Iron-based catalysts for the hydrogenation of esters to alcohols

Article abstract of DOI:10.1021/ja504034q

Hydrogenation of esters is vital to the chemical industry for the production of alcohols, especially fatty alcohols that find broad applications in consumer products. Current technologies for ester hydrogenation rely on either heterogeneous catalysts operating under extreme temperatures and pressures or homogeneous catalysts containing precious metals such as ruthenium and osmium. Here, we report the hydrogenation of esters under relatively mild conditions by employing an iron-based catalyst bearing a PNP-pincer ligand. This catalytic system is also effective for the conversion of coconut oil derived fatty acid methyl esters to detergent alcohols without adding any solvent.

Full text of DOI:10.1021/ja504034q

Communication
pubs.acs.org/JACS
Iron-Based Catalysts for the Hydrogenation of Esters to Alcohols
Sumit Chakraborty,†,§ Huiguang Dai,†,§ Papri Bhattacharya,† Neil T. Fairweather,*,‡ Michael S. Gibson,‡
Jeanette A. Krause,† and Hairong Guan*,†
†Department of Chemistry, University of Cincinnati, Cincinnati, Ohio 45221-0172, United States
‡Procter & Gamble Company, 11510 Reed Hartman Highway, Cincinnati, Ohio 45241, United States
S
* Supporting Information
substantially more reactive esters than those without a strongly
ABSTRACT: Hydrogenation of esters is vital to the
chemical industry for the production of alcohols, especially
fatty alcohols that find broad applications in consumer
products. Current technologies for ester hydrogenation
rely on either heterogeneous catalysts operating under
extreme temperatures and pressures or homogeneous
catalysts containing precious metals such as ruthenium and
osmium. Here, we report the hydrogenation of esters
under relatively mild conditions by employing an iron-
based catalyst bearing a PNP-pincer ligand. This catalytic
system is also effective for the conversion of coconut oil
derived fatty acid methyl esters to detergent alcohols
without adding any solvent.
electron-withdrawing group (e.g., methyl benzoate and fatty
acid methyl esters). Catalytic systems amenable to unactivated
esters, however, still suffered from extreme reaction con-
ditions.5,6 Major breakthroughs were made around 2006 by the
Milstein group7 and Firmenich SA,8,9 which independently
developed Ru-based catalysts for ester hydrogenation under
relatively low temperatures and pressures. The Milstein catalyst
features a pyridine-derived PNN-pincer ligand (Chart 1) and
Chart 1. Representative Homogeneous Catalysts for Ester
Hydrogenation
ydrogenation of esters is an industrially important
Hprocess and is used to manufacture alcohols on a
multimillion ton scale per annum for numerous applications.
Long-chain primary or fatty alcohols, in particular, are widely
used as precursors to surfactants, plasticizers, and solvents. In
2012, world consumption of fatty alcohols grew to 2.2 million
metric tons, and the global demand was projected to increase at
a compound annual growth rate of 3−4% from 2012 to 2020.1
Currently, about 50% of fatty alcohols are considered “natural
fatty alcohols” as they are produced through hydrogenation of
fatty acid methyl esters that are derived from coconut and palm
kernel oils, among other renewable materials. This process is
typically accomplished by using a heterogeneous catalyst mainly
consisting of copper chromite.2 While effective, the copper
chromite catalyst operates under very harsh reaction conditions
(250−300 °C and 2000−3000 psig of H2 pressure). As far as
energy costs for operation and capital costs for new capacity are
concerned, developing a homogeneous catalytic system for
ester hydrogenation is highly desirable because of its potential
to be effective under much milder conditions. Furthermore,
substrate compatibility or functional group tolerance is
expected to be higher with a homogeneous catalyst, and the
hydrogenation technology could be more broadly applied to
specialty chemical synthesis.
operates at 115 °C under 63 psig of H2 pressure. The
Firmenich catalysts contain bidentate amino-phosphine or
tetradentate imino-phosphine ligands and are effective at 60−
100 °C under 130−710 psig of H2 pressure. In both catalytic
systems, metal−ligand cooperativity was thought to be critical
for H2 activation and/or reduction of the ester CO bond.
Since these two studies, many other Ru- or Os-based catalysts
have been developed with the aim to improve catalyst
efficiency;10−27 these results have been thoroughly discussed
in recent reviews.28−30 One notable example is Takasago’s Ru-
MACHO catalyst, which was used to convert more than 2 t of
(R)-lactate to (R)-1,2-propanediol with the stereocenter
preserved.14 In this specific case, the hydrogenation reaction
was carried out at ambient temperature under 565−594 psig of
H2 pressure. It is also worth mentioning that an osmium PNP-
pincer complex developed by Gusev et al.31 was successfully
used to catalyze the hydrogenation of saturated triglycerides to
cetyl and stearyl alcohols at 220 °C under 935 psig of H2
pressure.32
The development of homogeneous catalysts capable of
hydrogenating esters has lagged way behind the research on
hydrogenation of other carbonyl substrates such as aldehydes
and ketones. This is mainly due to the fact that the carbonyl
group in esters is less electrophilic than that in aldehydes and
ketones. Studies prior to the early 2000s were primarily focused
on dimethyl oxalate3 and fluorinated esters,4 which are
Received: April 22, 2014
© XXXX American Chemical Society
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Despite the progress, almost all ester hydrogenation catalysts
developed to date contain a precious metal: ruthenium or
osmium. This is reminiscent of the early stage of catalyst design
for the hydrogenation of other unsaturated double bonds. In
recent years, significant effort has been made to develop various
reduction processes catalyzed by earth-abundant transition
metals.33 Within this context, iron has been a particularly
attractive choice of metal for catalysis due to its low cost and
low impact on the environment.34 In terms of hydrogenation of
esters to alcohols, we are aware of only one iron-based
homogeneous catalytic system, which contains a pyridine-
linked diphosphine ligand and was reported very recently by
Milstein et al.35 However, the substrates employed in this study
are limited to fluorinated esters, which are significantly
activated. In this paper, we report iron PNP-pincer complexes
as efficient catalysts for the hydrogenation of a much broader
range of esters. Most importantly, our catalytic system can be
applied to fatty acid methyl esters that are widely used in
industry and the reaction can be carried out without adding an
external solvent.
that another molecule was found in the unit cell being H-
bonded to a THF solvent molecule (Figure S2).
Complex 2 was first tested as an ester hydrogenation catalyst
using methyl benzoate as the substrate. Upon investigating a
variety of conditions (Table S2), it was determined that the
reaction was best carried out in toluene at 115 °C under 150
psig of H2 pressure. In the presence of 3 mol % of 2, a
quantitative conversion of methyl benzoate (∼1.4 M) to benzyl
alcohol was observed within 3 h, as judged by GC and NMR.
Complex 3 was also found to be an active catalyst, but 10 mol
% of KOtBu was needed as an additive and the reaction had to
be conducted in THF to ensure that KOtBu was fully dissolved.
In addition, despite a high conversion of methyl benzoate, the
GC yield for benzyl alcohol was merely 72%.38
Because complex 2 has the advantage of being an active
catalyst without an added base and because it leads to higher
selectivity for alcohol formation, we decided to focus on 2 for
studying the substrate scope of iron-catalyzed ester hydro-
genation reactions. As shown in Table 1, aromatic esters 4a−g
a
Given the success of Ru-MACHO and Gusev catalysts, we
sought to synthesize analogous iron pincer complexes 1−3
bearing a PNP-pincer ligand (Scheme 1). During the
Table 1. Hydrogenation of Esters Catalyzed by 2
Scheme 1. Synthesis of Iron PNP−Pincer Complexes
development of this project, Beller et al. also reported the
synthesis of these compounds but used them as catalysts for the
release of H2 from methanol.36 Meanwhile, Hazari, Schneider,
and co-workers prepared compound 2 from the PNP-pincer
ligand and FeCl2.37 In our laboratory, compounds 1−3 were
synthesized by slightly different procedures. The trans-dibromo
complex 1 was shown to react with excess NaBH4 in ethanol to
yield a hydridoborohydride complex 2. When the amount of
NaBH4 was reduced to 1 equiv with respect to 1, a
hydridobromide complex 3 was obtained as a mixture of syn
and anti isomers (defined by the relationship between NH and
FeH hydrogens), which is similar to what Beller et al. observed
for the reaction of 1 with NaHBEt3.36 We however found that
recrystallization of the isomeric mixture in toluene−pentane at
0 °C led to the isolation of only the anti isomer, as confirmed
by X-ray crystallography. The solid-state structure also revealed
3 being a dimer linked by N−H···Br hydrogen bonds (Figure
S5). Structural analysis of the dibromo complex 1 showed
similar H-bonding interactions between two molecules, except
a
General conditions for hydrogenation: 0.83 mmol of ester, 25 μmol
of 2 (3 mol % loading), 0.5 mL of toluene (or THF for 4g), 115 °C,
p(H2) = 150 or 230 psig. The numbers in the parentheses are reaction
time and isolated yield of RCH2OH.
were hydrogenated under 150 psig of H2 pressure, and the
corresponding alcohol products were isolated in high yield. The
catalytic system is compatible with functionalities including
CF3, MeO, and Cl groups. Ester 4e, which contains an electron-
donating MeO substituent at the para position of the aromatic
ring, was shown to react slowly, consistent with the less
electrophilic nature of the carbonyl group. The more
challenging aliphatic esters 4i−l were also hydrogenated
successfully, albeit requiring a higher H2 pressure (230 psig)
and a longer reaction time. For methyl cinnamate (4m), both
B
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CO and CC bonds were hydrogenated, leading to a fully
saturated alcohol. Hydrogenation of cinnamyl alcohol under
the same catalytic conditions gave 5m in 23% yield
(determined by NMR). Interestingly, the reaction of methyl
salicylate (4n) did not yield any product, perhaps due to the
acidic phenol hydrogen.
Scheme 2. Formation, Stability, and Catalytic Role of the
trans-Hydride Complex
Having established the catalytic utility of 2 in hydrogenating
esters that are commonly investigated in the literature, we
shifted our attention to an industrial sample, CE-1270, which is
derived from coconut oils and consists of methyl laurate (C12,
73%), methyl myristate (C14, 26%), and a small amount of
C10 and C16 methyl esters (∼1%).39 In our study, hydro-
genation of CE-1270 was carried out under neat conditions,
which would simplify separation, and the low boiling byproduct
methanol could be readily recycled for the manufacturing of
methyl esters from natural oils. At 135 °C under 750 psig of H2
pressure, when 2 was used as the catalyst (1 mol %), CE-1270
(typically 1.6−1.7 g) was fully converted in 3 h, producing a
mixture of fatty alcohols in a combined GC yield of 98.6%
(Table 2). Decreasing the hydrogen pressure to 300 psig led to
atmosphere, the in situ generated 7 (from 3 and KOtBu) was
converted to 6 in >90% yield without much decomposition.
Hydrogen transfer from 6 to an ester substrate RCO2R′ could
lead to 7, RCHO, and R′CH2OH, which may or may not
involve a hemiacetal intermediate RCH(OH)OR′. Further
reduction of RCHO to RCH2OH by 6 completes the overall
hydrogenation process. How exactly does the hydrogen transfer
from 6 occur, and whether or not the reduced product remains
coordinated to 7 are beyond the scope of this report, but they
are as important as the information on how 6 is initially formed
and regenerated and the extent of catalyst decomposition. The
catalyst loading, temperature, and hydrogen pressure men-
tioned earlier for the catalytic studies are likely to be a balance
struck among all these factors.
Table 2. Catalytic Hydrogenation of CE-1270
catalyst
(mol %)
additive
(mol %)
p(H2)
(psig)
time
(h)
alcohol yield
a
(%)
In conclusion, we have reported the first iron-based
homogeneous catalysts for the hydrogenation of unactivated
esters to alcohols. This catalyst system is not only applicable to
a variety of aromatic and aliphatic esters but also amenable to
industrial samples and can be performed under neat conditions.
In terms of catalytic efficiency, iron catalysts described herein
are comparable to many ruthenium catalysts, but not yet as
competitive as the most active ruthenium catalysts.8,9 Never-
theless, we have demonstrated the viability of using iron
catalysts for homogeneous hydrogenation of esters, and more
in-depth mechanistic studies are expected to lead to the
discovery of more efficient and practical catalysts.
2 (1.0)
2 (1.0)
2 (1.2)
1 (1.0)
3 (1.1)
none
750
300
750
750
750
3
3
1
6
3
98.6
72.6
96.2
0.8
none
none
NaOMe (2.0)
NaOMe (2.2)
b
52.2
a
b
Combined GC yield of all fatty alcohols. 23.3% fatty−fatty esters
present.
a lower yield of alcohols. The dibromo complex 1 proved to be
an inactive catalyst even in the presence of a base. In contrast,
hydridobromide complex 3, when combined with 2 equiv of
NaOMe, was found to be catalytically active. However, a
significant amount of fatty−fatty or wax esters2 was also
obtained. In an effort to scale up the hydrogenation process and
reduce the catalyst loading, 150 g of CE-1270 were mixed with
0.26 mol % of 3 and heated at 135 °C under 750 psig of H2
pressure. The combined yield of fatty alcohols reached the
maximum of ∼25% within 1 h (Table S3 and Figure S6),
suggesting that significant catalyst degradation had occurred. A
similar hydrogenation reaction carried out at 115 °C extended
the catalyst lifetime and improved the maximum alcohol yield
to 40%, thus giving a turnover number (TON) of 154 and an
initial turnover frequency (TOF) of 137 h−1 (for the first hour).
More detailed mechanistic studies of this catalytic system are
in progress. Based on the current understanding of related
ruthenium chemistry,7,9,12,19 we propose that the real catalyti-
cally active species is a trans-dihydride complex 6 (Scheme 2).
This compound was generated when a solution of 2 in toluene-
d8 was heated at 100 °C but quickly converted to 7 as a result of
losing H2. Alternatively, 6 could be produced from 2 at rt
through the trapping of BH3 by P(nBu)3. Under an argon
atmosphere, loss of H2 from 6 was observed even at rt, and
upon standing, the mixture of 6 and 7 eventually decomposed
to intractable species. However, under an H2 (∼1 atm)
ASSOCIATED CONTENT
* Supporting Information
Experimental details and crystallographic data for 1−3 (CIF
and PDF). This material is available free of charge via the
Internet at http://pubs.acs.org.
■
S
AUTHOR INFORMATION
Corresponding Authors
fairweather.nt@pg.com (N.T.F.)
hairong.guan@uc.edu (H.G.)
■
Author Contributions
§S.C. and H.D. contributed equally.
Notes
Portions of this work have been disclosed in a provisional
patent application with a serial number of 61/972927.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the Procter & Gamble Company and the Alfred P.
Sloan Foundation (research fellowship to H.G.) for financial
support. X-ray data were collected either on a Bruker
SMART6000 diffractometer (funded by an NSF-MRI grant;
C
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