High Catalytic Efficiency Combined with High Selectivity for the Aldehyde-Water Shift Reaction using (para-cymene)Ruthenium Precatalysts

Article abstract of DOI:10.1021/acscatal.6b02130

A family of (para-cymene)Ru^II complexes are shown to be competent precatalysts for the oxidation of aldehydes to carboxylic acids using water as the oxidant. This reaction, known as the "aldehyde-water shift" (AWS), has been previously demonstrated to be in competition with aldehyde disproportionation. For the few reported mononuclear catalysts for this reaction, either high selectivity for AWS and low conversion or low AWS selectivity and high conversion is observed. A homogeneous precatalyst which is both highly selective for the desired AWS and is highly efficient for conversion of the aldehyde to products is reported herein. In addition, catalyst activity is found to be general to a variety of sterically unencumbered aliphatic aldehydes producing the corresponding carboxylic acid and hydrogen gas.

Full text of DOI:10.1021/acscatal.6b02130

Letter
pubs.acs.org/acscatalysis
High Catalytic Efficiency Combined with High Selectivity for the
Aldehyde−Water Shift Reaction using (para-cymene)Ruthenium
Precatalysts
Timothy P. Brewster,† Jonathan M. Goldberg, Jeremy C. Tran, D. Michael Heinekey,*
and Karen I. Goldberg*
Department of Chemistry, University of Washington, Seattle, Washington 98195-1700, United States
S
* Supporting Information
ABSTRACT: A family of (para-cymene)RuII complexes are shown to be
competent precatalysts for the oxidation of aldehydes to carboxylic acids
using water as the oxidant. This reaction, known as the “aldehyde−water
shift” (AWS), has been previously demonstrated to be in competition with
aldehyde disproportionation. For the few reported mononuclear catalysts for
this reaction, either high selectivity for AWS and low conversion or low AWS
selectivity and high conversion is observed. A homogeneous precatalyst which
is both highly selective for the desired AWS and is highly efficient for
conversion of the aldehyde to products is reported herein. In addition,
catalyst activity is found to be general to a variety of sterically unencumbered
aliphatic aldehydes producing the corresponding carboxylic acid and hydrogen gas.
KEYWORDS: aldehyde−water shift, aldehyde oxidation, homogeneous catalysis, dehydrogenation, water
arboxylic acids are a fundamentally important class of
Maitlis investigated aqueous aldehyde disproportionation
Corganic compounds with a wide variety of applications. (Scheme 2) in which the substrate itself serves as a hydrogen
They are one of the monomer units of polyester plastics, and
they are frequently used as synthetic precursors to other
functional groups such as esters and amides. Oxidative synthesis
of carboxylic acids can be effected by many different reagents,
such as chromate, permanganate, hydrogen peroxide, and
molecular oxygen.1 An alternative method is through the
“aldehyde-water shift” reaction (AWS, Scheme 1),2,3 in which
water serves as the oxidant and reacts with an aldehyde to
produce the carboxylic acid with concomitant release of a
valuable coproduct, hydrogen gas.
Scheme 2. Aldehyde Disproportionation
acceptor.9,10 Previous work on the AWS in our group
investigated π-arene (or cyclopentadienyl) complexes of
iridium-, rhodium-, and ruthenium-containing bipyridine
ligands as precatalysts in aqueous solution.3 In many cases,
competing aldehyde disproportionation (Scheme 2) was
observed as the major reaction. Ruthenium-based π-arene
precatalysts were the most selective, producing large amounts
of carboxylic acid relative to the corresponding alcohol derived
from disproportionation. In the first example of a highly
selective AWS reaction in the absence of external additives, an
acid selectivity of 95% was achieved using [(p-cymene)Ru-
(bpy)OH2][OTf]2 (bpy =2,2′-bipyridine, OTf = trifluorome-
thanesulfonate) precatalyst and benzaldehyde as the substrate
(Scheme 3). However, this exceptional selectivity came at the
expense of conversion, with only 4% of the starting material
transformed after 20 h at 105 °C.
Scheme 1. Aldehyde−Water Shift
Murahashi first reported the conversion of aldehydes to
carboxylic acids with a ruthenium catalyst, a hydrogen acceptor,
and water as the oxidant.4 Later, Stanley observed carboxylic
acid byproducts in the course of hydroformylation reactions
with a rhodium catalyst and suggested the aldehyde−water shift
as a potential reaction pathway.2 In recent years, work by
Milstein,5 Grutzmacher,6 and Prechtl7 on the dehydrogenation
Computational studies suggest a mechanism involving a
metal hydride species as the key intermediate in the catalytic
cycle.11 This hydride is hypothesized to be the source of
̈
of alcohols to carboxylic acids proposed the AWS as an
intermediate reaction step involving dehydrogenation of a
hydrated aldehyde (geminal-diol). Computational insight into
the Milstein systems further supported the potential to use
water as an oxidant for aldehydes.8 In closely related work,
Received: July 27, 2016
© XXXX American Chemical Society
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Letter
Scheme 3. Previously Reported Highly Selective AWS3
Chart 1. Ruthenium(II) Diamine Precatalysts Tested
suggests that the PDA ligand can operate in a bifunctional
manner.19 For the sake of brevity, catalysts will be referred to
only by their diamine ligand for the remainder of this
manuscript, as shown in Chart 1.
selectivity for AWS versus disproportionation. As illustrated in
Scheme 4, a strongly basic hydride will be readily protonated to
produce hydrogen gas, whereas a weakly basic hydride can favor
disproportionation via nucleophilic attack of the carbonyl.
Precatalysts shown in Chart 1 were examined using our
standard test conditions (5.0 mmol acetaldehyde, 10 mL of
H2O, 0.020 mmol precatalyst, 105 °C, 20 h) and the reactions
Scheme 4. Proposed Origin of AWS Selectivity3,11
1
were analyzed by H NMR spectroscopy (Table 1). Reactions
ab
,
Table 1. Ruthenium Precatalyst Screen
catalyst
% conversion
% acid
Ru(TsDPEN)
Ru(PDA)
79(5)
92(1)
33(2)
71(4)
72(6)
0
85(6)
85(2)
89(1)
89(2)
86(2)
0
Ru(TsPDA)
Ru(TMEDA)
[(p-cymene)RuCl2]2
RuCl3
c
New prospective catalysts were, therefore, identified by
considering the basicity of the proposed metal-hydride
intermediate. From this criterion, the Noyori-type complex12
(p-cymene)Ru(TsDPEN)(H) (TsDPEN = (S,S)-
a
Reaction conditions: 5.0 mmol acetaldehyde, 0.020 mmol precatalyst,
b
10 mL of H2O, 105 °C, 20 h. Standard deviation in parentheses.
−
c
TsNCHPhCHPhNH2 ) was selected. The pKa of its conjugate
0.010 mmol precatalyst.
acid (16 in MeCN) suggests that this hydride is basic enough to
deprotonate water.13 The bifunctional TsDPEN ligand, utilized
in asymmetric transfer hydrogenation reactions,12 may also
assist in dehydrogenation of a gem-diol, likely the key organic
intermediate in the AWS reaction.10
using Ru(TsDPEN) and Ru(PDA) as precatalysts remained
homogeneous throughout the reaction. In contrast, the
solutions containing Ru(TsPDA) produced an insoluble red
solid over the course of the reaction, whereas Ru(TMEDA)
produced large quantities of dark heterogeneous material. All
precatalysts screened passed the mercury drop test, suggesting
that the active catalyst is likely to be a homogeneous species
and not metallic ruthenium nanoparticles.20
Initial studies with the commercially available precursor, (p-
cymene)Ru(TsDPEN)Cl (hereafter referred to as Ru-
(TsDPEN)), were performed in 10 mL of water and at a
precatalyst concentration of 2 mM (0.4 mol % relative to
substrate). At room temperature, the precatalyst was sparingly
soluble, but the reaction became homogeneous upon heating.
Acetaldehyde (5.0 mmol), a water-soluble aldehyde, was used
as the initial test substrate. The solution was heated to 105 °C
under nitrogen for 20 h in a Teflon-sealed glass reaction
Surprisingly, while the precatalysts pictured in Chart 1
displayed different conversions, the selectivities of the reactions
were all quite consistent at 87
2%. Following these
experiments, a control reaction using the synthetic precursor,
[(p-cymene)RuCl2]2,21 was run to test its catalytic capabil-
ities.22 Remarkably, this parent complex displayed conversion
and selectivity on par with the diamine complexes. The
ruthenium dimer also produced a coating of heterogeneous
material on the inside of the reaction vessel over the course of
the reaction, similar to that observed with Ru(TMEDA). In
fact, within error, Ru(TMEDA) and [(p-cymene)RuCl2]2
function identically (conversion and selectivity), suggesting
that the TMEDA ligand may dissociate over the course of the
reaction.
[(p-cymene)RuCl2]2 was tested at various temperatures to
gain a better understanding of factors that influence catalyst
performance and decomposition (Table 2). These experiments
demonstrated that a decrease in temperature does not
significantly affect the selectivity of the reaction, but does
decrease the percent conversion of aldehyde. In addition,
reactions run at 91 and 105 °C led to visible heterogeneous
decomposition products, whereas reactions run at 80 °C and
below appeared to remain homogeneous. The greater amount
of heterogeneous material present at 105 °C than at 91 °C may
vessel.14 Products and yields were determined via H NMR
1
spectroscopy using phenol as an internal standard. Analysis of
the reaction mixture revealed a remarkably high conversion of
79(5)%, significantly higher than that observed previously with
other ruthenium precatalysts.3 Moreover, this catalyst also
demonstrated high selectivity for acid production, with 85(6)%
of the reacted aldehyde being converted to carboxylic acid.15
Following the promising results using Ru(TsDPEN) as a
precatalyst, other diamine ligand frameworks were also
explored with ruthenium. Since no chiral centers can be
formed in the AWS reaction, the TsDPEN ligand seemed
unnecessarily complex. Three simpler diamine ligands were
thus tested: PDA (ortho-phenylenediamine),16 TsPDA (N-
tosyl-ortho-phenylenediamine),17 and TMEDA (N,N,N′,N′-
tetramethylethylenediamine).18 The precatalysts are shown in
Chart 1. In contrast to the other ligands presented, TMEDA is
not expected to function as a bifunctional ligand without
dissociation. Notably, the pentamethylcyclopentadienyl rho-
dium analogue of the PDA complex has been investigated
computationally for dehydrogenation reactions and that study
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Letter
a b
,
Table 2. Variable Temperature Reactions using [(p-
cymene)RuCl2]2
Table 4. Substrate Scope
a
temperature
% conversion
% acid
105 °C
91 °C
80 °C
71 °C
60 °C
72(6)
80(2)
68(1)
63(4)
34(4)
86(2)
86(1)
88(4)
89(0.3)
93(2)
a
Reaction conditions: 5.0 mmol acetaldehyde, 0.010 mmol precatalyst,
10 mL of H2O, 20 h. Standard deviation in parentheses.
account for the observed decrease in product yield at that
temperature.
To confirm H2 formation from AWS catalysis, a reaction was
examined in a 20 mL pressure-relief vial using modified
conditions to accommodate the smaller reaction vessel [2.5
mmol acetaldehyde, 5 mL of H2O, 0.010 mmol Ru(PDA), 105
°C, 20 h]. Hydrogen was detected by GC-TCD, and the
pressure buildup in the vial was quantified using a pressure
sensor.24
The substrate scope of the AWS reaction with the Ru(PDA)
precatalyst was explored with a variety of aliphatic and
conjugated aldehydes. Though addition of dioxane as a
cosolvent was found to decrease reaction efficiency and
selectivity (acetaldehyde as substrate, Ru(PDA) as precatalyst,
Table 3), the substrate scope was investigated using a 1:1 (v/v)
mixture of water and 1,4-dioxane as solvent to enhance
substrate solubility. Full results are shown in Table 4.14
a
Table 3. Effect of Added Dioxane
% dioxane in water by volume
% conversion
% acid
a
Conditions: 5.0 mmol substrate, 0.020 mmol precatalyst, 5 mL of
0
92(1)
92(1)
87(4)
82(3)
85(2)
82(1)
78(1)
72(1)
b
H2O, 5 mL dioxane, 105 °C, 20 h. Standard deviation in parentheses.
17
33
50
c
d
e
0.010 mmol precatalyst. Run in open system. 91(8)% conversion
calculated based on the 67(4)% recovered organic material.
a
Reaction conditions: 5.0 mmol acetaldehyde, 0.020 mmol Ru(PDA),
Sterically bulky pivaldehyde was not efficiently converted to
products, though selectivity for the AWS pathway remained
quite high. Conjugated species benzaldehyde and cinnamalde-
hyde were found to be unreactive; 99% of the recovered
material was starting aldehyde.
10 mL of total solvent volume, 105 °C, 20 h. Standard deviation in
parentheses.
Acetaldehyde was first examined under the chosen
conditions (105 °C, 20 h) using both the highly efficient
Ru(PDA) precatalyst and the [(p-cymene)RuCl2]2 catalyst
precursor. For both precatalysts, selectivity for acid production
dropped from approximately 85% in pure water to approx-
imately 73% in 1:1 water:dioxane. Interestingly, while
precatalyst activity was largely retained with the Ru(PDA)
system (92(1)% and 82(3)% conversion, in water and 1:1
water:dioxane, respectively), conversion was found to signifi-
cantly decrease from 72(6)% to 16(2)% on changing solvent
from water to 1:1 water dioxane using [(p-cymene)RuCl2]2 as
precatalyst. Corresponding to the low conversion, heteroge-
neous black particles were observed within 60 min suggesting
rapid catalyst decomposition. In contrast, the Ru(PDA)
precatalyst appears to remain in solution for the duration of
the reaction.
Heptaldehyde, which boils at a relatively high temperature
(153 °C) was also investigated in an open system using
Ru(PDA) as the precatalyst in 1:1 (v/v) water:dioxane
solvent.14 In this reaction, a Schlenk flask fitted with a reflux
condenser was used as the reaction vessel. A steady stream of
N2 was passed over the reaction mixture for the duration of the
20 h reaction allowing for efficient removal of any hydrogen
produced. Since (p-cymene)Ru(diamine) complexes are known
to be efficient ketone hydrogenation catalysts under low
pressures of hydrogen, it was postulated that efficient removal
of hydrogen would increase reaction selectivity. Indeed, 91(8)%
of the recovered material was found to be products (heptanoic
acid and n-heptanol) with 87(1)% selectivity for the acid
product; a marked improvement in reaction selectivity over
reactions run in a closed vessel (71(5)%).23
More complex aliphatic aldehydes, such as propionaldehyde,
isobutyraldehyde, heptaldehyde, and phenylacetaldehyde, were
all found to react with moderate to high efficiency and high
selectivity under the chosen conditions (Table 4). Conversion
for phenylacetaldehyde is found to be relatively low, possibly
because the substrate is still only partially soluble at 105 °C.
In conclusion, a series of (p-cymene)ruthenium(II) diamine
complexes have been shown to be competent in catalyzing the
aldehyde−water shift reaction. These precatalysts provide an
unprecedented combination of reaction efficiency and
selectivity for AWS over disproportionation. Interestingly, the
synthetic precursor to the diamine complexes, [(p-cymene)-
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Letter
(7) Choi, J.-H.; Heim, L. E.; Ahrens, M.; Prechtl, M. H. G. Dalton
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RuCl2]2, is also able to catalyze the aldehyde−water shift
reaction at similar levels of selectivity and conversion in pure
water. In a mixed solvent system, the diamine was found to be
essential for catalyst longevity. The best diamine precatalyst,
Ru(PDA), was found to be a competent precatalyst for the
oxidation of a range of aliphatic aldehydes. This reaction
provides a new, mild route for production of carboxylic acids
alongside a valuable byproduct, dihydrogen. Ongoing studies
are now investigating the reaction mechanism and the exact
nature of the active catalytic species for both the diamine-
ligated and [(p-cymene)RuCl2]2 precatalyst systems.
(8) Li, H.; Hall, M. B. J. Am. Chem. Soc. 2014, 136, 383−395.
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(14) For full details, see Supporting Information.
(15) Two products were observed in all reactions: the desired
carboxylic acid and the corresponding alcohol. % acid indicates the
percent of converted product observed as the carboxylic acid. The
remaining product, in all cases, is the alcohol. For example, 85(6)%
acid indicates 15(6)% alcohol.
ASSOCIATED CONTENT
■
S
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acscatal.6b02130.
(16) Garcia, G.; Solano, I.; Sanchez, G.; Santana, M. D.; Lopez, G.;
Casabo, J.; Molins, E.; Miravitlles, C. J. Organomet. Chem. 1994, 467,
119−126.
Experimental details (PDF)
(17) Bierenstiel, M.; Dymarska, M.; de Jong, E.; Schlaf, M. J. Mol.
Catal. A: Chem. 2008, 290, 1−14.
AUTHOR INFORMATION
■
(18) Zuccaccia, D.; Macchioni, A. Organometallics 2005, 24, 3476−
3486.
Corresponding Authors
*E-mail for D.M.H.: heinekey@chem.washington.edu.
*E-mail for K.I.G.: goldberg@chem.washington.edu.
(19) Nova, A.; Taylor, D. J.; Blacker, A. J.; Duckett, S. B.; Perutz, R.
N.; Eisenstein, O. Organometallics 2014, 33, 3433−3442.
(20) Crabtree, R. H. Chem. Rev. 2015, 115, 127−150.
(21) Bennett, M. A.; Huang, T.-N.; Matheson, T. W.; Smith, A. K.;
Ittel, S.; Nickerson, W. Inorg. Synth. 1982, 21, 74−78.
(22) This precursor was previously investigated for aldehyde
disproportionation activity at decreased temperature in references 9
and 10.
(23) Only 67(4)% of the substrate/products was recovered in this
reaction so a meaningful comparison of percent conversion is not
possible.
(24) Approximately 50% of the expected H2 pressure was detected by
this method (see Supporting Information). Some gas was noticeably
lost upon puncturing the pressure-relief vial with the pressure sensor
and this would account for the underdetection of pressure.
Present Address
†(T.P.B.) Department of Chemistry, University of Memphis,
Memphis, TN 38512
Author Contributions
All authors have given approval to the final version of the
manuscript.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was funded by NSF under the CCI Center for
Enabling New Technologies through Catalysis (CENTC),
CHE-1205189 and by the Washington NASA Space Grant
(research award to J.C.T.). The authors thank Dr. Sophia D. T.
Cherry for providing Ru(TsPDA), Danielle A. Henckel for help
with hydrogen quantitation, and Prof. Gojko Lalic for helpful
discussions.
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