Immobilized methyltrioxo rhenium (MTO)/H2O2 systems for the oxidation of lignin and lignin model compounds

Article abstract of DOI:10.1016/j.bmc.2006.03.046

A convenient and efficient application of heterogeneous methylrhenium trioxide (MTO) systems for the selective oxidation of lignin model compounds and lignins is reported. Environmental friendly and low-cost H₂O₂ was used as the oxygen atom donor. Overall, the data presented and discussed in this paper point toward the conclusion that the immobilized heterogeneous catalytic systems based on H₂O₂/and MTO catalysts are able to extensively oxidize both phenolic and non-phenolic, monomeric, and dimeric, lignin model compounds. Condensed diphenylmethane models were found also extensively oxidized. Technical lignins, such as hydrolytic sugar cane lignin (SCL) and red spruce kraft lignin (RSL), displayed oxidative activity with immobilized MTO catalytic systems. After oxidation, these lignins displayed the formation of more soluble lignin fragments with a high degree of degradation as indicated by the lower contents of aliphatic and condensed OH groups, and the higher amounts of carboxylic acid moieties. Our data indicate that immobilized MTO catalytic systems are significant potential candidates for the development of alternative totally chlorine-free delignification processes and environmental sustainable lignin selective modification reactions.

Full text of DOI:10.1016/j.bmc.2006.03.046

Bioorganic & Medicinal Chemistry 14 (2006) 5292–5302
Immobilized methyltrioxo rhenium (MTO)/H2O2 systems for the
oxidation of lignin and lignin model compounds
Claudia Crestini,a,* Maria Chiara Caponi,b Dimitris S. Argyropoulosc and
Raffaele Saladinob,*
a
`
Dipartimento di Scienze e Tecnologie Chimiche Universita di Tor Vergata, Via della ricerca Scientifica, 00133, Roma, Italy
b
`
Dipartimento di Agrobiologia e Agrochimica, Universita della Tuscia, Via San Camillo de Lellis, 01100, Viterbo, Italy
cForest Biomaterials Laboratory, North Carolina State University Raleigh, NC, USA
Received 30 January 2006; revised 20 March 2006; accepted 24 March 2006
Available online 18 April 2006
Abstract—A convenient and efficient application of heterogeneous methylrhenium trioxide (MTO) systems for the selective oxida-
tion of lignin model compounds and lignins is reported. Environmental friendly and low-cost H2O2 was used as the oxygen atom
donor. Overall, the data presented and discussed in this paper point toward the conclusion that the immobilized heterogeneous cat-
alytic systems based on H2O2/and MTO catalysts are able to extensively oxidize both phenolic and non-phenolic, monomeric, and
dimeric, lignin model compounds. Condensed diphenylmethane models were found also extensively oxidized. Technical lignins, such
as hydrolytic sugar cane lignin (SCL) and red spruce kraft lignin (RSL), displayed oxidative activity with immobilized MTO cata-
lytic systems. After oxidation, these lignins displayed the formation of more soluble lignin fragments with a high degree of degra-
dation as indicated by the lower contents of aliphatic and condensed OH groups, and the higher amounts of carboxylic acid
moieties. Our data indicate that immobilized MTO catalytic systems are significant potential candidates for the development of
alternative totally chlorine-free delignification processes and environmentally sustainable lignin selective modification reactions.
ꢀ 2006 Elsevier Ltd. All rights reserved.
1. Introduction
A novel catalyst potentially useful for this purpose is
methyltrioxorhenium (VII) (MeReO3, MTO).3 MTO in
combination with H2O2 has become in recent years an
important catalyst for a variety of synthetic transforma-
tions, such as oxidation of olefins,4 alkynes,5 sulfur com-
pounds,6 phosphines,7 Bayer–Villiger rearrangement,8
and oxidation of C–H bonds.9 Accordingly with this
high reactivity, MTO is able to catalyze the oxidation
of aromatic derivatives.10
In the paper production processes, environmental con-
cerns have prompted us to design pulping and bleaching
sequences avoiding the use of chlorinated compounds.
Totally chlorine-free (TCF) processes have been devel-
oped, as, for example, by the use of oxygen, hydrogen
peroxide (H2O2), and ozone as primary oxidants.1 How-
ever, their major drawback consists in a lack of selectiv-
ity in the oxidation of lignin, which leads to the partial
degradation of the cellulose contained in pulps, and ulti-
mately in a lower final product yield. The lack of selec-
tivity is due fundamentally to the formation of radical
intermediates, such as hydroxyl radicals, that are able
to attack both cellulose and lignin.2 Selective catalytic
processes based on a concerted oxygen atom transfer
from environmental friendly H2O2 might solve these
problems.
Irrespective of the substrate to be oxidized, the reaction
proceeds through the formation of a mono-peroxo
[MeRe(O2)] (A) and a bis-peroxo [MeRe(O2)2] complex.
These reactive intermediates transfer one oxygen atom
to the substrate by a concerted mechanism avoiding
the formation of any radical species.4
With the aim to design novel delignification and bleach-
ing processes, we recently investigated the reactivity of
MTO in the oxidation of lignins and lignin model
compounds with H2O2 as the primary oxidant.11
Keywords: Methylrhenium trioxide; Hydrogen peroxide; Lignin
oxidation; Lignin model compounds.
*
MTO showed to be a powerful and efficient catalyst for
the oxidation of phenolic and non-phenolic lignin model
Corresponding authors. Tel.: +39 06 7259 4734; fax: +39 06 7259
4328; e-mail: crestini@uniroma2.it
0968-0896/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmc.2006.03.046

C. Crestini et al. / Bioorg. Med. Chem. 14 (2006) 5292–5302
5293
compounds representative of the main bonding pattern
present within native lignins, affording both side-chain
oxidations and aromatic ring cleavage reactions. Diph-
enylmethane models, that are usually recalcitrant to oxi-
dation, were also found to be extensively degraded
mainly via cleavage of their interunit methylene linkag-
es. MTO was also able to catalyze the extensive degrada-
tion of selected technical lignins, increasing their degree
of solubility and reducing their content in condensed
subunits.
poly(4-vinylpyridine) 2% and 25% cross-linked (with
divinylbenzene)/MTO (PVP-2%/MTO I and PVP-25%/
MTO II, respectively), poly(4-vinylpyridine-N-oxide)
2% cross-linked/MTO (PVPN-2%/MTO III), and micro-
encapsulated polystyrene 2% cross-linked/MTO (PS-2%/
MTO IV), are schematically represented in Figure 1.
We report here that catalysts I–IV can be efficiently used
for the selective oxidation of lignins and lignin model
compounds with H2O2 as environmental friendly
oxidant.
The possibility for alternative environmentally sustain-
able delignification processes requires the use of clean oxi-
dants such as hydrogen peroxide coupled with techniques
for the recovery and reuse of the catalysts. From this point
of view immobilized catalysts present the advantage of an
easy recovery and possibility of reuse and a low environ-
mental impact. In an effort to develop more versatile and
environmental friendly heterogeneous catalysts, we de-
scribed the preparation of novel rhenium compounds of
general formula (polymer)f/(MTO)g (the f/g quotient
expresses the ratio by weight of the two components) by
heterogenization of MTO on easily available and low-cost
polymeric support, poly(4-vinylpyridine) or polysty-
rene,12 applying the ‘mediator’ concept13 and the micro-
encapsulation technique.14
We selected an array of monomeric and dimeric lignin
model compounds resembling the main bonding pat-
terns in native and technical lignins, and studied their
reactivity with supported MTO catalysts by character-
ization of the main oxidation products in the presence
of H2O2. Our attention was next turned to more com-
plex lignin polymers, hydrolytic sugar cane lignin
(SCL) and red spruce kraft lignin (RSL), that are repre-
sentative examples of widely diffused para-hydroxyphe-
nyl-guaiacyl, and guaiacyl lignins. Their oxidation was
analyzed by means of advanced 31P NMR techniques
that allow the quantitative determination of all labile
OH groups on the polymer—that is, aliphatic, different
kinds of phenolic OH groups, and carboxylic acids—
after phosphitylation of the sample.20,21
All the novel MTO compounds were characterized by
FT-IR, scanning electron microscopy (SEM), and
wide-angle X-ray diffraction (WAXS) analyses.12 To
the best of our knowledge, apart from silica supported
MTO complexes,15 NaY zeolite/MTO supercage sys-
tem,16 and a niobia supported MTO compound,17 no
further data are available in the literature about hetero-
geneous MTO catalysts. These polymer/MTO catalysts
have already proved as efficient and selective systems
for the epoxidation of simple olefins,18 and for the oxi-
dation of substituted phenol and anisole derivatives.19
2. Results and discussion
2.1. Oxidation of lignin model compounds
The reactivity of aromatic model compounds resembling
the most representative lignin bonding patterns is of
pivotal interest in order to rationalize the oxidative
behavior of this biopolymer. Thus, an array of
monomeric and dimeric, phenolic and non-phenolic
lignin model compounds was carefully selected for study
in order to clarify the reactivity of the various lignin
subunits with H2O2 and catalysts I–IV.
The structures of poly(4-vinylpyridine)/MTO and
polystyrene/MTO catalysts I–IV employed, namely
N
N
MTO
MTO
_
_
+
MTO
N
MTO
O
O
N
+
N
N
MTO
n
n
PVP-2%/MTO I or
PVP-25%/MTO II
PVPN-2%/MTO III
PS-2%/MTO IV
Figure 1. Structure of poly(4-vinylpyridine)/MTO and polystyrene/MTO catalysts I–IV.

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C. Crestini et al. / Bioorg. Med. Chem. 14 (2006) 5292–5302
Vanillyl alcohol 1, veratryl alcohol 6, 1-(4-hydroxy-3-
methoxyphenyl)-2-(2,6-dimethoxyphenoxy)propane-1,3-
diol 10, 1-(4-ethoxy-3-methoxyphenyl)-2-(2,6-dimeth-
oxyphenoxy)propane-1,3-diol 14, 2,20-dihydroxy-3,30-
dimethoxy-5,50-dimethyl-diphenyl methane 19, and
2,20,3,30-tetramethoxy-5,50-dimethyl-diphenyl methane
26 were studied as substrates.
oxybenzoic acid 3, the muconolactone 4, and the para-
benzoquinone derivative 5 (see Scheme 1 and Table 1).
In all cases products 2 and 3 were obtained in signifi-
cantly higher yields (Scheme 1). Catalysts I–III showed
a reactivity comparable to that of homogeneous MTO:
II and III yielded a quantitative conversion of the sub-
strate, while a 75% conversion was found with I (Table
1) irrespective of the catalyst used in the transformation.
The data suggest a common reaction pathway. The effi-
cient oxidation of 1, under relatively mild experimental
conditions, may be attributed to both the retained reac-
tivity of the mono-peroxo and the bis-peroxo rhenium
intermediates24 in the presence of the polymeric sup-
ports, and to the lack of a kinetic barrier of the substrate
to approach the supported rhenium complex.
As a general procedure reactions were carried out by
treating the appropriate substrate (1.0 mmol) with
H2O2 (35% aqueous solution, 1.5 mmol) and supported
MTO catalysts enumerated as structures I–IV (contain-
ing 1.0% w/w of the active MTO oxidizing species) in
CH3COOH (5.0 mL) at room temperature for 6.0 h.
Irrespective of the experimental conditions used for
the oxidation, a low mass balance (reported in the
Tables 1–7) with respect to the isolated products was
observed. This was rationalized on the basis of the high
efficiency of the reaction. More specifically and in accor-
dance with earlier literature data, the loss of material
from the reaction mixture might be due to formation
of polar hydrophilic over-oxidation products, not recov-
ered by the usual work-up procedures.11,22,23
The formation of compounds 2 and 3 is in accordance
with data previously reported on the reactivity of sim-
ple aromatic hydrocarbons, with H2O2 and MTO, in
which case the oxidation of the benzylic group was
the main observed process.11 Muconolactone 4 was
most likely obtained via an extensive oxidative ring
opening of 1 to a muconic acid intermediate (not
recovered under our experimental conditions) followed
by formation of the lactone moiety, probably catalyzed
by MTO, which is known to possess Lewis and Bro¨n-
sted acidic character. Muconolactone derivatives have
been previously recovered as minor products in the oxi-
dative degradation of lignin model compounds.25
Finally, the isolation of para-benzoquinone 5 is in
accordance with the known reactivity of methoxybenz-
enes with MTO.18
All reaction products were characterized by gas-chroma-
tography coupled to mass-spectroscopy (GC–MS)
analyses after derivatization with bis(trimethylsilyltriflu-
oroacetamide) (BSTFA) and, when necessary, by 1H
and 13C NMR spectroscopies. Notably, during our
control measurements which were carried out in the
absence of the catalyst, less than 5% conversion of
substrate took place, under otherwise identical
experimental conditions. Similar oxidations carried out
in the presence of MTO are reported as references.11
The fact that the mass balance measured for heteroge-
neous oxidations (Table 1) was significantly higher than
that obtained with homogeneous MTO was very reveal-
ing. This most likely suggests that in the presence of
immobilized catalysts further oxidation reactions,
yielding to polar hydrophilic or polymeric products,
are significantly reduced.11
The simplest lignin model compound selected for this
investigation was vanillyl alcohol 1. The oxidation of 1
by immobilized catalyst systems I–III proceeded with
high conversion of substrate affording products of alkyl
side-chain oxidation, vanillin 2 and 4-hydroxy-3-meth-
Table 1. Oxidation of vanillyl alcohol 1 and veratryl alcohol 6 with H2O2 and catalysts I–III
Catalyst
Conversion of 1 (%)
Product yield
Mass balance
Conversion of 6 (%)
Product yield
Mass balance
2
3
4
5
7
8
9
MTOa
98
78
98
98
3.7
8.8
4.9
3.3
1.8
4.3
6.9
5.5
1.4
4.2
7.9
4.5
16
45
44
49
98
70
98
86
3.4
6.7
7.8
3.9
2.6
1.2
2.3
5.9
4.5
12
45
39
44
I
II
III
11.0
14.2
13.0
18.9
21.0
12.1
12.5
a Homogeneous conditions.
CHO
COOH
CH2OH
CH2OH
O
O
O
MTO/H2O2
AcOH
OCH3
OCH3
OCH3
O
COOR
OR
OR
OR
OH
1,2,3,4
R=H
2, 7
1, 6
3, 8
4 , 9
5
6,7,8,9 R=CH3
Scheme 1.

C. Crestini et al. / Bioorg. Med. Chem. 14 (2006) 5292–5302
5295
A similar behavior was observed in the oxidation of
veratryl alcohol 6, a non-phenolic lignin model com-
pound. Upon treatment with H2O2 and MTO catalysts
I–III, products of alkyl side-chain oxidation, 3,4-
dimethoxybenzaldehyde 7 and 3,4-dimethoxybenzoic
acid 8, and the muconolactone 9 were obtained (Scheme
1). The conversion amounts ranged from 70% with cat-
alyst I to >98% with catalyst II (Table 1) and were thus
found comparable to MTO (>98% conversion). Once
again the highest mass balances were obtained for
reactions carried out with supported catalysts.
Furthermore, Ca oxidation products were abundant as
evidenced by the presence of 4-hydroxy-3-methoxyben-
zoic acid 3 and the hydroxyketone 11. The same prod-
ucts are also indicative of alkyl side-chain oxidation
with 11 deriving from the aromatic A-ring of the sub-
strate and 2,6-dimethoxyphenol 12 deriving from the
aromatic B-ring of the substrate. The muconolactone
13 was also recovered in appreciable yield. However, a
high molecular weight (>550) compound, probably a tri-
mer or tetramer, that was apparent in GC–MS possess-
ing a molecular peak fragment corresponding to benzyl
alcohol substructure, could not be unambiguously
identified.11
Our attention was next focused on the oxidation of
dimeric lignin model compounds. The b-O-4 dimeric
compound 10 represents the most abundant bonding
pattern in softwood and hardwood lignins (guaiacyl, G
and guaiacyl-syringyl-lignins, GS-lignins, respectively).
The oxidation of compound 10 resulted in an extensive
degradation of the substrate (>98% conversion with
MTO and comparable conversions were obtained with
catalysts I–IV) and showed a reactivity pattern close
to that observed for 1 (Scheme 2 and Table 2).
The oxidation of compound 14 that is a softwood (gua-
iacyl) non-phenolic lignin model compound afforded
products of alkyl side-chain oxidation and cleavage at
the a- and b-positions deriving both from the A-aromat-
ic ring of substrate, 15, 17, and 18, or from the B-aro-
matic ring, compound 16 (Scheme 3 and Table 3).
The mass balance for the oxidations of 10 and 14 with
hydrogen peroxide catalyzed by compounds I–IV was
found higher than in the presence of homogeneous
MTO . These data are in accord with a reduced reactiv-
ity and increased selectivity due to the immobilization
It is interesting to note that the oxidation of 10 yielded
almost exclusively fragmentation products along the b-
O-4 bond linking the two aromatic moieties together.
H3CO
HO
γ
OH
O
O
CH2OH
OCH3
O
B
O
OH
HO
O
α
β
MTO/H2O2
AcOH
H CO
3
OCH3
H3CO
OCH3
HO
A
OCH3
O
OH
OH
OH
10
3
11
12
13
Scheme 2.
Table 2. Oxidation of 1-(4-hydroxy-3-methoxyphenyl)-2-(2,6-dimethoxyphenoxy)-3-hydroxypropanol 10 with H2O2 and catalysts I–IV
Catalyst
Conversion (%)
Product yield (%)
Mass balance (%)
3
11
12
13
9.3
MTOa
98
75
98
98
97
16.3
9.8
14.9
4.2
11.9
23.4
26.3
32.5
29.4
50
71
61
68
58
I
12.4
19.5
4.5
II
17.2
25.0
21.2
13.2
13.7
5.1
III
IV
6.8
a Homogeneous conditions.
HO
HO
HO
CHO
CHO
O
OH
OCH3
O
MTO/H2O2
AcOH
OCH3
OCH2CH3
OCH3
OCH2CH3
OCH3
OCH3
OCH2CH3
OCH2CH3
15
16
17
18
14
Scheme 3.

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C. Crestini et al. / Bioorg. Med. Chem. 14 (2006) 5292–5302
Table 3. Oxidation of 1-(4-ethoxy-3-methoxyphenyl)-2-(2-methoxyphenoxy)propane-1,3-diol 14 with H2O2 and catalysts I–IV
Catalyst
Conversion (%)
Product yield (%)
Mass balance (%)
15
3.4
16
17
18
7.3
MTOa
95
48
78
74
10
24.4
28.0
22.1
17.8
1.5
5.8
15.1
4.6
48
87
73
72
88
I
3.1
25.0
14.0
2.1
1.0
5.2
II
III
IV
8.3
2.0
12.6
2.2
a Homogeneous conditions.
process with respect to MTO. This trend was especially
evident in the oxidation of the less reactive compound
14. More specifically, in this case supported MTO cata-
lysts I–IV yielded % of mass balance ranging from
78.9% to 97.8% thus indicating the virtual absence of
further oxidation products. In accordance with the low-
er reactivity displayed by the non-phenolic lignin model
compounds toward oxidants,12 low values of conversion
of 14 were obtained with catalysts I–IV and H2O2 with
respect to 10.
(>550) compound, probably a trimer or tetramer, that
showed in GC–MS a molecular peak fragment corre-
sponding to 4-ethoxy-3-methoxy benzyl alcohol sub-
structure, could not be unambiguously identified.
Diphenylmethane subunits that are formed during lignin
pulping processes (their amounts vary upon the specific
wood species and pulping procedure used27) show high
recalcitrance to oxidation and their efficient degradation
requires severe reaction conditions in bleaching process-
es.26 In order to study the reactivity of such lignin sub-
units toward the H2O2/supported MTO systems, two
diphenylmethane lignin model compounds 19 and 26
were oxidized in the presence of catalysts I–IV. The oxi-
dation of 19 performed under previously described
experimental conditions gave products displaying vary-
ing degrees of oxidation at the benzylic positions, that
is, compounds 20, 21, and 22, while compound 23
showed alkyl side-chain oxidation and cleavage of the
diphenylmethane bridge. Similarly, compounds 24 and
25 were derived via the oxidative cleavage of the other
aromatic ring as displayed by the presence of the two
carbon atom alkyl side chain (Scheme 4 and Table 4).
Compound 16, that is a typical acidolysis product from
b-O-4 linkages, was probably obtained by formation of
a benzyl cation followed by b-hydrogen elimination and
hydrolytic cleavage. The effective formation of a benzyl
cation under acidolytic cleavage of b-O-4 lignin model
compounds was previously detected by means of ESI/
MS analysis.26
In the case of compounds 17 and 18, the alkyl side chain
was found dehydrated in accord with the acidic Lewis
and Bro¨nsted character of MTO.4 In analogy with the
oxidation of 10 reported above, a high molecular weight
CH2OH
R
CH2OH
MeO
MeO
OMe
COOH
OH
OH
OH
MTO/H2O2
AcOH
20 R= Me
21 R= CH2OH
22 R= CHO
23
R
OMe
MeO
OH
OH
COOH
H CO
3
OH
19
24 R= Me
25 R= CH2OH
Scheme 4.
Table 4. Oxidation of 2,20-methylenebis(6-methoxy-4-methylphenol) 19 with H2O2 and catalysts I–IV
Catalyst
Conversion (%)
Product yield (%)
Mass balance (%)
20
2.6
21
22
23
24
25
MTOb
98
98
98
98
98
1.5
0.1
0.3
0.4
0.9
Ta
2.4
Ta
0.8
0.2
0.1
Ta
3.8
8.0
1.4
1.8
0.4
13
15
11
29
17
I
3.5
2.9
0.15
0.2
Ta
Ta
II
1.0
0.2
0.2
III
IV
21.1
9.7
0.4
a Traces.
b Homogeneous conditions.

C. Crestini et al. / Bioorg. Med. Chem. 14 (2006) 5292–5302
5297
The recovery of compounds 23–25 is significant from an
industrial point of view since it suggests that MTO
based immobilized catalysts can effectively afford the
oxidative degradation of otherwise recalcitrant technical
lignins containing high amounts of oxidatively inert
diphenylmethane subunits. When the non-phenolic
diphenylmethane lignin model compound 26 was sub-
mitted to oxidation under the same experimental condi-
tions, several products of side-chain oxidation to benzyl
alcohol 27 and 28, aldehyde and carboxylic acid, com-
pound 29, were detected. Moreover, products of
demethylation at the alkyl-arylether moieties, 30, 31,
and 32, and deriving from the oxidative cleavage of
one of the aromatic rings, compound 33, were also
found (Scheme 5 and Table 5).
ide biomimetic oxidation with manganese and iron
porphyrins.31 In the latter case, the site of oxidation
was determined by the distribution of the electronic den-
sity on the aromatic ring, which was in turn modulated
by the electronic effect of the substituents.
In the case of diphenylmethane model compounds 19
and 26 all catalysts I–IV showed enhanced reactivity
as evidenced by the quantitative conversion of 19 (Table
4) and the 74–98% conversion range of 26 (Table 5).
Thus, unlike other oxidants it appears that MTO based
immobilized catalytic systems efficiently degrade diphen-
yl methane units. Furthermore, the mass balances at the
end of the reactions were found to be significantly lower
than the analogous mass balances observed for the reac-
tions of b-O-4 arylether model compounds 10 and 14,
thus pointing out to the occurrence of additional and
at the moment salient oxidative processes (Tables 4
and 5).
It is interesting to note that the methyl ester of 33 (not
shown) was previously recovered in low amounts after
the ozonation of 26.28 In accordance with the displayed
reactivity of MTO, it is likely that compound 33 was
formed by the initial oxidative ring opening of one of
the aromatic rings of compound 26 yielding the corre-
sponding muconic acid derivative followed by a stepwise
oxidative degradation.28,29
Some considerations can be drawn about the catalytic
behavior of compounds I–IV depending on their struc-
tural properties. The reactivity and selectivity of immo-
bilized MTO compounds can be finely tuned by the
chemical and physical properties of the resin used as
support. In this context, two main parameters appear
of great relevance for the lignin model compound
oxidations with poly(4-vinylpyridine) based catalysts:
the reticulation grade of the resin and the oxidation state
of the pyridinyl moieties (i.e., pyridine vs pyridine
Products of oxidation of the activated benzylic position
and oxidative cleavage of one of the aromatic moieties
were recently observed in the treatment of phenolic
and non-phenolic diphenylmethane lignin model com-
pounds with polyoxometalate30 and by hydrogen perox-
R1
R2
MeO
OMe
OMe
MeO
OMe
OMe
OMe
OH
27 R1= Me, R2=CH2OH
28 R1= R2=CH2OH
30
29 R1= COOH, R2=CHO
MTO/H2O2
AcOH
R1
R2
OMe
MeO
COOH
OMe
OMe
H CO
3
MeO
OMe
OMe
OMe
OMe
26
31 R1= R2=CH2OH
32 R1= Me, R2=CHO
33
Scheme 5.
Table 5. Oxidation of 1,10-methylenebis(2,3-dimethoxy-5-methylbenzene) 26 with H2O2 and catalysts I–IV
Catalyst
Conversion (%)
Product yield (%)
Mass balance (%)
27
28
29
30
31
32
33
MTOb
93
74
75
83
98
Ta
9.6
0.5
0.7
Ta
24.3
0.7
5.3
2
Ta
Ta
Ta
Ta
44
43
47
34
18
I
9.9
0.8
Ta
Ta
0.4
0.7
Ta
2.1
5.2
7.3
2.1
Ta
II
2.1
0.9
1.8
4.9
3.1
2.3
III
IV
1.6
2.0
1.9
1.9
a Traces.
b Homogeneous conditions.

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C. Crestini et al. / Bioorg. Med. Chem. 14 (2006) 5292–5302
N-oxide as anchorage site for the rhenium atom). In the
first case, the catalyst obtained with the most reticulated
resin, PVP-25%/MTO (catalyst II), was more reactive
than that characterized by a low value of this parameter
(PVP-2%/MTO, catalyst I) in the oxidation of
monomeric and dimeric b-O-4 lignin model compounds
(Tables 1–3). Moreover, irrespective of the reticulation
grade, with the increase of the oxidation state of the res-
in, that is poly(4-vinylpyridine) vs poly(4-vinylpyridine-
N-oxide), the reactivity of the catalyst appears to
increase, as shown, for example, by the reactivity of
catalysts I (PVP-2%/MTO) and III (PVPN-2%/MTO)
toward the oxidation of all model compounds studied.
The effect of the resins on the reactivity of MTO in
the activation of hydrogen peroxide is in accordance
with several data previously reported on the oxidation
of natural substances.12,19
plex network of such phenolic and non-phenolic lignin
structures, present during bleaching processes, we select-
ed a hydrolytic sugar cane lignin (SCL) and a red spruce
kraft lignin (RSL) as representative examples of para-
hydroxyphenyl-guaiacyl, and guaiacyl lignins.
These lignins were then submitted to oxidation with
H2O2 and the catalytic systems I–IV in acetic acid at
25 ꢁC. Homogeneous oxidations were also carried out
with the H2O2/MTO system as reference runs. After
the reactions, the lignins were recovered by filtration.
The oxidized samples were then phosphitylated with
2-chloro-4,4,5,5-tetramethyl-1,3,2-dioxaphospholane in
the presence of a known amount of cholesterol as inter-
nal standard followed by quantitative 31P NMR acquisi-
tion.13,14 Table 6 shows the amounts of the different
labile protons present in these lignins, expressed as
mmol/g of lignin, as measured by the enumerated proce-
dure. Since the oxidations were carried out in glacial
acetic acid, the occurrence of acidolytic side processes
should also be taken into account when interpreting
the following data.11,32 For this reason data regarding
the control homogeneous experiments carried out by
treating the samples with acetic acid alone are also
reported in Table 6.
Overall, the data presented and discussed so far point
toward the conclusion that the immobilized heteroge-
neous catalytic systems based on H2O2/and MTO cata-
lysts I–IV are able to extensively oxidize both phenolic
and non-phenolic, monomeric, and dimeric, lignin mod-
el compounds. In all examined cases the cleavage of the
alkyl side chain, or both alkyl side-chain oxidation and
aromatic ring cleavage were the operative processes. Re-
calcitrant diphenylmethane units were also efficiently
degraded.
Overall Table 6 displays the oxidation of both SCL and
RSL with H2O2 and immobilized catalytic MTO sys-
tems I–IV. These oxidations caused an appreciable de-
crease in the content of aliphatic OH groups. This is
indicative of the occurrence of side-chain oxidation reac-
tions. Moreover, all lignin samples showed an increased
content of COOH units after the treatments in accor-
dance with the displayed reactivity of MTO with the
model compounds depicted in Schemes 2, 4, and 5.
For SCL the decrease in the amount of the condensed
units, apparent under all experimental conditions, sug-
gests a structure more prone to further oxidation and
solubilization compared to RSL. Furthermore, the actu-
al decrease in the amounts of condensed units points to-
ward the lack of radical coupling processes which are
common events in many oxidative pathways involving
peroxide. These data are in accord with a concerted oxy-
gen atom transfer from the activated rhenium peroxy
2.2. Oxidative degradation of lignins
Once the reactivity of immobilized MTO catalytic sys-
tems toward lignin model compounds was clarified,
our attention was focused on the oxidation of the lignin
biopolymer. Technical lignins are samples of lignin
recovered after commercial delignification processes.
As such they are chemically modified and contain signi-
ficative amounts of carbon–carbon and carbon–oxygen
condensed subunits heavily recalcitrant to further oxida-
tion treatments. The renowned inert nature of such lig-
nins necessitates the existence of multiple oxidative
bleaching stages in a modern pulp mill. In an effort to
thoroughly examine and verify the ability of immobi-
lized MTO catalystic systems I–IV to degrade the com-
Table 6. Oxidation of hydrolytic sugar cane lignin (SCL) and red spruce kraft lignin (RSL) with H2O2 and catalysts I–IV
Lignina treatment
Aliphatic OH
(mmol/g)
Condensed OH
(mmol/g)
Guaiacyl OH
(mmol/g)
para-Hydroxy phenyl
OH (mmol/g)
COOH
(mmol/g)
SCL/CH3COOH
SCL/MTO/H2O2
SCL/I/H2O2
1.70
0.92
1.55
1.26
1.32
1.63
1.59
0.53
1.05
1.08
1.13
0.91
0.82
0.29
0.63
0.49
0.48
0.75
0.71
0.29
0.88
0.62
0.81
0.48
0.50
0.35
0.60
0.58
0.47
0.38
0.28
0.17
0.44
0.31
0.41
0.25
0.56
0.55
0.67
0.52
0.56
0.81
1.26
0.87
1.01
1.07
1.76
0.88
1.50
1.18
1.51
1.22
0.88
c
SCL/II/H2O2
SCL/III/H2O2
SCL/IV/H2O2
RSL/CH3COOH
RSL/MTO
0.50
b
b
b
b
b
b
RSL/I/H2O2
RSL/II/H2O2
RSL/III/H2O2
RSL/IV/H2O2
a RSL, Red spruce kraft lignin MW 28000; SCL, Sugar Cane hydrolysis lignin.
b Not present.
c Homogeneous conditions.

C. Crestini et al. / Bioorg. Med. Chem. 14 (2006) 5292–5302
5299
complexes to the lignin substrate. Unlike SCL, the
amounts of condensed units in red spruce lignin (RSL)
did not display as clear a trend. These moieties were
found to somewhat increase after oxidation with catalyt-
ic systems I and II, while they were found to decrease
with catalytic systems II and IV. Overall, however, the
variations in condensed moieties detected were always
modest (Table 6).
phenolic and non-phenolic lignin model compounds
was apparent as displayed with alkyl side chains being
subjected to oxidation and fragmentation reactions as
well as aromatic moieties being hydroxylated, demethy-
lated and oxidative ring-opening reactions. The efficien-
cy of catalysts I–IV was also found to be high toward
recalcitrant condensed lignin model compounds such
as phenolic and non-phenolic diphenylmethanes. Such
compounds were found to be subjected to both alkyl
side-chain oxidation and cleavage of the diphenylme-
thane bridge and of the aromatic rings.
Even if the efficiency of homogeneous MTO toward the
oxidation of SCL and RSL was found to be appreciably
higher than that of immobilized catalysts I–IV, overall
all the supported catalysts were found to be rather reac-
tive toward lignins. This implies that there is not any
prohibitive kinetic barrier to the approach of the heter-
ogeneous catalyst to the polymeric substrate. Alterna-
tively, the possibility that small oxidized fragments
may work as oxidation carriers cannot be ruled out.
Technical lignins, such as hydrolytic sugar cane lignin
(SCL) and red spruce kraft lignin (RSL), displayed oxi-
dative activity with immobilized catalytic systems I–IV.
Our data suggest that the lower Lewis acidity of immo-
bilized MTO catalysts I–IV with respect to homoge-
neous MTO would direct their reactivity toward
aliphatic C–H insertion and Dakin-like reactions rather
than aromatic ring oxidation, thus resulting in a final
product with a higher amount of free phenolic guaiacyl
groups.
The content of guaiacyl units in lignins treated with
MTO and catalytic systems I–IV allowed to further
evolve into the different selectivities operating between
homogeneous and immobilized MTO catalysts. In fact,
the guaiacyl (G) units were found decreased upon
H2O2/MTO treatments; on the contrary in the presence
of catalysts I–IV an increase of the G units was evi-
denced both on the RSL and the SCL (Table 6). The in-
crease of G units in treated lignins may be explained by
the occurrence of aliphatic lignin side-chain oxidation
processes with C–H insertion reactions and Dakin-like
reactions on a-carbonyl units, rather than aromatic ring
oxidations. These reactions occurring preferentially on
the aliphatic lignin interunit linkages would lead to
residual lignins with a higher phenolic content. Our find-
ings are in accord with the reported reactivity of immo-
bilized MTO catalysts. In fact, the nitrogen ligands
present on the polymeric support are able to tune the
Lewis acidity and the reactivity of MTO. Moreover, it
has been reported that supported MTO shows a higher
stability of the corresponding peroxo complex interme-
diates yielding to a tendency to perform C–H insertion
and Dakin-like reactions on a-carbonyl units rather
than aromatic ring oxidation.
Our data indicate that immobilized MTO catalytic sys-
tems are significant potential candidates for the develop-
ment of alternative totally chlorine free delignification
processes and environmentally sustainable lignin selec-
tive modification reactions.
4. Experimental
1H NMR, 13C NMR, and 31P NMR spectra were
recorded on a Bruker AM 400 or Bruker 200 spectrom-
eter. Mass spectroscopy (MS) was performed with a GC
Shimadzu GC-17A and a mass-selective detector QP
6000. All solvents were of ACS reagent grade and were
redistilled and dried according to standard procedures.
Chromatographic purifications were performed on col-
umns packed with Merck silica gel 60, 230–400 mesh
for flash technique. Thin-layer chromatography was car-
ried out using Merck platten Kieselgel 60 F254. Lignin
samples were purchased from Aldrich and used without
further purification. Quantitative 31P NMR spectra were
obtained using methods identical to those described by
Argyropoulos and co-workers.20,21 The chemical shifts
were referenced to phosphoric acid.
Our experimental data with the lignin oxidation reac-
tions clearly indicate the occurrence of different reaction
pathways between soluble and immobilized catalysts.
These data are extremely significant and relevant since
they address the issue of selectivity during the oxidative
modification of lignins. The selective degradation of
interunit linkages with the eventual production of more
soluble, easily oxidizable products represents a formida-
ble task toward the development of novel green lignin
bleaching and modification processes.
4.1. Preparation of lignin model compounds
Lignin model compounds 1-(4-hydroxy-3-methoxyphe-
nyl)-2-(2,6-dimethoxyphenoxy)-3-hydroxypropanol 10,
1-(4-ethoxy-3-methoxyphenyl)-2-(2-methoxyphenoxy)pro-
pane-1,3-diol 14, 2,20-methylenebis(6-methoxy-4-meth-
ylphenol) 19, and 1,10-methylenebis(2,3-dimethoxy-5-
methylbenzene) 26 were synthesized according to
literature procedures.33,34
3. Conclusions
Immobilized MTO catalytic systems I–IV were found to
be efficient catalysts for the oxidation of phenolic and
non-phenolic lignin model compounds with environ-
mental benign H2O2 as the oxygen atom donor. Excep-
tional reactivity toward monomeric and dimeric,
4.2. Preparation of supported MTO catalysts
Poly(4-vinylpyridine)/MTO (PVP-2%/MTO I, PVP-
25%/MTO II, and PVPN-2%/MTO III) and polysty-
rene/MTO (PS-2%/MTO IV) catalysts were prepared

5300
C. Crestini et al. / Bioorg. Med. Chem. 14 (2006) 5292–5302
as previously reported.12 In summary, MTO (77 mg,
0.3 mmol) was added to a suspension of the appropriate
resin (600 mg) in ethanol (4 mL) or tetrahydrofuran in
the case of polystyrene. The mixture was stirred for
1 h using a magnetic stirrer. Coacervates were found
to envelop the solid core dispersed in the medium and
hexane (5 mL) was added to harden the capsule walls.
The solvent was removed by filtration, and the solid res-
idue was washed with ethyl acetate and finally dried un-
der high vacuum. In every case, MTO was completely
included into the polymer. This result was confirmed
by spectroscopic analysis of the residue obtained after
evaporation of the organic layers. The catalysts were
used without any further purification.
room temperature. At the end of the reaction the cata-
lyst was filtered off and the solvent was evaporated un-
der reduced pressure. The residues were dissolved in
20 lL of pyridine in the presence of 3,4-dimethoxytolu-
ene as an internal standard for GC–MS analysis. The
mixture was than derivatized with bis(trimethylsilyltri-
fluoroacetamide) (BSTFA) and analyzed.
Gas chromatography and gas chromatography–mass
spectrometry of the reaction products were performed
using a DB1 column (30 m · 0.25 mm and 0.25 mm film
thickness), and an isothermal temperature profile of
100 ꢁC for the first two min, followed by a 20 ꢁC/min
temperature gradient to 300 ꢁC, and finally an isother-
mal period at 300 ꢁC for 10 min. The injector tempera-
ture was 280 ꢁC. Chromatography grade helium was
used as the carrier gas. The mass balance reported in
Tables 1–5 is the sum of the % of unreacted substrate
and the oxidation products.
4.3. Quantitative 31P NMR
Derivatization of the lignin samples with 2-chloro-
4,4,5,5-tetramethyl-1,3,2-dioxaphospholane was per-
formed as previously described.20,21 Samples of lignin,
(30 mg) accurately weighed, were dissolved in a solvent
mixture composed of pyridine and deuterated chloro-
form, 1.6:1 v/v ratio (0.5 mL). The phospholane
(100 lL) was then added, followed by the internal stan-
dard and the relaxation reagent solution (100 lL each).
The 31P NMR data reported in this effort are averages
of three phosphitylation experiments followed by
quantitative 31P NMR acquisitions. The maximum
standard deviation of the reported data was
2 · 10ꢀ2 mmol/g, while the maximum standard error
was 1 · 10ꢀ2 mmol/g.
The identification of vanillin 2, 2,6-dimethoxyphenol
12, 4-ethoxy-3-methoxybenzaldehyde 15, and (2E)-3-
(4-ethoxy-3-methoxyphenyl)acetaldehyde
16
was
carried out by comparison with sample of authentic
products. 2-hydroxy-5-(hydroxymethyl)benzo-1,4-qui-
none 5, 2-hydroxy-1-(4-hydroxy-3-methoxyphenyl)eth-
anone 11, (5-oxo-2,5-dihydrofuran-3-yl)acetic acid 13,
(2E)-3-(4-ethoxy-3-methoxyphenyl)prop-2-en-1-ol 18,
[3-(2,3-dimethoxy-5-methylbenzyl)-4,5-dimethoxyphe-
nyl]methanol 27, 4-(hydroxymethyl)-2-[5-(hydroxymeth-
yl)-2,3-dimethoxybenzyl]-6-methoxyphenol 28, 3-(5-
formyl-2,3-dimethoxybenzyl)-4,5-dimethoxybenzoic acid
29, and 2-(2,3-dimethoxy-5-methylbenzyl)-6-methoxy-
4-methylphenol 30 were assigned by comparison with
the GC–MS fragmentation spectra of original
compounds.16,29,35–37
4.4. Typical procedure for the oxidation of lignin model
compounds
The model compounds (1.0 mmol) to be oxidized and
H2O2 (1.5 mmol, 35% water solution) were added to a
solution of the catalyst (1.0% w/w of the active species)
in CH3COOH (5 mL), and the mixtures were stirred at
4-Hydroxy-3-methoxybenzoic acid 3, (2Z)-3-(5-oxo-2,5-
dihydrofuran-3-yl)acrylic acid 4, 3,4-dimethoxybenzal-
Table 7. Mass spectrometric data of compounds 9, 11–33
Product
Derivativea
MS (m/z) data (%)
9
11
12
13
15
16
17
18
20
21
22
23
24
25
27
28
29
30
31
32
33
—
168 (M+, 12), 136 (100), 124 (53)
–Si(CH3)3
—
–Si(CH3)3
254 (M+, 28), 212 (68), 197 (32), 182 (100), 73 (93).
154 (M+, 100), 139 (55), 93 (41), 96 (32), 65 (30), 111 (30)
214 (M+, 52), 213 (100), 169 (95), 139 (91), 111 (86), 75 (62), 73 (48)
180 (M+, 37), 151 (100), 109 (17), 95 (10), 81 (20), 65 (25)
124 (M+, 74), 109 (100), 81 (75), 77 (4), 65 (7)
336 (M+, 12), 316 (6), 207 (20), 117 (29), 75 (100), 73 (89)
280 (M+, 6), 206 (24), 103 (18), 73 (100)
–Si(CH3)3
–Si(CH3)3
–Si(CH3)3
–Si(CH3)3
–Si(CH3)3
–Si(CH3)3
–Si(CH3)3
–Si(CH3)3
–Si(CH3)3
–Si(CH3)3
–Si(CH3)3
–Si(CH3)3
–Si(CH3)3
448 (M+, 3), 313 (78), 299 (49), 207 (43), 132 (48), 117 (83), 75 (98), 73 (100)
464 (M+, 4), 282 (8), 207 (100), 85 (61), 73 (98)
534 (M+, 2), 516 (8), 309 (17), 287 (24), 197 (85), 147 (52), 73 (100)
356 (M+, 12), 341 (23), 309 (18), 207 (100), 132 (31), 117 (61), 75 (88), 73 (81)
340 (M+, 8), 339 (22), 309 (24), 147 (38), 117 (32), 75 (54), 73 (100)
414 (M+, 36), 413 (100), 309 (38), 251 (46), 207 (75), 73 (79)
404 (M+, 12), 351 (6), 347 (8), 207 (43), 73 (100)
492 (M+, 21), 462 (16), 207 (100), 73 (87)
432 (M+, 12), 431 (38), 401 (8),281 (6), 207 (100), 96 (16), 73 (43)
374 (M+, 92), 344 (100), 313 (20), 193 (36), 162 (28), 151 (32), 73 (81).
464 (M+, 12), 404 (9), 207 (100), 73 (68)
446 (M+, 2), 431 (46), 207 (100), 73 (49)
282 (M+, 38), 252 (12), 223 (18), 208 (43), 193 (21), 73 (100)
a Underivatized; –Si(CH3)3: trimethylsilylated with N,O-bis(trimethylsilyl)-acetamide.

C. Crestini et al. / Bioorg. Med. Chem. 14 (2006) 5292–5302
5301
dehyde 7, 3,4-dimethoxybenzoic acid 8, and methyl
(2Z)-3-(5-oxo-2,5-dihydrofuran-3-yl)acrylate were
4.10. Oxidation of lignin. General procedure
9
recovered in appreciable amount after flash chromato-
graphy of the respective crude and characterized by
1H NMR and 13C NMR analyses.
Oxidations of hydrolytic sugar cane lignin (SCL) and
red spruce kraft lignin (RSL) were carried out in acetic
acid (5 mL), in the presence of 100 mg of lignin,
1.0 mg MTO (1.0% w/w of the active species), and
500 lL H2O2 (35% water solution). After 24 h, the reac-
tion mixtures were evaporated, washed with water,
centrifuged, and freeze-dried.
(2E)-3-(4-Ethoxy-3-methoxyphenyl)acrylaldehyde 17,
2-[2-hydroxy-5-(hydroxymethyl)-3-methoxybenzyl]-6-
methoxy-4-methylphenol
20,
2,20-methylenebis[4-
(hydroxymethyl)-6-methoxyphenol] 21, 4-hydroxy-3-
[2-hydroxy-5-(hydroxymethyl)-3-methoxybenzyl]-
5-methoxybenzaldehyde 22, 2-hydroxy-5-(hydroxy-
methyl)-3-methoxybenzoic acid 23, (2-hydroxy-3-meth-
oxy-5-methylphenyl)acetic acid 24, [2-hydroxy-5-
(hydroxymethyl)-3-methoxyphenyl]acetic acid 25, 4-
(hydroxymethyl)-2-[5-(hydroxymethyl)-2,3-dimethoxy-
References and notes
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166.6 (CO), 150.4 (C), 146.5 (C), 123.9 (CH), 121.3
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(9)
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6.30 (m, 1H, HCO), 6.12 (d, 1H, J = 12.4 Hz, CH),
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