Microwave-enhanced aqueous biphasic dehydration of carbohydrates to 5-hydroxymethylfurfural

Article abstract of DOI:10.1039/c5ra25564c

We describe herein an efficient microwave-assisted aqueous biphasic dehydration of carbohydrates to 5-hydroxymethylfurfural (HMF). The effects of several alkali metal salts in aqueous phase, organic solvents as an extractive phase and Lewis acids are evaluated on the reaction. Specifically, starting from fructose, the use of bromide salts in aqueous phase and the common organic solvent MeCN or lignocellulose-derived γ-valerolactone (GVL) as organic extractors are highly beneficial, leading to excellent HMF yields of up to 91% with HCl as a Br?nsted acid catalyst. In conjunction with an isomerization catalyst, the method was applicable to glucose as well as various disaccharides and cellulose, affording HMF in notably good yields, particularly with GVL as an extractor and reusable Amberlyst-38(wet) as an acid catalyst. The exceptionally high HMF yields obtained in aqueous solutions is attributed to the combined effect of the biphasic reaction system and the application of microwaves, which ensures short reaction times and minimized by-product formation thereof.

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Microwave-Enhanced Aqueous Biphasic Dehydration of
Carbohydrates to 5-Hydroxymethylfurfural
Received 00th January 20xx,
Accepted 00th January 20xx
P. Wrigstedt, J. Keskiväli and T. Repo *
We describe herein an efficient microwave-assisted aqueous biphasic dehydration of carbohydrates to 5-
hydroxymethylfurfural (HMF). The effects of several alkali metal salts in aqueous phase, organic solvents as extractive
phase and Lewis acids are evaluated on the reaction. Specifically, starting from fructose, the use of bromide salts in
aqueous phase and common organic solvent MeCN or lignocellulose-derived γ-valerolactone (GVL) as organic extractors
are highly beneficial, leading to excellent HMF yields of up to 91% with HCl as Brønsted acid catalyst. In conjunction with
an isomerization catalyst, the method was applicable to glucose as well as various disaccharides and cellulose, affording
HMF in notably good yields, particularly with GVL as an extractor and reusable Amberlyst-38(wet) as an acid catalyst. The
exceptionally high HMF yields obtained in aqueous solutions is attributed to the combined effect of the biphasic reaction
system and the application of microwaves, which ensures short reaction times and minimized by-products formation
thereof.
DOI: 10.1039/x0xx00000x
www.rsc.org/
reaction systems, such as water-MIBK,[13] and water-(MIBK+2-
BuOH)[14] systems, resulted in fair HMF yields of 69% and 60%,
respectively. Systems with additional modifiers in aqueous
phase, such as DMSO,[15] NMP[16] or PVP[15] resulted in very
good HMF yields of up to 83%. However, contamination of the
organic phase by the modifier can lead to complex separation
of solvent and product at the end of the process.
Introduction
Over the last decade the dehydration of carbohydrates to 5-
hydroxymethylfurfural (HMF) has attracted increasing
attention for the sustainable production of chemicals (Scheme
1).[1] For instance, HMF can be oxidized to 2,5-
furandicarboxylic acid as
a potential replacement for
Recently, the presence of alkali metal salts, such as NaCl and
KBr, has been reported to improve the HMF yields in glucose
dehydration in organic solvents[5] and aqueous biphasic
systems[17]. This was ascribed to the Cl- and Br- anions
influencing the reaction by enhancing the fructose dehydration
step (the reaction proceeds through fructose intermediate).[5]
Also, in aqueous biphasic systems the addition of an excess of
salt is beneficial in increasing the HMF distribution to organic
phase during the reaction (salting-out effect), and enabling the
use of water-miscible solvents as the organic phase, such as
THF and MeCN, which are expected to dissolve HMF better
than common water-immiscible solvents. Exploiting this
strategy with fructose, Hansen and co-workers reported an
increase in HMF yield from 28% to 45% by the addition of NaCl
into the H3BO3(aq)-MIBK biphasic system.[18] Cao et al.
described the use of NaHSO4(aq)-THF biphasic solvent system
with tetraethyl ammonium salts, obtaining HMF yield of
81%.[19] Recently, high HMF yield of 88% was reported for (IL-
HSO4)aq-MeCN system with acidic ionic liquid (IL) as excess
salt.[20]
terephthalic acid in the production of polyesters,[2] or
converted to high energy density biofuel dimethylfuran.[3]
Dehydration of fructose to HMF using both homogeneous
and heterogeneous catalytic systems has been investigated
extensively.[4] Moderate to excellent yields of HMF have been
achieved using mineral acids,[5] ion exchange resins,[6] oxides[7]
and zeolites[8] as catalysts in monophasic ionic liquids,[9] high-
boiling organic solvents (e.g. dimethylacetamide[5] and
DMSO[10]) and their mixtures.[11] However, the high cost of the
solvents, and high downstream separation costs limits their
economic feasibility. In this respect, aqueous processes are
favored yet unfortunately inefficient (HMF yields < 50%)
because side reactions, such as polymer formation and HMF
rehydration into levulinic acid and formic acid, are promoted
in water (Scheme 1).[12] Consequently, the challenge is to make
aqueous processes more efficient, that is, to increase the HMF
selectivity by reducing the formation of by-products during the
reaction. The development of various water-organic biphasic
In general, aqueous acid-catalyzed dehydration reaction is
fairly slow process and high temperature is commonly
required for high product yield. In contrast to conventional
heating, microwave irradiation generates high input of energy,
thus rapidly overcoming the energy barrier necessary for
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product formation. In many occasions, microwave processing biomass-derived γ-valerolactone (GVL), the latter of which has
has been shown to dramatically reduce reaction times and to been extensively studied as a renewable solvent for biomass
increase product yields and purities compared to conversion,[26] in place of traditionally used MIBK/2-BuOH,
conventionally heated experiments.[21] In this respect, the THF, DMF or alcoholic solvents, such as 2-BuOH and i-PrOH, as
implementation of microwaves appears to be a method of an organic phase resulted in faster fructose conversion rate
choice for accelerating the fructose dehydration reaction. To and better HMF selectivity and yields. The high HMF yield of
this date, only few reports[4] describe the microwave-assisted 85% and 84% obtained with KBr/MeCN and KBr/GVL systems
synthesis of HMF from fructose or glucose employing aqueous are comparable to those of obtained in ionic liquids and high-
mono[22] or biphasic[22c, 23] conditions.
boiling organic solvents,[4] and considerably better than
22b]
Herein, we report high-yield transformation of carbohydrates obtained in aqueous
monophasic solutions.[22a,
to HMF applying the combination of microwaves and biphasic Importantly, the use of those solvents as extractors prevented
reaction systems.
the formation of insoluble humins and the most common by-
products levulinic acid and formic acid due to HMF
rehydration (HPLC), ascribed to short reaction time and mild
conditions. Also, we did not observe the presence of
acetamide or acetic acid (HPLC) caused by an acid-catalyzed
acetonitrile hydrolysis. It is noteworthy that after the reaction
the aqueous and organic phases were fully separated,
consequently allowing an easy separation of HMF. For
example, the low boiling point of MeCN could be
advantageous in the distillation process described by Dumesic
et al. with 2-BuOH-MiBK as an extraction solvent.[15] The
addition
of
aldose-to-ketose
isomerization
catalyst
(CrCl3×6H2O) decreased HMF yields from 85% to 79% (Entry
15). Hence, the use of isomerization catalysts, such as AlIII, CrIII
and LaIII halides, in the fructose dehydration is not beneficial
because the metal cations converts fructose to glucose or
mannose (equilibrium), which are significantly more difficult to
dehydrate to HMF.[4a]
Scheme 1. Fructose conversion to HMF and its transformation to valuable
products.
Results and Discussion
The role of alkali metal salts in the fructose dehydration to
HMF is well-established in organic solvents, in which bromide
Table 1. The influence of alkali metal salts and organic solvents in the microwave-
assisted aqueous biphasic fructose dehydration to HMF.[a]
anions (NaBr or KBr) in place of chlorides (NaCl or KCl) enhance
the reaction resulting in higher HMF yields.[5,
24]
This was
Entry
1[c]
2
Salt [b]
KBr
NaBr
KBr
NaCl
KCl
Organic phase
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
GVL[d]
Conversion (%)
Yield (%)
<1
82
85
77
78
68
67
-
ascribed to bromide anions promoting 1,2-enol formation
from fructofuranosyl oxocarbenium ion, generated by
Brønsted acid-catalyzed dehydration of C2 in fructose, more
efficiently than the corresponding chlorides.[5] However, in
aqueous mono or biphasic media the results of the impact of
salts are not consistent.[4, 17] For example, chlorides performed
better in the fructose dehydration to HMF using (Boric
acid+salt)aq-MIBK[18] or HClaq-nBuOH biphasic system,[25]
whereas better HMF yields were reported with bromides in
(CrCl3×6H2O+salt)aq-(acetone+toluene) system.[17] Therefore,
we initiated the studies by investigating the effect of different
sodium and potassium salts in an aqueous phase and
microwave-compatible organic solvents as an extractive phase
on the fructose conversion to HMF at 160 °C in the presence of
0.1 M HCl catalyst (Table 1).
1
>99
>99
98
3
4
5
97
6
NaI
KI
94
7
96
8
KF
99
9
KBr
NaCl
KBr
NaCl
KBr
KBr
KBr
KBr
KBr
>99
96
84
79
76
68
6
10
11
12
13
14
15
16
17[f]
GVL
THF
95
THF
83
DMF
11
n.d.[e]
i-PrOH
2-BuOH
MIBK/2-BuOH
MeCN
73
61
74
79
79
98
In comparison to NaCl and KCl, the reactions with NaBr and
KBr clearly resulted in faster fructose conversion and 6-8%
higher HMF yields, regardless of the extractive solvent. The
use of NaI and KI reduced the HMF yields further and no
reaction occurred with the corresponding fluorides. The
positive effect of halide ions on HMF yields decreased in the
order Br > Cl > I ≠ F, which is in agreement with previous
results using organic solvents or comparable biphasic system
under conventional heating.[5, 17] Notably, the use of MeCN or
96
[a] Reaction conditions: ~10 wt% fructose in (0.1 M HCl-salt)(aq)-solvent 1:2
v/v, MW 160 °C, 1 min.; [b] saturated solution; [c] without HCl; [d] GVL=γ-
valerolactone; [e] Fructose and i-PrOH peak overlapped (HPLC); [f] with 5
mol% CrCl3×6H2O.
We next explored the impact of HCl concentration (0.025 M,
0.05
M
and 0.1 M) on the reaction outcome using
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(HCl+KBr)(aq)-MeCN system at 160 °C, shown in Figure 1. It product yields. It is worth adding that the short reaction time
should be noted that with MW instrument (Biotage Initiator) and high yield experienced in the single phasic dehydration of
the heating from r.t. to 160 °C took 80 sec, after which the fructose to HMF makes the process applicable for continuous
reaction time was measured. For example, the total heating flow manufacturing where short residence times are essential
time for 1 and 60 sec reactions were therefore 81 and 140 sec, to achieve
respectively (see Figure S1 and S2 in Supporting Info for MW continuous flow microwave process, recently described by
heating profiles). Morschhäuser et al., which operates under high-
The initial fructose conversion rate was surprisingly fast, temperature/high-pressure conditions with throughput of
a
high throughput.[27] Particularly, industrial
[28]
accelerating with increasing acid concentration, and high 82%, 20L/h, could be ideal for this type of reaction.
Obviously,
96% and 98% conversions were recorded in only 1 second the throughput of the system can be readily increased by
reaction time at 160 °C. Full fructose conversions were parallel reactors.
reached with 0.025 M HCl in 75 seconds, with 0.05 M HCl in 30
In view of the ample reports describing the reaction with
seconds and with 0.1 M HCl in 15 seconds. The maximum HMF different acids,[4] we further attempted to improve the HMF
yields were linked to HCl concentration, exhibiting a tradeoff yields by assessing the effect of different homogenous (H2SO4,
between accelerating the formation rate of HMF and HCl, HNO3, H3PO4, TFA and ammonium salts) and
increasing formation rate of the by-products (Figure 1). Albeit heterogeneous (Dowex-50 and Amberlyst-38) acid catalysts on
the formation rate of HMF was accelerated with 0.1M HCl in the reaction. The experiments were performed in
respect to 0.05M HCl, the concurrent increase in the by- (acid+KBr)(aq)-MeCN system at 160 °C for 1 minute reaction
product formation rate led to lower HMF yields. time (Figure 2). The acid concentration was set to 0.05 M
Correspondingly, the deceleration in the HMF formation rate except with Amberlyst-38 and Dowex-50, the amounts of
with 0.025M HCl increased the reaction time and thus, in which were optimized in separate experiments (see Table S4 in
comparison to the reaction in 0.05M HCl, exposed the formed Supporting Info).
HMF to by-product formation resulting in lower yields. The
decomposition rate of HMF was markedly fast with 0.1 M HCl,
HMF yield decreasing from 88% to 83% in 60 second time
interval (see Table S2 in Supporting info). After 300 seconds
the HMF yield decreased to 76%, demonstrating that the acid-
promoted undesired products formation was indeed very rapid
under MW conditions. In the case of 0.05M HCl the presence
of intermediate dehydration products was evident as the
maximum HMF yield was recorded approximately 30 seconds
after the full conversion of fructose. However, we were not
able to identify these intermediates by HPLC analysis.
Figure 2. The effect of various acids on HMF yields (conditions: ~10 wt% fructose in
(0.05 M acid+KBr)(aq)-MeCN 1:2 v/v, MW 160 °C, 1 min, except with ammonium halides
2 min). (a) GVL used as an organic phase (b) PBS=phosphate buffer pH 2.1 using
(PBS+KBr)(aq)-MeCN and (c) (PBS+KBr)(aq)-MIBK-2-BuOH.
From Figure 2, HCl was the most efficient acid, affording HMF
in 91% yield with >99% fructose conversion. However, almost
comparable HMF yields of 85%, 87%, 86% and 88% were
recorded with H2SO4, HNO3, TFA and Amberlyst-38 catalysts,
respectively. The effect of the homogeneous Brønsted acids on
HMF yields decreased in order HCl > HNO3 ≥ TFA ≥ H2SO4 >>
Figure 1. The effect of HCl concentration on fructose conversion and HMF yields in the
H3PO4. To our surprise, by replacing KBr with weakly acidic
fructose dehydration to HMF (reaction conditions: ~10 wt% fructose in (0.025-0.1 M
ammonium halides (NH4Cl, NH4Br and NH4I, saturated
HCl+KBr)(aq)-MeCN 1:2, MW 160 °C, 1 to 90 sec).
solution), the reaction gave relatively high HMF yields of up to
81% (with NH4Br) and without additional strong Brønsted
By conducting the reaction in a single-phase manner, using
acids. The solid heterogeneous acids, Dowex-50WX4 and
catalytic amount of KBr in place of saturated solution in a 0.1M
Amberlyst-38(wet), readily dehydrated fructose furnishing
HCl-MeCN (1:4 v/v) system for 1 min at 160 °C, afforded HMF
HMF in very good 83% and 88% yields, respectively. The
in surprisingly good 82% yield (see Table S1 in Supporting
application of phosphate buffer solution (PBS, pH 2.1) as a
info). Without KBr only 30% HMF yield was recorded, showing
reactive phase resulted in low HMF selectivity and yields,
that the presence of bromide anions was crucial for good
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contrary to an earlier report employing PBS/MIBK-2-BuOH microwave heating become more energy efficient as the scale
biphasic system,[22c] wherein very high HMF yield of 88% were increases, partly due to efficient transfer of microwave energy
reported under microwave conditions.
to a larger reaction mass.[32] Therefore, we performed scale-up
The main advantage in the microwave-assisted synthesis is experiments using higher initial fructose concentrations from
an increase in reaction rate,[29] reducing exposure time of the 10 to 50 wt%. As Figure 4 illustrates, the fructose conversion
product to decomposition and increasing space-time-yield, was very high (>98%) in all experiments. In accordance with
which is an important feature in potential industrial the previous reports the best HMF yield of 90% was obtained
applications. To assess the extent of the effect of MW with the lowest fructose concentration.[22a, 22b] Small decrease
irradiation on the reaction, we conducted experiments under in HMF yield and selectivity was then observed with increasing
conventional oil-bath heating at 160 °C applying biphasic fructose concentration gradually by 10 wt%, and the lowest
(HCl+KBr)(aq)-MeCN system (Figure 3).
HMF yield of 77% was obtained with the highest fructose
concentration of 50 wt%. The HMF yield of 84% obtained with
fructose concentration of 30 wt% is noticeably better than
reported earlier for aqueous mono[22a] or biphasic systems.[22c,
25]
Figure 3. Fructose dehydration to HMF under conventional oil-bath heating (conditions:
~10 wt% fructose (0.05 M HCl+KBr)(aq)-MeCN 1:2 v/v, 160 °C, 10-40 min).
In comparison to MW irradiation, the conversion rate of
fructose was considerably slower, agreeing with the previous
report on fructose dehydration to HMF.[30] After 10 min of the
reaction the fructose conversion was only 62% with an HMF
yield of 38%, which then gradually increased to 94% and 79%
at 40 min, respectively. Likewise with MW irradiation, the
presence of unidentified intermediates was obvious as the
HMF selectivity increased with increasing reaction time from
64% (10 min) to 85% (30 min). Thereafter the selectivity
decreased due to the governing formation rate of side-
products such as humins. Similarly to the reactions conducted
under MW heating, the yield of levulinic acid was negligible
(<1%) in all experiments and, as a result, can be attributed to
the biphasic system (MeCN). In contrast to microwave heated
experiments, the presence of visible insoluble humins, the
amount of which increased with time, were observed after the
reaction. According to the results above, we may deduce that
in comparison to conventional heating, a short-term reaction
under MW irradiation is more efficient in promoting the
dehydration of fructose to HMF by greatly reducing the
reaction time, and consequently, the formation of by-products
such as soluble and insoluble humins resulting in higher HMF
selectivity and yield.
Figure 4. Results of fructose dehydration to HMF with increasing fructose
concentration (conditions: 10 to 50 wt% fructose (9 mol-% HCl+KBr)(aq)-MeCN 1:2 v/v,
MW 160 °C, 1 min).
The use of glucose-to-fructose isomerization catalyst
enables a one-pot tandem isomerization-dehydration process
to produce HMF directly from glucose and glucose-containing
carbohydrates, as depicted in Scheme 2.[33] High HMF yields of
up to 63 % from glucose have been reported for aqueous
systems involving various catalyst such as LaIII, CrIII and AlIII
halides, boric acid and borates.[4] In view of this, we tested the
efficiency of our system, described above, in the dehydration
of glucose to HMF. Accordingly, an isomerization catalysts
34]
35]
(Boric acid,[18,
sodium borate,[22c] CrCl3×6H2O[17,
or
[36]
AlCl3×6H2O
) was added to the (acid+KBr)(aq)-GVL or
(acid+KBr)(aq-MeCN system applying Amberlyst-38 (wet) or HCl
as acid catalysts (Table 2).
In the dehydration of fructose to HMF one of the major
challenges is the acid-catalyzed by-product formation, which
can be reduced by using dilute solutions.[22a] However, from
the industrial and economical viewpoints, higher initial
fructose concentrations are desirable due to the small reactor
volumes, and more efficient separation and purification
Scheme 2 Cascade glucose transformation to HMF trough fructose.
In contrast to fructose dehydration, we found that
Amberlyst-38(wet) as an acid catalyst performed equally or
slightly better than 0.05 M HCl in the reaction. Also, MeCN was
found to be less suitable solvent than GVL as an organic
steps.[31]
Moreover, several reports have shown that
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extractive phase (constantly 1-4% better yields using GVL, See 140 °C by significantly decelerating glucose-to-fructose
35a]
This was ascribed to the restrained
Table 2 and Table S5 in Supporting Info). The use of THF as an isomerization.[17,
organic phase led to decreased HMF yield compared to those formation of the chromium–glucose chelate complex with
of MeCN and GVL (Entry 12).
increasing acidity, leading to the change in the rate-
determining step from fructose dehydration to glucose-to-
fructose isomerization.[17] The strong retardation of the
glucose-to-fructose isomerization, arising from the presence of
Brønsted acid, resulted in lower substrate conversions, HMF
selectivity and yield. According to our results, this tendency
can be avoided by conducting the reaction rapidly at high
temperature under MW irradiation.
Table 2. Results of glucose dehydration to HMF with various isomerization
catalysts in (Amberlyst-38+KBr)aq-GVL biphasic system .[a]
Entry
Time
Isomerization
Catalyst
Glucose
HMF Yield
(min)
Conversion (%)
(%)
10
-
1
2[b]
3
3
3
3
1
2
3
4
3
3
3
3
3
3
Boric acid
30
1
Boric acid
We also studied the (Amberlyst-38+KBr)(aq)-GVL catalytic
system for the dehydration of mannose, various disaccharides
(lactose, cellobiose and sucrose) and polysaccharides (inulin
and cellulose) with or without CrCl3×6H2O additive, depending
on the carbohydrate constituent (Table 3).
Sodium borate
CrCl3×6H2O
CrCl3×6H2O
CrCl3×6H2O
CrCl3×6H2O
AlCl3×6H2O
AlCl3×6H2O
CrCl3×6H2O
CrCl3×6H2O
CrCl3×6H2O
CrCl3×6H2O
61
87
93
98
99
82
93
98
97
98
92
-
4
59
70
74
73
40
66
71
65
70
54
5
6
7
8
9[c]
10[d]
11[b]
12[e]
13[f]
Table 3. The results of dehydration of various carbohydrates with Amberlyst-38
(wet) catalysts in KBraq-GVL biphasic system.[a]
Entry
1
Carbohydrate
Mannose + CrCl3×6H2O
Lactose + CrCl3×6H2O
Cellobiose + CrCl3×6H2O
Cellobiose + CrCl3×6H2O
Sucrose + CrCl3×6H2O
Sucrose
Time (min)
HMF Yield (%)
3
3
3
3
3
3
1
3
69
55
71
67
77
49
80
40
2
[a] Reaction conditions: 10 mol% metal halide catalyst, 20 mol-% boric
acid or borate, 21 mg Amberlyst-38 (wet) ~10 wt% glucose in KBr(aq)-GVL
1:2 v/v, MW 160°C, 1-4 min. [b] without Amberlyst-38(wet). [c] 30 mol-%
AlCl3×6H2O. [d] 0.05 M HCl as catalyst. [e] MeCN as an organic phase. [f]
THF as an organic phase.
3
4[b]
5
6[c]
7
Inulin
8[d]
MC Cellulose + CrCl3×6H2O
Boric acid and sodium borate (Borax) were reported as
efficient catalysts in glucose-to-fructose isomerization in ionic
[34]
[a] Reaction conditions: 10 mol% CrCl3×6H2O, 21mg Ambelyst-38(wet) and 150
mg of carbohydrate in KBr(aq)-GVL 1:2 v/v, MW 160°C, 1-3 min. [b] MeCN as
organic phase. [c] 38% glucose remaining after the reaction [d] T=175 oC.
liquid
and biphasic aqueous phosphate buffer-(MIBK+2-
[22c]
BuOH) system,
affording HMF yields of 41% and 63%,
respectively. However, when applied to our system these
catalysts were inefficient. The use of boric acid gave HMF in a
low 10% yield with poor selectivity after 3 minutes (Entry 1). In
the absence of strong Brønsted acid only 1% glucose
conversion occurred (Entry 2). Surprisingly, with sodium borate
as catalyst no HMF was formed albeit 61% glucose conversion
was observed after the reaction (Entry 3). Of the isomerization
catalysts investigated in this study, CrCl3×6H2O was the most
efficient under MW irradiation conditions and, in agreement
with previous reports, performed better than AlCl3×6H2O
(Entries 6, 8-9).[17, 35b] Thus, the best HMF yield of 74% with
HMF yields with disaccharides were only slightly lower than
those of glucose under the same reaction conditions, showing
that no additional strong Brønsted acid along with Amberlyst-
38(wet) was necessary to promote the hydrolysis of the
glycosidic linkage of disaccharides. The system worked notably
well with cellobiose and inulin leading to good HMF yields of
71% and 80%, respectively. Additionally, the reaction with
sucrose together with CrCl3×6H2O gave HMF in 77% yield. As
expected, the absence of an isomerization catalyst reduced the
HMF yield to 49%. With cellulose as a substrate an elevated
temperature of 175 °C was necessary for efficient
depolymerization to obtain reasonable HMF yield of 40%.
glucose
conversion
of
98%
was
obtained
in
(CrCl3×6H2O+Amberlyst-38+KBr)(aq)-GVL system in 3 minutes
that is, up to now, the best HMF yield obtained from glucose in
aqueous systems.[4] As with fructose, levulinic acid was
detected only in trace amounts (<1%), which is remarkably low
if compared to biphasic systems with similar glucose
Conclusions
conversions under conventional heating, wherein 5-10% of
levulinic acid is typically produced.[17,
35a]
We have studied several aqueous biphasic systems to
efficiently promote the fructose dehydration to HMF under
MW irradiation. In comparison to conventional heating, a
short-term reaction implementing microwaves was more
efficient by greatly reducing the reaction time and
consequently, the formation of by-products, especially
levulinic acid, leading to higher HMF selectivity and yield.
Particularly, the use of bromide salts in aqueous phase and
Notably, without
strong Brønsted acid catalyst (0.05 M HCl or Amberlyst-38)
lower HMF yield of 65% from glucose with CrCl3×6H2O was
obtained (the dehydration step proceeds because of the
intrinsic Brønsted acidity of CrCl3×6H2O in aqueous solutions,
entry 10 vs 11). Recently, it was reported that additional
strong mineral acids affect the CrCl3×6H2O catalyzed glucose
dehydration to HMF under conventional oil-bath heating at
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common organic solvent MeCN or lignocellulose-derived GVL
To a 2-5 ml microwave vial with a magnetic stirring bar containing
as an organic extractive phase were highly advantageous fructose (0.15g, 0.83 mmol) was added 1.5 mL of aqueous saturated salt
resulting in excellent HMF yields of up to 91% with catalytic solution (NaCl, NaBr, KCl, KBr, NaI, KI, KF, NH4Cl, NH4Br or NH4I containing
amount of HCl (9 mol-%) as acid catalyst. Only small decrease the required amount of acid). After dissolution of fructose, desired organic
in HMF yield occurred when Amberlyst-38(wet) catalyst was solvent (3 mL) was added, the vial was closed with aluminum/silicone crimp
applied in the system. Also, the reaction was scalable up to cap and the biphasic solution was heated at 160 °C in the microwave reactor
fructose concentration of 50 wt% with only small decrease in (Biotage Initiator) or in preheated the oil-bath (160 °C) if used. After
HMF selectivity.
required time, the vial was immediately cooled down to room temperature
In contrast to fructose dehydration, the biphasic system with and water added to make a total volume of 50 mL. HMF yield and fructose
added isomerization catalyst performed better with glucose conversion were determined from this solution by HPLC analysis (1:4
when GVL and Amberlyst-38(wet) were used in place of MeCN dilution with water, 1mL).
and HCl, resulting in very good HMF yield of 74%. The high
All MW reactions were performed using synthesis platform (Chemspeed
HMF yield from glucose was ascribed to microwave heating,
SLT106 Swing Synthesizer) equipped with microwave reactor (Biotage
which promoted the Lewis acid-catalyzed glucose dehydration
Initiator).
by overcoming the rate-determining glucose-to-fructose
equilibrium barrier, arising from the presence of additional
Glucose dehydration in biphasic KBr(aq)-GVL/MeCN/THF system
Brønsted acid to enhance the fructose dehydration step.
with Isomerization and, Amberlyst-38 (wet) or HCl catalyst
Additionally, this method proved efficient in one-pot cascade
hydrolysis-isomerization-dehydration process to produce HMF
To a 2-5 ml microwave vial with a magnetic stirring bar containing glucose
from disaccharides without additional strong Brønsted acids, (0.15g, 0.83 mmol), 21 mg Amberlyst-38(wet) and 10 mol% of required
and could be applied to more complex carbohydrates such as isomerization catalyst (CrCl3×6H2O, AlCl3×6H2O, boric acid or sodium borate)
cellulose. In terms of HMF yields the reported results are, to were added 1.5 mL of aqueous saturated KBr solution. After dissolution of
our knowledge, the best fructose and glucose dehydration glucose, GVL, THF or MeCN (3 mL) was added, the vial was closed with
results achieved in mono or biphasic aqueous media, and aluminum/silicone crimp cap and the biphasic solution was heated at 160 °C
comparable to the best of those obtained in high-boiling in the microwave reactor (Biotage Initiator). After required time (1-4 min),
organic solvents and ionic liquids.[4]
the vial was immediately cooled down to room temperature and water
added to make a total volume of 50 mL. HMF yield and glucose conversion
were determined from this solution by HPLC analysis (1:4 dilution with
water, 1mL). All reactions were performed using synthesis platform
(Chemspeed SLT106 Swing Synthesizer) equipped with microwave reactor
(Biotage Initiator).
Experimental
General Experimental Details
All solvents, carbohydrates, CrCl3×6H2O, AlCl3×6H2O, boric acid and sodium
borate were purchased from Acros Organics or Sigma-Aldrich and were used
as received, except THF which was dried by VAC solvent purification system
(Vacuum Atmosphere Systems).
Dehydration of disaccharides and polysaccharides in biphasic
(Amberlyst-38-KBr)(aq)-GVL system
To a 2-5 ml microwave vial with magnetic stirring bar containing the
desired carbohydrate (0.15 g), 21 mg Amberlyst-38(wet) and 10 mol% of
CrCl3×6H2) were added 1.5 mL of aqueous saturated KBr solution. Then GVL
was added, the vial closed with aluminum/silicone crimp cap and heated at
160 °C in the microwave reactor (Biotage Initiator). After required time (1-3
min), the vial was immediately cooled down to room temperature and water
added to make a total volume of 50 mL. HMF yield and glucose conversion
were determined from this solution by HPLC analysis (1:4 dilution with
water, 1mL).
HMF, glucose and fructose yields were determined with High Pressure
Liquid Chromatography (HPLC). HPLC runs were performed using Agilent
1200 HPLC system equipped with a Phenomenex Rezex ROA (300 x 7.8 mm)
column. Sulfuric acid (0.25 mM) in water was used as an eluent at 40 °C with
a flow rate 0.35 ml/min. HMF was detected using UV-detector, whereas
fructose and glucose were analyzed using refractive index (RID) detector.
The exact yields were calculated from calibration curves prepared for all the
compounds from commercially available reagents using six different
concentrations.
Acknowledgements
All the reactions were carried out in 2-5 ml glass vials using a Biotage
Initiator microwave reactor (2.45 GHz magnetron). The instrument uses one
IR sensor to measure temperature of the reaction mixture and adjusts the
heating power accordingly. The absorption level was set to “very high” and
the reaction mixture was stirred with magnetic stirring at 600 rpm. In all
reactions the heating from r.t. to 160 °C took 80 sec, after which the desired
reaction time was measured.
Funding from Magnus Ehrnrooth Foundation and TEKES (the
Finnish Funding Agency for Technology and Innovation) is
gratefully acknowledged.
Notes and references
General procedure for the fructose dehydration experiments in
salt(aq)/organic solvent biphasic systems
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