NaBr/DMSO-induced synthesis of 2,5-diformylfuran from fructose or 5-(hydroxymethyl)furfural

Article abstract of DOI:10.1002/cctc.201400023

2,5-Diformylfuran (DFF) was obtained by heating a solution of 5-(hydroxymethyl)furfural in DMSO. The addition of acids or salts improved the selectivity, especially if bromides were employed. Good yields of DFF were obtained with HBr or NaBr as the catalyst. One-pot procedures were developed from fructose, which led to DFF in medium yields. This transformation occurs through the formation of 5-(bromomethyl)furan-2-carbaldehyde followed by a Kornblum-type reaction. In the presence of bromide salts, the in situ formation of the catalyst involves the thermolysis of DMSO and the association of the resulting strong acids with the bromides. With a pinch of salt: The association of NaBr as a catalyst and DMSO as a solvent allows the synthesis of 2,5-diformylfuran from 5-(hydroxymethyl)furfural (HMF) or fructose in 75 or 50 % yield, respectively. This transformation occurs through the formation of 5-(bromomethyl)furan-2-carbaldehyde followed by a Kornblum-type reaction.

Full text of DOI:10.1002/cctc.201400023

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DOI: 10.1002/cctc.201400023
NaBr/DMSO-Induced Synthesis of 2,5-Diformylfuran from
Fructose or 5-(Hydroxymethyl)furfural
Caroline Laugel,[a, b] Boris Estrine,*[a] Jean Le Bras,*[b] Norbert Hoffmann,[b] Sinisa Marinkovic,[a]
and Jacques Muzart[b]
2,5-Diformylfuran (DFF) was obtained by heating a solution of
5-(hydroxymethyl)furfural in DMSO. The addition of acids or
salts improved the selectivity, especially if bromides were em-
ployed. Good yields of DFF were obtained with HBr or NaBr as
the catalyst. One-pot procedures were developed from fruc-
tose, which led to DFF in medium yields. This transformation
occurs through the formation of 5-(bromomethyl)furan-2-car-
baldehyde followed by a Kornblum-type reaction. In the pres-
ence of bromide salts, the in situ formation of the catalyst in-
volves the thermolysis of DMSO and the association of the re-
sulting strong acids with the bromides.
0.75 equivalents of the catalyst.[3] A one-pot/two-step synthesis
of DFF was achieved by catalytic conversion of glucose over
CrCl3·6H2O/NaBr followed by NaVO3·2H2O-catalyzed oxidation,
and DFF was obtained in 55% yield based on glucose; the
one-pot process led to the formation of DFF in 18% yield.[4]
DFF was synthesized from glucose in 25% yield in N,N-dime-
thylformamide through isomerization, dehydration, and oxida-
tion through the stepwise addition of hydrotalcite, Amberlyst-
15, and Ru/hydrotalcite catalysts.[5] The two latter catalysts also
allowed the preparation of DFF from fructose in 49% yield.[5]
Notably, these one-pot syntheses of DFF usually require the
stepwise addition of the catalyst; the coexistence of both de-
hydration and oxidation catalysts from the initial stage of the
reactions produces low yields of DFF owing to undesired side
reactions that convert carbohydrates into humins.
2,5-Diformylfuran (DFF) is an important platform molecule that
can be synthesized from renewable resources.[1] Such a com-
pound is produced by oxidation of 5-(hydroxymethyl)furfural
(HMF), which is prepared by dehydration of carbohydrates
such as fructose. The routes reported for the synthesis of DFF
are mostly based on the oxidation of pure HMF, but its high
price limits the production of DFF. This drawback and
the low stability of HMF in organic solvents have led
to the development of one-pot procedures from fruc-
tose to avoid the isolation of HMF. DMSO is known
to promote dehydration efficiently and to stabilize
HMF, and one-pot methods have therefore been de-
veloped in such a solvent. Grushin reported the first
practical method for the synthesis of DFF directly
from fructose by using a two-step procedure involv-
ing the dehydration of fructose by an acidic resin fol-
lowed by filtration of the resin and air oxidation of
Herein, we report that simple salts, in one-pot transforma-
tions, can replace transition-metal catalysts for the conversion
of fructose or HMF into DFF in DMSO as the solvent
(Scheme 1). Preliminary mechanistic studies are also discussed.
Scheme 1. Synthesis of DFF from fructose.
the resulting HMF by vanadium catalyst at 1508C.
Thus, DFF was isolated in 45% overall yield.[2] The
one-pot synthesis of DFF from fructose was achieved in 80%
yield through the stepwise addition of the catalyst, that is,
a magnetic solid acid, Fe3O4-SBA-SO3H, and a porous manga-
nese oxide, K-OMS-2. However, the oxidation step required
The dehydration of fructose is known to occur in DMSO at
high temperature.[1a,6] This transformation is generally per-
formed in a few hours at 1508C. Upon studying the stability of
HMF in DMSO at this temperature, we observed that DFF was
produced after 18 h in 30% yield (Table 1, entry 1).[7] We sus-
pected that the decomposition products of DMSO at high tem-
perature could act as catalysts for the oxidation of HMF. Swern
observed that thermolysis of DMSO in air led to the formation
of strong acids such as sulfuric and methanesulfonic acids.[8]
We indeed observed acidification of the reaction mixture.[9] Var-
ious Brønsted acids were then evaluated as catalysts for the
oxidation of HMF in DMSO. Full conversion of HMF was ach-
ieved by using H2SO4 (30 mol%), and thermal conditions gave
better selectivity than microwave irradiation (Table 1, entries 2
and 3). HCl, HI, and PTSA·H2O (PTSA=p-toluenesulfonic acid)
[a] Dr. C. Laugel, Dr. B. Estrine, Dr. S. Marinkovic
Green Chemistry Department
Agro-industrie Recherches et Dꢀveloppements
Route de Bazancourt, Pomacle 51110 (France)
E-mail: b.estrine@a-r-d.fr
[b] Dr. C. Laugel, Dr. J. Le Bras, Dr. N. Hoffmann, Dr. J. Muzart
Institut de Chimie Molꢀculaire de Reims, UMR 7312
CNRS-Universitꢀ de Reims Champagne-Ardenne
UFR des Sciences Exactes et Naturelles, Reims 51100 (France)
E-mail: jean.lebras@univ-reims.fr
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/cctc.201400023.
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Table 1. Oxidation of HMF to DFF in DMSO.[a]
Entry
Catalyst, loading [mol%]
DFF, yield [%][b]
1
–
30
2
H2SO4 , 30
H2SO4 , 30
HCl, 30
54
29
28
3[c]
4
5
6
7
8
HI, 30
PTSA·H2O, 30
HBr, 30
LiBr, 30
NH4Br, 30
NaI, 30
NaCl, 30
NaBr, 30
53[d]
29
85 (75)
66
61
7
9
10
11
12
10
85 (75)
Scheme 2. One-pot preparation of DFF from fructose.
[a] Conditions: HMF (1.0 mmol), catalyst, DMSO (2 mL), 1508C, 18 h, con-
version 100%. [b] Yields were determined by GC analysis; yields of the
isolated products are given in parentheses. [c] Performed under micro-
wave irradiation (115 W, 20 min, T8max =1278C). [d] The formation of FFCA
was observed.
tained with NaBr (Scheme 2b). The concentration of HBr was
probably too high during the dehydration step of fructose,
which led to secondary reactions. The yield of the isolated
product was 50% for the one-pot procedure from fructose by
using NaBr and for the two-step procedure with the use of HBr
as the catalyst.
were less efficient, whereas HBr greatly improved the selectivi-
ty and provided the product in good yield (Table 1, entries 4–
7).[10] Given that strong acids can be obtained from the ther-
molysis of DMSO, simple halide compounds were also tested
as additives. Bromides were more efficient than chlorides and
iodides, and NaBr led to a good yield of DFF (Table 1, en-
tries 8–12).
A mechanism was proposed for the dehydration of fructose
to HMF in which DMSO acted as the catalyst.[11] We rather sus-
pect that the strong acids produced during the thermolysis of
DMSO are the true catalytic species.[12] Concerning the oxida-
tion step, we envisaged three possible pathways (Figure S1).
We first envisioned that protonation of the alcohol group of
HMF leads to the formation of a cationic intermediate, which
would undergo nucleophilic addition of DMSO. Intramolecular
deprotonation of a hydrogen atom to lead to DFF and Me2S
could follow two paths: through the formation of an ylide or
through direct deprotonation of the hydrogen atom at C1 (Fig-
ure S1a). A similar approach would involve (halogenomethyl)-
furan-2-carbaldehyde as neutral intermediate (Figure S1b). The
last pathway would involve the protonation of DMSO. The re-
sulting sulfonium would react with the alcohol functionality of
HMF. Intramolecular rearrangement would lead to DFF, Me2S,
and H2O (Figure S1c). This last step does not depend on the
structure of HX, and the results showed that the nature of the
counteranion of the acid had a strong impact on the efficiency
of the reaction. The first two approaches are more credible,
and the main differentiation between these two paths is the
nature of the intermediate, which would be ionic or neutral.
We therefore prepared (halogenomethyl)furan-2-carbaldehydes
and studied their reactivities in DMSO.
Other solvents such as DMF, sulfoxides, and sulfolane were
tested in the presence of NaBr, but they all led to inferior re-
sults (Table S1, Supporting Information). The influence of the
amount of NaBr, the concentration of HMF, and the tempera-
ture was then studied in DMSO (Table S2). Increasing the con-
centration of HMF from 5.7 to 11.4 wt% had no impact on the
yield (Table S2, entries 1 and 2), whereas a concentration of
22.8 wt% HMF led to 57% yield (Table S2, entry 3). When the
amount of catalyst was reduced to 10 mol% by using
a 11.4 wt% HMF solution, the yield was 71% (Table S2,
entry 4). A higher temperature (1708C) with a 5.7 wt% HMF so-
lution and 30 mol% catalyst was detrimental to the yield
(Table S2, entry 5), whereas a high yield of DFF (84%) was
reached with 10 mol% catalyst at 1708C (Table S2, entry 6). At
this temperature, an increase in the concentration of HMF had
a negative impact on the efficiency of the process (Table S2,
entry 7). The best conditions for the oxidation of HMF into DFF
are the use of 30 mol% NaBr, 1508C, and concentrations of
HMF between 5.7 and 11.4 wt%.
The one-pot synthesis of DFF from fructose was then stud-
ied. In the absence of a catalyst, a low yield (12%) was ob-
served. A two-step procedure was first evaluated on the basis
of the DMSO-induced dehydration of fructose followed by an
oxidation step performed in the presence of HBr or NaBr. DFF
was obtained in 65–68% yield according to GC analysis
(Scheme 2a). The influence of the nature of the catalyst was
much more pronounced if the procedure was performed in
one step. The presence of HBr in the initial stage of the trans-
formation had a strong negative impact on the yield of DFF,
whereas a good yield (67%, according to GC analysis) was ob-
Upon heating 5-(bromomethyl)furan-2-carbaldehyde and 5-
(chloromethyl)furan-2-carbaldehyde in DMSO at 1508C for
18 h, DFF was obtained in 57 and 81% yield, respectively
(Scheme 3). Under similar conditions, 5-(iodomethyl)furan-2-
carbaldehyde led to DFF in 62% yield and to 5-formylfuran-2-
carboxylic acid (FFCA) in 22% yield (Scheme 3). The formation
of FFCA was also observed for the HI-catalyzed oxidation of
HMF (Table 1, entry 5).
The kinetics of oxidation of 5-(bromomethyl)furan-2-carbal-
dehyde and the catalyzed oxidation of HMF in the presence of
HBr in DMSO were monitored (Figure 1). Both kinetics followed
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Scheme 3. Reactions of (halogenomethyl)furan-2-carbaldehydes in DMSO.
Figure 3. Kinetics of the oxidation of HMF in the presence of acids and NaBr.
HMF (1.0 mmol), acid (0.3 mmol), NaBr (0 or 0.3 mmol), DMSO (2 mL), 1508C.
a low selectivity was observed with H2SO4 owing to the forma-
tion of 5-[(methylthio)methyl]furan-2-carbaldehyde as a by-
product. Upon using NaBr in conjunction with H2SO4, the yield
of DFF improved. A similar result was achieved by using a mix-
ture of PTSA·H2O and NaBr. The association of a strong acid
with NaBr led to the in situ formation of HBr and to the forma-
tion of the neutral 5-(bromomethyl)furan-2-carbaldehyde inter-
mediate, which induced a selective transformation. In the ab-
sence of NaBr, the strong acid led to the formation of the
more reactive cationic intermediate (Scheme S1a), which af-
forded an unselective reaction.
Figure 1. Kinetics of the oxidation of 5-(bromomethyl)furan-2-carbaldehyde
and HMF. Conditions: HMF (1 mmol), HBr (0.3 mmol), DMSO (2 mL), and
&
1508C ( ); 5-(bromomethyl)furan-2-carbaldehyde (1 mmol), DMSO (2 mL),
Finally, given that levunilic and formic acids can be pro-
duced from HMF,[12] we monitored the oxidation of HMF in
their presence (Figure 3). These weak acids were strong
enough to catalyze the dehydration of fructose,[12] but they did
not show any activity for the oxidation of HMF in DMSO
(Figure 3).[12]
1508C (ꢁ).
a similar trend, which suggested that the slow step of the HBr-
catalyzed oxidation of HMF is the oxidation of 5-(bromome-
thyl)furan-2-carbaldehyde by DMSO. The catalyzed oxidation
would occur through a Kornblum-type reaction, in which the
counteranion of the acid would act as a base (Scheme S1b).
The kinetics of oxidation of HMF in the presence of NaBr
and HBr as catalysts were compared (Figure 2). An induction
period was observed in the presence of NaBr, whereas this
In conclusion, the preparation of DFF from fructose or HMF
in DMSO generally requires transition-metal catalysts, and we
showed that simple halides (acids or salts) could induce this
transformation. Bromides led to the best results, and DFF was
prepared from fructose through a one-pot reaction under
simple conditions. The in situ formation of strong acids from
the thermolysis of DMSO seemed to be involved as catalysts,
and the presence of bromides increased the selectivity. Such
catalyzed procedures can be involved if DMSO is used as the
solvent and should be taken into account especially if halides
are present in the reaction mixture.
Acknowledgements
The authors gratefully acknowledge financial support by the
Champagne-Ardenne Region and FEDER for this project (Fura-
synth program).
Figure 2. Kinetics of the oxidation of HMF in the presence of HBr or NaBr.
HMF (1.0 mmol), HBr or NaBr (0.3 mmol), DMSO (2 mL), 1508C, air or argon.
Keywords: 2,5-diformylfuran
· carbohydrates · fructose ·
phenomenon was nonexistent with HBr. The induction period
is probably related to the formation of strong acids by ther-
molysis of DMSO in air. Indeed, under an atmosphere of argon,
the induction period was more pronounced (Figure 2).
oxidation · oxygen heterocycles
[1] For recent reviews highlighting the syntheses and uses of DFF, see
a) R.-J. van Putten, J. C. van der Waal, E. de Jong, C. B. Rasrendra, H. J.
Heeres, J. G. de Vries, Chem. Rev. 2013, 113, 1499–1597; b) L. Hu, G.
Zhao, W. Hao, X. Tang, Y. Sun, L. Lin, S. Liu, RSC Adv. 2012, 2, 11184–
11206; c) P. Gallezot, Chem. Soc. Rev. 2012, 41, 1538–1558; d) M. J. Cli-
ment, A. Corma, S. Iborra, Green Chem. 2011, 13, 520–540; e) A. A. Rosa-
The kinetics of the oxidation of HMF in the presence of
strong acids were then monitored (Figure 3). No induction
period was observed in the presence of such species. However,
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COMMUNICATIONS
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tella, S. P. Simeonov, R. F. M. Frade, C. A. M. Afonso, Green Chem. 2011,
13, 754–793; f) X. Tong, Y. Ma, Y. Li, Appl. Catal. A 2010, 385, 1–13; g) A.
Corma, S. Iborra, A. Velty, Chem. Rev. 2007, 107, 2411–2502.
[2] a) G. A. Halliday, R. J. Young, V. V. Grushin, Org. Lett. 2003, 5, 2003–
2005; b) V. Grushin, N. Herron, G. A. Halliday, PCT Int. Appl., WO
2003024947, CAN138:271525, 2003.
Hernꢂndez-Benitez, J. A. AviÇa, E. BurgueÇo-Tapia, J. Tamariz, Synthesis
2011, 1106–1112.
[8] T. M. Santosussol, D. Swern, J. Org. Chem. 1976, 41, 2762–2768.
[9] The reaction mixture obtained with conditions of Table 1, entry 1 was
diluted with H2O (2 mL) and an acidic pH was measured (pH 0).
[10] Since 33% HBr solutions in acetic acid were used for all experiments,
AcOH was also tested as catalyst (30%), but the reaction performed at
1508C over 18 h led to 28% yield of DFF.
[3] Z.-Z. Yang, J. Deng, T. Pan, Q.-X. Guo, Y. Fu, Green Chem. 2012, 14,
2986–2989.
[4] X. Xiang, L. He, Y. Yang, B. Guo, D. Tong, C. Hu, Catal. Lett. 2011, 141,
735–741.
[11] A. S. Amarasekara, L. D. William, C. C. Ebede, Carbohydr. Res. 2008, 343,
3021–3024.
[5] A. Takagaki, M. Takahashi, S. Nishimura, K. Ebitani, ACS Catal. 2011, 1,
1562–1565.
[12] It has been shown that even weak acids, such as levulinic and formic
acid, catalyze the dehydration of fructose, through an autocalytic pro-
cess: A. Ranoux, K. Djanashvili, I. W. C. E. Arends, U. Hanefeld, ACS Catal.
2013, 3, 760–763.
[6] a) S. De, S. Dutta, B. Saha, Green Chem. 2011, 13, 2859–2868; b) K.-i. Shi-
mizu, R. Uozumi, A. Satsuma, Catal. Commun. 2009, 10, 1849–1853;
c) X. Qi, M. Watanabe, T. M. Aida, R. L. Smith, Jr., Catal. Commun. 2009,
10, 1771–1775; d) H. Yan, Y. Yang, D. Tong, X. Xiang, C. Hu, Catal.
Commun. 2009, 10, 1558–1563; e) R. M. Musau, R. M. Munavu, Biomass
1987, 13, 67–74.
Received: January 10, 2014
Revised: February 3, 2014
[7] Traces of DFF have also been observed upon heating a DMSO solution
of sucrose under microwave irradiations, see H. Quiroz-Florentino, R. I.
Published online on March 12, 2014
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