One-Pot Homogeneous and Heterogeneous Oxidation of Glycerol to Ketomalonic Acid Mediated by TEMPO

Article abstract of DOI:10.1002/adsc.200390043

Glycerol, an increasingly abundant by-product of biodiesel production, is selectively converted to ketomalonic acid in one pot at pH 10 using NaOCl as regenerating oxidant in water at 2 °C in the presence of catalytic Br ^- along with the radical TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl) . The reaction can also be conducted at completion over a sol-gel silica glass doped with the nitroxyl radical. Considering the stability and versatility of such doped glasses, these materials show real promise as reusable metal-free catalysts for the conversion of a readily available and renewable biofeedstock into a highly valued compound.

Full text of DOI:10.1002/adsc.200390043

FULL PAPERS
One-Pot Homogeneous and Heterogeneous Oxidation of
Glycerol to Ketomalonic Acid Mediated by TEMPO
Rosaria Ciriminna, Mario Pagliaro*
Institute for the Study of Nanostructured Materials, Section of Palermo, CNR, via Ugo La Malfa 153, 90146 Palermo, Italy
Phone: ( ‡ 39)-91-680-9370, Fax: ( ‡ 39)-91-680-9399, e-mail: pagliaro@pa.ismn.cnr.it
Received: September 9, 2002; Accepted: November 14, 2002
Abstract: Glycerol, an increasingly abundant by- Considering the stability and versatility of such doped
product of biodiesel production, is selectively con- glasses, these materials show real promise as reusable
verted to ketomalonic acid in one pot at pH 10 using metal-free catalysts for the conversion of a readily
NaOCl as regenerating oxidant in water at 2 8C in the available and renewable biofeedstock into a highly
presence of catalytic BrÀ along with the radical valued compound.
TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl). The
reaction can also be conducted at completion over a Keywords: glycerol; heterogeneous catalysis; oxida-
sol-gel silica glass doped with the nitroxyl radical. tion; sodium hypochlorite; sol-gel catalyst; TEMPO
Introduction
tance of the obtainable oxygenated derivatives (Scheme
1).[5]
The catalytic oxidation of alcohols to carbonyl com-
The oxidation of a primary alcohol group of glycerol,
pounds and to carboxylic acids is a highly active research for instance, yields glyceric acid and, subsequently,
field[1] due to the synthetic and commercial relevance of tartronic acid, both commercially useful compounds
these compounds as fine chemicals and to the growing obtained by glycerol oxidation with HNO3;[6] on the
environmental and economic problems posed by tradi- other hand, the oxidation of a secondary hydroxy group
tional industrial oxidation processes using (at best) of glycerol yields the important fine chemical dihydrox-
stoichiometric amounts of heavy metals or mineral yacetone, while the oxidation of both primary and
acids.[2] The selective oxidation of carbohydrates, in secondary alcohol groups affords the highly functional-
particular, is a highly desirable conversion due to the ised molecule ketomalonic (or mesoxalic) acid, a
numberofusefulsubstances that could be obtainedfrom valuable compound with potential applications as an
renewable and readily available feedstocks.[3]
organic synthon[7] whose chlorophenylhydrazone was
Similarly, the selective oxidation of glycerol (1,2,3- recently found to show relevant biological activity as an
propanetriol) is an important research goal due also to anti-HIV agent.[8]
its increasing abundance as by-product in the biodiesel
Similarly to what happens with carbohydrates, how-
production (esterification of oil seeds triglycerides with ever, the extensive functionalisation of the triol glycerol
methanol)[4a] that renders the production of glycerin molecule with hydroxy groups of similar reactivity
independent of market demand.[4b] Clearly, an efficient renders its selective conversion particularly difficult.
oxidative route would open new markets for this Moreover, glycerol is easily converted to formaldehyde,
abundant commodity due to the commercial impor- formic acid and CO2 and in some cases mass balances as
low as 20% were observed[9] with good selectivities at
high glycerol conversion difficult to achieve due to rapid
overoxidation, and high selectivities becoming more
OH
OH
O
difficult as the compounds become more oxidised.
Hence, for instance, the catalytic aerobic oxidation of
glycerol in water over carbon-supported Pt at 50 8C
yields glyceric acid with a maximum 70% yield obtained
at pH 11;[5] while supported over CeO2, Pt catalyses the
oxidation of both primary alcohols giving tartronic acid
in 40% yield.[10] Finally, at acidic pH a Pt/C catalyst
promoted with bismuth favours the formation of
dihydroxyacetone[11] with an optimised maximum 37%
yield at 70% glycerol conversion.[5]
HO
OH
HO
OH
HO
OH
O
O
O
O
O
glyceric acid
tartronic acid
O
OH
ketomalonic acid
HO
OH
O
glycerol
HO
OH
HO
OH
O
dihydroxyacetone
Scheme 1. Products obtainable from the selective oxidation
of glycerol.
Adv. Synth. Catal. 2003, 345, No. 3
¹ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim 1615-4150/03/34503-383 388 $ 17.50+.50/0
383

Rosaria Ciriminna, Mario Pagliaro
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These differences in selectivity can be exploited to TEMPO was recently found to be a reusable catalyst for
catalytically synthesise ketomalonic acid in a 2-step the same conversion.[16]
aerobic process with an overall 40% yield converting
Now, we report that at pH 10 TEMPO is a selective
glycerol first to tartronic acid over a Pt/CeO2 catalyst, and highly active catalyst for the homogeneous oxida-
and then tartronic acid to ketomalonic acid by replacing tion of glycerol in one pot, affording high yields of
the first catalyst with PtBi/C;[10] interestingly, when a ketomalonic acid with NaOCl/BrÀ as regenerating
single multifunctional supported BiPtPd/CeO2 catalyst oxidant. We also show that microporous sol-gel silica
is used either under basic[12a] or acidic[12b] conditions, glasses doped with TEMPO are stable heterogeneous
glycerol is directly converted to poly(ketomalonate) in catalysts for the same conversion allowing easy catalyst
an elegant one-pot oxidative polymerisation process separation from the reaction mixture and recycle.
affording a high molecular weight polycarboxylate.
Oxidative dehydrogenations of alcohols over sup-
ported noble metal catalysts, however, generally suffer Results and Discussion
from the low stability of supported metals in the
oxidative environment requiring high metal/substrate
Homogeneous Oxidation
ratios, along with a thorough control of the reaction
conditions to minimise the formation of undesired by-
products which, nonetheless, are always present in the The reaction started immediately after adding TEMPO
reaction mixture.[5,7,9 12]
to the reactants in solution with extremely fast gener-
On the other hand, stable organic nitroxyl radicals ation of acid. No induction time typical of TEMPO-
of the TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl) mediated sugar oxidations was observed (Figure 1):
family are increasinglyused for the catalytic oxidation of
alcohols to carbonyl (and carboxyl) compounds due to
ꢀ1†
the pronounced selective activity and versatility of the
‡
actual oxidant species TEMPO , easily (re)generated in
situ by a variety of primary oxidants under mild
conditions either in water, in organic solvents or in The 13C NMR (Figure 2) and FT-IR spectra show
biphasic systems.[13] A TEMPO-mediated process in evidence that the reaction product is the sodium salt of
water using bleach as primary oxidant, for example, is ketomalonic acid with the NMR signals of the carbonyl
now commercially used for the synthesis of uronates in carbon resonating at 175 ppm and the carboxyl signal
high yields starting from carbohydrates (Scheme 2),[14] observed at 168 ppm; the infrared spectrum, in its turn,
which is based on the regioselectivity of the oxoammo- coincides with that of authentic sodium ketomalonate.
‡
nium ion TEMPO for the oxidation of primary vs.
Consumption of 3mmol of hydroxy groups per mmol
substrate indicates complete oxidation of glycerol×s
secondary alcohols in alkaline environment.
It is therefore somehow surprising that, in contrast to alcoholic groups, with TEMPO being the actual oxida-
the number of studies on catalytic dehydrogenations tion mediator since when no TEMPO is added to the
over noble metals mentioned above, to the best of our glycerol solution in the presence of NaOCl and Br- at pH
knowledge no study reports on the employment of
TEMPO in the oxidation of glycerol. This is even more
surprising considering that the superiority of TEMPO
over metal catalysis for sugar oxidations was report-
ed,[15] and also that encapsulated sol-gel silica-entrapped
–
–
OCl /Br
Primary
alcohol groups
Aldehydes
Carboxylates
TEMPO
–
–
OCl /Br
N
O
N
O
N
OH
TEMPO
–
–
Br
OBr
–
–
Cl
OCl
Figure 1. Kinetics of the NaOBr glycerol oxidation at 2 8C
mediated by (a) homogeneous TEMPO and, (b) by sol-gel
silica-entrapped TEMPO.
Scheme 2. Catalytic TEMPO oxidation cycle with OClÀ/BrÀ
as terminal oxidant.
384
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One-Pot Oxidations of Glycerol to Ketomalonic Acid Mediated by TEMPO
FULL PAPERS
Finally, the pH of the oxidation had a crucial influence
on the activity, which is typical of TEMPO mediated
oxidations.[13] Hence, at pH 7 the reaction did not
proceed while the reaction rate increased up to a
maximum at pH 10, decreasing at more alkaline pH
‡
probablydue to consumption ofTEMPO throughbasic
dismutation.[18]
Heterogeneous Oxidation
Having recently introduced sol-gel silica glasses doped
with TEMPO as recyclable catalysts for carbohydrate
oxidation,[15] we attempted the oxidation of glycerol
over such sol-gels using as catalyst a microporous
xerogel prepared from a sol at pH 6 (SG-TEMPO, 300
mmol radical/g).
Under the same conditions as for the homogeneous
process, oxidation started immediately upon the addi-
tion of the solid catalyst as shown by rapid acid
generation (Figure 1b). Again, glycerol was converted
to ketomalonate with low amounts of dihydroxyacetone
Figure 2. 13C NMR spectrum of sodium mesoxalate obtained
upon glycerol oxidation mediated by TEMPO.
10, the oxidation proceeds very slowly (0.130 mmol of and tartronic acid produced as intermediate by-products
OHÀ consumed after 2 h) yielding low amounts of even if, due to the diffusional limitations imposed by the
dihydroxyacetone and glyceric acid (5% and 2%, narrow pore network (pores average size ~15 ä), the
respectively) but no ketomalonic acid.
Upon the addition of 6.5% mol TEMPO, on the other in the homogeneous conversion.
reaction rate was considerably lower (~ TOF 4 hÀ1) than
hand, after 30 minutes only, most of the added glycerol
However, in each catalytic run mediated by the doped
substrate was directly converted to ketomalonic acid sol-gel no leaching of the encapsulated active species in
(average TOF ~70 hÀ1), while the by-products tartronic solution was detected(elemental analysis ofthe reaction
acid (~0.6%, rt ˆ 13.43 min) and dihydroxyacetone filtrate) and the reaction was heterogeneous in nature as
(~10%, rt ˆ 24.35 min) also present in solution were proved by the lack of further reactivity of the reaction
progressively oxidised to ketomalonic acid until, after 3 filtrate obtained upon separation of the catalyst shortly
h of reaction, a modest amount of dihydroxyacetone (30 min) after the beginning of reaction.
(~2%) was the sole by-product left in solution, with an
overall 98% selectivity to ketomalonic acid at complete
glycerol conversion.
Catalyst Stability and Recyclability
The low temperature and the pH applied in the
reaction minimise the oxidation of primary and secon- Heterogeneous catalyst stability is truly measured by
dary hydroxy groups by hypochlorite,[17] and it is the intermediate yields after a given reaction time in
TEMPO that mediates also the oxidation of the latter consecutive reaction runs, since in case of absolute
alcohol groups. Indeed, we attempted the oxidation of stability a constant yield in all subsequent runs should be
authentic tartronic acid under the same conditions as for expected.[1,19]
glycerol oxidation and no formation of ketomalonate
Reaction yields after 1 h of reactions presented in
was observed until the addition of catalytic TEMPO Figure 3show indeed that SG-TEMPO is remarkably
(6.5 mol %), whereupon the oxidation of tartronic acid×s stable and this is in contrast to the low stability of silica-
H-C-OH function suddenly started with fast base anchored TEMPO employed in water in the analogous
consumption (due to consumption of hypochlorite in oxidation of methyl-glucose with OClÀ/BrÀ.[20]
equilibrium with HOCl, Equations 2 and 3), eventually
To explain these differences in stability, it should be
yielding quantitative conversion of tartronic to ketoma- considered that in contrast to traditional surface deriva-
lonic acid.
tisation methods that leave the anchored nitroxyl
radicals unprotected at the material surface, the sol-gel
homogeneous encapsulation isolates the radicals within
nanoporous sol-gel cages, that is within the hundreds of
square metres per gram of internal surface area (430
m2/g for SG-TEMPO) compared to the negligible
amount of molecules entrapped at the outer reaches
ꢀ2†
ꢀ3†
Adv. Synth. Catal. 2003, 345, 383 388
385

Rosaria Ciriminna, Mario Pagliaro
FULL PAPERS
Figure 3. Degree of oxidation of glycerol (GLY D.O.) over
SG-TEMPO with OClÀ/BrÀ as primary oxidant after 1 h
reaction time in consecutive reaction runs.
(1 2 m2/g) of the particulate material.[21] And it is
precisely this unique structural feature of sol-gels that
protects the radicals from the intramolecular quenching
of the molecules bound in proximity at the silica sur-
face, that was recently found to be responsible for the
continuous decrease in the activity of silica-anchored
Figure 4. EPR spectra of the xerogel SG-TEMPO before
(above) and after (below) reaction in aqueous bleach.
Finally, the catalyst morphology revealed by scanning
TEMPO in consecutive alcohol oxidation runs with electron microscopy (SEM) shows that the xerogel is
OClÀ/BrÀ as internal oxidant.[1]
essentially constituted of silica aggregates and magnifi-
To investigate thus the effect of reaction on the cation up to a 50,000 factor (Figure 5) reveals that in
structure of the catalyst sol-gel cages, the EPR spectra of contrast to most powders the gel is nanostructured
SG-TEMPO before and after oxidation were recorded which given that the surface geometry experienced by
(Figure 4).
the approaching reactant molecules has a profound
Besides analogous peak intensities (the spectra are effect on the material reactivity,[24] and that the struc-
qualitative, taken on powder samples packed in a glass tural properties of sol-gels can be tailored to meet a vast
tube for the analysis), the EPR signals show that upon range of requirements[25] may be a relevant subject for
reaction both the distance between the outer lines further investigations aimed at optimisation of the
(related to the nitrogen hyperfine coupling constant of materials catalytic performance.
the interaction of the unpaired electron with the spin of
14N nucleus)[22] and the line width (related to the probe
rotation correlation times)[22] remain practically unvar-
ied showing, respectively, no change in the polarity and Conclusions
in the viscosity sensed by the entrapped spin label
chemically bound[16] to the sol-gel cage. This is likely due In conclusion, we have discovered that TEMPO is an
to the pronounced amount of bound water molecules active and selective catalyst affording high yields of
within the cages of the original hydrophilic silica gel ketomalonic acid from glycerol by simply using NaOCl
resulting in an high degree of hydrogen bonding as primary oxidant under very mild conditions. More-
between the Si-OH groups at the cage surface and said over, we show that sol-gel silica xerogels doped with the
water molecules, which is unmodified upon reaction of radical are recyclable heterogeneous catalysts for the
the catalyst in aqueous bleach.
same high-yield conversion while retaining their selec-
Evidence for a lack of degradation of the catalyst silica tive activity. Considering the enormous versatility of
structure in the buffered alkaline reaction environment both technologies (the sol-gel process for the production
was obtained by FT-IR analysis of the catalyst prior to of reactive materials[25] and TEMPO-mediated alcohol
and after 7 oxidative runs with the broad signals oxidations[13]) together with the usefulness of ketoma-
overlapping in the 1085 1100 cmÀ1 region due to the lonic acid, these findings might open the way to an high
Si-O-Si asymmetric stretching[23] showing that the silica value-added commercial conversion[26] of an increas-
polymeric backbone is unaffected by the prolonged use ingly abundant biomass product into a valuable fine
in the reaction system.
chemical.
386
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One-Pot Oxidations of Glycerol to Ketomalonic Acid Mediated by TEMPO
FULL PAPERS
When the reaction was complete (no more acid formation), the
reaction product was precipitated with cold ethanol (50 mL,
À 20 8C), filtered and extensively washed with EtOH (80%, v/
v), prior to drying at 40 8C and analysis of the resulting white
powder by NMR and FT-IR. In the heterogeneous oxidation,
after reaction was complete the reaction mixture was filtered
and the powdered solid catalyst recovered, washed with water
and EtOH, air-dried and reused as such in a consecutive
reaction run.
General Methods
Acid formation was monitored by an automatic titrator
(Mettler-Toledo DL50) and the reaction products detected at
215 nm. The HPLC column system (Alltech IOA 1000 for
organic acids) was connected in series with a UV-Vis detector
(Shimadzu) using 0.005 M H2SO4 as mobile phase. Yields were
calculated by the calibration curves obtained using authentic
reagents and by the isolated product. The NMR spectra in D2O
were recorded on a Bruker spectrometer working at a proton
resonating frequency of 250 MHz; the EPR experiment was
conducted on a Bruker spectrometer working at medium
frequency (50 kHz) and low amplitude (0.504 G) modulation.
The FT-IR spectra were obtained on a Bruker Vector 22
spectrometer from samples dispersed in KBr, and the SEM
photographs taken with a Philips XL 30 ESEM scanning
electron microscope. Textural N2-BET values of the sol-gel
were obtained on a Carlo Erba 1900 Sorptomatic surface
analyzer for powders.
Figure 5. SEM photographs of the SG-TEMPO xerogel at
500 (a) and 50,000 (b) magnifications.
Acknowledgements
Experimental Section
Thanks are due to Dr. A. Bonetti (Mettler-Toledo Italia, Milan)
and to University of Palermo×s Dr. F. Saiano (Laboratory of
Agriculture Chemistry) for the FT-IR measurements, Dr. G.
MarcÏ (Dept. of Chemical Engineering) for the SEM photo-
graphs and Prof. L. La Martina (Dept. of Pharmaceutical
Chemistry) for the NMR measurements. We warmly acknowl-
edge Dr Paul McMorn (Dept. of Chemistry, University of
Cardiff) for his contributions offered in helpful correspondence.
Materials and Reagents
Aqueous sodium hypochlorite (13% w/w, 1.2 g mLÀ1) was
obtained by Fluka (Buchs, Switzerland). Glycerol (99.9%
purity) and all other chemicals were obtained by Aldrich (St.
Louis, MO, USA) and used without further purification. The
preparation of the catalytic xerogel (SG-TEMPO, obtained by
a sol precursor with molar ratio Si:H2O:MeOH ˆ 1:8:5)
through reductive amination of 4-oxo-TEMPO with 3-amino-
propyltrimethoxysilane followed by sol-gel hydrolysis and co-
polycondensation with Si(OMe)4 was reported elsewhere.[16]
References and Notes
[1] For a recent account on recent important advancements
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General Oxidation Procedures
A solution of glycerol (62.5 mL, 1 mmol) and NaBr (6.78 mg,
6.6% mol) in 25 mL of distilled water immersed in an ice-bath
was added with NaOCl (2.80 mL, 6 mmol) in 20% molar excess
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value throughout the oxidation by the addition of 0.5 M NaOH,
controlled by a pH stat. The reaction started immediately after
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of SG-TEMPO), and the oxidation was followed by the
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Adv. Synth. Catal. 2003, 345, 383 388
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FULL PAPERS
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388
Adv. Synth. Catal. 2003, 345, 383 388