A Prolific Catalyst for Selective Conversion of Neat Glycerol to Lactic Acid

Article abstract of DOI:10.1021/acscatal.5b02732

We report the synthesis and reactivity of a very robust iridium catalyst for glycerol to lactate conversion. The high reactivity and selectivity of this catalyst enable a sequence for the conversion of biodiesel waste stream to lactide monomers for the preparation of poly(lactic acid). Furthermore, experimental data collected with this system provide a general understanding of its reactive mechanism.

Full text of DOI:10.1021/acscatal.5b02732

Letter
pubs.acs.org/acscatalysis
A Prolific Catalyst for Selective Conversion of Neat Glycerol to Lactic
Acid
Zhiyao Lu, Ivan Demianets, Rasha Hamze, Nicholas J. Terrile, and Travis J. Williams*
Donald P., Katherine B. Loker Hydrocarbon Institute and Department of Chemistry, University of Southern California, Los Angeles,
California 90089-1661, United States
*
S Supporting Information
ABSTRACT: We report the synthesis and reactivity of a very
robust iridium catalyst for glycerol to lactate conversion. The
high reactivity and selectivity of this catalyst enable a sequence
for the conversion of biodiesel waste stream to lactide
monomers for the preparation of poly(lactic acid). Further-
more, experimental data collected with this system provide a
general understanding of its reactive mechanism.
KEYWORDS: glycerol, lactic acid, iridium, dehydrogenation, biodiesel
lycerol is a byproduct of biodiesel production and of other
Scheme 1. (A) Formic Acid Dehydrogenation System 1/2, (B)
8
G
fine chemical syntheses, such as those of perfumes,
Syntheses, and (C) Molecular Structures of Novel Iridium
1
a
fragrances, and pharmaceuticals. Currently the biodiesel
Complexes
industry in the United States produces 2.0 billion gallons of
2
3
glycerol each year, with an increase projected in the future.
Because glycerol constitutes about 10% of the weight of crude
biodiesel, the utilization of this “waste” is an opportunity for new
4
technology. Significant effort has been invested in catalytic
5
conversion of glycerol to value-added products. Selective
dehydrogenation of glycerol to lactic acid is particularly
appealing, because lactic acid is both a valuable feedstock for
organic synthesis and a precursor for poly(lactic acid) (PLA), a
biodegradable polymer. The market demand of PLA is estimated
6
at 150 000 tons by 2017 and 400 000 tons by 2022. Moreover,
when such conversions are conducted by acceptorless dehydro-
genation, the byproduct H is a readily separable energy carrier
2
that has value as such. In these regards, homogeneous conversion
of glycerol to lactic acid has shown promising reactivity and good
7
selectivity.
Here we report the most robust and selective catalyst to date
for the conversion of glycerol and new insights into its reactive
mechanism. Our system enables high conversion of neat glycerol,
even if isolated crude from biodiesel production, to sodium
lactate with >99% selectivity. We also show that lactic acid can be
easily isolated from our reaction mixture and then converted to
rac- and meso-lactides, the precursors for PLA synthesis.
Our entry into glycerol dehydrogenation stemmed from our
diiridium catalyst (2) for formic acid dehydrogenation (Scheme
a
Ellipsoids drawn at the 50% probability level.
9
1a). In this prior study, we found that 2 forms from monomer 1
and that the (pyridyl)methylphosphine ligand plays a vital part in
enabling dimer formation and catalyst longevity: other P−N and
C−N ligands did not efficiently dimerize or display the reactivity
of 1/2. We further observed that once dimerized, complex 2 had
little dehydrogenation reactivity with substrates other than
formic acid. On these bases, we designed complexes 5 and 9
ligands that apparently inhibit an analogous dimerization and
enable more general dehydration reactivity.
Received: December 1, 2015
Revised: January 25, 2016
(Scheme 1bc), which feature bidentate (pyridyl)methylcarbene
©
XXXX American Chemical Society
2014
DOI: 10.1021/acscatal.5b02732
ACS Catal. 2016, 6, 2014−2017

ACS Catalysis
Letter
a
Table 1. Dehydrogenation of Neat Glycerol to Lactic Acid
entry
1
catalyst (ppm)
temp (°C)
time
base (mol %)
TON
conversion
25.9%
20 (5)
0.1 (5)
20 (5)
20 (5)
100 (5)
100 (5)
20 (5)
20 (5)
20 (5)
200 (5)
200 (5)
20 (6)
20 (6)
20 (9)
20 (9)
0.1 (9)
20 (9)
140 (9)
145
145
145
145
180
180
180
180
180
145
145
145
145
145
145
145
145
145
3 day
8 days
6 days
6 days
1 h
25
12964
1057172
14901
17285
119
b
2
25
10.5%
c,d
3
4
5
6
7
8
50
29.8% (22%)
34.6%
100
1
1.2%
1.5 h
10
1162
11.6%
10 h
10
5215
10.4%
15 h
25
13113
15894
1909
26.2%
9
15 h
50
31.9%
e
10
11
12
13
14
15
16
17
18
5 days
5 days
6 days
6 days
3 days
3 days
32 days
7 days
7 days
50
38.2%
e
100
50
3445
68.9%
7490
15.0%
100
50
10785
25015
37083
4557487
40889
45010
21.6%
c
50.0% (37%)
c
100
100
100
100
74.2% (54.0%)
45.6%
b
e,
g
c
c
81.7% (55.6%)
90.0% (61.2%)
f,g
a
Typical reaction conditions are 5 mL of glycerol, Ir catalyst, and base (KOH/NaOH weighed and mixed in air). Reaction progress was monitored
b
c
d
e
by gas evolution. The reaction started with 100 mL glycerol and was active when quenched. Isolated yield. 73% based on conversion. The
volume of glycerol is 2 mL in this reaction. 9.3 g of glycerol isolated from biodiesel transesterification was used. NaOH is used in place of KOH.
f
g
Heating compound 5 in air with KOH and glycerol results in
find, however, that the less sterically hindered pyridine-carbene
complex 9 enables more rapid reactions than 5. For example, in a
typical run with a catalyst loading as low as 20 ppm, over 80% of
glycerol can be converted to lactate (entries 17, 18). This
conversion is higher than any other homogeneous catalyst in neat
glycerol. In a particular run, 9 remains reactive over 32 days
delivering a total TON of over 4.5 million (Table 1, entry 14). The
catalysis is fast at 145 °C, with a turnover frequency (TOF) of up
the selective formation of H and lactate (>95%, Table 1) with no
2
other products detectable. For example, in a particular run, we
observe absence of common side products in glycerol oxidation,
such as ethelene glycol, proplene glycol, and 1,3-propane diol by
NMR; GC data corroborate the absence of any nonproduct
signals (see Supporting Information). The robustness of the
catalyst is evident from an experiment in which we observe over 1
million turnovers in 8 days (entry 2). This TON is higher than
any other homogeneous system reported to date. For example,
maximum reported turnover number (TON) for the Crabtree
4
−1
to 4 × 10 h in the first hour, and the reaction also takes place at
−1
as low as 110 °C, with a TOF up to 190 h in the first hour. By
switching the base to NaOH, the reaction eudiometry kinetic
profile appeared a little slower yet steadier through a higher
conversion; furthermore, the sodium salt enables more facile
product isolation (vide infra).
7
a
7b
(
Ir) and Beller (Ru) systems are 30 100 and 256 326,
respectively. In a case of a polymeric iridium catalyst, the
7c
maximum TON is 124 000. Further, our system is robust at
higher temperatures: at 180 °C the reaction time is shortened
from days to hours (entries 5−9). We think that the greater
stability and longevity of catalyst 9 is due, in part, to the bidentate
architecture of the (pyridyl)carbene. This appears to inhibit
ligand scrambling processes, which are observed in the Crabtree
While our reaction mixtures are suspensions because of the
sparing solubility of the hydroxide base, we find that that
dehydrogenation catalysis is most likely homogeneous on the
basis of (1) physical appearance, (2) clean kinetics, and (3)
tolerance of liquid mercury. Quantitative poisoning results are
7
a
7,10
system.
less useful with this reaction:
surprisingly, 1,10-phenanthro-
Because these reactions are free of solvent, the medium is very
viscous, and the hydroxide base is a partially dissolved
suspension. Upon completion, the reaction mixture comprises
mostly lactate salt. Thus, the reaction reaches a solid, unstirrable
line, a popular catalyst poison that quantitatively deactivates 2 in
formic acid dehydrogenation, was found to have no significant
impact on the reaction kinetics, even when present in large excess
(35 equiv to [Ir]). We thus find that 9 is tolerant of nitrogen-
containing compounds. Triphenylphosphine, another strong
poison for homogeneous iridium catalysts, was also used in our
glycerol dehydrogenation reaction. With a substoichiometric
amount of the poison (0.5 equiv to [Ir]), the reaction rate is
within error of the parent. With 600 equiv of triphenylphosphine
to catalyst, the reaction stopped after ca. 3% conversion, 1500
TON.
state at its end, when H ceases to evolve. At this point, the
2
reaction system is no longer a fluid. The reaction rate slows after
ca. 25−30% conversion. We expect that this is a result of the very
high viscosity of the reaction mixture limiting mixing and heat
flow, rather than chemical deactivation of the catalyst itself.
Accordingly, higher catalyst loading will affect higher conversion
(compare entries 4 and 11).
While 5 is very robust, we sought a faster and more efficient
Key to the value of this contribution is the ability to convert
crude output from biodiesel production to value added material.
Along these lines, we have demonstrated the conversion of
soybean oil to fatty acid methyl esters (FAMEs, a biodiesel
7a
catalyst. Unlike Crabtree’s iridium systems, our CO-coordi-
nated catalyst precursor (6) shows a mild decrease in catalytic
reactivity relative to 5 (compare Table 1, entries 4 and 13). We
2
015
DOI: 10.1021/acscatal.5b02732
ACS Catal. 2016, 6, 2014−2017

ACS Catalysis
Letter
component) and crude glycerol, then further conversion of the
resulting crude glycerol to lactate salt. Thus, we treated 100 mL
More interesting to us is the mechanism of the catalytic
oxidation cycle (Scheme 2b). We propose that the active catalytic
species is monomeric: unlike species 1, species 5 and 9 do not
undergo dimerization in the presence of buffered formic acid and
lack 1’s reactivity in formic acid dehydrogenation. Particularly,
under comparable conditions (140 ppm [Ir], 280 ppm base in 2
(
93.2 g) of Wesson soy bean oil with sodium methoxide and
successfully isolated 100 mL of FAMEs and 9.3 g glycerol, the
latter with >95% NMR purity. With no purification other than
solvent removal, this glycerol was catalytically converted to an
isolated aliquot of 5.6 g of lactic acid.
mL HCO H, 3.5 h), a 1-catalyzed reaction undergoes >97%
2
Of further importance to the utility of this technology is a facile
route to convert the crude lactate salt to rac- and meso-lactide
monomers for use in poly(lactic acid) synthesis. We have
achieved this using a simple pH extraction followed by known
transformations for lactide preparation (see Supporting
Information). Thus, lactic acid can be thermally oligomerized
directly from our concentrated extract to yield a prepolymer,
which can then be treated with SnO to convert the material to
crude rac- and meso-lactide mixture. Recrystallization of the
lactide mixture successfully afforded rac-lactide with high purity
and a yield of 69% from crude lactic acid, with a small fraction of
meso-lactide available from the mother liquor.
conversion of formic acid, whereas the conversion is below 3%
when 5 or 9 is used. Conversely, 1 does not lead to efficient
glycerol to lactate conversion under the conditions used in Table
1. In a representative example, when 200 ppm 1 is heated with
glycerol and hydroxide, lactate is formed with <5% conversion at
the point that catalyst turnover ceases.
Unfortunately, study of this mechanism is frustrated by a
complicated network of exchangeable protons and rapidly
substituting labile oxygen ligands. We believe that catalysis
initiates from 9 by solvent displacement of 9’s cyclooctadiene
ligand, which we observe to be rapid, even at room temperature.
We then believe that our ligand is deprotonated to make a
charge-neutral complex. This deprotonated form of 9 is deeply
purple in color, which is observed at room temperature only
Beyond glycerol conversion, we find that 9 is a catalyst for
general alcohol dehydrogenation. For example, we can effect
methanol dehydrogenation in a refluxing alkaline solution of 25%
aqueous methanol. From the reaction solution, we evolve
13
when 9 is treated with base in the absence of glycerol. If 9 is
treated with base in the presence of glycerol, the red solution of 9
assumes a light yellow color, which is characteristic of our
working catalyst. We therefore expect that the deprotonated
catalyst cleaves glycerol’s O−H bond cooperatively, rather than
by simple proton transfer, because we observe that 9 is more
acidic than glycerol. One possibility for this O−H cleavage is
illustrated as 10. We think that the catalyst rests as a mixture of
coordination adducts of deprotonated glycerol, which are
sketched as 11.
hydrogen with 461 turnovers of H in 12 h and isolate a crystal
2
Na CO ·NaHCO ·H O as the byproduct.
2
3
3
2
Although we do not yet have a complete understanding of the
mechanism of our reaction, we do have a working model
11
(
Scheme 2). The fate of the organic species is known: an initial,
Scheme 2. Mechanistic Model for Catalytic Glycerol
Dehydrogenation with 9
We used dehydrogenation of 1-phenylethanol as simplified
model to probe reaction kinetics. The turnover-limiting step of
catalysis appears to be β-hydride elimination from an iridium
alkoxide such as 11. Three key data points support this finding:
(
1) we observe a first-order dependence on the concentration of
the alcohol substrate, which is inconsistent with rate-determining
H−H bond formation or H loss. (2) We find an insignificant
2
KIE
of 1.1(1), which is inconsistent with kinetic relevance
OH/OD
of any transition state involving O−H cleavage or H−H
formation. (3) A more electron-rich substrate, 1-(4-
methoxyphenyl)ethanol, dehydrogenates with a rate ca. 3 times
faster than 1-phenethylethanol. This indicates a negative
(
electrophilic) Hammett reaction parameter, which is better fit
to β-hydride elimination than H−H bond formation or ligand
14
substitution as a turnover-limiting step.
We do not know which hydroxyl group of glycerol is oxidized:
i
in two parallel experiments in which aqueous solutions of PrOH
n
and PrOH are dehydrogenated with 9 and base, we see rates that
are identical within error. Either of these β-hydride elimination
reactions should form an iridium hydride, which is sketched as 12
in Scheme 2. Hydrogen is likely released from hydride 12 by
protonation with an alcohol O−H group. While we see no
evidence for an iridium hydride under the catalytic conditions,
we can observe a diversity of iridium hydride species at room
temperature when 9 is treated with a stoichiometric portion of
isopropanol in alkaline solution. We therefore find that an
iridium hydride is a plausible intermediate, although not a resting
state of catalysis.
rate-determining dehydrogenation of either of the alcohol
positions of glycerol enables facile dehydration and rearrange-
ment according to Scheme 2a. We know that catalytic oxidation
is the slow step in this sequence for us because we see no organic
species other than glycerol and lactate >1% by NMR under the
catalytic conditions. In addition, conversion of glyceraldehyde to
lactate is known to be rapid at temperatures as low as 25 °C in
In conclusion, we present here a high-utility technique for the
conversion of crude glycerol to value-added lactides based on the
oxidative conversion of glycerol to lactate. This oxidation utilizes
a structurally novel iridium catalyst supported by a bidentate
1
2
alkali media.
2
016
DOI: 10.1021/acscatal.5b02732
ACS Catal. 2016, 6, 2014−2017

ACS Catalysis
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ASSOCIATED CONTENT
Supporting Information
■
*
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acscatal.5b02732.
CDCC #1438246 (5) and #1438247 (9) contain supplementary
crystallographic data for this paper. These data can be obtained
free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
́
Santos, L. L.; Leyva-Perez, A.; Sabater, M. J.; Iborra, S.; Corma, A. J.
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& Materials Opportunity Assessment, January, 2014. Available at the
following: http://www.usda.gov/oce/reports/energy/USDA_
RenewChems_Jan2014.pdf.
Experimental procedures, graphical, and tabular character-
ization information (PDF)
X-ray data for 5 (CIF)
X-ray data for 9 (CIF)
The carbonate product of methanol dehydrogenation, as
described in the SI (CIF)
(
7) (a) Sharninghausen, L. S.; Campos, J.; Manas, M. G.; Crabtree, R.
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8) CCDC 1415049 (1), 1415050 (2), 1438246 (5) and 1438247 (9)
contain supplementary crystallographic data for known (1, 2) and novel
5, 9) Ir compounds.
9) Celaje, J. J. A.; Lu, Z.; Kedzie, E. A.; Terrile, N. J.; Williams, T. J.
Nat. Energy, unpublished results.
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AUTHOR INFORMATION
Corresponding Author
E-mail: travisw@usc.edu.
■
(
(
*
Notes
(
The authors declare no competing financial interest.
3
28−337. Maris, E. P.; Ketchie, W. C.; Murayama, M.; Davis, R. J. J.
Catal. 2007, 251, 281−294. (c) Roy, D.; Subramaniam, B.; Chaudhari,
ACKNOWLEDGMENTS
This work was sponsored by the National Science Foundation
CHE-1054910) and the Hydrocarbon Research Foundation.
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(
1
research instrumentation. Fellowship assistance from The
Sonosky Foundation of the USC Wrigley Institute (ZL) is
gratefully acknowledged. We thank Dr. Ralf Haiges for help with
X-ray crystallography and Nemal Gobalasingham and Michael
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