Solvent-free mechanochemical oxidation and reduction of biomass-derived 5-hydroxymethyl furfural

Article abstract of DOI:10.1039/c8gc02481b

The simultaneous synthesis of 5-hydroxymethyl-2-furoic acid and 2,5-hydroxymethylfuran from biomass-derived 5-hydroxymethyl furan was developed using a solvent-free mechanochemical approach. The results obtained for the Cannizzaro disproportionation reaction show quantitative conversions of the starting materials with reaction times of only 5 min. Employing solvent-free conditions allows for a more sustainable synthetic approach that is reflected in an E_factor 7 times smaller than that in previous reports. Additionally, initial results of the use of a sacrificial reagent, with the same solvent-free mechanochemical approach, for the selective reduction and oxidation of HMF are presented.

Full text of DOI:10.1039/c8gc02481b

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Solvent-free mechanochemical oxidation and
reduction of biomass-derived 5-hydroxymethyl
furfural†
Cite this: Green Chem., 2018, 20,
261
5
Received 6th August 2018,
Accepted 14th October 2018
a
a
a
a
a,b
F. Chacón-Huete, C. Messina, F. Chen, L. Cuccia,
X. Ottenwaelder
and
a,b
DOI: 10.1039/c8gc02481b
P. Forgione
*
rsc.li/greenchem
The simultaneous synthesis of 5-hydroxymethyl-2-furoic acid and the major products. HMF is a versatile small molecule that can
2
,5-hydroxymethylfuran from biomass-derived 5-hydroxymethyl serve as a substrate for the production of a multitude of furan
1
0,11
furan was developed using
a
solvent-free mechanochemical derivatives (Fig. 1).
These biomass-derived platform chemi-
approach. The results obtained for the Cannizzaro disproportiona- cals have potential application in multiple fields of synthetic
1
2
tion reaction show quantitative conversions of the starting chemistry.
materials with reaction times of only 5 min. Employing solvent- Previous reports have demonstrated the oxidation of HMF
free conditions allows for a more sustainable synthetic approach into 2,5-furandicarboxylic acid (FDCA) using various supported
1
3
that is reflected in an Efactor 7 times smaller than that in previous transition metal heterogeneous catalysts including PtBi/C,
reports. Additionally, initial results of the use of a sacrificial Pd/PVP, Au/HT, and Ru/C, among others,
1
4
15
16
17–20
but the
reagent, with the same solvent-free mechanochemical approach, partial oxidation into 5-hydroxymethylfuroic acid (HMFA) or
for the selective reduction and oxidation of HMF are presented.
even 2,5-diformylfuran (DFF) has been scarcely reported due
to the challenge in preventing complete oxidation (FDCA).
Domínguez de María and Li reported enzyme-mediated
methodologies in which HMFA and DFF were obtained
employing lipases and alcohol oxidases with good yields, but
with long reaction times.
2
1
22
Introduction
In the last decades, an uncontrolled overexploitation of fossil
resources has led to increasing levels of emissions produced
during the extraction and utilization of petrochemical-
The conversion of HMF into HMFA and 2,5-dihydroxy-
methylfuran (DHMF) is an important transformation that has
been scarcely reported when compared to the synthesis of the
1
based raw materials, thereby contributing to global warming.
Sustainable chemical resources, coupled with greener method-
ologies, have therefore become an attractive target for aca-
16,23–25
higher oxidation state derivatives like FDCA.
Nonetheless, these molecules have been highlighted as impor-
tant potential bio-monomers for the synthesis of polymers,
2
demic research and potential industrial application. The need
to find new sustainable resources for energy production has
been accompanied by a search for new sources of small mole-
26,27
28
such as polyurethane foams
and polyesters.
In 2013, Afonso and co-workers reported the use of a
Cannizzaro disproportionation reaction to synthesize both
HMFA and DHMF simultaneously from HMF, under basic
3
cules for the synthetic organic industry. In this context, much
attention has been paid to biomass as a potential source for a
4–7
wide variety of small molecules. Every year, 170 billion tons
of biomass are produced by photosynthesis. Seventy five percent
of this material can be classified as carbohydrates, but only less
than 4% is used as food and non-food consumables, which
29
conditions. The Cannizzaro reaction was originally reported
8
,9
leads to a vast accumulation of an untapped raw material.
The dehydration of common hexoses has been reported to
efficiently produce 5-hydroxymethylfurfural (HMF) as one of
a
Department of Chemistry and Biochemistry, Concordia University, Canada.
E-mail: pat.forgione@concordia.ca
b
Centre for Green Chemistry and Catalysis, Canada
†
Electronic supplementary information (ESI) available. See DOI: 10.1039/
Fig. 1 Biomass derived furans with potential use as eco-friendly start-
c8gc02481b
ing materials.
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0–32
in the 1850s as a facile mode to synthesize benzoic acids.
Table 1 Optimization
Cannizzaro disproportionation of HMF
for
the
solvent-free
mechanochemical
One of the most prescient limitations of this reaction is that it
allows for a maximum transformation of only 50% of the start-
ing material into a specific target (either the reduced or oxi-
dized product), which limits the efficiency of the overall reac-
tion. For the modification of HMF, however, employing the
Base
Cannizzaro disproportionation takes advantage of this reactiv- Entry (equiv.)
ity, since the simultaneous production of both HMFA and
DHMF is beneficial due to their potential applications as
Conditions
Time %HMFA %DHMF
1
2
3
4
5
6
7
8
9
NaOH (1.1) 24 °C [0.2 M] in H
NaOH (1.1) 24 °C [0.2 M] in H
2
O
O
24 h
36 h
67
<5
67
23
64
2
3
2–34
a
biomass-derived platform chemicals.
Our goal is to
NaOH (1.1) Manual grinding
5 min 64
5 min 12
5 min 76
5 min 88
5 min 66
5 min >99
5 min 87
b
KOH (1.1)
KOH (1.1)
KOH (2.0)
KOH (1.1)
KOH (2.0)
KOH (3.0)
Lysis milling
Auto. grinding
Manual grinding
12
76
88
66
develop conditions that allow for the synthesis of these
biomass-based materials with an even smaller impact on the
environment through a solvent-free methodology.
Solvents represent an estimated 80 to 90% by mass of the
waste produced in a typical pharmaceutical batch chemical
operation. A valuable strategy to circumvent this issue is the
use of mechanochemistry, which refers to solvent-free chemi-
cal transformations induced by mechanical energy, such as
c
a
d
Ball millingd
Ball milling
>99
87
a
Manual grinding
a
b
c
3
5
Reaction done under manual grinding with a mortar and pestle.
FastPrep24, MP Biomedicals, used with ceramic beads at max. speed.
Automatic mortar and pestle. Planetary ball mill at 60 Hz.
d
3
6
compression, shear, or friction. The environmental benefits
in the use of these greener reactions are extended to the work- Employing a slight excess of NaOH under manual grinding for
up (Fig. 2) and purification processes, often overlooked 5 minutes gave a 64% disproportionation of the starting
3
7
sources of chemical waste.
material that was essentially equivalent in yield to the solution
reaction while using no solvent, and reducing the reaction
time from 24 hours to 5 minutes (entry 3).
New mechanochemical techniques have been developed
over the years to automatize solvent-free approaches to physi-
Results and discussion
With the aim of developing new efficient and innovative meth- cal and chemical transformations. Lysis mill machines have
odologies for the production of the potential biomass-derived been employed as mechanochemical tools in synthetic chem-
3
9
platform chemicals HMFA and DHMF, Cannizzaro solvent-free istry, and we investigated the use of ceramic beads to
conditions were explored. The reaction was performed perform the disproportionation reaction under solvent-free
mechanically assisted with manual grinding, automatic grind- conditions (entry 4), but only a 12% yield was obtained. When
38
ing, lysis milling and planetary ball milling (Table 1).
the same reaction conditions were attempted with an auto-
Initial results derived from the conditions of previous work matic grinding apparatus, the yield increased to 76% (entry 5).
have satisfactory reproducibility when water was employed as An increase to 2 equivalents of base achieved an 88%
the solvent for the Cannizzaro reaction of HMF (entry 1), yield, but no further increase was observed with 3 equivalents
but when the reaction was carried out for 36 hours at room of base (entries 6 and 9). Recent publications highlight the
temperature, decomposition appears to have occurred, as no efficiency of employing ball milling systems in organic
1
40,41
product was observed by GC-MS and H NMR analysis. Even synthesis, especially under solvent-free conditions.
When
though the reaction proceeds with an acceptable yield, it was a assessing the efficiency of the reaction using a ball milling
valuable step towards greener conditions and hence the use of system, a quantitative conversion was achieved with two
a solvent-free mechanochemical approach was evaluated. equivalents of base (entry 8) in five minutes without the use of
solvents. Identical results were obtained with different alkaline
hydroxides.
Given the potential quantities of DHMF and HMFA that will
be needed for industrial applications, we decided to explore
the efficiency of our optimized solvent-free methodology in
larger reaction scales. Scaling up of the solvent free conditions
from 200 mg up to 12.80 g provided the products in excellent
yields in all cases (Table 2). When the 12.8 g reaction was spun
for 7 min instead of 5 min, a quantitative yield was obtained
(
Table S2†). These series of experiments suggest the continued
efficiency of using a solvent-free approach for the synthesis of
these small molecules at an industrial scale, with new machi-
neries that can take tons of material for grinding purposes,
highlighting the potential for sizable reductions in industrial
chemical waste production.
Fig. 2 Schematic representation and photographs regarding the large
scale work-up and isolation of the compounds (see experimental section
for details).
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Table 2 Scale-up for the disproportionation reaction using the plane-
tary ball mill apparatus
Disproportionation was found to occur in excellent yields
for several aromatic aldehydes (Table 3). Nonetheless, as the
reaction is carried out in highly basic media, the scope is
limited to substrates that do not bear any base-sensitive func-
tionalities. A variety of other biomass derived furanecarboxal-
dehydes and their derivatives (entries 1–3) gave quantitative
yields for this disproportionation. We also evaluated the possi-
bility of employing benzaldehydes as substrates with the opti-
mized conditions, and found that these also exhibited excel-
lent results, with quantitative yields for arenes bearing
different functionalities. This reaction represents a great
advantage when compared to the classical Cannizzaro
approach in both time and reagents. For in-solution
Entry
HMF scale
%HMFA
%DHMF
1
2
3
4
5
0.200 g
0.400 g
0.800 g
3.200 g
12.80 g
>99
>99
>99
96
>99
>99
>99
96
92
92
It is remarkable to say that the optimized reaction is both Cannizzaro disproportionation, reported reaction times vary
4
2
efficient in time and in its green chemistry indicators, with from a few hours to days, but with the solvent-free mechano-
2
9
an Efactor of 0.55. Previous reports describe a methodology chemical conditions reported herein, this time is reduced to
with an Efactor of approximately 3.6, considering a 90% of re- only 5 minutes or less.
use of the solvent, and 34 when no-solvent is recycled. This
new solvent-free approach pushes the limits of this chemical maximum of only 50% of the starting material transformed
transformation in both simplicity and green efficiency.
into a primary alcohol and 50% to a carboxylic acid, which
Cannizzaro disproportionation leads to a theoretical
Initially this method was developed towards biomass- limits the quantity of the desired material produced. To miti-
derived 5-hydroxymethylfurfural, however efforts were under- gate this outcome, some groups have studied the use of sacrifi-
4
3,44
taken to evaluate the optimized conditions with other sub- cial agents in a cross-Cannizzaro reaction.
For this, a stoi-
strates for Cannizzaro disproportionation reactions (Table 3).
chiometric amount of a sacrificial molecule is employed
within the reaction that can be fully reduced or oxidized, with
the objective of transforming the starting material to the
corresponding fully oxidized or reduced moiety, respectively.
Towards this end, we evaluated several sacrificial agents in
order to control the production of one of the two possible
Cannizzaro products for this reaction.
Table 3 Scope of different aldehydes with the optimized disproportio-
nation reaction conditions
Several sacrificial reagents were employed for the cross-
Cannizzaro reaction of HMF, including several readily available
aldehydes (Table S1†). Benzaldehyde, acetaldehyde and
D-glucose did not enhance the selectivity of the desired pro-
ducts. Anisaldehyde gave a small selectivity (1.2 : 1) favouring
the synthesis of DHMF, but when paraformaldehyde was
employed in slight excess, the reaction was specific towards
the synthesis of DHMF, affording 90% yield. The oxidation of
HMF to HMFA definitely represents a bigger challenge syn-
thetically, since the presence of the primary alcohol creates a
wider range of possible oxidation products. Based on the
reported mechanism for the cross-Cannizzaro reaction, it is
necessary to have first a nucleophilic addition of the hydroxide
anion into the aldehyde moiety of HMF, to produce a tetra-
hedral intermediate that collapses through a hydride transfer
Entry
1
Substrate
% Acid
>99
% Alcohol
>99
2
3
4
5
>99
>99
98
>99
>99
98
>99
>99
6
90
91
7
8
9
98
95
95
92
98
94
95
92
1
0
Fig. 3 Preliminary results of the selective solvent-free mechanochem-
ical cross Cannizzaro reaction of HMF employing sacrificial reagents.
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to the sacrificial agent, producing a carboxylic acid group. For was then filtered through a short Celite pad. Once the solvent
this reason, we decided to employ p-quinones as our sacrificial is evaporated under vacuum, the solid/oil mixture is washed
reagents as these are known to be readily available, excellent three times with EtOAc. After evaporating the solvent of the
4
5
hydride acceptors. After evaluating several p-quinones, a 7 : 3 combined EtOAc washes, a pale yellow oil is obtained (DHMF).
selectivity towards the oxidation of HMF was obtained, albeit For the solid that did not solubilize with the EtOAc washes,
in relatively low yields (Fig. 3). These preliminary results indi- recrystallization in EtOH : EtOAc (2 : 98) was performed.
cate that the solvent-free complete conversion of HMF selec- Additionally this salt can be converted to free acid after an
tively to HMFA is possible and further studies toward this aim acid–base extraction. For a detailed description of the pro-
are currently underway.
cedure please refer to the ESI†.
Conclusions
Conflicts of interest
A new solvent-free, facile protocol was developed for the simul- The authors declare no conflicts of interest.
taneous synthesis of 5-hydroxymethylfuroic acid and 2,5-
dihydroxymethylfuran through the Cannizzaro disproportiona-
tion under mechanochemical assistance with a planetary ball
milling apparatus of biomass-derived 5-hydroxymethylfurfural,
Acknowledgements
with an Efactor of 0.55, (7 times smaller than that in previous This work was funded by the Natural Sciences and
reports), and a reaction time of 5 min. The optimized con- Engineering Research Council (NSERC) and Le Fonds de
ditions proved adaptable to several aromatic aldehydes, includ- Recherche du Québec, Nature et Technologies (FRQNT).
ing other biomass derivatives of HMF, affording excellent Support was also kindly provided by the Centre for Green
yields. Also, initial results towards the selective oxidation or Chemistry and Catalysis (CGCC), Le Réseau Québécois de
reduction of HMF via a cross-Cannizzaro reaction under Recherche sur les Médicaments (RQRM) and Concordia
solvent-free conditions are presented, with promising prelimi- University. Special thanks to Jiang Tian Liu and Fadil Taç for
nary results that will be expanded in future work.
their valuable advice.
It is of tremendous importance to develop reactions that
allow for the efficient transformation of biomass-derived
materials to useful synthetic intermediates. This work high-
lights the importance of not only the employment of renew-
able sources, but also synthetic targets that use greener reac-
tion conditions that minimize waste and use of solvents,
especially when these reactions are expected to occur at indus-
trial scales in the future.
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