Biorefinery via Achmatowicz Rearrangement: Synthesis of Pentane-1,2,5-triol from Furfuryl Alcohol

Article abstract of DOI:10.1002/cssc.201900601

A new scalable synthesis of pentane-1,2,5-triol from the furanics platform has been developed. Excellent yields of up to 92 % are obtained under flow conditions by using readily available catalysts from the existing pool. The strategy exploits the highly functionalized Achmatowicz product as a key intermediate, thus circumventing problems related to the low reactivity of the parent furfural and furfuryl alcohol. Besides expanding the portfolio of biomass-derived C₅ alcohols, this strategy may also be further applied for the establishment of a versatile bio-based chemical platform.

Full text of DOI:10.1002/cssc.201900601

Accepted Article
Title: Novel biorefinery concept via Achmatowicz rearrangement,
synthesis of pentane-1,2,5-triol from furfuryl alcohol
Authors: Svilen P. Simeonov, Martin Ravutsov, and Marko D
Mihovilovic
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10.1002/cssc.201900601
ChemSusChem
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Novel biorefinery concept via Achmatowicz rearrangement,
synthesis of pentane-1,2,5-triol from furfuryl alcohol
Svilen P. Simeonov,*[a] Martin A. Ravutsov[a] and Marko D. Mihovilovic[b]
Abstract: A new scalable synthesis of pentane-1,2,5-triol via
Achmatowicz rearrangement of furfuryl alcohol was
developed. Excellent yields of up to 91-92% were achieved
under flow conditions using readily available catalysts from
the existing pool. Our strategy is based on the use of the
harsh conditions with low selectivity.
In the early 70s Osman Achmatowicz
demonstrated the formation of 6-hydroxy-(2H)-pyran-
3(6H)-one 1 (Scheme 1) from the reaction of furfuryl
alcohol with Br2 in MeOH.4 Later on this
transformation was achieved in a single step under
oxidative conditions (Scheme 1).5 In contrast with its
precursors, the Achmatowizc product 1 is highly
functionalized, thus, herein is foreseen as an
intermediate to further extend the scope of the
furanics platform.
highly functionalized Achmatowicz product as
a key
intermediate, thus enabling to circumvent the low reactivity of
the parenting furfural and furfuryl alcohol. Therefore, beyond
the expansion of the portfolio of the biomass-derived C5
alcohols this strategy may be further applied for the
establishment of a versatile bio-based chemical platform.
Nowadays the biorefinery became into the
spotlight as a promising approach to replace the use
of fossil resources, which although cheap and easy to
obtain lack any sustainability. Among other primary
biorenewable building blocks, furfural and its
derivative furfuryl alcohol emerged as privileged
candidates due to their large availability from the
sugar platform.1 Moreover, their production from
lignocellulosic biomass is industrialized in multi
hundred tones. Both furfural and furfuryl alcohol are
important precursors for the manufacture of resins2
and biofuels.3 However, their relatively low
functionalization limits the scope of the direct synthetic
transformations, which are often accomplished under
Scheme 1. Achmatowizc rearrangement of furfuryl alcohol.
The Achmatowicz rearrangement was developed
through the years mainly as a tool for the fine organic
synthesis.6 Interestingly, this transformation has been
rarely considered as an approach for the production of
commodity chemicals. The logical explanation for this
observation is the lack of suitable synthetic methods
for industrial production, as the classical known
protocols require the use of toxic reagents and
stoichiometric expensive oxidants, such as m-CPBA,5
t-BuOOH/VO(acac)2,7 t-BuOOH/Ti(Oi-Pr)4/Diisopropyl
tartrate.8 However, several more recent reports
highlight the potential for upscale production, including
enzymatic9 and photochemical10 oxidation, Oxone11
and Ti/silicate catalysis (TS-1)/H2O2.12
[a]
[b]
Dr. S. P. Simeonov and M. A. Ravutsov
Institute of Organic Chemistry with Centre of Phytochemistry
Bulgarian Academy of Sciencies
Acad. G. Bontchev str. Bl. 9, 1113 Sofia, Bulgaria
E-mail: svilen@orgchm.bas.bg
Prof. Dr. M. D. Mihovilovic
The biomass derived alcohols are important
commodity chemicals. They are widely used as
monomers in the manufacture of polyesters,
polyurethanes, and polyethers, and additives in the
Institute of Applied Synthetic Chemistry, TU Wien,
Getreidemarkt 9/163, 1060 Wien, Austria
Supporting information for this article is given via a link at the
end of the document.
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10.1002/cssc.201900601
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fuel industry.13 The portfolio of biorenewable C5
alcohols available from the furanics platform includes
1,5-pentanediol14 and 1,2-pentanediol,15 which are
produced via challenging C-O bond cleavage
reactions,16 and 1,4-pentanediol derived from the
hydrogenation of γ-valerolactone.17 The synthesis of
pentane-1,2,5-triol (125PTO) has been rarely reported
albeit it is a homolog of the large-scale produced
butane-1,2,4-triol18 used as monomer,19 solvent and
precursor of the propellant 1,2,4-butanetriol trinitrate.20
To our knowledge, the current synthetic methods
include synthesis from glutamic acid21 and OsO4
dihydroxylation of the expensive 4-penten-1-ol22 or its
tosylate.23 More recently, Tomishige et al.24 reported
the synthesis of enantiopure 125PTO via two step
reduction of methyl β-L-arabinopyranoside. Several
recent papers describe the synthesis of 125PTO from
the furfural platfom (Scheme 2). Liu et al.25 reported
19% yield of 125PTO as a side product from the
hydrogenation of furfural to 1,2-pentanediol in
presence of Rh-Ir alloy. More recently Borgna et al.
detected low yeilds of 125PTO derived from the
hydrolysis of tetrarahydrofurfuryl alcohol (THFA) in the
course of the hydrogenolysis of the latter over Ni
catalysts.26 However, the synthesis of 125PTO from
the furanics platform still remains challenging and
suffers serious drawbacks due to the low selectivity of
the ring opening reactions (Scheme 2).
Scheme 2. Selected examples of 125PTO synthesis from the furfural
platfom.
focused our attention on the selective synthesis of the
intermediate 5-hydroxy-4-oxopentanal 2 (Scheme 3).
In addition, to our knowledge this is the first report on
the synthesis of 2, which can be also considered as a
versatile biorenewable building block. The reactions
were carried out under flow conditions using Thales
Nano H-cub Pro reactor (Table 1). As was expected,
10% Pd/C provided the product in excellent yield in
EtOH at 60°C and 1 mL/min flow rate (Table 1, entry
5). A slower reaction rate was observed in the non-
protic EtOAc. However, 100% yield was achieved at
60°C and 0.5 mL/min (Table 1, entry 4). Surprisingly
the less active Lindlar catalyst exhibited similar
performance as Pd/C and provided quantitative yields
(Table 1, entry 7), while Raney-Ni was completely
inactive.
Driven by the aforementioned considerations we
foresaw 1 as a more suitable intermediate, which may
allow to circumvent these drawbacks and showcase
the advantages provided by its rich chemistry.
Accordingly, herein we report the first high yield
synthesis of 125PTO based on a strategy that
involves only olefin and carbonyl hydrogenations that
can be selectively achieved in presence of readily
available catalysts (Scheme 2).
The NMR spectra of 5-hydroxy-4-oxopentanal in
CDCl3 showed the existence of an equilibrium
between two major forms, open 2 and closed 2’
(Scheme 3), together with other not determined more
complex associates, possibly hemiacetal self-
oligomers (see figure S5 and S6 in SI). As might be
expected, the equilibrium was influenced by the type
Taking advantage of the higher olefin vs carbonyl
reactivity in hydrogenation reactions, we have initially
1
of solvent. The H NMR spectra in DMSO-d6 showed
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10.1002/cssc.201900601
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predominant formation of complex associates (Figure
S7 in SI), while in ACN-d3 prevalent existence of the
open form 2 was detected (Figure S8 in SI). We
further acidified the ACN-d3 by the addition of a small
portion of 1N aq. HCl, which led to further shift
towards 2 (Figure S9 in SI), thus demonstrating that
the equilibrium and the occurrence of more complex
associates is pH dependent.
residence time resulted in an unsatisfactory yield of
only 27% from 1 (Table 2, entry 15). Furthermore, we
used the non-protic EtOAc as a solvent. However, no
125PTO formation from either 1 or 2 was detected at
100°C and 1 mL/min (Table 2, entry 16 and 17) and
only up to 10% yields were achieved from 2 at longer
residence times (Table 2, entry 18 and 19). We
observed that 125PTO exhibit limited solubility in
EtOAc, a possible cause for adsorption on the surface
of the catalyst and consequent inhibition. Therefore,
we used EtOAc/EtOH 80/20 mixture as a solvent and
were glad to observe significant improvement resulting
in up to 63% yield from 1 (Table 2, entry 20-22) and
up to 75% from 2 (Table 2, entry 23-26). Furthermore,
we observed that in EtOAc/EtOH (80/20) the
temperature had significant effect only over the
hydrogenation of 1 (Table 2, entry 20 vs 21), whereas
the hydrogenation of 2 led to similar outcome under
various conditions (Table 2, entry 23-27). 5% Ru/C
catalyst exhibited superior performance as compared
to Pt catalysts and provided up to 98% yield directly
from 1 at 50°C in EtOH, thus avoiding the use of more
complex solvent mixtures (Table 2, entry 28 and 29).
However, decreased yield of 90% was observed at
70°C (Table 2, entry 30), demonstrating that high
reaction temperatures have negative effect. Under the
optimized conditions, the reaction was scalable up to
0.05M (Table 2, entry 31 vs 32). Since we have
already recognized that higher temperatures have to
be avoided, we attempted to further scale up the
reaction by varying only the residence time and
pressure. However, these attempts were unsuccessful
(Table 2, entry 33 and 34). Considering that the olefin
reduction may be a rate determining step, as was
observed for PtO2 (Table 1, entry 20 vs 23), we further
studied the scalability of the hydrogenation of
intermediate 2 and were glad to achieve 97% yield at
Scheme 3. Synthesis of 5-hydroxy-4-oxopentanal.
Under batch conditions at 1 bar H2, 94% yield in
presence 10% Pd/C and 98% in presence of Lindlar
catalyst were achieved after 5h or 7h, respectively
(Table 1, entry 9 and 10).
Table 1. Synthesis of 2.a,b
Temp.
°C
rt
Flow
mL/min
1.0
0.8
0.5
0.5
1.0
1.0
1.0
Yield
%
30
45
85
>99
80
>99
>99
0
Catalyst
Solvent
1
2
3
4
5
6
7
8
9
10% Pd/C
10% Pd/C
10% Pd/C
10% Pd/C
10% Pd/C
10% Pd/C
Lindlar
Raney-Ni
10% Pd/C
Lindlar
EtOAc
EtOAc
EtOAc
EtOAc
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
rt
rt
60
rt
60
60
60
rt
1.0
5hc
94
98
10
rt
7hc
a
The flow experiments were performed using 70 mm
cartridge (approx. 700 mg catalyst) and 0.01M solution of 1. b
The flow experiments were performed at Full H2 mode of the
c
reactor, typically 5-8 bar.
(balloon).
Batch synthesis at 1 bar H2
With the optimized conditions for the synthesis of 2
in hand, we proceeded with the synthesis of 125PTO
starting either directly from the Achmatowicz product 1
or from the intermediate 2 (Table 2). To this end the
catalytic activity of readily available Pt or Ru catalysts
under flow conditions was studied. 10% and 5% Pt/C
catalysts were inactive under various conditions
(Table 2, entry 1-11). PtO2 catalyst provided only 10%
from 2 and 4% yield from 1 at 1 mL/min in EtOH
(Table 2, entry 12,13 and 14). The increased
0.1M
concentration
(Table
2,
entry
35).
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Table 2. Flow synthesis of 125PTO.a
Catalyst
Compound
Solvent
Molarity
Flow
mL/min
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
0.5
0.5
1.0
1.0
1.0
0.2
1.0
1.0
0.5
0.3
1.0
1.0
0.5
1.0
0.5
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
0.8
1.0
1.0
Temp.
°C
rt
rt
rt
50
Pressure
Yieldb,c
%
bar
6-9d
10
1
1
1
1
1
1
2
1
2
2
2
2
2
1
2
1
2
2
2
1
1
1
2
2
2
2
2
1
1
1
1
1
1
1
2
1
2
3
4
5
6
7
8
9
5% Pt/C
5% Pt/C
5% Pt/C
5% Pt/C
5% Pt/C
5% Pt/C
5% Pt/C
10% Pt/C
10% Pt/C
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOAc
EtOAc
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.05
0.1
0
0
0
0
0
0
0
0
50
6-9d
6-9d
50
100
100
100
100
100
100
100
50
100
100
100
100
100
100
100
80
100
100
80
100
80
100
100
rt
50
50
50
50
0
0
0
10 10% Pt/C
11 10% Pt/C
70
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
PtO2
PtO2
PtO2
PtO2
PtO2
PtO2
PtO2
PtO2
PtO2
PtO2
PtO2
PtO2
PtO2
PtO2
PtO2
PtO2
5% Ru/C
5% Ru/C
5% Ru/C
5% Ru/C
5% Ru/C
5% Ru/C
5% Ru/C
5% Ru/C
6-9d
6-9d
6-9d
6-9d
6-9d
6-9d
6-9d
6-9d
6-9d
6-9d
6-9d
6-9d
6-9d
10
traces
10
4
27
0
0
4
EtOAc
EtOAc
10
40
63
62
65
70
70
73
75
85
98
90
97
80
85
83
97
EtOAc/EtOHf
EtOAc/EtOHf
EtOAc/EtOHf
EtOAc/EtOHf
EtOAc/EtOHf
EtOAc/EtOHf
EtOAc/EtOHf
EtOAc/EtOHf
EtOH
10
20
6-9d
6-9d
6-9d
6-9d
6-9d
6-9d
20
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
50
70
50
50
50
50
50
0.1
0.1
0.1
6-9d
a All the experiments were performed using 70 mm catalyst cartridge (approx. 700 mg catalyst); b Determined by GC using borneol as
internal standard (Figure S2 in SI); Average from 3 reactions; Experiments were performed at uncontrolled pressure mode (Full
c
d
f
H2) of the Thales Nano H-cub Pro reactor and typically varies in the range of 6-9 bar;
EtOAc/EtOH (80/20).
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Table 3. Batch synthesis of pentane-1,2,5-triol from 2.
Surprisingly, as opposed to flow, under batch conditions
the hydrogenation of 2 in presence of 5% Ru/C was
unsuccessful at 1 bar H2 in EtOH (Table 3, entry 1 and 2).
The use of higher pressures led to unsatisfactory yields of up
to 5% (Table 3, entry 3 and 4). PtO2 catalyzed hydrogenation
in EtOH also didn’t provide satisfactory results and only up to
25% yield was achieved at 15 bar H2 (Table 3, entry 5 and
6). Furthermore, as was already observed under flow
conditions, the use of EtOAc led to inhibition of the catalysis
(Table 3, entry 7 and 8). 5% Ru/C was also inactive in
EtOAc/EtOH (80/20) mixture (Table 3, entry 9), whereas the
PtO2 catalyzed hydrogenation of 2 in the same solvent
allowed up to 89% yield at 15 bar H2 after 10h (Table 3, entry
10 and 11). Finally, 90% yield of 125PTO was achieved from
2 via a NaBH4 reduction (Table 3, entry 15).
Pressure
bar
1d
Yield
%
0
0
traces
<5
0
25
0
0
0
0
89
<10h
37h
33h
90j
Catalyst a
Solvent
Temp°C
c
1b 5%Ru/C
2b 5%Ru/C
3b 5%Ru/C
4b 5%Ru/C
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOAc
EtOAc
rt
50
50
50
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
1d
10e
30e
1d
5b
6b
7b
PtO2
PtO2
PtO2
15e
1d
8b 5%Ru/C
1d
9b 5%Ru/C EtOAc/EtOHf
1d
10b PtO2
11b PtO2
12g PtO2
13g PtO2
14g PtO2
15l none
EtOAc/EtOHf
EtOAc/EtOHf
EtOH
1d
15e
15e
15e
50e
NaBH4
EtOAc/EtOHf
EtOAc/EtOHf
MeOH
a 10%w catalyst loading; b 10h reaction time; c Determined by GC; Balloon;
d
e
Experiments were performed using stainless steel laboratory pressure reactor
(Buchiglasuster); f EtOAc/EtOH (80/20); g 3h reaction time; h Determined by 1H
NMR; l 1h reaction time; j isolated yield.
In order to explain these results, we acquired several
1HNMR spectra (in presence of di-Boc piperazine as internal
standard) of the crude reactions after different reaction times.
In presence of 5% Ru/C no significant hydrogenation of 2
was evident up to 10h at 1 bar H2 in both EtOH and
EtOAc/EtOH (80/20) (Figures S13 and S14 in SI), whereas
under the same conditions in presence of Pt2O partial
hydrogenation of the aldehyde to give the intermediate 1,5-
dihydroxypentan-2-one 3 (Figure 1; Figures S15 and S16 in
SI) was observed. However, further hydrogenation of the
ketone to form 125TPO did not occur in presence of PtO2 at
1 bar in both solvents. The formation of 125PTO was only
evident at 15 bar in presence of PtO2 and we observed that
as compared to pure EtOH the use of EtOH/EtOAc (20/80)
had positive effect on the catalytic activity, leading to
accelerated formation of intermediate 3 (Figure 1; Figures
S17-S19 in SI) and 125PTO (Table 3, entry 12 vs 13). These
results indicate that PtO2 is indeed the more active catalyst,
whereas 5% Ru/C is only active at the very high catalyst to
starting material ratios and the intense mixing with H2
achievable only under flow conditions. However, it’s worth
mention that due to the absence of inert support in reality the
amount of active catalytic sites is higher for PtO2 as
compared to 5% Ru/C under the same w/w % catalyst
loading, which may be a possible cause for the observed
behavior. Finally, we also observed that pressures above 15
bar were not beneficial for the formation of 125PTO (Table 3,
entry 13 vs 14).
Figure 1. 1H NMR (600 MHz, ACN-d3) of the batch hydrogenation at 15 bar H2
after 3h. A) EtOH; B). EtOAc/EtOH (80/20); (Figure S19 in SI)
Furthermore, we turn our attention to the development of
a continuous process for 125PTO production. To this end,
we applied the method described by Wahlen et al.12 using
simple TS-1/H2O2 system, which to our knowledge is
currently one of the best to achieve high yield Achmatowicz
rearrangement of furfuryl alcohol. Moreover, TS-1 catalyst
allows easy packing into a cartridge and operation under flow
conditions.
Initially, we performed the Achmatowicz rearrangement
of furfuryl alcohol under batch conditions. After 3.5h at 40°C
in acetonitrile, we achieved 95% yield, which was similar to
the 93% reported by Wahlen et al. However, acetonitrile
cannot be considered
a suitable solvent for further
hydrogenation reactions. With the idea to directly use the
reaction mixture after simple removal of the TS-1 catalyst or
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10.1002/cssc.201900601
ChemSusChem
in a single stream flow process, we studied EtOH and
EtOAc/EtOH 80/20 as solvents. In EtOAc/EtOH 80/20 under
batch conditions, we achieved 1 in 94% isolated yield after
4h at 40°C. As reported by Wahlen et al.12 the reaction was
slower in pure protic solvents. Full conversion of furfuryl
alcohol in EtOH was achieved only after 14h at 40°C and led
to a 92% isolated yield. However, we successfully overcame
this drawback under flow conditions using Thales Nano H-
cube Pro reactor. TS-1 catalyst was packed in a 70 mm
cartridge and 0.1M solution of furfuryl alcohol containing 1.2
equiv. 30% aq. H2O2 was passed through. Full conversion of
the furfuryl alcohol was achieved at 0.5 mL/min flow rate and
40°C providing 93% isolated yield of 1 (Scheme 4). The
purity of the isolated crude product was suitable (above 95%
by GC) for direct use without additional purification.
However, higher purity (>99% by GC) can be achieved by
simple crystallization of 1 from isopropanol/hexane as
reported by Benkovics et al.27
Scheme 5. Continuous synthesis of 125PTO.
In summary, we reported the first high yield synthesis of
pentane-1,2,5-triol from the furanics platform. Up to 91%
isolated yield from furfuryl alcohol at 0.1M concentration has
been achieved in a 3 steps continuous process. Our strategy
was based on the hydrogenation of olefin and carbonyl
functionalities of Achmatowicz rearrangement product thus
allowing to circumvent catalytically challenging C-O bonds
cleavage reactions and consequently enabled the use of
readily available catalysts and mild conditions.
Apart from upgrading the portfolio of biomass-derived C5
alcohols, our studies showcased the potential of the
Achmatowicz rearrangement as
a
key step for the
biorefinery. Further studies in this line are currently ongoing
in our laboratory.
Experimental section
Scheme 4. Batch and flow Achmatowizc rearrangement of furfuryl
alcohol.
General: Unless stated otherwise, all reagents were
purchased from Sigma-Aldrich and Acros and were used
without further purification. Furfuryl alcohol - F19906 Aldrich,
PtO2 (80% Pt) - Fluka, Lindlar catalyst - Acros 19507-0100,
5% Ru/C - 206180 Aldrich, 5% Pd/C - 205680 Aldrich. NMR
spectra were recorded on Bruker MX300 operating at 300
MHz and Bruker Avance II+ 600 (1H at 600.13 MHz; 13C at
150.92 MHz) spectrometers. Yields were determined by GC
using Shimadzu GC-17A equipped with flame ionization
detector (FID) or Thermo Scientific Focus GC/FID. The flow
hydrogenations were carried out using Thales Nano H-cube
Pro Continuous Flow Hydrogenation Reactor equiped with
Gilson GX271 Autosampler. High preasure batch
hydrogenations were carried out using Buchiglasuster
300°C/100 bar stainless steel laboratory pressure reactor
system (Figure S1 in SI).
With optimized conditions for the flow synthesis of 1 and
125PTO in hand, we developed a continuous process using
Thales Nano H-cube Pro reactor. The synthesis of 125PTO
was achieved in 92% isolated yield when a mixture of 1.2
equv. H2O2 and 0.05M EtOH solution of furfuryl alcohol was
subsequently passed through TS-1 and 5%Ru/C catalyst at
0.5 mL/min. The process was further scaled up to 0.1M using
3 step protocol. By this approach, 125PTO was achieved in
91% via subsequent use of TS-1, Lindlar and 5% Ru/C
catalysts (Scheme 5).
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Synthesis of TS-1 catalyst: TS-1 was prepared according
to the procedure described by Romano et al.28 with
modifications. Tetraisopropyl orthotitanate (0.93 g) and of
tetraethyl orthosilicate (22.5 g) were dissolved in 50 mL 20
wt% aqueous solution of tetrapropylammonium hydroxide
(TPAOH) under vigorous stirring. The resulting mixture was
kept at 60°C for 3h. The final molar ratios in the solution
were: SiO2/TiO2 = 32.7, TPAOH/SiO2 = 0.46, H20/SiO2 = 35.
The mixture was transfered to a stainless steel autoclave
and heated in an oven at 175°C, under autogenous
pressure, in static conditions for 24h. After cooling to room
temperature, the crystalline product was filtered, washed
several times with water, dried at 100°C for 2h, and finally
calcined at 550°C in air for 5h.
hydroxy-(2H)-pyran-3(6H)-one, 1.07 g (94%) as pale yellow
oil that crystallizes in freezer (-12°C). The product was
recrystallized from hexane/i-PrOH to give the pure final
product (1 g, 89%) as white crystalline solid.
C) 25 mL round-bottom flask was charged with freshly
distilled furfuryl alcohol (980 mg, 10 mmol) and 10 mL EtOH,
TS-1 (100 mg) and 1.5 mL (12 mmol) 30% aq. H2O2were
added and the reaction mixture was stirred at 40°C. After
14h furfuryl alcohol was fully consumed by TLC (EtOAc/PE
1:1). The reaction mixture was cooled down and filtered
through a pad of Celite. The solvent was evaporated; the
crude was dissolved in DCM and dried over MgSO4. The
solvent was evaporated to give crude 6-hydroxy-(2H)-pyran-
3(6H)-one 1.04 g (92%) as pale yellow oil that crystallizes in
the freezer (0°C). The product was recrystallized from
hexane/i-PrOH to give the pure final product (0.97 g, 86%)
as white crystalline solid.
Batch synthesis of 6-hydroxy-(2H)-pyran-3(6H)-one 1.
A) 25 mL round-bottom flask was charged with freshly
distilled furfuryl alcohol (980 mg, 10 mmol) and 10 mL
acetonitrile. TS-1 (100 mg) and 1.5 mL (12 mmol) 30% aq.
H2O2 were added and the reaction mixture was stirred at
40°C. After 3.5h furfuryl alcohol was fully consumed by TLC
(EtOAc/PE 1:1). The reaction mixture was cooled down and
filtered through a pad of celite. The solvent was evaporated
and the crude was dissolved in DCM and dried over MgSO4.
The solvent was evaporated to give crude 6-hydroxy-(2H)-
pyran-3(6H)-one, 1.07 g (94%) as pale yellow oil that
crystallizes in the freezer (−12°C). The product was
recrystallized from hexane/i-PrOH2 to give the pure final
Flow synthesis of 1 – TS1 catalyst was packed in a sealed
70 mm cartridge (approx. 400 mg catalyst) using Thales
Nano CatCart Packer and connected to ThalesNano H-Cube
reactor. The H2 production was switched off and pure EtOH
was passed through the cartridge for 15 min at 0.5 mL/min
then 50 mL 0.5M solution of freshly distilled furfuryl alcohol in
EtOH containing 1.2 eqiuv. 30% H2O2 was continuously
passed through the cartridge at 0.5 mL/min and 40°C and
collected. The solvent was evaporated to give 2.65 g (93%)
of 6-hydroxy-(2H)-pyran-3(6H)-one as pale yellow oil that
crystallizes in the freezer (0°C). The purity of the crude
product was determined to be 95% by GC.
1
product (1 g, 89%) as white crystalline solid. H NMR (600
MHz, CDCl3) δ 6.98 (dd, J = 10.3, 2.9 Hz, 1H), 6.18 (d, J =
10.4 Hz, 1H), 5.64 (d, J = 2.7 Hz, 1H), 4.58 (d, J = 16.9 Hz,
1H), 4.15 (d, J = 16.9 Hz, 1H), 3.80 (s, 1H). 13C NMR (151
MHz, CDCl3) δ 194.82, 145.97, 127.86, 88.18, 66.58.
(Figures S3 and S4 in SI)
Flow synthesis of 5-hydroxy-4-oxopentanal 2 – Lindlar or
10% Pd/C catalyst were packed in a sealed 70 mm
cartridges (approx. 700 mg of catalyst) using Thales Nano
CatCart Packer. The hydrogenations were performed using
ThalesNano H-Cube reactor. Before each experiment, the
catalysts were pretreated for 15 min at Full H2 mode and 1
mL/min pure solvent. Then 5 mL 0.1M solution of 1 in the
corresponding solvent was passed through the cartridge at
Full H2 mode (5-9 bar) and collected using Gilson GX271
Autosampler. (Table 1)
B) 25 mL round-bottom flask was charged with freshly
distilled furfuryl alcohol (980 mg, 10 mmol) and 10 mL
EtOAc/EtOH (80/20). TS-1 (100 mg) and 1.5 mL (12 mmol)
30% aq. H2O2 were added and the reaction mixture was
stirred at 40°C. After 4h furfuryl alcohol was fully consumed
by TLC (EtOAc/PE 1:1). The reaction mixture was cooled
down and filtered through a pad of Celite. The solvent was
evaporated and the crude was dissolved in DCM and dried
over MgSO4. The solvent was evaporated to give crude 6-
Batch synthesis of 5-hydroxy-4-oxopentanal 2 – 50 mL
two-necked round-bottom flask was charged with 6-hydroxy-
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COMMUNICATION
10.1002/cssc.201900601
ChemSusChem
(2H)-pyran-3(6H)-one 1 (1 g, 8.7 mmol), 20 mL of EtOH and
100 mg of Lindar catalyst or 10% Pd/C. The atmosphere was
changed to H2 (balloon) and the reaction was stirred at rt for
5h in presence of 5% Pd/C or 7h in presence of Lindlar
catalyst. Then the reaction mixture was filtered through a pad
of Celite and the solvent was evaporated to give 1 g (98%) of
chromatography (EtOAc/MeOH 80/20) to give pentane-1,2,5-
triol as a colorless oil, 1.08 g (90%).
Continuous synthesis of pentane 1,2,5-triol from furfuryl
alcohol
Method A (2 steps) TS-1 and 5% Ru/C catalysts were
packed in sealed 70 mm cartridges using Thales Nano
CatCart Packer. The cartridge containing TS-1 was attached
to Thales Nano H-Cube reactor. The H2 production was
switched off and pure EtOH was passed through the
cartridge for 15 min at 0.5 mL/min. Then 50 mL 0.05M
solution of freshly distilled furfuryl alcohol in EtOH containing
1.2 eqiuv. 30% H2O2 was continuously passed through the
cartridge at 0.5 mL/min and 40°C and collected. The TS-1
cartridge was replaced with the 5% Ru/C cartridge and the
catalyst was pretreated for 15 min at Full H2 mode and 1
mL/min EtOH. Then the collected solution was continuously
passed through at 1 mL/min, 50°C, Full H2 mode. The
solvent was evaporated to give 276 mg (92%) of pentane-
1,2,5-triol as a colorless oil.
1
2 as pale yellow oil. 5-hydroxy-4-oxopentanal H NMR (300
MHz, CDCl3) δ 9.78 (s, 1H), 4.33 (s, 2H), 2.91 – 2.83 (m,
2H), 2.67 (t, J = 6.4 Hz, 2H), 13C NMR (75 MHz, CDCl3) δ
208.10, 200.02, 68.21, 37.37, 30.39 (Figures S5 and S6 in
SI).
Flow synthesis of pentane-1,2,5-triol – The catalysts were
packed in sealed 70 mm cartridges (approx. 700 mg of
catalyst) using Thales Nano CatCart Packer. The
hydrogenations were performed using ThalesNano H-Cube
reactor. Before each experiment, the catalysts were
pretreated for 15 min at Full H2 mode and 1 mL/min pure
solvent. Then 5 mL solution of compound 1 or 2 containing
borneol as an internal standard was passed through the
cartridge and collected using Gilson GX271 Autosampler.
The yields were determined by GC (Table 1).
Method B (3 steps) TS-1, Lindlar, and 5% Ru/C catalysts
were packed in sealed 70 mm cartridges using Thales Nano
CatCart Packer. The cartridge containing TS-1 was attached
to ThalesNano H-Cube reactor. The H2 production was
switched off and pure EtOH was passed through the
cartridge for 15 min at 0.5 mL/min. Then 50 mL 0.1M solution
of freshly distilled furfuryl alcohol in EtOH containing 1.2
eqiuv. 30% H2O2 was continuously passed through the
cartridge at 0.5 mL/min and 40°C and collected. The TS-1
cartridge was replaced with the Lindlar cartridge and the
catalyst was pretreated for 15 min at Full H2 mode and 1
mL/min EtOH. Then the collected solution was continuously
passed through at 1 mL/min, 50°C, Full H2 mode and
collected. The Lindlar cartridge was replaced with the 5%
Ru/C cartridge and the catalyst was pretreated for 15 min at
Full H2 mode and 1 mL/min EtOH. Then the second collected
solution was continuously passed through at 1 mL/min, 50°C,
Full H2 mode. The solvent was evaporated to give 546 mg
Batch synthesis of pentane 1,2,5-triol
Method A: 100 mL 2 neck round bottom flask was charged
with 20 mL 0.1M solution of 2 in the corresponding solvent
and 10% w/w of the catalyst. The atmosphere was changed
to H2 (ballon) and the reaction mixture was stirred for 10h at
the corresponding temperature. The yields were determined
by GC using borneol as an internal standard.
Method B: Stainless steel Laboratory pressure reactor
system (Figure S1 in SI) was charged with 20 mL 0.1M
solution of 2 in the corresponding solvent and 10% w/w of
the catalyst. The atmosphere was changed to H2 and the
pressure adjusted to the corresponding value. The reaction
mixture was stirred at the corresponding temperature for
10h. The yields were determined by GC using borneol as an
internal standard.
Method C: 50 mL round bottom flask was charged with 2
(1.16 g, 10 mmol) and 25 mL MeOH. The reaction mixture
was cooled down to 0°C (ice bath) and NaBH4 (2 g, 50 mmol)
was carefully added. The reaction mixture was allowed to
warm up to rt and stirred for 1h. Then the mixture was filtered
through a pad of Celite concentrated and purified by column
1
(91%) of pentane-1,2,5 triol as a colorless oil. H NMR (400
MHz, D2O) δ 3.7-3.64 (m, 1H), 3.64 – 3.49 (m, 3H), 3.46 –
3.42 (m, 1H), 1.68 – 1.47 (m, 3H), 1.44 – 1.34 (m, 1H). 13C
NMR (63 MHz, D2O) δ 71.75, 65.56, 61.80, 28.92, 27.66
(Figures S10 and S11 in SI).
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COMMUNICATION
10.1002/cssc.201900601
ChemSusChem
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Acknowledgments
The authors acknowledge National Science Fund of Bulgaria
(grant КП-06-OПР-01/2) and PhosAgro/UNESCO/IUPAC,
2015 Green Chemistry for Life Grant for the financial
support. The authors would also like to thank Dr. Yavor
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Keywords: Pentane-1,2,5-triol biorefinery • Achmatowicz
rearrangement • furfuryl alcohol • continuous production •
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10.1002/cssc.201900601
ChemSusChem
COMMUNICATION
Entry for the Table of Contents
COMMUNICATION
New
biorefinery
concept
based
on
Svilen P. Simeonov*, Martin A. Ravutsov
and Marko D. Mihovilovic
Achmatowicz rearrangement as a key step
was developed. This approach allowed the
synthesis of pentane-1,2,5-triol in excellent
yields under environmental and scalable flow
and batch conditions using readily available
catalysts. Furthermore, our studies uncover
the potential of the Achmatowicz product to
serve as a biorenewable platform molecule.
Page No. – Page No.
Novel
biorefinery
concept
via
Achmatowicz
rearrangement,
synthesis of pentane-1,2,5-triol from
furfuryl alcohol
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