Synthesis of functionalized tetrahydrofuran derivatives from 2,5-dimethylfuran through cascade reactions

Article abstract of DOI:10.1039/c9gc01060b

A three-step strategy is proposed for the functionalization of the methyl group of 2,5-dimethylfuran, encompassing the ring opening of 2,5-dimethylfuran to 2,5-hexanedione, its further aldol condensation with aldehydes, and hydrogenation-cyclization of the condensation intermediate to generate alkylated tetrahydrofuran. Active and selective catalysts could be identified for the aldol condensation and hydrogenation-cyclization reactions.

Full text of DOI:10.1039/c9gc01060b

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Synthesis of functionalized tetrahydrofuran derivatives from 2,5-
dimethylfuran through cascade reactions
J. Li,a,b E. Muller,c M. Pera-Titus,b* F. Jérôme,a and K. De Oliveira Vigiera,*
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
A three-step strategy is proposed for the functionalization of the generate valuable downstream chemicals,10 such as methyl-
methyl group of 2,5-dimethylfuran, encompassing the ring opening and dimethylfuran or tetrahydrofuran,11 levulinic acid,
-
of 2,5-dimethylfuran to 2,5-hexanedione, its further aldol valerolactone,12 and diketones,13 as well as furoic,
condensation with aldehydes, and hydrogenation-cyclization of the furandicarboxylic14 maleic,15 and fumaric acids,16 and even
condensation intermediate to generate alkylated tetrahydrofuran. hydrocarbons.17
Active and selective catalysts could be identified for the aldol
condensation and hydrogenation-cyclization reactions.
Despite their great potential, the amount of furanic
derivatives potentially synthesized from carbohydrates is rather
limited. Functionalizing bio-based furanic derivatives in a
minimum number of synthetic steps is of huge interest to
increase the molecular diversity and complexity. It is well
established that the nature of the chemical group on the 2
position of the furanic ring will govern the reactivity of the 5
position of furans. In this view, one interesting reaction is the
functionalization of furanic compounds with alcohols and
olefins, which has been seldom explored. The Friedel-Crafts
reaction can be employed for alkylating aromatic substrates
using -activated alcohols or the corresponding esters in the
presence of Lewis acid catalysts. However, in the case of (alkyl)
furans, the reaction often leads to polymerization reactions and
requires the use of strong acids (e.g., HClO4, CF3SO3H, HBF4),
noble metal salts (PdCl2, triflates) and hazardous solvents (e.g.,
dichloromethane, dioxane).18 Furans can also undergo
alkylation reactions with alkenes following a Heck-type reaction
mechanism. Nonetheless, the reaction requires Pd(II) salts or
complexes, oxidants (e.g., copper salts, benzoquinone,
pyridine) to regenerate Pd(II) from Pd0.19
Introduction
Due to the depletion of fossil reserves, lignocellulosic biomass,
mostly composed of carbohydrates (75%), has gained great
interest as a huge reservoir of renewable carbon with an annual
production estimated at 180 billion metric tons per year.1
Hence, current research programs target the conversion of
carbohydrates into value added chemicals.2 For instance, lactic,
itaconic and succinic acids, as well as ethanol and 1,3-
propanediol, are industrially produced by the fermentation of
carbohydrates.3 Other catalytic routes convert carbohydrates
into sorbitol,4 xylitol,5 furfural,6 ethylene glycol,7 and
alkylpolyglycosides.8
Among the different intermediates that can be produced
from carbohydrates, furanic compounds hold a strategic place.
In particular, furfural and 5-hydroxymethylfurfural (HMF) can
be synthesized by the acid-catalyzed dehydration of hexoses
and pentoses,6,9 respectively. These two bio-based furanic
derivatives can be further oxidized, hydrolyzed or reduced to
As an alternative to alkylation reactions, herein we report a
catalytic route for selectively functionalizing the methyl group
of an important furanic derivative, i.e. dimethylfuran (DMF).
DMF can be produced either by the hydrogenolysis of HMF,11 or
a. IC2MP UMR CNRS_Université de Poitiers 7285, ENSIP 1 rue Marcel Doré, TSA
41195, 86073 Poitiers Cedex 9, France, email: karine.vigier@univ-poitiers.fr
b. Eco-Efficient Products and Processes Laboratory (E2P2L), UMI 3464 CNRS-Solvay,
3966 Jin Du Road, Xin Zhuang Ind. Zone, 201108 Shanghai, China, email:
marc.pera-titus-ext@solvay.com
directly
dehydration/hydrogenolysis reaction.20 Despite the fact that
the conversion of DMF to p-xylene through
from
fructose
through
a
tandem
a
Diels−Alder/dehydration sequence was extensively reported,21
only few examples are related to other synthetic
manipulations.22 Therefore, the exploration of strategically new
reactivity of DMF to functionalize biomass derived furans
appears to be of importance. The strategy presented here
c SOLVAY-Advanced Organic Chemistry & Molecule Design Laboratory, Recherche &
Innovation Centre de Lyon, 85 Avenue des Frères Perret, 69192 Saint Fons, France
† Footnotes relating to the title and/or authors should appear here.
Electronic Supplementary Information (ESI) available: [details of any supplementary
information available should be included here]. See DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
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consists of three consecutive steps (Scheme 1): (i) acid- according to reported protocols.23 On the one hand, in gas-
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DOI: 10.1039/C9GC01060B
catalyzed ring opening of DMF to 2,5-hexanedione (HxD), (ii) phase rehydration, the sample was flowed under wet nitrogen
basic-catalyzed aldol condensation of HxD with aldehydes, and at room temperature for 24 h. On the other hand, in liquid-
(iii) hydrogenation-cyclization of the functionalized HxD to a phase rehydration, the sample was introduced into ultrapure
tetrahydrofuran derivative. To the best of our knowledge this is water and stirred at room temperature for 2 h, followed by
the first time that the functionalization of the methyl group of filtration, drying under vacuum, and storage under nitrogen
DMF is reported.
atmosphere.
Catalytic tests
Aldol condensation of HxD with benzaldehyde (bzd)
The aldol condensation reaction of HxD with bzd was performed
in a 10-mL round bottom glass flask with a screw-sealing cap. In
a typical test, a given amount of catalyst was introduced into
the reaction flask under magnetic stirring. Then, 10 mmol of bzd
(around 1.06 g, 2 equiv with respect to HxD) were added,
followed by 5 mmol of HxD (around 0.57 g). In the case of the
use of solvent, 6 mL of ethanol, toluene or 1-butanol were
added. After sealing, the reactor was placed in an oil bath, the
reactor mixture was stirred and the temperature was adjusted
to the desired value.
Scheme 1. Direct conversion of DMF to functionalized THF derivatives.
One-pot hydrolysis of DMF with aldol condensation with bzd
The reaction was performed in a 10-mL round bottom glass flask
with a screw-sealing cap. In a typical one-pot reaction between
DMF and bzd, two solid acid and basic catalysts, i.e. PW98 and
A26, respectively, were added to the reaction flask. Then, 20 wt%
of ultrapure water (with regards to DMF) were introduced,
followed by 15 mmol of bzd (around 1.59 g, 3 equiv with respect
to DMF) and 5 mmol of DMF (around 0.48 g). The reactor was
further introduced into a pre-heated oil bath and the reaction
mixture was stirred.
Experimental
Chemicals
Benzaldehyde (≥99.5%), 2,5-dimethylfuran (99%) and 2,5-
hexanedione (≥98%), all supplied by Sigma-Aldrich, were used
as reagents. Benzaldehyde was freshly distilled under vacuum
before use and stored under nitrogen at 4 oC, whereas the other
reagents were used as received. Hydrogen (>99.99%) was
procured from Air Liquide and was used for the hydrogenation-
cyclization reactions. Silicagel (60 Å, 40-63 ), provided by Carlo
Erba, was used for purifying the reaction products. 1-Butanol
(99.8%), chloroform-d (99.8%), dichloro-methane (≥99.8%),
dimethyl sulfoxide-d6 (99.9%), ethyl acetate (99.5%) and
toluene (≥99.5%), all supplied by Sigma-Aldrich, were used as
solvents. Besides, acetone (≥99.8%) and a mixture of heptane
isomers (pure) were procured from Carlo Erba, while ethanol
absolute (≥99.98%) was provided by VWR Chemicals. All the
solvents were used as received without further purification.
Amberlyst®A26 (grey beads, Sigma-Aldrich), Amberlyst®A15
(pink beads, Sigma-Aldrich) and Aquivion®PW98 (white powder,
Solvay) were used in the acid-base catalyzed reactions without
Hydrogenation-cyclization of HxD
The hydrogenation-cyclization reaction of HxD was performed
in a stainless-steel autoclave reactor from Taiatsu (30 mL). In a
typical reaction, around 0.4 g of HxD (2 mmol) was loaded into
the autoclave. Next, the catalyst pre-reduced under hydrogen
at 180 oC for 30 min using a heating ramp of 5 oC/min, and 2 mL
of absolute ethanol were added to the autoclave. The autoclave
was then sealed, purged with hydrogen for three times,
pressurized with hydrogen at room temperature, and heated to
the desired temperature. After the reaction, the reactor was
cooled down to room temperature.
Analytical methods
activation. Mg6Al2(CO3)(OH)164H2O (white powder, Sigma-
Aldrich) was calcined and activated before use using the
protocols described below. Pd/C, Pt/C and Ru/C, all with 5 wt.%
metal loading, were supplied by Johnson Matthey.
Phosphomolybdic acid was supplied by Sigma Aldrich.
Gas chromatography analyses of the reactants and products
were performed on a Varian Bruker 450 GC equipped with a
flame ionization detector (FID) and a DB-WAX UI column (30 m
x 0.32 mm x 0.25 μm). The calibration was performed using
biphenyl as internal standard and acetone as solvent.
Flash chromatography was used to separate the reaction
products using a silicagel column. Silicagel was placed in a
beaker with an elution of heptane and ethyl acetate (80 : 20 v/v)
and stirred with a glass stick to degas the gel. Then, the gel was
transferred to a glass column. The mixture of condensation
products was first concentrated by rotation evaporation and re-
Activation of Mg6Al2(CO3)(OH)164H2O
First, Mg6Al2(CO3)(OH)16

4H2O was calcined to regenerate the
o
metal oxides. The sample was heated to 450 C at a rate of 5
o
oC/min, held at 450 C for 3 h, and cooled down to room
temperature under dry nitrogen. Subsequently, the calcined
sample was subjected to either gas or liquid-phase rehydration
2 | J. Name., 2012, 00, 1-3
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diluted with dichloromethane before introduction into the top
of the column. An elution mixture of heptane and ethyl acetate
(80 : 20 v/v) was used to separate the different compounds. In
the case of hydrogenation products, the silicagel was prepared
with heptane, and the product mixture was re-diluted using
silica powder (solid deposition method), because one of the
products was relatively apolar. Gradient elution was employed
to separate the different products with a heptane/ethyl acetate
volume ratio varying from 100 : 0 to 50 : 50. After separation,
푷
푹
∆푯풐풓
∆푺풐풓
=
풊=ퟎ ∆푯풐풇,풊
−
풊=ퟎ ∆푯풐풇,풊
(1)
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DOI: 10.1039/C9GC01060B
∑
∑
푷
푹
풊=ퟎ ∆푺풐풇,풊
−
풊=ퟎ ∆푺풐풇,풊
(2)
∑
∑
=
Given the heat and entropy of reaction, the free energy of
reaction (∆Gro) was calculated as follows
∆푮풐풓 = ∆푯풐풓 − 푻∆푺풐풓
(3)
glass tubes were used to collect the different product fractions, The equilibrium constant, 퐾푒푞 , for each reaction was computed
while Thin-Layer Chromatography (TLC) was used to track the using the expression
entire separation. TLC was performed on 0.20 mm silicagel 60
∆푮풐풓,푻 = −푹푻 풍풏(푲풆풒
)
(4)
with fluorescent indicator UV254 plates. The TLC plates were
revealed by reaction with a 20% v/v phosphomolybdic acid
solution in ethanol. After collecting the different product
fractions, the solvent was removed by rotation evaporation,
and solvent traces were further dried under high vacuum.
1H NMR and 13C NMR spectra of the different products were
recorded on a Bruker Advance 300 MHz NMR spectrometer.
Chemical shifts were given with respect to TMS.
where R is the constant of perfect gases (8.314 Pa.m3.mol-1.K-1).
Besides, the equilibrium constant for the aldol condensation
reaction of HxD with bzd can be expressed as follows
푿
푯ퟐ
][
풙ퟐ
[
][
]
푶
푲풆풒
=
=
(5)
[
]
(
)
ퟏ−풙 ∗(풏−풙)
푯풙푫 풃풛풅
where [HxD], [bzd] and [X] are the equilibrium concentrations
of HxD, bzd and product X, respectively, and n is the number of
bzd equivalents with respect to HxD.
Catalyst characterization
Thermogravimetric analysis (TGA) was used to characterize the
nature of adsorbed species on the spent catalysts after reaction.
The thermal profiles were measured on a SDT-Q600 instrument
with a flow gas system. The catalysts (~10 mg in a Pt crucible)
were treated from room temperature to 700 °C with a heating
rate of 10 °C.min-1 at 100 mL(STP).min-1 air flow.
FT-IR spectra were measured on the spent catalysts by
dispersing the catalysts in KBr (1 mg catalyst in 150 mg KBr). The
spectra were measured from 500-4000 cm-1 on a Perkin Elmer
One FT-IR instrument with 4 cm-1 resolution. Each spectrum was
measured using 30 scans. Before analysis, the samples were
washed with warm ethanol (3 times), dried in an oven overnight
at 60 oC, and grinded.
The nature and surface composition of the spent Pt/C was
analyzed by X-ray photoelectron spectroscopy (XPS) using a
Kratos Axis Ultra DLD apparatus equipped with a hemispherical
analyzer and a delay line detector. The spectra were recorded
using an Al monochromated X-ray source (10 kV, 15 mA) with a
pass energy of 20 eV (0.1 eV/step) for high resolution spectra,
and a pass energy of 160 eV (1 eV/step) for survey spectrum in
hybrid mode and slot lens mode, respectively. The adventitious
C1s binding energy (284.4 eV) was used as an internal reference.
ퟐ
푲풆풒 풏+ퟏ − 푲풆풒 (풏+ퟏ)ퟐ−ퟒ풏푲풆풒(푲풆풒−ퟏ)
(
) √
푿 풚풊풆풍풅 =
(6)
ퟐ(푲풆풒−ퟏ)
Results and discussion
In a first set of experiments, 5 mmol of DMF (around 0.46 g)
was reacted in 2 mL of water and heated at 100 °C in the
presence of Aquivion®PW98 perfluorinated sulfonic acid resin
(MW = 980 g/mole). Our choice was motivated by the
hydrophobic properties of PW98 combined with its water
tolerance for having a stable catalyst. DMF hydrolysis took place
selectively over PW98 and HxD could be generated in
quantitative yield after only 2 h. The catalyst was further filtered
and HxD was separated from water by distillation.
Next, the aldolization of HxD was investigated using bzd as a
representative aldehyde to obtain the target mono
condensation product (E)-7-phenylhept-6-ene-2,5-dione (X).
This reaction is not easy due to the symmetry of HxD, leading to
the double condensation product, (1E,7E)-1,8-diphenylocta-
1,7-diene-3,6-dione (Y), and to possible polymerization driven
by consecutive condensation reactions. The conversion of the
reactants and the yield of products were determined by gas
1
Thermodynamic calculations
chromatography and confirmed by H NMR. In this section,
Amberlyst-26 (A26) and hydrotalcite were selected as solid base
catalysts and the results are presented in Table 1. A26 is a
macroreticular ion exchange resin constituted of styrene and
The heat and entropy of reaction (∆Hro and ∆Sro, respectively)
were computed by DFT using Spartan software. The heat of
formation (∆Hfo,i) of the different compounds was computed
using a T1 method, while the entropy of formation (∆Sfo,i) was
computed using the B3LYP hybrid functional method and a 6-
311+G** basis set. All the calculations were conducted in the
gas phase without taking into account solvation effects. The
heat and entropy of reaction were calculated from the heat and
entropy of formation of the reactants (R) and products (P)
+
divinylbenzene, and functionalized with quaternary R-NH3 HO-
groups (0.8 mmol/g). We chose A26 because of its strong
basicity, high ion exchange capacity and great resistance in the
reaction media. On the other hand, hydrotalcites are a well-
known family of anionic clay materials consisting of a layered
structure with positively charged brucite like layers and
interlayers containing the charge balancing anions and water
molecules. Hydrotalcites have been widely reported as active
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Table 1. Catalytic aldolization of HxD with bzd in the presence of A26 and HTC basic catalysts
bzd/HxD
(molar ratio)
Time
(h)
T
HxD conversion
(%)
X yield
(%)
Y yield
(%)
X + Y sel
(%)
Sel. to other
products (%)
Entry
Catalyst
A26
Solvent
(oC)
1
2
3
4
5
6
7a
8
Ethanol
Toluene
Toluene
1
1
1
1
2
3
2
2
2
2
2
2
2
1
1
1
0.25
0.25
0.25
0.25
7
7
5
5
7
60
60
33
37
58
83
87
80
17
36
50
73
77
53
70
10
14
15
30
45
47
4
10
34
48
34
35
37
1
1
3
33
41
31
43
69
78
24
31
82
79
67
59
69
57
31
22
76
69
18
21
110b
100
100
100
100
120
140
160
160
140
160
-
-
-
-
-
-
-
-
-
-
6
15
15
0
1
7
HTC-liq
9
10
10a
11
12
10
HTC-gas
b
5
11
75
69
25
31
5
a
After recycling; Under reflux
and stable solid base catalyst for biomass transformations.24 (Fig. S3), leading to poisoning. Heavy molecules with high
The difference between A26 and HTC catalysts in term of retention time were also detected by GC analysis in the solution
basicity is the strength of the basic sites as HTC is known to have after the reaction.
basic sites with different strength25 whereas only strong basic
Hydrotalcite (HTC), an abundant mineral in nature with
sites are present on A26. In the case of A26, the use of solvents basic properties, was also used for conducting the aldol
(toluene, ethanol) exerted a negative effect on both the activity condensation reaction of HxD and bzd. Before use, the HTC was
and selectivity (Table 1, entries 1-4) which can be due to dilution calcined and activated by rehydration in liquid- and gas-phase
that affects the conversion of HxD and the yield to X. Under conditions (denoted as HTC-liq and HTC-gas, respectively) as
solvent-fre conditions, a HxD conversion of 83% was achieved described in the ESI in order to tune the basicity. The catalytic
at 100
C for a bzd/HxD molar ratio of 1 with 30% and 6% yield tests were carried out at solvent-free conditions for a bzd/HxD
of products X and Y, respectively, but with only 43% total molar ratio of 2. In the case of HTC-liq, the HxD conversion
o
o
selectivity (X+Y). A bzd/HxD molar ratio of 2 enhanced the yield increased from 36% to 73% from 120 C to 160 C (Table 1,
of products X and Y to 45% and 15% after 15 min with 69% total entries 8-10). The highest yield of X (48%) was achieved at 160
selectivity and 87% HxD conversion (Table 1, entry 5). A higher oC after 5 h. A similar behavior was observed for HTC-gas (Table
bzd/HxD molar ratio of 3 did not affect appreciably the catalytic 1, entries 11, 12). HTC-liq led to a higher yield of product X
performance (Table 1, entry 6). In all cases, the reaction was far compared to HTC-gas (48% vs. 37%). The different selectivity at
from chemical equilibrium, with X + Y equilibrium yields of 70% 160 oC between both catalysts could be ascribed to the different
o
and 78% at 100 C for bzd/HxD ratios of 2 and 3, respectively
,
density of basic OH groups.26 For HTC-liq, the yield of X dropped
according thermodynamic calculations (
Fig. S1). The A26 activity from 48% to 34% after the 2nd catalytic run, while the HxD
dropped significantly after the 1st run with a decrease of the conversion kept almost unchanged. In contrast, the yield of X
HxD conversion and X yield from 83% to 17%, and from 45% to and Y declined dramatically after the 3rd run after only 30 min
4%, respectively (Table 1, entry 7). As mentioned above, (11% and 1%, respectively), together with the HxD conversion
multiple condensation reactions could occur simultaneously. (25%). TGA analysis of the spent HTC reveals an additional
Indeed, heavy condensation products were observed on A26 weight loss appearing at 533°C for the spent HTC-gas and 525 °C
after reaction as inferred from FT-IR (Fig. S2) and TG analysis for the spent HTC-liq, which was not present in the fresh
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catalysts (Fig. S4 and S5). These weight losses can be ascribed
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With these results in hand, we conducted the one-pot
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to organic molecules adsorbed on catalyst. This hypothesis was hydrolysis of DMF to HxD, followed by tDhOeI:a1l0d.o10l3c9o/Cn9dGeCn0s1a0t6io0nB
confirmed by analyzing the liquid mixture after the reaction by reaction with bzd, by combining Aquivion®PW98 and A26
o
TGA using the same temperature program used for the catalysts. (Scheme 2). These reactions were conducted at 100 C using a
One clear weight loss region was visible at around 540 °C, bzd/HxD molar ratio of 3. To initiate HxD hydrolysis, a catalytic
indicating that one fraction of the reaction residue decomposed amount of water was added to the reaction system in order to
at this temperature (Fig. S6). One can mention that an favor the ring opening of DMF. DMF was fully converted after 2
agglomeration of HTC was observed at the end of the reaction. h reaction with 40% and 10% yield of products X and Y,
If a comparison is made between the catalysts, the strength of respectively, and 25% yield of HxD (Figure 1). The yield of the
the basicity could be an explanation for the highest activity and different products kept unchanged after 2 h, suggesting a
selectivity of A26 compared to HTC.
Next, it was interesting to extend the reaction scope. To this aim,
possible deactivation of one or both catalysts, most likely due
to side reactions leading to oligomerization products poisoning
the catalysts.
a
series of p-substituted benzaldehyde derivatives (4-
methoxybenzaldehyde, 4-(methylthio)benzaldehyde and 4-
phenoxybenzaldehyde) were used in the aldol condensation
reaction of 2,5-hexanedionein the presence of A26 as catalyst.
The reactions were performed under the same optimal reaction
conditions as for the reaction of 2,5-hexanedione with
benzaldehyde (Table2, entries 1-3). Overall, the 2,5-
hexanedione conversion was higher than 80% with a yield of the
mono condensation product M in the range 30-40%, which is
lower than the yield obtained on benzaldehyde (45%). The yield
of the double condensation products D was much lower for the
p-substituted benzaldehyde derivatives. In all cases,
oligomers/polymers were present in solution after reaction.
Table 2. 2,5-Hexanedione aldolization with benzaldehyde derivatives. Reaction
conditions: A26 40 wt%, X /benzaldehydes derivatives = ½ under solvent free conditions,
100 °C.
Figure 1. One-pot reaction catalyzed by PW98 and A26. Reaction conditions:
100 oC, bzd/DMF = 3, 20 wt% water, 20 wt% PW98, 40 wt % A26.
A26
+
+
The final step was the ring closure of the functionalized HxD to
the corresponding THF-derivatives by hydrogenation-
cyclization. Depending on the degree of hydrogenation, four
products of interest can be obtained as depicted in Scheme 3. A
series of commercial carbon-supported metal catalysts based
on Ru, Pd and Pt (5 wt% metal) were tested in the
hydrogenation-cyclization of product X (Figure 2).
Solvent free, 100°C
X conv.
(%)
M yield
(%)
D yield
(%)
Entry
1
R
t (h)*
0.5
1
82
83
36
39
4
4
2
3
1
94
30
2
* optimized reaction time
Scheme 2. One-pot conversion of DMF towards product X.
Scheme 3. Potential products that can be obtained from the hydrogenation of the aldol
intermediate.
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With no catalyst, the X conversion was only 10% with 3% yield mixture of commercial Pt/C and the acid resin AmberliteIR-120
of A product (hydrogenation of C=C bond). Among the catalysts allows the formation 2,5-dimethyltetrahydrofuran from HxD. 27
tested, Ru/C and Pd/C were more selective for C=C bond Based on this study, to boost ring closure of product B, an acid
hydrogenation with A being the major product (38% and 86%, catalyst was added to the reaction mixture. In the presence of a
respectively), at 49% and 100% conversion, respectively. In the solid acid catalyst such as A15, product B could be fully
presence of Pt/C, full X conversion was achieved at short converted into products C and D with 49% and 33% yield,
reaction times with B and C as major products. The kinetic respectively. To increase the selectivity towards product C, the
profiles of the reaction catalyzed by Pt/C revealed that B was effect of the H2 pressure was optimized in the presence of Pt/C
not an intermediate generating C and D (Figure 3). Hence, after and A15. The reaction was conducted at 90 C in the H2 pressure
7 h of reaction, 22% yield of product B (hydrogenation of C=C range 10-30 bar (Table 3). Independently of the H2 pressure, full
bond and carbonyl group), 58% and 6% yield of ring closure conversion of X was achieved after 3 h. Traces of diol B were
products C and D, respectively, were obtained, together with observed at the end of the reaction. A yield of product C up to
trace amounts of unidentified products.
70% could be achieved at 20 bar H2 together with 14% yield of
product D. At 10 bar H2, 51% yield of the target product C and
5% yield of product D were obtained along with 24% yield of
product A. The lower yield of product C at 10 bar H2 can be
explained by the lower H2 solubility in the reaction media. In
contrast, when the reaction was performed at 30 bar H2, 49%
and 33% yield of products C and D, respectively, were obtained,
which can be explained by a higher rate of C towards D and a
higher H2 solubility. To promote the formation of product C, 20
bar H2 pressure was selected in the following experiments.
Table 3. Effect of the H2 pressure in the hydrogenation-cyclization of reactant X.
Reaction conditions: Pt/C 5 wt%, A15 5 wt%, X 20 wt% in ethanol, 90 °C, 3 h.
P
(bar)
X conv.
(%)
A yield
(%)
B yield
(%)
C yield
(%)
D yield
(%)
Figure 2. Product distribution during catalyst screening. Reaction conditions: 90 °C, 3 h,
5 wt% cat, 20 wt% X in ethanol, 3 MPa H2.
10
20
30
100
100
100
24
4
1
2
3
2
51
70
49
5
14
33
The effect of the temperature on the hydrogenation-
cyclization reaction of reactant X over Pt/C and A15 was further
investigated at 20 bar H2 pressure. Full kinetic profiles were
measured at 60 oC, 90 oC and 120 oC (Figure 4). In all cases, full
X conversion was achieved at very short times. Product A was
fast consumed during the first 3 h to form products C and D,
whereas product B exhibited very low selectivity (<5%) even at
short reaction times. Product C exhibited an almost constant
selectivity of ca. 70% from 3 h to 17 h, whereas it was totally
o
converted into product D after 48 h at 60 C. Interestingly, this
o
time was reduced to 24 h at 90 C. Opposing this behavior,
o
product C was preeminent over D at 120 C even after 64 h
reaction (71% selectivity). This observation suggests a partial
o
inhibition of the hydrogenation of product C into D at 120 C,
Figure 3. Kinetic profiles of the hydrogenation-cyclization reaction of X over Pt/C.
Reaction conditions: Pt/C 5 wt%, X 20 wt% in ethanol, 90 °C, 30 bar H2.
which can be explained by a selective deactivation during the
reaction.
This was in accordance to the study of Zhou et al.27 who
reported that in the presence of Pt/C the main product was
hexanediol from HxD. Thus they reported that a physical
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Figure 5. Evolution of the catalytic performance in consecutive catalytic runs for the
hydrogenation-cyclization reaction of X over Pt/C + A15. Reaction conditions: Pt/C 5 wt%,
A15 5 wt%, X 20 wt% in ethanol, 120 oC, 16 h, 20 bar H2.
To gain more insight into the catalyst evolution during the
reaction, the spent Pt/C catalyst was analyzed by XPS after the
5th run (Table S1 and Fig. S7 and S8). Most of the Pt (90.3 atom %)
kept in metal form, suggesting that the apparent decrease of
selectivity is not attributed to Pt oxidation. One can note that,
about 1.5 wt% sulfur was present on the spent Pt/C after the 5th
run, which can be ascribed to interactions between A15 and
Pt/C catalysts. Besides, we cannot exclude partial poisoning
due to carbon deposits on Pt, which were difficult to ascertain
due to the presence of the carbon support.
Conclusion
The aldol condensation reaction of 2,5-hexanedione with
benzaldehyde was conducted over two basic catalysts, i.e.
Amberlyst®A26 and a Mg-Al hydrotalcite, affording the mono-
condensation product with ca. 50% yield. Oligomerization
products were responsible for catalyst deactivation. One can
mention that the selectivity towards X from Y could be steered
by converting X as soon as it is formed to the THF products. This
strategy required the control of the kinetic of the reactions and
the design of an appropriate reactor. Nevertheless, it was
possible to directly convert DMF into functionalized 2,5-
hexanedione in a one-pot reaction by physically mixing
Aquivion®PW98 and Amberlyst®A26.
Figure 4. Kinetic profiles for hydrogenation-cyclization reaction of of X over Pt/C
at 60 oC (top), 90 oC (middle) and 120 oC (bottom). Reaction conditions: Pt/C 5 wt%,
A15 5 wt%, X 20 wt% in ethanol, 20 bar H2.
The recycling and reuse of the Pt/C + A15 system was further
explored in five consecutive runs at 120 oC for 16 h at 20 bar H2
(Figure 5). After each run, the catalyst mixture was separated
from the reaction mixture by centrifugation, washed with
o
ethanol (x3), and dried in an oven at 80 C for 10 h under
vacuum. The spent catalyst was then re-used without any
further purification. Reactant X reached full conversion after
each run. Trace amount of product B were observed, indicating
that the acid catalyst A15 remained active in all the catalytic
runs. However, after the 4th and 5th runs, the selectivity of
product C dropped dramatically in favor of product A. The
amount of catalyst (mostly Pt/C) decreased after each run until
50% Pt after the 5th run. A catalytic test with 50% of the initial
Pt/C loading and A15 was further conducted, affording 71%
selectivity of product C. This result points out that the observed
change of selectivity after the 3rd run cannot be attributed to a
decrease of the Pt/C loading after each run, but to an intrinsic
change of the hydrogenation performance of Pt/C during
reaction.
Finally, the hydrogenation-cyclization reaction of the mono-
condensation product towards the THF-derivative was
successfully achieved over Pt/C combined with Amberlyst®15.
The best selectivity towards the target product was achieved at
o
120 C for 16 h at 20 bar H2 pressure. The catalytic system
remained selective to the target product during the first three
runs, but favored the synthesis of less hydrogenated products
in the 4th and 5th runs due to partial deactivation of Pt.
In this study, we proposed an original strategy to synthesize
THF-derivatives by combining classic aldol condensation and
hydrogenation-cyclization reactions. This integrated process
can be an attractive route to synthesize alkylated furans in the
absence of organic solvents. Noteworthy, this strategy offers
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Acknowledgements
The authors express their gratitude to SOLVAY for the PhD
funding of JL via a CIFRE grant. Authors are also grateful to the
CNRS, the university of Poitiers and the French Ministry of
Research and Education for financial supports. The region
Nouvelle-Aquitaine and Europe is also acknowledged for the
funding of the FEDER/CPER program. The authors also thank Dr.
Raphael Wischert for his help in the thermodynamic
calculations.
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Graphical Abstract
Synthesis of functionalized tetrahydrofuran derivatives from 2,5-dimethylfuran through cascade
reactions
Lignocellulosic Biomass
Catalytic
functionalization of
DMF
O
Specialty Chemicals
O
Convenient catalytic route for selectively functionalizing the methyl group of an important bio-based
furanic derivatives (DMF).