactivity of glycerol.
Moreover, we found that micellar catalysis in glycerol offers
a remarkable advantage compared with water because the
emulsions formed in glycerol were found to be unstable.
Consequently, two phases rapidly formed at the end of the
reaction, which allowed an easy extraction of the reaction
products without the assistance of any organic solvents, as is
generally the case in water.
[a] A. Karam, Dr. N. Villandier, M. Delample, Dr. J. Barrault,
Dr. F. Jꢁrꢂme
Laboratoire de Catalyse en Chimie Organique
Universitꢁ de Poitiers/CNRS
40 avenue du recteur Pineau, 86022 Poitiers (France)
Fax : (+33)549-453-349
In the first set of experiments, we investigated the base-
catalyzed ring opening of 1,2-epoxydodecane with dodeca-
noic acid as a model reaction. For the reasons mentioned
above, when this reaction was performed at 1108C in glycer-
ol by using conventional basic catalysts, such as chitosan,
silica-supported methylamine, ZnO or K2CO3, the reaction
rate was low and total conversion only occurred after 18 h
(Table 1, entries 2–5). Similarly, the selectivity of the reac-
tion was poor because glycerol ethers that resulted from the
E-mail: francois.jerome@univ-poitiers.fr
[b] C. K. Koerkamp, Dr. R. Granet, Prof. P. Krausz
Laboratoire de Chimie des Substances Naturelles
Facultꢁ des Sciences et Techniques
La Borie, 123 avenue Albert Thomas 87060 Limoges (France)
[c] M. Delample, Dr. J.-P. Douliez
INRA Nantes, BIA ꢁquipe Interfaces et Systꢃmes Dispersꢁs
Rue de la Gꢁraudiꢃre, 44316 Nantes (France)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200801495.
10196
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Chem. Eur. J. 2008, 14, 10196 – 10200

COMMUNICATION
Table 1. Ring opening of 1,2-epoxydodecane with dodecanoic acid, catalyzed
by different bases in glycerol.[a]
amphiphilic intermediate may act as a phase-transfer agent
that favours better diffusion of organic substrates in the
glycerol phase. However, despite this clear rate acceleration,
glycerol ethers were unfortunately still produced as a side
product in more than 10% yield, which confirmed the harm-
ful reactivity of glycerol towards 1,2-epoxydodecane.
To overcome this problem, we synthesised a new family
of SCCs. As observed in water, the SCCs were expected to
form some hydrophobic environments in glycerol. Thanks to
hydrophobic–hydrophilic interactions, diffusion of glycerol
inside these hydrophobic pockets should be difficult, which
thus makes the development of selective catalytic processes
possible. The success of this approach closely depends on
the localization of the catalytic sites, which have to be as
close as possible to this hydrophobic environment. To reach
our goal, we prepared different aminopolysaccharides
(APs). These APs were synthesised by oxidation of hydrox-
yethylcellulose with sodium periodate[7] followed by a cata-
lytic reductive amination[8] over Pd/C starting from dodecyl-
amine, octylamine and butylamine to afford the basic cata-
Entry Catalyst
Time [h] Conv.[b] [%] Ester[c] [%] Ether[c] [%]
1
–
18
18
18
18
18
6
30
98
98
80
70
98
98
90
95
98
98
20
54
80
70
60
70
95
85
85
95
95
5
15
15
10
10
10
2
3
4
5
chitosan
SiO2-NHMe
ZnO[d]
K2CO3
6
HN
N
7
8
AP-1a
AP-2
3
5
trace
5
9
AP-3
6
5
10
11
AP-1b
4
6
trace
trace
AP-1a[e]
[a] Epoxide (1 mmol) and carboxylic acid (1 mmol) were stirred in glycerol
(4 mL) at 1108C in the presence of catalyst (20 mol%). [b] Conversion of 1,2- lysts AP-1a,b, -2 and -3, respectively (Scheme 1). Physico-
epoxydodecane. [c] Determined by gas chromatography (GC) with dodecane
as internal standard. GC response factors are given in the SIES. [d] 5 wt%.
Supporting Information Experimental Section (SIES). The
[e] Reaction performed at 908C.
chemical data concerning these APs are provided in the
structures of these APs are highly interesting owing firstly
to their amphiphilic properties and secondly because the hy-
drophobic core is surrounded by some amino moieties that
addition of glycerol to 1,2-epoxidodecane were produced as
secondary products in 10–15% yield.
can act as basic catalysts.
As expected, when a solution of AP-1a (25 gLÀ1, which
corresponds to catalytic conditions) in glycerol was vigo-
rously stirred with 2 mL of a solution of 1,2-epoxydodecane
(0.1m) in ethyl acetate, a white turbid mixture, correspond-
ing to the diffusion of the 1,2-epoxydodecane solution in
glycerol, formed rapidly (see Figure 1, left).
Interestingly, compared with other tested catalysts, use of
diethanolamine led to a decrease in reaction time from 18
to 6 h (Table 1, entry 6). In this case, we assumed that dieth-
anolamine rapidly reacted with dodecanoic acid at the inter-
face to form an amphiphilic ammonium carboxylate. This
Scheme 1. Synthesis of amphiphilic AP catalysts. DS=degree of substitution, MS=molecular weight and is commonly used to describe hydroxyethylcel-
lulose. Conditions: i) NaIO4, H2O, 24 h, ii) MeOH/H2O (80:20), fatty amine, Pd/C, H2 (10 bar), 308C, 15 h.
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F. Jꢁrꢂme et al.
with dodecanoic acid in glycerol and 2) the hydrophobic
AHCTUNGTREGeNNUN nvironments created by APs are crucial for performing
highly selective organic reactions in glycerol.
The scope of this method was then studied by conducting
the reaction with different carboxylic acids and epoxides.
Reactions were performed at 908C in the presence of AP-
1a (20 mol% of basic sites; Table 2). Interestingly, in all
cases AP-1a was found to be highly selective and the de-
sired esters were always produced as the exclusive product.
Indeed, this catalytic process was highly tolerant of the pres-
ence of functional carboxylic acids or epoxides, and their
corresponding esters were obtained in yields of 80–95%
(Table 2, entries 1–8). Lower yields were obtained when
Figure 1. Micelles in a mixture of AP-1a and a solution of 1,2-epoxydo-
decane in glycerol, as detected by phase contrast microscopy.
The average size of spherical colloidal particles formed in
glycerol from AP-1a and 1,2-epoxydodecane was deter-
mined by phase-contrast microscopy. This analysis showed a
large distribution of particle sizes (from 5 to 30 mm;
Figure 1, right), which is in perfect agreement with the struc-
ture of AP-1a. As mentioned in the SIES, an important
fragmentation of the polysaccharide structure occurs during
the synthesis of APs, and AP-1a is actually a mixture of dif-
ferent oligomers with a large distribution of molecular
weights, which might explain the large distribution of parti-
cle sizes observed by phase-contrast microscopy.
Table 2. Selective ring opening of epoxides with carboxylic acids, cata-
lyzed by AP-1a (20 mol% of basic sites) in glycerol.[a]
Entry Acid
Epoxide
Conv.[b] Ester[c] Ether[d]
[%]
[%]
[%]
1
2
3
4
5
6
7
8
95
80
trace
Taking into account the unique ability of AP-1a to form
emulsions in glycerol in the presence of an organic sub-
strate, we investigated its catalytic performances, activity
and selectivity in the ring opening of 1,2-epoxydodecane
with dodecanoic acid. As shown herein, if amphiphilic AP-
1a was used as the catalyst, the reaction rate was considera-
bly increased and total conversion was achieved within 3 h
(Table 1, entry 7). Decreasing the hydrocarbon chain length
of APs from dodecyl to octyl and butyl resulted in a de-
crease in the reaction rate, which further indicates the key
role played by the amphiphilic nature of APs in conducting
organic transformations in glycerol (Table 1, entries 7–9).
To our great delight, as described above, the hydrophobic
environment created by APs in glycerol decreased the side-
formation of glycerol ethers. Indeed, use of AP-2 and -3 as
the catalyst led to a drop in the yields of glycerol ether from
10–15% in the case of conventional basic catalysts to only
5% yield (Table 1, entries 8, 9). Further increasing the fatty
chain length from butyl/octyl to dodecylamine afforded an
even more selective catalyst. Indeed, with AP-1a catalyst,
glycerol ethers were only detected as trace and the desired
ester was produced in 95% yield (Table 1, entry 7). A de-
crease in the number of fatty chains grafted on APs from a
DSNH of 0.5 to 0.3 (AP-1b) led to only a slight decrease in
reaction rate but no change in selectivity was observed
(Table 1, entries 7, 10). Interestingly, the catalytic reaction
can be also successfully carried out at 908C without any
change in selectivity, whereas the other tested catalysts were
found to be poorly active at such temperatures (Table 1,
entry 11).
95
90
90
98
97
98
98
90
80
80
95
85
90
80
trace
trace
trace
<2
trace
<2
trace
9
85
60
<2
10
95
65
trace
[a] Epoxide (1 mmol) and carboxylic acid (1 mmol) were stirred over-
night at 908C in glycerol (4 mL). [b] Conversion of epoxide. [c] Isolated
yield. [d] Determined by GC at the end of the reaction, trace means
below the detection limit of the GC.
These experiments clearly demonstrate that 1) the amphi-
philic properties of APs are responsible for the increase in
the reaction rate of the ring opening of 1,2-epoxydodecane
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Sugar-Based Surfactant Combined Catalysts
COMMUNICATION
starting from 2-(3,4-dimethoxyphenyl)acetic acid and cyclo-
hexanecarboxylic acid (60–65%; Table 2, entries 9, 10). In
these cases the epoxides were partially degraded, which ex-
plains the observed drop in yield. However, in both cases,
only trace amounts of glycerol ethers were detected, which
confirms the great efficiency of APs.
Following these results, we then studied the extraction of
the reaction products with the aim of recycling the homo-
ACHTUNGTRENNUNGgeneous amphiphilic AP catalysts and showing all the possi-
bilities offered by glycerol as a solvent. To our great delight,
we found that the emulsion formed by APs in glycerol was
much less stable than in water (Figure 2). Consequently,
Figure 3. Recycling experiments in the presence of 20 mol% of AP-1b
(conditions: dodecanoic acid (1 mmol), 1,2-epoxydodecane (1 mmol),
glycerol (2 mL), 1108C, 3 h).
To show the versatility of our procedure, we then moved
on to other base-catalyzed reactions and in particular
screened some Knoevenagel-type reactions between malo-
nonitrile and benzaldehyde derivatives and the Henry reac-
tion and Michael addition of nitroethane to 2-cyclohexen-1-
one (Table 3).
Remarkably, whereas in most cases diethanolamine cata-
lyzed these reactions with a lot of difficulty, mainly because
of the poor solubility of the reactants in glycerol (except for
the Michael addition), AP-1b afforded all the desired prod-
ucts in yields ranging from 85 to 96%. Moreover, as ob-
served above for the ring opening of epoxides, AP-1b was
easily recycled by simple decantation/extraction of the reac-
tion products. In this way, it was possible to successfully per-
form three successive catalytic runs for the Michael addi-
tion, which shows the versatility of our methodology.
In conclusion, we showed herein that glycerol could be a
very convenient solvent for conducting environmentally
friendly organic reactions. Like water, glycerol is safe and
Figure 2. Emulsion behaviour of APs in A) water during the reaction
(70% yield after 8 h at 908C), B) in water after centrifugation at the end
of the reaction, C) in glycerol during the reaction and D) in glycerol after
centrifugation at the end of the reaction.
after centrifugation at the end of the reaction, the reaction
media rapidly became biphasic, which allowed direct extrac-
tion of the reaction products without the assistance of any
organic solvents as is generally required in water.
Based on this remarkable advantage of glycerol compared
with water, we chose to examine the possibility of catalyst
recycling. After extraction of the reaction products by
simple decantation, 1,2-epoxy-
dodecane and dodecanoic acid
Table 3. Versatility of AP-1a for conducting base-catalyzed reactions in glycerol.[a]
were reloaded for another cata-
lytic run. With AP-1a, a de- Electrophile
crease in the catalytic activity
was observed cycle after cycle,
mainly because of its partial
solubilization in the product
phase (see the SIES). However,
AP-1b, which has a lower fatty
chain content, was found to be
totally insoluble in the reaction
product phase. Consequently,
by using AP-1b as the homoge-
neous catalyst, up to ten con-
secutive catalytic runs were suc-
cessfully performed without any
change in activity or selectivity,
which shows the great advant-
age of using glycerol as a sol-
Nucleophile
Catalyst
HN(C2H4OH)2
AP-1b
Product
Yield[b] [%]
G
<5
95
HN
N
25
85
AP-1b
HN
N
35
96
AP-1b
[c]
[c]
HN
G
15
86
AP-1b[c]
HN
N
85
88
85
87
vent (Figure 3).
[a] Electrophile (1 mmol) and nucleophile acid (1 mmol) were stirred overnight in the presence of AP-1b
(20 mol% of basic sites) at 708C in glycerol (4 mL). [b] Isolated yield. [c] 2 mmol of nitroethane was used.
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F. Jꢁrꢂme et al.
very cheap, but its use as solvent requires the development
of surfactant combined catalysts to favour better diffusion
of organic substrates in glycerol and to limit the intrinsic re-
activity of glycerol. However, if we showed here that glycer-
ol behaves similarly to water as a solvent, note that glycerol
also offers a unique advantage compared with water. Emul-
sions formed in glycerol were found to unstable, which thus
allows easy extraction of the reaction products without the
assistance of any organic solvents. This particular property
of glycerol allowed the homogeneous AP-1b catalyst to be
recycled up to ten times without any change in selectivity or
reaction rate. Moreover, note that many renewable resour-
ces were used in this study, which further increases the envi-
ronmental friendliness of this approach. We strongly believe
that the use of glycerol as a solvent will provide improved
results compared with those observed in water, and further
investigations are currently underway in our group on this
topic.
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The authors thank the French Ministry of Research and the Centre Na-
tional de la Recherche Scientifique (CNRS) for their financial support.
The authors are also grateful to Agence de l’Environnement et de la
Maꢅtrise de l’Energie (ADEME) for funding (AGRICE grant number
0401C0051). N.V. thanks ADEME and the Region Poitou-Charentes for
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the Syrian Government for his PhD grant.
Keywords: aminopolysaccharides
chemistry homogeneous catalysis
surfactant combined catalysts
·
glycerol
·
·
green
·
solvent effects ·
Received: July 23, 2008
Published online: October 15, 2008
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Chem. Eur. J. 2008, 14, 10196 – 10200