Towards a green process for bulk-scale synthesis of ethyl acetate: Efficient acceptorless dehydrogenation of ethanol

Article abstract of DOI:10.1002/anie.201200625

Green is a go: An efficient acceptorless dehydrogenative dimerization of ethanol to give ethyl acetate was realized (see scheme). The reaction proceeds under mild reaction conditions in the presence of a ruthenium catalyst with concomitant liberation of molecular hydrogen, which can be used as a valuable product itself. At low catalyst loading (50 ppm), high yields of ethyl acetate and excellent catalyst turnover numbers are achieved. Copyright

Full text of DOI:10.1002/anie.201200625

Angewandte
Chemie
DOI: 10.1002/anie.201200625
Homogeneous Catalysis
Towards a Green Process for Bulk-Scale Synthesis of Ethyl Acetate:
Efficient Acceptorless Dehydrogenation of Ethanol**
Martin Nielsen, Henrik Junge, Anja Kammer, and Matthias Beller*
In 2008, the world market for ethyl acetate was estimated to
be 2.5 million tons per annum.[1] This industrially, highly
important intermediate is one of the major derivatives of
acetic acid.[2] Apart from being used as solvent it is an
important intermediate in the food industry, and for various
customer applications such as glues, inks, and perfumes.
Today, its manufacture mainly relies on three procedures:
a) the Fischer esterification reaction of acetic acid,[3] b) the
Tishchenko reaction by combination of two acetaldehyde
molecules,[4] and c) the addition of acetic acid to ethylene.[5]
All these processes use petrochemical feedstocks derived
primarily from fossil fuels, a limited and intrinsically polluting
supply.[6]
In contrast, ethanol—an inexpensive starting material for
ethyl acetate—is easily accessed from biomass and represents
an important renewable building block.[7] Obviously, the
development of novel catalytic processes employing such
renewable resources constitutes a key tool towards more
sustainable production and the advancement of green
chemistry. In fact, the valorization of bioethanol to a range
of bulk intermediates including polymers is currently being
intensively investigated.[7,8]
Based on our general interest in hydrogen production
from alcohols,[9] and formic acid,[10] we were intrigued by the
idea of synthesizing ethyl acetate by acceptorless dehydro-
genative coupling directly from ethanol. To date, the accep-
torless dehydrogenative synthesis of ethyl acetate from
ethanol has been largely studied by using heterogeneous
catalysts[11] with a special focus on copper-based catalysts.[11a–c]
In general, this reaction requires high temperatures
(> 2008C) and significant energy input, and it tends to lead
to moderate selectivity. Hence, yields up to only 56% have
been achieved. In contrast, despite the recent advancements
in homogeneously catalyzed dehydrogenation reactions of
both primary and secondary alcohols,[9,12] limited progress has
been observed with ethanol as a substrate.[9,12a,b] To the best of
our knowledge, no reports on preparative acceptorless
dehydrogenation of ethanol to form ethyl acetate exist.
Obviously, applying known hydrogen acceptors to facilitate
the reaction inherently results in low atom economy and
waste formation. Thus, regarding cost and sustainability such
procedures are not applicable on a larger scale. Therefore,
developing a catalyst system capable of transforming ethanol
into ethyl acetate under acceptorless and neat conditions is
a major challenge.
Herein, we show that the ruthenium-based PNP pincer
catalyst 1 (see Table 1 for structure) efficiently catalyzes the
direct formation of ethyl acetate from ethanol. Notably,
neither solvent nor additional hydrogen acceptors are
employed in this green procedure.
Recently, pincer complexes have been proven to be highly
efficient catalysts for acceptorless dehydrogenation of alco-
hols.[13,14] We therefore turned our attention to this type of
complex. At the start of our investigations a selection of
various ruthenium and iridium pincer complexes were tested
for their activities in the target reaction (Table 1). Notably, in
our system mild reaction conditions with refluxing ethanol in
an open system are employed. This is a considerably lower
reaction temperature compared to all known acceptorless
dehydrogenations of other alcohols.
We were pleased to find that the HPNPPh/Ru complex 1[9]
showed high activity with a turnover frequency (TOF) of
1134 hÀ1 (Table 1, entry 1). The catalyst 2,[12m] reported by
Table 1: Acceptorless dehydrogenation of ethanol to give ethyl acetate.[a]
Entry
Catalyst
TOF [hÀ1 [b]
]
1
2
3
4
5
6
1
2
3
4
5
6
1134
<100
1107
898
<100
<100
[*] Dr. M. Nielsen, Dr. H. Junge, A. Kammer, Prof. Dr. M. Beller
Leibniz-Institut fꢀr Katalyse e.V. an der Universitꢁt Rostock
Albert-Einstein-Strasse 29a, 18059 Rostock (Germany)
E-mail: matthias.beller@catalysis.de
Homepage: http://www.catalysis.de
[**] M.N. thanks the Alexander von Humboldt Foundation for financial
support.
[a] Performed with indicated catalyst (1–6; 25 ppm, 4.2 mmol) and
NaOEt (1.3 mol%, 2.2 mmol) in refluxing EtOH (10 mL, 171.3 mmol),
with an internal standard (1 mL hexadecane). [b] Determined by burette
measurements after 2 h of reaction time.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201200649.
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Milstein and co-workers, unfortunately showed no activity for
this transformation under the given reaction conditions
(entry 2). To the contrary, the in situ system 3,[9] comprising
an HPNPiPr ligand coordinated to a RuH2-type structure,
TOF(10 h) of 730 hÀ1 (see the Supporting Information). This
diminished activity is probably due to the exhaustion of
ethanol during the reaction course. Apparently, ethyl acetate
formation does not impede the reaction nor does the catalyst
seem to be considerably deactivated over time.
showed an activity similar to that of 1. Barattaꢀs catalyst[15]
4
also showed decent activity, however at a lower level than that
of 1 and 3 (entry 4 versus entries 1 and 3). In addition, we
tested two iridium complexes in the target reaction. However,
both the Nozaki catalyst[16] 5 and the HPNPiPr-based Gusev–
Abdur–Rashid complex[17] 6 unfortunately led to very little
conversion (entries 5 and 6, respectively). These results
suggest that utilizing aliphatic PNP pincer ligands on a ruthe-
nium-based system is required to achieve significant catalytic
activity in this reaction. Having two equally active catalysts,
1 and 3, in hand, we continued our investigations with the
commercially available complex 1.
Performing the reaction with 1-octanol instead of ethanol
shows that other alcohols are applicable in this dehydrogen-
ative esterification as well (Scheme 1a). Thus, the catalyst
TOF is only lower by a factor of 1.5 for 1-octanol compared to
that of ethanol under the same reaction conditions. This is
expected because of a lower hydroxy/carbon chain ratio in 1-
octanol.
After testing a series of different base additives (see
Table SI3 in the Supporting Information), NaOEt was
identified to be the optimal choice, thus leading to the
highest turnover frequency. Within the range of 0.3–3.2 mol%
NaOEt, similar activity is observed (see Table SI4). From
a practical point of view it is important to note that the
catalyst activity proved to be steady over at least a 10 hour
reaction period and with up to approximately 90% conver-
sion (see Tables and Figures SI5-6).
Next, we turned out attention to improving the yield for
ethyl acetate and the catalyst turnover numbers (TON).
Table 2 summarizes the results collected by varying the
catalyst loading and temperature, and conducting the reaction
Scheme 1. a) Acceptorless dehydrogenation of 1-octanol to give the
corresponding ester. b) Coupling of octanal and ethanol.
From a mechanistic point of view it is important to note
that applying the same reaction conditions on equivalent
amounts of octanal and ethanol led to no formation of either
ethyl octanate or ethyl acetate (Scheme 1b). In agreement
with this observation no hydrogen evolution is obtained. In
fact, only products arising from the aldol condensation of
octanal were observed by in situ 1H NMR spectroscopy.
Apparently, the presence of large amounts of aldehyde
inhibits the catalyst. These experiments suggest that the
concentration of “free” aldehyde should be kept at a mini-
mum during the reaction course of acetate formation. This is
also in agreement with the data of the 1H NMR spectra of the
crude reaction mixture for the ethanol to ethyl acetate
reaction (see 1H NMR spectra SI7-9 in the Supporting
Information). During the entire reaction course, neither
acetaldehyde nor its aldol condensation product (croton
aldehyde) was observed. Therefore, the formation of ethyl
acetate by a Tishchenko-type reaction can be clearly ruled
out. Furthermore, this observation suggests that the rate-
determining step of the process is the initial dehydrogenation
step.
Table 2: Acceptorless dehydrogenation of ethanol catalyzed by 1 to give
ethyl acetate.[a]
Entry
1 (ppm)
NaOEt (mol%)
T [8C][b]
Yield [%][c]
TON
1620
1400
15400
1
2
3
500
500
50
1.3
1.3
0.6
90
70
90
81
70
77
[a] Performed with catalyst 1 (amount given in Table 2) and NaOEt
(amount given in Table 2) in EtOH (10 mL, 171.3 mmol) with an internal
standard (1 mL hexadecane). An oil trap was employed immediately after
the condenser. All reactions were conducted until gas evolution had
ceased (6 h in entry 1, 24 h in entry 2, 46 h in entry 3). [b] Applied
temperature. [c] Determined by GC.
until gas evolution had ceased. Increasing the catalyst loading
from 25 to 500 ppm, and conducting the reaction until gas
evolution ceased led to 81% yield of ethyl acetate with a TON
of 1620 and a TOF, after 2 h, of 498 hÀ1. An attempt to lower
the reaction temperature resulted in a slightly lower yield and
TON (70% and 1400, respectively). Nevertheless, this
example demonstrates that the reaction can be performed
even at temperatures below that of reflux, and the catalyst is
active even at 608C, albeit at a lower rate (see the Supporting
Information). To the best of our knowledge, this is the first
example of acceptorless dehydrogenation of ethanol.
Notably, during their studies on the synthesis of amides
from alcohols and amines, Madsen and co-workers suggested
that the initially formed aldehyde stays coordinated to the
metal complex.[12d,17] However, in their system dehydrogen-
ation of the alcohol is still observed even in the presence of
large amounts of aldehyde, albeit at a lower rate.
Finally, employing only 50 ppm of 1 led to a high yield of
ethyl acetate with a TON of 15400. The TOF of the active
catalyst species is almost constant for the first 10 hours of the
reaction with an overall TOF(2 h) of 934 hÀ1 and overall
As the presence of aldehyde completely blocks any
dehydrogenation activity in our system, the Madsen mecha-
nistic proposal may not be applied here. The fact that the
amount of NaOEt is crucial for maintaining a steady catalyst
2
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Based on these observations, we propose the reaction
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Scheme 2. Proposed mechanism for the acceptorless dehydrogenation
of ethanol to give ethyl acetate.
hydrogen is released from the ruthenium center (step b). The
formed acetaldehyde likely stays in the vicinity of the catalyst,
or is even coordinated to the metal center, when another
molecule of ethanol attacks the aldehyde to form a hemiacetal
(step c). Probably, an ethoxide anion is responsible for this
attack, thus leading to an anionic hemiacetal. Finally, a second
b-hydride elimination step leads to ethyl acetate (step d) and
the catalyst is regenerated after hydrogen release.
In conclusion, we have developed the first catalytic
acceptorless dehydrogenation of ethanol to ethyl acetate.
This industrially important reaction allows a cost-efficient
synthesis of ethyl acetate which produces hydrogen as an
additional value-generating product. Applying catalyst load-
ings in the ppm range led to a high yield of ethyl acetate with
a TONs exceeding 15000. In addition, we show that other
primary alcohols are converted into their corresponding
esters as well. This report constitutes an important example
of using renewable feedstocks for more benign production of
bulk chemicals.
Received: January 23, 2012
Published online: && &&, &&&&
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Keywords: alcohols · green chemistry · homogeneous catalysis ·
renewable resources · ruthenium
.
[1] ICIS Chemical Business (ICB), see www.icis.com.
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Angewandte
Communications
Communications
Homogeneous Catalysis
Green is a go: An efficient acceptorless
dehydrogenative dimerization of ethanol
to give ethyl acetate was realized (see
scheme). The reaction proceeds under
mild reaction conditions in the presence
of a ruthenium catalyst with concomitant
liberation of molecular hydrogen, which
can be used as a valuable product itself.
At low catalyst loading (50 ppm), high
yields of ethyl acetate and excellent
M. Nielsen, H. Junge, A. Kammer,
M. Beller*
&&&& — &&&&
Towards a Green Process for Bulk-Scale
Synthesis of Ethyl Acetate: Efficient
Acceptorless Dehydrogenation of Ethanol
catalyst turnover numbers are achieved.
4
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Angew. Chem. Int. Ed. 2012, 51, 1 – 4
These are not the final page numbers!