FULL PAPER

DOI: 10.1002/ejoc.201001539

Synthesis of 5-Bromomethylfurfural from Cellulose as a Potential Intermediate

for Biofuel

Nitee Kumari,[a] Jens Kruse Olesen,[a] Christian M. Pedersen,[a] and Mikael Bols*[a]

Keywords: Biofuels / Oxygen heterocycles / Sustainable chemistry / Reaction mechanisms / Kinetics

Cellulose can be converted into 5-bromomethylfurfural was also obtained in high yields. The mechanism of BMF
(BMF), a brand new biofuel or biofuel intermediate, in 80 % formation was investigated, and the results indicate that this
yield by treatment with HBr and LiBr and continuous extrac- furfural is formed during the depolymerization of cellulose
tion with toluene. From other carbohydrates and straw, BMF and that glucose is not an intermediate.

Introduction of obtaining a biofuel from cellulose. Inspired by this work

and Zhang’s report that Cr ions could improve furfural for-
With the worrying growth in global CO2 levels and the
mation,[6] we wondered if the formation of 1 could be im-
potential climate changes that may be the result of this de-
proved by addition of CrCl2. However, the information that
velopment, it is increasingly clear to most people that mod-
bromide is a poorer ligand for Cr than chloride led us to
ern society’s dependence on fossil fuels is a problem that
investigate the reaction of carbohydrates with HBr. In this
has to be solved. While solar, wind, and nuclear power may
paper we report the results of these investigation and show
be relied upon to provide much of the future energy supply,
that HBr is an excellent reagent for the conversion of bio-
they will not be practical for transportation fuels. Combus-
mass carbohydrates into 5-bromomethylfurfural (3, Fig-
tible, liquid organic compounds are much more practical,
ure 1). Compound 3 is formed in higher yield than 1 and
but these will unavoidably lead to CO2 emission. The solu-
can be converted into 2 or dimethylfuran allowing HBr to
tion to this problem may be to obtain these fuels from car-
be recycled.
bon sources already present in the biosphere, so-called bio-
fuels, thereby avoiding increasing the amount of carbon and
CO2 in circulation. Ethanol obtained by fermentation is the
biofuel that has received most attention, but there are alter-
natives that indeed may prove to be better solutions. Etha-
nol as a fuel has the drawbacks of corrosiveness, a compar-
atively low energy content, and a costly and low-yielding Figure 1. 5-Ethoxymethylfurfural, 5-chloromethylfurfural, and 5-
production method (when produced by fermentation). Al- bromomethylfurfural (BMF).
ternatives that have been suggested to solve some or all of
these problems are butanol,[1] methanol, dimethylfuran,[2]
5-ethoxymethylfurfural,[3] γ-valerolactone, and alkanes pro-
duced from biomass.[4,5] Many of these alternatives rely on Results and Discussion
conversion of biomass carbohydrates into furfural deriva- In a paper from 1922, 5-bromomethylfurfural (BMF, 3)
tives, and the methods of furfural synthesis are rapidly pro- was prepared in 28–48 % yield by treatment of cellulose
gressing.[6–9] One of the promising new methods of doing with HBr in chloroform.[13] Curiously, glucose and cello-
that was reported by Mascal who showed that cellulose biose gave significantly lower yields (10–23 %). Otherwise, 3
could be converted into 5-chloromethylfurfural (1) in 71 % was prepared from 5-hydroxymethylfurfural (HMF, 4) by
yield by treatment with HCl/LiCl and continuous extrac- substitution of the hydroxy group, which is a facile reac-
tion with dichloroethane.[3] From 1, potential biofuel 2 tion.[14] However, when a procedure equivalent to Mascal’s
could be obtained in quantitative yield by reaction with eth- was employed, replacing concentrated HCl with concen-
anol. This method has been further improved and simpli- trated HBr and LiCl with LiBr, excellent yields of 3
fied,[10] and 1 has been converted into biodiesel prod- (Scheme 1) were obtained. These experiments were done in
ucts.[11,12] It is one of the most direct and high-yielding ways an apparatus equipped for continuous extraction either for
solvents denser or lighter than water. Fructose gave a yield
[a] Department of Chemistry, University of Copenhagen,
Universitetsparken 5, 2100 Copenhagen, Denmark of 68 % of 3 after chromatography, when dichloroethane
E-mail: bols@kemi.ku.dk was used as the extraction solvent. Variation in the solvent

1266 © 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Eur. J. Org. Chem. 2011, 1266–1270
Synthesis of 5-Bromomethylfurfural as a Potential Intermediate for Biofuel

showed that toluene improved the yield (82 %), whereas

tetrahydrofuran gave no product. A decrease in the amount
of LiBr used (Table 1, Entry 4) gave a lower yield; obviously
a high bromide concentration is important.

Scheme 1. Synthesis of 3.

Table 1. Yields of purified 5-bromomethylfurfural (3) obtained

from carbohydrates and biomass.
Entry Substrate Solvent[a] Temp.[b] LiBr Time Yield Scheme 2. Classical mechanism of 5-hydroxymethylfurfural forma-
[°C] [equiv.] [h] [%] tion adapted to BMF. The mechanism supposes formation of glu-
cose and isomerization to fructose.
1 fructose DCE 25 20 48 68
2 fructose MePh 25 20 48 82
3 fructose THF 25 20 48 0 resulted in a rate enhancement, especially for cellulose. This
4 fructose MePh 25 2 48 70
5 glucose MePh 65 20 48 50
suggest that CrII/CrIII catalyze both the transformation of
6 cellulose MePh 65 20 28 80 glucose and cellulose. Finally, it was observed that the reac-
7 straw MePh 65 20 48 68 tion of fructose is faster than the process of continuous ex-
[a] DCE = 1,2-dichloroethane, MePh = toluene, THF = tetra- traction: When manual extraction was performed on reac-
hydrofuran. [b] Temperature applied to the reaction chamber. tion samples, a higher rate is obtained. The above rates were
determined simply by evaporating the extraction solvent
When the reaction is applied to other carbohydrates the and weighing the residue. NMR spectroscopy was used to
following results were obtained: glucose gave a 50 % yield verify that the product was essentially 1.
of 3, whereas cellulose (microcrystalline) surprisingly (but
in accordance with ref.[13]) gave a 80 % yield of 3 (Table 1).
Finally 68 % of 3 can be obtained from straw, showing that
the method is easily applied to biomass. This yield is that
after chromatography and does not include some furfural
coming from hemicellulose. In these reactions, the rate
is slower and heating was therefore (unlike for fructose)
applied to the reaction chamber.
Formation of 3 would normally be expected to follow
the mechanism shown in Scheme 2: Cellulose is degraded
to glucose by the strong acid, glucose isomerizes to fructose
by acid-catalyzed enolization, fructose undergoes several
dehydrations to give 4, which has a very reactive alcohol
that reacts with HBr to form 3. An alternative mechanism,
where 3-deoxy-2-ketoglucose, and not fructose is an inter-
mediate, is also possible.[15] However, the fact that both
fructose and cellulose give a much higher yield than glucose
is not consistent with these mechanisms.
To gain better insight into what is happening in this reac-
tion, we followed the rate of formation of both BMF (3) Figure 2. Yield of 1 obtained after different times by treatment of
and CMF (1). The CMF experiments were essentially per- carbohydrates with conc. HCl/LiCl and continuous extraction with
DCE. Fructose (manual extraction, ♦), fructose (䊏), cellulose (w.
formed as described above and should be identical to those Cr, 䊉), glucose (w. Cr, 䉫), glucose (䊐), cellulose (䊊).
by Mascal[3] subject to possible differences associated with
equipment and setup (see the Experimental Section). Pre- The rate of formation of 3 from different starting materi-
paratively, we obtained 90–95 % yield of 1 from fructose, als is shown in Figure 3. These rates were determined by
62 % of 1 from glucose, 63 % of 1 from microcrystalline HPLC analysis of the extraction solvent – manual extrac-
cellulose, and 56 % of 1 from cotton. The rate of these reac- tion was performed to avoid potential problems of con-
tions is shown in Figure 2. It is seen that formation of 1 tinuous extraction being rate limiting. Formation of BMF
from fructose was very fast, the formation of 1 from glucose (3) from fructose was again very fast, but the reaction from
is slower, and formation of cellulose even more so. This is cellulose was faster than that from glucose. Even the reac-
basically in accordance with the mechanism in Scheme 2. tion from straw was faster than the reaction from glucose.
Addition of CrCl2 to the reaction of glucose and cellulose Addition of CrBr3 led to a slight decrease in the formation

Eur. J. Org. Chem. 2011, 1266–1270 © 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim www.eurjoc.org 1267
FULL PAPER
of BMF (3) from cellulose and a large increase in formation
of BMF (3) from glucose. Altogether, these rate results are
not consistent with the mechanism in Scheme 2, because
the reaction from glucose is clearly slower than that from
cellulose.
Figure 3. Yield of 3 obtained after different times by treatment of
carbohydrates with conc. HBr/LiBr and continuous extraction with
toluene. fructose (♦), cellulose (䊏), cellulose (w. Cr, 䊉), glucose (w.
Cr, 䉫), straw (䊐), glucose (䊊).
A faster reaction from cellulose, compared to that from
glucose, suggests that the 4-O-acetal link somehow is an
advantage in the dehydration reaction. To confirm this, we
prepared 4-O-methylglucose (8) as outlined in Scheme 3:
From methyl 2,3,6-tri-O-benzyl-d-glucopyranoside (5)
methylation with MeI/NaH gave an excellent yield of 6, hy-
drolysis with H2SO4 gave 40 % 7, and finally hydrogenolysis
led to 8 in 80 % yield. Treatment of 8 with HBr/LiBr and
continuous extraction with toluene gave an 80 % yield of
BMF (3). That means that 8 is as good a substrate as cellu-
lose and much better than glucose.
Scheme 3. Conversion of 4-O-methylglucose into BMF (3).
On the basis of the above, we suggest a revised mecha-
nism for the formation BMF (3), in which glucose is not an
1268 www.eurjoc.org © 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
N. Kumari, J. K. Olesen, C. M. Pedersen, M. Bols
intermediate (Scheme 4). The reaction occurs by transfor-
mation of cellulose from the reducing end. The terminal
residue undergoes acid-catalyzed rearrangement to a fruc-
tofuranoside, which subsequently undergoes dehydration.
However, depolymerization does not occur by glycoside
cleavage but by elimination of the 4-OR groups as part of
the dehydration.
Scheme 4. Revised mechanism for the formation of 3 from cellulose
not involving the formation of glucose (top). Suggested mechanism
for CrIII catalysis for the formation of 3 from glucose (bottom).
Remaining is the question of the influence of Cr catalysis
on these reactions, because a significant rate acceleration
was observed for the transformation of glucose into BMF
(3) and for cellulose into CMF (1). It has been suggested
that the effect of Cr in furfural synthesis is to catalyze isom-
erization of glucose into fructose.[6,7] However, it has been
shown by Mønsted that various pentoses upon complex-
ation with CrIII undergo elimination of the 3-OH group,
whereas 2-epimerization, which is a sign of 1,2-enolization,
does not occur.[16] It therefore seems more plausible that
glucose undergoes elimination of the 3-OH group in the
presence of chromium catalysis (Scheme 4, bottom). This
leads to the 3-deoxy-2-ketoglucose that then rearranges into
2,5-furanose and undergoes further elimination to give 3.[15]
The bromine in BMF (3) was found to be very reactive;
thus, 3 could readily be converted into 2 by gentle reflux in
ethanol or into HMF (4) by simple dissolution in water
(Scheme 5). Both reactions gave a quantitative yield and
potentially allow recovery of the HBr formed in the reac-
tion.
Scheme 5. Conversion of BMF (3) into 2 and 5-hydroxymethylfur-
fural (HMF, 4).
Conclusions
We have shown that 5-bromomethylfurfural (BMF, 3)
can be made very efficiently from cellulose or straw by treat-
ment with concentrated aqueous HBr. The mechanism does
Eur. J. Org. Chem. 2011, 1266–1270
Synthesis of 5-Bromomethylfurfural as a Potential Intermediate for Biofuel
not involve the intermediate formation of glucose, and the
reaction is suggested to occur from the reducing end of the
polysaccharide. BMF (3) can be readily converted into po-
tential biofuel 4 and HMF (2) by ethanolysis and hydroly-
sis, respectively.
Experimental Section
Conversion of Cellulose into 5-Bromomethylfurfural (BMF, 3): Tolu-
ene was introduced into the extraction chamber of a standard ap-
paratus for continuous extraction with a solvent lighter than water.
A homogeneous suspension of microcrystalline cellulose (2.05 g,
5 % water by mass) was prepared in a solution of lithium bromide
(10 g) in concentrated hydrobromic acid (150 mL), and this was
added to the extraction chamber. A boiling flask containing tolu-
ene (150 mL) and anhydrous sodium sulfate was attached to the
apparatus, and the solvent was heated to reflux. The aqueous slurry
was kept at 65 °C. During the extraction, the boiling flask was emp-
tied every 6 h and replaced with fresh toluene (150 mL). The com-
bined organic extracts were distilled to recover the solvent, and
the residual oil (1.69 g) was purified by chromatography (silica gel;
petroleum ether/ethyl acetate, 2:1) to give 3 (80 %). 1H NMR
(300 MHz, CDCl3): δ = 4.46 (s, 2 H), 6.55 (d, J = 3.6 Hz, 1 H),
7.16 (d, J = 3.3 Hz, 1 H), 9.59 (s, 1 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 21.8, 112.3, 122.2, 153.0, 156.4, 177.9 ppm. HRMS:
calcd. for C6H5BrO2 188.9551; found 188.9551.
Conversion of Glucose into BMF (3): Using the general procedure
described above, glucose (2.01 g) gave a crude product that was
purified by chromatography to give 3 (1.0 g, 50 %).
Conversion of Fructose into BMF (3): Using the general procedure
described above, fructose (2.00 g) gave 3 (1.75 g, 82 %).
Conversion of Straw into BMF (3): Using the general procedure
described above, straw (2.00 g) gave a crude product (1.43 g) that
was purified by chromatography to give 3 (1.2 g, 68 %).
Conversion of Cellulose into 5-Chloromethylfurfural (CMF, 1): 1,2-
Dichloroethane (DCE) was added to the reaction chamber of a
standard setup for continuous extraction with solvents denser than
water. Microcrystalline cellulose (1.24 g) was added to a solution
of lithium chloride (6.08 g) in concentrated hydrochloric acid
(90 mL). The suspension was added to the reaction chamber, which
was kept at 65 °C, whilst the collection flask was kept at 140 °C
thereby continuously refluxing DCE through the aqueous solution.
The collection flask was emptied every 30 min, and the contents
was concentrated on a rotary evaporator, noting the mass of the
resulting oily crude product. The reaction was stopped after 30 h,
yielding 1 as an oily crude product (0.63 g, 63 %). 1H NMR
(300 MHz, CDCl3): δ = 4.62 (s, 2 H), 6.60 (d, J = 3.3 Hz, 1 H),
7.22 (d, J = 3.0 Hz, 1 H), 9.65 (s, 1 H) ppm.
Conversion of Glucose into CMF (1): Carried out as above, except
replacing cellulose with glucose (1.37 g). The reaction was stopped
after 26 h, affording 62 % of crude 1 (0.68 g).
Conversion of Fructose into CMF (1): Carried out as above, except
replacing cellulose with fructose (1.24 g). The reaction was stopped
after 30 h, affording 90 % of crude 1 (0.89 g).
Conversion of Fructose into CMF (1) with Manual Extraction: Lith-
ium chloride (6.23 g) was dissolved in concentrated hydrochloric
acid (90 mL) and fructose (1.23 g) was added to the solution, which
was kept at 65 °C. The reaction mixture was manually extracted
with dichloromethane (100 mL) after 25, 60, and 100 min. After
Eur. J. Org. Chem. 2011, 1266–1270 © 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
100 min, the reaction was stopped and the extracts were concen-
trated, affording 95 % of crude 1 (0.93 g).
Chromium-Catalyzed Experiments: The chromium-catalyzed reac-
tions were carried out by using the procedures above, except that
chromium(III) bromide (1.12 g) was added for the preparation of
3 or chromium(II) chloride (0.25 g) was added for the preparation
of 1.
HPLC Experiments: Carbohydrate (500 mg) and LiBr (4.8 g) were
mixed with HBr (55 %, 4 mL). At different intervals, a 0.5-mL ali-
quot was extracted with toluene (2 mL). A 0.5-mL sample of this
mixture was diluted with toluene to 8 mL, and the concentration
of 3 in this solution was determined by HPLC. The HPLC column
used was ACE 5 C18 and the solvent MeOH/H2O (3:2,
0.5 mL min). BMF was monitored by UV at 254 nm and gave a
retention time of 5.6 min.
Methyl 2,3,6-Tri-O-benzyloxy-4-O-methyl-α-D-glucopyranoside (6):
To a suspension of NaH (80 mg, 3.3 mmol) in dry DMF (7 mL)
was added dropwise a solution of methyl 2,3,6-tri-O-benzyloxy-α-
d-glucopyranoside (5; 700 mg, 1.508 mmol) in DMF (3 mL) at
0 °C. The reaction mixture was stirred for 1 h at 0 °C and methyl
iodide (0.14 mL, 2.2 mmol) was added to the reaction mixture. The
reaction mixture was stirred for another 2 h to complete the reac-
tion. The reaction was quenched by adding the reaction mixture
into ice-cold water, which was then extracted with ethyl acetate
(2 ⫻ 25 mL). The collected organic layers were washed with brine,
dried with Na2SO4, and concentrated to obtain alkylated product
6, which was purified by column chromatography. Yield: 95 %, vis-
cous liquid Rf = 0.50 (petroleum ether/ethyl acetate, 4:1), 1H NMR
(300 MHz, CDCl3) as reported.[17]
2,3,6-Tri-O-benzyloxy-4-O-methyl-D-glucopyranose (7): Compound
6 (500 mg, 1.1 mmol) in a solution of 1 n H2SO4/CH3COOH (1:2)
was heated at reflux for 7 h to get product 7 (200 mg, 40 %). Vis-
cous liquid Rf = 0.50 (petroleum ether/ethyl acetate, 6:4), 1H NMR
(300 MHz, CDCl3) as reported.[18] 13C NMR (75 MHz, CDCl3): δ
= 138.9, 138.8, 138.2, (Cquat, Ph) 128.7, 128.6, 128.57, 128.4, 128.3,
128.2, 128.1, 127.9, 127.8, (Ph), 97.7 (C-1β), 91.5 (C-1α), 84.6
(Bnβ), 83.1 (Bnβ), 81.9 (Bnα), 80.1 (Bnβ), 80.0 (Bnα), 79.8 (Bnα),
75.8, 75.7, 74.9, 73.7, 73.7 (2 C), 73.4, 70.5, 69.3, 68.9 (C-2, C-3,
C-4, C-5, C-6), 60.9 (2 C, OMe) ppm.
4-O-Methyl-D-glucose (8): Compound 7 (200 mg) was dissolved in
MeOH and subjected for debenzylation in H-cube by using
Pd(OH)2 as catalyst at 50 bar at 50 °C for 2 h. Yield 80 %. 1H NMR
(300 MHz, D2O, 1:1 mixture of anomers): δ = 5.09 (d, J = 3.5 Hz,
1 H) 4.84 (s, 1 H), 4.44 (d, J = 7.8 Hz, 1 H), 3.85–3.61 (m, 7 H),
3.55 (s, 6 H), 3.47–3.19 (m, 4 H), 3.17–3.00 (m, 3 H) ppm. 13C
NMR (75 MHz, MeOD): δ = 98.2, 93.9 (C-1), 81.3, 81.1, 78.2, 77.1
76.5, 75.0 74.0, 72.2 (C-2, C-3, C-4, C-5), 62.5, 62.4 (C-6), 61.0,
60.9 (OMe) ppm.
Conversion of 4-O-Methylglucose into BMF: Using the general pro-
cedure described above for BMF formation, 4-O-methylglucose (8,
2.00 g) gave 3 in 80 % yield.
5-Ethoxymethylfurfural (2): BMF (3, 500 mg) was dissolved in eth-
anol (10 mL), and the solution was heated at reflux for 3 h. The
solution was concentrated and subjected to chromatography
(CH2Cl2/diethyl ether, 2:1). This gave 2 in quantitative yield. 1H
NMR (300 MHz, CDCl3): δ = 9.40 (s, 1 H), 7.06 (d, J = 3.1 Hz, 1
H), 6.34 (d, J = 3.5 Hz, 1 H), 4.32 (s, 2 H), 3.39 (q, 2 H), 1.04 (t,
3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 176.7, 157.9, 151.8,
121.8, 110.3, 65.3, 63.6, 14.1 ppm.
www.eurjoc.org 1269
FULL PAPER
5-Hydroxymethylfurfural (4): BMF (3, 500 mg) was dissolved in
distilled water (10 mL), and the solution was stirred for 1 h. The
solution was concentrated and subjected to chromatography
(CH2Cl2/diethyl ether, 2:1). This gave 4 in quantitative yield. 1H
NMR (300 MHz, CDCl3): δ = 9.57 (s, CHO), 7.13 (d, J = 3.6 Hz,
1 H), 6.53 (d, J = 3.3 Hz, 1 H), 4.56 (s, 2 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 178.2, 161.6, 153.4, 121.8, 111.3, 57.1 ppm.
Acknowledgments
We thank the Forskningsrådet for Teknologi og Produktion (FTP)
for financial support.
[1] D. F. Savage, J. Way, P. A. Silver, ACS Chem. Biol. 2008, 3, 13–
16.
[2] Y. Roma’n-Leshkov, C. J. Barrett, Z. Y. Liu, J. A. Dumesic, Na-
ture 2007, 447, 982–986.
[3] M. Mascal, E. B. Nikitin, Angew. Chem. 2008, 120, 8042; An-
gew. Chem. Int. Ed. 2008, 47, 7924–7926.
[4] G. W. Huber, J. N. Chheda, C. J. Barrett, J. A. Dumesic, Sci-
ence 2005, 308, 1446–1450.
[5] J. Q. Bond, D. M. Alonso, D. Wang, R. M. West, J. A. Dum-
esic, Science 2010, 327, 1110–1114.
1270 www.eurjoc.org © 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
N. Kumari, J. K. Olesen, C. M. Pedersen, M. Bols
[6] H. Zhao, J. E. Holladay, H. Brown, Z. C. Zhang, Science 2007,
316, 1597–1600.
[7] J. B. Binder, R. T. Raines, J. Am. Chem. Soc. 2009, 131, 1979–
1985.
[8] A. Takagaki, M. Ohara, S. Nishimura, K. Ebitani, Chem. Com-
mun. 2009, 6276–6278.
[9] Y. Su, H. M. Brown, X. Huang, X.-D. Zhou, J. E. Amonette,
Z. C. Zhang, Appl. Catal. A 2009, 361, 117–122.
[10] M. Mascal, E. B. Nikitin, ChemSusChem 2009, 2, 859–861.
[11] M. Mascal, E. B. Nikitin, Energy Fuels 2010, 24, 2170–2171.
[12] M. Mascal, E. B. Nikitin, Green Chem. 2010, 12, 370–373.
[13] H. Hibbert, H. S. Hill, J. Am. Chem. Soc. 1922, 44, 176–182.
[14] P. Villain-Guillot, M. Gualtieri, L. Bastide, F. Roquet, J. Marti-
nez, M. Amblard, M. Pugniere, J.-P. Leonetti, J. Med. Chem.
2007, 50, 4195–4204.
[15] A. Corma, S. Iborra, A. Velty, Chem. Rev. 2007, 107, 2411–
2502.
[16] J. Eriksen, L. Mønsted, O. Mønsted, Acta Chem. Scand. 1995,
49, 713–721.
[17] W. Hakamata, T. Nishio, R. Sato, T. Mochizuki, K. Tsuchiya,
M. Yasuda, T. Oku, J. Carbohydr. Res. 2000, 19, 359–377.
[18] Y. Yoneda, T. Kawada, T. Rosenau, P. Kosma, Carbohydr. Res.
2005, 340, 2428–2435.
Received: November 15, 2010
Published Online: January 21, 2011
Eur. J. Org. Chem. 2011, 1266–1270