Cyclopentanone Derivatives from 5-Hydroxymethylfurfural via 1-Hydroxyhexane-2,5-dione as Intermediate

Article abstract of DOI:10.1002/cssc.201702100

An efficient strategy for the conversion of biomass derived 5-hydroxymethylfurfural (HMF) into 2-hydroxy-3-methylcyclopent-2-enone (MCP) by an intramolecular aldol condensation of 1-hydroxyhexane-2,5-dione (HHD) has been developed. Further transformations of MCP towards the diol, enol acetate, levulinic acid and N-heterocyclic compounds are also reported.

Full text of DOI:10.1002/cssc.201702100

Accepted Article
Title: Cyclopentanone derivatives from 5-hydroxymethylfurfural via 1-
hydroxyhexane-2,5-dione as intermediate
Authors: Bartosz Wozniak, Anke Spannenberg, Yuehui Li, Sandra
Hinze, and Johannes Gerardus de Vries
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10.1002/cssc.201702100
ChemSusChem
COMMUNICATION
Cyclopentanone derivatives from 5-hydroxymethylfurfural via 1-
hydroxyhexane-2,5-dione as intermediate
Bartosz Wozniak,[a] Anke Spannenberg,[a] Yuehui Li,[b] Sandra Hinze,[a] Johannes G. de Vries[a]*
Abstract: An efficient strategy for the conversion of biomass derived
5-hydroxymethyl-furfural (HMF) to 2-hydroxy-3-methylcyclopent-2-
enone (MCP) via intramolecular aldol condensation of 1-
hydroxyhexane-2,5-dione (HHD) has been developed. Further
transformations of MCP towards the diol, enol acetate, levulinic acid
and N-heterocyclic compounds are also reported.
half-sandwich complexes[10-12] appeared to be most promising.
Fu and co-workers[12] increased the selectivity to 99%, by using
such a complex with electron-donating ligands, and adjusting the
pH during the reaction. However, they only obtained high
conversions and selectivities using formic acid as the hydrogen
source. None of the above papers reported an isolation
procedure. The catalytic hydrogenation of 5-HMF to HHD still
needs to be improved and development of an effective HHD
isolation method remains a major challenge.[10-12] Furthermore,
to the best of our knowledge, no further conversions of HHD as
a starting material have been reported.
In view of the dwindling supply of fossil resources new scenarios
need to be developed for the manufacture of the chemicals our
lives depend upon, such as pharmaceuticals or plastics, which
are currently derived from crude oil. We are interested in the
catalytic conversion of platform chemicals derived from
renewable resources to existing or new chemicals.[1] 5-Hydroxy-
methyl)furfural (HMF, Scheme 1, 1) is obtained from the dehy-
dration of fructose, and has become a well-known platform
chemical for the production of numerous valuable chemicals,
such as 2,5-furan-dicarboxylic acid.[2] Recently, we became
interested in the further development of 1-hydroxyhexane-2,5-
dione (HHD, 2), a product of the hydrogenation/hydrolytic ring
opening of HMF (Scheme 1).
H
N
OMe
H
N
+
+
2+
Ph2P
Ru
H
PPh2
H
H
CO
N
L
N
N
Ir
N
H2O
OH2
M
H3B
OH2
Ir
Cl
III
N
Cl
*Cp
:
II
=
=
=
Ir, L
Ru, L
IV
V
I
M
M
Cp*
=
:
p-cymene
Figure 1. Iridium and ruthenium complexes used.
O
OH
Cat. H2
H2O
H
Base
O
O
OH
Herein, we present an improved protocol for the synthesis of
HHD. We report the first isolation procedure as well as the full
characterization of HHD. To establish HHD as a platform
chemical we show its potential as a building block, namely its
transformation to 2-hydroxy-3-methylcyclopent-2-enone (MCP,
3) and potentially useful follow-up products.
OH
O
O
1
2
3
MCP
HMF
HHD
isolated
yields
to 69%
up
OAc
OH
N
O
OH
O
OH
N
O
Concerning the development of new homogeneous catalysts
for the conversion of 5-HMF to HHD, limitations arise from the
requirements of water solubility and stability under acidic
conditions. Thus, activated base metal catalysts, used for hydro-
genation and transfer hydrogenation reactions, did not show any
selectivity towards HHD. We evaluated a series of air and
moisture stable iridium and ruthenium complexes (Fig. 1) that
Scheme 1. Conversion of HMF (1) to MCP (3) via HHD (2) and further
possible reactions.
Several catalytic systems have been reported to produce
HHD. Hydrogenation of 5-HMF to HHD in acidic media catalysed
by Pt/C was published by Mentech et al.[3] Various hetero-
geneous catalysts were then reported for the hydrogenative ring
opening of 5-HMF, including Rh-Re/SiO2,[4] Pd/C[5,6] and Au
nanoparticles on metal oxide supports.[7,8] However, these
require high H2 pressures, with selectivities varying from 57% to
81%. Higher HHD selectivities are obtained in processes
catalyzed by homogeneous catalysts.[9-12] In particular, Cp*Ir(III)
Table 1. Screening of catalysts I-V for HHD formation in aqueous media.[a]
O
H
I-V H O
,
2
O
OH
120 o 10 bar H
C,
2,
OH
O
O
1
2
Entry
Catalyst
Time
Conv. (%)[b]
Yield (%)[b]
1
I
II
2 h
4 h
1 h
2 h
2 h
4 h
4 h
>99
97
76 (69)[c]
2
42
60
5
[a]
[b]
B. Wozniak, Dr. A. Spannenberg, Dr. S. Hinze, Prof. Dr. J. G. de
Vries
Leibniz-Institut für Katalyse e.V. an der Universität Rostock
Albert-Einstein-Str. 29a, 18059 Rostock
E-mail: johannes.devries@catalysis.de
Prof. Y. Li
3
III
IV
V
I
>99
93
4
5
6[d]
34
25
67
71
>99
>99
State Key Laboratory for Oxo Synthesis and Selective Oxidation
Institute of LICP, Lanzou Institute of Chemical Physics (LICP),
Chinese Academy of Sciences
7[d]
III
[a] Reaction
conditions: 5-HMF (4 mmol), water (20 mL), I-V (0.5 mol%),
Lanzhou 730000 P.R. China
120oC, 10 bar H2. [b] Determined by 1H NMR using (CH3)4NBF4 as an internal
standard. [c] Isolated yield. [d] 5-HMF (40 mmol), PBS (200 mL, 0.1 M, pH=
2.5), cat (0.075 mol%), 140oC, 20 bar H2.
Supporting information for this article is given via a link at the end of
the document.
This article is protected by copyright. All rights reserved.

10.1002/cssc.201702100
ChemSusChem
COMMUNICATION
OH
O
have not been previously used for the hydrogenation of HMF to
HHD. The best results were obtained with the half-sandwich
[Cp*Ir(dpa)Cl]Cl (dpa= dipyridylamine) catalyst I (Table 1, entry
1), which is a known catalyst for water oxidation[13] and the
transfer hydrogenation of levulinic acid.[14] Poor selectivities were
observed with ruthenium complexes II, IV and V. After further
optimization, the best results were obtained with I (0.5 mol%)
with 10 bar H2 at 120 °C in water and HHD was isolated in 69%
yield. The major byproduct was found to be an insoluble
polymeric solid, presumably humins, which is consistent with the
observations of other groups.[6,12] In addition, the utilization of
phosphoric acid/sodium phosphate buffer solution allowed
processing with lower catalyst loading (0,05 mol%), however no
improvement in yield was observed.
bases
inorganic
work
acidic metal oxides
O
O
OH
HO
this
Ohyama/Satsuma 8,15
O
3
4
2
Scheme 2. Aldol condensation products starting from 2.
Table 2. Influence of the amount of base on the synthesis of MCP (3) from
HHD (2)[a]
OH
O
60o H O
C,
2
O
+
OH
KOH
O
2
3
Entry
KOH (eq.)
Time
Conv. (%)[b]
Yield (%)[b]
Single crystals were grown from a DCM/pentane mixture at -
30oC, and the crystal structure was determined for the first time
by X-ray diffraction analysis (Figure 2). With reasonable
amounts of clean compound in hand, we started to investigate
further reactions using HHD as a starting material.
1
2
3
4
5
6
7
8
-
8 h
8 h
-
-
0.1
0.4
0.7
1.0
1.2
1.5
1.5
-
-
8 h
-
-
16 h
1 h
>99
>99
>99
>99
>99
47
65
68
72
70
30 min
15 min
1.5 h
[a] Reaction conditions: HHD (0.4 mmol), KOH, water (2 mL), 60oC. [b]
Determined by TLC. [c] Reaction carried out at room temperature.
using 1.5 eq. of base at 60oC. The results of solvent and base
screenings are shown in Table 3. Simple inorganic bases such
as alkaline hydroxides promote the aldol condensation when
water and alcohols were used as solvents (Table 3, entries 1-2,
5-6). However, the utilization of potassium tert-butoxide in THF
led to full conversion in 5 minutes in higher isolated yield (Table
3, entry 9). It is worth to mention that no formation of 4 was
observed. The only byproduct present was an insoluble
polymeric substance, which was also reported by Ohyama,
Sutsuma and co-workers.[15]
We also established a one-pot synthesis of MCP directly
from 5-HMF. Under optimized conditions, the hydrogena-
tion/hydrolytic ring opening of 5-HMF followed by intramolecular
aldol condensation led to 55% isolated yield of MCP (Scheme 3).
Crystals of MCP suitable for X-ray diffraction analysis were
obtained (Figure 3).
We then turned our attention to the conversion of MCP into
valuable biomass-based chemicals (Scheme 4). Hydrogenation
of MCP catalysed by Ru-MACHO-BH[23] (Figure 1, cat IV)
(Scheme 4, i) gave full conversion of MCP (3) after 16 h. 3-
Methyl-1,2-cyclopentanediol (5) was isolated in near-quantitative
yield as a mixture of 3 diastereomers (3.3 : 1.6 : 5.0). Access to
5 is limited and its synthesis usually requires harsh conditions.[24]
Recently, 5 was used by Chavan and Bhanage in oxidative
carbonylation reactions to form cyclic carbonates, which play an
Figure 2. ORTEP representation of HHD (2) showing intermolecular O-H…O
hydrogen bonds (for more details see Supporting Information). Displacement
ellipsoids correspond to 30% probability.
Interestingly, base-promoted aldol condensation led to 2-
hydroxy-3-methylcyclopent-2-enone (MCP, 3) instead of the
expected 3-hydroxymethyl-cyclopent-2-en-1-one (HCPEN, 4) as
shown in Scheme 2.[8,15] MCP is a known flavor ingredient in
roasted coffee and maple syrup, and is widely used in the food
industry. It also finds use as a precursor for the biosynthesis of
antibiotics,[16] as fragrance in perfumery[17] and as ligand in metal
complexes.[18] Several routes towards MCP are discussed in the
literature, starting from isoprene,[19] 2-keto-glutaric acid,[20]
dimethyl adipate[21] or 1-acetoxy3-buten-2-one.[22] We report the
efficient synthesis of MCP starting from biomass-derived 5-HMF
in a two-step-process, involving HHD as an intermediate. We
optimized the reaction by investigating the role of base in the
aldol condensation reaction of HHD at 60oC (Table 2). Without
base or in the presence of small amounts of KOH, no conversion
was observed even after 8h (Table 2, entries 1-3). Increasing
the KOH/HHD ratio to 1.5, full conversion was achieved in 15
minutes, yielding 72% of MCP (Table 2, entry 7). Similar results
were obtained at room temperature after 1.5 h (Table 2, entry 8).
Based on these results, we carried out further optimizations
important
role
in
pharmaceuticals,
polymers
and
agrochemicals.[25] The addition of sodium periodate to aqueous
MCP solutions led to the formation of levulinic acid (6) (Scheme
4, ii), a well-known precursor for a variety of compounds with a
broad range of applications.[26]
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10.1002/cssc.201702100
ChemSusChem
COMMUNICATION
OH
OH
Table 3. Solvent and base screening in the intramolecular aldol condensation
Ru-MACHO-BH
mol%)
(0.5
O
O
O
OH
mixture of isomers
of HHD.[a]
i)
96%
yield
20 bar H2, 100 °C, THF, 16 h
OH
O
3
5
60o solvent
C,
O
+
OH
base
OH
O
O
NaIO
eq.)
4 h
4 (3
2
OH
3
ii)
67%
yield
RT, H
2O,
Entry
Base
Solvent
Time
Conv. (%)[b]
Yield (%)[b]
O
3
6
R
OH
HN
N
1
2
3
4
5
6
7
8
9
NaOH
KOH
H2O
H2O
15 min
15 min
20 h
>99
>99
>99
>99
>99
>99
-
70
72
62
71
61
57
-
H2N
R
NH2
(1.1
eq.)
N
N
iii)
or
80 °C, EtOH
CsCO3
K3PO4
KOH
H2O
,
CH2CH2
99%
3
7. R1
9. R3 o-Ph, 96%
=
=
yield
98%
yield
8. R2
=
1,2-Cy,
H2O
2 h
OAc
OH
Ac O
eq)
(1
2
EtOH
MeOH
ACN
THF
THF
15 min
15 min
24 h
O
O
Et N
3
eq)
(1.5
iv)
97%
yield
KOH
RT, EtOH, 1h
10
3
KOH
KOH
22 h
>99
>99
60
80
KOtBu
5 min
Scheme 4. Conversion of MCP into valuable biomass-based chemicals. : i)
MCP (2.2 mmol), RU-MACHO-BH (0.5 mol%), THF (10 mL), 10 bar H2, 100°C,
16h; ii) MCP (2.2 mmol), NaIO4 (6.6 mmol), H2O (10 ml), RT, 6h; iii) MCP (2.2
mmol), diamine (2.4 mmol), EtOH (5 mL), 80°C; iv) MCP (4.45 mml), Ac2O
(4.45 mmol), Et3N (6.79 mmol), EtOH (5 mL), RT
[a] Reaction conditions: HHD (0.4 mmol), base (0.6 mmol), solvent (2 mL),
60oC. [b] Determined by TLC.
OH
cat
ii) KOH
I
10 bar H
eq.)
mol%),
H
(1.5
30 min, 60 o H O
O
i)
(0.5
120 o H O
2
In conclusion, we have described a novel pathway for the
conversion of biomass-based 5-HMF into MCP via HHD. Aldol
condensation of HHD using inorganic bases led to MCP as sole
product. Both HHD and MCP were isolated and fully
characterized. We obtained MCP directly from 5-HMF in 55%
isolated yield. Finally, we demonstrated that MCP can be further
transformed into useful building blocks in excellent yields.
O
2
h,
C,
C,
2
2
OH
O
3
1
55
%
yield
Scheme 3. One-pot synthesis of MCP (3). Reaction conditions: i) 5-HMF (7.9
mmol), water (40 mL), cat (0.5 mol%), 120°C, 10 bar H2, 2h, ii) KOH (11.9
mmol), 60°C, 30 min.
Acknowledgements
We thank the Leibniz Foundation for financial support (SAW-
LIKAT-1 523).
Keywords: biomass • homogeneous catalysis • platform
chemical • renewable resources • cyclopentanone derivatives
Figure 3. ORTEP representation of MCP (3) showing intermolecular O-H…O
hydrogen bonds (for more details see Supporting Information). Displacement
ellipsoids correspond to 30% probability.
[1]
[2]
(a) Top Value-Added Chemicals from Biomass Vol. I—Results of
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So, naturally occurring MCP is a potential alternative to 5-HMF
for the production of 6.
Furthermore, α,β-unsaturated imines
7
and
8
and
quinoxaline derivative 9 were obtained in excellent yields by
°
addition of diamines to MCP in EtOH at 80 C (Scheme 4, iii).
Unsaturated imines were used in numerous studies related to C-
C and C-N bond formations,[27] and quinoxalines are important
pharmaceutical intermediates, based on their antiviral,
anticancer and antifungal properties.[28]
In another example, MCP was acetylated to the
corresponding enol acetate 10 in excellent yield (Scheme 4, iv).
This compound is of use in the synthesis of fragrances (e.g.
dihydrojasmone).[17]
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10.1002/cssc.201702100
ChemSusChem
COMMUNICATION
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ChemSusChem
COMMUNICATION
Layout 2:
COMMUNICATION
Bartosz Wozniak, Anke Spannenberg,
Yuehui Li, Sandra Hinze, Johannes G.
de Vries*
Page No. – Page No.
Cyclopentanone derivatives from 5-
hydroxymethylfurfural via 1-
hydroxyhexane-2,5-dione as
intermediate
Text for Table of Contents
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