Electrochemical Aminoxyl-Mediated Oxidation of Primary Alcohols in Lignin to Carboxylic Acids: Polymer Modification and Depolymerization

Article abstract of DOI:10.1021/jacs.9b07243

An electrochemical process has been developed for chemoselective oxidation of primary alcohols in lignin to the corresponding carboxylic acids. The electrochemical oxidation reactions proceed under mildly basic conditions and employ 2,2,6,6-tetramethyl-1-piperidine N-oxyl (TEMPO) and 4-acetamidoO (ACT) as catalytic mediators. Lignin model compounds and related alcohols are used to conduct structure-reactivity studies that provide insights into the origin of the reaction selectivity. The method is applied to the oxidation of lignin extracted from poplar wood chips via a mild acidolysis method, and the reaction affords a novel polyelectrolyte material. Gel permeation chromatography data for the oxidized lignin shows that this material has a molecular weight and molecular weight distribution very similar to that of the extracted lignin, but notable differences are also evident. Base titration reveals a significant increase in the acid content, and the oxidized lignin has much higher water solubility relative to the extracted lignin. Treatment of the oxidized lignin under acidic conditions results in depolymerization of the material into characterized aromatic monomers in nearly 30 wt% yield.

Full text of DOI:10.1021/jacs.9b07243

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Article
Electrochemical Aminoxyl-Mediated Oxidation of Primary Alcohols in
Lignin to Carboxylic Acids: Polymer Modification and Depolymerization
Mohammad Rafiee, Manar Alherech, Steven D Karlen, and Shannon S. Stahl
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.9b07243 • Publication Date (Web): 04 Sep 2019
Downloaded from pubs.acs.org on September 5, 2019
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Electrochemical Aminoxyl-Mediated Oxidation of
Primary Alcohols in Lignin to Carboxylic Acids:
Polymer Modification and Depolymerization
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a,†
a
b,c
a
Mohammad Rafiee, Manar Alherech, Steven D. Karlen, Shannon S. Stahl *
a
Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue
Madison, WI, 53706, United States
b
Department of Energy Great Lakes Bioenergy Research Center, the Wisconsin Energy Institute,
University of Wisconsin-Madison, Madison, WI 53726, USA.
c Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
stahl@chem.wisc.edu
RECEIVED DATE
Abstract: An electrochemical process has been developed for chemoselective oxidation of
primary alcohols in lignin to the corresponding carboxylic acids. The electrochemical oxidation
reactions proceed under mildly basic conditions and employ 2,2,6,6-tetramethyl-1-piperidine N-
oxyl (TEMPO) and 4-acetamido-TEMPO (ACT) as catalytic mediators. Lignin model compounds
and related alcohols are used to conduct structure-reactivity studies that provide insights into the
origin of the reaction selectivity. The method is applied to the oxidation of lignin extracted from
poplar wood chips via a mild acidolysis method, and the reaction affords a novel polyelectrolyte
material. Gel permeation chromatography data for the oxidized lignin shows that this material has
a molecular weight and molecular weight distribution very similar to that of the extracted lignin,
but notable differences are also evident. Base titration reveals a significant increase in the acid
content, and the oxidized lignin has much higher water solubility relative to the extracted lignin.
Treatment of the oxidized lignin under acidic conditions results in depolymerization of the material
into characterized aromatic monomers in nearly 30 wt% yield.
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Introduction
Lignin is a major constituent of nonedible biomass that is biosynthesized via radical coupling
1
of phenylpropanoid units. The lignin polymer, which features a non-regular pattern of methoxy-
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substituted aromatic groups linked together via aliphatic ether fragments (Scheme 1a), represents
the largest source of naturally occurring aromatic chemicals in nature. The complex structure and
composition of the covalent bonds in the polymer backbone, however, complicate selective
breakdown of this material, and it is typically treated as a waste product and burned as an energy
2
3-8
source in the paper and pulp industry. Marketable applications have been identified for lignin,
but the installation of cellulosic ethanol plants and preparations for future biorefineries have
highlighted the need to gain increased value from lignin and/or lignin-derived materials.9-12 Major
efforts have been directed toward conversion of lignin into low molecular weight chemicals that
could potentially serve as fuels or as feedstocks for the chemical industry.13-20 These efforts have
led to a number of effective lignin depolymerization approaches, including pyrolysis, acid or base
treatment, catalytic hydrogenolysis or related reductive methods, and oxidation methods. The
reduction and oxidation methods have been shown to be capable of converting lignin into a small
collection of aromatic monomers in relatively high yields (i.e., ≥ 30 wt% relative to the lignin
precursor).
The electron-rich aromatic groups in lignin are susceptible to outer-sphere electron transfer,21
and oxidative degradation of lignin by laccase and peroxidase enzymes is the primary pathway for
lignin breakdown in nature.22,23 In addition, the aliphatic ethers that connect the aromatic groups
in the polymer chain often feature primary or secondary alcohols that are susceptible to oxidation
(
Scheme 1a). The most prevalent fragment is the b-O-4 unit, which features a benzylic secondary
9
alcohol and a primary aliphatic alcohol (Scheme 1b). In 2013, we evaluated a wide range of
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stoichiometric and catalytic alcohol oxidation methods in an effort to assess their ability to promote
2
4
selective oxidation of one of these two alcohols. In fact, a number of oxidation methods and
reagents examined led to chemoselective oxidation of a single alcohol in the b-O-4 unit, and both
oxidation products undergo facile cleavage of C–C and/or C–O bonds of the aliphatic ether linker
to afford monoaromatic products (Scheme 1c).25,26
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Scheme 1. a) Representative Structure of Lignin, b) Lignin Units Bearing Alcohol Groups, and
c) Chemoselective Alcohol Oxidation Strategies for Cleavage of b-O-4 Lignin Model.
MeO
a)
O
HO
OMe
HO
HO
O
OMe
MeO
OH
MeO
HO
HO
OH
MeO
O
O
O
MeO
OMe
O
O
O
OMe
O
OH
MeO
MeO
OH
OH
O
O
MeO
OMe
OH
OH
OH
O
O
HO
O
OMe
OH
OMe OH
OMe
HO
O
O
OMe
OH
OMe
OMe
OH
OH
HO
HO
b)
HO
HO
OMe
O
HO
O
O
OMe
OMe
OMe
MeO
O
O
OMe
O
β-O-4 (45-62%)
β-5 (3-12%)
β-1 (2-9%)
O
c)
O
HO
1º
OMe
+
HO
OMe
OMe
HO
HO
OMe
OMe
R
O
OMe
HO
Bond
Cleavage
OMe
O
O
OMe
O
OMe
OMe
+
HO
2
º
OMe
OMe
OMe
OMe
OMe
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Numerous selective alcohol oxidation methods have now been identified for lignin and lignin
model compounds by our group and others, and the majority of these examples promote selective
oxidation of the secondary benzylic position.24,27-41 Although partial oxidation of primary alcohols
in lignin was observed in the process of oxidative pulp treatment by TEMPO/bleach (TEMPO =
0
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,2,6,6-tetramethyl-1-piperidine N-oxyl),42-44 relatively few methods have been identified for
selective oxidation of the primary alcohols in lignin, and successful examples typically afford the
aldehyde as the product.24,45-48
Organic aminoxyls (also called nitroxyls), such as TEMPO and ACT (4-acetamido-TEMPO)
(
Scheme 2a), are especially effective stoichiometric reagents and catalysts for alcohol oxidation in
lignin.24,28,29,42,45 Aminoxyl-mediated alcohol oxidation has an extensive history, and catalytic
methods are widely used in industrial chemical synthesis.50,51 The methods are initiated by
oxidation of the aminoxyl radical (or the corresponding hydroxylamine) to the oxoammonium
species. Under acidic conditions, the oxammonium promotes alcohol oxidation via a bimolecular
hydride transfer mechanism that strongly favors reaction with the secondary benzylic alcohol in
lignin (Scheme 2b). In contrast, under basic conditions, the oxoammonium mediates alcohol
oxidation by an inner sphere mechanism that favors reaction with the less sterically hindered
primary alcohol (Scheme 2b).49,52,53 The different conditions pair different terminal oxidants with
49
the aminoxyl catalyst, however. The acidic conditions are capable of using O
2
,24,29,54 while basic
-based
conditions typically employ chlorine- or hypervalent iodine-based oxidants.24,42-45 The NO
x
co-catalyst that enables aerobic regeneration of the oxoammonium species under acidic
55
conditions is not effective under basic conditions. On the other hand, aminoxyl catalysts have
been widely studied in the context of electrochemical alcohol oxidation,56,57 including oxidation
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of biomass-derived carbohydrates and sugars,58-61 and such approaches would provide a
sustainable alternative to the use of undesirable stoichiometric oxidants (Schemes 2c and 2d).62-66
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Scheme 2. a) Structure of TEMPO and ACT; b) Mechanism of Alcohol Oxidation by
Oxoammonium Under Basic and Acidic Conditions; c) Chemical and d) Electrochemical
Oxidation of Lignin Mediated by Aminoxyl Radicals.
NHAc
a)
TEMPO =
ACT =
N
O
N
O
basic conditions
b)
H
O
1
R
R
N
R
R2
O
R
R
R
R
N
N
OH
R1 R2
O X–
selective for 1°
O
OH
– H+
R1 R2
acidic conditions
HO
O
R
N
R
R1
H
2
R
selective for 2°
c)
d)
R
R
R
R
R
N
O
N
O
[O]H2
Lignin
Lignin
R
R
R
[O]
N
LigninOx
LigninOx
N
OH
OH
In the present study, we show that electrochemical aminoxyl-mediated oxidation methods
enable efficient and selective conversion of primary alcohols in lignin to the corresponding
carboxylic acids.67,68 Studies of model compounds are used to compare reactivity of different
alcohols and provide insights into the reaction selectivity. The electron-deficient aminoxyl
derivative ACT is shown to be more reactive than TEMPO and a preferred electrocatalyst for these
reactions,69-71 and the optimized conditions are shown to be capable of converting lignin isolated
from poplar into a water-soluble polyelectrolyte. This material undergoes cleavage of the lignin
backbone under acidic conditions resulting in nearly 30 wt% yield of monomeric aromatic
compounds.
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Results and Discussion
Electrochemical Study. We initiated our study using cyclic voltammetry (CV) and
chronoamperometry72,73 for the study of TEMPO-mediated electrochemical oxidation of the β-O-
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lignin model 1a under mild basic conditions (pH 10, Figure 1). In the absence of 1a, the CV of
TEMPO shows an anodic peak corresponding to oxidation of TEMPO to oxoammonium
+
(TEMPO ) (labeled A
1
in Figure 1, trace a) and a cathodic peak for the reduction of
+
electrogenerated TEMPO at the electrode surface (labeled C in Figure 1, trace a). Two major
1
changes are observed for the CV of TEMPO in the presence of 1a (Figure 1 trace b): the cathodic
peak is absent and the anodic peak current exhibits a 10-fold increase in magnitude. These changes,
+
which indicate the consumption of TEMPO and generation/regeneration of TEMPOH (the
reduced form of TEMPO) by the substrate, respectively, provide evidence for an electrocatalytic
HO
HO
HO
HO
O
O
O
TEMPO +
Base
OMe
OMe
OMe
OMe
OMe
OMe
HO
HO
b
5
4
2
1
-
5.0
0.0
5.0
0.0
5.0
55.0
40.0
25.0
10.0
-5.0
O
OMe
d
OMe
TEMPO
+ S1 ua b
OMe
1
a
Q
TEMPO+1a – QTEMPO
A
1
a
c
Q
TEMPO
TEMPO
C
1
0
0.25
0.5
0.75
1
0
6
12
t (s)
18
24
E (V) vs. Ag/AgCl
Figure 1. Cyclic voltammograms (left) and chronoamperograms (right) of 1.0 mM TEMPO in the
presence (red, b and d) and absence (blue, a and c) of 10 mM 1a. Solution condition: H O/CH CN
(70/30), NaHCO /Na CO electrolyte (0.07/0.07 M, pH 10), scan rate for cyclic voltammetry is 10
2
3
3
2
3
–
1
mVs and applied potential for chronoamperometry is 0.7 V vs. Ag/AgCl, the above scheme
represents the possible mechanism for TEMPO catalyzed alcohol oxidation.
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reaction. The enhancement of the oxidation peak current in the presence of the lignin model
compound is proportional to the catalytic turnovers that occur on the CV time scale.
Chronoamperometry was used to obtain quantitative data complementary to the CV data. A
chronoamperogram of TEMPO in the absence of 1a (Figure 1, trace c) shows the diffusion-
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+
controlled oxidation current corresponding to the oxidation of TEMPO to TEMPO at the electrode
surface. Addition of 1a to the TEMPO solution leads to an increase in the oxidation current (Figure
1
, trace d) due to the catalytic turnover of TEMPOH. Integration of the resulting current/time
traces, depicted by the shaded regions under the chronoamperogram traces, provides the total
consumed charge in the redox reaction. The ratio of the consumed charge in the presence and
absence of substrate during the chronoamperometry experiments, together with the reaction
stoichiometry, provides the basis for the TOF of the catalytic reactions.74
Analogous chronoamperometry experiments were then conducted with a number of different
model compounds and subunits bearing lignin-type alcohol groups (1a – 7a, Figure 2). The results
clearly demonstrate higher TOFs with primary alcohols (e.g., 2a > 3a), in addition to higher
reactivity with alcohols bearing an ether oxygen atom in the b position of the alcohol (1a > 4a, 2a
> 5a and 6a/7a > 3a). The presence of electron-donating methoxy group on the benzene ring has
+
minimal effect on the reactivity of benzylic alcohol groups toward oxidation by TEMPO (6a vs
7
a).
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174
120
1
a
2a
3a
4a
5a
6a
7a
O
OMe
OH
O
OMe
OH
O
OMe
OH
O
OMe
HO
HO
HO
HO
OH
MeO
OMe
MeO
OMe
MeO
OMe
MeO
OMe
1
a
3a
MeO
5a
7a
OMe
O
OMe
OH
O
OMe
OH
HO
HO
OH
HO
MeO
OMe
MeO
OMe
MeO
OMe
2
a
4a
6a
Figure 2. TOFs for TEMPO-catalyzed electrochemical oxidation of various lignin-related
alcohols, derived by chronoamperometric experiments. Alcohol structures are shown in red; gray
portions of the structures are not part of molecule, but are included to show the relationship to the
lignin substructures. Reaction conditions: H
0), applied potential for chronoamperometry 0.7 V vs. Ag/AgCl.
2
O/CH
3
CN (70/30), NaHCO
3
/Na
2
CO electrolyte (pH
3
1
In previous studies, we have shown that TEMPO derivatives with higher redox potentials
perform better than TEMPO in electrochemical alcohol oxidation, and ACT is one of the most
appealing aminoxyls, owing to its low cost, good stability, and excellent catalytic performance.69-
7
1
Cyclic voltammetry analysis of TEMPO and ACT in the presence of 1a confirms the improved
performance of ACT. Chronoamperometric analysis of ACT-catalyzed electrochemical oxidation
-1
1
a, 2a and 6a revealed TOFs of 1045, 1065 and 316 h , respectively, all of which represent
significant improvements relative to the results obtained with TEMPO (cf. Figure 3, and Figure
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S2-S4 in Supporting Information). As a result of these observation, bulk electrolysis experiments
were carried out with ACT.
85
d, ACT
+
1a
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4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
c, TEMPO
5
2
-
5
5
5
+
1a
a, TEMPO
b, ACT
0.8
E (V) vs. Ag/AgCl
0
.2
0.4
0.6
1
Figure 3. Cyclic voltammograms of 1.0 mM TEMPO and ACT in the absence (a and b) and
presence of 10 mM 1a (c and d), highlighting the increased activity of ACT. Solution condition:
H
2
O/CH
3
CN (70/30), NaHCO
3
/Na
2
CO electrolyte (0.07/0.07 M, pH 10), scan rate for cyclic
3
–1
voltammetry is 10 mVs and applied potential for chronoamperometry is 0.7 V vs. Ag/AgCl.
Bulk Electrolysis. ACT-mediated bulk electrolysis reactions were performed under constant-
potential conditions (0.80 V vs. Ag/AgCl) in order to probe the preparative utility of the reactions
described above and to establish the identity of the reaction products. The results of these
experiments are presented in Table 1. Oxidation of the guaiacyl-derived β-O-4 model compound
1a undergoes oxidation to the corresponding β-hydroxy acid (1c) in 91% isolated yield,
highlighting the selectivity for primary alcohol oxidation. No product derived from oxidation of
the secondary alcohol group was observed under these conditions, and attempts to promote further
oxidation to the β-ketoacid under more strongly basic conditions (pH 11.2, using Na
and sole supporting electrolyte) led to only partial oxidation of the secondary alcohol group (<
0% after 2 h). The substrates bearing lignin-like subunits, with only primary or secondary alcohol
2
CO
3
as base
3
groups, undergo clean oxidation in excellent yields to the corresponding
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1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Table 1. ACT mediated electrolysis reactions of various lignin models.
Entry
Substrate
Products, Yield
OH
OH
O
MeO
MeO
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
MeO
MeO
OH
OH
1
O
O
MeO
a
MeO
1c, 91%
1
O
O
O
OH
OH
2
3
2a
3a
2c, 91%
OH
O
MeO
MeO
3b, 95%
OH
MeO
MeO
MeO
MeO
MeO
OH
O
4
5
O
MeO
OH
4
5
a
a
OMe
4c, 79%
4d, 86%
OMe
O
OH
OH
5
c, 93%
OH
O
O
O
6
7
MeO
MeO
7b, 98%
7a
OH
O
O
O
MeO
MeO
MeO
MeO
8b, 97%
8
a
OH
MeO
HO
MeO
O
O
OH
8
9
O
O
OH
O
OMe
OMe
OMe
MeO
9
a
9c, 52%
9d, 36%
MeO
HO
MeO
O
O
O
OMe
OMe
9c, 59%
9
b
Conditions: 0.05 mmol of ACT and 1 mmol of each substrate in 8 mL H
2
O/CH
3
CN (70/30),
NaHCO /Na CO electrolyte pH 10, electrolysis at 0.80 V vs. Ag/AgCl, the reactions were terminated when
3
2
3
1
the current reached to 5% of the initial current. Yield determined by H NMR spectroscopy; int. std. = 1,3,5-
trimethoxybenzene.
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carboxylic acid (2c and 5c) or ketone (3b, 7b and 8b) products. Oxidation of compound 4a, bearing
a β-1 linkage (i.e., lacking the ether present in 1a; see also, Scheme 1b), results in cleavage of the
aliphatic ether unit, affording products that arise from the retro-aldol reaction of the initially
formed aldehyde intermediate to generate 3,4-dimethoxybenzaldehyde and the homologous
aliphatic aldehyde fragment. The aliphatic aldehyde then undergoes oxidation to generate
carboxylic acid 4d, while the benzaldehyde does not undergo oxidation under these reaction
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
7
0
conditions due to its lower susceptibility to hydrate formation. Lignin models bearing a free
phenol group, 9a and 9b, undergo direct electron transfer at the electrode surface at potentials
similar to redox potentials of ACT or TEMPO; therefore, subjecting these molecules to the
standard electrochemical oxidation conditions affords 2,6-dimethoxyquinone (9c) as the major
product.75
Substrates 1a and 4a differ only in the presence or absence of a β-ether group in the aliphatic
tether between the two aryl groups; however, these two substrates exhibit substantial differences
in reactivity toward oxidative cleavage. To probe the basis for these differences, we analyzed the
reaction progress for the simplified substrate analogs 2a and 5a (Figure 4a). The data show nearly
direct conversion of 2a into the corresponding carboxylic acid 2c, with little build-up of the
intermediate aldehyde 2b (Figure 4b). In contrast, the oxidation of 5a leads to significant build-up
of the intermediate aldehyde 5b (Figure 4c). This difference is again rationalized by the relative
preference for formation of the aldehyde hydrate, which is favored for more electron deficient
7
6
aldehydes (2b > 5b). These results suggest the aldehyde product arising from initial oxidation of
a may have sufficient lifetime to undergo retro-aldol cleavage of the C–C bond, while the
4
analogous intermediate derived from oxidation of 1a has negligible lifetime and undergoes further
oxidation to the carboxylic acid product 1c.
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1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
a)
b)
X
ACT +
X
ACT +
X
HO
O
HO
O
2
a, 5a X = O (2), CH2 (5) 2b, 5b
2c, 5c
c)
R
OH
R
OH
1
00
100
2
a
5a
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
X = O
75
X = CH
2
7
5
2
5
0
5
0
OH
OH
R
O
50
R
O
2
c
R
O
5c
5
b
25
R
O
2
b
0
0
25
50
75 100
0
25
50
75
100
Q (C)
d)
HO
O
HO
HO
O
O
HO
HO
O
O
+
+
ACT
ACT
OMe
OMe
OMe
Base
OMe
1c
Base
OMe
OMe
1b
OMe
Base
OMe
OMe
1
a
Retro
aldol
Retro
aldol
Base
O
O
O
OH
O
+
O
ACT
O
+
+
OMe
OMe
1e
Base
OMe
OMe
OMe
OMe 1d
Figure 4. (a) Reaction sequence showing oxidation of alcohols 2a and 5a to aldehydes 2b and 5b
and then to carboxylic acids 2c and 5c. (b and c) Reaction progress data showing the concentration
profiles of the alcohol, aldehyde and carboxylic acids as a function of charge passed for the
oxidation of 2a and 5a during the bulk electrolysis reactions. (d) Mechanistic proposal to account
for the products obtained from oxidation and oxidative cleavage of the β-O-4 substrate 1a.
Reaction conditions: 0.05 mmol of ACT and 1 mmol of each substrate in 8 mL H
2
O/CH CN
3
(70/30), NaHCO /Na CO electrolyte pH 10, electrolysis at 0.80 V vs. Ag/AgCl.
3
2
3
The observations in Figure 4a-c and mechanistic rationale in Figure 4d prompted us to test
whether the branching between retro-aldol cleavage of 1b vs oxidation to the carboxylic acid 1c
could be influenced by the solution pH. The effect of pH was evaluated by examining ACT-
mediated oxidation 1a from pH 9.2 – 12.5, by varying the composition of the buffering electrolyte
(
cf. Table 2). At pH 9.2 and 10.1, the carboxylic acid product 1b was obtained as the major product
(94% and 89% yields, respectively; Table 2, entries 1 and 2). At higher pH (11.5 and 12.5),
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however, increasing quantities of retro-aldol C–C cleavage products 1b and 1c were observed
(
entries 3 and 4).
a
Table 2. Oxidation and oxidative cleavage of β-O-4 lignin linkage.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
HO
O
OH
HO
O
O
OH
HO
O
O
ACT +
OMe
OMe
Or
+
O
Base
OMe
OMe
OMe
OMe
OMe
1c
OMe
OMe
1
a
1b
1d
Yields
1b 1c 1d
Solvent
ratio)
Entry
1
Base (M)
(pH)
9.2
(
H
2
O/MeCN
NaHCO
3
(0.13)
94
3
0
(75/25)
2 3
Na CO (0.02)
H
2
O/MeCN
NaHCO
3
(0.07)
(0.07)
2
10.1
89
9
7
(75/25)
Na
2
CO
3
H
2
O/MeCN
3
4
Na
2
CO
3
(0.15)
(0.15)
11.5
12.5
59
9
33 28
88 76
(75/25)
H
2
O
3 4
Na PO
a
Reaction conditions: 0.05 mmol of ACT and 1 mmol 1a in 8 mL solution, electrolysis at 0.80 V, the
reactions were terminated when the currents reached to 5% of the initial current. Reported yields obtained
1
by HNMR spectroscopy (internal standard = 1,3,5-trimethoxybenzene).
Lignin Oxidation and Characterization of Oxidized Lignin. With these insights from the
lignin model studies in hand, we turned our attention to experiments with lignin itself. The lignin
sample was obtained from poplar wood chips via a previously reported mild acidolysis extraction
method,39,77 which affords a native-like lignin material (44% yield based on compositional
analysis; see Supporting Information for details), with considerable retention of the desired b-O-4
subunits. The CV of ACT in the presence of poplar lignin demonstrates a well-defined oxidative
catalytic feature (Figure 5a, red trace), while the lignin in the absence of ACT doesn’t show
significant redox activity in the potential range of ACT oxidation (Figure 5a, blue trace). Bulk
electrolysis of the lignin under constant-potential conditions (0.80 V vs Ag/AgCl, Figure 5b)
–
–
suggests a removal of somewhat more than 2e per monomer unit of lignin (i.e., 2.4 e per each
1
80 AU of lignin). The oxidized lignin exhibits significantly higher solubility in water than the
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1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
original unoxidized lignin (14 g/L vs < 2 g/L, respectively, at pH 9). This observation is
rationalized by the presence of carboxylate functional groups that will enhance the water solubility
of the polymer. An acid-base titration of the oxidized lignin with NaOH (Figure 5c) reveals the
presence of approximately 2.3 mmol of acid functional groups per gram of the oxidized lignin.
This value may be compared to the much lower value of approximately 0.2 mmol of acid per gram
of unoxidized lignin.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
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a)
3
5.0
5.0
5.0
ACT & lignin
2
1
ACT
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
5
.0
lignin
-
5.0
0
0.25
0.5
0.75
1
E (V) vs. Ag/AgCl
b)
HO
HO
HO
HO
O
O
O
+
ACT
OMe
OMe
Base
OMe
Lignin
OMe
O
O
Ligninox
1
5.0
2.0
9.0
150
120
90
60
30
0
current
charge
1
6
3
0
.0
.0
.0
0
1
O
2
3
4
5
t (h)
Na+ –O
HO
O
O
c)
HO
HO
O
OMe
equiv NaOH
OMe
OMe
OMe
O
O
12
1
0
8
6
4
2
native lignin
oxidized lignin
0
0.5
1
1.5
2
2.5
-
1
CO H functional group (mmolg )
2
Figure 5. (a) Cyclic voltammograms of poplar lignin (blue), ACT (black) and mixture of ACT and
lignin (red); (b) ACT mediated electrochemical oxidation of lignin; the resulting current and
consumed charge curves for controlled potential electrolysis (at 0.80 V vs Ag/AgCl). Reaction
Conditions: 0.23 mmol of ACT and 100 mg of lignin in 8 mL H
NaHCO /Na CO electrolyte pH 10, scan rate for cyclic voltammetry 100 mVs , electrolysis at
.80 V vs. Ag/AgCl. c) Acid-Base of oxidized lignin; and titration curves of lignin before (black
2
O/CH CN (70/30),
3
–1
3
2
3
0
trace) and after ACT-mediated oxidation (green trace) in 10 ml mixture of H
using 0.01 M aqueous NaOH.
2
O/CH CN (70/30)
3
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1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Analysis of the lignin before and after oxidation by gel-permeation chromatography (GPC)
revealed an approximately 30% reduction in the molecular weight of the material (Figure 6), as
reflected by the M
untreated) and 1.49 and 5.05 kDa (oxidized), respectively. This observation suggests that some
depolymerization occurs as a result of the electrochemical oxidation at pH 10; however, the
n
and M values derived for untreated and oxidized lignin: 1.94 and 7.92 kDa
w
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(
1
13
material clearly retains a polymeric structure. Analysis of the 2D H- C HSQC NMR spectra of
the lignin samples before and after oxidation provides further evidence for conversion of primary
alcohol groups to the corresponding carboxylic acids (Figure 7). The oxidized lignin exhibits a
decrease in intensity of the signal corresponding to the g- and b-hydrogens for the b-O-4 and b-5
lignin residues, together with the appearance of a new signal corresponding to the b-hydrogen of
the oxidized b-O-4 residue. Moreover, the signal corresponding to the a-hydrogens of the b-O-4
lignin residues remain comparatively unchanged, supporting preferential oxidation of the primary
aliphatic over the secondary benzylic alcohol groups.
15
10
50
0
66 kDa
15.7 kDa 3.47 kD 0a .14 kDa
a
b
0
3
6
9
12
15
Volume (mL)
Figure 6. GPC chromatograms of (a) untreated and (b) oxidized poplar lignin. Conditions: PSS
PolarSil Linear S column with solution of 0.1 M lithium bromide (LiBr) in dimethyl formamide
(
DMF) as the mobile phase (flow rate of 0.3 mL/min).
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a)
Before Oxidation
After Oxidation
C
β
C
β
OMe
Α
γ
Αγ
B
γ
B
γ
A
α
C
γ
A
α
C
γ
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Aʼ
α
C
α
A
β
C
α
Aʼ
β
A
β
13C
1
H (ppm)
5
4
5
4
3
S/G
b) HO
HO
HO
O
O
γ
O
S/G
OH
S/G
HO
O
α
β
O
β
β
γ
α
β
α
γ
α
O
S/G
S/G
S/G
S/G
A
A′
B
C
c)
Before Oxidation
After Oxidation
S
2/6
S
2/6
Sʼ2/6
G
2
G
2
Gʼ
2
Η
3/5
Η
3/5
G
5/6
G
5/6
G
5/6
G
5/6
Py
Py
Η
2/6
Ms
Η
2/6
13C
1H (ppm)
8
7
8
7
O
OH
OH
OH
d)
2
6
2
6
2
6
5
2
6
5
3
MeO
OMe
MeO
OMe
MeO
S′/G′
S
G
H
Figure 7. HSQC spectra of lignin before (left) and after (right) ACT-mediated electrochemical
oxidation: a) aliphatic region, and c) aromatic region, b) and d) structures of lignin fragments with
corresponding NMR signals.
Depolymerization of Carboxylated Lignin. The pH-dependent bulk electrolysis results in
Table 2, together with the modest reduction in the molecular weight of the lignin polymer
following oxidation at pH 10, suggested that it may be possible to achieve effective one-step
1
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1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
oxidative depolymerization of lignin under more basic conditions. Efforts to achieve this goal,
however, led to suboptimal results. Bulk electrolysis of the lignin sample at pH 12, for example,
afforded ≤ 8 wt% yield of monomeric aromatic products relative to the mass of the initial lignin
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(
see section 5 in the Supporting Information for details). The products derived from lignin
depolymerization under these conditions are susceptible to recondensation/oligomerization or
oxidative degradation.78-82
In order to bypass this complication, we targeted a two-step oxidation/depolymerization
sequence in which the lignin polymer could be oxidized and then treated under modified conditions
to induce depolymerization. Cleavage of β-hydroxy acids has been reported under basic
8
3
conditions; however, subjecting the oxidized model compound 1c or oxidized lignin material to
more basic conditions (0.1 M NaOH, see section 9, Supporting Information) afforded less than 5%
yield of cleavage products. In contrast, treatment of the oxidized lignin model compound 1c under
various acidic conditions generated a mixture of the monomeric aromatic compounds, 1d-h
(
Figure 8a). This distribution of products may be rationalized by the reaction sequence shown in
Figure 8b. The process is initiated by acid-induced elimination of the benzylic hydroxyl group
from 1a to afford a vinyl ether that is susceptible to hydrolysis and generation of an a-ketoacid
that resembles the Hibbert ketones.84-86 Subsequent decarboxylation of the ketoacid generates the
observed products, guaiacol 1f and the aliphatic aldehyde 1g. The aldehyde 1g is susceptible to
acid-catalyzed dimerization, via aldol condensation, electrophilic addition to the arene, and loss of
water to form the naphthalene derivative 1h. Building on a report by Barta and de Vries, the H
2
SO
4
8
7
conditions from Figure 8a, entry 3 were repeated in the presence of ethylene glycol (eq 1). Under
these conditions, 1g was trapped as the acetal 1i, which prevented further conversion of 1g into
1h. In addition to the products obtained from the sequence in Figure 8b, a small quantity of
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products arising from retro-aldol cleavage of 1c, generating 1d and 1e (Figure 8c) were also
observed under the conditions noted in entries 1, 2, and 5 of Figure 8a.
a) Entry Acid Solution t (h) 1c 1f 1g 1h(x2) 1d 1e Yield
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
H O/Acetone
(50/50) 1M HCl
1
2
2
6
4
3
3
4
–
66 38
69 41
73 66
68 50
34
44
11
5
9
–
84
90
H O/CH CN
2
3
(
50/50) 1M HCl
H O/CH CN
2
3
3
–
–
29
36
5
–
–
–
95
86
42
(
50/50) 1M H SO
2
4
H O/HCO H
2
2
4
5
–
(10/90)
H O/CH CO H
2
3
2
12 52 15 21
16 11
(10/90)
b)
HO
HO
O
HO
O
acid
treatment
O
O
OMe
OMe
–
H2O
MeO
MeO
1c
OMe
OMe
+
H2O
HO
MeO
+
O
HO
O
OMe
MeO
1
f
– CO2
MeO
MeO
via
MeO
enol formation
OMe
OMe
O
–
2 H2O
MeO
1h
1g
c) Minor Pathway
HO
O
O
HO
HO
O
acid
treatment
O
OMe
+
O
MeO
OMe
MeO
OMe
OMe 1c
1d
1e
Figure 8. Acid-induced cleavage data with 1c (a) together with major and b) minor cleavage
pathways that explain the origin of the observed depolymerization products. Reaction conditions
1
for (a): 70 mg 1c, 5 mL solvent, 110 °C (100 °C for entry 3), yields of 1d-h determined by H
NMR spectroscopy (int. std. = trimethoxybenzene). Note: yield obtained for 1h is multiplied by
two to account for the dimeric nature of this product.
The oxidized lignin sample described above was then subjected to the H
Figure 8a, entry 3), which afforded the highest yield of cleavage products, and the H
conditions (Figure 8a, entry 4), which were used previously in the cleavage of lignin oxidized at
2
SO
4
conditions
(
2
O/HCO
2
H
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1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
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6
the benzylic position.26 Both conditions induced depolymerization of the resulting lignin, as
revealed by GPC analysis of the material (cf. Figure S8). HPLC analysis of the product mixtures
revealed significant quantities of aromatic products (Figure 9), with higher depolymerization
yields from treatment with formic acid relative to those obtained when using sulfuric acid: 29 wt%
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(
H
2
O/HCO
2
H) and 24 wt% (H
2
SO ; yields reported vs the original mass of untreated lignin). The
4
significant yield of syringyl (S)- and guaiacyl (G)-derived aldehydes is consistent with the
reactivity observed with the model compound 1c in Figure 8b and 8c. On the other hand, the
significant yield of S- and G-derived a-diketones and carboxylic acids suggests that other cleavage
pathways are occurring within the oxidized lignin that are not evident from the oxidized model
compound 1c. We note that the HSQC NMR data in Figure 7 indicates the electrochemical
oxidation leads to some oxidation of the benzylic alcohol groups, in addition to oxidation of the
primary alcohols that produce the carboxylated lignin. Acid treatment of lignin oxidized at the
benzylic position has been shown to generate a-diketones.26
30.0
O
O
O
O
4
.8
2
2
1
5.0
0.0
5.0
2
.8
3.7
OMe MeO
OMe
OH
O
OH
2.0
O
7.8
0.8
7.8
OMe
OH
MeO
OMe
OH
0
.6
OH
OH
10.0
5.0
O
OH
O
O
6
.8
5.8
1
3
.5
.2
2
2
.7
.3
OMe
MeO
OMe
OH
OH
OH
0
.0
a
b
Figure 9. Aromatic monomers (weight percent) obtained from treatment of oxidized lignin with
a) sulfuric acid and (b) formic acid. Reaction conditions: 50 mg oxidized lignin, 6 mL 1 M H SO
in CH CN for (a) and 5 mL H O/HCO H 1:9 for (b), 100 °C for 12 h for (a) and 110 °C for 24 h,
product yields determined by HPLC (see Supporting Information for details).
(
2
4
3
2
2
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Overall, the results show that oxidation of the primary alcohols within lignin provides the basis
for effective depolymerization of lignin into low molecular weight aromatic compounds. The
yields of aromatic monomers are somewhat lower than those obtained from oxidation methods
that favor reaction with the benzylic position;26,39 however, optimal results can vary as a function
of the biomass source material, lignin extraction method, among other variables. In this context,
the present methods offer a useful complement for future consideration.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Conclusion.
The aminoxyl-mediated electrochemical oxidation method described here exhibits high
selectivity for oxidation of primary alcohols groups within lignin model compounds, and the
method has been shown to be effective for the oxidation of lignin extracted from poplar. Structure-
reactivity correlations of small molecules has provided valuable insights into the reaction
selectivity, including the synergistic role of other functional groups within the lignin structure on
the oxidative reactivity of the alcohols. Conversion of the primary alcohols in lignin to carboxylic
acids results in formation of a polyelectrolyte that is complementary to established lignosulfonate
8
8
materials and that warrants further investigation among the growing number of other lignin-
derived polymer applications.89-91 In addition, the electrocatalytic oxidation method renders the
modified lignin susceptible to depolymerization, allowing for conversion of lignin into monomeric
aromatic chemicals in good yields.
ASSOCIATED CONTENT
Supporting Information. Experimental procedures and compound characterization data (PDF).
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AUTHOR INFORMATION
Corresponding Author
*
stahl@chem.wisc.edu
Present Address
†Department of Chemistry, University of Missouri-Kansas City, 5009 Rockhill Rd., Kansas City,
MO 64110
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Notes
67
A patent application describing some of the content described in this study has been submitted.
Acknowledgements.
We thank Dr. Hao Luo (UW-Madison) for assistance with HPLC data acquisition and analysis.
Financial support for this project was provided by the Great Lakes Bioenergy Research Center
(
DOE Office of Science BER DE-FC02-07ER64494 and DE-SC0018409). Spectroscopic
instrumentation was partially supported by the NIH (S10 OD020022) and the NSF (CHE-
1048642).
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