Upgrading ethanol to 1-butanol with a homogeneous air-stable ruthenium catalyst

Article abstract of DOI:10.1039/c5cc09913g

An amide-derived N,N,N-Ru(ii) complex catalyzes the conversion of EtOH to 1-BuOH with high activity. Conversion to alcohol upgraded products exceeds 250 turnovers per hour (>50% conversion) with 0.1 mol% catalyst loading. In addition to high activity for ethanol upgrading, catalytic reactions can be set up under ambient conditions with no loss in activity.

Full text of DOI:10.1039/c5cc09913g

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Upgrading Ethanol to 1‐Butanol with a Homogeneous Air‐Stable
Ruthenium Catalyst
Kuei‐Nin T. Tseng, Steve Lin, Jeff W. Kampf and Nathaniel K. Szymczak*
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/chemcomm
An amide‐derived N,N,N‐Ru(II) complex catalyzes the
conversion of EtOH to 1‐BuOH with high selectivity. Conversion
to alcohol upgraded products exceeds 250 turnovers per hour
(>50% conversion) with 0.1 mol% catalyst loading. In addition
to high activity for ethanol upgrading, catalytic reactions can
be set up under ambient conditions with no loss in activity.
upgrading EtOH to 1‐BuOH, EtOH dehydrogenation affords
acetaldehyde, which undergoes aldol coupling to generate
crotonaldehyde. Hydrogenation of crotonaldehyde
produces 1‐BuOH. Key parameters used to evaluate this
reaction are the turnover number (TON), turnover
frequency (TOF), and selectivity (yield of 1‐BuOH divided by
the total yield of Guerbet products). A few recent reports
have demonstrated this reaction with heterogeneous9,10
and homogeneous11 catalysts. To date, the best TONs
reported with >30% conversion are 458,11d 314,11b 340,11a
and 304,11c while the highest TOF reported was 79 h‐1 (314
TONs), using a Ru(II) complex with a bidentate P–N
ligand.11b A recent report demonstrated extremely high
selectivity at the sacrifice of activity using a two‐component
Ir catalyst (99%, TON = 185, TOF = 8 h‐1). However, for
large‐scale applications required for the transportation
sector, higher conversion and turnover are required.
Interest in alternative energy solutions for the
transportation sector is driven largely by the finite supply of
fossil fuels.1 One potentially interim approach is to replace
or blend gasoline with sustainable biofuels, such as
alcohols.2 Ethanol (EtOH), which is a direct product of
biomass fermentation, has been widely used as a blend
additive with gasoline.3 However, challenges associated
with the widespread use of EtOH have limited broad
implementation in the global transportation sector. Key
roadblocks remaining are that EtOH: (1) has ~70% energy
density of gasoline, (2) is corrosive to engine technology
and fuel pipelines, and (3) forms an azeotrope with H2O,
and over extended timeframes, separates from gasoline
blends; both leading to storage problems.4 These
disadvantages are generally mitigated for higher order
alcohols, including 1‐butanol (1‐BuOH), whose fuel
properties more closely resemble those of gasoline (~90%
energy density of gasoline). Furthermore 1‐BuOH can be
blended in higher 1‐BuOH:gasoline ratios, and is immiscible
with water.5 Although 1‐BuOH is a highly desirable biofuel,
the large‐scale synthesis (fermentative production) from
bio‐feedstocks has been fraught with low conversion and
poor selectivity.6
As an alternative to fermentation, an atom‐economical
approach for the bulk synthesis of 1‐BuOH is the Guerbet
reaction.7 This route applies a series of reactions related to
“borrowed hydrogen” chemistry for the conversion of
primary alcohols into higher order alcohol products.8 For
Scheme 1
Previous work demonstrated reversible transformations between
ketones and alcohols via sequential hydrogenation‐acceptorless dehydrogenation
reactions mediated by 1. This work presents the catalytic conversion of EtOH to 1‐
BuOH using the same family of Ru(II) complexes.
We recently reported an N,N,N‐bMepi (bMepi = 1,3‐
bis(6’‐methyl‐2’‐pyridylimino)isoindolate) Ru(II) hydride
Department of Chemistry, University of Michigan, 930 N. University Ave., Ann
Arbor, MI 48109, USA. E‐mail: nszym@umich.edu
† Electronic Supplementary Information (ESI) available: Experimental procedures,
characterization, and reaction details. See DOI: 10.1039/x0xx00000x
complex (
1
, HRu(bMepi)(PPh3)2) capable of mediating
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Table 1 Catalytic Conversion of EtOH to 1‐BuOHa
Entry
1
2
3
4
5
6
7
8
Catalyst
1
Base
Modifications/Additives
Conversion (%)b
Yield (%) Selectivity (%)c
TONd
100
300
280
250
39
230
300
92
410
420
500
630
1400
340
390
350
490
530
Final TOFe
50
150
140
125
18
115
150
46
205
210
250
315
700
170
195
175
245
265
NaOEt
NaOEt
NaOEt
NaOEt
LiOEt
—
—
—
—
—
10
30
28
25
3.9
23
30
27
41
42
25
6.3
1.4
34
39
35
49
53
10
25
24
21
3.9
19
26
23
28
31
20
5.4
1.4
27
29
23
38
37
100
91
89
89
100
89
90
89
78
82
81
86
100
83
89
85
84
78
2‐H
2‐OMe
2‐Cl
2‐H
2‐H
2‐H
2‐H
2‐H
2‐H
2‐H
2‐H
2‐H
2‐H
2‐H
2‐H
2‐H
2‐H
KOEt
—
—
NaOH
NaOEt
NaOEt
NaOEt
NaOEt
NaOEt
NaOEt
NaOEt
NaOEt
NaOEt
NaOEt
NaOEt
0.3 mol% 2‐H
180 °C
9
10
11
12
13
14
15
16f
17
18
10 mol% NaOEt
0.05 mol% 2‐H
0.01 mol% 2‐H
0.001 mol% 2‐H
Set up under air
10 mol% NaOEt under air
20% 1‐BuOH by volume
0.1 mol% PPh3
0.4 mol% PPh3
a All reactions were performed on a 17.1 mmol scale in neat EtOH under an inert atmosphere and were stopped after 2 h. The conversion, yield, and selectivity were
determined by GC‐FID integration of the reaction mixture using naphthalene as an internal standard. b Total conversion of EtOH to Guerbet products. c Total selectivity
to 1‐BuOH determined by mmol of 1‐BuOH per mmol of all Guerbet products. d TON based on mmol of substrate converted to products per mmol of Ru. e Final TOF
based on mmol of substrate converted to products per mmol of Ru after proceeding for 2 h. f With 0.2 mL of 1‐BuOH added (20% by volume).
reversible transformations between ketones and alcohols
of C6 alcohols (2‐ethylbutanol and 1‐hexanol, see Table S1)
as side products, consistent with Guerbet coupling of 1‐
BuOH with EtOH. Control experiments showed that 2‐H and
NaOEt were both required for catalysis (see Table S1). In
addition, electronic modifications of the pincer scaffold had
no effect on the activity and selectivity. For instance, the
conversion and selectivity were within the experimental
error (3%)15 when 2‐OMe (Table 1, entry 3) or 2‐Cl (Table 1,
via
sequential
hydrogenation‐acceptorless
dehydrogenation reactions (Scheme 1).12 Mechanistic
analysis of the acceptorless alcohol dehydrogenation
(AAD)13 revealed that
1 operated via an inner‐sphere β‐H
elimination pathway where β‐H elimination is the turnover‐
limiting step at high alcohol concentration. Because of the
steric hindrance of the methyl groups on the β‐H
elimination process, higher catalytic AAD activity was
observed when Ru‐b4Rpi complexes (2‐R) were used. As a
entry 4) was used instead of 2‐H
.
Guided by the high selectivity for 1‐BuOH exhibited by
2‐H, we investigated conditions to improve the activity. The
identity of the alkali metal had a significant effect. For
example, lower activities were observed when LiOEt (Table
1, entry 5) or KOEt (Table 1, entry 6) was used instead of
NaOEt, while NaOH (Table 1, entry 7) produced the same
results as NaOEt (consistent with solvent leveling effects).
Unfortunately, a higher catalyst loading (0.3 mol%, Table 1,
entry 8) did not improve activity and selectivity. However,
at high temperature (180 °C, Table 1, entry 9) or higher
NaOEt base loading (10 mol%, Table 1, entry 10), the
conversion increased, with concomitant decrease in
selectivity for 1‐BuOH. For instance, when 10 mol% NaOEt
was used, 42% conversion of EtOH to Guerbet alcohols was
noted with 82% selectivity for 1‐BuOH. Analysis of the
reaction products showed higher yield of side products,
which included C6 alcohols (10%) and C8 alcohols (2% yield
of 2‐ethylhexanol and 1‐octanol, see Table S1).
result of the ability of
hydrogenation‐dehydrogenation
hypothesized that, if using
1 to promote successive
reactions,
our family
we
of
bis(pyridylimino)isoindolate (bpi) Ru(II) complexes, similar
“borrowed hydrogen” chemistry might be adapted for
alcohol upgrading reactions. Herein, we report the
application of 2‐R as homogeneous catalysts that promote
the conversion of EtOH to 1‐BuOH with unprecedented
activity and high selectivity
We initiated studies on Guerbet catalysis with EtOH
using our previously reported Ru‐bpi complexes (1 and 2‐R).
Standard reaction conditions employed a 10 mL vial
containing 17.1 mmol EtOH, 5 mol% NaOEt base, and 0.1
mol% Ru(II) precatalyst.14 After the reaction mixture was
heated to 150 °C for 2 h, the product distribution was
determined by GC‐FID using naphthalene as an internal
standard. Higher activity (>3×) was found when 2‐H (Table
1, entry 2) was used instead of
of the reaction products (Table 1, entry 2) showed high
selectivity (91%) for the production of 1‐BuOH and 4% yield
1
(Table 1, entry 1). Analysis
Air‐stable catalysts provide significant practical
advantages, and are more easily deployed on an industrial‐
scale. We found that the activity of 2‐H was retained when
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set up under ambient conditions. For example, when
weighing all reagents in the air and adding air saturated
solvents followed by heating the sealed vessel containing
17.1 mmol EtOH, 0.1 mol% 2‐H, and 5 or 10 mol% NaOEt to
150 °C for 2 h (Table 1, entries 14 and 15) resulted in 34%
and 39% conversion (30% under N2) respectively. These
results clearly demonstrate that catalytic performance is
unaffected in the presence of O2, which suggests that the
active species is neither decomposed nor oxidized to a
higher‐valent ruthenium complex. Based on known reports
of upgrading EtOH to 1‐BuOH, our system 2‐H is the first
ruthenium catalyst to mediate this reaction under air.
resulted in the clean conversion to Ru(bMepi)(PPh3)(Cl)CO
(3
). The 31P{1H} NMR spectrum exhibited a singlet at 43.5
ppm, and the IR spectrum displayed a νCO band at 1929 cm‐
1. The solid‐state structure revealed CO ligand trans to the
isoindolate nitrogen atom (Fig. 2).
To assess the overall reaction efficiency, a time
dependence study was conducted by varying the reaction
time at 150 °C (Fig. 1). When evaluated over 24 h, the
reaction profile displayed a linear region and reached
culmination after approximately 4 h. Analysis of the
reaction profile and the reaction products revealed an
increase in production of higher order alcohols (10% to 14%
C6 and C8 Guerbet products from 4 to 6 h) while the yield of
1‐BuOH remained constant. We hypothesized that high
concentration (ca. 2.1 M or 25% yield) of 1‐BuOH could
compete with EtOH as a substrate, and thus impede
production of 1‐BuOH by competitive Guerbet pathways to
generate longer chain alcohols. In support, a control
experiment using 20% of 1‐BuOH by volume (Table 1, entry
16) afforded similar conversion and yield. However, the
yield of longer chain alcohols increased from 4% to 12% and
the yield of 1‐BuOH remained 23% (25% without the
addition of 1‐BuOH), which is consistent with competitive
1‐BuOH binding/reactivity at high concentration.
Fig. 2
Crystal structures of 3 and 4 with thermal ellipsoids depicted at 50%
probability (30% probability for 4a‐OMe). The hydrogen atoms and PPh3 phenyl
groups are omitted for clarity. Selected bond distances (angstroms) for 3: Ru1—
C39, 1.867(3); and O1—C39, 1.155(3). Selected bond distances (angstroms) for 4‐
OMe: Ru1—C39, 1.859(9); and O3—C39, 1.096(9). Selected bond distances
(angstroms) for 4b: Ru1—C19, 1.910(7); Ru1—C20, 1.903(9); O1—C19, 1.146(9);
and O2—C20, 1.12(1).
Carbonyl complexes with the bpi ligand were prepared
using a similar method. The addition of 30 psig CO to a
solution of 2‐H resulted in a mixture of 4a‐H and 4b in a
37:1 ratio. The 31P{1H} NMR spectrum displayed one major
resonance at 10.7 ppm with concomitant formation of free
PPh3, and the IR spectrum showed one major νCO band at
1966 cm‐1. After 24 h, the mixture fully converted to the
bis‐CO complex (4b), and the IR spectrum exhibited new νCO
bands at 2046 and 1977 cm‐1, while the solid state structure
revealed a Ru(II) center coordinated to two cis CO ligands
and a chloride (Fig. 2). Although a crystal structure of 4a
19
could not be obtained, a substituted variant (4a‐OMe
)
Fig. 1
Reaction profile of conversion of EtOH to 1‐BuOH catalyzed by 2‐H. The
conditions were identical to Table 1, entry 2 except the reaction time. Each data
point represents an average of two runs with a maximum experimental error of
3%.
that featured a very similar νCO band (1958 cm‐1) was
structurally characterized by X‐ray (Fig. 2). Because of the
close proximity of the νCO bands between
3 and the
decomposition product from Guerbet reactions (1929 vs.
1923 cm‐1), we propose that the deactivated catalyst
contains a CO ligand (resulting from decarbonylation) trans
to the isoindolate nitrogen atom.
To optimize activity by preventing a competitive EtOH
decarbonylation pathway, excess PPh3 was added to
suppress phosphine dissociation. Addition of 1 equiv of
PPh3 (with respect to catalyst) to the standard reaction
To complement the time dependence study that
demonstrated minimal catalyst activity after 6 h, we
targeted Ru‐bpi compounds with CO ligands that likely bear
similarity to the catalyst deactivation product (νCO band at
1923 cm‐1 observed by IR spectroscopy).16‐18 Three different
types of CO complexes were prepared from bpi variants to
aid in the assignment of the decomposition products. The
addition of CO (30 psig) to a solution of Ru(bMepi)(PPh3)Cl
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8
9
For reviews on hydrogen borrowing chemistry see: (a) G.
E. Dobereiner and R. H. Crabtree, Chem. Rev., 2010, 110
681; (b) M. H. S. A. Hamid, P. A. Slatford and J. M. J.
Williams, Adv. Synth. Catal., 2007, 349, 1555.
For a review on heterogeneous catalysts for the Guerbet
reaction see: A. Galadima and O. Muraza, Ind. Eng. Chem.
Res., 2015, 54, 7181.
conditions (0.1 mol% 2‐H, 5 mol% NaOEt, 150 °C; Table 1,
entry 17) enhanced the catalyst activity to 49% conversion
(an increase of 76% based on conversion and 72% based on
TOF). Increasing the PPh3 loading to 4 equiv had a minimal
increase on the catalyst activity (53%; Table 1, entry 18).20
Prior state‐of‐the‐art catalysts afforded a TON of 458 (46%
conversion; TOF = 19 h‐1)11d or 314 (31% conversion; TOF =
79 h‐1).11b Thus, our system surpassed the activity of the
previous premier systems by exhibiting a higher TON of
530, with a TOF of 265 h‐1 at 53% conversion for
catalytically upgrading EtOH.
,
10 T. Riittonen, E. Toukoniitty, D. K. Madnani, A.‐R. Leino, K.
Kordas, M. Szabo, A. Sapi, K. Arve, J. Warna and J.‐P.
Mikkola, Catalysts, 2012, 2, 68.
11 (a) S. Chakraborty, P. E. Piszel, C. E. Hayes, R. T. Baker and
W. D. Jones, J. Am. Chem. Soc., 2015, 137, 14264. (b) R. L.
Wingad, P. J. Gates, S. T. G. Street and D. F. Wass, ACS
Catal., 2015, 5822; (c) G. Xu, T. Lammens, Q. Liu, X. Wang,
L. Dong, A. Caiazzo, N. Ashraf, J. Guan and X. Mu, Green
Chem., 2014, 16, 3971; (d) G. R. M. Dowson, M. F.
Haddow, J. Lee, R. L. Wingad and D. F. Wass, Angew.
Chem., Int. Ed., 2013, 52, 9005; (e) K. Koda, T. Matsu‐ura,
Y. Obora and Y. Ishii, Chem. Lett., 2009, 38, 838.
In conclusion, we have developed Ru‐bpi complexes (2‐
R
) capable of converting EtOH to 1‐BuOH with up to 91%
selectivity. Higher activity (>50% conversion) was obtained
at the sacrifice of selectivity (~10%) when using 1‐4
additional equiv PPh3. Note that currently used liquid fuels
such as gasoline, are blends of hydrocarbons rather than
single components. Thus, mixtures of higher order alcohols
can likely serve a similar role as drop‐in gasoline additives.
Although prior studies have demonstrated homogeneous
catalysts for EtOH upgrading, to our knowledge, our system
is the most active, with a TOF of 265 h‐1 at over 50%
conversion. Of particular note, complex 2‐H upgrades EtOH
to 1‐BuOH when set up in air with minimal loss of catalytic
activity. This improvement in catalyst performance
represents a substantial step forward toward processes
that use a bio‐derived feedstock for one‐step fuel‐forming
reactions with minimal intervention required to the existing
transportation infrastructure. Ongoing efforts are focused
on mechanistic analyses as well as other sustainable energy
applications derived from renewable biomass feedstocks.
12 (a) K.‐N. T. Tseng, J. W. Kampf and N. K. Szymczak, ACS
Catal., 2015, 5, 5468; (b) K.‐N. T. Tseng, J. W. Kampf and
N. K. Szymczak, Organometallics, 2013, 32, 2046.
13 For recent examples see: (a) D. Spasyuk, S. Smith and D.
G. Gusev, Angew. Chem., Int. Ed., 2012, 51, 2772; (b) M.
Nielsen, H. Junge, A. Kammer and M. Beller, Angew.
Chem., Int. Ed., 2012, 51, 5711; (c) M. Nielsen, E. Alberico,
W. Baumann, H.‐J. Drexler, H. Junge, S. Gladiali and M.
Beller, Nature, 2013, 495, 85; (d) R. E. Rodríguez‐Lugo, M.
Trincado, M. Vogt, F. Tewes, G. Santiso‐Quinones and H.
Grützmacher, Nat Chem, 2013, 5, 342.
14 Note that the reaction glass vessel was etched after the
reaction was completed. This can be avoided by
performing the reaction in a Parr bomb or a Teflon vessel,
which produced the same results (see Table S1).
15 The experimental error was determined by >3 runs of the
standard reaction (Table 1, entry 2).
16 Decarbonylation is a common deactivation pathway
observed in EtOH dehydrogenation, see: (a) E. Delgado‐
Lieta, M. A. Luke, R. F. Jones, D. J. Cole‐ Hamilton,
Polyhedron, 1982, 1, 836; (b) N. Sieffert; R. Réocreux; P.
Lorusso; D. J. Cole‐Hamilton; M. Bühl, Chem. Eur. J., 2014,
20, 4141.
Notes and references
1
For reviews on alternative energy see: (a) M. Höök and X.
Tang, Energy Policy, 2013, 52, 797; (b) N. S. Lewis and D.
G. Nocera, Proc. Natl. Acad. Sci, 2006, 103, 15729.
For reviews on biofuels: (a) A. J. Ragauskas, C. K. Williams,
B. H. Davison, G. Britovsek, J. Cairney, C. A. Eckert, W. J.
Frederick, J. P. Hallett, D. J. Leak, C. L. Liotta, J. R. Mielenz,
R. Murphy, R. Templer and T. Tschaplinski, Science, 2006,
311, 484; (b) M. Guo, W. Song and J. Buhain, Renewable
Sustainable Energy Rev., 2015, 42, 712.
For a report on EtOH in the global energy economy see:
U. N. E. P. B. W. Group and U. N. E. P. I. P. f. S. R.
Management, Towards sustainable production and use of
resources: assessing biofuels, UNEP/Earthprint, 2009.
For a review on bioethanol see: M. Balat, Energy Convers.
Manage., 2011, 52, 858.
For reviews on 1‐BuOH as a biofuel see: (a) B. G. Harvey
and H. A. Meylemans, J. Chem. Technol. Biotechnol.,
2011, 86, 2; (b) C. Xue, X.‐Q. Zhao, C.‐G. Liu, L.‐J. Chen and
F.‐W. Bai, Biotechnol. Adv., 2013, 31, 1575; (c) C. Jin, M.
Yao, H. Liu, C.‐f. F. Lee and J. Ji, Renewable Sustainable
Energy Rev., 2011, 15, 4080.
17 Aldehyde decarbonylation has been reported for many
late transition‐metal complexes. For recent examples see:
(a) H.‐A. Ho, K. Manna and A. D. Sadow, Angew. Chem.
Int. Ed., 2012, 51, 8607; (b) J. G. Melnick, A. T.
Radosevich, D. Villagran and D. G. Nocera, Chem.
Commun., 2010, 46, 79.
18 To further characterize the ruthenium species during
catalysis, allowing 2‐H to react with NaOEt resulted in
multiple species (65.9 ppm, 55.1 ppm, and free PPh3) as
observed by 31P NMR spectroscopy.
19 Single crystals of 4a‐OMe were obtained from vapor
diffusion of pentane into a C6H6 solution (see cif file),
which confirmed the structure of 4a. Complex 4a‐OMe
shared similar 1H and 31P NMR features, which included a
31P NMR resonance at 10.8 ppm (10.7 ppm for 4a‐H).
20 The active catalyst was probed using mercury and
substoichiometric ligand poisoning experiments; the
results were consistent with a homogeneous system (see
Table S2).
2
3
4
5
6
7
For a review on the fermentative production of 1‐BuOH
see: E. M. Green, Curr. Opin. Biotechnol., 2011, 22, 337.
For a review on the Guerbet reaction catalyzed by
transition‐metal complexes see: D. Gabriels, W. Y.
Hernandez, B. Sels, P. Van Der Voort and A.
Verberckmoes, Catal. Sci. Technol., 2015, 5, 3876.
This journal is © The Royal Society of Chemistry 20xx
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