Biobased Aldehydes from Fatty Epoxides through Thermal Cleavage of β-Hydroxy Hydroperoxides**

Article abstract of DOI:10.1002/cssc.202002364

The ring-opening of epoxidized methyl oleate by aqueous H₂O₂ has been studied using tungsten and molybdenum catalysts to form the corresponding fatty β-hydroxy hydroperoxides. It was found that tungstic acid and phosphotungstic acid gave the highest selectivities (92–93 %) towards the formation of the desired products, thus limiting the formation of the corresponding fatty 1,2-diols. The optimized conditions were applied to a range of fatty epoxides to give the corresponding fatty β-hydroxy hydroperoxides with 30–80 % isolated yields (8 examples). These species were fully characterized by ¹H and ¹³C NMR spectroscopy and HPLC-HRMS, and their stability was studied by differential scanning calorimetry. The thermal cleavage of the β-hydroxy hydroperoxide derived from methyl oleate was studied both in batch and flow conditions. It was found that the thermal cleavage in flow conditions gave the highest selectivity towards the formation of aldehydes with limited amounts of byproducts. The aldehydes were both formed with 68 % GC yield, and nonanal and methyl 9-oxononanoate were isolated with 57 and 55 % yield, respectively. Advantageously, the overall process does not require large excess of H₂O₂ and only generates water as a byproduct.

Full text of DOI:10.1002/cssc.202002364

Chemistry–Sustainability–Energy–Materials
Accepted Article
Title: Biobased aldehydes from fatty epoxides through thermal
cleavage of β-hydroxy hydroperoxides
Authors: Thomas De Dios Miguel, Nam Duc Vu, Marc Lemaire, and
Nicolas Duguet
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ChemSusChem
10.1002/cssc.202002364
FULL PAPER
Biobased aldehydes from fatty epoxides through thermal
cleavage of -hydroxy hydroperoxides
Thomas De Dios Miguel,[a] Nam Duc Vu,[a] Marc Lemaire,[a] and Nicolas Duguet*[a]
[
a]
T. De Dios Miguel, Dr N. D. Vu, Pr M. Lemaire, Dr N. Duguet
Univ Lyon, Universitꢀ Claude Bernard Lyon 1, CNRS, INSA-Lyon, CPE-Lyon, Institut de Chimie et Biochimie Molꢀculaires et Supramolꢀculaires, ICBMS,
UMR 5246, Equipe CAtalyse, SYnthꢁse et ENvironnement (CASYEN),
Bꢂtiment Lederer, 1 rue Victor Grignard, F-69100 Villeurbanne, France
E-mail: nicolas.duguet@univ-lyon1.fr
Supporting information for this article is given via a link at the end of the document.
Abstract: The ring-opening of epoxidized methyl oleate by aqueous
has been studied using tungsten and molybdenum catalysts to
Complementarily, the cleavage of unsaturated fatty acid
derivatives can produce aliphatic linear aldehydes. These
aldehydes are of prime importance since they can used to
prepare 100% bio-based surfactants by reductive etherification
of polyols and sugar derivatives.[10] In addition, functionalized
aldehydes can be transformed to monomers for the preparation
of polyesters and polyamides through reduction or reductive
amination, respectively.[11] The cleavage of fatty acid derivatives
2 2
H O
form the corresponding fatty -hydroxy hydroperoxides. It was found
that tungstic acid and phosphostungstic acid gave the highest
selectivities (92-93%) towards the formation of the desired products,
thus limiting the formation of the corresponding fatty 1,2-diols. The
optimized conditions were applied to a range of fatty epoxides to
give the corresponding fatty -hydroxy hydroperoxides with 30-80%
isolated yields (8 examples). These species were fully characterized
is usually carried out in the presence of strong oxidants (i.e.,
1
13
[12]
by H and C NMR, HPLC-HRMS and their stability was studied by
DSC. The thermal cleavage of the -hydroxy hydroperoxide derived
from methyl oleate was studied both in batch and flow conditions. It
was found that the thermal cleavage in flow conditions gave the
highest selectivity towards the formation of aldehydes with limited
amounts of byproducts. The aldehydes were both formed with 68%
GC yield and nonanal and methyl 9-oxononanoate were isolated
with 57 and 55% yield, respectively. Advantageously, the overall
oxidative cleavage).
This means that fatty aldehydes are
difficult to obtain selectively through these methods since they
are readily oxidized to carboxylic acids under these conditions.
In this context, other strategies should be employed.
The cleavage of fatty epoxides or 1,2-diols to aldehydes was
, respectively.[13]
4 4
traditionally be carried out using HIO or NaIO
However, the use of these stoichiometric oxidants leads to the
generation of large quantities of waste that could not be
valorized. One of the most efficient, clean and general method to
produce fatty aldehydes is reductive ozonolysis.[14] In that case,
unsaturated fatty acids are over-oxidized with ozone to give the
corresponding ozonides. These reactive intermediates are then
process does not require large excess of H
water as a byproduct.
2 2
O and only generates
reduced
-
typically
using
zinc,
dimethylsulfide,
Introduction
triphenylphosphine or hydrogen - to aldehydes, thus limiting the
formation of carboxylic acids as contaminants. Reductive
ozonolysis is very attractive from an atom-economy point of view
but suffers from the use of ozone that is extremely toxic for both
humans and environment. Moreover, ozonolysis is a very
energy-intensive process as ozone is produced from oxygen
using an electric discharge. Recently, our group has reported an
alternative approach consisting in the catalytic cleavage of fatty
Aldehydes are ubiquitous in organic chemistry as they serve as
platform towards other organic functions such as alcohols,
carboxylic acids, acetals, imines, amines, and many others.[1]
For several years now, the production of bio-based building-
blocks from biomass as a renewable feedstock has become the
subject of very intense research.[2] Contrary to carboxylic acids,
only a few bio-based aldehydes are readily accessible from
renewable resources. On the one hand, furanic aldehydes such
as furfural,[ 5-hydroxymethyl furfural (5-HMF)[4] and 2,5-
-hydroxyketones to aldehydes under non– oxidative conditions.
First, -hydroxyketones were prepared by selective catalytic
oxidation or dehydrogenation of fatty 1,2-diols.
intermediates were organocatalytically cleaved by retro-benzoin
condensation in the presence of thiazoliums salts to give the
corresponding aldehydes.[16] Albeit that this catalytic route could
be attractive, it has not been demonstrated on a large scale yet.
Finally, it was shown that ricinoleic derivatives, obtained from
castor oil, can be thermally cleaved at high temperature
3]
[15]
Then, these
[
5]
diformylfuran can be obtained from lignocellulosic biomass. In
addition, other aromatic aldehydes such as vanillin and its
derivatives can be produced from lignin.[6] On the other hand,
[
7]
vegetable oils are interesting renewable resources to prepare
aliphatic aldehydes.
[
8]
Hydroformylation of unsaturated vegetable oils and their fatty
acid derivatives can give access to the corresponding
homologated branched aldehydes. However, despite its high
atom-economy and feasibility at the industrial scale,
hydroformylation involves the use carbon monoxide and
hydrogen, thus requiring specialized high-pressure equipments.
(
typically >300°C) to give bio-based heptanal and undecylenic
[
9]
[17]
acid through a retro-ene reaction. Noteworthy, this process is
carried out on the industrial scale since undecylenic acid can be
further converted to 11-aminoundecanoic acid, which is the
precursor of nylon-11 (Rilsan®). Despite that this cleavage
1
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ChemSusChem
10.1002/cssc.202002364
FULL PAPER
process is specific to ricinoleic derivatives and could not been
applied to other fatty acid derivatives, it clearly demonstrates
that the thermal cleavage of vegetable oil derivatives can be an
economically-viable route. However, so far, the thermal
cleavage of other fatty acid derivatives has been largely
underexploited. Recently, the cleavage of fatty epoxides to
formation (45% NMR yield) of the corresponding 1,2-diol as a
by-product. Overall, these two works show that the direct
oxidation of oleic acid derivatives is giving fatty -hydroxy
hydroperoxides with low yields. This is probably due to the use
2 2
of a large excess of H O , resulting in the production of many
by-products.
aldehydes has been proposed using H
presence of WO
,[18] WO /MCM-41,[19] and H
1,[20] even at room temperature. However, in these studies, the
2
O
2
as an oxidant in the
In this context, we have first investigated the preparation of fatty
-hydroxy hydroperoxides by ring-opening of epoxidized methyl
oleate using a 35% aqueous solution of H O . Several
2 2
3
3
2
WO @Al-MCM-
4
4
authors have only reported GC yields and no aldehydes were
parameters were screened such as the nature of the catalyst,
the catalyst loading, the concentration of starting material and
the temperature. However, despite a full conversion of the
starting material, the selectivity did not reach more than 80%
due to the formation of the corresponding 1,2-diol. This diol is
formed by ring-opening of the epoxide with water, that is a
competing nucleophile for hydrogen peroxide. Therefore, in
order to limit the formation of this diol, a 50% aqueous solution
isolated.[
21]
In sharp contrast, in the present work, we
demonstrate that these reported conditions do not lead to the
formation of aldehydes but only produce -hydroxy
hydroperoxide species as reaction intermediates (vide infra).
In this context, we now report here the preparation, the isolation
and the characterisation (including DSC) of fatty -hydroxy
hydroperoxides prepared from epoxides. Moreover, we also
report their thermal cleavage into fatty aldehydes in batch and in
flow (Scheme 1).[22]
2 2
O
was used for further optimization.[34] A range of catalysts
of H
was first screened for the ring-opening of epoxidized methyl
oleate 1 using aq. 50% H (Table 1).
2
O
2
Table 1. Optimization for the preparation of fatty -hydroxy hydroperoxides by
[a]
2
.
ring-opening of epoxidized methyl oleate with H
2
O
Cat.
Temp.
Conv.[b]
1
Ratio[b]
2
Ratio[b]
3
Entry
(loading,
(°C)
(%)
(%)
(%)
mol%)
Scheme 1. Cleavage of fatty epoxides to aldehydes through -hydroxy
hydoperoxides.
1
2
3
4
5
6
7
8
9
10
MoO
WO
PMA (10)
WO (10)
4
(10)
20
20
20
20
20
20
20
10
5
16
11
6
5
3
(10)
6
0
Results and Discussion
> 99
> 99
> 99
> 99
> 99
> 99
67
85
93
20
80
90
92
61
44
3
15
7
Preparation of fatty -hydroxy hydroperoxides
H
2
4
The chemistry of -hydroxy hydroperoxides is relatively
PTA (10)
PTA (1)
PTA (0.1)
PTA (0.1)
PTA (0.1)
PTA (0.1)
-
66
20
10
8
unexplored.[
23]
These species are usually prepared by ring-
.[
24]
opening of epoxides with H
acids as catalysts such as HClO
Lewis acids such as SnCl
phosphomolybdic acid (PMA) were also used to promote the
reaction.
phosphomolybdate[
molybdenum[31] were reported as recoverable and recyclable
catalysts. Despite that these methods provide -hydroxy
hydroperoxides with high yields, they require the use of neat or
2
O
2
Early works used Brönsted
[
25]
H.[26] Moreover,
4
and CF
,[27]
3
CO
SbCl
2
[28]
4
3
/SiO
2
and
[
29]
Recently,
magnetic
nanoparticules-supported
6
30]
and nano-graphene oxide-supported
0
50
6
11
10
6
3
2 2
ethereal H O . In sharp contrast with other oxidized fatty
[
a] Reaction conditions: epoxide 1 (1.00 g, 2.90 mmol), aq. 50%-H
mL, 3.18 mmol, 1.1 equiv), catalyst (0.1-10 mol%), tert-amyl alcohol (12 mL),
0°C, 16 hours. [b] Conversion and ratio were determined by HPLC. PMA:
phosphomolybdic acid (H PO .12MoO ), PTA: phosphotungstic acid
(H PO .12WO ).
2 2
O (0.22
derivatives, fatty -hydroxy hydroperoxides has been scarcely
reported. To the best of our knowledge, the first synthesis of an
oleochemical -hydroxy hydroperoxide was reported by Hiroko
et al. in a patent.[32] In this work, methyl oleate was treated with 5
2
3
4
3
3
4
3
2 2
equivalents of aqueous 30% H O at 35°C, in the presence of
The reaction was performed in tert-amyl alcohol at 20°C for 16
hours. Molybdenum and tungsten oxides were first tested but
they gave poor results (Table 1, entries 1-2). The use of
phosphosmolybdic acid (PMA) allows to reach full conversion
and the desired peroxide 2 was obtained with 85% selectivity
tungstic acid. Under these conditions, the corresponding -
hydroxy hydroperoxides was obtained with only 28% yield.
Similarly, Ruffo et al. have reported the direct oxidation of oleic
2 2
acid using an excess of 30% H O (4 equiv.) in the presence of
tungstic acid.[ After 4 hours at 70°C, the desired -hydroxy
33]
(
Table 1, entry 3). A slightly better selectivity (93%) was
hydroperoxide was obtained with only 45%, mainly due to the
2
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ChemSusChem
10.1002/cssc.202002364
FULL PAPER
obtained with tungstic acid (Table 1, entry 4). Surprisingly,
phosphotungstic acid (PTA) only give 20% of 2 and the
corresponding 1,2-diol was obtained as the major product with
2 2
Then, the scope for the ring-opening of epoxides with H O was
next investigated with a range of fatty epoxides under our
optimized conditions (Figure 1).
66% HPLC ratio (Table 1, entry 5). However, by decreasing the
catalyst loading from 10 to 0.1 mol%, the selectivity towards 2
can be improved until 90% (Table 1, entries 6-7). Moreover, a
selectivity of 92% can be reached by decreasing the
temperature to 10°C (Table 1, entry 8). However, no further
improvement can be achieved by decreasing the temperature to
5
or 0°C (Table 1, entries 9-10). Finally, a blank experiment was
carried out without catalyst under the optimized conditions.
Under these conditions, the conversion of 1 reached 6% and
only 3% of peroxide 2 was formed (Table 1, entry 11). This
result demonstrates the crucial role of PTA to activate H
recently reported in a patent.[35]
2 2
O , as
From our results, it is striking to see that only -hydroxy
hydroperoxides were produced and no aldehydes were obtained,
in sharp contrast with reported studies carried out under similar
conditions.[
18-20]
In order to understand these differences, we
have reproduced the conditions previously described in the
literature with unsupported WO and H WO (Table 2). The data
3
2
4
presented below is the average of triplicates (see ESI).
Table 2. Reproduction of previously reported conditions.
Figure 1. Scope for the formation of fatty -hydroxy hydroperoxides. [ The
corresponding 1,2-diol was recovered as the main product. 0.2 mol% of PTA
a]
Cat.
Temp.
Conv.[d]
1
Ratio[d]
2
Ratio[d]
3
[b]
Entry
2 2
was used (0.1 mol% by epoxide function) and 2.2 equiv of 50%-H O .
(loading,
(°C)
(%)
(%)
(%)
mol%)
1[a]
2b]
WO
(1.7)
(1.7)
70
25
25
5
4
1
3
Epoxidized methyl oleate 1 gave the corresponding -hydroxy
hydroperoxide 2 with 80% isolated yield after purification by
column chromatography. This demonstrates that fatty -hydroxy
hydroperoxides are quite robust species and are not sensitive to
slightly acidic conditions such as silica. Compound 2 was first
characterized by NMR. In the H NMR spectrum, the chemical
shifts at 11.2 and 4.3 ppm are characteristic signals for -OOH
and -OH groups, respectively (Figure 2).
WO
3
74
> 99
58
85
16
15
3[c]
2 4
H WO (1.7)
1
[
(
a] Conditions taken from ref. 18: epoxide 1 (1.56 g, 5 mmol), aq. 30%-H
6.5 mmol, 1.3 equiv), WO
Conditions taken from ref. 20: epoxide 1 (3.12 g, 10 mmol), aq. 30%-H
mmol, 1.2 equiv), WO (0.17 mmol, 1.7 mol%), tert-butanol (5 mL), 25°C, 18h
c] Conditions taken from ref. 20: epoxide 1 (3.12 g, 10 mmol), aq. 30%-H
12 mmol, 1.2 equiv), H WO (0.17 mmol, 1.7 mol%), tert-butanol (5 mL),
5°C, 2h. [d] Conversion and ratio were determined by HPLC.
2
O
2
3
(0.085 mmol, 1.7 mol%), neat, 70°C, 20 min [b]
(12
2 2
O
3
[
(
2
2 2
O
2
4
Using WO
3
at 70°C for 20 min under neat conditions,[18] the
conversion of 1 was only 5% and -hydroxy hydroperoxide 2
was obtained with 4% HPLC ratio (Table 2, entry 1). Using either
at room temperature (25°C) in tert-butanol[20] led
3 2 4
WO or H WO
to 74 and 99% conversion and the HPLC ratio of -hydroxy
hydroperoxide 2 reached 58 and 85%, respectively (Table 2,
entries 2-3). Our results clearly demonstrate that the reported
conditions are adequate to form -hydroxy hydroperoxides but
are ineffective for producing aldehydes, contrary to what was
previously claimed.[18-20] This is explained by the fact that, in
these works, the yield of aldehydes was determined by GC
without checking the full conversion of hydroxy hydroperoxide
intermediates (e.g., by NMR or HPLC). Therefore, it is
misguiding because we found that hydroxy hydroperoxides
readily decomposed in the GC injector to form the desired
aldehydes during the analysis (vide infra).
Figure 2. 1H-NMR spectrum (300 MHz, DMSO-d
) of β-hydroxy hydroperoxide
6
2.
3
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FULL PAPER
Moreover, two signals at 69 and 87 ppm in 13C NMR clearly
indicate the presence of the two CH of the -hydroxy
hydroperoxide function (see spectrum in ESI). Finally, the mass
of 2 was also confirmed by HPLC-HRMS (see ESI). Then, ethyl
oleate was also considered and it gave the corresponding -
hydroxy hydroperoxides 4 with 77% isolated yield. Similarly,
hydroperoxide 5, obtained from epoxidized methyl erucate, was
obtained with 76% isolated yield. It should be noted that
products 2, 4-5 were obtained as
a 50:50 mixture of
regioisomers. The fatty epoxides derived from the self-
metathesis products of methyl oleate were also used as starting
materials and the corresponding -hydroxy hydroperoxides 6
and 7 were isolated with 73% and 77% yield, respectively. For
methyl ricinolate derivatives, very contrasting results were
obtained: hydroperoxide 8 was obtained with 73% yield starting
from epoxidized methyl ricinoleate (i.e. with unprotected alcohol
at the position 12), while its O-acyl-protected analogue only
Figure 3. GC Chromatogram of β-hydroxy hydroperoxide
decomposition to aldehydes (injector temperature = 300°C).
2 showing its
gave hydroperoxide
9 with 30% yield. In that case, the
corresponding 1,2-diol was formed as the major compound. The
presence of the 12-OAc group may bring enough steric
hindrance to prevent the addition of H O and thus favours the
2 2
nucleophilic addition of water. Finally, the bis-epoxide prepared
from methyl linoleate was also subjected to the ring-opening with
2 2
H O and the corresponding bis-(-hydroxy hydroperoxide) 10
However, hydroperoxides species are known to be energetic
compounds that could present safety risks. That is the reason
why the thermal stability of fatty -hydroxy hydroperoxide 2
(
neat) was first studied by Differential Scanning Calorimetry
(
Table 3 and ESI).
was isolated with 55% yield. Interestingly, the product is a
mixture of 8 isomers (as observed by 1H NMR) resulting from
2 2
unselective nucleophilic addition of H O to a mixture of cis-cis
Table 3. Comparison of decomposition enthalpies of fatty -hydroxy
hydroperoxides and ozonides.[
a]
and cis-trans epoxides. However, this lack of selectivity is not a
problem considering that all isomers will be thermally cleaved to
give the corresponding aldehydes.
T (°C)
Entry
Fatty compound
MW
g/mol)
DSC decomposition
enthalpy
(
Thermal cleavage of fatty -hydroxy hydroperoxides
(
J/g)
(KJ/mol)
- 211
The cleavage of -hydroxy hydroperoxides has been scarcely
1
Hydroperoxide 2
346.5
360.5
358.5
358.5
358.5
- 611
- 628
- 684
- 742
- 737
107
113
156
137
139
reported in the literature. Early works showed that these species
[
36]
[37]
can undergo acid- or base-catalyzed decomposition to give
a variety of carbonyl compounds. More recently, Salomon et al.
have investigated the fragmentation of hydroperoxide species in
water under physiological conditions.[38] The authors have shown
2
Hydroperoxide 4
- 226
3[40]
Ethyl oleate ozonide
Ethyl oleate ozonide
Ethyl elaidate ozonide
- 245
[41]
4
- 266
that the combination of vitamin C and metal cations such as Fe3
and Cu2+ can give aldehydes – as hydrated form – with up to
+
5[41]
- 264
6
6% yield. While studying the oxidative cleavage of olefins to
[
a] Values obtained from the thermal analysis by DSC.
carboxylic acids, Venturello et al. have also shown that an
aliphatic -hydroxy hydroperoxide can decompose at 85°C in the
presence of a quaternary ammonium dioxoperotungstate.[39] In
that case, the conversion reached 63% and the selectivity
towards aldehydes was only 62% due to the formation of the
corresponding acids (11%), -hydroxyketone (14%) and 1,2-diol
The thermal analysis shows that compound 2 decomposes with
a peak at 107°C and the decomposition enthalpy reaches -611
J/g (Table 3, entry 1). Similar results were obtained with the -
hydroxy hydroperoxide derived from ethyl oleate (Table 3, entry
2
). The thermal analysis data for the other fatty -hydroxy
(
8%) as byproducts. During the characterization of -hydroxy
hydroperoxides is given in the supporting information. By
comparison, the DSC analysis of the thermal decomposition of
the ozonides prepared from ethyl oleate gives a decomposition
enthalpy of -684 J/g and a decomposition temperature of 156°C,
as reported by Cataldo (Table 3, entry 3).[40] In another studies,
hydroperoxide 2 by gas chromatography, we observed that the
compound was not detected on the GC chromatogram,
suggesting that it was completely degraded.[22] However, the
chromatogram was clean with
2 major peaks, that were
assigned to nonanal 11 and methyl 9-oxononanoate (methyl
azelaaldehydate) 12 (Figure 3). A minor product was also
detected and was assigned to the corresponding -
hydroxyketone 13. This demonstrates that hydroperoxide 2 was
totally converted in the GC injector (set at 300°C) to give the
corresponding aldehydes. Hence, we envisioned that -hydroxy
the same author has also shown that the ozonides prepared
from either ethyl oleate or ethyl elaidate gave very similar
decomposition enthalpies and temperatures (Table 3, entries 4-
).[41] This preliminary study on the thermal behaviour of fatty -
5
hydroxy hydroperoxides shows that these oxygenated species
decompose at lower temperature than the corresponding
ozonides but release less energy. Interestingly, similarly than
fatty ozonides, the shape of the heat decomposition of fatty -
hydroperoxide
2
could be selectively cleaved to the
corresponding aldehydes by thermal cleavage under catalyst-
free conditions.
4
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FULL PAPER
hydroxy hydroperoxides is very broad, indicating a gradual
release of heat. For comparison, the shape of explosive azide
compounds is usually very sharp and release much more energy
3
continuous flow conditions. A solution of 2 in CH CN (10 g/L)
was first introduced at a flow rate of 2 mL/min into an oven at
100°C (Table 5).[ Under these conditions, the conversion only
reached 20%, indicating that the reaction temperature was not
high enough at this flow rate (Table 5, entry 1). Increasing the
temperature from 100 to 300°C led to a 90% conversion (Table
5, entries 2-3). No attempt has been made to further increase
this temperature. Doubling the concentration to 20 g/L only led
to 54% conversion (Table 5, entry 4). Increasing the flow rate to
43]
(
e.g., a heat release of 1770 kJ/kg for the Zhdankin reagent,
ABX).[ The cleavage of fatty -hydroxy hydroperoxide 2 was
first studied in batch conditions (Table 4). The reaction was
initially conducted in tert-amylalcohol at 80°C (Table 4, entry 1).
42]
Table 4. Optimization for the thermal cleavage of fatty -hydroxy
hydroperoxide 2 in batch conditions.[a]
5
or 10 mL/min reduced the residence time to 36 and 18 s,
respectively, thus leading to a drastic drop of the conversion
Table 5, entries 5-6). On the contrary, decreasing the flow rate
to 1 mL/min gave a full conversion of -hydroxy hydroperoxide 2
Table 5, entry 7).
(
(
Table 5. Optimization for the thermal cleavage of fatty -hydroxy
hydroperoxide 2 in continuous flow conditions.[
a]
S.[b]
11-12
S.[b]
14-15
(%)
S.[b]
3
(%)
S.[b]
13
T
°C)
Time
(h)
Entry
1
Solvent
(
(%)
(%)
t-amyl-
OH
8
0
4
45
27
5
16
2
3
t-BuOH
80
80
60
4
44
68
76
76
71
61
63
12
6
13
8
20
10
9
Flow
(mL/min)
Conv.[b]
2 (%)
Ratio[c]
11 and
Ratio[c]
3 and
13 (%)
Entry
T
°C)
Residence
time (s)
(
CH
CH
3
CN
CN
4
1
2 (%)
nd
8
4
3
16
2.5
2.5
2.5
2.5
5
5
1
2
100
200
300
300
300
300
300
2
2
90
90
20
33
90
54
10
0
20
9
5
C
C
C
C
2
2
2
2
H
5
CN
CN
CN
CN
100
100
100
100
2
5
13
14
20
13
6[c]
7[d]
8[e]
H
H
H
5
5
5
1
5
3
2
90
58
14
nd
-
22
29
10
-
1
10
18
4[d]
5
2
90
1
5
36
[
a] Reaction conditions: 25-mL Schlenk flask, -hydroxy hydroperoxide 2 (173
mg g, 0.5 mmol), solvent (2 mL, 0.25M). The conversion of 2 was determined
by NMR and was found to be complete in all cases. [b] Selectivities were
3 2
determined by GC. [c] CH CH CN (4 mL, 0.12M) was used. [d] the reaction
6
10
1
18
7
180
> 99
81
12
was carried out in the presence of Amberlite-15 (10 wt%). [e] DBU (10 mol%)
was used.
[a] Reaction conditions: -hydroxy hydroperoxide 2 (10 g/L in CH
conversion of 2 was determined by HPLC. [c] Ratio were determined by GC.
[d] [2 in CH CN] = 20 g/L. nd = not determined.
3
CN). [b] The
Under these conditions, the conversion was full after 4 hours.
However, the selectivity towards aldehydes 11 and 12 only
reached 45% due to the formation of acids 14 and 15 (27%),
3
Under these conditions, the aldehydes 11 and 12 were obtained
with 81% selectivity. A reaction was performed starting from
about 1 g of hydroperoxide 2 under the optimized conditions
1,2-diol 3 (5%) and -hydroxyketone 13 (16%). A similar
selectivity was obtained in tert-butanol but less acids and more
diol were produced (Table 4, entry 2). Satisfyingly, the selectivity
towards aldehydes increased to 68% when the reaction was
carried out in acetonitrile (Table 4, entry 3). This selectivity was
further increased to 76% when the reaction was performed at
(
6
Scheme 2). In that case, only aldehydes were obtained with
8% GC yield. These results remain satisfying considering the
high volatility of such aldehydes. Purification of the mixture by
column chromatography gave nonanal 11 and methyl 9-
oxononanoate 12 with 57 and 55% isolated yield, respectively.
60°C, provided a prolonged reaction time (Table 4, entry 4).
More interestingly, similar results could be obtained in
propionitrile at 100°C in only 2.5 hours (Table 4, entry 5). Other
parameters were tested such as the concentration of substrate
and the addition of acid or base catalyst (Table 4, entries 6-8).
However, no improvement could be obtained under these
conditions. In conclusion, the preliminary results obtained for the
cleavage of -hydroxy hydroperoxide 2 in batch conditions
suggest that the selectivity of aldehydes 11-12 could be further
improved by increasing the temperature. Therefore, we
envisioned that the thermal cleavage could be carried out at
higher temperature in a very short time, i.e., working under
Scheme 2. Thermal cleavage of fatty -hydroxy hydroperoxide in flow
conditions. GC yield were obtained using hexadecane as an internal standard
using calibration curves. Isolated yields in brakets.
5
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ChemSusChem
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FULL PAPER
This result clearly demonstrates the feasibility of a continuous Conclusion
flow process to prepare aldehydes from fatty epoxides through

-hydroxy hydroperoxides and paves the way for further process
In conclusion, we have developed an original method for the
cleavage of fatty epoxides to aldehydes through the formation of
development.

-hydroxy hydroperoxide intermediates. The ring-opening of
Mechanistic considerations
epoxidized fatty derivatives with aqueous H in the presence
2 2
O
of phosphostungstic acid gave a range of fatty -hydroxy
hydroperoxides with 30-80% isolated yields (8 examples). These
species were fully characterized by 1H and 13C NMR, HPLC-
HRMS and their stability was studied by DSC. The thermal
cleavage of -hydroxy hydroperoxides was first studied in batch
conditions but higher selectivities towards the formation of
aldehydes were obtained under flow conditions. Advantageously,
In addition to its synthetic utility for the production of aldehydes
from fatty -hydroxy hydroperoxides, this work also contributes
to give some insights on the reaction mechanism for the
2 2
O
. In a recent work,[20]
oxidative cleavage of epoxides using H
Lu et al. have proposed that the ring-opening of epoxide with
(1.2 equiv) in the presence of tungstic acid first produced
2 2
H O
the corresponding 1,2-diol and that this species is oxidized to
either -hydroxyketone or-hydroxy hydroperoxide. According
to our work, the formation of -hydroxy hydroperoxide through
their proposed pathway seems unlikely. In our case, the ring-
opening of epoxide with aqueous 50% H O in the presence of
2 2
tungstic acid gave 93% of -hydroxy hydroperoxide 2 and 7% of
diol 3 (see Table 1, entry 4).
2 2
the overall process does not require large excess of H O and
water was generated as the only byproduct. Finally, the fatty
aldehydes obtained are excellent building-blocks for the
production of bio-based additives (e.g., surfactants and
hydrotropes) and monomers.
Experimental Section
Procedure for the preparation of fatty β-hydroxy hydroperoxides. In
a 100-mL double jacketed reactor, fatty epoxide derivative (1 equiv) was
added in t-amyl alcohol (2M2B; 0.25 M), phosphotungstic acid (PTA, 0.1
2 2
mol%) was added and then 1.1 equivalent of H O (50 wt% in water) was
added dropwise. The flask was closed under argon atmosphere and
magnetically stirred at 10°C for 16 hours (the conversion of the epoxide
was followed by GC and TLC). The reaction mixture was filtered over a
celite pad and washed with ethyl acetate. The filtrate was concentrated
under reduced pressure to give the crude product that was purified by
column chromatography (Cyclohexane/Ethyl acetate 100:0 to 60:40).
Procedure for the thermal cleavage of fatty β-hydroxy
hydroperoxides to aldehydes. A solution of β-hydroxy hydroperoxide in
MeCN was prepared with a concentration of 10 g/L. The solution was
pumped through an oven heated at 300°C with a flow rate between 1 to 2
mL/min. The solution of aldehydes was recovered and analyzed by
HPLC (for the conversion of β-hydroxy hydroperoxide) and by GC (for the
yields of aldehydes). Then, the solvent was evaporated under reduced
pressure. The residue was purified by column chromatography
Figure 4. Mechanistic proposal for the cleavage of fatty -hydroxy
hydroperoxide to aldehydes.
(cyclohexane / ethyl acetate: 100:0 to 80:20).
2 2
This clearly demonstrates that H O is a better nucleophile than
water,[44] if not, products 2 and 3 would have been obtained in
almost equimolar ratio. So, the ring-opening of epoxide 1 with
Acknowledgements
aqueous 50% H
a 1:1 mixture of regioisomers (Figure 4, a). The formation of diol
results from the ring-opening of epoxide 1 with water as a
2 2
O mainly affords -hydroxy hydroperoxide 2 as
The region Auvergne Rhône-Alpes is also acknowledged for a
Ph.D. grant to T.D.D.M. (Pack Ambition Recherche – project
VALCOUPENZ). This project has been labeled by AXELERA,
pꢃle de compꢀtitivitꢀ Chimie-environnement in Auvergne-
Rhꢃne-Alpes. The authors also thank the SAS PIVERT for a
Ph.D. grant to N.D.V. (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. L. Joucla
3
competitive reaction. Noteworthy, diol 3 could not be thermally
cleaved to the corresponding aldehydes under our reaction
conditions. Moreover, no conversion of diol 3 has been obtained
when treated under the same conditions than the reported
2 2
systems using H O for the ring-opening of epoxides. On the
contrary, -hydroxy hydroperoxide 2 could self-arrange in a six-
membered transition state, in which the C-C bond could break
upon heating, thus releasing the desired aldehydes and water as
a co-product (Figure 4, b). Advantageously, both regioisomers
afford the same aldehydes in this process. In addition, a
molecule of water could be also eliminated from -hydroxy
hydroperoxide 2 to form -hydroxyketone 13 as a 1:1 mixture of
regioisomers (Figure 4, c).
(
LHCEP, Lyon) is also acknowledged for preliminary safety tests
on -hydroxy hydroperoxides. The “Centre Commun de
6
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ChemSusChem
10.1002/cssc.202002364
FULL PAPER
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8
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FULL PAPER
Entry for the Table of Contents
Biobased aldehydes were prepared from fatty epoxides through thermal cleavage of -hydroxy hydroperoxide species.
Institute and/or researcher Twitter usernames: @UnivLyon1, @ICBMSLyon
9
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