Robust Organocatalysts for the Cleavage of Vegetable Oil Derivatives to Aldehydes through Retrobenzoin Condensation

Article abstract of DOI:10.1002/chem.201800091

A series of thiazolium salts was prepared and tested for the cleavage of the α-hydroxyketone derived from methyl oleate. The robustness of these precatalysts was determined by dynamic thermogravimetric analyses (TGA). It has been shown that the stability of these species is mainly governed by the nature of the counter-anion and some of them were found to be stable until 350–400 °C. The α-hydroxyketone derived from methyl oleate was cleaved under reactive distillation conditions using optimized, thermally robust N-butylthiazolium triflate to give the cleavage product, namely, nonanal and methyl azelaaldehydate, with 85 and 70 % yields. A range of α-hydroxyketones derived from several fatty acids was cleaved to give the corresponding bio-based aldehydes with up to 98 % isolated yields. Finally, this protocol was successfully applied to a high-oleic sunflower oil derivative.

Full text of DOI:10.1002/chem.201800091

A Journal of
Accepted Article
Title: Robust organocatalysts for the cleavage of vegetable oil
derivatives to aldehydes through retro-benzoin condensation
Authors: Nam Duc Vu, Souleymane Bah, Elsa Deruer, Nicolas Duguet,
and Marc Lemaire
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To be cited as: Chem. Eur. J. 10.1002/chem.201800091
Link to VoR: http://dx.doi.org/10.1002/chem.201800091
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Robust organocatalysts for the cleavage of vegetable oil
derivatives to aldehydes through retro-benzoin condensation
Nam Duc Vu, Souleymane Bah, Elsa Deruer, Nicolas Duguet* and Marc Lemaire*
Abstract: A series of thiazolium salts was prepared and tested for
the cleavage of the -hydroxyketone derived from methyl oleate.
The robustness of these precatalysts was determined by dynamic
thermogravimetric analyses (TGA). It has been shown that the
stability of these species is mainly governed by the nature of the
counter-anion and some of them were found stable until 350-400°C.
The -hydroxyketone derived from methyl oleate was cleaved under
reactive distillation conditions using optimized, thermally robust N-
butylthiazolium triflate to give the cleavage product, namely, nonanal
and methyl azelaaldehydate, with 85 and 70% yields. A range of -
hydroxyketones derived from several fatty acids was cleaved to give
the corresponding bio-based aldehydes with up to 98% isolated
yields. Finally, this protocol was successfully applied to a high-oleic
sunflower oil derivative.
used for a broad variety of transformations. For example, linear
aldehydes can be used for the preparation of bio-based
surfactants through reductive alkylation of polyols.[13] Moreover,
functionalized aldehydes can be transformed to monomers for
the preparation of polyesters and polyamides through reduction
or reductive amination, respectively.[8] However, there are not so
many methods to produce aldehydes from vegetable oils or fatty
acid derivatives. Thermal cracking of methyl ricinoleate obtained
from castor oil produces bio-heptanal as a co-product of nylon-
11 (Rilsan®) synthesis.[14] This route is very specific to ricinoleic
derivatives and requires elevated temperature (> 300°C). Cross-
metathesis of unsaturated fatty acid derivatives with ethylene
(ethenolysis)[15] produces terminal alkenes that can be further
transformed to the corresponding homologated aldehydes
through carbonylation.[16] This sequence is very attractive from a
green chemistry point of view but implies the use of gases and
requires specialized high-pressure equipments. Other reported
routes involve the formation of oxidized intermediates that are
cleaved to the desired aldehydes (Scheme 1). Reductive
ozonolysis of fatty acid derivatives provides aldehydes with
excellent atom-economies.[17] However, this method requires the
use of ozone (O3) which is highly toxic and involves the
formation of explosive ozonide intermediates. Moreover, the
generation of ozone is a highly energy-intensive process, that
also constitutes a serious drawback. Alternatively, fatty epoxides
or diols, which are also industrially relevant oleochemicals, can
be also cleaved to aldehydes but only using HIO4 or NaIO4 as
stoichiometric oxidants,[18] respectively. In this context, new
methodologies should be developed to produce fatty aldehydes
to guarantee their use in biobased products.
Introduction
Vegetable oils and animal fats (triglycerides) are attractive
renewable raw materials for the chemical industry.[1] Indeed,
their competitive cost and wide availability (about 202 million
tons in 2015)[2] make them adequate for numerous high-volume
commercial applications. For instance, they can be used as
biofuel[3] (biodiesel) but can be best converted to valuable
building blocks for applications in pharmaceuticals, cosmetics,
paints, coatings, packaging materials, lubricants, surfactants,
fine chemicals and polymers.[4] Most of the reactions on
oleochemicals occur at the fatty acid carboxy group and they are
comparatively few examples on the alkyl chain. However, the
presence of double bond(s) in unsaturated fatty acid derivatives
allows the installation of a range of organic functions[5] including
aldehyde,[6] epoxide,[7] diol,[8] ketone and diketone,[9] -
hydroxyketone,[10] carbonate,[11] among others.[12] More
importantly, cleavage reactions – mainly using methyl oleate as
archetype – can give access to building-blocks with higher
added-value, essentially for surfactants and polymer
applications. In this respect, the formation of fatty mono- and
difunctionalized aldehydes is of great interest as they can be
[a]
N. D. Vu, S. Bah, E. Deruer, Dr N. Duguet, Pr M. Lemaire
Univ Lyon, Université Claude Bernard Lyon1, CNRS, INSA, CPE-
Lyon, Institut de Chimie et Biochimie Moléculaires et
Supramoléculaires, ICBMS, UMR 5246, Equipe CAtalyse, SYnthèse
et ENvironnement (CASYEN), 43, bd du 11 novembre 1918, F-
69622 Villeurbanne cedex, France.
Scheme 1. Main routes to fatty aldehydes from methyl oleate.
Fax: +33(0)-472-431-408; phones: +33(0)-472-448-507, +33(0)-472-
431-407.
E-mails: nicolas.duguet@univ-lyon1.fr, marc.lemaire.chimie@univ-
lyon1.fr
Enzymatic catalysis occupies a pivotal place in the utilization
of biomass as renewable feedstock as enzymes are inherently
involved in both biosynthetic or biodegradation pathways. Most
enzymes produce aldehydes in protected or masked forms
(carbohydrates) or use them as transient intermediates. One of
Supporting information for this article is given via a link at the end of
the document.
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these enzymes is the transketolase (TK) (EC 2.2.1.1). This
thiamine diphosphate (ThDP)-dependent enzyme is involved in
the metabolism of carbohydrates. Indeed, TK catalyzes in vivo
the formation of D-glyceraldehyde 3-phosphate from D-xylulose
5-phosphate (aldehyde donor) through the transfer of a two-
carbon ketol unit (glycolaldehyde) to D-ribose 5-phosphate
(aldehyde acceptor) to give D-sedoheptulose.[19] However, the
synthetic utility of this transformation is limited due to the
reversibility of the process. Some strategies have employed
hydroxypyruvic acid as the ketol donor to render the
transformation irreversible but free aldehydes could not be
produced through these methods.[20]
treated with thiamine pyrophosphate (ThPP) 6, thiamine
hydrochloride (vitamine B1.HCl) 7.HCl and thiamine-derived
thiazolium salt 8 in the presence of K2CO3 at 150°C under
microwave irradiation.[26]
Table 1. Screening of commercially available thiazolium salts.[a]
The analogous organocatalyzed process, i.e. the chemical
formation of aldehydes from the corresponding -hydroxyketone,
is called “retro-benzoin condensation”. Contrary to the
(asymmetric) benzoin condensation that was extensively studied
using cyanides, thiazolium salts and related N-Heterocyclic
Carbenes (NHCs),[21] only little attention has been paid to the
opposite process.[22] Miyashita et al. were the first to
synthetically exploit the retro-benzoin condensation for the
preparation of ketones from -substituted benzoins.[23] The
reaction was catalysed either by cyanide ion or NHCs. In that
case, the equilibrium of the reaction was shifted towards the
formation of ketones, probably thanks to their higher stability.
More recently, Chi et al. have reported a bio-inspired approach
for the generation of formaldehyde equivalents from
carbohydrates through a retro-benzoin process catalysed by a
thiazolium salt.[24] The reactive formyl anion equivalent was
reacted with enones to give -formylketones, thus exploiting the
irreversible character of the Stetter reaction to shift the
equilibrium of the reaction. However, free aldehydes could not
be isolated through the use of these two methodologies.
Yield[b] (%)
Thiazolium
salt
Conv[b]
(%)
Entry
2
0
3
0
4
0
5
0
In this context, we have previously reported the cleavage of
the -hydroxyketone derived from methyl oleate to aldehydes
through a retro-benzoin process catalyzed by a thiazolylidene
species.[25] We have shown that the aldehydes produced are in
equilibrium with their corresponding acyloins. The free
aldehydes, i.e. nonanal and methyl azelaaldehydate, were
recovered by reactive distillation under vacuum and were
isolated with poor yields.
1
2[c]
3
6
7
0
0
0
0
0
0
8
0
0
0
0
0
4
9
7
7
7
0
0
5
10
11
26
39
22
29
22
29
4
4
We now report here an efficient, robust catalytic system
based on a thiazolium salt that allows the cleavage of a series of
-hydroxyketones derived from vegetable oils with high yields.
6
10
10
[a] Conditions: Microwave tube, -hydroxyketone
1 (1:1 mixture of
regioisomers, 0.2 mmol), thiazolium salt (20 mol%), K2CO3 (20 mol%), dry
CH3CN (2 mL), 150°C (W), 30 min. [b] Determined by GC using
hexadecane as internal standard. [c] 40 mol% of K2CO3 were used in this
case.
Results and Discussion
We have previously identified that only thiazolium salts were
efficient precatalysts for the cleavage of the -hydroxyketone
derived from methyl oleate. This observation is in accordance
with the work of Chi[24] who has also proved the superiority of
thiazolium salts (over imidazolium, imidazolinium and triazolium
salts) to promote the cleavage of carbohydrate derivatives
through a retro-benzoin process.
In the quest for an efficient catalytic system, we have first
screened a range of commercially available and structurally
diverse thiazolium salts (Table 1). First, -hydroxyketone 1 was
Under these conditions, no conversion of the starting material
was observed showing the inability of these catalysts to promote
this retro-benzoin process (Table 1, entries 1-3). This could be
attributed to the degradation of these catalysts under the
reaction conditions. For example, despite that 7 is stable until
about 200°C as a salt,[27] it could quickly degrade at moderate
temperature in organic basic solution.[28] With thiamine-derived
precatalysts 9 and 10, the conversion increased from 7% with N-
ethyl derivative 9 to 26% with precatalyst 10 bearing a N-methyl
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substituent (Table 1, entries 4-5). These results clearly indicate
that the steric bulkiness of the catalyst is deleterious for the
activity. Finally, when using less sterically demanding thiazolium
11, the conversion reached 39% and the aldehydes and their
corresponding acyloins were formed with 29 and 10%,
respectively (Table 1, entry 6).
results could not be significantly improved using 40 mol%,
indicating that a plateau is reached (Figure 1).
50
Conversion of 1
40
Yields of 2 and 3
A range of various solvents was next tested under standard
conditions using thiazolium 11 (20 mol%), K2CO3 (20 mol%) at
150°C under microwave irradiation for 30 minutes (Table 2).
DMF and EtOAc gave moderate conversion compared to
CH3CN while non-polar solvents such as toluene and heptane
were not found suitable to efficiently promote the reaction (Table
2, entries 1-5). Ethereal solvents such as THF, 2Me-THF, MTBE
and DBE were also screened but gave poor results (2-6 %
conversion) (Table S1 in ESI). Finally, methyl stearate was
investigated as bio-based solvent but no conversion was
observed under these conditions and -hydroxyketone 1 was
recovered unaltered (Table 2, entry 6).
30
20
Yields of 4 and 5
10
0
0
10
20
30
40
Catalyst loading (mol%)
Figure 1. Influence of catalyst loading on conversion and yields. Reaction
conditions: Microwave tube, -hydroxyketone 1 (1:1 mixture of regioisomers,
0.2 mmol), thiazolium 11, K2CO3, dry CH3CN (2 mL), 150°C (W), 30 min. The
conversion of 1 (blue diamonds), yields of aldehydes 2 and 3 (red squares)
and yields of -hydroxyketones 4 and 5 (green triangles) were determined by
GC using hexadecane as internal standard.
Table 2. Solvent screening.[a]
Nevertheless, at 170°C, the conversion reached 56% after 30
minutes and was further improved to 60% after 1 hour. Under
these conditions, aldehydes 2-3 and acyloins 4-5 were formed
with 40% and 20% yields, respectively (Table S2 in ESI).
However, the synthetic utility of this methodology is limited due
to the fact that the whole system is in equilibrium. That is the
reason why, the cleavage of -hydroxyketone 1 was carried out
by reactive distillation in order to shift the equilibrium towards the
formation of aldehydes 2 and 3. This strategy should also
prevent the formation of symmetrical acyloins 4 and 5. Thus,
thiazolium salt 11 (10 mol%) was treated with K2CO3 (10 mol%)
in CH3CN for 10 min at 25°C. The resulting solution was
transferred to a distillation flask containing the starting material
and CH3CN was removed in vacuo. Then, neat -hydroxyketone
1 (4.00 g) was heated at 180°C (oil bath) and the aldehydes
were simultaneously distilled (Scheme 2).
Yield[b] (%)
Conv.
Entry
Solvent
[b] (%)
2
29
13
13
4
3
29
13
13
4
4
10
5
5
10
5
1
2
3
4
5
CH3CN
DMF
39
18
15
4
EtOAc
toluene
heptane
2
2
0
0
3
2
2
1
1
methyl
stearate
6
0
0
0
0
0
[a] Conditions: Microwave tube, -hydroxyketone
1 (1:1 mixture of
regioisomers, 0.2 mmol), thiazolium 11 (20 mol%), K2CO3 (20 mol%), dry
solvent (2 mL), 150°C (W), 30 min. [b] Determined by GC using
hexadecane as internal standard. THF = tetrahydrofuran, 2Me-THF = 2-
methyl tetrahydrofuran, MTBE = methyl tert-butylether, DBE = dibutylether,
DMF = dimethylformamide.
Scheme 2. Recovery of aldehydes by reactive distillation.
The catalyst loading was next probed at 150°C using optimal
thiazolium salt 11 (Figure 1). Expectedly, when increasing the
loadings of both the thiazolium salt and the base from 2 to 20%,
the conversion increased from 7 to 39% and the yields of the
desired aldehydes improved to 29 % (Table S2 in ESI). These
The distillation stopped after 3 hours and aldehydes 2-3 were
recovered with 36 wt% combined yield as a 63:37 GC ratio
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(Figure 2). Satisfyingly, the residue showed no significant sign of
elimination shifts the equilibrium of the reaction.[30] For further
optimization, the preliminary deprotonation will be avoided as it
usually shortens the life time of the catalyst and the thiazolium
salt will be used as a reservoir for the thiazolylidene active
species.
degradation and starting material
1 and acyloin 5 were
recovered with 64 wt% combined yield as a 95:5 GC ratio (see
Figure S1 in ESI).
Structural modifications of the initial precatalyst have been made
in order to increase its stability. Two strategies have been
envisioned: i) to increase the length or the bulkiness of the N-
alkyl group, ii) to reduce the nucleophilicity of the couter-ion. The
thiazolium salts were prepared either from 4,5-dimethylthiazole
by direct alkylation with a range of alkyl halide (I, Br) or
pseudohalide (OTf) or from thiazolium iodide 11 by anion
metathesis using silver or lithium salts of charge-delocalized soft
anions (see ESI). All the thiazolium salts 11-24 prepared in this
study are presented in Figure 3.
Figure 2. GC chromatogram of the distillate.
These results were encouraging but the yield of aldehydes could
not be improved after a prolonged time. We hypothesized that
the catalyst has been deactivated or degraded during the
reactive distillation under these conditions. This hypothesis has
been confirmed by the presence of 4,5-dimethylthiazole – a
catalyst fragment – on the GC chromatogram of the distillate
Figure 3. Thiazolium salts used as precatalysts in this study.
(peak at 2.90 min, Figure 2). We proposed
a
catalyst
It should be noted that thiazolium acetate 23 was specifically
prepared in order to install a basic counter-ion that could prevent
the use of external base for the generation of the free carbene.
degradation pathway to account for the formation of this catalyst
byproduct. On the one hand, the active thiazolylidene species
could be protonated (e.g. by the OH group of the -
hydroxyketone) and the released nucleophile could react with
the activated N-methyl group to give 4,5-dimethylthiazole
(Scheme 3, a).
1
However, even if this compound has been characterized by H
NMR (see ESI), the product degrades quickly at room
temperature. The thermal decomposition of imidazolium
carboxylates has already been reported but these species were
found stable until 100-200°C.[31] The fact that thiazolium acetate
23 readily degrades at room temperature has been attributed to
the fact that thiazolium protons are more acidic than their
imidazolium counterparts. As a result, the acetate anion has
been replaced by a benzoate anion and the corresponding
thiazolium benzoate 24 was prepared. Interestingly, the salt
crystallizes with one molecule of benzoic acid and the structure
has been confirmed by single-crystal X-ray diffraction (Figure 4
and Figure S2 in ESI).
Scheme 3. Proposed catalyst degradation pathway.
On the other hand, the degradation could directly occur from the
thiazolium iodide, that could be still present in the reaction
mixture due to incomplete deprotonation. In that case, the iodide
ion could attack the activated N-methyl group to cleave the C-N
bond leading to 4,5-dimethylthiazole and iodomethane (Scheme
3, b). This degradation pathway, known as the reverse
Menshutkin reaction, is quite well established for imidazolium
halide salts.[29] In our case, the degradation process is
accelerated under vacuum since iodomethane is volatile and its
Figure 4. X-ray diffraction of thiazolium benzoate 24.PhCO2H.
The activity of the synthesized thiazolium salts has been
evaluated in the retro-Benzoin condensation of the -
hydroxyketone 1. The influence of the alkyl chain length was first
probed using
a range of thiazolium iodides (Table 3).
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Table 3. Catalytic tests using thiazolium iodides.[a]
Thiazolium salts
Yield[b] (%)
Entry
Conv.[b] (%)
R
Me
X
I
2
3
4
11
4
5
11
4
1
2
3
4
5
6
11
12
13
14
16
17
45
25
25
-
23
20
16
17
18
2
23
18
16
17
16
1
Et
I
n-Bu
n-Oct
Et
I
0
0
I
0
0
Br
Br
24
3
4
4
i-Pr
0
0
[a] conditions: microwave tube, α-hydroxyketone 1 (1:1 mixture of regioisomers, 0.2 mmol), thiazolium salts (0.04 mmol), K2CO3 (0.04 mmol), dry MeCN (2
mL), 150 °C, 30 min. [b] Yields were determined by GC using n-hexadecane as internal standard.
The increase of the alkyl chain length led to a drop of conversion
8-10%, respectively (Table 4, entries 1-5). Therefore, and not
from 45% with N-methyl substituent to 17% with N-octyl (Table 3, surprisingly, the nature of the anion has little impact on the
entries 1-4). Similarly, the yields of aldehydes 2-3 and acyloins
4-5 dropped from 23 to 16% and from 11 to 0%, respectively.
With thiazolium 17, almost no conversion was observed
indicating that a bulky group is deleterious for the activity of the
catalyst (Table 3, entry 6). From these results, thiazolium iodide
11 was found the best catalyst and was selected for further
optimization. The influence of the anion of a range of N-methyl-
thiazolium salts was next investigated (Table 4). Using I, Br,
CF3SO3 (OTf), BF4 and CF3CO2 anions, the conversion of -
hydroxyketone 1 reached around 34-39% and the yields of
aldehydes 2-3 and acyloins 4-5 established around 23-29% and
catalytic activity as the latter arises from the corresponding N-
methyl-thiazolylidene species. However, the conversion is much
higher (52%) with thiazolium triflimide 22, indicating that this
catalyst also promotes side-reactions (Table 4, entry 6).
Thiazolium benzoate 24.PhCO2H also catalyzes the retro-
benzoin condensation but afforded lower yields (Table 4, entry
7). Interestingly, the reaction also proceeds without external
base showing the ability of the benzoate ion to act as an internal
base for the generation of the active thiazolylidene species
(Table 4, entry 8).
Table 4. Catalytic tests using N-methyl-thiazolium salts.[a]
Thiazolium salt
Yield[b] (%)
Entry
Conv.[b] (%)
anion
2
3
4
5
1
2
I
11
15
39
36
29
25
29
23
10
8
10
8
Br
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3
4
CF3SO3
BF4
19
39
35
34
52
30
36
26
23
25
21
15
20
24
23
25
18
14
17
10
10
9
10
10
9
20
21
5
CF3CO2
(CF3SO2)2N
PhCO2
6
22
3
3
7
24.PhCO2H
24.PhCO2H
3
3
8[c]
PhCO2
4
4
[a] Conditions: microwave tube, α-hydroxyketone 1 (1:1 mixture of regioisomers, 0.2 mmol), thiazolium salts (0.04 mmol), K2CO3 (0.04 mmol), dry MeCN (2 mL),
150 °C, 30 min. [b] Yields were determined by GC using n-hexadecane as internal standard. [c] No base was used in this condition.
The thermal stability of most of the precatalysts was evaluated
by dynamic thermogravimetric analysis (TGA). Even if this
method overestimates the thermal stability, it usually provides
useful information on the short-term thermal stability of ionic
liquids and is generally used for comparative purposes.[32]
Moreover, contrary to imidazolium-based ionic-liquids, few TGAs
were reported on thiazolium derivatives.[33] First, the influence of
the alkyl chain length on the stability has been probed with a
range of thiazolium iodides 11-14 and dynamic TGAs were
measured under nitrogen at a heating rate of 20°C.min-1 (Figure
5). Several thermal properties including Tonset and Tpeak are
gathered in Table S3 in ESI.
anion on the thermal stability has been probed with a range of
N-methyl-thiazolium salts (Figure 6).
Figure 6. Dynamic TGA curves of N-methyl-thiazolium salts.
In this case, the thermal stability of thiazolium precatalysts is
considerably affected by the nature of the anion. Halide anions
such as I and Br display very similar behavior with comparable
Tonset, Tpeak and Tendset (Table S5 in ESI). In sharp contrast,
stabilized fluorinated anions present huge differences. While
CF3CO2 anion reduces the thermal stability compared to halides,
the use of BF4, OTf and NTf2 anions increases the
decomposition temperature to at least 100°C. Noteworthy, the
NTf2 anion, which is usually giving the best thermal stabilities in
the imidazolium series, showed two degradation waves in our
case. This could be probably explained by two different mode of
degradation, one from the thiazolium cation and other one from
the NTf2 anion. These results show that the overall thermal
stability of thiazolium salts is mainly governed by the nature of
the anion and the relative robustness of these species could be
ranked as follows: OTf > BF4 > NTf2 > I > Br > CF3CO2. Finally,
thiazolium triflate 19 was found to be the more stable precatalyst
with a degradation temperature of about 395°C.
Figure 5. Dynamic TGA curves of thiazolium iodides.
The thermal stability of thiazolium salts is not significantly
affected with the increase of the alkyl chain length from methyl
to n-octyl as the dynamic TGA curves are almost superimposed.
However, slight differences can be observed on the Tonset that is
decreasing with the increase of the alkyl chain length (Table S5
in ESI). These results are in accordance with the behavior of
imidazolium-based ionic liquids.[34] Then, the influence of the
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The cleavage of -hydroxyketone 1 under reactive distillation
conditions was re-investigated using thiazolium triflate 19 that
was selected as the best catalyst in terms of stability and activity
(Table 5). Thus, neat -hydroxyketone 1 was heated at 180°C in
the presence of thiazolium salt 19 (20 mol%) and K2CO3 (10
mol%) and the aldehydes were simultaneously distilled under
reduce pressure (1-3 mbar). Pleasingly, the distillate was
recovered with an overall 75 wt% yield after only 15 minutes and
the yields of aldehydes 2 and 3 were calculated to 84 and 70%,
respectively (Table 5, entry 1). However, we have noticed that
some of thiazolium 19 has been sublimated under these
conditions. In order to prevent such inconvenience, n-butyl
analog 25 has been synthesized (see ESI) and used in the same
reaction. Satisfyingly, aldehydes 2 and 3 were recovered with
similar results and no sign of sublimation has been observed
(Table 5, entry 2). Decreasing the temperature to 160°C led to
similar proportions of aldehydes but the overall yield dropped to
70 wt% (Table 5, entry 3). A crude sample of -hydroxyketone 1
(83% GC purity) was also used as starting material and the
aldehydes 2 and 3 were recovered with 85 and 71% yields,
based on the purity of the starting material (Table 5, entry 4).
These results highlight the robustness of the catalytic system
developed.
Table 5. Cleavage of α-hydroxyketone 1 under reactive distillation conditions.[a]
Distillate
Temp. [b]
Entry
R
Yield 2[c]
Yield 3[c]
(°C)
m 2+3
Yield 2+3
GC ratio
(g)
(wt%)
2 : 3
(%)
(%)
1
2
Me
180
180
160
180
3.00
3.07
2.82
2.48
75
75
70
75
61:39
60:40
60:40
62:38
84
85
80
85
70
71
67
71
n-Bu
n-Bu
n-Bu
3
4[d]
[a] Conditions: distillation set-up, -hydroxyketone 1 (1:1 mixture of regioisomers, 4.00 g), thiazolium salt (20 mol%), K2CO3 (10 mol%), neat, 1-3 mbar, 15 min. [b]
Temperature of the oil bath. [c] Calculated yields based on calibration. [d] Crude starting material containing -hydroxyketone 1 (83%), the corresponding
diketone (5%), the corresponding diol (3%) and nonanoic acid (about 6%).
The scope of the cleavage of -hydroxyketones derived from
vegetable oils has been next investigated using the previously
optimized conditions (Table 6). These fatty -hydroxyketones
were prepared from the corresponding diols, either by oxidation
using a homogeneous palladium-neocuproine complex or by
dehydrogenation using a heterogeneous ruthenium catalyst.[10a]
Symmetrical -hydroxyketones 4 and 5, derived from self-
metathesis products of methyl oleate,[35] gave nonanal 2 and
methyl azelaaldehydate 3 with 88 and 80% isolated yields,
respectively (Table 6, entries 1-2). This protocol was also
applied to other fatty acid derivatives. Unsymmetrical -
hydroxyketones 26 and 28 derived from butyl and 2-ethylhexyl
oleate gave nonanal 2 with 82 and 93% yield, respectively
(Table 6, entries 3-4). In these cases, the remaining bifunctional
aldehydes could not be distilled due to their high boiling point
and undergo NHC-catalysed self-benzoin condensation.
Consequently, symmetrical acyloins 27 and 29 were isolated
from the residue by column chromatography and were obtained
with 39 and 54% yields, respectively. Similarly, -hydroxyketone
30 derived from methyl erucate gave nonanal 2 with an excellent
98% yield and symmetrical acyloin 31 was isolated from the
residue with 30% yield (Table 6, entry 5). The -hydroxyketone
32 derived from methyl ricinoleate was next cleaved to give (R)-
3-methoxynonanal 33 and aldehyde 3 but only poor yields were
obtained (Table 6, entry 6). We hypothesized that the methoxy
group was bulky enough to prevent the addition of the N-butyl
catalyst 25 onto the carbonyl group. For that reason, the
reaction was repeated with N-methyl catalyst 19. Satisfyingly,
the yields of aldehydes 33 and 3 improved to 15 and 30%,
respectively (Table 6, entry 6, results in brakets). However,
these results are not as good as those obtained previously. In
fact, due to the presence of the methoxy group, the starting
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material 32 exists as a mixture of four inseparable isomers
(NMR ratio = 25:18:21:36), i.e. two diastereoisomers for each
regioisomer. It is likely that one of these species reacts faster
cleaved under the current conditions. This opens the possibility
to valorize waste vegetable oils to value-added aldehydes, that
could be used as such or for the preparation of bio-based
than the others with catalyst 19 to give the cleavage compounds, surfactants. Moreover, bifunctional aldehydes and symmetrical
thus leading to some regio- or diastereoselection. This could
also explain why some starting material was recovered from the
residue. Tris(-hydroxyketone) 34, prepared from high-oleic
sunflower oil (85% oleic acid content) and containing about 60%
of -hydroxyketone functionality, was also subjected to the
cleavage conditions (Table 6, entry 7). Remarkably, nonanal 2
was obtained with 25% yield (25% with thiazolium 19) indicating
that challenging substrates such as triglycerides could be also
acyloins obtained through this methodology could be also used
as building-blocks for the preparation of bio-based polyesters
and polyamides. Finally, to further demonstrate the interest of
this methodology, benzoin 35 was cleaved under reactive
distillation conditions (Table 6, entry 8). Satisfyingly,
benzaldehyde 36 was obtained with 90% isolated yield, thus
showing the versatility of the method developed.
Table 6. Scope of of α-hydroxyketones derived from vegetable oils.[a]
Yields[b] (%) of cleavage
compounds in distillate
Entry
1[d]
α-hydroxyketones
Yields[c] (%) of the main product in the residue
88
80
82
–
–
–
–
2
3
2
4
5
2
3
39
27
26
4
5
93
54
30
2
2
29
31
28
30
98
6[c]
(15)[c,e]
33
3
6
mainly starting material
–
32
9[c]
(30) [c,e]
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25
7
–
–
(25)[e]
2
34
8[f]
90
–
–
36
35
[a] Conditions: distillation set-up, -hydroxyketone (1:1 mixture of regioisomers), thiazolium salt (20 mol%), K2CO3 (10 mol%), neat, 180°C (oil bath temperature),
vacuum = 1-3 mbar, 15 min. [b] Isolated yields. [c] Isolated yields after purification by column chromatography. [d] The vacuum pressure was set at 10 mbar to
avoid the distillation of the starting material. [e] Yield in brackets was obtained using catalyst 19. [f] The vacuum pressure was set at 50 mbar.
3-ium triflate 25 (766.5 mg, 2.4 mmol, 20 mol%) and -
hydroxyketone (12 mmol) were added and the distillation set-
up was installed. Then, the mixture was heated at 180°C (oil
bath pre-heated at 180°C) under reduced pressure (vacuum
Conclusions
= 1-3 mbar, except for the case of -hydroxyketones 4 and
In conclusion, we have developed a robust catalytic system
35). The distillate was collected, weighted and analysed by
based on thiazolium salts for the cleavage of the -
GC, using n-hexadecane as internal standard. The residue
hydroxyketone derived from methyl oleate. The reaction
was also weighted and analyzed by GC and NMR. If needed,
proceeds through
a retro-benzoin process under reactive
the aldehydes could be further purified by flash
distillation conditions. The cleavage products, namely, nonanal
and methyl azelaaldehydate, were obtained with 85 and 70%
yields, respectively. A range of -hydroxyketones derived from
several fatty acids has been also cleaved to give the
corresponding bio-based aldehydes with up to 98% isolated
yields. Finally, this protocol was also found applicable to a high-
oleic sunflower oil derivative, opening the possibility to valorize
waste vegetable oils. The aldehydes produced through this
methodology are excellent platforms for the preparation of bio-
based surfactants or building-blocks for polymer applications.
chromatography (cyclohexane/EtOAc 99.8:0.2  95:5).
Acknowledgements
The authors thank the SAS PIVERT for a Ph.D. grant to N. D.
Vu (GENESYS program – project WP3P21-Bioaldehydes). This
work was performed in partnership with the SAS PIVERT, within
the frame of the French Institute for the Energy Transition
(Institut pour la Transition Energétique (ITE) P. I. V. E. R. T.
(http://www.institut-pivert.com)) selected as an Investment for
the Future (“Investissements d’Avenir”). This work was
supported, as part of the Investments for the Future, by the
French Government under the reference ANR-001-01. The
authors would also like to thank Dr E. Jeanneau (ISA-Lyon) for
X-Ray analysis and Dr C. Negrell (ENSCM-Montpellier) for TGA
analyses.
Experimental Section
General procedure for the thiazolylidene-catalysed cleavage
of -hydroxyketone under microwave conditions: In a 5-mL
microwave tube, 9(10)-hydroxy-10(9)-oxooctadecanoate 1
(1:1 mixture of regioisomers) (65.7 mg, 0.2 mmol, 1 equiv),
the thiazolium salt (0.04 mmol, 20 mol%) and K2CO3 (5.5 mg,
0.04 mmol, 20 mol%) were added. The tube was flushed with
argon and dry CH3CN (2 mL) was added. The mixture was
stirred under microwave irradiation at the desired
temperature for a period of time. The mixture was cooled
down to room temperature and analyzed by GC using
hexadecane as internal standard.
Keywords: Vegetable oils • Thiazolium salts • α-hydroxyketones
• Retro-benzoin condensation • Aldehydes
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Nam Duc Vu, Souleymane Bah, Elsa
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Robust organocatalysts for the
cleavage of vegetable oil derivatives
to aldehydes through retro-benzoin
condensation
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