Microwave- or microreactor-assisted conversion of furfuryl alcohols into 4-hydroxy-2-cyclopentenones

Article abstract of DOI:10.1055/s-0030-1258534

The conversion of a variety of furfuryl alcohols, derived from renewable non edible resources such as bran, into 4-hydroxy-2-cyclopentenones was accomplished using microwave irradiation. In subcritical water (220° C, 15.5 bar) without the need for any catalyst the reaction proceeds approximately two orders of magnitude faster with up to twice the yield compared to methods previously reported that apply conventional heating techniques. For the parent furfuryl alcohol the process could be transferred to a microreactor, allowing the synthesis of 4-hydroxy-2-cyclopentenone in a continuous flow system on multigram scale. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0030-1258534

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2037
Microwave- or Microreactor-Assisted Conversion of Furfuryl Alcohols into
-Hydroxy-2-cyclopentenones
4
C
K
onversion of
F
ur
a
f
uryl
A
lcoh
t
ols into
h
4-Hydroxy-
r
2-cyclop
i
e
nteno
n
nes Ulbrich, Peter Kreitmeier, Oliver Reiser*
Institut für Organische Chemie der Universität Regensburg, Universitätsstr. 31, 93053 Regensburg, Germany
Fax +49(941)9434121; E-mail: oliver.reiser@chemie.uni-regensburg.de
Received 14 June 2010
sis of 2 can be achieved within minutes in water under
Abstract: The conversion of a variety of furfuryl alcohols, derived
from renewable non edible resources such as bran, into 4-hydroxy-
subcritical conditions with considerably improved yields
using microwave irradiation.7 Moreover, we have been
,8
2
-cyclopentenones was accomplished using microwave irradiation.
able to transfer those conditions to a microreactor in a
In subcritical water (220 °C, 15.5 bar) without the need for any cat-
9
alyst the reaction proceeds approximately two orders of magnitude continuous flow setup, being especially attractive for
faster with up to twice the yield compared to methods previously re-
large-scale synthesis.
ported that apply conventional heating techniques. For the parent
furfuryl alcohol the process could be transferred to a microreactor,
allowing the synthesis of 4-hydroxy-2-cyclopentenone in a contin-
uous flow system on multigram scale.
O
O
OH
Key words: green chemistry, organic synthesis in water, micro-
wave chemistry, carbohydrates, biomass, furfuryl alcohol
OH
1
2
H+ – H2O
In recent years, increasing efforts are made to establish
new technologies for the conversion of biomass into fuels
or basic chemicals that can be further used for the produc-
tion of fine chemicals, materials, or pharmaceuticals. The
use of renewable resources is one of the key aspects of
sustainable development considering upcoming changes
on the oil market and thereby ensuring future supply of
raw materials. The decline of fossil resources and there-
fore increasing oil prices will make products from bio-
mass economically advantageous. Furthermore, the use of
O
OH
H O
2
H+
–
O
3
4
Scheme 1 Conversion of furfuryl alcohol (1) into 4-hydroxy-2-
cyclopentenone (2)
Following the leads previously reported and in agreement
with the mechanism proposed calling for 3 as an interme-
diate protic conditions seem to be a requirement for the
transformation of 1 to 2 (Scheme 1). Nevertheless, even
under reflux conditions in water in the presence of various
acids the reaction still proceeds sluggishly. Moreover, sta-
bility problems of 2 at higher temperatures are being en-
countered, making long reaction times not desirable. We
therefore set out to investigate the rearrangement of furfu-
ryl alcohols under more forcing conditions, that is, using
microwave irradiation in closed vessels that readily al-
lows to carrying out reactions well above the boiling point
of water at elevated pressure.
renewable resources is desirable since they are CO neu-
2
tral, nevertheless, also the technologies for converting
them into viable products need to be energy-efficient and
1
environmentally friendly.
Many processes to convert biomass into fuel or fine chem-
icals start from starch (glucose), thus colliding with food
production. Materials derived from nonedible renewable
resources, ideally being produced as byproducts in the
process of food production, are therefore especially valu-
able starting materials for chemistry. Therefore, we have
a continuing interest to develop chemistry starting from
2
3
furfural, being produced from hemicellulose, derived
from agricultural waste products like bran or bagasse.4
Aqueous solutions of furfuryl alcohol (1, 0.25, 0.50 and 1
mol/L) were heated in water as solvent using a commer-
cial mircowave (CEM Discover) in a closed vessel. At
Furfuryl alcohol (1) can be converted into 4-hydroxy-2-
cyclopentenone (2), the latter being a valuable intermedi-
5
ate for the synthesis of natural products and analogues. A
3
2
00 W a maximum temperature of the reaction mixture of
00–210 °C and 15.5–17.6 bar was reached. Notably,
number of protocols have been developed for this trans-
formation, generally calling for heating 1 in aqueous me-
with increasing concentrations of 1 faster upheating and
higher end temperatures were observed, suggesting that 1
is especially effective in absorbing microwave irradia-
dia for 22–48 hours, giving rise to 2 in approximately 40–
6
5
0% yield. In this report we demonstrate that the synthe-
1
0
tion. In all cases 1 was completely consumed within 3–
minutes, giving rise to the desired cyclopentenone 2 but
being accompanied by polymeric byproducts. The forma-
SYNLETT 2010, No. 13, pp 2037–2040
x
x
.x
x
.2
0
1
0
4
Advanced online publication: 28.07.2010
DOI: 10.1055/s-0030-1258534; Art ID: Y01810ST
©
Georg Thieme Verlag Stuttgart · New York

2
038
K. Ulbrich et al.
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tion of the latter could be supressed at lower concentra- Table 1 Rearrangement of Substituted Furfuryl Alcohols 5a
tions of 1 in water, giving rise to 2 in up to 80% yield (GC,
Figure 1 and Figure 2).
O
OH
O
H O
2
R
R
MW (300 W)
OH
5
6
Entry Compound R
Time
syn/anti Yield
b
(
min)
(%)
1
2
3
4
5a
5b
5c
5d
5e
Ph
2
5
1:5
1:12
1:7
1:7
–
96
73
54
65
0
CH CH=CHMe
2
Et
15
15
30
n-pentyl
n-dodecyl
5
a
Conditions: 5 (1.5 mmol) in H O (6 mL), microwave irradiation
2
(
300 W) under closed vessel conditions (200–210 °C, 15 bar).
Isolated yield.
b
Figure 1 Conversion of furfuryl alcohol (1) in H O under microwa-
2
ve irradiation (300 W): a: 1.0 mol/L; b: 0.5 mol/L; c: 0.25 mol/L; con-
version determined by GC with an internal standard method.
ume of 1.77 mL, coiled up, and immersed in a heating
bath at 240 °C by a HPLC pump (inlet A) within approx-
imately one minute, thus closely resembling the tempera-
ture conditions previously present in the microwave
reactor. However, in order to achieve complete conver-
sion of 1 it was found to be beneficial to adjust the pH to
4
with acetic acid. Since some polymers form during time,
we introduced toluene through a second inlet (B), the lat-
ter effectively dissolving the byproducts thus preventing
blockage of the steel tube. Conveniently, the product 2
completely remains in the aqueous phase, thus after col-
lection of the reaction mixture at the end of the reactor,
only a simple separation of the organic phase and extrac-
tion of the aqueous phase with methyl-tert-butyl ether was
needed for purification. After evaporation of water, 2 was
obtained on a multigram scale in 87% yield (GC purity
9
7%), which could be further purified by distillation if de-
sired (74% yield, GC purity 99%).
Figure 2 Yield (GC; decane as internal standard) of 4-hydroxy-2-
cyclopentenone 2: MW 300 W; H O as solvent; a: 1.0 mol/L; b: 0.5
2
1000 psi
mol/L; c: 0.25 mol/L.
Likewise, substituted furfurylalcohols 5a–d could be rear-
ranged successfully in water to the corresponding cyclo-
pentenones 6a–d in good yields under microwave
irradiation within minutes (Table 1), again greatly short-
ening the reaction times compared to previous reports.11
Only 5e bearing an unpolar side chain did not undergo the
A
B
2
40 °C
20 °C
desired reaction under the reaction conditions, most likey Figure 3 Microreactor setup: A: inlet for 3a in water (0.25 mol/L)
adjusted to pH 4 with AcOH at a flow rate of 1.8 mL/min, B: inlet for
due to its low miscibility with water.
toluene at a flow rate of 0.2 mL/min; average residence time in the
Having found suitable conditions that greatly accelerate
the rearrangement of furfuryl alcohols in a batch reactor,
we next wanted to develop reaction conditions being suit-
able for upscale. Using 1 being arguably the most useful5
furfuryl alcohol for this process, we investigated its rear-
rangement to 2 in a microreactor (Figure 3). An aqueous
solution of 1 was passed through a reaction chamber con-
sisting of a four-meter length of steel tube with a total vol-
reactor 53 s.
In conclusion, the rearrangement of furfuryl alcohols can
be greatly accelerated in water at high temperature and
pressure (220–240 °C), conditions that can be readily
achieved in a microwave or microreactor. The latter al-
lowed the development of a continuous flow process for
Synlett 2010, No. 13, 2037–2040 © Thieme Stuttgart · New York

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Conversion of Furfuryl Alcohols into 4-Hydroxy-2-cyclopentenones
2039
the rearrangement of furfuryl alcohol (1) to cyclopenten- 162.4, 141.2, 139.2, 134.9, 134.6, 115.7, 114.6, 73.2, 72.6, 60.0,
5
9.3, 36.1, 35.8, 17.5, 14.6.
one 2 with considerable improvement of yield. The short
residence time of 1 (<1 min) in the microreactor setup
overcome problems of stability of the product 2 being en-
countered under conventional heating conditions that re-
quired reaction times of 22–48 hours.
5
-Ethyl-4-hydroxycyclopenten-2-enone (5c)
1
Yield 54% (trans/cis = 7:1). H NMR (300 MHz, CDCl ): d = 7.52–
3
7
4
.49 (dd, 1 H, J = 5.8, 2.2 Hz), 6.20–6.17 (dd, 1 H, J = 5.8, 1.2 Hz),
.7 (br s, 1 H), 2.22–2.16 (m, 1 H), 1.93–1.84 (m, 1 H), 1.58–1.48
1
3
(
=
m, 1 H), 1.02 (t, 3 H, J = 7.4 Hz). C NMR (75.5 MHz, CDCl ): d
3
208.2, 161.9, 134.4, 76.3, 56.6, 21.5, 11.6.
Conversion of Furfuryl Alcohol (1) into 4-Hydroxy-2-cyclopen-
tenone (2) in a Microreactor
Reactor Setup (Figure 3)
Two HPLC pumps (inlet A and B) were connected to a 5 m stainless
steel tube (0.75 mm i.d.) via a T-connector; 4 m of this steel tube
were coiled up and immersed in a heating bath, followed by a 0.3 m
coiled cooling zone (approx. 20 °C). The outlet of the reactor was
connected to a 68.9 bar back pressure regulator, followed by a 0.4
mm PTFE syringe filter (Ø 25 mm) to crack the resulting emulsion.
The residence volume of the heated coil was 1.77 mL.
4
-Hydroxy-5-pentylcyclopenten-2-enone (5d)
1
Yield 65% (E/Z = 1:1; trans/cis = 7:1). H NMR (300 MHz, CDCl ):
3
d = 7.50–7.48 (dd, 1 H, J = 5.8, 2.2 Hz), 6.17–6.14 (dd, 1 H, J = 5.8,
1
1
CDCl ): d = 208.8, 162.2, 134.2, 70.1, 55.4, 31.9, 28.6, 27.0, 22.5,
1
.2 Hz), 4.65 (m, 1 H), 2.14–2.18 (m, 1 H), 1.85–1.78 (m, 1 H),
1
3
.42–1.29 (m, 6 H), 0.86 (t, 3 H, J = 7.0 Hz). C NMR (75.5 MHz,
3
4.1.
Acknowledgment
Procedure
This work was supported by the Deutsche Bundesumweltstiftung
(KONAROM, AZ 26920) and the Fonds der Chemischen Industrie.
A solution of 12.5 g (127 mmol) furfuryl alcohol (1) in H O was ad-
2
justed to pH 4.0 with diluted AcOH (total volume 500 mL). The
heating bath was brought to 240 °C. The aq furfuryl alcohol solu-
tion was introduced to inlet A at a flow rate of 1.8 mL/min, toluene
was introduced to inlet B at flow rate of 0.2 mL/min (total flow rate
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(
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4
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3
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(
1
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